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Sample records for adult mdma users

  1. Treatment Implications for Young Adult Users of MDMA (3,4-Methylenedyoxymethamphetamine)

    ERIC Educational Resources Information Center

    Dew, Brian J.; Elifson, Kirk W.; Sterk, Claire E.

    2006-01-01

    Young adults' 3,4-methylenedyoxymethamphetamine (MDMA) use is a national public health concern. Although research on the epidemiology of MDMA use has increased, inquiry into intervention and treatment is needed. The authors examine results from an epidemiological investigation from a clinical perspective and provide suggestions for clinicians…

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

    PubMed Central

    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

  3. Functional Magnetic Resonance Imaging in Abstinent MDMA Users: A Review.

    PubMed

    Garg, Aayushi; Kapoor, Saloni; Goel, Mishita; Chopra, Saurav; Chopra, Manav; Kapoor, Anirudh; McCann, Una D; Behera, Chittaranjan

    2015-01-01

    Ecstasy or 3,4-methylenedioxymethamphetamine (MDMA) is a popular drug of abuse. In the animal studies MDMA has been shown to have deleterious effects on the serotonergic neurotransmitter system. Understanding the adverse effects of MDMA on human brain function is of considerable importance owing to the rising number of MDMA users. Various neuroimaging studies have investigated the structural, chemical and functional differences in the brain integrity of chronic MDMA users. Various neurocognitive domains like working memory, episodic memory, semantic memory, visual stimulation, motor function and impulsivity have been compared between chronic MDMA users and nonusers using fMRI. The fMRI studies remain much more sensitive in studying the neurological deficits associated with chronic MDMA use as compared to the cognitive studies alone and therefore they serve as a prelude in our understanding of MDMA induced neurotoxicity. However they still face certain limitations contributing to inconsistency in the results and further research is needed before we can draw definitive conclusions regarding the neurotoxic effects of MDMA.

  4. Effect of MDMA (ecstasy) on activity and cocaine conditioned place preference in adult and adolescent rats.

    PubMed

    Aberg, Maria; Wade, Dean; Wall, Erin; Izenwasser, Sari

    2007-01-01

    MDMA (ecstasy) is a drug commonly used in adolescence, and many users of MDMA also use other illicit drugs. It is not known whether MDMA during adolescence alters subsequent responses to cocaine differently than in adults. This study examined the effects of MDMA in adolescent and adult rats on cocaine conditioned reward. At the start of these experiments, adolescent rats were at postnatal day (PND) 33 and adult rats at PND 60. Each rat was treated for 7 days with MDMA (2 or 5 mg/kg/day or vehicle) and locomotor activity was measured. Five days later cocaine conditioned place preference (CPP) was begun. Rats were trained for 3 days, in the morning with saline and in the afternoon with 10 mg/kg cocaine in 30 min sessions, and tested on the fourth day. MDMA stimulated activity in both age groups, but with a greater effect in the adult rats. Sensitization to the locomotor-stimulant effects of the lower dose of MDMA occurred in adult rats and in both groups to the higher dose. Cocaine did not produce a CPP in vehicle-treated adolescent rats, but a significant CPP was observed subsequent to treatment with MDMA. In contrast, cocaine-induced CPP was diminished after MDMA in adult rats. These effects were still evident 2 weeks later upon retest. Thus, under the present conditions, MDMA increased cocaine conditioned reward in adolescent and decreased it in adult rats. These findings suggest that exposure to MDMA during this critical developmental period may carry a greater risk than during adulthood and that male adolescents may be particularly vulnerable to the risk of stimulant abuse after use of MDMA.

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

    PubMed

    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.

  6. Risky Car Following in Abstinent Users of MDMA

    PubMed Central

    Dastrup, Elizabeth; Lees, Monica; Bechara, Antoine; Dawson, Jeffrey D.; Rizzo, Matthew

    2011-01-01

    Ecstasy (MDMA) use raises concerns because of its association with risky driving. We evaluated driving performance and risk taking in abstinent recreational MDMA users in a simulated car following task that required continuous attention and vigilance. Drivers were asked to follow two car lengths behind a lead vehicle (LV). Three sinusoids generated unpredictable LV velocity changes. Drivers could mitigate risk by following further behind the erratic LV. From vehicle trajectory data we performed a Fourier analysis to derive measures of coherence, gain, and delay. These measures and headway distance were compared between the different groups. All MDMA drivers met coherence criteria indicating cooperation in the car following task. They matched periodic changes in LV velocity similar to controls (abstinent THC users, abstinent alcohol users, and non-drug users), militating against worse vigilance. While all participants traveled approximately 55mph (89kph), the MDMA drivers followed 64m closer to the LV and demonstrated 1.04s shorter delays to LV velocity changes than other driver groups. The simulated car following task safely discriminated between driving behavior in abstinent MDMA users and controls. Abstinent MDMA users do not perform worse than controls, but may assume extra risk. The control theory framework used in this study revealed behaviors that might not otherwise be evident. PMID:20380914

  7. Risky car following in abstinent users of MDMA.

    PubMed

    Dastrup, Elizabeth; Lees, Monica N; Bechara, Antoine; Dawson, Jeffrey D; Rizzo, Matthew

    2010-05-01

    Ecstasy (MDMA) use raises concerns because of its association with risky driving. We evaluated driving performance and risk taking in abstinent recreational MDMA users in a simulated car following task that required continuous attention and vigilance. Drivers were asked to follow two car lengths behind a lead vehicle (LV). Three sinusoids generated unpredictable LV velocity changes. Drivers could mitigate risk by following further behind the erratic LV. From vehicle trajectory data we performed a Fourier analysis to derive measures of coherence, gain, and delay. These measures and headway distance were compared between the different groups. All MDMA drivers met coherence criteria indicating cooperation in the car following task. They matched periodic changes in LV velocity similar to controls (abstinent THC users, abstinent alcohol users, and non-drug users), militating against worse vigilance. While all participants traveled approximately 55 mph (89 kph), the MDMA drivers followed 64 m closer to the LV and demonstrated 1.04 s shorter delays to LV velocity changes than other driver groups. The simulated car following task safely discriminated between driving behavior in abstinent MDMA users and controls. Abstinent MDMA users do not perform worse than controls, but may assume extra risk. The control theory framework used in this study revealed behaviors that might not otherwise be evident.

  8. The Influence of Genetic and Environmental Factors among MDMA Users in Cognitive Performance

    PubMed Central

    Cuyàs, Elisabet; Verdejo-García, Antonio; Fagundo, Ana Beatriz; Khymenets, Olha; Rodríguez, Joan; Cuenca, Aida; de Sola Llopis, Susana; Langohr, Klaus; Peña-Casanova, Jordi; Torrens, Marta; Martín-Santos, Rocío; Farré, Magí; de la Torre, Rafael

    2011-01-01

    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. PMID:22110616

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

    PubMed Central

    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 (p<0.05; corrected). Lifetime MDMA 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

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

    PubMed Central

    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

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

    PubMed

    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; p<0.001). Hence the regular use of Ecstasy/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.

  12. Learning, Memory, and Executive Function in New MDMA Users: A 2-Year Follow-Up Study

    PubMed Central

    Wagner, Daniel; Tkotz, Simon; Koester, Philip; Becker, Benjamin; Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

    2015-01-01

    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 2-year period would lead to further decreases in cognitive performance, especially in visual paired association learning tasks. Ninety-six 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 2 years. No further deterioration in continuing MDMA-users was observed in the second follow-up period. 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, the groups differed in their use of concomitant use of

  13. Learning, Memory, and Executive Function in New MDMA Users: A 2-Year Follow-Up Study.

    PubMed

    Wagner, Daniel; Tkotz, Simon; Koester, Philip; Becker, Benjamin; Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

    2015-01-01

    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 2-year period would lead to further decreases in cognitive performance, especially in visual paired association learning tasks. Ninety-six 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 2 years. No further deterioration in continuing MDMA-users was observed in the second follow-up period. 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, the groups differed in their use of concomitant use of

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

    PubMed

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

    2014-12-01

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

  15. Intermittent prenatal MDMA exposure alters physiological but not mood related parameters in adult rat offspring.

    PubMed

    Adori, Csaba; Zelena, Dóra; Tímár, Júlia; Gyarmati, Zsuzsa; Domokos, Agnes; Sobor, Melinda; Fürst, Zsuzsanna; Makara, Gábor; Bagdy, György

    2010-01-20

    The recreational party drug "ecstasy" (3,4-methylenedioxymethamphetamine MDMA) is particularly popular among young adults who are in the childbearing age and thus there is a substantial risk of prenatal MDMA exposure. We applied an intermittent treatment protocol with an early first injection on pregnant Wistar rats (15 mg/kg MDMA s.c. on the E4, E11 and E18 days of gestation) to examine the potential physiological, endocrine and behavioral effects on adult male and female offspring. Prenatal MDMA-treatment provoked reduced body weight of offspring from the birth as far as the adulthood. Adult MDMA-offspring had a reduced blood-glucose concentration and hematocrit, altered relative spleen and thymus weight, had lower performance on wire suspension test and on the first trial of rotarod test. In contrast, no alteration in the locomotor activity was found. Anxiety and depression related behavioral parameters in elevated plus maze, sucrose preference or forced swimming tests were normal. MDMA-offspring had elevated concentration of the ACTH-precursor proopiomelanocortin and male MDMA-offspring exhibited elevated blood corticosterone concentration. No significant alteration was detected in the serotonergic marker tryptophan-hydroxylase and the catcholaminergic marker tyrosine-hydroxylase immunoreactive fiber densities in MDMA-offspring. The mothers exhibited reduced densities of serotonergic but not catecholaminergic fibers after the MDMA treatment. Our findings suggest that an intermittent prenatal MDMA exposure with an early first injection and a relatively low cumulative dose provokes mild but significant alterations in physical-physiological parameters and reduces motor skill learning in adulthood. In contrast, these adult offspring do not produce anxiety or depression like behavior. PMID:19782105

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

    PubMed

    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.

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

    PubMed

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

    2016-01-01

    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.

  18. Coping with Loneliness: Young Adult Drug Users.

    ERIC Educational Resources Information Center

    Rokach, Ami; Orzeck, Tricia

    Since there appears to be a connection between substance use (and abuse) and loneliness it is of theoretical and clinical interest to explore the differences of coping with loneliness which drug users employ. The present study examined the manner in which MDMA (Ecstasy) users in comparison with non-MDMA (Non-Ecstasy) users and the general…

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

    PubMed Central

    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.

    2012-01-01

    Rationale Ecstasy (MDMA) polydrug users have verbal memory performance that is statistically significantly lower than comparison control subjects. Studies have correlated long-term MDMA use with altered brain activation in regions that play a role in verbal memory. Objectives 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. Methods 23 abstinent ecstasy polydrug users (age=24.57) and 11 controls (age=22.36) performed a two-part 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<0.05). Results During the encoding phase, 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 (rs=0.43, p=0.042). Behavioral performance did not differ between groups. Conclusions 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. PMID:23241648

  20. Acquisition and reinstatement of MDMA-induced conditioned place preference in mice pre-treated with MDMA or cocaine during adolescence.

    PubMed

    Daza-Losada, Manuel; Rodríguez-Arias, Marta; Aguilar, María A; Miñarro, José

    2009-09-01

    Those who take ecstasy are more likely to consume other drugs than non-users with cocaine abuse being reported by 75.5% of high school student MDMA (+/- 3,4-methylenedioxymetamphetamine hydrochloride) users. The aim of this work was to evaluate the effects of exposure during adolescence to MDMA, cocaine or to both drugs on the MDMA-induced conditioned place preference (CPP) in adult mice. Animals received two daily administrations of saline, 10 mg/kg of MDMA, 25 mg/kg of cocaine or 10 mg/kg of MDMA plus 25 mg/kg of cocaine over 3 days (from PD28 to 30). Three weeks after pre-treatment, the MDMA-induced CPP procedure was initiated (PD52). Acquisition of CPP was induced with a sub-threshold dose of MDMA (1.25 mg/kg) only in animals treated during adolescence with MDMA alone. Preference was established in all the groups after conditioning with 10 mg/kg of MDMA, while the time required to achieve extinction was longer in those pre-treated with cocaine or MDMA alone (46 and 28 sessions, respectively). Moreover, preference was reinstated with progressively lower priming doses of MDMA in mice pre-treated with MDMA or cocaine alone. These results demonstrate that early exposure to MDMA or cocaine induces long-lasting changes that last until adulthood and modify the response of animals to MDMA.

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

    PubMed

    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.

  2. Event-related potentials (ERPs) in ecstasy (MDMA) users during a visual oddball task.

    PubMed

    Mejias, S; Rossignol, M; Debatisse, D; Streel, E; Servais, L; Guérit, J M; Philippot, P; Campanella, S

    2005-07-01

    Ecstasy is the common name for a drug mainly containing a substance identified as 3,4-methylenedioxymethamphetamine (MDMA). It has become popular with participants in "raves", because it enhances energy, endurance and sexual arousal, together with the widespread belief that MDMA is a safe drug [Byard, R.W., Gilbert, J., James, R., Lokan, R.J., 1998. Amphetamine derivative fatalities in South Australia. Is "ecstasy" the culprit? Am. J. Forensic Med. Pathol. 19, 261-265]. However, it is suggested that this drug causes a neurotoxicity to the serotonergic system that could lead to permanent physical and cognitive problems. In order to investigate this issue, and during an ERP recording with 32 channels, we used a visual oddball design, in which subjects (14 MDMA abusers and 14 paired normal controls) saw frequent stimuli (neutral faces) while they had to detect as quickly as possible rare stimuli with happy or fearful expression. At a behavioral level, MDMA users imply longer latencies than normal controls to detect rare stimuli. At the neurophysiological level, ERP data suggest as main result that the N200 component, which is involved in attention orienting associated to the detection of stimulus novelty (e.g. [Campanella, S., Gaspard, C., Debatisse, D., Bruyer, R., Crommelinck, M., Guerit, J.M., 2002. Discrimination of emotional facial expression in a visual oddball task: an ERP study. Biol. Psychol. 59, 171-186]), shows shorter latencies for fearful rare stimuli (as compared to happy ones), but only for normal controls. This absence of delay was interpreted as an attentional deficit due to MDMA consumption. PMID:15925034

  3. The Variety of Ecstasy/MDMA Users: Results from the National Epidemiologic Survey on Alcohol and Related Conditions

    PubMed Central

    Wu, Li-Tzy; Parrott, Andy C.; Ringwalt, Christopher L.; Yang, Chongming; Blazer, Dan G.

    2011-01-01

    This study investigates the potential heterogeneity of ecstasy or MDMA (3,4-methylenedioxy-N-methylamphetamine) users. Data came from the 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Latent class analysis (LCA) and multinomial logistic regression procedures were used to identify subtypes of ecstasy users. Approximately 1.6% (n=562) of adult participants (N=43,093) reported lifetime ecstasy use. LCA identified three subtypes of ecstasy users. Class 1 exhibited pervasive use of most drug classes (ecstasy–polydrug users, 37%). Class 2 reported a high rate of use of marijuana and cocaine and a moderate use of amphetamines (ecstasy–marijuana–stimulant users, 29%). Class 3 was characterized by a high rate of use of marijuana and a low use of primarily prescription-type drugs (ecstasy– marijuana users, 34%). Subtypes were distinguished by family income, history of substance abuse treatment, and familial substance abuse. Class 1 exhibited the highest prevalence of disorders related to the use of marijuana (77%), tobacco (66%), amphetamines (36%), opioids (35%), sedatives (31%), and tranquilizers (30%). The recent resurgence in ecstasy use among adults underscores the need to monitor trends in its use. PMID:19874166

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

    PubMed

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

    2004-06-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

  6. Effects of acute social stress on the conditioned place preference induced by MDMA in adolescent and adult mice.

    PubMed

    García-Pardo, Maria P; Rodríguez-Arias, Marta; Maldonado, Concepcion; Manzanedo, Carmen; Miñarro, Jose; Aguilar, Maria A

    2014-09-01

    Exposure to social defeat stress increases the rewarding effects of psychostimulants in animal models, but its effect on 3,4-methylenedioxymethylamphetamine (MDMA) reward has received little attention. In the present study, we evaluated the influence of social defeat on the rewarding effects of MDMA in adolescent [postnatal day (PND) 29-40] and adult (PND 50-61) male mice using the conditioned place preference paradigm. Experimental mice were exposed to social defeat in an agonistic encounter before each session of conditioning with 1.25 or 10 mg/kg of MDMA. The effects of social defeat on corticosterone levels and the motor or the anxiogenic effects of MDMA were also evaluated. Mice exposed to social defeat during adulthood did not show conditioned place preference after conditioning with either dose of MDMA. Conversely, social defeat did not affect the anxiogenic and motor effects of MDMA. Adult mice exposed to social defeat showed higher levels of corticosterone than their controls and adolescent mice. Social stress did not induce behavioural effects in adolescent mice. Our results show that stress induced by social defeat decreases the sensitivity of adult mice to the rewarding effects of MDMA.

  7. MDMA (Ecstasy)

    MedlinePlus

    ... synthetic, meaning it's manmade. MDMA works by altering chemical reactions in the brain. Most users take it as a pill or capsule. The effects usually last about 3 to 6 hours. Short-Term ... of serotonin, a "feel-good" chemical that plays a role in mood, sleep, sexual ...

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

    PubMed

    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.

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

    PubMed

    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. PMID:26068050

  10. Effect of intermittent exposure to ethanol and MDMA during adolescence on learning and memory in adult mice

    PubMed Central

    2012-01-01

    Background Heavy binge drinking is increasingly frequent among adolescents, and consumption of 3,4-methylenedioxymethamphetamine (MDMA) is often combined with ethanol (EtOH). The long-lasting effects of intermittent exposure to EtOH and MDMA during adolescence on learning and memory were evaluated in adult mice using the Hebb-Williams maze. Methods Adolescent OF1 mice were exposed to EtOH (1.25 g/kg) on two consecutive days at 48-h intervals over a 14-day period (from PD 29 to 42). MDMA (10 or 20 mg/kg) was injected twice daily at 4-h intervals over two consecutive days, and this schedule was repeated six days later (PD 33, 34, 41 and 42), resulting in a total of eight injections. Animals were initiated in the Hebb-Williams maze on PND 64. The concentration of brain monoamines in the striatum and hippocampus was then measured. Results At the doses employed, both EtOH and MDMA, administered alone or together, impaired learning in the Hebb-Williams maze, as treated animals required more time to reach the goal than their saline-treated counterparts. The groups treated during adolescence with EtOH, alone or plus MDMA, also presented longer latency scores and needed more trials to reach the acquisition criterion score. MDMA induced a decrease in striatal DA concentration, an effect that was augmented by the co-administration of EtOH. All the treatment groups displayed an imbalance in the interaction DA/serotonin. Conclusions The present findings indicate that the developing brain is highly vulnerable to the damaging effects of EtOH and/or MDMA, since mice receiving these drugs in a binge pattern during adolescence exhibit impaired learning and memory in adulthood. PMID:22716128

  11. Elevated impulsivity and impaired decision-making in abstinent Ecstasy (MDMA) users compared to polydrug and drug-naïve controls.

    PubMed

    Morgan, Michael John; Impallomeni, Lara Chiara; Pirona, Alessandro; Rogers, Robert David

    2006-07-01

    Ecstasy (MDMA; 3,4-methylenedioxymethamphetamine) has a well-recognized neurotoxic effect on central serotonergic (5-HT) systems in animals, and there is some evidence of persistent serotonergic dysregulation in human ecstasy users. Serotonin is believed to mediate impulsive behavior and effective decision-making. Thus, the aim of the present study was to investigate impulsive behavior and decision-making in abstinent regular ecstasy users. Three groups were compared: 'ecstasy users' (recreational ecstasy users who reported modest use of illicit drugs other than cannabis), 'polydrug controls' (ecstasy naïve illicit drug users), and 'drug-naïve controls'. All participants completed personal details and general drug history questionnaires, the National Adult Reading Test, Matching Familiar Figures Test (MFF20), a risky decision-making task (RDMT), and the Card Arranging Reward Responsivity Objective Test (CARROT). The groups did not differ on the CARROT measure of responsiveness to financial incentive; however, the ecstasy group displayed significantly elevated MFF20 impulsivity, and showed reduced discrimination between magnitudes of prospective gains and losses when making risky decisions, compared to the 'polydrug' and 'drug-naïve' control groups. These findings may reflect a vulnerability of 5-HT systems in the orbital prefrontal cortex and interconnected corticolimbic circuitry to the cumulative neurotoxic effects of ecstasy and have clinical significance for regular ecstasy users. The combination of elevated impulsivity and impaired use of reinforcement cues in uncertain decision-making may comprise risk factors for continued drug abuse and everyday functioning. PMID:16292322

  12. Urinary MDMA, MDA, HMMA, and HMA Excretion Following Controlled MDMA Administration to Humans

    PubMed Central

    Abraham, Tsadik T.; Barnes, Allan J.; Lowe, Ross H.; Spargo, Erin A. Kolbrich; Milman, Garry; Pirnay, Stephane O.; Gorelick, David A.; Goodwin, Robert S.; Huestis, Marilyn A.

    2011-01-01

    3,4-Methylenedioxymethamphetamine (MDMA), or ecstasy, is excreted as unchanged drug, 3,4-methylenedioxyamphetamine (MDA), and free and glucuronidated/sulfated 4-hydroxy-3-methoxymethamphetamine (HMMA), and 4-hydroxy-3-methoxyamphetamine (HMA) metabolites. The aim of this paper is to describe the pattern and timeframe of excretion of MDMA and its metabolites in urine. Placebo, 1.0 mg/kg, and 1.6 mg/kg oral MDMA doses were administered double-blind to healthy adult MDMA users on a monitored research unit. All urine was collected, aliquots were hydrolyzed, and analytes quantified by gas chromatography–mass spectrometry. Median Cmax, Tmax, ratios, first and last detection times, and detection rates were determined. Sixteen participants provided 916 urine specimens. After 1.6 mg/kg, median Cmax were 21,470 (MDMA), 2229 (MDA), 20,793 (HMMA), and 876 ng/mL (HMA) at median Tmax of 13.9, 23.0, 9.2 and 23.3 h. In the first 24 h, 30.2–34.3% total urinary excretion occurred. HMMA last detection exceeded MDMA’s by more than 33 h after both doses. Identification of HMMA as well as MDMA increased the ability to identify positive specimens but required hydrolysis. These MDMA, MDA, HMMA, and HMA pharmacokinetic data may be useful for interpreting workplace, drug treatment, criminal justice, and military urine drug tests. Measurement of urinary HMMA provides the longest detection of MDMA exposure yet is not included in routine monitoring procedures. PMID:19874650

  13. The effect of MDMA-induced anxiety on neuronal apoptosis in adult male rats' hippocampus.

    PubMed

    Karimi, S; Jahanshahi, M; Golalipour, M J

    2014-01-01

    Ecstasy or MDMA as a psychoactive drug and hallucinogen is considered one of the most commonly used drugs in the world. This psychotropic substance is discussed both as sexually stimulating and reducing fear and anxiety. Amphetamines also destroy neurons in some brain areas. The aim of this study was to investigate the effects of MDMA on anxiety and apoptosis of hippocampal neurons. Forty-two male Wistar rats of mean weight 200-220 g were used and distributed into six groups [control, control-saline, and experimental groups (1.25, 2.5, 5, 10 mg/kg)]. Rats in experimental groups received MDMA at different doses for seven days by intraperitoneal injection and the control-saline group received saline (1 ml/kg); anxiety was then investigated by plus-maze test. Forty-eight hours after behavioural testing brains were taken from animals and fixed, and after tissue processing, slices were stained with TUNEL kit for apoptotic cells. The area densities of apoptotic neurons were measured throughout the hippocampus and compared in all groups (P < 0.05). Physiological studies showed that 1.25 mg/kg and 2.5 mg/kg doses caused anti-anxiety behaviour and 5 and 10 mg/kg doses of MDMA caused anxietylike behaviour. Moreover, our histological study showed that ecstasy increased apoptotic cell numbers and the highest increase was observed with the 10 mg/kg dose of MDMA. We concluded that MDMA can cause different responses of anxiety-like behaviour in different doses. This phenomenon causes a different ratio of apoptosis in hippocampal formation. Reduction of anxiety-like behaviour induced by the 2.5 mg/kg dose of MDMA can control apoptosis. PMID:25152052

  14. MDMA effects consistent across laboratories

    PubMed Central

    Kirkpatrick, Matthew G.; Baggott, Matthew J.; Mendelson, John E.; Galloway, Gantt P.; Liechti, Matthias E.; Hysek, Cédric M.; de Wit, Harriet

    2014-01-01

    Rationale Several laboratories have conducted placebo-controlled drug challenge studies with MDMA, providing a unique source of data to examine the reliability of the acute effects of the drug across subject samples and settings. We examined the subjective and physiological responses to the drug across three different laboratories, and investigated the influence of prior MDMA use. Methods Overall, 220 healthy volunteers with varying levels of previous MDMA experience participated in laboratory-based studies in which they received placebo or oral MDMA (1.5 mg/kg or 125 mg fixed dose) under double blind conditions. Cardiovascular and subjective effects were assessed before and repeatedly after drug administration. The studies were conducted independently by investigators in Basel, San Francisco and Chicago. Results Despite methodological differences between the studies and differences in the subjects' drug use histories, MDMA produced very similar cardiovascular and subjective effects across the sites. The participants' prior use of MDMA was inversely related to feeling `Any Drug Effect' only at sites testing more experienced users. Conclusions These data indicate that the pharmacological effects of MDMA are robust and highly reproducible across settings. There was also modest evidence for tolerance to the effects of MDMA in regular users. PMID:24633447

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

    PubMed

    Davis, Alan K; Rosenberg, Harold

    2016-06-01

    This prospective study was designed to test whether the variables proposed by the Theory of Planned Behavior (TPB) were associated with baseline intention to implement and subsequent use of 2 MDMA/ecstasy-specific harm reduction interventions: preloading/postloading and pill testing/pill checking. Using targeted Facebook advertisements, an international sample of 391 recreational ecstasy users were recruited to complete questionnaires assessing their ecstasy consumption history, and their attitudes, subjective norms, perceived behavioral control, habit strength (past strategy use), and intention to use these two strategies. Attitudes, subjective norms, and perceived behavioral control were significantly associated with baseline intention to preload/postload and pill test/pill check. Out of the 391 baseline participants, 100 completed the two-month follow-up assessment. Baseline habit strength and frequency of ecstasy consumption during the three months prior to baseline were the only significant predictors of how often participants used the preloading/postloading strategy during the follow-up. Baseline intention to pill test/pill check was the only significant predictor of how often participants used this strategy during the follow-up. These findings provide partial support for TPB variables as both correlates of baseline intention to implement and predictors of subsequent use of these two strategies. Future investigations could assess whether factors related to ecstasy consumption (e.g., subjective level of intoxication, craving, negative consequences following consumption), and environmental factors (e.g., accessibility and availability of harm reduction resources) improve the prediction of how often ecstasy users employ these and other harm reduction strategies. (PsycINFO Database Record PMID:27322805

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

    PubMed Central

    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

  17. The case for MDMA (ecstasy) regulation.

    PubMed

    Donelly, Joshua

    2015-06-01

    Drug-related harm is the most rational means of determining a substance's legal status. The available evidence suggests that compared to other drugs, 3,4-methylenedioxy-N-methamphetamine (MDMA or "ecstasy") poses a low level of harm to most individual users and causes negligible harm to society. There is no sound justification for criminalising the use of MDMA. .The depenalisation model adopted in Australia does not have any benefits that cannot be achieved by removing minor MDMA offences from criminal law entirely. The current model also operates within a prohibition framework that is costly to society and increases harm to ecstasy users. These arguments support the proposal by David Penington in 2012 that MDMA should be regulated on a legal market. The supply of MDMA from pharmacies appears to be a practicable law reform option with the potential to reduce harm associated with ecstasy use and the costs of prohibition. PMID:26349381

  18. The case for MDMA (ecstasy) regulation.

    PubMed

    Donelly, Joshua

    2015-06-01

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

  19. Repeated exposure to MDMA provides neuroprotection against subsequent MDMA-induced serotonin depletion in brain

    PubMed Central

    Bhide, Nirmal S.; Lipton, Jack; Cunningham, Jacobi; Yamamoto, Bryan K.; Gudelsky, Gary A.

    2009-01-01

    Repeated exposure to sub-lethal insults has been reported to result in neuroprotection against a subsequent deleterious insult. The purpose of this study was to evaluate whether repeated exposure (preconditioning) to a non-5-HT depleting dose of MDMA in adult rats provides neuroprotection against subsequent MDMA induced 5-HT depletion. Treatment of rats with MDMA (10 mg/kg, ip every 2 hrs for 4 injections) resulted in a 50-65% depletion of 5-HT in the striatum, hippocampus and cortex, and these depletions were significantly attenuated in rats that received a preconditioning regimen of MDMA (10 mg/kg, ip daily for 4 days). The 5-HT depleting regimen of MDMA also resulted in a 40-80% reduction in 5-HT transporter immunoreactivity (SERTir), and the reduction in SERTir also was completely attenuated in MDMA preconditioned animals. Preconditioning with MDMA (10 mg/kg, i.p.) daily for 4 days provided neuroprotection against methamphetamine-induced 5-HT depletion, but not DA depletion, in the striatum. Additional studies were conducted to exclude the possibility that alterations in MDMA pharmacokinetics or MDMA induced hyperthermia in rats previously exposed to MDMA contributes towards neuroprotection. During the administration of the 5-HT depleting regimen of MDMA, there was no difference in the extracellular concentration of the drug in the striatum of rats that had received 4 prior, daily injections of vehicle or MDMA. Moreover, there was no difference in the hyperthermic response to the 5-HT depleting regimen of MDMA in rats that had earlier received 4 daily injections of vehicle or MDMA. Furthermore, hyperthermia induced by MDMA during preconditioning appears not to contribute toward neuroprotection, inasmuch as preconditioning with MDMA at a low ambient temperature at which hyperthermia was absent did not alter the neuroprotection provided by the preconditioning regimen. Thus, prior exposure to MDMA affords protection against the long-term depletion of brain 5-HT

  20. Dance Clubbing on MDMA and during Abstinence from Ecstasy/MDMA: Prospective Neuroendocrine and Psychobiological Changes

    PubMed Central

    Parrott, A.C.; Lock, J.; Conner, A.C.; Kissling, C.; Thome, J.

    2013-01-01

    Background/Aims The present study is the first to prospectively compare a group of recreational Ecstasy users when dance clubbing on 3,4-methylenedioxymethamphetamine (MDMA) and when clubbing during abstinence from Ecstasy/MDMA. Methods Twelve normal healthy volunteers (mean age = 23.2 years) were assessed at a Saturday night dance club under self-administered MDMA. On the other weekend they went to the same dance club without taking MDMA (order counterbalanced). Both conditions involved 5 test sessions conducted at similar times: pre-drug baseline, 1 h post-drug clubbing, 2.5 h post-drug clubbing, and 2 and 4 days later. The assessments included body and ambient temperature, physical activity (pedometer), as well as self-ratings for mood state, physical activity, thermal comfort and thirst. Saliva samples were analyzed for MDMA, cortisol and testosterone. Results The cortisol levels increased significantly by 800% when dance clubbing on MDMA, while testosterone increased significantly by 75%; neither neuroendocrine measure was altered during abstinence. Saliva analyses confirmed the presence of MDMA when dancing on Ecstasy and its absence when dancing off Ecstasy. The pedometer values and self-rated levels of dancing were similar at both weekends. Hot and cold flushes and feeling hot increased significantly under MDMA. The mean body temperature did not change significantly, although there was a borderline trend for increased values after MDMA. Feelings of happiness and excitement increased under MDMA, although they were not significantly greater than when clubbing during abstinence. Conclusions Neurohormonal release may be an important part of the acute MDMA experience. The large cortisol increase provides further data on the bioenergetic stress model of recreational Ecstasy/MDMA. PMID:18654086

  1. MDMA and the "ecstasy paradigm".

    PubMed

    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.

  2. Behavioural and neurochemical comparison of chronic intermittent cathinone, mephedrone and MDMA administration to the rat.

    PubMed

    Shortall, Sinead E; Macerola, Alice E; Swaby, Rabbi T R; Jayson, Rebecca; Korsah, Chantal; Pillidge, Katharine E; Wigmore, Peter M; Ebling, Francis J P; Richard Green, A; Fone, Kevin C F; King, Madeleine V

    2013-09-01

    The synthetic cathinone derivative, mephedrone, is a controlled substance across Europe. Its effects have been compared by users to 3,4-methylenedioxymethamphetamine (MDMA), but little data exist on its pharmacological properties. This study compared the behavioural and neurochemical effects of mephedrone with cathinone and MDMA in rats. Young-adult male Lister hooded rats received i.p. cathinone (1 or 4 mg/kg), mephedrone (1, 4 or 10mg/kg) or MDMA (10mg/kg) on two consecutive days weekly for 3 weeks or as a single acute injection (for neurochemical analysis). Locomotor activity (LMA), novel object discrimination (NOD), conditioned emotional response (CER) and prepulse inhibition of the acoustic startle response (PPI) were measured following intermittent drug administration. Dopamine, 5-hydroxytryptamine (5-HT) and their major metabolites were measured in striatum, frontal cortex and hippocampus by high performance liquid chromatography 7 days after intermittent dosing and 2h after acute injection. Cathinone (1, 4 mg/kg), mephedrone (10mg/kg) and MDMA (10mg/kg) induced hyperactivity following the first and sixth injections and sensitization to cathinone and mephedrone occurred with chronic dosing. All drugs impaired NOD and mephedrone (10mg/kg) reduced freezing in response to contextual re-exposure during the CER retention trial. Acute MDMA reduced hippocampal 5-HT and 5-HIAA but the only significant effect on dopamine, 5-HT and their metabolites following chronic dosing was altered hippocampal 3,4-dihydroxyphenylacetic acid (DOPAC), following mephedrone (4, 10mg/kg) and MDMA. At the doses examined, mephedrone, cathinone, and MDMA induced similar effects on behaviour and failed to induce neurotoxic damage when administered intermittently over 3 weeks.

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

    PubMed Central

    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

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

    PubMed

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

    2014-08-01

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

  5. MDMA decreases the effects of simulated social rejection.

    PubMed

    Frye, Charles G; Wardle, Margaret C; Norman, Greg J; de Wit, Harriet

    2014-02-01

    3-4-Methylenedioxymethamphetamine (MDMA) increases self-reported positive social feelings and decreases the ability to detect social threat in faces, but its effects on experiences of social acceptance and rejection have not been determined. We examined how an acute dose of MDMA affects subjective and autonomic responses to simulated social acceptance and rejection. We predicted that MDMA would decrease subjective responses to rejection. On an exploratory basis, we also examined the effect of MDMA on respiratory sinus arrhythmia (RSA), a measure of parasympathetic cardiac control often thought to index social engagement and emotional regulation. Over three sessions, healthy adult volunteers with previous MDMA experience (N=36) received capsules containing placebo, 0.75 or 1.5 mg/kg of MDMA under counter-balanced double-blind conditions. During expected peak drug effect, participants played two rounds of a virtual social simulation task called "Cyberball" during which they experienced acceptance in one round and rejection in the other. During the task we also obtained electrocardiograms (ECGs), from which we calculated RSA. After each round, participants answered questionnaires about their mood and self-esteem. As predicted, MDMA decreased the effect of simulated social rejection on self-reported mood and self-esteem and decreased perceived intensity of rejection, measured as the percent of ball tosses participants reported receiving. Consistent with its sympathomimetic properties, MDMA decreased RSA as compared to placebo. Our finding that MDMA decreases perceptions of rejection in simulated social situations extends previous results indicating that MDMA reduces perception of social threat in faces. Together these findings suggest a cognitive mechanism by which MDMA might produce pro-social behavior and feelings and how the drug might function as an adjunct to psychotherapy. These phenomena merit further study in non-simulated social environments.

  6. MDMA (Ecstasy/Molly)

    MedlinePlus

    ... is a synthetic drug that alters mood and perception (awareness of surrounding objects and conditions). It is ... pleasure, emotional warmth, and distorted sensory and time perception. MDMA was initially popular in the nightclub scene ...

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

    PubMed

    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.

  8. Involvement of NMDA glutamate receptors in the acquisition and reinstatement of the conditioned place preference induced by MDMA.

    PubMed

    García-Pardo, Maria P; Escobar-Valero, Carla; Rodríguez-Arias, Marta; Miñarro, Jose; Aguilar, Maria A

    2015-08-01

    Some 3,4-methylenedioxymethamphetamine (MDMA) users become dependent as a result of chronic consumption. A greater understanding of the neurobiological basis of the rewarding effects of MDMA could contribute to developing effective pharmacotherapies for MDMA-related problems. The present study evaluated the role of N-methyl-D-aspartate (NMDA) glutamate receptors (NMDARs) in the acquisition and reinstatement of conditioned place preference (CPP) induced by MDMA. Adolescent male mice were conditioned with 1 or 10 mg/kg MDMA and pretreated with 5 or 10 mg/kg of the NMDAR antagonist memantine during acquisition of conditioning (experiment 1), or before a reinstatement test (experiment 2). In addition, the effects of memantine on acquisition of chocolate-induced CPP and the effects of memantine and MDMA on a passive avoidance task were evaluated. Memantine did not exert any motivational effects, but blocked the acquisition of MDMA-induced CPP. Moreover, following acquisition and extinction of MDMA-induced CPP, memantine did not induce reinstatement but blocked reinstatement of the CPP induced by priming with MDMA. Memantine did not block the CPP induced by chocolate, and it partially reversed the impairing effects of MDMA on memory. Our results demonstrate that NMDARs are involved in acquisition of the conditioned rewarding effects of MDMA and in priming-induced reinstatement of CPP following extinction. Moreover, they suggest the validity of memantine for the treatment of MDMA abuse.

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

    PubMed

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

    2014-03-01

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

  10. Effects of MDMA and Intranasal oxytocin on social and emotional processing.

    PubMed

    Kirkpatrick, Matthew G; Lee, Royce; Wardle, Margaret C; Jacob, Suma; de Wit, Harriet

    2014-06-01

    MDMA (± 3,4-methylenedioxymethamphetamine, 'ecstasy') is used recreationally, reportedly because it increases feelings of empathy, sociability, and interpersonal closeness. One line of evidence suggests that MDMA produces these effects by releasing oxytocin, a peptide involved in social bonding. In the current study, we investigated the acute effects of MDMA and oxytocin on social and emotional processing in healthy human volunteers. MDMA users (N = 65) participated in a 4-session, within-between-subjects study in which they received oral MDMA (0.75, 1.5 mg/kg), intranasal oxytocin (20 or 40 IU), or placebo under double-blind conditions. The primary outcomes included measures of emotion recognition and sociability (desire to be with others). Cardiovascular and subjective effects were also assessed. As expected, MDMA dose-dependently increased heart rate and blood pressure and feelings of euphoria (eg, 'High' and 'Like Drug'). On measures of social function, MDMA impaired recognition of angry and fearful facial expressions, and the larger dose (1.5 mg/kg) increased desire to be with others, compared with placebo. Oxytocin produced small but significant increases in feelings of sociability and enhanced recognition of sad facial expressions. Additionally, responses to oxytocin were related to responses to MDMA with subjects on two subjective measures of sociability. Thus, MDMA increased euphoria and feelings of sociability, perhaps by reducing sensitivity to subtle signs of negative emotions in others. The present findings provide only limited support for the idea that oxytocin produces the prosocial effects of MDMA.

  11. Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats.

    PubMed

    Shen, Erica Y; Ali, Syed F; Meyer, Jerrold S

    2011-12-01

    Most recreational users of 3, 4-methylenedioxymethamphetamine (MDMA or "ecstasy") also take cannabis, in part because cannabis can reduce the dysphoric symptoms of the ecstasy come-down such as agitation and insomnia. Although previous animal studies have examined the acute effects of co-administering MDMA and Δ(9)-tetrahydrocannabinol (THC), which is the major psychoactive ingredient in cannabis, research on chronic exposure to this drug combination is lacking. Therefore, the present study was conducted to investigate the effects of chronic adolescent administration of both THC and MDMA on behavior and on regional serotonin transporter (SERT) binding and serotonin (5-HT) concentrations as indices of serotonergic system integrity. Male Sprague-Dawley rats were divided into four drug administration groups: (1) MDMA alone, (2) THC alone, (3) MDMA plus THC, and (4) vehicle controls. MDMA (2 × 10 mg/kg × 4 h) was administered every fifth day from postnatal day (PD) 35 to 60 to simulate intermittent recreational ecstasy use, whereas THC (5mg/kg) was given once daily over the same time period to simulate heavy cannabis use. THC unexpectedly produced a modest hyperthermic effect when administered alone, but in animals co-treated with both THC and MDMA, there was an attenuation of MDMA-induced hyperthermia on dosing days. Subsequent testing conducted after a drug washout period revealed that THC reduced MDMA-related behavioral changes in the emergence and social interaction tests of anxiety-like behavior and also blunted the MDMA-induced decrease in exploratory behavior in the hole-board test. THC additionally attenuated MDMA -induced decreases in 5-HT levels and in SERT binding in the frontal cortex, parietal cortex, and striatum, but not in the hippocampus. These results suggest that chronic co-administration of THC during adolescence can provide some protection against various adverse physiological, behavioral, and neurochemical effects produced by MDMA. PMID

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

    PubMed

    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.

  13. Saturday night fever in ecstasy/MDMA dance clubbers: Heightened body temperature and associated psychobiological changes

    PubMed Central

    Parrott, Andrew C; Young, Lucy

    2014-01-01

    Aims and rationale: to investigate body temperature and thermal self-ratings of Ecstasy/MDMA users at a Saturday night dance club. Methods: 68 dance clubbers (mean age 21.6 years, 30 females and 38 males), were assessed at a Saturday night dance club, then 2–3 d later. Three subgroups were compared: 32 current Ecstasy users who had taken Ecstasy/MDMA that evening, 10 abstinent Ecstasy/MDMA users on other psychoactive drugs, and 26 non-user controls (predominantly alcohol drinkers). In a comparatively quiet area of the dance club, each unpaid volunteer had their ear temperature recorded, and completed a questionnaire on thermal feelings and mood states. A similar questionnaire was repeated 2–3 d later by mobile telephone. Results: Ecstasy/MDMA users had a mean body temperature 1.2°C higher than non-user controls (P < 0.001), and felt significantly hotter and thirstier. The abstinent Ecstasy/MDMA polydrug user group had a mean body temperature intermediate between the other 2 groups, significantly higher than controls, and significantly lower than current Ecstasy/MDMA users. After 2–3 d of recovery, the Ecstasy/MDMA users remained significantly ‘thirstier’. Higher body temperature while clubbing was associated with greater Ecstasy/MDMA usage at the club, and younger age of first use. Higher temperature also correlated with lower elation and poor memory 2–3 d later. It also correlated positively with nicotine, and negatively with cannabis. Conclusions: Ecstasy/MDMA using dance clubbers had significantly higher body temperature than non-user controls. This heightened body temperature was associated with a number of adverse psychobiological consequences, including poor memory. PMID:27626048

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

    ERIC Educational Resources Information Center

    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…

  15. Adult heavy and low users of dental services: treatment provided.

    PubMed

    Nihtilä, Annamari; Widström, Eeva; Elonheimo, Outi

    2016-01-01

    The aim of this study was to compare treatment provided to adult heavy and low users of dental services in the Finnish Public Dental Service (PDS) and to analyse changes in patients' oral health status. We assigned all adults who attended the PDS in Espoo in 2004 to a group of heavy users (n = 3,173) if they had made six or more dental visits and to a comparison group of low users (n = 22,820), if they had made three or fewer dental visits. Data were obtained from the patient register of the PDS. A sample of 320 patients was randomly selected from each group. Baseline information (year 2004) on age, sex, number and types of visits, oral health status and treatment provided was collected from treatment records. Both groups were followed-up for five years. Restorative treatment measures dominated the heavy and low users'treatments; 88.8% of heavy users and 79.6% low users had received restorations during the five-year period. Fixed prosthetic treatments were provided to just 2% of the heavy users and 0.8% of the low users. Emergency visits were more common for heavy users (74.8%) than for low users (21.6%) (p < 0.001). Fewer than half of the heavy (46.1%) or low (46.5%) users were examined twice. Typical for heavy use of oral health services was a cycle of repetitive repair or replacement of restorations, often as emergency treatment, a lack of proper examinations and preventive care; crown therapy was seldom used. Immediately after the major dental care reform in Finland, the PDS in Espoo had problems providing good quality dental care for the new adult patients. Older patients with lower social class background were not accustomed to regular dental care and the PDS did not actively propose proper comprehensive regular care for adults.

  16. Adult heavy and low users of dental services: treatment provided.

    PubMed

    Nihtilä, Annamari; Widström, Eeva; Elonheimo, Outi

    2016-01-01

    The aim of this study was to compare treatment provided to adult heavy and low users of dental services in the Finnish Public Dental Service (PDS) and to analyse changes in patients' oral health status. We assigned all adults who attended the PDS in Espoo in 2004 to a group of heavy users (n = 3,173) if they had made six or more dental visits and to a comparison group of low users (n = 22,820), if they had made three or fewer dental visits. Data were obtained from the patient register of the PDS. A sample of 320 patients was randomly selected from each group. Baseline information (year 2004) on age, sex, number and types of visits, oral health status and treatment provided was collected from treatment records. Both groups were followed-up for five years. Restorative treatment measures dominated the heavy and low users'treatments; 88.8% of heavy users and 79.6% low users had received restorations during the five-year period. Fixed prosthetic treatments were provided to just 2% of the heavy users and 0.8% of the low users. Emergency visits were more common for heavy users (74.8%) than for low users (21.6%) (p < 0.001). Fewer than half of the heavy (46.1%) or low (46.5%) users were examined twice. Typical for heavy use of oral health services was a cycle of repetitive repair or replacement of restorations, often as emergency treatment, a lack of proper examinations and preventive care; crown therapy was seldom used. Immediately after the major dental care reform in Finland, the PDS in Espoo had problems providing good quality dental care for the new adult patients. Older patients with lower social class background were not accustomed to regular dental care and the PDS did not actively propose proper comprehensive regular care for adults. PMID:27464379

  17. Methylenedioxymethamphetamine (MDMA, ‘Ecstasy’): Neurodegeneration versus Neuromodulation

    PubMed Central

    Puerta, Elena; Aguirre, Norberto

    2011-01-01

    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.

  18. Designing User Interfaces for Older Adults.

    ERIC Educational Resources Information Center

    Hutchison, Douglas; And Others

    1997-01-01

    Of 45 adults over 50 who had computer experience, 44% reported difficulty reading screens, 53% were frustrated by complex software, and 27% had difficulty with the mouse. The physical characteristics of aging should be considered in designing special software features such as dynamic text resizing and menu buttons instead of pull-down menus. (SK)

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

    PubMed

    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.

  20. Human Pharmacology of Mephedrone in Comparison with MDMA.

    PubMed

    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.

  1. Human Pharmacology of Mephedrone in Comparison with MDMA.

    PubMed

    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. PMID:27206266

  2. Musical FAVORS: Reintroducing music to adult cochlear implant users.

    PubMed

    Plant, Geoff

    2015-09-01

    Music represents a considerable challenge for many adult users of cochlear implants (CIs). Around half of adult CI users report that they do not find music enjoyable, and, in some cases, despite enhanced speech perception skills, this leads to considerable frustration and disappointment for the CI user. This paper presents suggestions to improve the musical experiences of deafened adults with CIs. Interviews with a number of adult CI users revealed that there were a number of factors which could lead to enhanced music experiences. The acronym FAVORS (familiar music, auditory-visual access, open-mindedness, and simple arrangements) summarizes the factors that have been identified, which can help CI users in their early music listening experiences. Each of these factors is discussed in detail, along with suggestions for how they can be used in therapy sessions. The use of a group approach (music focus groups) is also discussed and an overview of the approach and exercises used is presented. The importance of live music experiences is also discussed.

  3. Musical FAVORS: Reintroducing music to adult cochlear implant users.

    PubMed

    Plant, Geoff

    2015-09-01

    Music represents a considerable challenge for many adult users of cochlear implants (CIs). Around half of adult CI users report that they do not find music enjoyable, and, in some cases, despite enhanced speech perception skills, this leads to considerable frustration and disappointment for the CI user. This paper presents suggestions to improve the musical experiences of deafened adults with CIs. Interviews with a number of adult CI users revealed that there were a number of factors which could lead to enhanced music experiences. The acronym FAVORS (familiar music, auditory-visual access, open-mindedness, and simple arrangements) summarizes the factors that have been identified, which can help CI users in their early music listening experiences. Each of these factors is discussed in detail, along with suggestions for how they can be used in therapy sessions. The use of a group approach (music focus groups) is also discussed and an overview of the approach and exercises used is presented. The importance of live music experiences is also discussed. PMID:26561887

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

    PubMed

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

    2014-08-01

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

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

    PubMed

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

    2014-08-01

    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is used recreationally to improve mood and sociability, and has generated clinical interest as a possible adjunct to psychotherapy. One way that MDMA may produce positive 'prosocial' effects is by changing responses to emotional stimuli, especially stimuli with social content. Here, we examined for the first time how MDMA affects subjective responses to positive, negative and neutral emotional pictures with and without social content. We hypothesized that MDMA would dose-dependently increase reactivity to positive emotional stimuli and dampen reactivity to negative stimuli, and that these effects would be most pronounced for pictures with people in them. The data were obtained from two studies using similar designs with healthy occasional MDMA users (total N = 101). During each session, participants received MDMA (0, 0.75 and 1.5 mg/kg oral), and then rated their positive and negative responses to standardized positive, negative and neutral pictures with and without social content. MDMA increased positive ratings of positive social pictures, but reduced positive ratings of non-social positive pictures. We speculate this 'socially selective' effect contributes to the prosocial effects of MDMA by increasing the comparative value of social contact and closeness with others. This effect may also contribute to its attractiveness to recreational users. PMID:24682132

  6. Chronic exposure to ethanol exacerbates MDMA-induced hyperthermia and exposes liver to severe MDMA-induced toxicity in CD1 mice.

    PubMed

    Pontes, Helena; Duarte, José Alberto; de Pinho, Paula Guedes; Soares, Maria Elisa; Fernandes, Eduarda; Dinis-Oliveira, Ricardo Jorge; Sousa, Carla; Silva, Renata; Carmo, Helena; Casal, Susana; Remião, Fernando; Carvalho, Félix; Bastos, Maria Lourdes

    2008-10-30

    3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is an amphetamine derivative drug with entactogenic, empathogenic and hallucinogenic properties, commonly consumed at rave parties in a polydrug abuse pattern, especially with cannabis, tobacco and ethanol. Since both MDMA and ethanol may cause deleterious effects to the liver, the evaluation of their putative hepatotoxic interaction is of great interest, especially considering that most of the MDMA users are regular ethanol consumers. Thus, the aim of the present study was to evaluate, in vivo, the acute hepatotoxic effects of MDMA (10mg/kg i.p.) in CD-1 mice previously exposed to 12% ethanol as drinking fluid (for 8 weeks). Body temperature was continuously measured for 12h after MDMA administration and, after 24h, hepatic damage was evaluated. The administration of MDMA to non pre-treated mice resulted in sustained hyperthermia, which was significantly increased in ethanol pre-exposed mice. A correspondent higher increase of hepatic heat shock transcription factor (HSF-1) activation was also observed in the latter group. Furthermore, MDMA administration resulted in liver damage as confirmed by histological analysis, slight decrease in liver weight and increased plasma transaminases levels. These hepatotoxic effects were also exacerbated when mice were pre-treated with ethanol. The activities of some antioxidant enzymes (such as SOD, GPx and Catalase) were modified by ethanol, MDMA and their joint action. The hepatotoxicity resulting from the simultaneous exposure to MDMA and ethanol was associated with a higher activation of NF-kappaB, indicating a pro-inflammatory effect in this organ. In conclusion, the obtained results strongly suggest that the consumption of ethanol increases the hyperthermic and hepatotoxic effects associated with MDMA abuse.

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

    PubMed

    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.

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

    PubMed

    Heifets, Boris D; Malenka, Robert C

    2016-07-14

    MDMA, better known as the recreational drug "ecstasy," is well known for stimulating a feeling of closeness and empathy in its users. We advocate that exploring its mechanism of action could lead to new treatments for psychiatric conditions characterized by impairments in social behavior. PMID:27419864

  9. MDMA, cannabis, and cocaine produce acute dissociative symptoms.

    PubMed

    van Heugten-Van der Kloet, Dalena; Giesbrecht, Timo; van Wel, Janelle; Bosker, Wendy M; Kuypers, Kim P C; Theunissen, Eef L; Spronk, Desirée B; Jan Verkes, Robbert; Merckelbach, Harald; Ramaekers, Johannes G

    2015-08-30

    Some drugs of abuse may produce dissociative symptoms, but this aspect has been understudied. We explored the dissociative potential of three recreational drugs (3,4-methylenedioxymethamphetamine (MDMA), cannabis, and cocaine) during intoxication and compared their effects to literature reports of dissociative states in various samples. Two placebo-controlled studies were conducted. In Study 1 (N=16), participants received single doses of 25, 50, and 100 mg of MDMA, and placebo. In Study 2 (N=21), cannabis (THC 300 µg/kg), cocaine (HCl 300 mg), and placebo were administered. Dissociative symptoms as measured with the Clinician-Administered Dissociative States Scale (CADSS) significantly increased under the influence of MDMA and cannabis. To a lesser extent, this was also true for cocaine. Dissociative symptoms following MDMA and cannabis largely exceeded those observed in schizophrenia patients, were comparable with those observed in Special Forces soldiers undergoing survival training, but were lower compared with ketamine-induced dissociation. Cocaine produced dissociative symptoms that were comparable with those observed in schizophrenia patients, but markedly less than those in Special Forces soldiers and ketamine users. Thus, MDMA and cannabis can produce dissociative symptoms that resemble dissociative pathology. The study of drug induced dissociation is important, because it may shed light on the mechanisms involved in dissociative psychopathology.

  10. MDMA, cannabis, and cocaine produce acute dissociative symptoms.

    PubMed

    van Heugten-Van der Kloet, Dalena; Giesbrecht, Timo; van Wel, Janelle; Bosker, Wendy M; Kuypers, Kim P C; Theunissen, Eef L; Spronk, Desirée B; Jan Verkes, Robbert; Merckelbach, Harald; Ramaekers, Johannes G

    2015-08-30

    Some drugs of abuse may produce dissociative symptoms, but this aspect has been understudied. We explored the dissociative potential of three recreational drugs (3,4-methylenedioxymethamphetamine (MDMA), cannabis, and cocaine) during intoxication and compared their effects to literature reports of dissociative states in various samples. Two placebo-controlled studies were conducted. In Study 1 (N=16), participants received single doses of 25, 50, and 100 mg of MDMA, and placebo. In Study 2 (N=21), cannabis (THC 300 µg/kg), cocaine (HCl 300 mg), and placebo were administered. Dissociative symptoms as measured with the Clinician-Administered Dissociative States Scale (CADSS) significantly increased under the influence of MDMA and cannabis. To a lesser extent, this was also true for cocaine. Dissociative symptoms following MDMA and cannabis largely exceeded those observed in schizophrenia patients, were comparable with those observed in Special Forces soldiers undergoing survival training, but were lower compared with ketamine-induced dissociation. Cocaine produced dissociative symptoms that were comparable with those observed in schizophrenia patients, but markedly less than those in Special Forces soldiers and ketamine users. Thus, MDMA and cannabis can produce dissociative symptoms that resemble dissociative pathology. The study of drug induced dissociation is important, because it may shed light on the mechanisms involved in dissociative psychopathology. PMID:26003508

  11. Young adults as users of adult healthcare: experiences of young adults with complex or life-limiting conditions.

    PubMed

    Beresford, B; Stuttard, L

    2014-08-01

    Awareness is growing that young adults may have distinctive experiences of adult healthcare and that their needs may differ from those of other adult users. In addition, the role of adult health teams in supporting positive transitions from paediatrics is increasingly under discussion. This paper contributes to these debates. It reports a qualitative study of the experiences of young adults - all with complex chronic health conditions - as users of adult health services. Key findings from the study are reported, including an exploration of factors that help to explain interviewees' experiences. Study findings are discussed in the context of existing evidence from young adults in adult healthcare settings and theories of 'young adulthood'. Implications for training and practice are considered, and priorities for future research are identified.

  12. Intake of micronutrients among Danish adult users and non-users of dietary supplements

    PubMed Central

    Tetens, Inge; Biltoft-Jensen, Anja; Spagner, Camilla; Christensen, Tue; Gille, Maj-Britt; Bügel, Susanne; Banke Rasmussen, Lone

    2011-01-01

    Objectives To evaluate the intake of micronutrients from the diet and from supplements in users and non-users of dietary supplements, respectively, in a representative sample of the Danish adult population. A specific objective was to identify the determinants of supplement use. Design A cross-sectional representative national study of the intake of vitamins and minerals from the diet and from dietary supplements. Method The Danish National Survey of Dietary Habits and Physical Activity, 2000–2004. Participants (n=4,479; 53% females) aged 18–75 years gave information about the use of dietary supplements in a personal interview. The quantification of the micronutrient contribution from supplements was estimated from a generic supplement constructed from data on household purchases. Nutrient intakes from the diet were obtained from a self-administered 7-day pre-coded dietary record. Median intakes of total nutrients from the diets of users and non-users of supplements were analysed using the Wilcoxon rank-sum test. Results Sixty percent of females and 51% of males were users of supplements. With the exception of vitamin D, the intake of micronutrients from the diet was adequate at the group level for all age and gender groups. Among females in the age group 18–49 years, the micronutrient intake from the diet was significantly higher compared with the non-users of dietary supplements. The use of dietary supplements increased with age and with ‘intention to eat healthy.’ Conclusion Intake of micronutrients from the diet alone was considered adequate for both users and non-users of dietary supplements. Younger females who were supplement users had a more micronutrient-dense diet compared to non-users. PMID:21909288

  13. MDMA intoxication and verbal memory performance: a placebo-controlled pharmaco-MRI study.

    PubMed

    Kuypers, Kim P C; Wingen, Marleen; Heinecke, Armin; Formisano, Elia; Ramaekers, Johannes G

    2011-08-01

    The aim of the present study was to identify the neural substrate underlying memory impairment due to a single dose of MDMA (3,4-methylenedioxymethamphetamine) by means of pharmaco-MRI. Based on previous behavioral results it was hypothesized that this deficit could be attributed to a specific influence of MDMA on encoding. Fourteen Ecstasy users participated in this double-blind, placebo-controlled, within-subject study with two treatment conditions: MDMA (75 mg) and placebo. Memory performance was tested by means of a word learning task including two words lists, one addressing reading processes (control task, CWL) and a second (experimental task, EWL) addressing encoding and reading processes. Behavioral data showed that under the influence of MDMA, EWL performance was worse than placebo. Imaging data showed that Encoding was situated mainly in (pre)frontal, temporal and parietal areas. MDMA by Encoding interaction was situated in three areas: the left middle frontal gyrus (BA10), the right fusiform gyrus (BA19), and the left cuneus (BA18). Behavioral and functional data only correlated in BA10. It appeared that EWL performance caused BOLD signal change in BA10 during placebo treatment but not during MDMA intoxication. It is concluded that MDMA influences middle frontal gyrus processes resulting in impoverished memory encoding.

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

    PubMed

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

    2014-01-01

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

  15. Audio-vocal responses elicited in adult cochlear implant users

    PubMed Central

    Loucks, Torrey M.; Suneel, Deepa; Aronoff, Justin M.

    2015-01-01

    Auditory deprivation experienced prior to receiving a cochlear implant could compromise neural connections that allow for modulation of vocalization using auditory feedback. In this report, pitch-shift stimuli were presented to adult cochlear implant users to test whether compensatory motor changes in vocal F0 could be elicited. In five of six participants, rapid adjustments in vocal F0 were detected following the stimuli, which resemble the cortically mediated pitch-shift responses observed in typical hearing individuals. These findings suggest that cochlear implants can convey vocal F0 shifts to the auditory pathway that might benefit audio-vocal monitoring. PMID:26520350

  16. Contextual profiles of young adult Ecstasy users: a multisite study

    PubMed Central

    Ramtekkar, Ujjwal P.; Striley, Catherine W; Cottler, Linda B

    2010-01-01

    These analyses assess contextual profiles of 612 young adult Ecstasy users, 18–30 years of age, from St. Louis (USA), Miami (USA) and Sydney (Australia). Bivariate analyses revealed different contextual factors influencing Ecstasy use. Friends were the most common sources of Ecstasy at all sites and most used with friends. St. Louis and Miami use mostly occurred in residences, whereas in Sydney use was mostly at clubs, bars or restaurants. Ecstasy consumption at public places and in cars, trains or ferries was significantly higher in Miami (89% and 77%) than in St. Louis (67% and 65%) and Sydney (67% and 61%). At all sites, simultaneous use of LSD/mushroom and nitrous oxide with Ecstasy was common; concurrent amphetamines predominated in Sydney and heroin/opiates in St. Louis Contextual factors influencing Ecstasy use among young adults vary by geographic region. Their inclusion may help tailor effective prevention programs to reduce or ameliorate Ecstasy use. PMID:21094585

  17. Expression of bax and bcl2 Genes in MDMA-induced Hepatotoxicity on Rat Liver Using Quantitative Real-Time PCR Method through Triggering Programmed Cell Death

    PubMed Central

    Behroozaghdam, Mitra; Hashemi, Mehrdad; Javadi, Gholamreza; Mahdian, Reza; Soleimani, Mansoureh

    2015-01-01

    Background: 3-4methylenedioxymethamphetamine (MDMA) is a synthetic and psychoactive drug, which is known popularly as Ecstasy and has toxic effects on human organs. Objectives: Considering the potential toxic interaction, this study was performed to quantify the expression of bax and bcl2 genes in MDMA-induced hepatotoxicity on rat liver. Subsequently, we evaluated pentoxifylline as a possible protective drug on hepatotoxicity. Materials and Methods: Adult male Wistar rats weighting 250 - 300 grams were used in the study. The rats were equally distributed into four experimental groups (5 rat/group). MDMA was dissolved in PBS and injected intraperitoneally (IP) including untreated control, MDMA (MDMA dissolved in PBS), treated-1 (MDMA followed by PTX) and treated-2 (PTX followed by MDMA). All animals given MDMA received 3 doses of 7.5mg/kg with two hours gap between doses. Liver tissue was removed after anaesthetizing. Subsequently, RNA isolation, cDNA synthesis and Real-Time PCR were performed. Finally, data analyzed statistically to determine significantly differences between the groups (P value < 0.05). Results: Using Real-Time quantitative PCR results, the gene expression ratio of bcl2 were calculated 93.80±20.64, 340.45 ± 36.60 and 47.13 ± 5.84 fold in MDMA, treated-1 and treated-2 groups, respectively. Furthermore, this ratio for bax gene obtained 2.13±0.33 fold in MDMA, 1.55 ± 0.26 fold in treated-1 and 10.44 ± 1.56 fold in treated-2 groups. Conclusions: The present study focused on molecular mechanism of MDMA in programmed cell death using gene expression quantification of a pro-apoptotic and anti-apoptoic gene in MDMA-induced hepatotoxocity. The results showed that MDMA prompted apoptosis in liver and pentoxifylline protected against hepatotoxicity before and after taking MDMA. PMID:26732379

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

    PubMed

    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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24654568

  20. MDMA enhances emotional empathy and prosocial behavior.

    PubMed

    Hysek, Cédric M; Schmid, Yasmin; Simmler, Linda D; Domes, Gregor; Heinrichs, Markus; Eisenegger, Christoph; Preller, Katrin H; Quednow, Boris B; Liechti, Matthias E

    2014-11-01

    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') releases serotonin and norepinephrine. MDMA is reported to produce empathogenic and prosocial feelings. It is unknown whether MDMA in fact alters empathic concern and prosocial behavior. We investigated the acute effects of MDMA using the Multifaceted Empathy Test (MET), dynamic Face Emotion Recognition Task (FERT) and Social Value Orientation (SVO) test. We also assessed effects of MDMA on plasma levels of hormones involved in social behavior using a placebo-controlled, double-blind, random-order, cross-over design in 32 healthy volunteers (16 women). MDMA enhanced explicit and implicit emotional empathy in the MET and increased prosocial behavior in the SVO test in men. MDMA did not alter cognitive empathy in the MET but impaired the identification of negative emotions, including fearful, angry and sad faces, in the FERT, particularly in women. MDMA increased plasma levels of cortisol and prolactin, which are markers of serotonergic and noradrenergic activity, and of oxytocin, which has been associated with prosocial behavior. In summary, MDMA sex-specifically altered the recognition of emotions, emotional empathy and prosociality. These effects likely enhance sociability when MDMA is used recreationally and may be useful when MDMA is administered in conjunction with psychotherapy in patients with social dysfunction or post-traumatic stress disorder.

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

    PubMed

    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.

  2. Anthropometric data of adult wheelchair users for Mexican population.

    PubMed

    Lucero-Duarte, Karla; de la Vega-Bustillos, Enrique; López-Millán, Francisco; Soto-Félix, Selene

    2012-01-01

    The aim of the study was to obtain anthropometric data of adult wheelchair users at Mexico. This study count with 108 disabled people (56 men and 52 women) using the wheelchair and having the upper extremities sufficiently efficient to perform professional activities. The subjects were aged 18-60. From the measurements obtained, it can be said that in each of these measures was observed that men have larger dimensions than women, except for body depth, in which women had a slightly greater difference. When comparing the data in this study against other studies it shows that there is a significant difference between the averages of these studies. Similar results were obtained when comparing our data against data of standard population. Anthropometric data obtained through this study appear to be the only of this kind in Mexico and showed significant differences between measures of disabled persons and standard persons. the use of these data may be helpful for the proper design of workstations designed for use by adults who use.

  3. Adolescent pre-exposure to ethanol or MDMA prolongs the conditioned rewarding effects of MDMA.

    PubMed

    Do Couto, B Ribeiro; Rodríguez-Arias, M; Fuentes, S; Gagliano, H; Armario, A; Miñarro, J; Aguilar, M A

    2011-07-01

    Adolescents often take ethanol (EtOH) in combination with MDMA (3,4-methylenedioxymethylamphetamine). In the present work we studied the effect of repeated intermittent adolescent pre-exposure to both drugs on the behavioral and neurochemical effects of MDMA in mice. Sixteen days after pre-treatment, the rewarding and reinstating effects of MDMA in the conditioned place preference (CPP) paradigm were evaluated, along with the levels of biogenic amines, basal motor activity and corticosterone response to different challenges. Pre-exposure to EtOH, MDMA or EtOH+MDMA did not affect the CPP induced by 10mg/kg of MDMA. However, adolescent exposure to EtOH or MDMA increased the duration of the conditioned rewarding effects of MDMA. Following extinction of the CPP, a priming dose of 5mg/kg of MDMA elicited reinstatement in all the groups, with the duration of this reinstated CPP being longer in mice pre-treated with MDMA. After reinstatement, an increase in monoamine levels was observed in mice pre-exposed to EtOH (DA, DOPAC and 5-HT in the striatum and 5-HIAA in the cortex and hippocampus) or MDMA (5-HT in the hippocampus). Basal motor activity and basal levels of corticosterone were not affected by any of these pre-treatments, but the group pre-exposed to MDMA showed higher levels of corticosterone in response to the administration of 10mg/kg of MDMA. Behavioral and hormonal effects of adolescent exposure to MDMA were reversed by co-administration of EtOH. Our results suggest that exposure to EtOH or MDMA during adolescence prolongs the rewarding properties of MDMA.

  4. Acquisition of MDMA self-administration: pharmacokinetic factors and MDMA-induced serotonin release.

    PubMed

    Bradbury, Sarah; Bird, Judith; Colussi-Mas, Joyce; Mueller, Melanie; Ricaurte, George; Schenk, Susan

    2014-09-01

    The current study aimed to elucidate the role of pharmacokinetic (PK) parameters and neurotransmitter efflux in explaining variability in (±) 3, 4-methylenedioxymethamphetamine (MDMA) self-administration in rats. PK profiles of MDMA and its major metabolites were determined after the administration of 1.0 mg/kg MDMA (iv) prior to, and following, the acquisition of MDMA self-administration. Synaptic levels of 5-hydroxytryptamine (5HT) and dopamine (DA) in the nucleus accumbens were measured following administration of MDMA (1.0 and 3.0 mg/kg, iv) using in vivo microdialysis and compared for rats that acquired or failed to acquire MDMA self-administration. Effects of the 5HT neurotoxin, 5,7 dihydroxytryptamine (5, 7-DHT), on the acquisition of MDMA and cocaine self-administration were also determined. In keeping with previous findings, approximately 50% of rats failed to meet a criterion for acquisition of MDMA self-administration. The PK profiles of MDMA and its metabolites did not differ between rats that acquired or failed to acquire MDMA self-administration. MDMA produced more overflow of 5HT than DA. The MDMA-induced 5HT overflow was lower in rats that acquired MDMA self-administration compared with those that did not acquire self-administration. In contrast, MDMA-induced DA overflow was comparable for the two groups. Prior 5,7-DHT lesions reduced tissue levels of 5HT and markedly increased the percentage of rats that acquired MDMA self-administration and also decreased the latency to acquisition of cocaine self-administration. These data suggest that 5HT limits the initial sensitivity to the positively reinforcing effects of MDMA and delays the acquisition of reliable self-administration.

  5. Oral administration of 3,4-methylenedioxymethamphetamine (MDMA) produces selective serotonergic depletion in the nonhuman primate.

    PubMed

    Ali, S F; Newport, G D; Scallet, A C; Binienda, Z; Ferguson, S A; Bailey, J R; Paule, M G; Slikker, W

    1993-01-01

    MDMA (3,4-methylenedioxymethamphetamine) has been reported to produce serotonergic depletion in nonhuman primates at doses as low as 2.5 mg/kg (1-2 times the typical human dose). The current study evaluated the dose-response relationships of MDMA (1.25-20.0 mg/kg) using regional concentrations of serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and home cage behavior as endpoints. Adult female rhesus monkeys (n = 16) were treated orally with 0, 1.25, 2.5, or 20.0 mg/kg MDMA twice daily for 4 consecutive days. Eighteen behaviors were measured in the home cage prior to, during, and after MDMA treatment. One month after the last dose, the animals were sacrificed and brains dissected into several regions for neurochemical analyses. 5-HT and 5-HIAA were analyzed via HPLC/EC. The lower doses of MDMA (1.25 and 2.5 mg/kg) did not significantly alter 5-HT or 5-HIAA concentrations in any brain region except hippocampus in which 5-HT concentrations were decreased after 2.5 mg/kg. MDMA at 20.0 mg/kg significantly decreased 5-HT and 5-HIAA concentrations in several cortical and midbrain structures. However, 5-HT and 5-HIAA concentrations in brain stem and hypothalamus were not significantly altered after any dose of MDMA. Combined with previous data from this laboratory, these results indicate that the decreased concentrations of 5-HT and 5-HIAA in selected brain regions show a selective dose-response relationship for MDMA-induced neurotoxicity as measured by serotonergic depletion in the nonhuman primate. PMID:7685472

  6. Cognitive impairments from developmental exposure to serotonergic drugs: citalopram and MDMA

    PubMed Central

    Schaefer, Tori L.; Grace, Curtis E.; Braun, Amanda A.; Amos-Kroohs, Robyn M.; Graham, Devon L.; Skelton, Matthew R.; Williams, Michael T.; Vorhees, Charles V.

    2015-01-01

    We previously showed that developmental 3,4-methylenedioxymethamphetamine (MDMA) treatment induces long-term spatial and egocentric learning and memory deficits and serotonin (5-HT) reductions. During brain development, 5-HT is a neurotrophic factor influencing neurogenesis, synaptogenesis, migration, and target field organization. MDMA (10 mg/kg×4/d at 2 h intervals) given on post-natal day (PD) 11–20 in rats (a period of limbic system development that approximates human third trimester brain development) induces 50% reductions in 5-HT during treatment and 20% reductions when assessed as adults. To determine whether the 5-HT reduction is responsible for the cognitive deficits, we used citalopram (Cit) pretreatment to inhibit the effects of MDMA on 5-HT reuptake in a companion study. Cit attenuated MDMA-induced 5-HT reductions by 50% (Schaefer et al., 2012). Here we tested whether Cit (5 or 7.5 mg/kg×2/d) pretreatment attenuates the cognitive effects of MDMA. Within each litter, different offspring were treated on PD11–20 with saline (Sal)+MDMA, Cit+MDMA, Cit+Sal or Sal+Sal. Neither spatial nor egocentric learning/memory was improved by Cit pretreatment. Unexpectedly, Cit+Sal (at both doses) produced spatial and egocentric learning deficits as severe as those caused by Sal+MDMA. These are the first data showing cognitive deficits resulting from developmental exposure to a selective serotonin reuptake inhibitor. These data indicate the need for further research on the long-term safety of antidepressants during pregnancy. PMID:23308402

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

    PubMed

    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. PMID:27067625

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

    PubMed

    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.

  9. Adolescent MDMA exposure diminishes the physiological and neurotoxic consequences of an MDMA binge in female rats.

    PubMed

    Piper, Brian J; Henderson, Christina S; Meyer, Jerrold S

    2014-07-01

    Intermittent MDMA pretreatment blocked the reductions in serotonin transporter (SERT) binding induced by an MDMA binge in a prior study in adolescent male rats. The objective of this investigation was to determine if the physiological, behavioral, and neurochemical responses to MDMA are sexually dimorphic. Female Sprague-Dawley rats received MDMA (10 mg/kg × 2) or Saline on every fifth day from postnatal day (PD) 35-60 and an MDMA binge (5 mg/kg × 4) on PD 67. The MDMA binge induced a pronounced temperature dysregulation in MDMA-naïve, but not MDMA-pretreated, groups. Similarly, MDMA-pretreated animals were resistant to the binge-induced SERT reductions, especially in the hippocampus. Motor activity at PD 68 was not reduced by the binge, unlike the responses found in males. These results show that female rats differ from males in their responses to an MDMA binge but are similar with respect to preconditioning from prior MDMA exposure.

  10. Childhood Conduct Problems and Other Early Risk Factors in Rural Adult Stimulant Users

    ERIC Educational Resources Information Center

    Kramer, Teresa L.; Han, Xiaotong; Leukefeld, Carl; Booth, Brenda M.; Edlund, Carrie

    2009-01-01

    Context: Understanding childhood risk factors associated with adult substance use and legal problems is important for treatment and prevention. Purpose: To examine the relationship of early substance use, conduct problems before age 15, and family history of substance abuse on adult outcomes in rural, stimulant users. Methods: Adult cocaine and…

  11. Designer Drug Confusion: A Focus on MDMA.

    ERIC Educational Resources Information Center

    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.…

  12. A Lead User Approach to Universal Design - Involving Older Adults in the Design Process.

    PubMed

    Raviselvam, Sujithra; Wood, Kristin L; Hölttä-Otto, Katja; Tam, Victoria; Nagarajan, Kamya

    2016-01-01

    The concept of Universal Design has received increasing appreciation over the past two decades. Yet, there are very few existing designs that cater to the needs of extraordinary users who experience some form of physical challenge. Previous work has shown promising results on involving users with physical challenges as lead users - users who have the potential to identify needs that could be latent among the general population. It has also been shown that older adults can act as such lead users. They can help design universal product ideas that satisfy both older adults and the general population. In this paper we build on this and examine if involving older adults in the design phase can result in universal products, products preferred by both older adults and the general population over a current option. Eighty-nine older adult participants and thirty-four general population participants took part in the study. Products were redesigned and prototyped based on the needs of older adults and tested among both populations. Results show that, although older adults and the general population did share certain needs and demands, the majority of older adults had needs and demands that were different from those of the general population. However, even though the needs differed between the populations, on average 89% of the general population participants preferred products designed based on design needs expressed by older adults over the current option. This provides further evidence supporting the use of older adults in designing products for all.

  13. A Lead User Approach to Universal Design - Involving Older Adults in the Design Process.

    PubMed

    Raviselvam, Sujithra; Wood, Kristin L; Hölttä-Otto, Katja; Tam, Victoria; Nagarajan, Kamya

    2016-01-01

    The concept of Universal Design has received increasing appreciation over the past two decades. Yet, there are very few existing designs that cater to the needs of extraordinary users who experience some form of physical challenge. Previous work has shown promising results on involving users with physical challenges as lead users - users who have the potential to identify needs that could be latent among the general population. It has also been shown that older adults can act as such lead users. They can help design universal product ideas that satisfy both older adults and the general population. In this paper we build on this and examine if involving older adults in the design phase can result in universal products, products preferred by both older adults and the general population over a current option. Eighty-nine older adult participants and thirty-four general population participants took part in the study. Products were redesigned and prototyped based on the needs of older adults and tested among both populations. Results show that, although older adults and the general population did share certain needs and demands, the majority of older adults had needs and demands that were different from those of the general population. However, even though the needs differed between the populations, on average 89% of the general population participants preferred products designed based on design needs expressed by older adults over the current option. This provides further evidence supporting the use of older adults in designing products for all. PMID:27534296

  14. The role of monoamines in the changes in body temperature induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives.

    PubMed

    Docherty, J R; Green, A R

    2010-07-01

    Hyperthermia is probably the most widely known acute adverse event that can follow ingestion of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) by recreational users. The effect of MDMA on body temperature is complex because the drug has actions on all three major monoamine neurotransmitters [5-hydroxytryptamine (5-HT), dopamine and noradrenaline], both by amine release and by direct receptor activation. Hyperthermia and hypothermia can be induced in laboratory animals by MDMA, depending on the ambient temperature, and involve both central thermoregulation and peripheral changes in blood flow and thermogenesis. Acute 5-HT release is not directly responsible for hyperthermia, but 5-HT receptors are involved in modulating the hyperthermic response. Impairing 5-HT function with a neurotoxic dose of MDMA or p-chlorophenylalanine alters the subsequent MDMA-induced hyperthermic response. MDMA also releases dopamine, and evidence suggests that this transmitter is involved in both the hyperthermic and hypothermic effects of MDMA in rats. The noradrenergic system is also involved in the hyperthermic response to MDMA. MDMA activates central alpha(2A)-adrenoceptors and peripheral alpha(1)-adrenoceptors to produce cutaneous vasoconstriction to restrict heat loss, and beta(3)-adrenoceptors in brown adipose tissue to increase heat generation. The hyperthermia occurring in recreational users of MDMA can be fatal, but data reviewed here indicate that it is unlikely that any single pharmaceutical agent will be effective in reversing the hyperthermia, so careful body cooling remains the principal clinical approach. Crucially, educating recreational users about the potential dangers of hyperthermia and the control of ambient temperature should remain key approaches to prevent this potentially fatal problem. PMID:20590597

  15. The role of monoamines in the changes in body temperature induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives

    PubMed Central

    Docherty, JR; Green, AR

    2010-01-01

    Hyperthermia is probably the most widely known acute adverse event that can follow ingestion of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) by recreational users. The effect of MDMA on body temperature is complex because the drug has actions on all three major monoamine neurotransmitters [5-hydroxytryptamine (5-HT), dopamine and noradrenaline], both by amine release and by direct receptor activation. Hyperthermia and hypothermia can be induced in laboratory animals by MDMA, depending on the ambient temperature, and involve both central thermoregulation and peripheral changes in blood flow and thermogenesis. Acute 5-HT release is not directly responsible for hyperthermia, but 5-HT receptors are involved in modulating the hyperthermic response. Impairing 5-HT function with a neurotoxic dose of MDMA or p-chlorophenylalanine alters the subsequent MDMA-induced hyperthermic response. MDMA also releases dopamine, and evidence suggests that this transmitter is involved in both the hyperthermic and hypothermic effects of MDMA in rats. The noradrenergic system is also involved in the hyperthermic response to MDMA. MDMA activates central α2A-adrenoceptors and peripheral α1-adrenoceptors to produce cutaneous vasoconstriction to restrict heat loss, and β3-adrenoceptors in brown adipose tissue to increase heat generation. The hyperthermia occurring in recreational users of MDMA can be fatal, but data reviewed here indicate that it is unlikely that any single pharmaceutical agent will be effective in reversing the hyperthermia, so careful body cooling remains the principal clinical approach. Crucially, educating recreational users about the potential dangers of hyperthermia and the control of ambient temperature should remain key approaches to prevent this potentially fatal problem. PMID:20590597

  16. Age differences in (±) 3,4-methylenedioxymethamphetamine (MDMA)-induced conditioned taste aversions and monoaminergic levels.

    PubMed

    Cobuzzi, Jennifer L; Siletti, Kayla A; Hurwitz, Zachary E; Wetzell, Bradley; Baumann, Michael H; Riley, Anthony L

    2014-05-01

    Preclinical work indicates that adolescent rats appear more sensitive to the rewarding effects and less sensitive to the aversive effects of abused drugs. The present investigation utilized the conditioned taste aversion (CTA) design to measure the relative aversive effects of (±)3,4-methylenedioxymethamphetamine (MDMA; 0, 1.0, 1.8, or 3.2 mg/kg) in adolescent and adult Sprague-Dawley rats. After behavioral testing was complete, monoamine and associated metabolite levels in discrete brain regions were quantified using high-performance liquid chromatography coupled to electrochemical detection (HPLC-ECD) to determine if adolescent animals displayed a different neurochemical profile than did adult animals after being exposed to subcutaneous low doses of MDMA. Adolescent rats displayed less robust MDMA-induced taste aversions than adults during acquisition and on a final two-bottle aversion test. MDMA at these doses had no consistent effect on monoamine levels in either age group, although levels did vary with age. The relative insensitivity of adolescents to MDMA's aversive effects may engender an increased vulnerability to MDMA abuse in this specific population.

  17. The prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA): Controlled studies in humans and laboratory animals.

    PubMed

    Kamilar-Britt, Philip; Bedi, Gillinder

    2015-10-01

    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

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

    PubMed Central

    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

  19. The prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA): Controlled studies in humans and laboratory animals.

    PubMed

    Kamilar-Britt, Philip; Bedi, Gillinder

    2015-10-01

    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.

  20. Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research.

    PubMed

    Parrott, A. C.

    2001-12-01

    MDMA (3,4-methylenedioxymethamphetamine) or 'Ecstasy' was scheduled as an illegal drug in 1986, but since then its recreational use has increased dramatically. This review covers 15 years of research into patterns of use, its acute psychological and physiological effects, and the long-term consequences of repeated use. MDMA is an indirect monoaminergic agonist, stimulating the release and inhibiting the reuptake of serotonin (5-HT) and, to a lesser extent, other neurotransmitters. Single doses of MDMA have been administered to human volunteers in double-blind placebo-controlled trials, although most findings are based upon recreational MDMA users. The 'massive' boost in neurotransmitter activity can generate intense feelings of elation and pleasure, also hyperactivity and hyperthermia. This psychophysiological arousal may be exacerbated by high ambient temperatures, overcrowding, prolonged dancing and other stimulant drugs. Occasionally the 'serotonin syndrome' reactions may prove fatal. In the days after Ecstasy use, around 80% of users report rebound depression and lethargy, due probably to monoaminergic depletion. Dosage escalation and chronic pharmacodynamic tolerance typically occur in regular users. Repeated doses of MDMA cause serotonergic neurotoxicity in laboratory animals, and there is extensive evidence for long-term neuropsychopharmacological damage in humans. Abstinent regular Ecstasy users often display reduced levels of 5-HT, 5-HIAA, tryptophan hydroxylase and serotonin transporter density; functional deficits in learning/memory, higher cognitive processing, sleep, appetite and psychiatric well-being, and, most paradoxically, 'loss of sexual interest/pleasure'. These psychobiological deficits are greatest in heavy Ecstasy users and may reflect serotonergic axonal loss in the higher brain regions, especially the frontal lobes, temporal lobes and hippocampus. These problems seem to remain long after the recreational use of Ecstasy has ceased

  1. Comparing Intervention Strategies among Rural, Low SES, Young Adult Tobacco Users

    ERIC Educational Resources Information Center

    Zanis, David A.; Hollm, Ronald E.; Derr, Daniel; Ibrahim, Jennifer K.; Collins, Bradley N.; Coviello, Donna; Melochick, Jennifer Ryan

    2011-01-01

    Objective: To evaluate 3-month tobacco quit rates of young adult tobacco users randomized to 2 intervention conditions. Methods: Overall 192 non-treatment-seeking 18-to-24-year-old tobacco users received educational information and advice to quit smoking. Participants were then block randomized to 2 brief intervention conditions: (1) a telephone…

  2. Involving Adult Service Users with Learning Disabilities in the Training of Speech and Language Therapy Students

    ERIC Educational Resources Information Center

    Harding, Celia

    2009-01-01

    This article describes a pilot project carried out at City University London, Department of Language and Communication Science, where adult service users with learning disabilities trained first-year speech and language therapy students. The training involved presentations by the service users on their involvement in interviewing support staff,…

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

    PubMed

    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. PMID:25498417

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

    PubMed

    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.

  5. Stages in Learning New Technology: Naive Adult Email Users.

    ERIC Educational Resources Information Center

    Russell, Anne L.

    1995-01-01

    Identifies six stages adult learners pass through as they become confident using electronic mail. Understanding the stages of learning to use technology empowers the learner through the knowledge that feelings of tension and frustration will be overcome. (Author/AEF)

  6. Evaluating Websites for Older Adults: Adherence to "Senior-Friendly" Guidelines and End-User Performance

    ERIC Educational Resources Information Center

    Hart, T. A.; Chaparro, B. S.; Halcomb, C. G.

    2008-01-01

    Older adults in the US are the fastest-growing demographic, and also the largest-growing group of internet users. The aim of this research was to evaluate websites designed for older adults in terms of (1) how well they adhere to "senior-friendly" guidelines and (2) overall ease of use and satisfaction. In Experiment I, 40 websites designed for…

  7. Characteristics and Outcomes of Young Adult Opiate Users Receiving Residential Substance Abuse Treatment.

    PubMed

    Morse, Siobhan; MacMaster, Samuel

    2015-01-01

    Opiate use patterns, user characteristics, and treatment response among young adults are of interest due to current high use prevalence and historical low levels of treatment engagement relative to older populations. Prior research in this population suggests that overall, young adults present at treatment with different issues. In this study the authors investigated potential differences between young adult (18-25 years of age) and older adult (26 and older) opiate users and the impact of differences relative to treatment motivation, length and outcomes. Data for this study was drawn from 760 individuals who entered voluntary, private, residential treatment. Study measures included the Addiction Severity Index (ASI), the Treatment Service Review (TSR), and University of Rhode Island Change Assessment (URICA). Interviews were conducted at program intake and 6-month post-discharge. Results indicate that older adults with a history of opiate use present at treatment with higher levels of severity for alcohol, medical, and psychological problems and young adults present at treatment with greater drug use and more legal issues. Significant improvement for both groups was noted at 6 months post treatment; there were also fewer differences between the two age groups of opiate users. Results suggest different strategies within treatment programs may provide benefit in targeting the disparate needs of younger opiate users. Overall, however, results suggest that individualized treatment within a standard, abstinence-based, residential treatment model can be effective across opiate users at different ages and with different issues, levels of severity, and impairment at intake.

  8. Characteristics and Outcomes of Young Adult Opiate Users Receiving Residential Substance Abuse Treatment.

    PubMed

    Morse, Siobhan; MacMaster, Samuel

    2015-01-01

    Opiate use patterns, user characteristics, and treatment response among young adults are of interest due to current high use prevalence and historical low levels of treatment engagement relative to older populations. Prior research in this population suggests that overall, young adults present at treatment with different issues. In this study the authors investigated potential differences between young adult (18-25 years of age) and older adult (26 and older) opiate users and the impact of differences relative to treatment motivation, length and outcomes. Data for this study was drawn from 760 individuals who entered voluntary, private, residential treatment. Study measures included the Addiction Severity Index (ASI), the Treatment Service Review (TSR), and University of Rhode Island Change Assessment (URICA). Interviews were conducted at program intake and 6-month post-discharge. Results indicate that older adults with a history of opiate use present at treatment with higher levels of severity for alcohol, medical, and psychological problems and young adults present at treatment with greater drug use and more legal issues. Significant improvement for both groups was noted at 6 months post treatment; there were also fewer differences between the two age groups of opiate users. Results suggest different strategies within treatment programs may provide benefit in targeting the disparate needs of younger opiate users. Overall, however, results suggest that individualized treatment within a standard, abstinence-based, residential treatment model can be effective across opiate users at different ages and with different issues, levels of severity, and impairment at intake. PMID:25879396

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

    PubMed

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

    2014-06-01

    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.

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

    PubMed Central

    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

  11. Residual Neural Processing of Musical Sound Features in Adult Cochlear Implant Users

    PubMed Central

    Timm, Lydia; Vuust, Peter; Brattico, Elvira; Agrawal, Deepashri; Debener, Stefan; Büchner, Andreas; Dengler, Reinhard; Wittfoth, Matthias

    2014-01-01

    Auditory processing in general and music perception in particular are hampered in adult cochlear implant (CI) users. To examine the residual music perception skills and their underlying neural correlates in CI users implanted in adolescence or adulthood, we conducted an electrophysiological and behavioral study comparing adult CI users with normal-hearing age-matched controls (NH controls). We used a newly developed musical multi-feature paradigm, which makes it possible to test automatic auditory discrimination of six different types of sound feature changes inserted within a musical enriched setting lasting only 20 min. The presentation of stimuli did not require the participants’ attention, allowing the study of the early automatic stage of feature processing in the auditory cortex. For the CI users, we obtained mismatch negativity (MMN) brain responses to five feature changes but not to changes of rhythm, whereas we obtained MMNs for all the feature changes in the NH controls. Furthermore, the MMNs to deviants of pitch of CI users were reduced in amplitude and later than those of NH controls for changes of pitch and guitar timber. No other group differences in MMN parameters were found to changes in intensity and saxophone timber. Furthermore, the MMNs in CI users reflected the behavioral scores from a respective discrimination task and were correlated with patients’ age and speech intelligibility. Our results suggest that even though CI users are not performing at the same level as NH controls in neural discrimination of pitch-based features, they do possess potential neural abilities for music processing. However, CI users showed a disrupted ability to automatically discriminate rhythmic changes compared with controls. The current behavioral and MMN findings highlight the residual neural skills for music processing even in CI users who have been implanted in adolescence or adulthood. Highlights: -Automatic brain responses to musical feature changes

  12. Differential effects of cocaine and MDMA self-administration on cortical serotonin transporter availability in monkeys.

    PubMed

    Gould, Robert W; Gage, H Donald; Banks, Matthew L; Blaylock, Brandi L; Czoty, Paul W; Nader, Michael A

    2011-01-01

    Cocaine self-administration alters brain dopaminergic and serotonergic function primarily in mesolimbic and prefrontal brain regions whereas 3,4-methylenedioxymethamphetamine (MDMA) self-administration predominately alters brain serotonergic function in a more widespread distribution across cortical regions. We previously reported that, compared to drug-naïve rhesus monkeys, self-administration of cocaine but not MDMA was associated with increased serotonin transporter (SERT) availability in two mesolimbic regions, the caudate nucleus and putamen, as measured by positron emission tomography (PET) using the SERT-specific ligand [(11)C]-3-amino-4(2-dimethylamino-methyl-phenylsulfanyl)-benzonitrile ([(11)C]DASB). The goal of the present study was to extend this comparison between cocaine and MDMA self-administration to SERT availability in cortical regions, which have been shown previously to be affected in human drug abusers and are associated with executive function. PET studies using [(11)C]DASB were conducted in adult male rhesus monkeys with a history of cocaine (mean intake = 742.6 mg/kg) or MDMA (mean intake = 121.0 mg/kg) self-administration, and drug-naïve controls (n = 4/group). Regions of interest were drawn for several cortical (prefrontal, temporal, parietal, occipital and midcingulate) and subcortical (thalamus, amygdala and hippocampus) areas. Cortical SERT availability was significantly higher in monkeys with a cocaine self-administration history compared to controls whereas MDMA self-administration resulted in lower levels of SERT availability. These data extend our previous findings indicating that cocaine and MDMA self-administration differentially alter SERT availability in subcortical and cortical regions, which may have implications for development of treatment drugs. PMID:21521647

  13. [A review of research on music perception ability for adult cochlear implant users].

    PubMed

    Liu, Ziye; Liu, Bo; Wang, Shuo

    2012-11-01

    A cochlear implant (CI) is a kind of surgically implanted electronic device that provides a sense of sound to a person who has severe to profound sensorineural hearing impairment. However, studies have shown that the performance in music perception for CI users has not been achieved to an ideal level. It is important to evaluate the ability to perceive music using well designed music perception test materials, in order to improve the quality of life for cochlear implant users. This paper reviewed the studies on assessing music perception ability for adult cochlear implant users from the existing literature. PMID:23379124

  14. Technical Report and Data File User's Manual for the 1992 National Adult Literacy Survey.

    ERIC Educational Resources Information Center

    Kirsch, Irwin; Yamamoto, Kentaro; Norris, Norma; Rock, Donald; Jungeblut, Ann; O'Reilly, Patricia; Berlin, Martha; Mohadjer, Leyla; Waksberg, Joseph; Goksel, Huseyin; Burke, John; Rieger, Susan; Green, James; Klein, Merle; Campbell, Anne; Jenkins, Lynn; Kolstad, Andrew; Mosenthal, Peter; Baldi, Stephane

    Chapter 1 of this report and user's manual describes design and implementation of the 1992 National Adult Literacy Survey (NALS). Chapter 2 reviews stages of sampling for national and state survey components; presents weighted and unweighted response rates for the household component; and describes non-incentive and prison sample designs. Chapter…

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

    PubMed

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

    2015-12-01

    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.

  16. Risk perceptions of smokeless tobacco among adolescents and adult users and nonusers

    PubMed Central

    Liu, Sherry T.; Nemeth, Julianna M.; Klein, Elizabeth G.; Ferketich, Amy K.; Kwan, Mei-Po; Wewers, Mary Ellen

    2015-01-01

    The recent growth in smokeless tobacco (ST) consumption has raised questions about consumer risk perceptions of ST products, especially in high-risk vulnerable populations. This qualitative study examined risk perceptions of ST among adolescent and adult users and non-users in Ohio Appalachia. Focus groups and interviews were held with adolescents (n=53; mean age of 17 years) and adults (n=63; mean age of 34 years) from four Ohio Appalachian counties. Participants were asked about their perceptions of ST-related health risks, ST safety, and the relative safety of ST compared to cigarettes. Transcriptions were coded independently by two individuals. Overall, participants were knowledgeable about health problems from ST use (e.g., oral cancers, periodontal disease). Nearly all participants stated that ST use is not safe; however, there was disagreement about its relative safety. Some perceived all tobacco products as equally harmful; others believed that ST is safer than cigarettes for either the user or those around the user. Disagreements about ST relative safety may reflect mixed public health messages concerning the safety of ST. Comprehensive consumer messages about the relative safety of ST compared to cigarettes are needed. Messages should address the effect of ST on the health of the user as well as those exposed to the user. PMID:25832126

  17. Making a medicine out of MDMA.

    PubMed

    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.

  18. An appraisal of the pharmacological and toxicological effects of a single oral administration of 3,4-methylenedioxymethamphetamine (MDMA) in the rat.

    PubMed

    De Souza, I; Kelly, J P; Harkin, A J; Leonard, B E

    1997-05-01

    This study examined some acute pharmacological and toxicological effects of 3,4 methylenedioxymethamphetamine (MDMA, "Ecstasy") over a range of doses (20, 40, 80, 160 and 320 mg/kg orally) in adult female rats. Deaths were observed from the 40 mg/kg MDMA group onwards. Reductions in body weight change, food and water intake were found in the 80 mg/kg group, whilst food intake alone was reduced in the 20 and 40 mg/kg groups. Significant hyperthermic responses were found over the first 8 hr following MDMA administration which were dose-related. A significant hyperactivity of approximately 9 hr duration was observed in the 20 mg/kg and 40 mg/kg groups, whereas there was evidence of a serotonin syndrome in the higher dosage groups. Thus, acute oral administration of MDMA results in a variety of measurable responses. The cause of death in this study is probably a combination of serotonin syndrome and hyperthermia.

  19. Optimizing Performance in Adult Cochlear Implant Users through Clinician Directed Auditory Training.

    PubMed

    Plant, Geoff; Bernstein, Claire Marcus; Levitt, Harry

    2015-11-01

    Clinician-directed auditory training using the KTH Speech Tracking Procedure can be a powerful approach for maximizing outcomes with adult cochlear implant (CI) users. This article first reviews prior research findings from an 8-week clinician-directed auditory training (AT) program using speech tracking that yielded significant gains in speech tracking rate and sentence recognition scores following training. The second focus of the article is to illustrate the value of intensive face-to-face long-term AT using speech tracking with adult CI users. A detailed case study report is presented that demonstrates major ongoing and progressive gains in tracking rate, sentence recognition, and improvements in self-perceived competence and confidence over the course of intensive long-term training. Given the potential of both short- and long-term clinician-directed auditory training via KTH speech tracking to help CI users reach their optimal performance level, consideration for more widespread clinical use is proposed in the overall rehabilitation of adult CI users. PMID:27587916

  20. National Assessment of Adult Literacy, 2003: Public-Use Data File User's Guide. NCES 2007-464

    ERIC Educational Resources Information Center

    Greenberg, Elizabeth; Jin, Ying; White, Sheida

    2007-01-01

    The U.S. Department of Education's National Center for Education Statistics has updated the household and prison public-use data files for the 2003 National Assessment of Adult Literacy and the 1992 National Adult Literacy Survey. The accompanying 2003 National Assessment of Adult Literacy Public-Use Data File User's Guide explains how the data…

  1. 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.

    PubMed

    Ball, Kevin T; Slane, Mylissa

    2014-11-01

    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 could predict subsequent patterns of MDMA-taking or -seeking behaviors we used the self-administration-extinction-reinstatement model to examine addiction-like behavior (i.e., escalation of MDMA self-administration and cue-induced reinstatement of MDMA seeking) in rats a priori characterized for either locomotor sensitization or tolerance to MDMA. Rats that developed tolerance to the locomotor-activating effects of MDMA had a significantly larger locomotor response to the first MDMA injection relative to rats that developed sensitization. Importantly, rats that developed tolerance subsequently displayed an escalation of MDMA self-administration over days, as well as clear cue-induced reinstatement of MDMA seeking following extinction. Conversely, rats that developed locomotor sensitization to MDMA subsequently maintained relatively stable levels of MDMA self-administration over days and showed no cue-induced reinstatement of MDMA seeking. These results show that differences in the level of psychomotor activation following acute and repeated MDMA administration can reliably predict two important addiction-like behaviors in rats, which may have implications in the prediction of compulsive MDMA use in humans.

  2. 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.

    PubMed

    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. PMID:25990558

  3. 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.

    PubMed

    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.

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

    PubMed

    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.

  5. A preliminary report of music-based training for adult cochlear implant users: rationales and development

    PubMed Central

    Gfeller, Kate; Guthe, Emily; Driscoll, Virginia; Brown, Carolyn J.

    2015-01-01

    Objective This paper provides a preliminary report of a music-based training program for adult cochlear implant (CI) recipients. Included in this report are descriptions of the rationale for music-based training, factors influencing program development, and the resulting program components. Methods Prior studies describing experience-based plasticity in response to music training, auditory training for persons with hearing impairment, and music training for cochlear implant recipients were reviewed. These sources revealed rationales for using music to enhance speech, factors associated with successful auditory training, relevant aspects of electric hearing and music perception, and extant evidence regarding limitations and advantages associated with parameters for music training with CI users. This information formed the development of a computer-based music training program designed specifically for adult CI users. Results Principles and parameters for perceptual training of music, such as stimulus choice, rehabilitation approach, and motivational concerns were developed in relation to the unique auditory characteristics of adults with electric hearing. An outline of the resulting program components and the outcome measures for evaluating program effectiveness are presented. Conclusions Music training can enhance the perceptual accuracy of music, but is also hypothesized to enhance several features of speech with similar processing requirements as music (e.g., pitch and timbre). However, additional evaluation of specific training parameters and the impact of music-based training on speech perception of CI users are required. PMID:26561884

  6. The effect of MDMA on sensitivity to reinforcement rate.

    PubMed

    Lie, Celia; Macaskill, Anne C; Harper, David N

    2016-04-01

    Administration of (±)3,4-methylenedioxymethamphetamine (MDMA) causes memory errors by increasing proactive interference. This might occur because MDMA alters sensitivity to reinforcement. The current 2 experiments investigated this directly by assessing the acute (Experiment 1) and chronic (Experiment 2) effects of MDMA on sensitivity to reinforcement. We presented 5 pairs of concurrent variable interval schedules within each session and calculated sensitivity to reinforcement for 3 acute doses of MDMA. In contrast to the related drug, d-amphetamine, and in spite of producing reductions in response rate, MDMA did not reduce sensitivity to reinforcement rate. Chronic administration of a fixed dose of MDMA following each session reduced response rate but did not affect sensitivity to reinforcement rate. In combination with previous research, these results indicate that related drugs may have different effects on sensitivity to reinforcement and that these effects should be considered when interpreting disruptions to operant task performance caused by drug administration. (PsycINFO Database Record

  7. The effect of MDMA on sensitivity to reinforcement rate.

    PubMed

    Lie, Celia; Macaskill, Anne C; Harper, David N

    2016-04-01

    Administration of (±)3,4-methylenedioxymethamphetamine (MDMA) causes memory errors by increasing proactive interference. This might occur because MDMA alters sensitivity to reinforcement. The current 2 experiments investigated this directly by assessing the acute (Experiment 1) and chronic (Experiment 2) effects of MDMA on sensitivity to reinforcement. We presented 5 pairs of concurrent variable interval schedules within each session and calculated sensitivity to reinforcement for 3 acute doses of MDMA. In contrast to the related drug, d-amphetamine, and in spite of producing reductions in response rate, MDMA did not reduce sensitivity to reinforcement rate. Chronic administration of a fixed dose of MDMA following each session reduced response rate but did not affect sensitivity to reinforcement rate. In combination with previous research, these results indicate that related drugs may have different effects on sensitivity to reinforcement and that these effects should be considered when interpreting disruptions to operant task performance caused by drug administration. (PsycINFO Database Record PMID:26820588

  8. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier integrity through a mechanism involving P2X7 receptors.

    PubMed

    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.

  9. Maternal MDMA administration in mice leads to neonatal growth delay.

    PubMed

    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.

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

    PubMed

    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.

  11. High risk and little knowledge: Overdose experiences and knowledge among young adult nonmedical prescription opioid users

    PubMed Central

    Frank, David; Mateu-Gelabert, Pedro; Guarino, Honoria; Bennett, Alex; Wendel, Travis; Jessell, Lauren; Teper, Anastasia

    2014-01-01

    Background Opioid-involved overdoses in the United States have dramatically increased in the last 15 years, largely due to a rise in prescription opioid (PO) use. Yet few studies have examined the overdose knowledge and experience of nonmedical PO users. Methods In depth, semi-structured, audio-recorded interviews were conducted with 46 New York City young adults (ages 18–32) who reported using POs nonmedically within the past 30 days. Verbatim interview transcripts were coded for key themes in an analytic process informed by grounded theory. Results Despite significant experience with overdose (including overdose deaths), either personally or within opioid-using networks, participants were relatively uninformed about overdose awareness, avoidance and response strategies, in particular the use of naloxone. Overdose experiences typically occurred when multiple pharmaceuticals were used (often in combination with alcohol) or after participants had transitioned to heroin injection. Participants tended to see themselves as distinct from traditional heroin users, and were often outside of the networks reached by traditional opioid safety/overdose prevention services. Consequently, they were unlikely to utilize harm reduction services, such as syringe exchange programs (SEPs), that address drug users' health and safety. Conclusions These findings suggest that many young adult nonmedical PO users are at high risk of both fatal and non-fatal overdose. There is a pressing need to develop innovative outreach strategies and overdose prevention programs to better reach and serve young PO users and their network contacts. Prevention efforts addressing risk for accidental overdose, including opioid safety/overdose reversal education and naloxone distribution, should be tailored for and targeted to this vulnerable group. PMID:25151334

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

    PubMed

    Sáez-Briones, P; Hernández, A

    2013-09-01

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

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

    PubMed Central

    Sáez-Briones, P.; Hernández, A.

    2013-01-01

    Besides stimulants and hallucinogens, whose psychotropic effects are shared by many structurally related molecules exhibiting different efficacies and potencies in humans, the phenylisopropylamine MDMA (3,4-methylenedioxymethamphetamine, XTC, “Ecstasy”) is the prototypical representative of a separate class of psychotropic substance, able to elicit the so-called entactogenic syndrome in healthy humans. This reversible altered state of consciousness, usually described as an “open mind state”, may have relevant therapeutic applications, both in psychotherapy and as a pharmacological support in many neuropsychiatric disorders with a high rate of treatment failure. Nevertheless, a comprehensive and systematic exploration of the structure-activity relationships associated with entactogenic activity has remained incomplete and controversial, highlighting the possibility that MDMA might represent a pharmacological rarity in the field of psychotropics. As the latter is still an open question, the pharmacological characterization of MDMA analogues remains the logical strategy to attempt the elucidation of the structural requirements needed to elicit typical MDMA-like effects. Intriguingly, almost no experimental evidence supports the existence of actual MDMA analogues that truly resemble the whole pharmacological profile of MDMA, probably due to its complex (and partially not fully understood) mechanism of action that includes a disruption of monoaminergic neurotransmission. The present review presents a brief summary of the pharmacology of MDMA, followed by the evidence accumulated over the years regarding the characterization of classical structurally related MDMA analogues in different models and how this state of the art highlights the need to develop new and better MDMA analogues. PMID:24403876

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

    PubMed

    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

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

    PubMed Central

    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

  16. Tobacco May Mask Poorer Episodic Memory among Young Adult Cannabis Users

    PubMed Central

    Schuster, Randi M.; Crane, Natania A.; Mermelstein, Robin; Gonzalez, Raul

    2014-01-01

    Objective Co-occurring cannabis and tobacco use has become increasingly prevalent among young adults, but it is not clear how tobacco use may alter the neurocognitive profile typically observed among cannabis users. Although there is substantial evidence citing cannabis and tobacco's individual impact on episodic memory and related brain structures, few studies have examined the impact of combined cannabis and tobacco use on memory. Method This investigation examined relationships between amount of past year cannabis and tobacco use on four different indices of episodic memory among a sample of young adults who identified cannabis as their drug of choice. Results Results indicated that more cannabis use was linked with poorer initial acquisition, total learning and delayed recall on the Hopkins Verbal Learning Test--Revised (HVLT-R), but only among cannabis users who sporadically smoked cigarettes in the past year. Conversely, amount of past year cannabis use was not associated with episodic memory performance among individuals who more consistently smoked cigarettes in the past year. These differences could not be explained by several relevant potential confounds. Conclusions These findings provide important insight into a potential mechanism (i.e., attenuation of cognitive decrements) that might reinforce use of both substances and hamper cessation attempts among cannabis users who also smoke cigarettes. Ongoing and future research will help to better understand how co-use of cannabis and tobacco impacts memory during acute intoxication and abstinence, and the stability of these associations over time. PMID:25558879

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

    SciTech Connect

    Chen, Da-Ren; Cheng, Mengdawn

    2007-01-01

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

  18. Perceptual dialect categorization by an adult cochlear implant user: a case study.

    PubMed

    Clopper, Cynthia G; Pisoni, David B

    2004-11-01

    Research on the perception of indexical properties of speech in normal-hearing listeners has revealed that speech perception and spoken word recognition involve not only encoding of the linguistic message, but also processing and storage of talker-specific "indexical" properties of the speech signal, such as age, gender, and dialect. The perceptual processing of talker-specific information in speech has also been shown to affect the speech perception abilities of pediatric and adult cochlear implant users. In the current study, "Mr. S.", a post-lingually deafened adult cochlear implant user with 8 years of implant experience participated in a six-alternative forced-choice perceptual dialect categorization task without training or feedback. Normal-hearing adults can categorize unfamiliar talkers by regional dialect of American English with about 30% accuracy in a six-alternative forced-choice task. While this performance is poor, it is statistically above chance. Like the normal-hearing listeners, "Mr. S."'s performance was also statistically above chance and his scores were within one standard deviation of the mean performance of 30 normal-hearing controls. The present results suggest that "Mr. S." was able to perceive and encode non-linguistic talker-specific information from the speech signal that he received through his implant and use that information in an explicit test of dialect categorization. PMID:21423817

  19. Perceptual dialect categorization by an adult cochlear implant user: a case study.

    PubMed

    Clopper, Cynthia G; Pisoni, David B

    2004-11-01

    Research on the perception of indexical properties of speech in normal-hearing listeners has revealed that speech perception and spoken word recognition involve not only encoding of the linguistic message, but also processing and storage of talker-specific "indexical" properties of the speech signal, such as age, gender, and dialect. The perceptual processing of talker-specific information in speech has also been shown to affect the speech perception abilities of pediatric and adult cochlear implant users. In the current study, "Mr. S.", a post-lingually deafened adult cochlear implant user with 8 years of implant experience participated in a six-alternative forced-choice perceptual dialect categorization task without training or feedback. Normal-hearing adults can categorize unfamiliar talkers by regional dialect of American English with about 30% accuracy in a six-alternative forced-choice task. While this performance is poor, it is statistically above chance. Like the normal-hearing listeners, "Mr. S."'s performance was also statistically above chance and his scores were within one standard deviation of the mean performance of 30 normal-hearing controls. The present results suggest that "Mr. S." was able to perceive and encode non-linguistic talker-specific information from the speech signal that he received through his implant and use that information in an explicit test of dialect categorization.

  20. Involvement of 5-HT2A receptors in MDMA reinforcement and cue-induced reinstatement of MDMA-seeking behaviour.

    PubMed

    Orejarena, María Juliana; Lanfumey, Laurence; Maldonado, Rafael; Robledo, Patricia

    2011-08-01

    The serotonergic system appears crucial for (±)-3,4-methylenedioxymethamphetamine (MDMA) reinforcing properties. Current evidence indicates that serotonin 5-HT2A receptors (5-HT2ARs) modulate mesolimbic dopamine (DA) activity and several behavioural responses related to the addictive properties of psychostimulants. This study evaluated the role of 5-HT2ARs in MDMA-induced reinforcement and hyperlocomotion, and the reinstatement of MDMA-seeking behaviour. Basal and MDMA-stimulated extracellular levels of DA in the nucleus accumbens (NAc) and serotonin and noradrenaline in the prefrontal cortex were also assessed. Self-administration of MDMA was blunted in 5-HT2AR knockout (KO) mice compared to wild-type (WT) littermates at both doses tested (0.125 and 0.25 mg/kg per infusion). Horizontal locomotion was increased by MDMA (10 and 20 mg/kg i.p.) to a higher extent in KO than in WT mice. DA outflow in the NAc was lower in KO compared to WT mice under basal conditions and after MDMA (20 mg/kg) challenge. In WT mice, MDMA (5 and 10 mg/kg i.p.) priming did not reinstate MDMA-seeking behaviour, while cue-induced reinstatement was prominent. This cue-induced reinstatement was blocked by administration of the selective 5-HT2AR antagonist, SR46349B (eplivanserin) at a dose of 0.5 mg/kg, but not at 0.25 mg/kg. Our results indicate that 5-HT2ARs are crucial for MDMA-induced reinforcement and cue-induced reinstatement of MDMA-seeking behaviour. These effects are probably due to the modulation of mesolimbic dopaminergic activity.

  1. The potential dangers of using MDMA for psychotherapy.

    PubMed

    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. PMID:24830184

  2. MDMA Impairs Response to Water Intake in Healthy Volunteers.

    PubMed

    Baggott, Matthew J; Garrison, Kathleen J; Coyle, Jeremy R; Galloway, Gantt P; Barnes, Allan J; Huestis, Marilyn A; Mendelson, John E

    2016-01-01

    Hyponatremia is a serious complication of 3,4-methylenedioxymethamphetamine (MDMA) use. We investigated potential mechanisms in two double-blind, placebo-controlled studies. In Study 1, healthy drug-experienced volunteers received MDMA or placebo alone and in combination with the alpha-1 adrenergic inverse agonist prazosin, used as a positive control to release antidiuretic hormone (ADH). In Study 2, volunteers received MDMA or placebo followed by standardized water intake. MDMA lowered serum sodium but did not increase ADH or copeptin, although the control prazosin did increase ADH. Water loading reduced serum sodium more after MDMA than after placebo. There was a trend for women to have lower baseline serum sodium than men, but there were no significant interactions with drug condition. Combining studies, MDMA potentiated the ability of water to lower serum sodium. Thus, hyponatremia appears to be a significant risk when hypotonic fluids are consumed during MDMA use. Clinical trials and events where MDMA use is common should anticipate and mitigate this risk. PMID:27403159

  3. The potential dangers of using MDMA for psychotherapy.

    PubMed

    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.

  4. MDMA modulates spontaneous firing of subthalamic nucleus neurons in vitro.

    PubMed

    Liebig, Luise; von Ameln-Mayerhofer, Andreas; Hentschke, Harald

    2015-01-01

    3,4-Methylene-dioxy-N-methylamphetamine (MDMA, 'ecstasy') has a broad spectrum of molecular targets in the brain, among them receptors and transporters of the serotonergic (5-hydroxytryptamine, 5-HT) and noradrenergic systems. Its action on the serotonergic system modulates motor systems in rodents and humans. Although parts of the basal ganglia could be identified as mediators of the motor effects of MDMA, very little is known about the role of the subthalamic nucleus (STN). Therefore, this study investigated the modulation of spontaneous action potential activity of the STN by MDMA (2.5-20 µM) in vitro. MDMA had very heterogeneous effects, ranging from a complete but reversible inhibition to a more than twofold increase in firing at 5 µM. On average, MDMA excited STN neurons moderately, but lost its excitatory effect in the presence of the 5-HT(2A) antagonist MDL 11,939. 5-HT(1A) receptors did not appear to play a major role. Effects of MDMA on transporters for serotonin (SERT) and norepinephrine (NET) were investigated by coapplication of the reuptake inhibitors citalopram and desipramine, respectively. Similar to the effects of 5-HT(2A) receptor blockade, antagonism of SERT and NET bestowed an inhibitory effect on MDMA. From these results, we conclude that both the 5-HT and the noradrenergic system mediate MDMA-induced effects on STN neurons.

  5. MDMA Impairs Response to Water Intake in Healthy Volunteers

    PubMed Central

    Garrison, Kathleen J.; Coyle, Jeremy R.; Galloway, Gantt P.; Huestis, Marilyn A.; Mendelson, John E.

    2016-01-01

    Hyponatremia is a serious complication of 3,4-methylenedioxymethamphetamine (MDMA) use. We investigated potential mechanisms in two double-blind, placebo-controlled studies. In Study 1, healthy drug-experienced volunteers received MDMA or placebo alone and in combination with the alpha-1 adrenergic inverse agonist prazosin, used as a positive control to release antidiuretic hormone (ADH). In Study 2, volunteers received MDMA or placebo followed by standardized water intake. MDMA lowered serum sodium but did not increase ADH or copeptin, although the control prazosin did increase ADH. Water loading reduced serum sodium more after MDMA than after placebo. There was a trend for women to have lower baseline serum sodium than men, but there were no significant interactions with drug condition. Combining studies, MDMA potentiated the ability of water to lower serum sodium. Thus, hyponatremia appears to be a significant risk when hypotonic fluids are consumed during MDMA use. Clinical trials and events where MDMA use is common should anticipate and mitigate this risk. PMID:27403159

  6. Cortisol and 3,4-Methylenedioxymethamphetamine: Neurohormonal Aspects of Bioenergetic Stress in Ecstasy Users

    PubMed Central

    Parrott, A.C.

    2009-01-01

    Aims 3,4-Methylenedioxymethamphetamine (MDMA) can affect both neurotransmitter and neurohormonal activity. This review will debate the role of the metabolic activation hormone cortisol for the psychobiological effects of ecstasy/MDMA. Methods The empirical literature on cortisol release following acute MDMA administration and cortisol functioning in drug-free recreational ecstasy/MDMA users will be reviewed. This will be followed by an overview of cortisol as a bioenergetic stress neurohormone, and a debate on how it could be modulating the acute and chronic psychobiological effects of MDMA. Results Cortisol release is increased by stimulatory factors, including physical activity, thermal stress and stimulant drugs. In laboratory studies MDMA leads to an acute cortisol increase of around 150% in sedentary humans. In MDMA-using dance clubbers, the cortisol levels are increased by around 800%, possibly due to the combined factors of stimulant drug, physical exertion and psychosocial stimulation. Regular ecstasy/MDMA users also demonstrate changes in baseline cortisol levels and cortisol reactivity, with compromised hypothalamic-pituitary-adrenal activity. Nonpharmacological research has shown how cortisol is important for psychological aspects such as memory, cognition, sleep, impulsivity, depression and neuronal damage. These same functions are often impaired in recreational ecstasy/MDMA users, and cortisol may be an important modulatory co-factor. Conclusions The energizing hormone cortisol is involved in the psychobiology of MDMA, probably via its effects on energy metabolism. Acute cortisol release may potentiate the stimulating effects of MDMA in dance clubbers. Chronically, cortisol may contribute to the variance in functional and structural consequences of repeated ecstasy usage. PMID:19893332

  7. Interactions between specific parameters of MDMA use and cognitive and psychopathological measures.

    PubMed

    Wagner, Daniel; Adolph, Sophia; Koester, Philip; Becker, Benjamin; Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

    2015-04-01

    The aim of the present study was to investigate the relevance of different parameters of 3,4-methylenedioxymethamphetamine (MDMA) use, including age of first use, cumulative lifetime dose and highest daily dose for predicting cognitive performance and self-reported psychopathology. Moreover, interactions between those parameters were examined. Ninety-six new MDMA users were interviewed to assess their drug use, and they completed a battery of cognitive tests concerning attention and information processing speed, episodic memory and executive functioning and self-reported psychopathology. Subjects participated again after 1year to provide follow-up data. Significant associations between age of first use and cumulative lifetime dose have been found for attention and information processing speed. Furthermore, the results showed a significant effect of age of first use on the recognition performance of the episodic memory. The findings of the current study provide a first estimation of the interactions between different MDMA use parameters. Future research should focus upon additional parameters of drug use and concentrate on consequent follow-up effects.

  8. Using the NIATx Model to Implement User-Centered Design of Technology for Older Adults

    PubMed Central

    Maus, Adam; Judkins, Julianne; Dinauer, Susan; Isham, Andrew; Johnson, Roberta; Landucci, Gina; Atwood, Amy K

    2016-01-01

    What models can effectively guide the creation of eHealth and mHealth technologies? This paper describes the use of the NIATx model as a framework for the user-centered design of a new technology for older adults. The NIATx model is a simple framework of process improvement based on the following principles derived from an analysis of decades of research from various industries about why some projects fail and others succeed: (1) Understand and involve the customer; (2) fix key problems; (3) pick an influential change leader; (4) get ideas from outside the field; (5) use rapid-cycle testing. This paper describes the use of these principles in technology development, the strengths and challenges of using this approach in this context, and lessons learned from the process. Overall, the NIATx model enabled us to produce a user-focused technology that the anecdotal evidence available so far suggests is engaging and useful to older adults. The first and fourth principles were especially important in developing the technology; the fourth proved the most challenging to use. PMID:27025985

  9. Interview as intervention: The case of young adult multidrug users in the club scene

    PubMed Central

    Kurtz, Steven P.; Surratt, Hilary L.; Buttram, Mance E.; Levi-Minzi, Maria A.; Chen, Minxing

    2012-01-01

    This paper reports on changes in substance use and substance dependence symptoms - without intervention - among young adult multidrug users in the club scene, ages 18–29, (N=444) who participated in a natural history study. Computer-assisted personal interviews at baseline and 6-, 12-, and 18-month follow-ups included well-tested measures of substance use and dependence. Changes in substance dependence symptoms and drug use frequencies were calculated using the Cohen’s d statistic. Mean age was 22; 40% were female; 58% Hispanic, 17% White, and 21% Black. At 18-month follow-up assessment, participants reported significantly fewer days of cocaine (d= −.85 at 18 months), ecstasy (d= −.93), benzodiazepine (d= −.82), and prescription opioid (d= −.81) use, as well as reduced substance dependence symptoms (d= −.42). These results, together with data from focus groups with completers, suggest that comprehensive health and social risk assessments may have quite strong intervention effects among young adult multidrug users. PMID:22971689

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

    PubMed Central

    Shortall, SE; Green, AR; Swift, KM; Fone, KCF; King, MV

    2013-01-01

    Background and Purpose 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. Experimental Approach 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. Key Results 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 α1-adrenoceptor and dopamine D1 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. Conclusions and Implications 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. PMID:23043631

  11. Associations of eHealth Literacy With Health Behavior Among Adult Internet Users

    PubMed Central

    Shibata, Ai; Ishii, Kaori; Oka, Koichiro

    2016-01-01

    Background In the rapidly developing use of the Internet in society, eHealth literacy—having the skills to utilize health information on the Internet—has become an important prerequisite for promoting healthy behavior. However, little is known about whether eHealth literacy is associated with health behavior in a representative sample of adult Internet users. Objective The aim of this study was to examine the association between eHealth literacy and general health behavior (cigarette smoking, physical exercise, alcohol consumption, sleeping hours, eating breakfast, eating between meals, and balanced nutrition) among adult Internet users in Japan. Methods The participants were recruited among registrants of a Japanese Internet research service company and asked to answer a cross-sectional Internet-based survey in 2012. The potential respondents (N=10,178) were randomly and blindly invited via email from the registrants in accordance with the set sample size and other attributes. eHealth literacy was assessed using the Japanese version of the eHealth Literacy Scale. The self-reported health behaviors investigated included never smoking cigarettes, physical exercise, alcohol consumption, sleeping hours, eating breakfast, not eating between meals, and balanced nutrition. We obtained details of sociodemographic attributes (sex, age, marital status, educational attainment, and household income level) and frequency of conducting Internet searches. To determine the association of each health behavior with eHealth literacy, we performed a logistic regression analysis; we adjusted for sociodemographic attributes and frequency of Internet searching as well as for other health behaviors that were statistically significant with respect to eHealth literacy in univariate analyses. Results We analyzed the data of 2115 adults (response rate: 24.04%, 2142/10,178; male: 49.74%, 1052/2115; age: mean 39.7, SD 10.9 years) who responded to the survey. Logistic regression analysis

  12. Cannabis Use Is Quantitatively Associated with Nucleus Accumbens and Amygdala Abnormalities in Young Adult Recreational Users

    PubMed Central

    Gilman, Jodi M.; Kuster, John K.; Lee, Sang; Lee, Myung Joo; Kim, Byoung Woo; Makris, Nikos; van der Kouwe, Andre; Blood, Anne J.

    2014-01-01

    Marijuana is the most commonly used illicit drug in the United States, but little is known about its effects on the human brain, particularly on reward/aversion regions implicated in addiction, such as the nucleus accumbens and amygdala. Animal studies show structural changes in brain regions such as the nucleus accumbens after exposure to Δ9-tetrahydrocannabinol, but less is known about cannabis use and brain morphometry in these regions in humans. We collected high-resolution MRI scans on young adult recreational marijuana users and nonusing controls and conducted three independent analyses of morphometry in these structures: (1) gray matter density using voxel-based morphometry, (2) volume (total brain and regional volumes), and (3) shape (surface morphometry). Gray matter density analyses revealed greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only. Significant shape differences were detected in the left nucleus accumbens and right amygdala. The left nucleus accumbens showed salient exposure-dependent alterations across all three measures and an altered multimodal relationship across measures in the marijuana group. These data suggest that marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures and is consistent with animal studies of changes in dendritic arborization. PMID:24741043

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

    PubMed

    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).

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

    PubMed

    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). PMID:24103254

  15. Hallucinogen-related disorders in a national sample of adolescents: the influence of ecstasy/MDMA use

    PubMed Central

    Wu, Li-Tzy; Ringwalt, Christopher L.; Weiss, Roger D.; Blazer, Dan G.

    2009-01-01

    Aims To present the prevalence and correlates of hallucinogen use disorders (HUDs: abuse or dependence) and subthreshold dependence. Methods The study sample included adolescents aged 12–17 years (N = 55,286) who participated in the National Survey on Drug Use and Health (2004–2006). Data were collected with a combination of computer-assisted personal interviewing and audio computer-assisted self-interviewing. Results The overall prevalence of HUDs among adolescents was low (<1%). However, more than one in three (38.5%) MDMA users and nearly one in four (24.1%) users of other hallucinogens reported HUD symptoms. MDMA users were more likely than users of other hallucinogens to meet criteria for hallucinogen dependence: 11% (95% confidence interval [CI]: 8.24–14.81) vs. 3.5% (95% CI: 2.22–5.43). Compared with hallucinogen use only, subthreshold dependence was associated with being female (adjusted odds ratio [AOR] = 1.8 [95% CI: 1.08–2.89]), ages 12–13 years (AOR = 3.4 [1.64–7.09]), use of hallucinogens ≥52 days (AOR = 2.4 [1.66–6.92]), and alcohol use disorder (AOR = 1.8 [1.21–2.77]). Compared with subthreshold dependence, abuse was associated with mental health service use (AOR = 1.7 [1.00–3.00]) and opioid use disorder (AOR = 4.9 [1.99–12.12]); dependence was associated with MDMA use (AOR = 2.2 [1.05–4.77]), mental health service use (AOR = 2.9 [1.34–6.06]), and opioid use disorder (AOR = 2.6 [1.01–6.90]). MDMA users had a higher prevalence of most other substance use disorders than users of non-hallucinogen drugs. Conclusions Adolescent MDMA users appear to be particularly at risk for exhibiting hallucinogen dependence and other substance use disorders. PMID:19500920

  16. Effects of MDMA on body temperature in humans

    PubMed Central

    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.

  17. Effects of MDMA on body temperature in humans

    PubMed Central

    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

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

    PubMed

    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.

  19. Adolescent pre-exposure to ethanol and 3,4-methylenedioxymethylamphetamine (MDMA) increases conditioned rewarding effects of MDMA and drug-induced reinstatement.

    PubMed

    Ribeiro Do Couto, Bruno; Daza-Losada, Manuel; Rodríguez-Arias, Marta; Nadal, Roser; Guerri, Consuelo; Summavielle, Teresa; Miñarro, Jose; Aguilar, Maria A

    2012-05-01

    Many adolescents often take ethanol (EtOH) in combination with 3,4-methylenedioxymethylamphetamine (MDMA). In the present work, we used a mouse model to study the effect of repeated pre-exposure during adolescence to EtOH (2 g/kg), MDMA (10 or 20 mg/kg) or EtOH + MDMA on the rewarding and reinstating effects of MDMA in the conditioned place preference (CPP) paradigm. Pre-exposure to EtOH, MDMA or both increased the rewarding effects of a low dose of MDMA (1.25 mg/kg). These pre-treatments did not affect the acquisition of the CPP induced by 5 mg/kg of MDMA. However, the CPP was more persistent in mice pre-exposed to both doses of MDMA or to EtOH + MDMA20. After extinction of the CPP induced by 5 mg/kg of MDMA, reinstatement was observed in all groups with a priming dose of 2.5 mg/kg of MDMA, in the groups pre-exposed to EtOH or MDMA alone with a priming dose of 1.25 mg/kg, and in the groups pre-treated with MDMA alone with a priming dose of 0.625 mg/kg. Pre-treatment during adolescence with MDMA or EtOH induced long-term changes in the level of biogenic amines [dihydroxyphenyl acetic acid, homovanillic acid, dopamine turnover, serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in the striatum, and 5-HT and 5-HIAA in the cortex] after the first reinstatement test, although these effects depended on the dose used during conditioning. These results suggest that exposure to EtOH and MDMA during adolescence reinforces the addictive properties of MDMA.

  20. 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.

    PubMed

    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.

  1. Evaluating User Perceptions of Mobile Medication Management Applications With Older Adults: A Usability Study

    PubMed Central

    Gates, Allison

    2014-01-01

    Background Medication nonadherence has a significant impact on the health and wellbeing of individuals with chronic disease. Several mobile medication management applications are available to help users track, remember, and read about their medication therapy. Objective The objective of this study was to explore the usability and usefulness of existing medication management applications for older adults. Methods We recruited 35 participants aged 50 and over to participate in a 2-hour usability session. The average age ranged from 52-78 years (mean 67 years) and 71% (25/35) of participants were female. Each participant was provided with an iPad loaded with four medication management applications: MyMedRec, DrugHub, Pillboxie, and PocketPharmacist. These applications were evaluated using the 10 item System Usability Scale (SUS) and visual analog scale. An investigator-moderated 30-minute discussion followed, and was recorded. We used a grounded theory (GT) approach to analyze qualitative data. Results When assessing mobile medication management applications, participants struggled to think of a need for the applications in their own lives. Many were satisfied with their current management system and proposed future use only if cognition and health declined. Most participants felt capable of using the applications after a period of time and training, but were frustrated by their initial experiences with the applications. The early experiences of participants highlighted the benefits of linear navigation and clear wording (eg, “undo” vs “cancel”) when designing for older users. While there was no order effect, participants attributed their poor performance to the order in which they tried the applications. They also described being a part of a technology generation that did not encounter the computer until adulthood. Of the four applications, PocketPharmacist was found to be the least usable with a score of 42/100 (P<.0001) though it offered a drug interaction

  2. Frequency of word occurrence in communication samples produced by adult communication aid users.

    PubMed

    Beukelman, D R; Yorkston, K M; Poblete, M; Naranjo, C

    1984-11-01

    Communication samples generated by five nonspeaking adults using Canon Communicators were collected for 14 consecutive days. Samples were analyzed to determine frequency of word occurrence. A core vocabulary of the 500 most frequently occurring words was analyzed further to determine spelling level and proportion of complete communication samples represented by subsets of the core vocabulary list. The 500 core vocabulary words represented 80% of the total words in the combined communication samples for the 5 subjects. Of all messages generated by the subjects, 33% could be communicated in their entirety using words from the core vocabulary list. The communication of the remaining messages required one or more words in addition to the core vocabulary. The spelling grade level of the words in the core vocabulary list did not exceed the seventh grade. The implications of the results for designing and customizing communication aids and for potential user training are discussed.

  3. Understanding self-harm and suicide websites: a qualitative interview study of young adult website users.

    PubMed

    Baker, Darren; Fortune, Sarah

    2008-01-01

    Self-harm and suicide websites have been heavily criticized both in the literature and the wider media, despite the fact that very little is known about them. To date, no study has interviewed users of these sites about them. This qualitative study aims to explore the accounts of young adults who engage in self-harming and suicidal behaviors and use websites dedicated to these issues, in order to develop a broader understanding of these websites and to identify potential implications for future research. In-depth interviews were conducted via e-mail with 10 participants, who were recruited directly from self-harm and suicide websites. Using discourse analysis, we identified three main ways in which participants wrote about the sites. They constructed them as sources of empathy and understanding, as communities, and as a way of coping with social and psychological distress. These discourses gave users access to important, socially valued identities, such as being understood, belonging to a community and coping with their problems. If health professionals and researchers hope to understand people who use self-harm and suicide websites, and engage them in their services, they must take a more balanced view and not focus solely on the possible risks associated with using such sites.

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

    PubMed

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

    2016-04-01

    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.

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

    PubMed

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

    2016-04-01

    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. PMID:26612394

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

    PubMed Central

    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

  7. Stereoselective effects of MDMA on inhibition of monoamine uptake

    SciTech Connect

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

    1986-03-05

    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 /sup 3/H-norepinephrine (NE) into hypothalamic synaptosomes and /sup 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 /sup 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/sub 50/ > 10/sup -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.

  8. Long-term neuronal damage and recovery after a single dose of MDMA: expression and distribution of serotonin transporter in the rat brain.

    PubMed

    Kirilly, Eszter

    2010-09-01

    "Ecstasy", 3,4-methylenedioxymethamphetamine (MDMA), an amphetamine analogue is one of the most widely used recreational drugs. In spite of the fact that neurotoxic effects of MDMA has been found in several species from rodents to non-human primates, and results increasingly point to damage also in human MDMA users, data about the sensitivity of different brain areas and the recovery after neuronal damage are scarce. Serotonin transporter (5-HTT) mRNA in the raphe nuclei also has not been examined. Humans with genetic predisposition for the slow metabolism of MDMA, the so-called "poor metabolizers" of debrisoquin are at higher risk. Five- 9% of the Caucasian population is considered to carry this phenotype. These studies were carried out in Dark Agouti rats, a special strain that show decreased microsomal CYP2D1 isoenzyme activity, and thus may serve as a model of vulnerable human users. These works were designed to characterize MDMA-induced damage and recovery of the serotonergic system including sleep and morphological changes within 180 days. In our experiments we investigated the 5-HTT mRNA expression in the brainstem and medullary raphe nuclei, 5-HTT immunoreactive (IR) fibre densities in several brain areas, and 16 functional measures of sleep in response to a single dose of +/- MDMA (15mg\\kg). Furthermore, behavioural experiments were performed 21 days after MDMA treatment. We found similar changes in 5-HTT mRNA expression in the examined raphe nuclei, namely transient increases 7 days after MDMA treatment followed by transient decreases at 21 days. Significant (20-40%), widespread reductions in 5-HTT-IR fibre density were detected in most brain areas at 7 and 21 days after MDMA administration. All cortical, but only some brainstem areas were damaged. Parallel to the neuronal damage we observed significant reductions in rapid eye movement (REM) sleep latency, increased fragmentation of sleep and increases in delta power spectra in non-REM sleep. At 180 days

  9. User Preferences for Content, Features, and Style for an App to Reduce Harmful Drinking in Young Adults: Analysis of User Feedback in App Stores and Focus Group Interviews

    PubMed Central

    Khadjesari, Zarnie; Fincham-Campbell, Stephanie; Deluca, Paolo; Watson, Rod; Drummond, Colin

    2016-01-01

    Background Electronic screening and brief intervention (eSBI) is effective in reducing weekly alcohol consumption when delivered by a computer. Mobile phone apps demonstrate promise in delivering eSBI; however, few have been designed with an evidence-based and user-informed approach. Objective This study aims to explore from a user perspective, preferences for content, appearance, and operational features to inform the design of a mobile phone app for reducing quantity and frequency of drinking in young adults engaged in harmful drinking (18-30 year olds). Methods Phase 1 included a review of user reviews of available mobile phone apps that support a reduction in alcohol consumption. Apps were identified on iTunes and Google Play and were categorized into alcohol reduction support, entertainment, blood alcohol content measurement (BAC), or other. eSBI apps with ≥18 user reviews were subject to a content analysis, which coded praise, criticism, and recommendations for app content, functionality, and esthetics. Phase 2 included four focus groups with young adults drinking at harmful levels and residing in South London to explore their views on existing eSBI apps and preferences for future content, functionality, and appearance. Detailed thematic analysis of the data was undertaken. Results In Phase 1, of the 1584 apps extracted, 201 were categorized as alcohol reduction, 154 as BAC calculators, 509 as entertainment, and 720 as other. We classified 32 apps as eSBI apps. Four apps had ≥18 user reviews: Change for Life Drinks Tracker, Drinksmeter, Drinkaware, and Alcohol Units Calculator. The highest proportion of content praises were for information and feedback provided in the apps (12/27, 44%), followed by praise for the monitoring features (5/27, 19%). Many (8/12, 67%) criticisms were for the drinking diary; all of these were related to difficulty entering drinks. Over half (18/32, 56%) of functionality criticisms were descriptions of software bugs, and over

  10. Influence of early linguistic experience on regional dialect categorization by an adult cochlear implant user: a case study.

    PubMed

    Tamati, Terrin N; Gilbert, Jaimie L; Pisoni, David B

    2014-01-01

    To investigate the ability of a cochlear implant user to categorize talkers by region of origin and examine the influence of prior linguistic experience on the perception of regional dialect variation. A postlingually deafened adult cochlear implant user from the Southern region of the United States completed a six-alternative forced-choice dialect categorization task. The cochlear implant user was most accurate at categorizing unfamiliar talkers from his own region and another familiar dialect region, and least accurate at categorizing talkers from less familiar regions. Although the dialect-specific information made available by a cochlear implant may be degraded compared with information available to normal-hearing listeners, this experienced cochlear implant user was able to reliably categorize unfamiliar talkers by region of origin. The participant made use of dialect-specific acoustic-phonetic information in the speech signal and previously stored knowledge of regional dialect differences from early exposure before implantation despite an early hearing loss.

  11. Intravenous self-administration of mephedrone, methylone and MDMA in female rats.

    PubMed

    Creehan, Kevin M; Vandewater, Sophia A; Taffe, Michael A

    2015-05-01

    Male rats will intravenously self-administer (IVSA) the substituted cathinone stimulants ("bath salts") mephedrone (4-methylmethcathione) and methylone (3,4-methylenedioxymethcathinone) robustly, whereas the IVSA of 3,4-methylenedioxymethamphetamine (MDMA) is inconsistent in many rat models. There are no data available on the self-administration of these drugs in female rats, thus a study was undertaken to contrast them directly. Groups of female Wistar rats were trained to self-administer mephedrone, methylone or MDMA (0.5 mg/kg/inf) under a Fixed-Ratio (FR) 1 schedule of reinforcement for 14 sessions. Following the acquisition interval, animals were evaluated in FR (0.0, 0.125, 0.25, 0.5, 1.0, 2.5 mg/kg/inf) and PR (0.125, 1.0 mg/kg/inf) dose-substitution procedures. The results show that female rats acquired the self-administration of all three compounds with intakes in mephedrone-trained rats that were significantly higher than that of methylone-trained or MDMA-trained rats. In dose-substitution under either FR or PR contingencies, however, the potencies of all three drugs were similar within the original training groups. The mephedrone-trained animals exhibited higher intakes of all drugs during dose-substitution, indicating lasting consequences of the training drug. Abuse liability of these three compounds is therefore predicted to be similar in established stimulant users but may differ in liability if they are primary drugs of initiation.

  12. Intravenous self-administration of mephedrone, methylone and MDMA in female rats.

    PubMed

    Creehan, Kevin M; Vandewater, Sophia A; Taffe, Michael A

    2015-05-01

    Male rats will intravenously self-administer (IVSA) the substituted cathinone stimulants ("bath salts") mephedrone (4-methylmethcathione) and methylone (3,4-methylenedioxymethcathinone) robustly, whereas the IVSA of 3,4-methylenedioxymethamphetamine (MDMA) is inconsistent in many rat models. There are no data available on the self-administration of these drugs in female rats, thus a study was undertaken to contrast them directly. Groups of female Wistar rats were trained to self-administer mephedrone, methylone or MDMA (0.5 mg/kg/inf) under a Fixed-Ratio (FR) 1 schedule of reinforcement for 14 sessions. Following the acquisition interval, animals were evaluated in FR (0.0, 0.125, 0.25, 0.5, 1.0, 2.5 mg/kg/inf) and PR (0.125, 1.0 mg/kg/inf) dose-substitution procedures. The results show that female rats acquired the self-administration of all three compounds with intakes in mephedrone-trained rats that were significantly higher than that of methylone-trained or MDMA-trained rats. In dose-substitution under either FR or PR contingencies, however, the potencies of all three drugs were similar within the original training groups. The mephedrone-trained animals exhibited higher intakes of all drugs during dose-substitution, indicating lasting consequences of the training drug. Abuse liability of these three compounds is therefore predicted to be similar in established stimulant users but may differ in liability if they are primary drugs of initiation. PMID:25600245

  13. MDMA alters emotional processing and facilitates positive social interaction

    PubMed Central

    Wardle, Margaret C.; de Wit, Harriet

    2014-01-01

    Background ±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. Methods Over three sessions 36 healthy volunteers with previous ecstasy use received MDMA (0.75mg/kg, 1.5mg/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. Results 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. Conclusions 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. PMID:24728603

  14. Evaluation of language and communication skills in adult key word signing users with intellectual disability: advantages of a narrative task.

    PubMed

    Meuris, Kristien; Maes, Bea; Zink, Inge

    2014-10-01

    The evaluation of language and communication skills in adults who use augmentative and alternative communication (AAC) in general and key word signing (KWS) in particular, can be an elaborate task. Besides being time-consuming and not very similar to natural communication, standard language tests often do not take AAC or KWS into account. Therefore, we developed a narrative task specifically for adults with intellectual disability (ID) who use KWS. The task was evaluated in a group of 40 adult KWS users. Outcome measures on the narrative task correlated significantly with measures of standard language and communication tests for verbal language, but not for use of manual signs. All narrative measures, for both verbal language and manual signing, correlated highly with similar measures from a conversation sample. The developed narrative task proved useful and valid to evaluate the language and communication skills of adults with ID taking into account both their verbal language and manual sign use.

  15. Gaze patterns during identity and emotion judgments in hearing adults and deaf users of American Sign Language.

    PubMed

    Letourneau, Susan M; Mitchell, Teresa V

    2011-01-01

    Deaf individuals rely on facial expressions for emotional, social, and linguistic cues. In order to test the hypothesis that specialized experience with faces can alter typically observed gaze patterns, twelve hearing adults and twelve deaf, early-users of American Sign Language judged the emotion and identity of expressive faces (including whole faces, and isolated top and bottom halves), while accuracy and fixations were recorded. Both groups recognized individuals more accurately from top than bottom halves, and emotional expressions from bottom than top halves. Hearing adults directed the majority of fixations to the top halves of faces in both tasks, but fixated the bottom half slightly more often when judging emotion than identity. In contrast, deaf adults often split fixations evenly between the top and bottom halves regardless of task demands. These results suggest that deaf adults have habitual fixation patterns that may maximize their ability to gather information from expressive faces. PMID:21882720

  16. Gaze patterns during identity and emotion judgments in hearing adults and deaf users of American Sign Language.

    PubMed

    Letourneau, Susan M; Mitchell, Teresa V

    2011-01-01

    Deaf individuals rely on facial expressions for emotional, social, and linguistic cues. In order to test the hypothesis that specialized experience with faces can alter typically observed gaze patterns, twelve hearing adults and twelve deaf, early-users of American Sign Language judged the emotion and identity of expressive faces (including whole faces, and isolated top and bottom halves), while accuracy and fixations were recorded. Both groups recognized individuals more accurately from top than bottom halves, and emotional expressions from bottom than top halves. Hearing adults directed the majority of fixations to the top halves of faces in both tasks, but fixated the bottom half slightly more often when judging emotion than identity. In contrast, deaf adults often split fixations evenly between the top and bottom halves regardless of task demands. These results suggest that deaf adults have habitual fixation patterns that may maximize their ability to gather information from expressive faces.

  17. Imaging brain activity in conscious monkeys following oral MDMA ("ecstasy").

    PubMed

    Brevard, Mathew E; Meyer, Jerrold S; Harder, Josie A; Ferris, Craig F

    2006-07-01

    Recreational use of 3,4-methylenedioxymethamphetamine (MDMA;"ecstasy") poses worldwide potential health problems. Clinical studies show that repeated exposure to low oral doses of MDMA has toxic effects on the brain, altering cognitive and psychosocial behavior. Functional magnetic resonance imaging in conscious marmoset monkeys was used to evaluate the sensitivity of the brain to an oral dose of MDMA (1 mg/kg). Following MDMA administration, the midbrain raphe nuclei and substantia nigra, major sources of serotonin and dopamine, were activated as were the hippocampus, hypothalamus and amygdala. The corticostriatal circuit of dorsal thalamus, sensorimotor cortex and basal ganglia showed a robust, coherent activation pattern. Two key reward areas, the nucleus accumbens and prefrontal cortex, and most other cortical regions showed little activation. The visual cortex, however, showed intense activation without applied visual stimuli. These data identify brain areas and functional circuits sensitive to a recreational dose of MDMA, some of which may be vulnerable to long-term intermittent exposure to this drug.

  18. Reinstatement of extinguished amphetamine self-administration by 3,4-methylenedioxymethamphetamine (MDMA) and its enantiomers in rhesus monkeys

    PubMed Central

    McClung, Jessica; Fantegrossi, William

    2010-01-01

    Rationale The effectiveness of MDMA and its enantiomers to reinstate responding previously maintained by drug self-administration has not been thoroughly investigated. Objectives The present study was designed to compare the reinstatement effects of amphetamine, the piperazine-analog BZP, SR(+/−)-MDMA, S(+)-MDMA, R(−)-MDMA, and fenfluramine on behavior maintained under a second-order schedule of intravenous amphetamine self-administration in rhesus monkeys (n=4). Methods Following saline substitution and extinction, a range of doses of amphetamine, BZP, SR(+/−)-MDMA, S(+)-MDMA, R(−)-MDMA, and fenfluramine were administered i.v. as non-contingent priming injections in order to characterize their effectiveness to reinstate responding previously maintained by amphetamine self-administration. Results Priming injections of amphetamine, BZP, SR(+/−)-MDMA, and S(+)-MDMA induced significant reinstatement effects. In contrast, neither R(−)-MDMA nor fenfluramine effectively reinstated behavior. Pretreatment with the selective serotonin transporter inhibitor, fluoxetine, attenuated the reinstatement effects of SR(+/−)-MDMA, S(+)-MDMA, and BZP but had no significant effect on amphetamine-primed reinstatement. Conclusions Given the profile of neurochemical effects published previously, these findings suggest that the reinstatement effects of MDMA are mediated primarily by dopamine release; however, the attenuation of MDMA-induced reinstatement by fluoxetine supports previous research demonstrating the complex behavioral pharmacology of MDMA-like drugs and that the reinstatement effects of MDMA are at least partially mediated by serotonergic mechanisms. PMID:20309529

  19. Neuropsychological Sex Differences Associated with Age of Initiated Use Among Young Adult Cannabis Users

    PubMed Central

    Crane, Natania A.; Schuster, Randi Melissa; Mermelstein, Robin J.; Gonzalez, Raul

    2015-01-01

    Introduction Earlier initiation of cannabis use is associated with poorer neuropsychological functioning across several domains. Given well-documented sex differences in neuromaturation during adolescence, initiation of cannabis use during this time may affect neuropsychological functioning differently for males and females. Method In the current study, we examined sex differences in the relationship between age of initiated cannabis use and neuropsychological performance after controlling for amount of lifetime cannabis use in 44 male and 25 female young adult cannabis users. Results We found that an earlier age of initiated use was related to poorer episodic memory, especially immediate recall, in females, but not in males. On the other hand, we found that, surprisingly, an earlier age of initiated use was associated with better decision-making overall. However, exploratory analyses found sex-specific factors associated with decision-making and age of initiated use, specifically that ADHD symptoms in females may drive the relationship between an earlier age of initiated use and better decision-making. Further, an earlier age of initiated use was associated with less education, a lower IQ, and fewer years of mother’s education for females, but more lifetime cannabis use for males. Conclusions Taken together, our findings suggest there are sex-differences in the associations between age of initiated cannabis use and neuropsychological functioning. The current study provides preliminary evidence that males and females may have different neuropsychological vulnerabilities that place them at risk for initiating cannabis use and continued cannabis use, highlighting the importance of examining the impact of cannabis on neuropsychological functioning separately for males and females. PMID:25832823

  20. Neurochemical substrates of the rewarding effects of MDMA: implications for the development of pharmacotherapies to MDMA dependence.

    PubMed

    Roger-Sánchez, Concepción; García-Pardo, María P; Rodríguez-Arias, Marta; Miñarro, Jose; Aguilar, María A

    2016-04-01

    In recent years, studies with animal models of reward, such as the intracranial self-stimulation, self-administration, and conditioned place preference paradigms, have increased our knowledge on the neurochemical substrates of the rewarding effects of 3,4-methylenedioxymetamphetamine (MDMA) in rodents. However, pharmacological and neuroimaging studies with human participants are scarce. Serotonin [5-hydroxytryptamine (5-HT)], dopamine (DA), endocannabinoids, and endogenous opiates are the main neurotransmitter systems involved in the rewarding effects of MDMA in rodents, but other neurotransmitters such as glutamate, acetylcholine, adenosine, and neurotensin are also involved. The most important finding of recent research is the demonstration of differential involvement of specific neurotransmitter receptor subtypes (5-HT2, 5-HT3, DA D1, DA D2, CB1, μ and δ opioid, etc.) and extracellular proteins (DA and 5-HT transporters) in the acquisition, expression, extinction, and reinstatement of MDMA self-administration and conditioned place preference. It is important to extend the research on the effects of different compounds acting on these receptors/transporters in animal models of reward, especially in priming-induced, cue-induced, and stress-induced reinstatement. Increase in knowledge of the neurochemical substrates of the rewarding effects of MDMA may contribute to the design of new pharmacological treatments for individuals who develop MDMA dependence. PMID:26650254

  1. Developing a User-Centred Planning Tool for Young Adults with Development Disorders: A Research-Based Teaching Project.

    PubMed

    Ribu, Kirsten; Patel, Tulpesh

    2016-01-01

    People with development disorders, for instance autism, need structured plans to help create predictability in their daily lives. Digital plans can facilitate enhanced independency, learning, and quality of life, but existing apps are largely general purpose and lack the flexibility required by this specific but heterogeneous user group. Universal design is both a goal and a process and should be based on a holistic approach and user-centered design, interacting with the users in all stages of the development process. At Oslo and Akershus University College (HiOA) we conducted a research-based teaching project in co-operation with the Department of Neuro-habilitation at Oslo University Hospital (OUS) with two employees acting as project managers and students as developers. Three groups of Computer Science bachelor students developed digital prototypes for a planning tool for young adults with pervasive development disorders, who live either with their families or in supervised residences, and do not receive extensive public services. The students conducted the initial planning phase of the software development process, focusing on prototyping the system requirements, whilst a professional software company programmed the end solution. The goal of the project was to develop flexible and adaptive user-oriented and user-specific app solutions for tablets that can aid this diverse user group in structuring daily life, whereby, for example, photos of objects and places known to the individual user replace general pictures or drawings, and checklists can be elaborate or sparse as necessary. The three student groups worked independently of each other and created interactive working prototypes based on tests, observations and short interviews with end users (both administrators and residents) and regular user feedback from the project managers. Three very different solutions were developed that were of high enough quality that an external software company were able to

  2. Developing a User-Centred Planning Tool for Young Adults with Development Disorders: A Research-Based Teaching Project.

    PubMed

    Ribu, Kirsten; Patel, Tulpesh

    2016-01-01

    People with development disorders, for instance autism, need structured plans to help create predictability in their daily lives. Digital plans can facilitate enhanced independency, learning, and quality of life, but existing apps are largely general purpose and lack the flexibility required by this specific but heterogeneous user group. Universal design is both a goal and a process and should be based on a holistic approach and user-centered design, interacting with the users in all stages of the development process. At Oslo and Akershus University College (HiOA) we conducted a research-based teaching project in co-operation with the Department of Neuro-habilitation at Oslo University Hospital (OUS) with two employees acting as project managers and students as developers. Three groups of Computer Science bachelor students developed digital prototypes for a planning tool for young adults with pervasive development disorders, who live either with their families or in supervised residences, and do not receive extensive public services. The students conducted the initial planning phase of the software development process, focusing on prototyping the system requirements, whilst a professional software company programmed the end solution. The goal of the project was to develop flexible and adaptive user-oriented and user-specific app solutions for tablets that can aid this diverse user group in structuring daily life, whereby, for example, photos of objects and places known to the individual user replace general pictures or drawings, and checklists can be elaborate or sparse as necessary. The three student groups worked independently of each other and created interactive working prototypes based on tests, observations and short interviews with end users (both administrators and residents) and regular user feedback from the project managers. Three very different solutions were developed that were of high enough quality that an external software company were able to

  3. Assessing the user experience of older adults using a neural network trained to recognize emotions from brain signals.

    PubMed

    Meza-Kubo, Victoria; Morán, Alberto L; Carrillo, Ivan; Galindo, Gilberto; García-Canseco, Eloisa

    2016-08-01

    The use of Ambient Assisted Living (AAL) technologies as a means to cope with problems that arise due to an increasing and aging population is becoming usual. AAL technologies are used to prevent, cure and improve the wellness and health conditions of the elderly. However, their adoption and use by older adults is still a major challenge. User Experience (UX) evaluations aim at aiding on this task, by identifying the experience that a user has while interacting with an AAL technology under particular conditions. This may help designing better products and improve user engagement and adoption of AAL solutions. However, evaluating the UX of AAL technologies is a difficult task, due to the inherent limitations of their subjects and of the evaluation methods. In this study, we validated the feasibility of assessing the UX of older adults while they use a cognitive stimulation application using a neural network trained to recognize pleasant and unpleasant emotions from electroencephalography (EEG) signals by contrasting our results with those of additional self-report and qualitative analysis UX evaluations. Our study results provide evidence about the feasibility of assessing the UX of older adults using a neural network that take as input the EEG signals; the classification accuracy of our neural network ranges from 60.87% to 82.61%. As future work we will conduct additional UX evaluation studies using the three different methods, in order to appropriately validate these results. PMID:27392644

  4. Assessing the user experience of older adults using a neural network trained to recognize emotions from brain signals.

    PubMed

    Meza-Kubo, Victoria; Morán, Alberto L; Carrillo, Ivan; Galindo, Gilberto; García-Canseco, Eloisa

    2016-08-01

    The use of Ambient Assisted Living (AAL) technologies as a means to cope with problems that arise due to an increasing and aging population is becoming usual. AAL technologies are used to prevent, cure and improve the wellness and health conditions of the elderly. However, their adoption and use by older adults is still a major challenge. User Experience (UX) evaluations aim at aiding on this task, by identifying the experience that a user has while interacting with an AAL technology under particular conditions. This may help designing better products and improve user engagement and adoption of AAL solutions. However, evaluating the UX of AAL technologies is a difficult task, due to the inherent limitations of their subjects and of the evaluation methods. In this study, we validated the feasibility of assessing the UX of older adults while they use a cognitive stimulation application using a neural network trained to recognize pleasant and unpleasant emotions from electroencephalography (EEG) signals by contrasting our results with those of additional self-report and qualitative analysis UX evaluations. Our study results provide evidence about the feasibility of assessing the UX of older adults using a neural network that take as input the EEG signals; the classification accuracy of our neural network ranges from 60.87% to 82.61%. As future work we will conduct additional UX evaluation studies using the three different methods, in order to appropriately validate these results.

  5. Ritanserin-sensitive receptors modulate the prosocial and the anxiolytic effect of MDMA derivatives, DOB and PMA, in zebrafish.

    PubMed

    Ponzoni, Luisa; Sala, Mariaelvina; Braida, Daniela

    2016-11-01

    Little is known about the pharmacological effects of amphetamine derivatives. In the present study, the effect on social preference and anxiety-like behavior of 2,5-dimetoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine (PMA), in comparison with 3,4 methylenedioxymethamphetamine (MDMA) was investigated in zebrafish, an emerging model to study emotional behavior in an inexpensive and quick manner. DOB (0.05-2mg/kg), PMA (0.0005-2mg/kg) or MDMA (0.25-20mg/kg), given i.m. to adult zebrafish, progressively increased the time spent in the proximity of nacre fish picture in a social preference test. However, high doses were ineffective. Similarly, in the novel tank diving and light-dark tests the compounds elicited a progressive anxiolytic effect in terms of time spent in the upper half of the tank and in the light compartment, respectively. All the above effects were interpolated by symmetrical parabolas. The 5-HT2A/C antagonist ritanserin (0.025-2.5mg/kg) in association with the maximal effective dose of MDMA, DOB and PMA blocked both the social and anxiolytic effect. Taken together these findings demonstrate for the first time the prosocial and anxiolytic properties of DOB and PMA and focus on the mechanisms of their action through the serotonergic-like system suggesting a potential clinical application. PMID:27506653

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

    PubMed

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

    2015-01-01

    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 upregulation 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

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

    PubMed

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

    2015-01-01

    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 upregulation 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.

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

    PubMed

    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. PMID:26940772

  9. The relationship between the speech perception and the degree of satisfaction among adult users of cochlear implants

    PubMed Central

    Granço, Fernanda Soares; Fernandes, Nayara Freitas; Morettin, Marina; Filho, Orozimbo Alves Costa; Bevilacqua, Maria Cecília

    2013-01-01

    Summary Introduction: In recent years, the benefits associated with the use of cochlear implants (CIs), especially with regard to speech perception, have proven to surpass those produced by the use of hearing aids, making CIs a highly efficient resource for patients with severe/profound hearing loss. However, few studies so far have assessed the satisfaction of adult users of CIs. Objective: To analyze the relationship between the level of speech perception and degree of satisfaction of adult users of CI. Method: This was a prospective cross-sectional study conducted in the Audiological Research Center (CPA) of the Hospital of Craniofacial Anomalies, University of São Paulo (HRAC/USP), in Bauru, São Paulo, Brazil. A total of 12 users of CIs with pre-lingual or post-lingual hearing loss participated in this study. The following tools were used in the assessment: a questionnaire, “Satisfaction with Amplification in Daily Life” (SADL), culturally adapted to Brazilian Portuguese, as well as its relationship with the speech perception results; a speech perception test under quiet conditions; and the Hearing in Noise Test (HINT)Brazil under free field conditions. Results: The participants in the study were on the whole satisfied with their devices, and the degree of satisfaction correlated positively with the ability to perceive monosyllabic words under quiet conditions. The satisfaction did not correlate with the level of speech perception in noisy environments. Conclusion: Assessments of satisfaction may help professionals to predict what other factors, in addition to speech perception, may contribute to the satisfaction of CI users in order to reorganize the intervention process to improve the users' quality of life. PMID:25992014

  10. Comparison of (+)-methamphetamine, ±}-methylenedioxymethamphetamine (MDMA), (+)-amphetamine and ±}-fenfluramine in rats on egocentric learning in the Cincinnati water maze

    PubMed Central

    Vorhees, Charles V.; He, Elizabeth; Skelton, Matthew R.; Graham, Devon L.; Schaefer, Tori L.; Grace, Curtis E.; Braun, Amanda A.; Amos-Kroohs, Robyn; Williams, Michael T.

    2010-01-01

    (+)-Methamphetamine (MA), (±)-3,4-methylenedioxymethamphetamine (MDMA), (+)-amphetamine (AMPH), and (±)-fenfluramine (FEN) are phenylethylamines with CNS effects. At higher doses, each induces protracted reductions in brain dopamine and/or serotonin. Chronic MA and MDMA users show persistent monoamine reductions and cognitive impairments. In rats, similar neurochemical effects can be induced, yet cognitive impairments have been difficult to demonstrate. We recently showed that rats treated on a single day with MA (10 mg/kg × 4 at 2 h intervals) exhibit impaired egocentric learning (Cincinnati water maze; CWM) without affecting spatial learning (Morris water maze) (Herring et al., 2008). Whether this effect is unique to MA or is a general characteristic of these drugs is unknown. Accordingly, this experiment compared these drugs on CWM performance. Drugs were given s.c. in four doses at 2 h intervals. MA doses were 10 or 12.5 mg/kg/dose, AMPH 25 mg/kg/dose (to match MA12.5-induced hyperthermia), MDMA 15 mg/kg/dose (previously established hyperthermia-inducing dose), and FEN 16.5 mg/kg/dose (equimolar to MA12.5). Two weeks later, rats were tested in the CWM (2 trials/day, 21 days). AMPH and MA (both doses) induced significant increases in CWM errors and latency to reach the goal with no differences in swim speed. MDMA and FEN did not significantly alter learning. Given that FEN selectively and MDMA preferentially affect serotonin whereas AMPH selectively and MA preferentially affect dopamine, the data suggest that egocentric learning may be predominantly dopaminergically-mediated. PMID:20730798

  11. Validation and User Evaluation of a Sensor-Based Method for Detecting Mobility-Related Activities in Older Adults

    PubMed Central

    Geraedts, Hilde A. E.; Zijlstra, Wiebren; Van Keeken, Helco G.; Zhang, Wei; Stevens, Martin

    2015-01-01

    Regular physical activity is essential for older adults to stay healthy and independent. However, daily physical activity is generally low among older adults and mainly consists of activities such as standing and shuffling around indoors. Accurate measurement of this low-energy expenditure daily physical activity is crucial for stimulation of activity. The objective of this study was to assess the validity of a necklace-worn sensor-based method for detecting time-on-legs and daily life mobility related postures in older adults. In addition user opinion about the practical use of the sensor was evaluated. Twenty frail and non-frail older adults performed a standardized and free movement protocol in their own home. Results of the sensor-based method were compared to video observation. Sensitivity, specificity and overall agreement of sensor outcomes compared to video observation were calculated. Mobility was assessed based on time-on-legs. Further assessment included the categories standing, sitting, walking and lying. Time-on-legs based sensitivity, specificity and percentage agreement were good to excellent and comparable to laboratory outcomes in other studies. Category-based sensitivity, specificity and overall agreement were moderate to excellent. The necklace-worn sensor is considered an acceptable valid instrument for assessing home-based physical activity based upon time-on-legs in frail and non-frail older adults, but category-based assessment of gait and postures could be further developed. PMID:26361009

  12. Characterisation of User-Defined Health Status in Older Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Starr, J. M.; Marsden, L.

    2008-01-01

    Background: Older adults with Intellectual Disabilities (ID) have an excess disease burden that standard health assessments are designed to detect. Older adults with ID have a broader concept of health with dimensions of well being in addition to absence of disease in line with the World Health Organization's health definition. We sought to…

  13. Understanding Tobacco-Related Attitudes among College and Noncollege Young Adult Hookah and Cigarette Users

    ERIC Educational Resources Information Center

    Lee, Youn Ok; Bahreinifar, Sareh; Ling, Pamela M.

    2014-01-01

    Objective: To examine differences in tobacco-related attitudes and hookah and cigarette use among college and noncollege young adults. Participants: Time-location samples of young adult bar patrons in San Diego, California ("N" = 2,243), Tulsa ("N" = 2,095) and Oklahoma City ("N" = 2,200), Oklahoma, Albuquerque…

  14. Multivitamin Use and Serum Vitamin B12 Concentrations in Older-Adult Metformin Users in REGARDS, 2003-2007.

    PubMed

    Kancherla, Vijaya; Garn, Joshua V; Zakai, Neil A; Williamson, Rebecca S; Cashion, Winn T; Odewole, Oluwaseun; Judd, Suzanne E; Oakley, Godfrey P

    2016-01-01

    Metformin, an insulin-sensitizing drug, is a first line treatment for type 2 diabetes. Long-term use of metformin has been associated with subsequent reductions in vitamin B12 concentrations. The objective of our study was to determine whether metformin use is associated with lower serum vitamin B12 concentrations in older adults, and whether concurrent use of multivitamins modifies this association. We examined 2,510 participants aged 50 years and over, participating in the national population-based Reasons for Geographic And Racial Differences in Stroke (REGARDS) Study. Multivariable linear and logistic regression models were used to assess associations between multivitamin use and serum vitamin B12 concentrations. We estimated adjusted odds ratios (aOR)s and confidence intervals (CI)s. Results were stratified by three metformin/diabetes sub-groups: 1) participants with diabetes who were metformin users; 2) participants with diabetes who were not metformin users; and 3) participants without diabetes. We found that diabetic metformin users had significantly lower geometric mean serum B12 concentrations (409 pmol/L) than the group with diabetes not taking metformin (485 pmol/L; P<0.01), and the group without diabetes (445 pmol/L; P = 0.02). The geometric mean serum B12 concentrations were greater for multivitamin users (509 pmol/L) compared to those who did not use multivitamins (376 pmol/L; p<0.01). Among the participants with diabetes who were on metformin therapy, multivitamin use was associated with geometric mean serum vitamin B12 concentrations that were 50% (or 161 pmol/L) higher, compared to those not using multivitamins. Among metformin users, multivitamin use was associated with lower prevalence of combined low and borderline vitamin B12 concentrations (aOR = 0.14; 95% CI = 0.04, 0.54) compared to those not using multivitamins. In conclusion, metformin use was associated with lower geometric mean serum vitamin B12 concentrations among diabetic older

  15. Multivitamin Use and Serum Vitamin B12 Concentrations in Older-Adult Metformin Users in REGARDS, 2003-2007

    PubMed Central

    Kancherla, Vijaya; Garn, Joshua V.; Zakai, Neil A.; Williamson, Rebecca S.; Cashion, Winn T.; Odewole, Oluwaseun; Judd, Suzanne E.; Oakley, Godfrey P.

    2016-01-01

    Metformin, an insulin-sensitizing drug, is a first line treatment for type 2 diabetes. Long-term use of metformin has been associated with subsequent reductions in vitamin B12 concentrations. The objective of our study was to determine whether metformin use is associated with lower serum vitamin B12 concentrations in older adults, and whether concurrent use of multivitamins modifies this association. We examined 2,510 participants aged 50 years and over, participating in the national population-based Reasons for Geographic And Racial Differences in Stroke (REGARDS) Study. Multivariable linear and logistic regression models were used to assess associations between multivitamin use and serum vitamin B12 concentrations. We estimated adjusted odds ratios (aOR)s and confidence intervals (CI)s. Results were stratified by three metformin/diabetes sub-groups: 1) participants with diabetes who were metformin users; 2) participants with diabetes who were not metformin users; and 3) participants without diabetes. We found that diabetic metformin users had significantly lower geometric mean serum B12 concentrations (409 pmol/L) than the group with diabetes not taking metformin (485 pmol/L; P<0.01), and the group without diabetes (445 pmol/L; P = 0.02). The geometric mean serum B12 concentrations were greater for multivitamin users (509 pmol/L) compared to those who did not use multivitamins (376 pmol/L; p<0.01). Among the participants with diabetes who were on metformin therapy, multivitamin use was associated with geometric mean serum vitamin B12 concentrations that were 50% (or 161 pmol/L) higher, compared to those not using multivitamins. Among metformin users, multivitamin use was associated with lower prevalence of combined low and borderline vitamin B12 concentrations (aOR = 0.14; 95% CI = 0.04, 0.54) compared to those not using multivitamins. In conclusion, metformin use was associated with lower geometric mean serum vitamin B12 concentrations among diabetic older

  16. A Contextual Comparison of Risk Behaviors Among Older Adult Drug Users and Harm Reduction in Suburban Versus Inner-City Social Environments

    PubMed Central

    Boeri, Miriam W.; Tyndall, Benjamin D.

    2012-01-01

    Recent epidemiological data show that older adults comprise a growing age group of drug users and new AIDS cases in the United States. Prevention and intervention studies show that risk behaviors leading to HIV infection are increasing among older users, particularly among the socially vulnerable. Yet older adults remain an under-researched population of drug users and little is known about their risk behaviors. Our aim is to address this gap in knowledge on older users by comparing contextual factors that influence risk behaviors and harm reduction strategies practiced by older drug users living in different communities. This study is based on ethnographic fieldwork in suburban and inner-city neighborhoods in a large metropolitan area in the southeastern USA. Interviewers conducted face-to-face, in-depth, life-history interviews with 69 older adults (age 45 and older) who used heroin, cocaine, and/or methamphetamine. Findings show that while risk behaviors were similar among older adult drug users living in suburban and inner-city environments, the provision of harm reduction education and paraphernalia varied widely. The results show the need for the expansion of harm reduction services focused on older adult drug users who are homeless, uninsured, or socially isolated. This application-oriented research will inform healthcare and treatment providers and generate new directions for future collaborative harm reduction services aimed to decrease the spread of HIV and other infectious diseases associated with drug use. PMID:23162176

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

    PubMed

    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 <20% of 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 < 0.0001) and core temperature correlated with MDA concentrations (r = 0.7595; P < 0.0001), suggesting that 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.

  18. Reliability and validity of the Marijuana Motives Measure among young adult frequent cannabis users and associations with cannabis dependence.

    PubMed

    Benschop, Annemieke; Liebregts, Nienke; van der Pol, Peggy; Schaap, Rick; Buisman, Renate; van Laar, Margriet; van den Brink, Wim; de Graaf, Ron; Korf, Dirk J

    2015-01-01

    The Marijuana Motives Measure (MMM) has so far been examined mainly in student populations, often with relatively limited involvement in cannabis use. This study evaluated the factor structure of the MMM in a demographically mixed sample of 600 young adult (18-30 years) frequent (≥ 3 days per week) cannabis users in the Netherlands. Analysis confirmed a five-factor solution, denoting coping, enhancement, social, conformity and expansion motives. Additionally, the original MMM was extended with two items (boredom and habit), which formed a distinct, internally consistent sixth factor labelled routine motives. In a multivariable logistic regression analysis, coping and routine motives showed significant associations with 12-month DSM-IV cannabis dependence. The results suggest general reliability and validity of the MMM in a heterogeneous population of experienced cannabis users.

  19. Andragogical Characteristics and Expectations of University of Hawai'i Adult Learners in a 3D Multi-User Virtual Environment

    ERIC Educational Resources Information Center

    Meeder, Rebecca L.

    2012-01-01

    The purpose of this study was to discover which andragogical characteristics and expectations of adult learners manifested themselves in the three-dimensional, multi-user virtual environment known as Second Life. This digital ethnographic study focused specifically on adult students within the University of Hawai'i Second Life group and their…

  20. Perspectives on Health among Adult Users of Illicit Stimulant Drugs in Rural Ohio

    ERIC Educational Resources Information Center

    Siegal, Harvey A.; Draus, Paul J.; Carlson, Robert G.; Falck, Russel S.; Wang, Jichuan

    2006-01-01

    Context: Although the nonmedical use of stimulant drugs such as cocaine and methamphetamine is increasingly common in many rural areas of the United States, little is known about the health beliefs of people who use these drugs. Purpose: This research describes illicit stimulant drug users' views on health and health-related concepts that may…

  1. Evaluating an Online Cognitive Training Platform for Older Adults: User Experience and Implementation Requirements.

    PubMed

    Haesner, Marten; Steinert, Anika; O'Sullivan, Julie Lorraine; Weichenberger, Markus

    2015-08-01

    Decline of cognitive function is a part of aging. However, intensive cognitive training can improve important cognitive functions, such as attention and working memory. Because existing systems are not older adult-friendly and are usually not based on scientific evidence, an online platform was developed for cognitive training with information and communication features and evaluated in an 8-week field test. In a randomized clinical trial with 80 older adults, findings from log data analysis and questionnaires revealed a good use of the online platform. Communication or assistive features were not used often. Good usability ratings were given to the cognitive exercises. Subjective improvements of cognitive functions due to the training were reported. The current article presents concrete requirements and recommendations for deploying cognitive training software in older adult residential homes.

  2. Identification of a Possible Role for Atrial Natiuretic Peptide in MDMA-induced hyperthermia

    PubMed Central

    Hrometz, Sandra L; Thatcher, Karen E; Ebert, Jeremy A; Mills, Edward M; Sprague, Jon E

    2011-01-01

    MDMA (3,4-methylenedioxymethamphetamine) induces thermogenesis in a mitochondrial uncoupling protein 3-dependent manner. There is evidence that this hyperthermia is mediated in part by the lipolytic release of free fatty acids, that subsequently activate uncoupling protein 3 in skeletal muscle mitochondria. We hypothesize that atrial natriuretic peptide (ANP), a strong lipolytic mediator, may contribute to the induction and maintenance of MDMA-induced thermogenesis. The specific aims of this study were to 1) determine if ANP is released following MDMA administration, and 2) use the ANP receptor antagonist, Anantin, to ascertain the role of ANP in MDMA-induced hyperthermia. ANP levels were measured in plasma at baseline, 10, 20, 30 and 60 min following MDMA (40 mg/kg, sc) administration in 16 male Sprague-Dawley rats. A robust increase in ANP was seen within ten min of MDMA administration. ANP levels returned to baseline at 20 min and then gradually rose over the 60 min monitoring period. The administration of Anantin (40 mg, ip), 15 min before and after MDMA, significantly attenuated the MDMA-induced hyperthermia. We conclude that ANP signaling contributes to the hyperthermia induced by MDMA. PMID:21827841

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

    PubMed

    Alsufyani, Hadeel A; Docherty, James R

    2015-07-01

    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.

  4. Neuroimaging in moderate MDMA use: A systematic review.

    PubMed

    Mueller, F; Lenz, C; Steiner, M; Dolder, P C; Walter, M; Lang, U E; Liechti, M E; Borgwardt, S

    2016-03-01

    MDMA ("ecstasy") is widely used as a recreational drug, although there has been some debate about its neurotoxic effects in humans. However, most studies have investigated subjects with heavy use patterns, and the effects of transient MDMA use are unclear. In this review, we therefore focus on subjects with moderate use patterns, in order to assess the evidence for harmful effects. We searched for studies applying neuroimaging techniques in man. Studies were included if they provided at least one group with an average of <50 lifetime episodes of ecstasy use or an average lifetime consumption of <100 ecstasy tablets. All studies published before July 2015 were included. Of the 250 studies identified in the database search, 19 were included. There is no convincing evidence that moderate MDMA use is associated with structural or functional brain alterations in neuroimaging measures. The lack of significant results was associated with high methodological heterogeneity in terms of dosages and co-consumption of other drugs, low quality of studies and small sample sizes. PMID:26746590

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

    PubMed

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

    2014-05-01

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

  6. [Prevalence and alcohol user profile in adult population in a south Brazilian city].

    PubMed

    Bortoluzzi, Marcelo Carlos; Traebert, Jefferson; Loguercio, Alessandro; Kehrig, Ruth Terezinha

    2010-05-01

    This is an observational cross-sectional survey which included 707 individuals from a south Brazilian city (Joaçaba, in Santa Catarina State) aiming to know the alcohol user prevalence as well as the profile of the user. The results showed that 45.5% (322) of that population consume alcohol on regular basis and had used it at least once in the last month. The regular alcohol consumption occurs predominantly on males (p <0.001), in people under 39 years old (p =0.007), occurring predominantly with ones working comparing to the ones not working, (p <0.001), have more than 8 years of education (p <0.001) and with income greater than 1738.00 reais - Brazilian currency (p <0.001). The regular alcohol consumption was greater on those who classified his health status as regular, good or very good (p <0.006), also this relation happen to those people who haven't been under hospital internment in the last year (p <0.013). The depression levels scored by the Beck Depression Inventory (BDI) showed low levels to those who regularly consume alcohol (p <0.047). PMID:20464180

  7. Dinosaur girls, Candy girls, and Trinity: Voices of Taiwanese Club Drug Users

    PubMed Central

    Leung, Kit-Sang; Li, Jih-Heng; Tsay, Wen-Ing; Callahan, Catina; Liu, Shu-Fen; Hsu, Jui; Hoffer, Lee; Cottler, Linda B.

    2008-01-01

    Research among Asian MDMA users is rare. To evaluate the feasibility of a study on abuse/dependence on Ecstasy, two focus groups with users (n=12) and one with health professionals (n=7) were conducted in Taiwan. Major results included blatant human testing with “candy/dinosaur girls” and a specific sequence of use called “Trinity” (MDMA, Ketamine, and marijuana). “Head-shaked bars” and “KTVs” were public places where illegal behaviors were implicitly allowed. Depression after MDMA use was not reported. For future studies, participants suggested that MRI could be a strong incentive for young users to enhance willingness to participate. Cultural issues are discussed. PMID:19042808

  8. Individual and socio-environmental factors associated with unsafe injection practices among young adult injection drug users in San Diego

    PubMed Central

    Muñoz, Fátima; Burgos, José Luis; Cuevas-Mota, Jazmine; Teshale, Eyasu; Garfein, Richard S.

    2014-01-01

    Unsafe injection practices significantly increase the risk of hepatitis C virus and human immunodeficiency virus (HIV) infection among injection drug users (IDUs). We examined individual and socio-environmental factors associated with unsafe injection practices in young adult IDUs in San Diego, California. Of 494 IDUs, 46.9% reported receptive syringe sharing and 68.8% sharing drug preparation paraphernalia in the last 3 months. Unsafe injection practices were associated with increased odds of having friends who injected drugs with used syringes, injecting with friends, sexual partners, and injecting heroin. Perceived high susceptibility to HIV and perceived barriers to obtaining sterile syringes were associated with increased odds of receptive syringe sharing, but not with sharing injection paraphernalia. Over half IDUs reported unsafe injection practices, and our results suggest that personal relationships might influence IDUs’ perceptions that dictate behavior. Integrated interventions addressing individual and socio-environmental factors are needed to promote safe injection practices in this population. PMID:24920342

  9. Individual and socio-environmental factors associated with unsafe injection practices among young adult injection drug users in San Diego.

    PubMed

    Muñoz, Fátima; Burgos, José Luis; Cuevas-Mota, Jazmine; Teshale, Eyasu; Garfein, Richard S

    2015-01-01

    Unsafe injection practices significantly increase the risk of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection among injection drug users (IDUs). We examined individual and socio-environmental factors associated with unsafe injection practices in young adult IDUs in San Diego, California. Of 494 IDUs, 46.9 % reported receptive syringe sharing and 68.8 % sharing drug preparation paraphernalia in the last 3 months. Unsafe injection practices were associated with increased odds of having friends who injected drugs with used syringes, injecting with friends or sexual partners, and injecting heroin. Perceived high susceptibility to HIV and perceived barriers to obtaining sterile syringes were associated with increased odds of receptive syringe sharing, but not with sharing injection paraphernalia. Over half the IDUs reported unsafe injection practices. Our results suggest that personal relationships might influence IDUs' perceptions that dictate behavior. Integrated interventions addressing individual and socio-environmental factors are needed to promote safe injection practices in this population. PMID:24920342

  10. Working memory training for adult hearing aid users: study protocol for a double-blind randomized active controlled trial

    PubMed Central

    2013-01-01

    Background One in ten people aged between 55 to 74 years have a significant hearing impairment in their better hearing ear (as defined by audiometric hearing thresholds). However, it is becoming increasingly clear that the challenges faced by older listeners cannot be explained by the audiogram alone. The ability for people with hearing loss to use cognition to support speech perception allows for compensation of the degraded auditory input. This in turn offers promise for new cognitive-based rehabilitative interventions. Working memory is known to be highly associated with language comprehension and recent evidence has shown significant generalization of learning from trained working memory tasks to improvements in sentence-repetition skills of children with severe to profound hearing loss. This evidence offers support for further investigation into the potential benefits of working memory training to improve speech perception abilities in other hearing impaired populations. Methods/Design This is a double-blind randomized active controlled trial aiming to assess whether a program of working memory training results in improvements in untrained measures of cognition, speech perception and self-reported hearing abilities in adult hearing aid users (aged 50 to 74 years) with mild-to-moderate hearing loss, compared with an active control group who receive a placebo version of the working memory training program. Discussion The present study aims to generate high-quality preliminary evidence for the efficacy of working memory training for adults with mild-to-moderate sensorineural hearing loss who are existing hearing aid users. This trial addresses a number of gaps in the published literature assessing training interventions for people with hearing loss, and in the general literature surrounding working memory training, such as the inclusion of an active control group, participant and tester blinding, and increased transparency in reporting. Trial registration

  11. Central amygdala nicotinic and 5-HT1A receptors mediate the reversal effect of nicotine and MDMA on morphine-induced amnesia.

    PubMed

    Tirgar, F; Rezayof, A; Zarrindast, M-R

    2014-09-26

    The present study was designed to investigate possible involvement of the central amygdala (CeA) nicotinic acetylcholine (nACh) and 5-hydroxytryptamine 1A (5-HT1A) receptors in the reversal effect of nicotine and 3,4-methylenedioxy-N-methylamphetamine (MDMA or ecstasy) on morphine-induced amnesia. Two guide cannulas were stereotaxically implanted in the CeA regions and a step-through passive avoidance task was used for the assessment of memory retrieval in adult male Wistar rats. Our results indicated that post-training s.c. administration of morphine (3-7-mg/kg) impaired memory retrieval. Pre-test administration of nicotine (0.3- and 0.5-mg/kg, s.c.) reversed morphine-induced amnesia. In addition, pre-test intra-CeA injection of MDMA (1-2-μg/rat) with an ineffective dose of nicotine (0.1-mg/kg, s.c.) improved memory retrieval, suggesting the interactive effect of the drugs on memory formation. It should be noted that that pre-test intra-CeA injection of 2-μg/rat of MDMA by itself produced amnesia. Interestingly, pre-test intra-CeA injection of mecamylamine, a nACh receptor antagonist (1-2-μg/rat) or (S)-WAY 100135 (0.25-1-μg/rat), a selective 5-HT1A receptor antagonist inhibited the improvement of morphine-induced amnesia which was produced by pre-test co-injection of nicotine and MDMA. Pre-test intra-CeA injection of the same doses of MDMA, mecamylamine or (S)-WAY 100135 by itself had no effect on morphine-induced amnesia. Moreover, pre-test injection of the same doses of mecamylamine or (S)-WAY 100135 into the CeA alone could not change memory retrieval. Taken together, it can be concluded that there is a functional interaction between morphine, nicotine and MDMA via the CeA nicotinic and serotonergic receptor mechanisms in passive avoidance memory retrieval. Moreover, cross state-dependent memory retrieval may have been induced between the drugs and this probably depends on the rewarding effects of the drugs.

  12. Young Adult Cannabis Users Report Greater Propensity for Risk-Taking Only in Non-Monetary Domains

    PubMed Central

    Gilman, Jodi M.; Calderon, Vanessa; Curran, Max T.; Evins, A. Eden

    2014-01-01

    BACKGROUND Though substance use is often associated with elevated risk-taking in real-world scenarios, many risk-taking tasks in experimental psychology using financial gambles fail to find significant differences between individuals with substance use disorders and healthy controls. We assessed whether participants using marijuana would show a greater propensity for risk-taking in distinct domains including, but not limited to, financial risk-taking. METHODS In the current study, we assessed risk-taking in young adult (age 18–25) regular marijuana users and in non-using control participants using a domain-specific risk-taking self-report scale (DOSPERT) encompassing five domains of risk-taking (social, financial, recreational, health/safety, and ethical). We also measured behavioral risk-taking using a laboratory monetary risk-taking task. RESULTS Marijuana users and controls reported significant differences on the social, health/safety, and ethical risk-taking scales, but no differences in the propensity to take recreational or financial risks. Complementing the self-report finding, there were no differences between marijuana users and controls in their performance on the laboratory risk-taking task. CONCLUSIONS These findings suggest that financial risk-taking may be less sensitive than other domains of risk-taking in assessing differences in risky behavior between those who use marijuana and those who do not. In order to more consistently determine whether increased risk-taking is a factor in substance use, it may be necessary to use both monetary risk-taking tasks and complementary assessments of non-monetary-based risk-taking measures. PMID:25577478

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

    PubMed

    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.

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

    PubMed

    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. PMID:26105141

  15. Comparing adult users of public and private dental services in the state of Minas Gerais, Brazil

    PubMed Central

    2014-01-01

    Background Studying the factors associated with the use of dental services can provide the necessary knowledge to understand the reasons why individuals seek out public healthcare services and the formulation of more appropriate public policies for the present-day reality. Methods This work was a cross-sectional epidemiological study consisting of a sample of adults found in a research databank concerning the conditions of the oral health of the population of the state of Minas Gerais, Brazil. This study examined both main oral health disorders and relevant socioeconomic aspects. The dependent variable was defined as the type of service used, categorized under public and private use. The independent variables were selected and grouped to be inserted in the analysis model according to an adaptation of the behavioral model described by Andersen and Davidson. A hierarchical model was used to analyze the data. The description of variables and bivariate analyses were performed in an attempt to verify possible associations. For each group of variables at each hierarchical level, the gross and adjusted odds ratios (OR) and the respective 95% confidence intervals (CI) were estimated by means of logistic regression. The Complex Samples model from the SPSS statistics program, version 19.0, was used to analyze the sample framework. Results In the final model, the factors associated with the use of public healthcare services by adults were directly related to the socioeconomic and demographic conditions of the individuals, including: being of a dark-skinned black race/color, belonging to families with more than four household residents and with a lower income level, residing in small towns, having more teeth that need treatment. Conclusions According to the findings from this study, socioeconomic and demographic factors, as well as normative treatment needs, are associated with the use of public dental services. PMID:25099268

  16. The Role of Study and Work in Cannabis Use and Dependence Trajectories among Young Adult Frequent Cannabis Users

    PubMed Central

    Liebregts, Nienke; van der Pol, Peggy; Van Laar, Margriet; de Graaf, Ron; van den Brink, Wim; Korf, Dirk J.

    2013-01-01

    Life course theory considers events in study and work as potential turning points in deviance, including illicit drug use. This qualitative study explores the role of occupational life in cannabis use and dependence in young adults. Two and three years after the initial structured interview, 47 at baseline frequent cannabis users were interviewed in-depth about the dynamics underlying changes in their cannabis use and dependence. Overall, cannabis use and dependence declined, including interviewees who quit using cannabis completely, in particular with students, both during their study and after they got employed. Life course theory appeared to be a useful framework to explore how and why occupational life is related to cannabis use and dependence over time. Our study showed that life events in this realm are rather common in young adults and can have a strong impact on cannabis use. While sometimes changes in use are temporary, turning points can evolve from changes in educational and employment situations; an effect that seems to be related to the consequences of these changes in terms of amount of leisure time and agency (i.e., feelings of being in control). PMID:23950748

  17. Alpha-lipoic acid prevents 3,4-methylenedioxy-methamphetamine (MDMA)-induced neurotoxicity.

    PubMed

    Aguirre, N; Barrionuevo, M; Ramírez, M J; Del Río, J; Lasheras, B

    1999-11-26

    A single administration of 3,4-methylenedioxymethamphetamine (MDMA, 20 mg/kg, i.p.), induced significant hyperthermia in rats and reduced 5-hydroxytryptamine (5-HT) content and [3H]paroxetine-labeled 5-HT transporter density in the frontal cortex, striatum and hippocampus by 40-60% 1 week later. MDMA treatment also increased glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus. Repeated administration of the metabolic antioxidant alpha-lipoic acid (100 mg/kg, i.p., b.i.d. for 2 consecutive days) 30 min prior to MDMA did not prevent the acute hyperthermia induced by the drug; however, it fully prevented the serotonergic deficits and the changes in the glial response induced by MDMA. These results further support the hypothesis that free radical formation is responsible for MDMA-induced neurotoxicity.

  18. Structural and Functional Imaging Studies in Chronic Cannabis Users: A Systematic Review of Adolescent and Adult Findings

    PubMed Central

    Batalla, Albert; Bhattacharyya, Sagnik; Yücel, Murat; Fusar-Poli, Paolo; Crippa, Jose Alexandre; Nogué, Santiago; Torrens, Marta; Pujol, Jesús; Farré, Magí; Martin-Santos, Rocio

    2013-01-01

    Background The growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using neuroimaging techniques to determine the effect of cannabis on brain structure and function. We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents. Methods Papers published until August 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only neuroimaging studies involving chronic cannabis users with a matched control group were considered. Results One hundred and forty-two studies were identified, of which 43 met the established criteria. Eight studies were in adolescent population. Neuroimaging studies provide evidence of morphological brain alterations in both population groups, particularly in the medial temporal and frontal cortices, as well as the cerebellum. These effects may be related to the amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of resting global and brain activity during the performance of several cognitive tasks both in adolescents and adults, which may indicate compensatory effects in response to chronic cannabis exposure. Limitations However, the results pointed out methodological limitations of the work conducted to date and considerable heterogeneity in the findings. Conclusion Chronic cannabis use may alter brain structure and function in adult and adolescent population. Further studies should consider the use of convergent methodology, prospective large samples involving adolescent to adulthood subjects, and data-sharing initiatives. PMID:23390554

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

    PubMed

    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'.

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

    PubMed

    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. PMID:27264435

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

    PubMed

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

    2011-01-01

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

  2. Illicit Use of Buprenorphine in a Community Sample of Young Adult Non-Medical Users of Pharmaceutical Opioids

    PubMed Central

    Daniulaityte, Raminta; Falck, Russel; Carlson, Robert G.

    2011-01-01

    BACKGROUND There is growing evidence about illicit use of buprenorphine in the U.S. The study aims to: 1) identify prevalence and predictors of illicit buprenorphine use in a community sample of 396 young adult (18-23 years old) non-medical users of pharmaceutical opioids; 2) describe knowledge, attitudes and behaviors linked to illicit buprenorphine use as reported by a qualitative sub-sample (n=51). METHODS Participants were recruited using respondent-driven sampling. Qualitative interview participants were selected from the larger sample. The sample (n=396) was 54% male and 50% white; 7.8% reported lifetime illicit use of buprenorphine. RESULTS Logistic regression analysis results indicate that white ethnicity, intranasal inhalation of pharmaceutical opioids, symptoms of opioid dependence, and a greater number of pharmaceutical opioids used in lifetime were statistically significant predictors of illicit buprenorphine use. Qualitative interviews revealed that buprenorphine was more commonly used by more experienced users who were introduced to it by their “junkie friends.” Those who used buprenorphine to self-medicate withdrawal referred to it as a “miracle pill.” When used to get high, reported experiences ranged from “the best high ever” to “puking for days.” Participants reported using buprenorphine/naloxone orally or by intranasal inhalation. Injection of buprenorphine without naloxone was also reported. CONCLUSION Our findings suggest that illicit buprenorphine use is gaining ground primarily among whites and those who are more advanced in their drug use careers. Continued monitoring is needed to better understand evolving patterns and trends of illicit buprenorphine use. PMID:22036303

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

    PubMed

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

    2006-11-01

    MDMA (3,4-methylenedioxy-N-methylamphetamine), better known as "Ecstasy", is a synthetic drug with psychedelic and stimulant effects which has gained great popularity. It is closely tied to the underground scene, but has also been used therapeutically as an adjunct to psychotherapy. Both scientific as well as newspaper articles communicate faulty or incomplete information on the origin of MDMA and the role of the German pharmaceutical-chemical company Merck in its development. One of the most common misconceptions is that the substance was synthesized with the goal of creating an anorectic but was not marketed by Merck because of side effects. It was our aim to clarify the circumstances of MDMA's discovery at Merck. An interdisciplinary working group conducted a comprehensive analysis of the original documents in Merck's historical archive in Darmstadt, Germany. It could be revealed that MDMA was in fact mentioned for the first time in files from 1912, but not under this name. In the lab journals it was called "Methylsafrylamin". In a patent certificate it was mentioned only with its chemical structure. Merck applied for this patent to protect an alternative chemical method for synthesizing the styptic hydrastinine, not appetite suppressants. MDMA was not the key substance in this patent, only a precursor. Archive documents revealed that Merck's scientists did not perform basic pharmacological tests with MDMA (now called "Safrylmethylamin") before 1927. These tests were halted for economic reasons. In the 1950s, primitive toxicological studies were conducted but MDMA was not tested in humans. PMID:17152992

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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. PMID:26088184

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

    PubMed

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

    2008-11-01

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

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

    PubMed

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

    2006-06-01

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

  10. Respondent-Driven Sampling to Recruit Young Adult Non-Medical Users of Pharmaceutical Opioids: Problems and Solutions

    PubMed Central

    Daniulaityte, Raminta; Falck, Russel; Li, Linna; Nahhas, Ramzi W.; Carlson, Robert G.

    2011-01-01

    Respondent-driven sampling (RDS) has been promoted as a superior method in recruiting hard-to-reach and hidden populations. Although its application has expanded enormously, there remains a need for empirical data evaluating the performance of RDS in different settings. This study describes the application of RDS to recruit a community sample (N=396) of young adults (18–23 years old) into a natural history study of non-medical pharmaceutical opioid use. Since recruitment targeted non-dependent pharmaceutical opioid users, and applied other eligibility restrictions, several modifications had to be made to make RDS work with this narrowly-defined target population. RDS recruitment was less efficient than expected, and produced greater numbers of African American recruits than anticipated. Although the sampling quota was met, sample analysis revealed a lack of equilibrium in terms of ethnic composition and very strong in-group recruitment tendencies among White and African American respondents. This study contributes potentially helpful insights into the strengths and limitations of using RDS which may benefit future studies. PMID:21885213

  11. Typology of club drug use among young adults recruited using time-space sampling.

    PubMed

    Ramo, Danielle E; Grov, Christian; Delucchi, Kevin; Kelly, Brian C; Parsons, Jeffrey T

    2010-03-01

    The present study examined patterns of recent club drug use among 400 young adults (18-29) recruited using time-space sampling in NYC. Subjects had used at least one of six club drugs (methylenedioxymethamphetamine (MDMA), ketamine, gamma-hydroxybutyrate (GHB), cocaine, methamphetamine, and D-lysergic acid diethylamide (LSD)) within the prior 3 months. We used latent class analysis (LCA) to estimate latent groups based on patterns of recent club drug use and examined differences in demographic and psychological variables by class. A 3-class model fit the data best. Patterns were: Primary cocaine users (42% of sample), Mainstream users (44% of sample), and Wide-range users (14% of sample). Those most likely to be Primary cocaine users were significantly less likely to be heterosexual males and had higher educational attainment than the other two classes. Those most likely to be Wide-range users were less likely to be heterosexual females, more likely to be gay/bisexual males, dependent on club drugs, had significantly greater drug and sexual sensation seeking, and were more likely to use when experiencing physical discomfort or pleasant times with others compared to the other two groups. Findings highlight the utility of using person-centered approaches to understand patterns of substance use, as well as highlight several patterns of club drug use among young adults. PMID:19939585

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

    PubMed

    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 < .05, fold change >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.

  13. Technical Report and Data File User's Manual: For the 2003 National Assessment of Adult Literacy. NCES 2009-476

    ERIC Educational Resources Information Center

    Baldi, Stephane, Ed.; Kutner, Mark; Greenberg, Elizabeth; Jin, Ying; Baer, Justin; Moore, Elizabeth; Dunleavy, Eric; Berlin, Martha; Mohadjer, Leyla; Binzer, Greg; Krenzke, Thomas; Hogan, Jacqueline; Amsbary, Michelle; Forsyth, Barbara; Clark, Lyn; Annis, Terri; Bernstein, Jared; White, Sheida

    2009-01-01

    The 2003 National Assessment of Adult Literacy (NAAL) assessed the English literacy skills of a nationally representative sample of more than 19,000 U.S. adults (age 16 and older) residing in households and correctional institutions. NAAL is the first national assessment of adult literacy since the 1992 National Adult Literacy Survey (NALS). The…

  14. Neural Correlates of the Severity of Cocaine, Heroin, Alcohol, MDMA and Cannabis Use in Polysubstance Abusers: A Resting-PET Brain Metabolism Study

    PubMed Central

    Moreno-López, Laura; Stamatakis, Emmanuel A.; Fernández-Serrano, Maria José; Gómez-Río, Manuel; Rodríguez-Fernández, Antonio; Pérez-García, Miguel; Verdejo-García, Antonio

    2012-01-01

    Introduction Functional imaging studies of addiction following protracted abstinence have not been systematically conducted to look at the associations between severity of use of different drugs and brain dysfunction. Findings from such studies may be relevant to implement specific interventions for treatment. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and the severity of use of cocaine, heroin, alcohol, MDMA and cannabis in a sample of polysubstance users with prolonged abstinence from all drugs used. Methods Our sample consisted of 49 polysubstance users enrolled in residential treatment. We conducted correlation analyses between estimates of use of cocaine, heroin, alcohol, MDMA and cannabis and brain metabolism (BM) (using Statistical Parametric Mapping voxel-based (VB) whole-brain analyses). In all correlation analyses conducted for each of the drugs we controlled for the co-abuse of the other drugs used. Results The analysis showed significant negative correlations between severity of heroin, alcohol, MDMA and cannabis use and BM in the dorsolateral prefrontal cortex (DLPFC) and temporal cortex. Alcohol use was further associated with lower metabolism in frontal premotor cortex and putamen, and stimulants use with parietal cortex. Conclusions Duration of use of different drugs negatively correlated with overlapping regions in the DLPFC, whereas severity of cocaine, heroin and alcohol use selectively impact parietal, temporal, and frontal-premotor/basal ganglia regions respectively. The knowledge of these associations could be useful in the clinical practice since different brain alterations have been associated with different patterns of execution that may affect the rehabilitation of these patients. PMID:22768136

  15. The association between psychopathology and substance use: adolescent and young adult substance users in inpatient treatment in Cape Town, South Africa

    PubMed Central

    Saban, Amina; Flisher, Alan; Laubscher, Ria; London, Leslie; Morojele, Neo

    2014-01-01

    Introduction Evidence suggests that comorbid psychopathology can negatively affect treatment outcomes in substance users. In South Africa, limited information exists regarding the prevalence, nature and role of psychiatric comorbidity in substance users. This study examined psychiatric comorbidity and its association with specific substance use, and young adult substance users in treatment for substance use. Methods Male and female inpatient substance users (n=95; ages 17-30 years) were sampled consecutively in order of admission from three clinics in Cape Town. An interview schedule was administered to elicit patients’ sociodemographic and substance use history details. The computer-assisted Diagnostic Interview Schedule DSM IV (C-DIS IV) was administered to screen patients for current psychiatric disorders. Resuls The sample was largely male, Coloured, Muslim and single. Cannabis (51.6%) and crystal methamphetamine (17.9%) were the most common first substances of use. Heroin (53.7%) and crystal methamphetamine (33.7%) were the most common substances for which treatment was sought (primary substances). The most common comorbid psychopathologies were anti-social personality disorder (ASPD 87.4%) and conduct disorder (CD 67.4%). Regression analyses showed a marginally significant association between specific phobia and first use of cannabis, but indicated no statistically significant associations between psychopathology and substance use. Conclusion The results demonstrated a high proportion of previously unidentified comorbid psychopathology in inpatient substance users. Further research is needed to investigate psychiatric comorbidity in inpatient substance users. PMID:24643118

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

    SciTech Connect

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

    2009-02-15

    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 {mu}g 100 {mu}L{sup -1} of estrogen or 100 {mu}g 100 {mu}L{sup -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{sup -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{sub 50} for Phe dose response curves increased only in the females treated with MDMA and T{sub 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 {alpha}{sub 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.

  17. Enantioselective degradation of amphetamine-like environmental micropollutants (amphetamine, methamphetamine, MDMA and MDA) in urban water.

    PubMed

    Evans, Sian E; Bagnall, John; Kasprzyk-Hordern, Barbara

    2016-08-01

    This paper aims to understand enantioselective transformation of amphetamine, methamphetamine, MDMA (3,4-methylenedioxy-methamphetamine) and MDA (3,4-methylenedioxyamphetamine) during wastewater treatment and in receiving waters. In order to undertake a comprehensive evaluation of the processes occurring, stereoselective transformation of amphetamine-like compounds was studied, for the first time, in controlled laboratory experiments: receiving water and activated sludge simulating microcosm systems. The results demonstrated that stereoselective degradation, via microbial metabolic processes favouring S-(+)-enantiomer, occurred in all studied amphetamine-based compounds in activated sludge simulating microcosms. R-(-)-enantiomers were not degraded (or their degradation was limited) which proves their more recalcitrant nature. Out of all four amphetamine-like compounds studied, amphetamine was the most susceptible to biodegradation. It was followed by MDMA and methamphetamine. Photochemical processes facilitated degradation of MDMA and methamphetamine but they were not, as expected, stereoselective. Preferential biodegradation of S-(+)-methamphetamine led to the formation of S-(+)-amphetamine. Racemic MDMA was stereoselectively biodegraded by activated sludge which led to its enrichment with R-(-)-enantiomer and formation of S-(+)-MDA. Interestingly, there was only mild stereoselectivity observed during MDMA degradation in rivers. This might be due to different microbial communities utilised during activated sludge treatment and those present in the environment. Kinetic studies confirmed the recalcitrant nature of MDMA. PMID:27182976

  18. Enantioselective degradation of amphetamine-like environmental micropollutants (amphetamine, methamphetamine, MDMA and MDA) in urban water.

    PubMed

    Evans, Sian E; Bagnall, John; Kasprzyk-Hordern, Barbara

    2016-08-01

    This paper aims to understand enantioselective transformation of amphetamine, methamphetamine, MDMA (3,4-methylenedioxy-methamphetamine) and MDA (3,4-methylenedioxyamphetamine) during wastewater treatment and in receiving waters. In order to undertake a comprehensive evaluation of the processes occurring, stereoselective transformation of amphetamine-like compounds was studied, for the first time, in controlled laboratory experiments: receiving water and activated sludge simulating microcosm systems. The results demonstrated that stereoselective degradation, via microbial metabolic processes favouring S-(+)-enantiomer, occurred in all studied amphetamine-based compounds in activated sludge simulating microcosms. R-(-)-enantiomers were not degraded (or their degradation was limited) which proves their more recalcitrant nature. Out of all four amphetamine-like compounds studied, amphetamine was the most susceptible to biodegradation. It was followed by MDMA and methamphetamine. Photochemical processes facilitated degradation of MDMA and methamphetamine but they were not, as expected, stereoselective. Preferential biodegradation of S-(+)-methamphetamine led to the formation of S-(+)-amphetamine. Racemic MDMA was stereoselectively biodegraded by activated sludge which led to its enrichment with R-(-)-enantiomer and formation of S-(+)-MDA. Interestingly, there was only mild stereoselectivity observed during MDMA degradation in rivers. This might be due to different microbial communities utilised during activated sludge treatment and those present in the environment. Kinetic studies confirmed the recalcitrant nature of MDMA.

  19. Acute and carryover effects in mice of MDMA ("ecstasy") administration during periadolescence.

    PubMed

    Morley-Fletcher, Sara; Bianchi, Mauro; Gerra, Gilberto; Laviola, Giovanni

    2002-07-12

    In spite of the increasing evidence concerning its neurotoxicity, young human individuals are often involved in the recreational use of amphetamine-type stimulants such as 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). A study aimed to investigate short- and long-term consequences of a repeated and intermittent MDMA administration (0, 5 or 10 mg/kg i.p., 3 days treatment history) was conducted in mice. Mice were injected at different phases in development, namely at early (28 days old), middle (38 days old) or late (52 days old) adolescence. When assessed for nociceptive response, a dose-dependent analgesia was found in middle and late adolescent mice. Carryover consequences of previous MDMA treatment were then investigated at adulthood (80 days old). In a social interaction test, levels of environment exploration and social behaviour resulted markedly increased in drug-free state as a function of drug exposure during development, whereas others behaviours were reduced. MDMA challenge (5-mg/kg dose) produced the expected hyperactivity, as well as a marked increment of hypothalamic serotonin (5-hydroxyhyptamine, 5-HT) levels. Mice treated chronically with MDMA during middle and late adolescence were associated with important reductions of the indoleamine. As a whole, these results indicate a differential long-term vulnerability to behavioural and neurotoxicant effects of MDMA as a function of the developmental stage of exposure.

  20. Release of (/sup 3/H)-monoamines from superfused rat striatal slices by methylenedioxymethamphetamine (MDMA)

    SciTech Connect

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

    1986-03-05

    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/sup -7/ - 10/sup -5/M MDMA and the serotonergic neurotoxin, p-chloroamphetamine, were equipotent releasers of (/sup 3/H)5HT being approximately 10x more potent than methamphetamine. However, methamphetamine was the more potent releaser of (/sup 3/H)DA by a factor of approximately 10x. MDMA-induced release of both (/sup 5/H)5HT and (/sup 3/H)DA was Ca/sup 2 +/-independent and inhibited by selective monoamine uptake blockers suggesting a carrier-dependent release mechanism. Synaptosomal uptake experiments with (+)(/sup 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.

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

    SciTech Connect

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

    1986-03-05

    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<0.001 in both cases) at the 40 mg/kg MDMA dose. Forty mg/kg MDMA also reduced the amounts of dopamine (DA) in STR (78.2 +/- 6.4%, p<0.001) and of norepinephrine (NE) in HIP (74.5 +/- 6.4%, P<0.025) and CTX (77.9 +/- 6.1%, p<0.05). In addition, 20 mg/kg MDMA markedly reduced the number of (/sup 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.

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

    PubMed

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

    2010-01-01

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

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

    PubMed

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

    2008-01-01

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

  4. Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers

    PubMed Central

    Wezenberg, E.; Valkenberg, M. M. G. J.; de Jong, C. A. J.; Buitelaar, J. K.; van Gerven, J. M. A.; Verkes, R. J.

    2008-01-01

    Rationale In Western societies, a considerable percentage of young people expose themselves to 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”). Commonly, ecstasy is used in combination with other substances, in particular alcohol (ethanol). MDMA induces both arousing as well as hallucinogenic effects, whereas ethanol is a general central nervous system depressant. Objective The aim of the present study is to assess the acute effects of single and co-administration of MDMA and ethanol on executive, memory, psychomotor, visuomotor, visuospatial and attention function, as well as on subjective experience. Materials and methods We performed a four-way, double-blind, randomised, crossover, placebo-controlled study in 16 healthy volunteers (nine male, seven female) between the ages of 18–29. MDMA was given orally (100 mg) and blood alcohol concentration was maintained at 0.6‰ by an ethanol infusion regime. Results Co-administration of MDMA and ethanol was well tolerated and did not show greater impairment of performance compared to the single-drug conditions. Impaired memory function was consistently observed after all drug conditions, whereas impairment of psychomotor function and attention was less consistent across drug conditions. Conclusions Co-administration of MDMA and ethanol did not exacerbate the effects of either drug alone. Although the impairment of performance by all drug conditions was relatively moderate, all induced significant impairment of cognitive function. PMID:18305926

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

    PubMed

    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. PMID:26521178

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  9. Modulation of MDMA-induced behavioral and transcriptional effects by the delta opioid antagonist naltrindole in mice

    PubMed Central

    Belkaï, Emilie; Scherrmann, Jean-Michel; Noble, Florence; Marie-Claire, Cynthia

    2009-01-01

    The delta opioid system is involved in the behavioral effects of various drugs of abuse. However, only few studies have focused on the possible interactions between the opioid system and the effects of MDMA. In order to examine the possible role of the delta opioid system in MDMA-induced behaviors in mice, locomotor activity and conditioned place preference were investigated in the presence of naltrindole, a selective delta opioid antagonist. Moreover, the consequences of acute and chronic MDMA administration on Penk (pro-enkephalin) and Pomc (pro-opioimelanocortin) gene expression were assessed by quantitative real-time PCR. The results showed that, after acute MDMA administration (9mg/kg; i.p.), naltrindole (5mg/kg, s.c.) was able to totally block MDMA-induced hyperlocomotion. Penk expression gene was not modulated by acute MDMA but a decrease of Pomc gene expression was observed that was not antagonized by naltrindole. Administration of the antagonist prevented the acquisition of MDMA-induced conditioned place preference, suggesting an implication of the delta opioid receptors in this behavior. Following chronic MDMA treatment only the level of Pomc was modulated. The observed increase was totally blocked by naltrindole pretreatment. All these results confirm the interactions between the delta opioid system (receptors and peptides) and the effects of MDMA. PMID:19523041

  10. Performance of Young Adult Cannabis Users on Neurocognitive Measures of Impulsive Behavior and their Relationship to Symptoms of Cannabis Use Disorders

    PubMed Central

    Gonzalez, Raul; Schuster, Randi Melissa; Mermelstein, Robin J.; Vassileva, Jasmin; Martin, Eileen M.; Diviak, Kathleen R.

    2012-01-01

    Recent studies suggest that abstinent cannabis users show deficits on neurocognitive laboratory tasks of impulsive behavior. But results are mixed and less is known on the performance of non-treatment seeking, young adult cannabis users. Importantly, relationships between performance on measures of impulsive behavior and symptoms of cannabis addiction remain relatively unexplored. We compared young adult current cannabis users (CU, n = 65) and non-using controls (NU, n = 65) on several laboratory measures of impulsive behavior, as well as on a measure of episodic memory commonly impacted by cannabis use. The CU group performed more poorly than the NU group on the Hopkins Verbal Learning Test-Revised Total Immediate Recall and Delayed Recall. No significant differences were observed on the measures of impulsive behavior (i.e., Iowa Gambling Task [IGT], Go-Stop Task, Monetary Choice Questionnaire, Balloon Analogue Risk Task). We examined relationships between neurocognitive performance and symptoms of cannabis use disorder symptoms (DSM-IV CUD) among the CU group, which revealed that poorer IGT performance was associated with more symptoms of DSM-IV CUD. Our results show poorer memory performance among young adult cannabis users relative to healthy controls, but no differences on measures of impulsive behavior. However, performance on a specific type of impulsive behavior (i.e., poorer decision-making) was associated with more cannabis use disorder symptoms. These results provide preliminary evidence to suggest that decision-making deficits may be more strongly associated with problems experienced from cannabis use, rather than solely being a consequence of cannabis use, per se. PMID:22882144

  11. Performance of young adult cannabis users on neurocognitive measures of impulsive behavior and their relationship to symptoms of cannabis use disorders.

    PubMed

    Gonzalez, Raul; Schuster, Randi Melissa; Mermelstein, Robin J; Vassileva, Jasmin; Martin, Eileen M; Diviak, Kathleen R

    2012-01-01

    Recent studies suggest that abstinent cannabis users show deficits on neurocognitive laboratory tasks of impulsive behavior. But results are mixed, and less is known on the performance of non-treatment-seeking, young adult cannabis users. Importantly, relationships between performance on measures of impulsive behavior and symptoms of cannabis addiction remain relatively unexplored. We compared young adult current cannabis users (CU, n = 65) and nonusing controls (NU, n = 65) on several laboratory measures of impulsive behavior, as well as on a measure of episodic memory commonly impacted by cannabis use. The CU group performed more poorly than the NU group on the Hopkins Verbal Learning Test-Revised Total Immediate Recall and Delayed Recall. No significant differences were observed on the measures of impulsive behavior (i.e., Iowa Gambling Task, IGT; Go-Stop Task; Monetary Choice Questionnaire; Balloon Analogue Risk Task). We examined relationships between neurocognitive performance and symptoms of cannabis use disorder symptoms (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, DSM-IV CUD) among the CU group, which revealed that poorer IGT performance was associated with more symptoms of DSM-IV CUD. Our results show poorer memory performance among young adult cannabis users than among healthy controls, but no differences on measures of impulsive behavior. However, performance on a specific type of impulsive behavior (i.e., poorer decision making) was associated with more cannabis use disorder symptoms. These results provide preliminary evidence to suggest that decision-making deficits may be more strongly associated with problems experienced from cannabis use, rather than solely being a consequence of cannabis use, per se. PMID:22882144

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

    PubMed

    Canales, Juan J; Ferrer-Donato, Agueda

    2014-01-01

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

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

    PubMed

    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.

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

    PubMed

    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

    2010-02-01

    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-) administration of MDMA and ethanol over time and in relation to the pharmacokinetics. We performed a four-way, double blind, randomized, crossover, placebo-controlled study in 16 healthy volunteers (nine men, seven women) between the ages of 18 and 29. MDMA (100 mg) was given orally while blood alcohol concentration was maintained at pseudo-steady state levels of approximately 0.6 per thousand for 3 h by a 10% intravenous ethanol clamp. MDMA significantly increased psychomotor speed but did not affect psychomotor accuracy and induced subjective arousal. Ethanol impaired both psychomotor speed and accuracy and induced sedation. Coadministration of ethanol and MDMA improved psychomotor speed but impaired psychomotor accuracy compared with placebo and reversed ethanol-induced sedation. Pharmacokinetics and pharmacodynamics showed maximal effects at 90-150 min after MDMA administration after which drug effects declined in spite of persisting MDMA plasma concentration, with the exception of ethanol-induced sedation, which manifested itself fully only after the infusion was stopped. In conclusion, results show that subjects were more aroused when intoxicated with both substances combined compared with placebo, but psychomotor accuracy was significantly impaired. These findings may have implications for general neuropsychological functioning as this may provide a sense of adequate performance that does not agree with a significant reduction in psychomotor accuracy.

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

    PubMed Central

    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

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

    PubMed

    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

  17. Assessment of the abuse potential of MDMA in the conditioned place preference paradigm: role of CB1 receptors.

    PubMed

    Rodríguez-Arias, Marta; Valverde, Olga; Daza-Losada, Manuel; Blanco-Gandía, M Carmen; Aguilar, María A; Miñarro, José

    2013-12-01

    Numerous reports have highlighted the role of the endocannabinoid system in the addictive potential of MDMA (3,4-methylenedioxy-methamphetamine). A previous report showed that CB1 knockout (KOCB1) mice do not acquire MDMA self-administration, despite developing conditioned place preference (CPP). This contradiction could be due to the particular procedure of place conditioning used. The present work compares MDMA-induced CPP in KOCB1 mice using unbiased and biased procedures of place conditioning. In the unbiased procedure, MDMA induced CPP and reinstatement of the extinguished preference in wild type (WT) mice, but not in KOCB1 mice. In contrast, in a biased protocol of CPP, MDMA produced preference in both types of mice. The anxiolytic response induced by MDMA in the elevated plus maze (EPM) was observed only in KOCB1 mice and may have been responsible, at least partially, for the CPP in the biased procedure. A neurochemical analysis revealed that KOCB1 mice presented higher striatal DA and DOPAC levels in response to MDMA, but no alterations in their levels of monoamine transporters. In line with previous self-administration studies, our data suggest that CB1 receptors play an important role in the reinforcing effects of MDMA, and that the experimental procedure of CPP employed should be taken into account when drawing conclusions. PMID:23959085

  18. MDMA for the treatment of mood disorder: all talk no substance?

    PubMed Central

    Titheradge, Daniel

    2015-01-01

    Background: Unipolar depression is the third highest contributor to the global burden of disease, yet current pharmacotherapies typically take about 6 weeks to have an effect. A rapid-onset agent is an attractive prospect, not only to alleviate symptoms before first-line antidepressants display therapeutic action, but as a further treatment option in nonresponsive cases. It has been suggested that 3,4-methylene-dioxymethamphetamine (MDMA) could play a part in the treatment of depression, either as a rapid-onset pharmacological agent or as an adjunct to psychotherapy. Whilst these hypotheses are in keeping with the monoamine theory of depression and the principles surrounding psychotherapy, explicit experimental evidence of an antidepressant effect of MDMA has rarely been established. Aims: To address the hypothesis surrounding MDMA as a rapid-onset antidepressant by examining pharmacological, psychological and behavioural studies. We consider whether this therapy could be safe by looking at the translation of neurotoxicity data from animals to humans. Method: A literature review of the evidence supporting this hypothesis was performed. Conclusions: The pharmacology of MDMA offers a promising target as a rapid-onset agent and MDMA is currently being investigated for use in psychotherapy in anxiety disorders; translation from these studies for use in depression may be possible. However, experimental evidence and safety analysis are insufficient to confirm or reject this theory at present. PMID:26199721

  19. Enantiomer profiling of high loads of amphetamine and MDMA in communal sewage: a Dutch perspective.

    PubMed

    Emke, Erik; Evans, Sian; Kasprzyk-Hordern, Barbara; de Voogt, Pim

    2014-07-15

    Analysis of wastewater with an aim of community-wide estimation of drug use is a new and very promising approach. Until now it was very difficult to determine if mass loads of studied drugs were actually originating from consumption, or disposal of unused drugs or production waste. This uncertainty in the estimation of community wide drugs use should not be underestimated. This paper aims to apply for the first time enantiomeric profiling in verifying sources of the presence of MDMA and amphetamine in wastewater based on a case study in two Dutch cities: Utrecht and Eindhoven. The results showed that MDMA is usually present in wastewater due to its consumption (MDMA enriched with R(-)-enantiomer). Excessively high mass loads of MDMA during a sampling campaign in Utrecht in 2011 proved to be racemic indicating direct disposal of unused MDMA possibly as a result of a police raid at a nearby illegal production facility. Enantiomeric profiling was also undertaken in order to verify the origin of unexpectedly high mass loads of amphetamine in the city of Eindhoven in 2011. Unfortunately, a distinction between consumption and direct disposal of unused amphetamine in Dutch wastewater could not be achieved. Further work will have to be undertaken to fully understand sources of amphetamine in Dutch wastewaters.

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

    PubMed

    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.

  1. Treadmill running restores MDMA-mediated hyperthermia prevented by inhibition of the dorsomedial hypothalamus.

    PubMed

    Zaretsky, Dmitry V; Zaretskaia, Maria V; Durant, Pamela J; Rusyniak, Daniel E

    2015-05-22

    The contribution of exercise to hyperthermia mediated by MDMA is not known. We recently showed that inhibiting the dorsomedial hypothalamus (DMH) attenuated spontaneous locomotion and hyperthermia and prevented deaths in rats given MDMA in a warm environment. The goal of this study was to confirm that restoring locomotion through a treadmill would reverse these effects thereby confirming that locomotion mediated by the DMH contributes to MDMA-mediated hyperthermia. Rats were randomized to receive bilateral microinjections, into the region of the DMH, of muscimol (80pmol/100nl) or artificial CSF followed by a systemic dose of either MDMA (7.5mg/kg, i.v.) or saline. Immediately after the systemic injection, rats were placed on a motorized treadmill maintained at 32°C. Rats were exercised at a fixed speed (10m/min) until their core temperature reached 41°C. Our results showed that a fixed exercise load abolished the decreases in temperature and mortality, seen previously with inhibition of the DMH in freely moving rats. Therefore, locomotion mediated by neurons in the DMH is critical to the development of hyperthermia from MDMA.

  2. Effects of cocaine and MDMA self-administration on serotonin transporter availability in monkeys.

    PubMed

    Banks, Matthew L; Czoty, Paul W; Gage, H Donald; Bounds, Michael C; Garg, Pradeep K; Garg, Sudha; Nader, Michael A

    2008-01-01

    Although serotonin (5-HT) can interact with dopamine (DA) systems to modulate the subjective and reinforcing effects of psychostimulants such as cocaine and 3,4-methyldioxymethamphetamine (MDMA, ecstasy), the long-term effects of exposure to psychostimulants on brain 5-HT systems are not well characterized. The present study assessed 5-HT transporter (SERT) availability using positron emission tomography (PET) in rhesus monkeys with the SERT-specific radioligand [(11)C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB). SERT availability was assessed in regions of interest including the caudate nucleus, putamen, anterior cingulate cortex, and cerebellum. [(11)C]DASB distribution volume ratios (DVRs) were calculated using the cerebellum as the reference region. DVRs were calculated in control monkeys and in cocaine or MDMA self-administering monkeys approximately 24 h after the last self-administration (SA) session. SERT availability did not differ between monkeys with a history of MDMA SA and control monkeys in any region examined. In contrast, monkeys with a history of cocaine SA showed significantly higher levels of SERT availability in the caudate nucleus and putamen compared to control subjects. These results suggest that chronic SA of cocaine, but not MDMA, leads to alterations in serotonergic function in brain areas relevant to drug abuse. The higher level of SERT availability in cocaine-experienced monkeys may lead to a reduced inhibitory tone of 5-HT on the DA system, which may explain, in part, differences in the abuse liability between cocaine and MDMA. PMID:17443127

  3. Patterns of User Engagement with Mobile- and Web-Delivered Self-Care Interventions for Adults with T2DM: A Review of the Literature.

    PubMed

    Nelson, Lyndsay A; Coston, Taylor D; Cherrington, Andrea L; Osborn, Chandra Y

    2016-07-01

    Technology-delivered interventions can improve the health behaviors and clinical outcomes of persons with diabetes, but only if end users engage with these interventions. To summarize the current knowledge on engagement with technology-based interventions, we conducted a review of recent mobile- and web-delivered intervention studies for adults with type 2 diabetes published from 2011 to 2015. Among 163 identified studies, 24 studies satisfied our inclusion criteria. There was substantial variation in how intervention engagement was reported across studies. Engagement rates were lower among interventions with a longer duration, and engagement decreased over time. In several studies, older age and lower health literacy were associated with less engagement, and more engagement was associated with intervention improvement in at least one outcome, including glycemic control. Future technology-based intervention studies should report on engagement, examine and report on associations between user characteristics and engagement, and aim to standardize how this is reported, particularly in longer trials.

  4. Cross-Modal Functional Reorganization of Visual and Auditory Cortex in Adult Cochlear Implant Users Identified with fNIRS

    PubMed Central

    Thorne, Jeremy D.; Bleichner, Martin G.; Debener, Stefan

    2016-01-01

    Cochlear implant (CI) users show higher auditory-evoked activations in visual cortex and higher visual-evoked activation in auditory cortex compared to normal hearing (NH) controls, reflecting functional reorganization of both visual and auditory modalities. Visual-evoked activation in auditory cortex is a maladaptive functional reorganization whereas auditory-evoked activation in visual cortex is beneficial for speech recognition in CI users. We investigated their joint influence on CI users' speech recognition, by testing 20 postlingually deafened CI users and 20 NH controls with functional near-infrared spectroscopy (fNIRS). Optodes were placed over occipital and temporal areas to measure visual and auditory responses when presenting visual checkerboard and auditory word stimuli. Higher cross-modal activations were confirmed in both auditory and visual cortex for CI users compared to NH controls, demonstrating that functional reorganization of both auditory and visual cortex can be identified with fNIRS. Additionally, the combined reorganization of auditory and visual cortex was found to be associated with speech recognition performance. Speech performance was good as long as the beneficial auditory-evoked activation in visual cortex was higher than the visual-evoked activation in the auditory cortex. These results indicate the importance of considering cross-modal activations in both visual and auditory cortex for potential clinical outcome estimation. PMID:26819766

  5. "CAN Stop" - Implementation and evaluation of a secondary group prevention for adolescent and young adult cannabis users in various contexts - study protocol

    PubMed Central

    2011-01-01

    Background Current research shows that overall numbers for cannabis use among adolescents and young adults dropped in recent years. However, this trend is much less pronounced in continuous cannabis use. With regard to the heightened risk for detrimental health- and development-related outcomes, adolescents and young adults with continuous cannabis use need special attention. The health services structure for adolescents and young adults with substance related problems in Germany, is multifaceted, because different communal, medical and judicial agencies are involved. This results in a rather decentralized organizational structure of the help system. This and further system-inherent characteristics make the threshold for young cannabis users rather high. Because of this, there is a need to establish evidence-based low-threshold help options for young cannabis users, which can be easily disseminated. Therefore, a training programme for young cannabis users (age 14-21) was developed in the "CAN Stop" project. Within the project, we seek to implement and evaluate the training programme within different institutions of the help system. The evaluation is sensitive to the different help systems and their specific prerequisites. Moreover, within this study, we also test the practicability of a training provision through laypersons. Methods/Design The CAN Stop study is a four-armed randomized wait-list controlled trial. The four arms are needed for the different help system settings, in which the CAN Stop training programme is evaluated: (a) the drug addiction aid and youth welfare system, (b) the out-patient medical system, (c) the in-patient medical system and (d) prisons for juvenile offenders. Data are collected at three points, before and after the training or a treatment as usual, and six months after the end of either intervention. Discussion The CAN Stop study is expected to provide an evidence-based programme for young cannabis users seeking to reduce or quit

  6. Chronic stress enhances the corticosterone response and neurotoxicity to +3,4-methylenedioxymethamphetamine (MDMA): the role of ambient temperature.

    PubMed

    Johnson, Bethann N; Yamamoto, Bryan K

    2010-10-01

    Stress facilitates drug abuse by humans. In rodents, stress enhances the neurochemical, neuroendocrine, and behavioral responses to psychostimulants. Although chronic unpredictable stress (CUS) enhances the acute hyperthermic and long-term monoamine-depleting effects of the psychostimulant +3,4-methylenedioxymethamphetamine (MDMA), the roles of hyperthermia and corticosterone (CORT) in mediating the stress-induced enhancement of MDMA-induced serotonin (5-HT) and dopamine (DA) depletions are unknown. Rats were exposed to 10 days of CUS and then challenged with MDMA (5 mg/kg i.p. once every 2 h for a total of four injections). Prior exposure to CUS augmented MDMA-induced hyperthermia and plasma CORT secretion and the long-term depletions in 5-HT content in striatum, hippocampus, and frontal cortex and DA content in striatum. A reduced ambient temperature of 21°C attenuated the hyperthermia, CORT secretion, and 5-HT decreases after MDMA in nonstressed rats. The lower ambient temperature also prevented the augmented hyperthermia, CORT secretion, and enhanced 5-HT and DA depletions after MDMA in chronically stressed rats to levels exhibited by nonstressed, MDMA-treated rats. To investigate the role of CORT on monoamine depletions in response to MDMA, stressed and nonstressed rats were treated with the CORT synthesis inhibitor metyrapone during exposure to MDMA. Metyrapone prevented CORT secretion in both stressed and nonstressed rats but did not modify 5-HT or DA depletions in any brain region examined. This study suggests that enhanced CORT is a consequence of enhanced hyperthermia and the CUS-induced enhancements of MDMA-induced monoamine depletions may be mediated by hyperthermia but not CORT.

  7. Activation of 5-HT3 receptors leads to altered responses 6 months after MDMA treatment.

    PubMed

    Gyongyosi, Norbert; Balogh, Brigitta; Katai, Zita; Molnar, Eszter; Laufer, Rudolf; Tekes, Kornelia; Bagdy, Gyorgy

    2010-03-01

    The recreational drug "Ecstasy" [3,4-methylenedioxymethamphetamine (MDMA)] has a well-characterised neurotoxic effect on the 5-hydroxytryptamine (5-HT) neurons in animals. Despite intensive studies, the long-term functional consequencies of the 5-HT neurodegeneration remains elusive. The aim of this study was to investigate whether any alteration of 5-hydroxytryptamine-3 (5-HT(3)) receptor functions on the sleep-wake cycle, motor activity, and quantitative EEG could be detected 6 months after a single dose of 15 mg/kg of MDMA. The selective 5-HT(3) receptor agonist m-chlorophenylbiguanide (mCPBG; 1 mg/kg, i.p.) or vehicle was administered to freely moving rats pre-treated with MDMA (15 mg/kg, i.p.) or vehicle 6 months earlier. Polysomnographic and motor activity recordings were performed. Active wake (AW), passive wake (PW), light slow wave sleep (SWS-1), deep slow wave sleep (SWS-2), and paradoxical sleep were classified. In addition, EEG power spectra were calculated for the second hour after mCPBG treatment for each stage. AW increased and SWS-1 decreased in the second hour after mCPBG treatment in control animals. mCPBG caused significant changes in the EEG power in states with cortical activation (AW, PW, paradoxical sleep). In addition, mCPBG had a biphasic effect on hippocampal theta power in AW with a decrease in 7 Hz and a stage-selective increase in the upper range (8-9 Hz). Effects of mCPBG on the time spent in AW and SWS-1 were eliminated or reduced in MDMA-treated animals. In addition, mCPBG did not increase the upper theta power of AW in rats pre-treated with MDMA. These data suggest long-term changes in 5-HT(3) receptor function after MDMA. PMID:20052506

  8. Factors associated with prevalent hepatitis C: differences among young adult injection drug users in lower and upper Manhattan, New York City.

    PubMed Central

    Diaz, T; Des Jarlais, D C; Vlahov, D; Perlis, T E; Edwards, V; Friedman, S R; Rockwell, R; Hoover, D; Williams, I T; Monterroso, E R

    2001-01-01

    OBJECTIVES: This study examined correlates of prevalent hepatitis C virus (HCV) infection among young adult injection drug users in 2 neighborhoods in New York City. METHODS: Injection drug users aged 18 to 29 years were street recruited from the Lower East Side and Harlem. Participants were interviewed about drug use and sex practices; venipuncture was performed for hepatitis B virus (HBV), HCV, and HIV serologies. RESULTS: In both sites, testing positive for HCV antibody (anti-HCV) was associated with having injected for more than 3 years. Additionally, HCV infection was positively associated with injecting with someone known to have had hepatitis (but the association was significant only in the Lower East Side) and with sharing cotton (but the association was statistically significant only in Harlem). Being in drug treatment and older than 24 years were associated with HCV in the Lower East Side but not in Harlem. Receiving money for sex was associated with anti-HCV positivity in Harlem but not in the Lower East Side. CONCLUSIONS: Several differences in factors associated with prevalent HCV infection existed among 2 populations of young injection drug users from the same city. Indirect transmission of HCV may occur. PMID:11189819

  9. Role of serotonin and/or norepinephrine in the MDMA-induced increase in extracellular glucose and glycogenolysis in the rat brain

    PubMed Central

    Pachmerhiwala, Rashida; Bhide, Nirmal; Straiko, Megan; Gudelsky, Gary A.

    2010-01-01

    The acute administration of MDMA has been shown to promote glycogenolysis and increase the extracellular concentration of glucose in the striatum. In the present study the role of serotonergic and/or noradrenergic mechanisms in the MDMA-induced increase in extracellular glucose and glycogenolysis was assessed. The relationship of these responses to the hyperthermia produced by MDMA also was examined. The administration of MDMA (10 mg/kg, i.p.) resulted in a significant and sustained increase of 65-100% in the extracellular concentration of glucose in the striatum, as well as in the prefrontal cortex and hippocampus, and a 35% decrease in brain glycogen content. Peripheral blood glucose was modestly increased by 32% after MDMA treatment. Treatment of rats with fluoxetine (10 mg/kg, i.p.) significantly attenuated the MDMA-induced increase in extracellular glucose in the striatum but had no effect on MDMA-induced glycogenolysis or hyperthermia. Treatment with prazosin (1 mg/kg, i.p.) did not alter the glucose or glycogen responses to MDMA but completely suppressed MDMA-induced hyperthermia. Finally, propranolol (3 mg/kg, i.p.) significantly attenuated the MDMA-induced increase in extracellular glucose and glycogenolysis but did not alter MDMA-induced hyperthermia. The present results suggest that MDMA increases extracellular glucose in multiple brain regions, and that this response involves both serotonergic and noradrenergic mechanisms. Furthermore, β-adrenergic and α-adrenergic receptors appear to contribute to MDMA-induced glycogenolysis and hyperthermia, respectively. Finally, hyperthermia, glycogenolysis and elevated extracellular glucose appear to be independent, unrelated responses to acute MDMA administration. PMID:20633550

  10. Experienced drug users assess the relative harms and benefits of drugs: a web-based survey.

    PubMed

    Carhart-Harris, Robin Lester; Nutt, David John

    2013-01-01

    A web-based survey was used to consult the opinions of experienced drug users on matters related to drug harms. We identified a rare sample of 93 drug users with personal experience with 11 different illicit drugs that are widely used in the UK. Asked to assess the relative harms of these drugs, they ranked alcohol and tobacco as the most harmful, and three "Class A" drugs (MDMA, LSD, and psilocybin) and one class B (cannabis) were ranked as the four least harmful drugs. When asked to assess the relative potential for benefit of the 11 drugs, MDMA, LSD, psilocybin, and cannabis were ranked in the top four; and when asked why these drugs are beneficial, rather than simply report hedonic properties, they referred to potential therapeutic applications (e.g., as tools to assist psychotherapy). These results provide a useful insight into the opinions of experienced drug users on a subject about which they have a rare and intimate knowledge.

  11. Localization of MDMA-induced brain activity in healthy volunteers using low resolution brain electromagnetic tomography (LORETA).

    PubMed

    Frei, E; Gamma, A; Pascual-Marqui, R; Lehmann, D; Hell, D; Vollenweider, F X

    2001-11-01

    3,4-Methylenedioxymethamphetamine (MDMA; 'Ecstasy') is a psychostimulant drug producing heightened mood and facilitated social communication. In animal studies, MDMA effects are primarily mediated by serotonin (5-HT), but also by dopamine (DA) and possibly noradrenaline (NA). In humans, however, the neurochemical and neurophysiological basis of acute MDMA effects remains unknown. The distribution of active neuronal populations after administration of a single dose of MDMA (1.7 mg/kg) or placebo was studied in 16 healthy, MDMA-naïve volunteers. Thirty-one-channel scalp EEGs during resting with open and closed eyes was analyzed in the different EEG frequency bands. Scalp maps of power showed significant, global differences between MDMA and placebo in both eye conditions and all frequency bands. Low resolution brain electromagnetic tomography (LORETA) was used to compute 3D, functional images of electric neuronal activity from the scalp EEG data. MDMA produced a widespread decrease of slow and medium frequency activity and an increase of fast frequency activity in the anterior temporal and posterior orbital cortex, concomitant with a marked enhancement of mood, emotional arousal and increased extraversion. This activation of frontotemporal areas indicates that the observed enhancement of mood and possibly the increased extroversion rely on modulation of limbic orbitofrontal and anterotemporal structures known to be involved in emotional processes. Comparison of the MDMA-specific EEG pattern with that of various 5-HT, DA, and NA agonists indicates that serotonin, noradrenaline, and, to a lesser degree, dopamine, contribute to the effects of MDMA on EEG, and possibly also on mood and behavior.

  12. Drug intelligence based on MDMA tablets data: 2. Physical characteristics profiling.

    PubMed

    Marquis, Raymond; Weyermann, Céline; Delaporte, Céline; Esseiva, Pierre; Aalberg, Laura; Besacier, Fabrice; Bozenko, Joseph S; Dahlenburg, Rainer; Kopper, Carola; Zrcek, Frantisek

    2008-06-10

    One of the tasks of the European project entitled "Collaborative Harmonisation of Methods for Profiling of Amphetamine Type Stimulants" (CHAMP) funded by the sixth framework programme of the European Commission was to develop a harmonised methodology for MDMA profiling and the creation of a common database in a drug intelligence perspective. Part I was dedicated to the analysis of organic impurities formed during synthesis in order to investigate traffic tendencies and highlight potential links between samples, whereas this part focuses on physical characteristics of the MDMA tablets. Diameter, thickness, weight and score were demonstrated to be reliable and relevant features in this drug intelligence perspective. Distributions of samples coming from the same post-tabletting batch (post-TB) and samples coming from different post-TB were very well discriminated by using the squared Euclidean or the Manhattan distance on standardised data. Our findings demonstrated the possibility to discriminate between MDMA samples issued from different post-TB and to find out links between samples coming from a same post-TB. Furthermore, the hypothesis that most of the MDMA samples found on the international market come from the same countries was supported.

  13. Effect of 3, 4-methylenedioxymethamphetamine (MDMA) on the toxicokinetics and sedative effects of the drug of abuse, γ-hydroxybutyric acid

    PubMed Central

    Vijay, Nisha; Morris, Marilyn E.

    2014-01-01

    γ-hydroxybutyric acid (GHB) is widely abused in combination with other club drugs such as 3,4-methylenedioxy methamphetamine (MDMA). The objectives of this study were to characterize the effects of MDMA on GHB toxicokinetics/toxicodynamics (TK/TD) and evaluate the use of monocarboxylate transporter (MCT) inhibition as a potential treatment strategy for GHB overdose when GHB is abused with MDMA. Rats were administered GHB 400 mg/kg i.v. alone or with MDMA (5 mg/kg i.v). Effects of MDMA and of the monocarboxylate transporter (MCT) inhibitor, L-lactate, on GHB TK and sedative effects were evaluated. The results of this study demonstrated no significant effect of MDMA on GHB TK or TD. GHB plasma concentrations were unchanged, and GHB concentration-effect relationships, based on plasma and brain concentrations and the return to righting reflex (RRR), were similar in the presence and absence of MDMA. L-lactate administration resulted in a significant decrease in the sedative effect (RRR) of GHB when it was co-administered with MDMA. Our results indicate that MDMA does not affect the TK/TD of GHB at the doses used in this study, and MCT inhibition using L-lactate, an effective overdose treatment strategy for GHB alone, is also effective for GHB overdose when GHB is co-ingested with MDMA. PMID:25174723

  14. Comparative potencies of 3,4-methylenedioxymethamphetamine (MDMA) analogues as inhibitors of [3H]noradrenaline and [3H]5-HT transport in mammalian cell lines

    PubMed Central

    Montgomery, T; Buon, C; Eibauer, S; Guiry, P J; Keenan, A K; McBean, G J

    2007-01-01

    Background and purpose: Illegal ‘ecstasy' tablets frequently contain 3,4-methylenedioxymethamphetamine (MDMA)-like compounds of unknown pharmacological activity. Since monoamine transporters are one of the primary targets of MDMA action in the brain, a number of MDMA analogues have been tested for their ability to inhibit [3H]noradrenaline uptake into rat PC12 cells expressing the noradrenaline transporter (NET) and [3H]5-HT uptake into HEK293 cells stably transfected with the 5-HT transporter (SERT). Experimental approach: Concentration–response curves for the following compounds at both NET and SERT were determined under saturating substrate conditions: 4-hydroxy-3-methoxyamphetamine (HMA), 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-methylenedioxy-N-hydroxyamphetamine (MDOH), 2,5-dimethoxy-4-bromophenylethylamine (2CB), 3,4-dimethoxymethamphetamine (DMMA), 3,4-methylenedioxyphenyl-2-butanamine (BDB), 3,4-methylenedioxyphenyl-N-methyl-2-butanamine (MBDB) and 2,3-methylenedioxymethamphetamine (2,3-MDMA). Key results: 2,3-MDMA was significantly less potent than MDMA at SERT, but equipotent with MDMA at NET. 2CB and BDB were both significantly less potent than MDMA at NET, but equipotent with MDMA at SERT. MBDB, DMMA, MDOH and the MDMA metabolites HMA and HMMA, were all significantly less potent than MDMA at both NET and SERT. Conclusions and implications: This study provides an important insight into the structural requirements of MDMA analogue affinity at both NET and SERT. It is anticipated that these results will facilitate understanding of the likely pharmacological actions of structural analogues of MDMA. PMID:17891159

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

    SciTech Connect

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

    2009-12-15

    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{sub last} and C{sub max} were 1.6- to 1.7-fold higher in males than in females given MDMA (5 mg/kg sc), while HMMA C{sub max} and AUC{sub 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{sub last} and t{sub 1/2} were 50% higher in females given MDMA (1 mg/kg iv). MDA C{sub max} and AUC{sub last} were 75-82% higher in males, with a 2.8-fold higher metabolic index. Finally, the AUC{sub 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.

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

    PubMed Central

    Kuypers, Kim P. C.; Theunissen, Eef L.; van Wel, Janelle H. P.; de Sousa Fernandes Perna, Elizabeth B.; Linssen, Anke; Sambeth, Anke; Schultz, Benjamin G.; Ramaekers, Johannes G.

    2016-01-01

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

  17. Improving smoking cessation policy by assessing user demand for an inpatient smoking cessation service in adult psychiatric wards.

    PubMed

    Liu, Kathy; Creamer, Andrew

    2015-01-01

    Smoking rates are higher among people with mental health conditions compared to the general population. Smoking reduces physical, mental and financial well-being, and interacts with psychotropic drugs. An inpatient admission provides an opportunity to engage and support smokers in smoking cessation. Compliance with Trust/NICE smoking cessation guidelines was assessed in two inpatient wards, and a questionnaire evaluated user demand for an inpatient smoking cessation service. A need for improved documentation of smoking status to identify and treat smokers routinely was revealed. A new electronic health form was designed and introduced, and a clear pathway for onward referrals was developed. This intervention preceded the introduction of the Trust-wide smoke free policy from October 2014. The intervention doubled rates of documentation of smoking status, cessation advice and offer of NRT/referral. There were large differences between the two wards, highlighting the need for a tailored approach. PMID:26734337

  18. Improving smoking cessation policy by assessing user demand for an inpatient smoking cessation service in adult psychiatric wards.

    PubMed

    Liu, Kathy; Creamer, Andrew

    2015-01-01

    Smoking rates are higher among people with mental health conditions compared to the general population. Smoking reduces physical, mental and financial well-being, and interacts with psychotropic drugs. An inpatient admission provides an opportunity to engage and support smokers in smoking cessation. Compliance with Trust/NICE smoking cessation guidelines was assessed in two inpatient wards, and a questionnaire evaluated user demand for an inpatient smoking cessation service. A need for improved documentation of smoking status to identify and treat smokers routinely was revealed. A new electronic health form was designed and introduced, and a clear pathway for onward referrals was developed. This intervention preceded the introduction of the Trust-wide smoke free policy from October 2014. The intervention doubled rates of documentation of smoking status, cessation advice and offer of NRT/referral. There were large differences between the two wards, highlighting the need for a tailored approach.

  19. Investigation of a secondary syringe exchange program for homeless young adult injection drug users in San Francisco, California, U.S.A.

    PubMed

    Sears, C; Guydish, J R; Weltzien, E K; Lum, P J

    2001-06-01

    This study investigated an HIV prevention program for homeless young adult injection drug users (IDUs) that combined a secondary syringe exchange program (SEP) with community-level activities. Homeless young IDUs were recruited from street-based settings in San Francisco, and a structured questionnaire was administered. The secondary SEP operated in a circumscribed geographic area, and for analytic purposes respondents were assigned to the intervention site group if they primarily spent time in this area (n = 67), or the comparison site group if they primarily spent time elsewhere (n = 55). Almost all (96%) intervention site youth had used the secondary SEP in the past 30 days and were significantly more likely to regularly use SEP. In bivariate analysis, comparison site IDUs were more likely to share syringes, reuse syringes, share the cotton used to filter drugs, and use condoms with casual sex partners only inconsistently. In multivariate analysis, comparison site remained positively associated with sharing syringes (adjusted odds ratio [AOR], 3.748; 95% confidence interval [CI], 1.406-9.988), reusing syringes (AOR, 2.769; 95% CI,1.120-6.847), and inconsistent condom use with casual sex partners (AOR, 4.825; 95% CI, 1.392- 16.721). This suggests that the intervention was effective in delivering SEP services to homeless young adult IDUs, and that IDUs who frequented the intervention site had a lower HIV risk than comparison group IDUs.

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

    PubMed

    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

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

    PubMed Central

    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

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

    PubMed

    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

  3. Cocaine use and characteristics of young adult users from 1987 to 1992: the CARDIA Study. Coronary Artery Risk Development in Young Adults.

    PubMed Central

    Braun, B L; Murray, D; Hannan, P; Sidney, S; Le, C

    1996-01-01

    OBJECTIVES: This study examined the relationship of sociodemographic factors and use of substances other than cocaine to cocaine use from 1987 to 1992 in a cohort of Black and White men and women 20 to 32 years of age. METHODS: Data were collected as part of the Coronary Artery Risk Development in Young Adults study. Self-reported cocaine use was analyzed through chi-square tests and repeated measures analyses of variance to determine the bivariate and multivariate relationships of sociodemographics and substance use behaviors to cocaine use over the 5-year period. RESULTS: Cocaine use declined in Whites but remained stable in Blacks from 1987 to 1992. Cross-sectional results showed that use was related to being Black, male and in the older half of the cohort, single, and unemployed; it was also related to higher levels of other substance use in 1987 and 1992. Over time, the magnitude and strength of the relationship were consistent for each variable except for increased odds of cocaine use among the unemployed and Blacks in 1992. CONCLUSIONS: Sociodemographic characteristics and substance use behavior consistently identify individuals at risk for cocaine use. As a result, intervention programs should be targeted at these high-risk groups. PMID:9003130

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

    PubMed

    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. PMID:26840064

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

    PubMed Central

    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. PMID:26840064

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

    PubMed

    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.

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

    PubMed

    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. PMID:27118529

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

    PubMed

    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.

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

    PubMed

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

    2011-01-01

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

  10. The recreational drug ecstasy disrupts the hypothalamic-pituitary-gonadal reproductive axis in adult male rats.

    PubMed

    Dickerson, Sarah M; Walker, Deena M; Reveron, Maria E; Duvauchelle, Christine L; Gore, Andrea C

    2008-01-01

    Reproductive function involves an interaction of three regulatory levels: hypothalamus, pituitary, and gonad. The primary drive upon this system comes from hypothalamic gonadotropin-releasing hormone (GnRH) neurosecretory cells, which receive afferent inputs from other neurotransmitter systems in the central nervous system to result in the proper coordination of reproduction and the environment. Here, we hypothesized that the recreational drug (+/-)-3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy'), which acts through several of the neurotransmitter systems that affect GnRH neurons, suppresses the hypothalamic-pituitary-gonadal reproductive axis of male rats. Adult male Sprague-Dawley rats self-administered saline or MDMA either once (acute) or for 20 days (chronic) and were euthanized 7 days following the last administration. We quantified hypothalamic GnRH mRNA, serum luteinizing hormone concentrations, and serum testosterone levels as indices of hypothalamic, pituitary, and gonadal functions, respectively. The results indicate that the hypothalamic and gonadal levels of the hypothalamic-pituitary-gonadal axis are significantly altered by MDMA, with GnRH mRNA and serum testosterone levels suppressed in rats administered MDMA compared to saline. Furthermore, our finding that hypothalamic GnRH mRNA levels are suppressed in the context of low testosterone concentrations suggests that the central GnRH neurosecretory system may be a primary target of inhibitory regulation by MDMA usage.

  11. Ecstasy (MDMA), methamphetamine, and date rape (drug-facilitated sexual assault): a consideration of the issues.

    PubMed

    Jansen, Karl L R; Theron, Lynn

    2006-03-01

    The term "date rape drug" has traditionally been applied by the media to powerful sedatives, such as gamma hydroxybutyrate (GHB) and flunitrazepam (Rohypnol), which can render a person unconscious and hence unable to resist and/or recall an assault. However, some law enforcement agents and others have recently obtained convictions by arguing that the empathy-generating and sensual effects of MDMA, and an occasional increase in disinhibition and sexual desire linked with methamphetamine use, remove a person's ability to give a reasoned consent, turning the person into "a helpless slave" to their own sexual desires and those of the alleged perpetrator. The argument holds that the victim becomes part of the assault because they may appear to be cooperating and colluding with activity which they would not have consented to without taking these drugs. This interpretation of the term "date rape" has been fed by data that sometimes finds MDMA and amphetamines in samples taken from sexual assault victims, and hence these prosecutions sometimes rely on expert testimony from toxicologists, pathologists and police officers rather than psychologists and psychiatrists who are expert in the human effects of these drugs. Some of those in the latter group have dismissed claims that MDMA is an aphrodisiac or a date rape drug as myths propagated by the media. In this article, these arguments and their respective strengths and weaknesses will be examined to assist professionals and others who may become involved in these cases. PMID:16681170

  12. Reduced Contextual Discrimination following Alcohol Consumption or MDMA Administration in Mice.

    PubMed

    Johansson, Emily M; García-Gutiérrez, María S; Moscoso-Castro, María; Manzanares, Jorge; Valverde, Olga

    2015-01-01

    The recreational drugs, alcohol and 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") have both been shown to cause immune activation in vivo, and they are linked to cognitive impairment and anxiety-like behaviors in rodents. The neuronal effects of these drugs in the hippocampal area, an area that has been a focus of studies aiming to explain the mechanisms underlying anxiety related-disorders, remains poorly understood. Therefore we investigated the specific inflammatory impact of alcohol and MDMA on this area of the brain and on a hippocampal-related behavioral task. We centered our study on two inflammatory factors linked to anxiety-related disorders, namely Interleukin-1β (IL-1β) and brain-derived neurotrophic factor (BDNF). We subjected drug-consuming mice to a battery of behavioral tests to evaluate general activity, anxiety-like and depressive-live behaviors. We then introduced them to a contextual fear discrimination task and immune-related effects were examined by immunohistochemical and biochemical studies. Our results suggest that there is a relationship between the induction of immune activated pathways by voluntary alcohol consumption and a high-dose MDMA. Furthermore, the ability of mice to perform a contextual fear discrimination task was impaired by drug consumption and we report long term inflammatory alterations in the hippocampus even several weeks after drug intake. This information will be helpful for discovering new selective drug targets, and to develop treatments and preventive approaches for patients with anxiety-related disorders. PMID:26566284

  13. Reduced Contextual Discrimination following Alcohol Consumption or MDMA Administration in Mice

    PubMed Central

    Johansson, Emily M.; García-Gutiérrez, María S.; Moscoso-Castro, María; Manzanares, Jorge; Valverde, Olga

    2015-01-01

    The recreational drugs, alcohol and 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) have both been shown to cause immune activation in vivo, and they are linked to cognitive impairment and anxiety-like behaviors in rodents. The neuronal effects of these drugs in the hippocampal area, an area that has been a focus of studies aiming to explain the mechanisms underlying anxiety related-disorders, remains poorly understood. Therefore we investigated the specific inflammatory impact of alcohol and MDMA on this area of the brain and on a hippocampal-related behavioral task. We centered our study on two inflammatory factors linked to anxiety-related disorders, namely Interleukin-1β (IL-1β) and brain-derived neurotrophic factor (BDNF). We subjected drug-consuming mice to a battery of behavioral tests to evaluate general activity, anxiety-like and depressive-live behaviors. We then introduced them to a contextual fear discrimination task and immune-related effects were examined by immunohistochemical and biochemical studies. Our results suggest that there is a relationship between the induction of immune activated pathways by voluntary alcohol consumption and a high-dose MDMA. Furthermore, the ability of mice to perform a contextual fear discrimination task was impaired by drug consumption and we report long term inflammatory alterations in the hippocampus even several weeks after drug intake. This information will be helpful for discovering new selective drug targets, and to develop treatments and preventive approaches for patients with anxiety-related disorders. PMID:26566284

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

    PubMed

    de la Torre, Rafael; Yubero-Lahoz, Samanta; Pardo-Lozano, Ricardo; Farré, Magí

    2012-01-01

    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 (PM) 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. PMID:23162568

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

    SciTech Connect

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

    2008-07-01

    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{sup -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.

  16. Incidence of acne vulgaris in young adult users of protein-calorie supplements in the city of João Pessoa - PB*

    PubMed Central

    Pontes, Thaís de Carvalho; Fernandes Filho, Gilson Mauro Costa; Trindade, Arthur de Sousa Pereira; Sobral Filho, Jader Freire

    2013-01-01

    BACKGROUND Based on personal observations of dermatologists, nutritionists and patients, a new problem emerges in the gyms: development and exacerbation of acne in users of whey protein, which is a protein derived from cow's milk. Whey Protein extract contains growth factors that may be related to acne. Its purity and composition are not fully known and there is no scientific research on its potential to cause acne. OBJECTIVES Assess the relationship between the use of proteincalorie supplements and onset or exacerbation of acne vulgaris in young adults in the city of João Pessoa. METHODS Descriptive observational study conducted in gyms and in a dermatology clinic. Each participant was examined for acne on three occasions and followed for 60 days. RESULTS 30 patients were examined. Onset or exacerbation of acneiform lesions were observed (p <0.0005). The effect was more prominent in females and in individuals without current acne and no family history of acne. CONCLUSION This study showed the onset of acne with the progressive use of protein-calorie supplementation, in a two-month period. It is suggested that this type of supplementation be discouraged. PMID:24474098

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

    PubMed

    Ray, Thomas S

    2016-02-01

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

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

    PubMed

    Ray, Thomas S

    2016-02-01

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

  19. “It’s not smoke. It’s not tar. It’s not 4000 chemicals. Case closed”: Exploring attitudes, beliefs, and perceived social norms of e-cigarette use among adult users

    PubMed Central

    Coleman, Blair N.; Johnson, Sarah E.; Tessman, Greta K.; Tworek, Cindy; Alexander, Jennifer; Dickinson, Denise M.; Rath, Jessica; Green, Kerry M.

    2016-01-01

    Background Electronic cigarette (e-cigarette) use is rapidly increasing among adults in the U.S. The purpose of this qualitative study was to explore consumer perceptions about e-cigarettes, including knowledge, attitudes, beliefs and perceived social norms. Methods A total of 14 focus groups (N = 116) were conducted with current adult e-cigarette users in five U.S. cities from March through May, 2014. Focus groups were segmented by age (young adults aged 18–29 and older adults aged 30 and older) as well as by e-cigarette use status (exclusive e-cigarette users and non-exclusive e-cigarette users). Focus group discussions lasted approximately 60-min and were audio-recorded and transcribed; data were analyzed using a phenomenological approach. Results Participants expressed many positive attitudes towards e-cigarettes and simultaneously reported a lack of information and knowledge about the products. Focus group participants overwhelmingly felt as though the ingredients of e-cigarettes were likely less harmful than conventional cigarettes. Additionally, many described positive reactions from family and friends, especially when e-cigarettes were used in place of conventional cigarettes. Conclusions Findings from this qualitative study provide insight into consumer knowledge, attitudes and beliefs about e-cigarettes increasing our understanding of why and how they are being used. Such information will help provide insight into the potential public health impact of these emerging products. PMID:26708706

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

    PubMed

    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.

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

    PubMed

    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.

  2. The profiling of MDMA tablets: a study of the combination of physical characteristics and organic impurities as sources of information.

    PubMed

    Milliet, Quentin; Weyermann, Céline; Esseiva, Pierre

    2009-05-30

    The profiling of MDMA tablets can be carried out using different sets of characteristics. The first type of measurements performed on MDMA tablets are physical characteristics (i.e. post-tabletting characteristics). They yield preliminary profiling data that may be valuable in a first stage for investigation purposes. However organic impurities (i.e. pre-tabletting characteristics) are generally considered to bring more reliable information, particularly for presentation of evidence in court. This work aimed therefore at evaluating the added value of combining pre-tabletting characteristics and post-tabletting characteristics of seized MDMA tablets. In approximately half of the investigated cases, the post-tabletting links were confirmed with organic impurities analyses. In the remaining cases, post-tabletting batches (post-TBs) were divided in several pre-tabletting batches (pre-TBs), thus supporting the hypothesis that several production batches of MDMA powder (pre-TBs) were used to produce one single post-TB (i.e. tablets having the same shape, diameter, thickness, weight and score; but different organic impurities composition). In view of the obtained results, the hypotheses were discussed through illustrating examples. In conclusion, both sets of characteristics were found relevant alone and combined together. They actually provide distinct information about MDMA illicit production and trafficking.

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

    PubMed

    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. PMID:26612383

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

    PubMed

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

    2014-12-01

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

  5. A one-generation reproductive toxicity study of 3,4-methylenedioxy-n-methamphetamine (MDMA, Ecstasy), an amphetamine derivative, in C57BL/6 mice.

    PubMed

    Kwack, Seung Jun; Yoon, Kyung Sil; Lim, Seong Kwang; Gwak, Hyo-Min; Kim, Ji Yun; Um, Yoon Mi; Lee, Jung Dae; Hyeon, Ji Hyeon; Kim, Yeon Joo; Kim, Hyung Sik; Lee, Byung-Mu

    2014-01-01

    3,4-Methylenedioxy-N-methamphetamine (MDMA, ecstasy) is an amphetamine derivative and is a popular type of drug that is abused due to its effects on the central nervous system (CNS), including alertness and euphoria. However, life-threatening (brain edema, heart failure, and coma) and fatal hyperthermia sometimes occur in some individuals taking MDMA. In a one-generation reproductive toxicity study, the potential toxicity of chronic exposure of MDMA was investigated on the reproductive capabilities of parental mice (F0), as well as the survival/development of their subsequent offspring (F1). Male and female C57BL/6 mice were administered orally MDMA at 0, 1.25, 5 or 20 mg/kg body weight (b.w.) throughout the study, beginning at the premating period, through mating, gestation, and lactation periods. MDMA did not produce any apparent clinical signs in F0 or F1 mice, and produced no significant changes in body weight, feed/water intake, or organ weights. In contrast, administration of MDMA produced external abnormalities in fetuses, stillbirth and labored delivery, and diminished viability and weaning indices in offspring, but these data were not significant. In addition, physical development of F1 mice was not markedly influenced by MDMA treatment. Nonetheless, serum biochemistry markers showed that levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) were markedly elevated in a dose-dependent manner from 5 mg and higher MDMA/kg b.w., whereas levels of triglycerides (TG), potassium (K), and uric acid (UA) were reduced. Data suggest that MDMA may exert a weak reproductive and developmental toxicity, and the no-observed-adverse-effect level (NOAEL) of MDMA is estimated to be 1.25 mg/kg b.w./d.

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

    PubMed Central

    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

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

    PubMed

    Ferraz-de-Paula, V; Stankevicius, D; Ribeiro, A; Pinheiro, M L; Rodrigues-Costa, E C; Florio, J C; Lapachinske, S F; Moreau, R L M; Palermo-Neto, J

    2011-05-01

    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.

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

    PubMed

    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.

  9. Club Drug Use among Young Adults Frequenting Dance Clubs and Other Social Venues in New York City

    ERIC Educational Resources Information Center

    Parsons, Jeffrey T.; Halkitis, Perry N.; Bimbi, David S.

    2006-01-01

    A convenience sample of young adults (ages 18-25) in New York City was recruited to complete anonymous surveys in social venues (either dance clubs or other social settings, such as coffee shops and university "hangouts") regarding their use of "club drugs" (e.g., MDMA/Ecstasy, GHB, ketamine, crystal methamphetamine, cocaine, and LSD).…

  10. Usage and Users of Online Self-Management Programs for Adult Patients With Atopic Dermatitis and Food Allergy: An Explorative Study

    PubMed Central

    van Leent- de Wit, Ilse; de Bruin-Weller, Marjolein; Knulst, André

    2015-01-01

    Background Two online self-management programs for patients with atopic dermatitis (AD) or food allergy (FA) were developed with the aim of helping patients cope with their condition, follow the prescribed treatment regimen, and deal with the consequences of their illness in daily life. Both programs consist of several modules containing information, personal stories by fellow patients, videos, and exercises with feedback. Health care professionals can refer their patients to the programs. However, the use of the program in daily practice is unknown. Objective The aim of this study was to explore the use and characteristics of users of the online self-management programs “Living with eczema,” and “Living with food allergy,” and to investigate factors related to the use of the trainings. Methods A cross-sectional design was carried out in which the outcome parameters were the number of log-ins by patients, the number of hits on the system’s core features, disease severity, quality of life, and domains of self-management. Descriptive statistics were used to summarize sample characteristics and to describe number of log-ins and hits per module and per functionality. Correlation and regression analyses were used to explore the relation between the number of log-ins and patient characteristics. Results Since the start, 299 adult patients have been referred to the online AD program; 173 logged in for at least one occasion. Data from 75 AD patients were available for analyses. Mean number of log-ins was 3.1 (range 1-11). Linear regression with the number of log-ins as dependent variable showed that age and quality of life contributed most to the model, with betas of .35 ( P=.002) and .26 (P=.05), respectively, and an R 2 of .23. Two hundred fourteen adult FA patients were referred to the online FA training, 124 logged in for at least one occasion and data from 45 patients were available for analysis. Mean number of log-ins was 3.0 (range 1-11). Linear regression

  11. Correlates of the Use of Different Tobacco Cessation Methods by Smokers and Smokeless Tobacco Users According to Their Socio-Demographic Characteristics: Global Adult Tobacco Survey (GATS) India 2009-10

    PubMed Central

    Ruhil, Rohini

    2016-01-01

    Background: Tobacco control has two aspects. One involves preventing non-tobacco users from using tobacco and the second involves tobacco cessation (quitting) by existing tobacco users. There are various methods of tobacco cessation. Pharmacotherapy [e.g., nicotine replacement therapy (NRT) and medications such as bupropion] and behavioral counselling are some of the internationally approved methods of tobacco cessation. Objective: This paper intends to study how age, gender, residence (rural/urban), education, and occupation influence the use of various tobacco cessation methods by smokers and smokeless tobacco users. Materials and Methods: The study was a cross-sectional secondary data analysis of the Global Adult Tobacco Survey (GATS) India 2009-2010. There were 3725 smokers and 6354 smokeless tobacco users included in the study who made attempts to quit in the 12 months prior to the survey by use of different cessation methods (NRT, drugs such as bupropion, counselling, and other methods). Results: A significant association was demonstrated between increasing educational attainment and use of cessation methods for all the methods among smokers. Being employed (Govt. or non-Govt.) was positively associated with the use of NRT as a cessation method by smokers. Students and homemakers had higher odds of using pharmacotherapy methods among smokers. A significant association was demonstrated for the gender and age of tobacco users with the use of counselling as a cessation method among smokeless tobacco users. Conclusion: The findings of this study have important implications for tobacco cessation service providers in view of supporting their decision of choosing a particular tobacco cessation method for tobacco users according to certain kinds of sociodemographic characteristics. PMID:27385871

  12. Methylphenidate and MDMA adolescent exposure in mice: long-lasting consequences on cocaine-induced reward and psychomotor stimulation in adulthood.

    PubMed

    Achat-Mendes, C; Anderson, K L; Itzhak, Y

    2003-07-01

    Pre-exposure to psychostimulants enhances the rewarding and psychomotor stimulating effects of subsequent drug exposure. Currently, there is a prevalence of adolescent exposure to the psychostimulants methylphenidate (MPD) and 3,4-methylenedioxymethamphetamine (MDMA). However, there is a paucity of investigation concerning the long-term behavioral consequences of exposure to these stimulants during adolescence. The aim of the present study was to investigate the effect of MPD and MDMA exposure in adolescence on cocaine-induced reward and psychomotor stimulation in adulthood. Adolescent Swiss-Webster mice received intraperitoneal injections of saline, MPD (10 mg/kg) or MDMA (10 mg/kg) from PD 26 to PD 32. Animal weights were monitored during and after drug administration. One month later, cocaine-induced conditioned place preference (CPP) and locomotor activity (LMA) were investigated. MPD and MDMA inhibited weight increase from PD 28 to PD 39 compared to the saline group, but weights amongst the three groups equalized by PD 46. MDMA exposure resulted in the same magnitude of cocaine (20 mg/kg)-induced CPP as saline exposure; however, MPD exposure caused significantly less CPP. Two weeks following extinction of CPP and withdrawal from cocaine, a priming injection of cocaine (5 mg/kg) reinstated significantly higher CPP in the MPD and MDMA groups than in the saline group. In the LMA experiments, cocaine (15 mg/kg) was administered for 5 consecutive days. On days 1 and 5, cocaine-induced hyperlocomotion in the MPD group was significantly higher than in the saline and MDMA groups. After a 2-week withdrawal period, cocaine (5 mg/kg) evoked significantly higher LMA responses in the MPD and MDMA groups compared to the saline group. Results suggest that exposure of mice to both MPD and MDMA during adolescence involves long-lasting neural adaptations, manifested as sensitized responses to cocaine-induced reward and psychomotor stimulation following cocaine withdrawal.

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

    PubMed

    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.

  14. Chemiluminescence detection of MDMA in street drug samples using tris(2,2'-bipyridine)ruthenium(III).

    PubMed

    Theakstone, Ashton G; Smith, Zoe M; Terry, Jessica M; Barnett, Neil W; Francis, Paul S

    2015-05-01

    Tris(2,2'-bipyridine)ruthenium(II) chemiluminescence was investigated for the detection of 3,4-methylenedioxymethamphetamine (MDMA) and several related compounds in street drug samples. Optimization using flow injection analysis showed that the selectivity of the reagent can be targeted towards the detection of secondary amines by altering the pH of the reaction environment. The greater selectivity of this mode of detection, compared to UV-absorbance, reduces the probability of false positive results from interfering compounds. The detection limit for MDMA under these conditions was 0.48 μM. A HPLC method incorporating post-column tris(2,2'-bipyridine)ruthenium(II) chemiluminescence detection was applied to the determination of MDMA in five street drug samples. The results obtained were in good agreement with quantification performed using traditional UV-absorbance detection, which demonstrates the viability of this method for confirmatory analysis of drug samples. This is the first report of tris(2,2'-bipyridine)ruthenium(II) chemiluminescence for the detection of MDMA and related amphetamine derivatives.

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

    PubMed

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

    2014-08-01

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

  16. A Comparison of the Effects of Classroom and Multi-User Virtual Environments on the Perceived Speaking Anxiety of Adult Post-Secondary English Language Learners

    ERIC Educational Resources Information Center

    Abal, Abdulaziz

    2013-01-01

    The population of English Language Learners (ELLs) globally has been increasing substantially every year. In the United States alone, adult ELLs are the fastest growing portion of learners in adult education programs (Yang, 2005). There is a significant need to improve the teaching of English to ELLs in the United States and other English-speaking…

  17. A league of their own: demographics, motivations and patterns of use of 1,955 male adult non-medical anabolic steroid users in the United States

    PubMed Central

    Cohen, Jason; Collins, Rick; Darkes, Jack; Gwartney, Daniel

    2007-01-01

    Background Rule violations among elite-level sports competitors and tragedies among adolescents have largely defined the issue of non-medical anabolic-androgenic steroid (NMAAS) use for the public and policy makers. However, the predominant and oft-ignored segment of the NMAAS community exists in the general population that is neither participating in competitive sports nor adolescent. A clearer profile of NMAAS users within the general population is an initial step in developing a full understanding of NMAAS use and devising appropriate policy and interventions. This survey sought to provide a more comprehensive profile of NMAAS users by accessing a large sample of user respondents from around the United States. Methods U.S.-based male NMAAS users (n = 1955) were recruited from various Internet websites dedicated to resistance training activities and use of ergogenic substances, mass emails, and print media to participate in a 291-item web-based survey. The Internet was utilized to provide a large and geographically diverse sample with the greatest degree of anonymity to facilitate participation. Results The majority of respondents did not initiate AAS use during adolescence and their NMAAS use was not motivated by athletics. The typical user was a Caucasian, highly-educated, gainfully employed professional approximately 30 years of age, who was earning an above-average income, was not active in organized sports, and whose use was motivated by increases in skeletal muscle mass, strength, and physical attractiveness. These findings question commonly held views of the typical NMAAS user and the associated underlying motivations. Conclusion The focus on "cheating" athletes and at risk youth has led to ineffective policy as it relates to the predominant group of NMAAS users. Effective policy, prevention or intervention should address the target population(s) and their reasons for use while utilizing their desire for responsible use and education. PMID:17931410

  18. Transcriptomic configuration of mouse brain induced by adolescent exposure to 3,4-methylenedioxymethamphetamine

    SciTech Connect

    Eun, Jung Woo; Kwack, Seung Jun; Noh, Ji Heon; Jung, Kwang Hwa; Kim, Jeong Kyu; Bae, Hyun Jin; Xie Hongjian; Ryu, Jae Chun; Ahn, Young Min; Min, Jin-Hye; Park, Won Sang; Lee, Jung Young; Rhee, Gyu Seek; Nam, Suk Woo

    2009-05-15

    The amphetamine derivative ({+-})-3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a synthetic amphetamine analogue used recreationally to obtain an enhanced affiliative emotional response. MDMA is a potent monoaminergic neurotoxin with the potential to damage brain serotonin and/or dopamine neurons. As the majority of MDMA users are young adults, the risk that users may expose the fetus to MDMA is a concern. However, the majority of studies on MDMA have investigated the effects on adult animals. Here, we investigated whether long-term exposure to MDMA, especially in adolescence, could induce comprehensive transcriptional changes in mouse brain. Transcriptomic analysis of mouse brain regions demonstrated significant gene expression changes in the cerebral cortex. Supervised analysis identified 1028 genes that were chronically dysregulated by long-term exposure to MDMA in adolescent mice. Functional categories most represented by this MDMA characteristic signature are intracellular molecular signaling pathways of neurotoxicity, such as, the MAPK signaling pathway, the Wnt signaling pathway, neuroactive ligand-receptor interaction, long-term potentiation, and the long-term depression signaling pathway. Although these resultant large-scale molecular changes remain to be studied associated with functional brain damage caused by MDMA, our observations delineate the possible neurotoxic effects of MDMA on brain function, and have therapeutic implications concerning neuro-pathological conditions associated with MDMA abuse.

  19. Optical multidimensional multiple access(O-MDMA): a new concept for free-space laser communication based on photonic mixer devices

    NASA Astrophysics Data System (ADS)

    Hess, Holger; Albrecht, Martin; Grothof, Markus; Hussmann, Stephan; Schwarte, Rudolf

    2004-01-01

    Working on optical distance measurement a new optical correlator was developed at the Institute for Data Processing of the University of Siegen in the last years. The so called Photonic Mixer Device (PMD), to be meant originally for laser ranging systems, offers a lot of advantages for wireless optical data communication like high speed spatial light demodulation up to the GHz range and inherent backlight suppression. This contribution describes the application of such PMDs in a free space interconnect based on the principle of Multi Dimensional Multiple Access (MDMA) and the advantages of this new approach, starting from the MDMA principle and followed by the fundamental functionality of PMDs. After that an Optical MDMA (O-MDMA) demonstrator and first measurement results will be presented.

  20. Differentiation of Psychoactive Drug Users and Non-Users and Prediction of Their Using Intention

    ERIC Educational Resources Information Center

    Tzeng, Oliver C. S.; Skafidas, Thomas

    1975-01-01

    Thirteen Semantic Differential bipolar variables representing various socio-cultural correlates and personality factors of psychoactive drug users as well as non-users were measured from a group of 80 college students and 20 adults. Drug users (n=44) within the last six months differed significantly from non-users in their intention of taking…

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

    PubMed

    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.

  2. 3,4-methylenedioxymethamphetamine (MDMA) interacts with therapeutic drugs on CYP3A by inhibition of pregnane X receptor (PXR) activation and catalytic enzyme inhibition.

    PubMed

    Antolino-Lobo, Irene; Meulenbelt, Jan; Nijmeijer, Sandra M; Maas-Bakker, Roel F; Meijerman, Irma; van den Berg, Martin; van Duursen, Majorie B M

    2011-05-30

    Metabolism of MDMA (3,4-methylenedioxymethamphetamine, Ecstasy) by the major hepatic drug-metabolizing enzyme cytochrome P450 3A (CYP3A), plays an important role in MDMA-induced liver toxicity. In the present study, we investigated interactions between MDMA and several therapeutic and recreational drugs on CYP3A and its regulator pregnane X receptor (PXR), using a human PXR-mediated CYP3A4-reporter gene assay, rat primary hepatocytes and microsomes. MDMA significantly inhibited hPXR-mediated CYP3A4-reporter gene expression induced by the human PXR activator rifampicin (IC₅₀ 1.26 ± 0.36 mM) or the therapeutic drugs paroxetine, fluoxetine, clozapine, diazepam and risperidone. All these drugs concentration-dependently inhibited CYP3A activity in rat liver microsomes, but in combination with MDMA this inhibition became more efficient for clozapine and risperidone. In rat primary hepatocytes that were pretreated with or without the rodent PXR activator pregnenolone 16alpha-carbonitrile (PCN), MDMA inhibited CYP3A catalytic activity with IC₅₀ values of 0.06 ± 0.12 and 0.09 ± 0.13 mM MDMA, respectively. This decrease appeared to be due to decreased activation of PXR and subsequent decreased CYP3A gene expression, and catalytic inhibition of CYP3A activity. These data suggest that in situations of repeated MDMA use in combination with other (therapeutic) drugs, adverse drug-drug interactions through interactions with PXR and/or CYP3A cannot be excluded.

  3. 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.

    PubMed

    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. PMID:26721607

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

    PubMed

    Chiu, Chuang-Hsin; Siow, Tiing-Yee; Weng, Shao-Ju; Hsu, Yi-Hua; Huang, Yuahn-Sieh; Chang, Kang-Wei; Cheng, Cheng-Yi; Ma, Kuo-Hsing

    2015-01-01

    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. PMID:26378923

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

    PubMed

    Chiu, Chuang-Hsin; Siow, Tiing-Yee; Weng, Shao-Ju; Hsu, Yi-Hua; Huang, Yuahn-Sieh; Chang, Kang-Wei; Cheng, Cheng-Yi; Ma, Kuo-Hsing

    2015-01-01

    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.

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

    PubMed

    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.

  7. 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.

    PubMed

    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.

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

    PubMed

    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. PMID:24590542

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

    PubMed

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

    2015-02-01

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

  10. Drug intelligence based on MDMA tablets data I. Organic impurities profiling.

    PubMed

    Weyermann, Céline; Marquis, Raymond; Delaporte, Céline; Esseiva, Pierre; Lock, Eric; Aalberg, Laura; Bozenko, Joseph S; Dieckmann, Susanne; Dujourdy, Laurence; Zrcek, Frantisek

    2008-05-01

    The main objectives of the European project "Collaborative Harmonization of Methods for Profiling of Amphetamine Type Stimulants" (CHAMP) funded by the sixth framework programme of the European Commission, included the harmonization of MDMA profiling methods and the creation of a common database in a drug intelligence perspective. In the preliminary stages of this project, the participating laboratories analysed the physical characteristics, the chemical composition and the organic impurities of MDMA tablets, using the previously harmonized methods. The aim of the present work was to apply statistical treatments to the recorded data in order to evaluate their potential in the fight against drug trafficking. Comparable working procedures were applied on the different types of data. The first part of this article deals with organic impurities data, while the second part focuses on the potential of the physical characteristics. Organic impurities data were recorded by a harmonized Gas Chromatography/Mass Spectrometry (GC/MS) method previously developed. Statistical analysis provided a selection of pertinent variables among the 46 organic impurities identified in the chromatograms. Correlation coefficients were used to yield separation between populations of samples coming from the same synthesis batch and samples coming from different batches. It was shown that correlation measurements based on Pearson and cosine functions applied to the data pre-treated by normalisation to the sum of peak responses followed by the square root provided an excellent discrimination between the two populations. The statistical methods applied to organic impurities profiles proved to be excellent techniques to differentiate samples from different batches and to highlight operational links between samples.

  11. Cocaine-dependent adults and recreational cocaine users are more likely than controls to choose immediate unsafe sex over delayed safer sex.

    PubMed

    Koffarnus, Mikhail N; Johnson, Matthew W; Thompson-Lake, Daisy G Y; Wesley, Michael J; Lohrenz, Terry; Montague, P Read; Bickel, Warren K

    2016-08-01

    Cocaine users have a higher incidence of risky sexual behavior and HIV infection than nonusers. Our aim was to measure whether safer sex discount rates-a measure of the likelihood of having immediate unprotected sex versus waiting to have safer sex-differed between controls and cocaine users of varying severity. Of the 162 individuals included in the primary data analyses, 69 met the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) criteria for cocaine dependence, 29 were recreational cocaine users who did not meet the dependence criteria, and 64 were controls. Participants completed the Sexual Discounting Task, which measures a person's likelihood of using a condom when one is immediately available and how that likelihood decreases as a function of delay to condom availability with regard to 4 images chosen by the participants of hypothetical sexual partners differing in perceived desirability and likelihood of having a sexually transmitted infection. When a condom was immediately available, the stated likelihood of condom use sometimes differed between cocaine users and controls, which depended on the image condition. Even after controlling for rates of condom use when one is immediately available, the cocaine-dependent and recreational users groups were more sensitive to delay to condom availability than controls. Safer sex discount rates were also related to intelligence scores. The Sexual Discounting Task identifies delay as a key variable that impacts the likelihood of using a condom among these groups and suggests that HIV prevention efforts may be differentially effective based on an individual's safer sex discount rate. (PsycINFO Database Record PMID:27454677

  12. User Antennas

    NASA Technical Reports Server (NTRS)

    Jamnejad, Vahraz; Cramer, Paul

    1990-01-01

    The following subject areas are covered: (1) impact of frequency change of user and spacecraft antenna gain and size; (2) basic personal terminal antennas (impact of 20/30 GHz frequency separation; parametric studies - gain, size, weight; gain and figure of merit (G/T); design data for selected antenna concepts; critical technologies and development goals; and recommendations); and (3) user antenna radiation safety concerns.

  13. A study of impurities in intermediates and 3,4-methylenedioxymethamphetamine (MDMA) samples produced via reductive amination routes.

    PubMed

    Gimeno, P; Besacier, F; Bottex, M; Dujourdy, L; Chaudron-Thozet, H

    2005-12-20

    Impurities found in various sources of precursors (sassafras oil, safrol, isosafrol, piperonal), intermediates (beta-nitroisosafrol, piperonylmethylketone (PMK)) and final product (3,4-methylenedioxymethamphetamine (MDMA)) are presented and discussed. Particular attention is paid to the chemical origin of each impurity found in the prepared samples. Impurity profiles of isosafrol, piperonal, and PMK samples obtained from industrial sources or from sassafras oil were first compared. Then PMK samples produced from isosafrol through isosafrol glycol or through beta-nitroisosafrol were compared. At last, attention was paid to the reductive amination of PMK to MDMA using different reductive agents. Possible use of this profiling method to determine the synthesis route is discussed for all products.

  14. A study to model the post-mortem stability of 4-MMC, MDMA and BZP in putrefying remains.

    PubMed

    Wenholz, Daniel S; Luong, Susan; Philp, Morgan; Forbes, Shari L; Stuart, Barbara H; Drummer, Olaf H; Fu, Shanlin

    2016-08-01

    There is currently limited data available on the stabilities of the three stimulants 4-methylmethcathinone (4-MMC), 3,4-methylenedioxymethamphetamine (MDMA) and N-benzylpiperazine (BZP) in a putrefying matrix. A Gas Chromatography Mass Spectrometry (GC-MS) method to determine the concentration of the three drugs in putrefying porcine liver over a three month period was developed and validated. Both 4-MMC and BZP were found to be unstable, becoming undetectable and having an average recovery of 52% respectively after one month at ambient room temperature (20°C). MDMA was found to be moderately stable, with an average recovery of 74% after three months at room temperature. This study indicated that the putrefaction process could have a significant impact on concentrations of 4-MMC and BZP in post-mortem cases involving putrefied remains. PMID:26829335

  15. Stability of 3,4-methylenedioxymethampetamine (MDMA), 4-methylmethcathinone (mephedrone) and 3-trifluromethylphenylpiperazine (3-TFMPP) in formalin solution.

    PubMed

    Maskell, Peter D; Seetohul, L Nitin; Livingstone, Alison C; Cockburn, Alexandra K; Preece, Jamie; Pounder, Derrick J

    2013-09-01

    Occasionally, the only postmortem samples available for analysis are contaminated with formaldehyde, either due to embalming prior to sampling or because analysis is carried out only when formalin-fixed tissues retained for histological study are available. Formaldehyde reacts with several drugs of forensic interest that contain either a primary or a secondary amine group to form their N-methyl derivatives. We investigated the stability of 3,4-methylenedioxymethampetamine (MDMA), 4-methylmethcathinone (mephedrone) and 3-trifluromethylphenylpiperazine (3-TFMPP) in formalin solutions using three different formaldehyde concentrations (5, 10 and 20%) and three different pHs (3.0, 7.0 and 9.5). Analysis was performed using high-performance liquid chromatography with diode array detection to determine the percentage degradation of each drug over time, up to 60 days. MDMA, mephedrone and 3-TFMPP are unstable in formalin solutions, with the degradation rate increasing with increasing pH. After 28 days in 20% formalin, pH 9.5, there remained 57% of the initial 3-TFMPP concentration, 11% of the initial MDMA concentration and 4% of the initial mephedrone concentration. Forensic toxicologists should be aware that, when analyzing for these drugs in an embalmed body or in tissues stored in formalin solutions, the methylated form of the secondary amine-containing drug could be a more useful analyte than the parent drug.

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

    PubMed

    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.

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

    PubMed

    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. PMID:27325011

  18. Experienced drug users assess the relative harms and benefits of drugs: a web-based survey.

    PubMed

    Carhart-Harris, Robin Lester; Nutt, David John

    2013-01-01

    A web-based survey was used to consult the opinions of experienced drug users on matters related to drug harms. We identified a rare sample of 93 drug users with personal experience with 11 different illicit drugs that are widely used in the UK. Asked to assess the relative harms of these drugs, they ranked alcohol and tobacco as the most harmful, and three "Class A" drugs (MDMA, LSD, and psilocybin) and one class B (cannabis) were ranked as the four least harmful drugs. When asked to assess the relative potential for benefit of the 11 drugs, MDMA, LSD, psilocybin, and cannabis were ranked in the top four; and when asked why these drugs are beneficial, rather than simply report hedonic properties, they referred to potential therapeutic applications (e.g., as tools to assist psychotherapy). These results provide a useful insight into the opinions of experienced drug users on a subject about which they have a rare and intimate knowledge. PMID:24377171

  19. Meta-analysis of molecular imaging of serotonin transporters in ecstasy/polydrug users.

    PubMed

    Roberts, Carl Alexander; Jones, Andrew; Montgomery, Catharine

    2016-04-01

    We conducted a meta-analysis on the available data from studies investigating SERTs in ecstasy users and polydrug using controls. From 7 studies we compared data from 157 ecstasy users and 148 controls across 14 brain regions. The main effect suggested ecstasy/MDMA related SERT reductions (SMD=0.52, 95% CIs [0.40, 0.65]; Z=8.36, p<.01, I(2)=89%). A significant effect of subgroups (X(2)=37.41, df=13, p<.01, I(2)=65.3%) suggested differential effects across brain ROIs. Ecstasy users showed significant SERT reductions in 11 out of the 14 regions, including every neocortical and limbic region analysed. Greatest effects were observed in the occipital cortex (SMD=1.09, 95% CIs [0.70, 1.48]). No group effects were observed in subcortical areas of the caudate, putamen and midbrain. Literature on Postsynaptic 5HT2A receptor imaging was synthesised with these results. We conclude that, in line with preclinical data, serotonin axons with the longest projections from the raphe nuclei appear to be most affected by ecstasy/MDMA use. PMID:26855234

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

    PubMed

    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. PMID:27320055

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

    PubMed Central

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

    2014-01-01

    Background and PurposeMany 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 Δ9-tetrahydrocannabinol (THC) and 3,4-methylenedioxymethamphetamine (MDMA) on diverse neuroinflammation and neurotoxic markers. Experimental ApproachMale 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. Key ResultsTHC 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. Conclusions and ImplicationsAdolescent exposure of rats to THC and/or MDMA induced long-term, sex-dependent neurochemical and glial alterations, and revealed interactions between the two drugs. Linked ArticlesThis 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 PMID:24236988

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

    PubMed

    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.

  3. The synthesis and characterisation of MDMA derived from a catalytic oxidation of material isolated from black pepper reveals potential route specific impurities.

    PubMed

    Plummer, Christopher M; Breadon, Thomas W; Pearson, James R; Jones, Oliver A H

    2016-05-01

    This work examines the chemical synthesis of 3,4-methylenedioxy-N-methylamphetamine (MDMA) from piperonal prepared via a catalytic ruthenium tetroxide oxidation of piperine extracted from black pepper. A variety of oxidation conditions were experimented with including different solvent systems and co-oxidants. A sample of prepared piperonal was successfully converted into MDMA via 3,4-methylenedioxyphenyl-2-nitropropene (MDP2NP) and 3,4-methylenedioxyphenyl-2-propanone (MDP2P) and the impurities within each product characterised by GC-MS to give a contaminant profile of the synthetic pathway. Interestingly, it was discovered that a chlorinated analogue of piperonal (6-chloropiperonal) was created during the oxidation process by an as yet unknown mechanism. This impurity reacted alongside piperonal to give chlorinated analogues of each precursor, ultimately yielding 2-chloro-4,5-methylenedioxymethamphetamine (6-Cl-MDMA) as an impurity within the MDMA sample. The methodology developed is a simple way to synthesise a substantial amount of precursor material with easy to obtain reagents. The results also show that chlorinated MDMA analogues, previously thought to be deliberately included adulterants, may in fact be route specific impurities with potential application in determining the origin and synthesis method of seized illicit drugs. PMID:27162021

  4. The synthesis and characterisation of MDMA derived from a catalytic oxidation of material isolated from black pepper reveals potential route specific impurities.

    PubMed

    Plummer, Christopher M; Breadon, Thomas W; Pearson, James R; Jones, Oliver A H

    2016-05-01

    This work examines the chemical synthesis of 3,4-methylenedioxy-N-methylamphetamine (MDMA) from piperonal prepared via a catalytic ruthenium tetroxide oxidation of piperine extracted from black pepper. A variety of oxidation conditions were experimented with including different solvent systems and co-oxidants. A sample of prepared piperonal was successfully converted into MDMA via 3,4-methylenedioxyphenyl-2-nitropropene (MDP2NP) and 3,4-methylenedioxyphenyl-2-propanone (MDP2P) and the impurities within each product characterised by GC-MS to give a contaminant profile of the synthetic pathway. Interestingly, it was discovered that a chlorinated analogue of piperonal (6-chloropiperonal) was created during the oxidation process by an as yet unknown mechanism. This impurity reacted alongside piperonal to give chlorinated analogues of each precursor, ultimately yielding 2-chloro-4,5-methylenedioxymethamphetamine (6-Cl-MDMA) as an impurity within the MDMA sample. The methodology developed is a simple way to synthesise a substantial amount of precursor material with easy to obtain reagents. The results also show that chlorinated MDMA analogues, previously thought to be deliberately included adulterants, may in fact be route specific impurities with potential application in determining the origin and synthesis method of seized illicit drugs.

  5. A long hangover from party drugs: residual proteomic changes in the hippocampus of rats 8 weeks after γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination.

    PubMed

    van Nieuwenhuijzen, Petra S; Kashem, Mohammed A; Matsumoto, Izuru; Hunt, Glenn E; McGregor, Iain S

    2010-07-01

    3,4-Methylenedioxymethamphetamine (MDMA) and gamma-hydroxybutyrate (GHB) are popular party drugs that are used for their euphoric and prosocial effects, and sometimes in combination. Both drugs increase markers of oxidative stress in the hippocampus and can cause lasting impairments in hippocampal-dependent forms of memory. To gain further information on the biochemical mechanisms underlying these effects, the current study examined residual changes in hippocampal protein expression measured 8 weeks after chronic administration of GHB (500mg/kg), MDMA (5mg/kg) or their combination (GHB/MDMA). The drugs were administered once a day for 10 days in an environment with an elevated ambient temperature of 28 degrees C. Results showed significant changes in protein expression, relative to controls, in all three groups: MDMA and GHB given alone caused residual changes in 8 and 5 proteins respectively, while the GHB/MDMA combination significantly changed 6 proteins. The altered proteins had roles in neuroplasticity, neuroprotection, intracellular signalling and cytoskeletal function. The largest change (-4.3-fold) was seen in the MDMA group with the protein C-crk: a protein implicated in learning-related neuroplasticity. The second largest change (3.0-fold) was seen in the GHB group in Glutathione-S-transferase (GST), a protein that protects against oxidative stress. Two cytoskeletal proteins (Tubulin Folding Cofactor B and Tropomyosin-alpha-3 chain) and one plasticity related protein (Neuronal Pentraxin-1 NP1) were similarly changed in both the MDMA and the GHB groups, while two intracellular signalling proteins (alpha-soluble NSF-attachment protein and subunits of the V-type proton ATPase) were changed in both the MDMA/GHB and the MDMA groups. These results provide some insight into the molecular pathways possibly underlying the lasting cognitive deficits arising from GHB and/or MDMA use.

  6. A C. elegans p38 MAP kinase pathway mutant protects from dopamine, methamphetamine, and MDMA toxicity

    PubMed Central

    Schreiber, Matthew A.; McIntire, Steven L.

    2011-01-01

    Biogenic amine systems are damaged by amphetamine abuse and in Parkinson's disease. The mechanisms mediating this damage are of high importance because of the public health impact of these problems. Here we have taken advantage of the C. elegans nematode model system to investigate genetic modifiers of biogenic amine toxicity. In a forward genetic screen, we identified a mutant resistant to the toxic effects of dopamine. This mutant was also resistant to toxic doses of methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA). In addition, this mutation conferred resistance to 6-hydroxydopamine damage to dopaminergic neurons in a Parkinson's disease model. Resistance was due to a mutation in the nsy-1 gene, orthologous to the mammalian ASK-1 MAPKKK. NSY-1 is in the highly conserved p38 MAP kinase pathway, which plays a crucial role in C. elegans innate immunity, suggesting that this pathway may play a role in biogenic amine toxicity system damage due to amphetamines and in the pathogenesis of Parkinson's disease in higher organisms. PMID:21565252

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

    PubMed Central

    Paixão, Márcio W.; Lourenço, Tiago C.

    2016-01-01

    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. PMID:27668862

  8. Tobacco Use, Quitting Behavior, and Health Characteristics Among Current Electronic Cigarette Users in a National Tri-Ethnic Adult Stable Smoker Sample

    PubMed Central

    Hayes, Rashelle B.; Scheuermann, Taneisha S.; Romero, Devan R.; Emami, Ashley S.; Resnicow, Ken; Olendzki, Effie; Person, Sharina D.; Ahluwalia, Jasjit S.

    2015-01-01

    Introduction: The present study characterizes the tobacco use, quitting behaviors, and health characteristics of cigarette smokers who did not change their smoking pattern over the past 6 months and have used electronic cigarettes (ECs) in the past 30 days. This is an important subpopulation to characterize if EC dual use with cigarettes continues to grow. Methods: Participants (N = 2,376) from a research survey panel completed an online cross-sectional survey between June and August 2012. Sampling was stratified to recruit equal numbers of cigarette smoking participants by race/ethnicity (Black, Hispanic, and Caucasian) and smoking frequency (nondaily and daily). All displayed a stable rate of smoking for the past 6 months and were not currently in treatment. Bivariate and multivariate analyses were used to examine correlates of current EC use (any use within the past 30 days). Results: Current EC use was reported by 9.2% (n = 219) of the total sample. Of current EC users, 44% reported having used ECs as a quit method. Bivariate and multivariate analyses showed that current EC use was significantly associated with greater nicotine dependence, concurrent poly-tobacco use, more past-year quit attempts, past use of multiple cessation methods, and more depressive symptoms. No demographic variables were significantly associated with current EC use. Conclusions: This study suggests that stable smokers who currently use ECs possess characteristics that are associated with difficulty in achieving smoking cessation. These characteristics should be considered when examining the effectiveness of ECs on cessation and in designing future cessation trials using ECs. PMID:25385875

  9. Sex-dependent effects of early maternal deprivation on MDMA-induced conditioned place preference in adolescent rats: possible neurochemical correlates.

    PubMed

    Llorente-Berzal, Alvaro; Manzanedo, Carmen; Daza-Losada, Manuel; Valero, Manuel; López-Gallardo, Meritxell; Aguilar, María A; Rodríguez-Arias, Marta; Miñarro, José; Viveros, Maria-Paz

    2013-09-01

    The early neonatal stage constitutes a sensitive period during which exposure to adverse events can increase the risk of neuropsychiatric disorders. Maternal deprivation (MD) is a model of early life stress that induces long-term behavioural and physiological alterations, including susceptibility to different drugs of abuse. In the present study we have used the conditioned place preference (CPP) paradigm to address the influence of MD on the rewarding effects of 3,4-methylenedioxymetamphetamine (MDMA) in adolescent animals of both sexes. We have previously observed in adolescent rats that MD induces modifications in the serotonergic and endocannabinoid systems, which play a role in the rewarding effects of MDMA. In light of this evidence, we hypothesized that MD would alter the psychobiological consequences of exposure to MDMA. Neonatal Wistar rats underwent MD (24h, on PND 9) or were left undisturbed (controls). The animals were conditioned with 2.5mg/kg MDMA during the periadolescent period (PND 34-PND 43) and were tested in the open-field test at the end of adolescence (PND 60). Animals were sacrificed on PND 68-75 and levels of serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid were measured in the striatum, hippocampus and cortex, while the expression of hippocampal CB1 cannabinoid receptor (CB1R) and circulating levels of corticosterone and leptin were also measured. Control males showed CPP after administration of MDMA. However, no MDMA-induced CPP was detected in control females or MD males, and MD had no effect on open field activity in any group. A reduction in striatal and cortical 5-HT levels, increased expression of hippocampal CB1R and a marked trend towards higher circulating leptin levels were observed in MDMA-treated MD males. Our results demonstrate for the first time that MD reduces the rewarding effects of MDMA in a sex-dependent manner. We propose that this effect is related, at least in part, with alterations of the serotonergic

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

    SciTech Connect

    Garcia-Rates, Sara; Camarasa, Jordi

    2010-05-01

    Previous work by our group demonstrated that homomeric alpha7 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{sup 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 alpha7 agonist PNU 282987 with IC{sub 50} values in the low micromolar range. Similarly, MDMA induced inward currents in Xenopus oocytes transfected with human alpha7 but not with alpha4beta2 nAChR and inhibited ACh-induced currents in both receptors in a concentration-dependent manner. The calcium response was inhibited by methyllycaconitine (MLA) and alpha-bungarotoxin but not by dihydro-beta-erythroidine. These results therefore indicate that MDMA acts as a partial agonist on alpha7 nAChRs and as an antagonist on the heteromeric subtypes. Subsequently, calcium-induced Ca{sup 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{sup 2+} levels and induced an increase in alpha-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 alpha7 nAChR. Sustained calcium entry and calpain activation could favor the

  11. A mobile/web app for long distance caregivers of older adults: functional requirements and design implications from a user centered design process.

    PubMed

    Williamson, Steven S; Gorman, Paul N; Jimison, Holly B

    2014-01-01

    Recent trends of population aging and globalization have required an increasing number of individuals to act as long distance caregivers (LDCs) to aging family members. Information technology solutions may ease the burden placed on LDCs by providing remote monitoring, easier access to information and enhanced communication. While some technology tools have been introduced, the information and technology needs of LDCs in particular are not well understood. Consequently, a needs assessment was performed by using video conferencing software to conduct semi-structured interviews with 10 LDCs. Interviews were enriched through the use of stimulus materials that included the demonstration of a prototype LDC health management web/mobile app. Responses were recorded, transcribed and then analyzed. Subjects indicated that information regarding medication regimens and adherence, calendaring, and cognitive health were most needed. Participants also described needs for video calling, activity data regarding sleep and physical exercise, asynchronous communication, photo sharing, journaling, access to online health resources, real-time monitoring, an overall summary of health, and feedback/suggestions to help them improve as caregivers. In addition, all respondents estimated their usage of a LDC health management website would be at least once per week, with half indicating a desire to access the website from a smartphone. These findings are being used to inform the design of a LDC health management website to promote the meaningful involvement of distant family members in the care of older adults.

  12. A Mobile/Web App for Long Distance Caregivers of Older Adults: Functional Requirements and Design Implications from a User Centered Design Process

    PubMed Central

    Williamson, Steven S.; Gorman, Paul N.; Jimison, Holly B.

    2014-01-01

    Recent trends of population aging and globalization have required an increasing number of individuals to act as long distance caregivers (LDCs) to aging family members. Information technology solutions may ease the burden placed on LDCs by providing remote monitoring, easier access to information and enhanced communication. While some technology tools have been introduced, the information and technology needs of LDCs in particular are not well understood. Consequently, a needs assessment was performed by using video conferencing software to conduct semi-structured interviews with 10 LDCs. Interviews were enriched through the use of stimulus materials that included the demonstration of a prototype LDC health management web/mobile app. Responses were recorded, transcribed and then analyzed. Subjects indicated that information regarding medication regimens and adherence, calendaring, and cognitive health were most needed. Participants also described needs for video calling, activity data regarding sleep and physical exercise, asynchronous communication, photo sharing, journaling, access to online health resources, real-time monitoring, an overall summary of health, and feedback/suggestions to help them improve as caregivers. In addition, all respondents estimated their usage of a LDC health management website would be at least once per week, with half indicating a desire to access the website from a smartphone. These findings are being used to inform the design of a LDC health management website to promote the meaningful involvement of distant family members in the care of older adults. PMID:25954469

  13. A mobile/web app for long distance caregivers of older adults: functional requirements and design implications from a user centered design process.

    PubMed

    Williamson, Steven S; Gorman, Paul N; Jimison, Holly B

    2014-01-01

    Recent trends of population aging and globalization have required an increasing number of individuals to act as long distance caregivers (LDCs) to aging family members. Information technology solutions may ease the burden placed on LDCs by providing remote monitoring, easier access to information and enhanced communication. While some technology tools have been introduced, the information and technology needs of LDCs in particular are not well understood. Consequently, a needs assessment was performed by using video conferencing software to conduct semi-structured interviews with 10 LDCs. Interviews were enriched through the use of stimulus materials that included the demonstration of a prototype LDC health management web/mobile app. Responses were recorded, transcribed and then analyzed. Subjects indicated that information regarding medication regimens and adherence, calendaring, and cognitive health were most needed. Participants also described needs for video calling, activity data regarding sleep and physical exercise, asynchronous communication, photo sharing, journaling, access to online health resources, real-time monitoring, an overall summary of health, and feedback/suggestions to help them improve as caregivers. In addition, all respondents estimated their usage of a LDC health management website would be at least once per week, with half indicating a desire to access the website from a smartphone. These findings are being used to inform the design of a LDC health management website to promote the meaningful involvement of distant family members in the care of older adults. PMID:25954469

  14. The preservation of in vivo phosphorylated and activated uncoupling protein 3 (UCP3) in isolated skeletal muscle mitochondria following administration of 3,4-methylenedioxymethamphetamine (MDMA aka ecstasy) to rats/mice.

    PubMed

    Kelly, Orlagh M; McNamara, Yvonne M; Manzke, Lars H; Meegan, Mary J; Porter, Richard K

    2012-01-01

    Previous researchers have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA) induced hyperthermia, in skeletal muscle of animals, is uncoupling protein 3 (UCP3) dependent. In light of our investigations that in vivo phosphorylation of UCP1 is augmented under conditions of cold-acclimation, we set out to investigate whether (a) UCP3 was phosphorylated in vivo and (b) whether in vivo phosphorylation of UCP3 resulted in increased proton leak following MDMA administration to animals. Our data demonstrate that MDMA treatment (but not PBS treatment) of animals results in both in vivo serine and tyrosine phosphorylation of UCP3 in skeletal muscle mitochondria, isolated in the presence of phosphatase inhibitors to preserve in vivo phosphorylation. In addition, proton leak is only increased in skeletal muscle mitochondria isolated from MDMA treated animals (in the presence of phosphatase inhibitors) and the increased proton leak is due to phosphorylated UCP3. UCP3 abundance in skeletal muscle mitochondria is unaffected by MDMA administration. Preservation of UCP3 phosphorylation and increased proton leak is lost when skeletal muscle mitochondria are isolated in the absence of phosphatase inhibitors. We conclude that MDMA treatment of animals increases proton leak in skeletal muscle mitochondria by activating UCP3 through in vivo covalent modification of UCP3 by phosphorylation. Furthermore, we deduce that the MDMA induced hyperthermia in skeletal muscle is due to increased proton leak in vivo as a result of activation of UCP3 through phosphorylation.

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

    PubMed

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

    2014-06-01

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

  16. 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.

    PubMed

    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. PMID:26967321

  17. 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

    PubMed Central

    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. PMID:26967321

  18. The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers.

    PubMed

    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. PMID:24904346

  19. Evaluation of Monitoring Schemes for Wastewater-Based Epidemiology to Identify Drug Use Trends Using Cocaine, Methamphetamine, MDMA and Methadone.

    PubMed

    Humphries, Melissa A; Bruno, Raimondo; Lai, Foon Yin; Thai, Phong K; Holland, Barbara R; O'Brien, Jake W; Ort, Christoph; Mueller, Jochen F

    2016-05-01

    Wastewater-based epidemiology is increasingly being used as a tool to monitor drug use trends. To minimize costs, studies have typically monitored a small number of days. However, cycles of drug use may display weekly and seasonal trends that affect the accuracy of monthly or annual drug use estimates based on a limited number of samples. This study aimed to rationalize sampling methods for minimizing the number of samples required while maximizing information about temporal trends. A range of sampling strategies were examined: (i) targeted days (e.g., weekends), (ii) completely random or stratified random sampling, and (iii) a number of sampling strategies informed by known weekly cycles in drug use data. Using a time-series approach, analysis was performed for four drugs (MDMA, methamphetamine, cocaine, methadone) collected through a continuous sampling program over 14 months. Results showed, for drugs with weekly cycles (MDMA, methamphetamine and cocaine in this sample), sampling strategies which made use of those weekly cycles required fewer samples to obtain similar information as sampling 5 days per week and had better accuracy than stratified random sampling techniques. PMID:27007609

  20. The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers.

    PubMed

    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.

  1. The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers

    PubMed Central

    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. PMID:24904346

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

    PubMed

    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.

  3. Environmental concentrations of 3,4-methylenedioxymethamphetamine (MDMA)-induced cellular stress and modulated antioxidant enzyme activity in the zebra mussel.

    PubMed

    Parolini, Marco; Magni, Stefano; Binelli, Andrea

    2014-09-01

    Recent monitoring studies showed measurable levels of the 3,4-methylenedioxymethamphetamine (MDMA) in aquatic environments. However, no information is currently available on its potential hazard to aquatic non-target organisms. The aim of this study was to investigate the potential sub-lethal effects induced by 14-day exposures to low MDMA concentrations (0.05 and 0.5 μg/L) to zebra mussel (Dreissena polymorpha) specimens through the application of a biomarker suite. The trypan blue exclusion method and the neutral red retention assay (NRRA) were used to assess MDMA cytotoxicity. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST), as well as the lipid peroxidation (LPO) and protein carbonyl content (PCC), were measured as oxidative stress indexes. The single cell gel electrophoresis (SCGE) assay, the DNA diffusion assay, and the micronucleus test (MN test) were applied to investigate DNA damage, while filtration rate was measured as physiological parameter. Despite significant decrease in lysosome membrane stability, hemocyte viability and imbalances in CAT and GST activities pointed out at the end of the exposure to 0.5 μg/L, no significant variations for the other end points were noticed at both the treatments, suggesting that environmentally relevant MDMA concentrations did not induce deleterious effects to the zebra mussel. PMID:24878561

  4. Environmental concentrations of 3,4-methylenedioxymethamphetamine (MDMA)-induced cellular stress and modulated antioxidant enzyme activity in the zebra mussel.

    PubMed

    Parolini, Marco; Magni, Stefano; Binelli, Andrea

    2014-09-01

    Recent monitoring studies showed measurable levels of the 3,4-methylenedioxymethamphetamine (MDMA) in aquatic environments. However, no information is currently available on its potential hazard to aquatic non-target organisms. The aim of this study was to investigate the potential sub-lethal effects induced by 14-day exposures to low MDMA concentrations (0.05 and 0.5 μg/L) to zebra mussel (Dreissena polymorpha) specimens through the application of a biomarker suite. The trypan blue exclusion method and the neutral red retention assay (NRRA) were used to assess MDMA cytotoxicity. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST), as well as the lipid peroxidation (LPO) and protein carbonyl content (PCC), were measured as oxidative stress indexes. The single cell gel electrophoresis (SCGE) assay, the DNA diffusion assay, and the micronucleus test (MN test) were applied to investigate DNA damage, while filtration rate was measured as physiological parameter. Despite significant decrease in lysosome membrane stability, hemocyte viability and imbalances in CAT and GST activities pointed out at the end of the exposure to 0.5 μg/L, no significant variations for the other end points were noticed at both the treatments, suggesting that environmentally relevant MDMA concentrations did not induce deleterious effects to the zebra mussel.

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

    PubMed

    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. PMID:24590541

  6. Justine user`s manual

    SciTech Connect

    Lee, S.R.

    1995-10-01

    Justine is the graphical user interface to the Los Alamos Radiation Modeling Interactive Environment (LARAMIE). It provides LARAMIE customers with a powerful, robust, easy-to-use, WYSIWYG interface that facilitates geometry construction and problem specification. It is assumed that the reader is familiar with LARAMIE, and the transport codes available, i.e., MCNPTM and DANTSYSTM. No attempt is made in this manual to describe these codes in detail. Information about LARAMIE, DANTSYS, and MCNP are available elsewhere. It i also assumed that the reader is familiar with the Unix operating system and with Motif widgets and their look and feel. However, a brief description of Motif and how one interacts with it can be found in Appendix A.

  7. PDBDiff user`s manual

    SciTech Connect

    Brown, S.A.

    1992-01-07

    The SABrE system provides a number of tools for working with PDB files in a fairly generic fashion. In particular, PDBDiff compares the contents of two PDB files and displays the differences (in a manner similar but not identical to the UNIX utility diff). PDBDiff can also be run in an interactive mode which lets a user compare two PDB files on an item by item basis. The PDB tools, PDBView, PDBLS, PDBDiff, and PDBComp, are all SX programs. SX is a dialect of the LISP programming language which consists of extensions to the SCHEME dialect of LISP. The extensions provide functionality for graphics, binary data handling, and other areas of functionality. PDBDiff has a {open_quotes}help{close_quotes} command which lists its commands.

  8. PST user`s guide

    SciTech Connect

    Rempe, J.L.; Cebull, M.J.; Gilbert, B.G.

    1996-10-01

    The Parametric Source Term (PST) software allows estimation of radioactivity release fractions for Level 2 Probabilistic Safety Assessments (PSAs). PST was developed at the Idaho National Engineering Laboratory (INEL) for the Nuclear Regulatory Commission`s (NRC`s) Accident Sequence Precursor (ASP) Program. PST contains a framework of equations that model activity transport between volumes in the release pathway from the core, through the vessel, through the containment, and to the environment. PST quickly obtains exact solutions to differential equations for activity transport in each volume for each time interval. PST provides a superior method for source term estimation because it: ensures conservation of activity transported across various volumes in the release pathway; provides limited consideration of the time-dependent behavior of input parameter uncertainty distributions; allows input to be quantified using state-of-the-art severe accident analysis code results; increases modeling flexibility because linkage between volumes is specified by user input; and allows other types of Light Water Reactor (LWR) plant designs to be evaluated with minimal modifications. PST is a microcomputer-based system that allows the analyst more flexibility than a mainframe system. PST has been developed to run with both MS DOS and MS Windows 95/NT operating systems. PST has the capability to load ASP Source Term Vector (STV) information, import pre-specified default input for the 6 Pressurized Water Reactors (PWRs) initially analyzed in the NRC ASP program, allow input value modifications for release fraction sensitivity studies, export user-specified default input for the LWR being modeled, report results of radioactivity release calculations at each time interval, and generate formatted results that can interface with other risk assessment codes. This report describes the PST model and provides guidelines for using PST.

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

    PubMed

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

    2012-03-01

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

  10. A comparative study on the acute and long-term effects of MDMA and 3,4-dihydroxymethamphetamine (HHMA) on brain monoamine levels after i.p. or striatal administration in mice

    PubMed Central

    Escobedo, Isabel; O'Shea, Esther; Orio, Laura; Sanchez, Veronica; Segura, Mireia; de la Torre, Rafael; Farre, Magi; Green, Alfred Richard; Colado, Maria Isabel

    2004-01-01

    This study investigated whether the immediate and long-term effects of 3,4-methylenedioxymethamphetamine (MDMA) on monoamines in mouse brain are due to the parent compound and the possible contribution of a major reactive metabolite, 3,4-dihydroxymethamphetamine (HHMA), to these changes. The acute effect of each compound on rectal temperature was also determined. MDMA given i.p. (30 mg kg−1, three times at 3-h intervals), but not into the striatum (1, 10 and 100 μg, three times at 3-h intervals), produced a reduction in striatal dopamine content and modest 5-HT reduction 1 h after the last dose. MDMA does not therefore appear to be responsible for the acute monoamine release that follows its peripheral injection. HHMA does not contribute to the acute MDMA-induced dopamine depletion as the acute central effects of MDMA and HHMA differed following i.p. injection. Both compounds induced hyperthermia, confirming that the acute dopamine depletion is not responsible for the temperature changes. Peripheral administration of MDMA produced dopamine depletion 7 days later. Intrastriatal MDMA administration only produced a long-term loss of dopamine at much higher concentrations than those reached after the i.p. dose and therefore bears little relevance to the neurotoxicity. This indicates that the long-term effect is not attributable to the parent compound. HHMA also appeared not to be responsible as i.p. administration failed to alter the striatal dopamine concentration 7 days later. HHMA was detected in plasma, but not in brain, following MDMA (i.p.), but it can cross the blood–brain barrier as it was detected in the brain following its peripheral injection. The fact that the acute changes induced by i.p. or intrastriatal HHMA administration differed indicates that HHMA is metabolised to other compounds which are responsible for changes observed after i.p. administration. PMID:15665862

  11. Binge Drinkers, Illicit Drug Users, and Polydrug Users: An Epidemiological Study of American Collegians.

    ERIC Educational Resources Information Center

    Feigelman, William; Gorman, Bernard S.; Lee, Julia A.

    1998-01-01

    Compares four subgroups of young adult drug users based on secondary analysis of data originally collected in 1993. Consistent with results from clinical studies, polydrug users were far more likely to engage in risk-taking behaviors. Findings demonstrate the need to offer a full complement of drug rehabilitation and education services to…

  12. [Psychedelics and quasi-psychedelics in the light of contemporary research: medical cannabis, MDMA, salvinorin A, ibogaine and ayahuasca].

    PubMed

    Szabó, Attila; Kazai, Anita; Frecska, Ede; Brys, Zoltán

    2015-09-01

    In lack of professional research and appropriate concepts our scientific knowledge of psychedelic agents is limited. According to the long-held official view these drugs are entirely harmful and have no medical use. However, a recent surge of clinical and pharmacological studies in the field indicates that many psychedelic-like agents have therapeutic potentials under proper circumstances. In this paper, from a biomedical and psychological perspective, we provide a brief review of the general effects and promising treatment uses of medical cannabis, 3,4-methylenedioxy-methamphetamine (MDMA), salvinorin A, ibogaine and the dimethyltryptamine-(DMT)-containing ayahuasca. In Hungary - similarly to many other countries - these compounds are classified as "narcotic drugs" and their research is difficult due to strict regulations. PMID:26485742

  13. Differences in binding affinities of MDA, MDMA, MDEA, Amphetamine, Methamphetamine, and their deuterated analogues to solid-phase extraction cartridges.

    PubMed

    Romberg, R W; Ntamack, A G; Blacik, L J; Kazarian, C M; Snyder, J Jacob; Welsh, E R

    2011-01-01

    This study evaluated the potential for partial separation of drugs from their deuterated internal standards using Cerex(®) Polycrom™ CLIN II solid-phase extraction (SPE) cartridges. After elution from the column and derivatization, gas chromatography-mass spectrometry results showed that the target compound eluted from the SPE cartridge prior to its deuterated form. This elution separation effect was greater for 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (MAMP) than for the other drugs studied. When the drugs were eluted in 0.5 mL increments from a 50 mg sorbent bed, no drug appeared in the first fraction. The drug to internal standard ratios (expected value 1.00) for subsequent fractions collected were 1.30, 1.07, and 0.83 for MDA/MDA-d(5); 1.65, 1.18, 0.67, and 0.56 for MDMA/MDMAd(5); and 1.37, 1.18, and 0.95 for MDEA/MDEA-d(6). For d-AMP and d-MAMP, the expected ratio was 0.40. The subsequent ratios were 0.63, 0.46, 0.35, and 0.34 for d-AMP/d-AMP-d(11); and 1.00, 0.59, 0.25, and 0.18 for d-MAMP/d-MAMP-d(14). The affinity of d-MAMPd(14) was shown to be greater than that of d-MAMP-d(5), and deuteration at the propyl end of the molecule was shown to increase binding more than deuteration on the phenyl group.

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

    PubMed

    Johansen, Sys Stybe; Jornil, Jakob

    2009-01-01

    The aim of this study was to develop a quantitative gas chromatography mass spectrometry (GC-MS) method to determine the classical amphetamines and their methylenedioxylated derivatives in human hair. The procedure involved liquid-liquid extraction of hydrolysed hair spiked with deuterated internal standards and direct derivatization with perfluorooctanoyl chloride. After evaporation of the organic phase and dissolution in butylacetate, the derivatized compounds were injected into a GC-MS. Method validation results showed a linear range from 0.25 to 25 ng/mg for the target compounds: amphetamine (AM), 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/mg and of quantification from 0.24 to 0.46 ng/mg, depending on compound. The method was applied on 40 authentic hair samples (segmented or pooled hair), of which 15 cases involved amphetamine and/or ecstasy. The hair concentrations ranged from LOD to 3.2 ng/mg of AM in 7 cases, to 0.4 ng/mg of MDA in 3 cases and to 5.9 ng/mg of MDMA in 13 cases. MA was only detected once at trace level. The method, including the derivatization procedure, is simple and robust with a sensitivity that is satisfactory for measurement of amphetamines and ecstasy in hair from abusers.

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

    PubMed

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

    2014-11-01

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

  16. [Recent abuse of 3,4-methylenedioxymethamphetamine ("yaoto-wang", "ecstasy")].

    PubMed

    Satsumi, Yuki Nishimura

    2002-01-01

    3,4-methylenedioxymethamphetamine ("Yaoto(head shifting)-wang", "Ecstasy"), designer drugs is popular world wide along with rave party, especially from the 1980s. Although there is a significant misconception of MDMA as "a safe drug", recent findings show its serotonin (5-HT) selective neurotoxity with memory disturbance and cognitive disorders, not only during its use but lasting for years. Hyperinnervation of 5-HT neurons has also been reported among non-human primates. Serotonin syndrome, serious dehydration and acute renal failure are reported as serious clinical symptoms and some deaths related to the use of MDMA have been reported. Unlike many stimulant users, MDMA users are likely to be socially adapted and epidemiological research suggests that, in the United States and European countries, 6-8% of students and 0.5-3% of adults have experienced MDMA use. Although criminal cases have been reported in Japan since the 1990s, there has been no empirical study of MDMA abuse, especially among youth. Based on the "Classification of Medicine and Drugs" of the Ministry of Health, Welfare and Labor. MDMA is classified as "compound narcotics: hallucinogens and stimulants" rather than individually. Another problem is that MDMA users are likely to visit emergency rooms rather than psychiatric clinics. The American Psychiatric Association has publicized the misconception of MDMA as a safe drug and informed people of its dangers. The author offers suggestions for Japanese psychiatrists to take steps to cope with this situation and recommends authorities to establish an appropriate drug policy.

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

    PubMed Central

    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

  18. Adolescent exposure to MDMA induces dopaminergic toxicity in substantia nigra and potentiates the amyloid plaque deposition in the striatum of APPswe/PS1dE9 mice.

    PubMed

    Abad, Sonia; Ramon, Carla; Pubill, David; Camarasa, Jorge; Camins, Antonio; Escubedo, Elena

    2016-09-01

    MDMA is one of the most used drugs by adolescents and its consumption has been associated with many psychobiological problems, among them psychomotor problems. Moreover, some authors described that early exposure to MDMA may render the dopaminergic neurons more vulnerable to the effects of future neurotoxic insults. Alzheimer disease (AD) is the main cause of dementia in the elderly and a percentage of the patients have predisposition to suffer nigrostriatal alterations, developing extrapyramidal signs. Nigrostriatal dysfunction in the brain of aged APPswe/PS1dE9 (APP/PS1), a mouse model of familiar AD (FAD), has also been described. The aim of the present study was to investigate the consequences of adolescent exposure to MDMA in APP/PS1 mice, on nigrostriatal function on early adulthood. We used a MDMA schedule simulating weekend binge abuse of this substance. Our MDMA schedule produced a genotype-independent decrease in dopaminergic neurons in the substantia nigra that remained at least 3months. Shortly after the injury, wild-type animals showed a decrease in the locomotor activity and apparent DA depletion in striatum, however in the APP/PS1 mice neither the locomotor activity nor the DA levels were modified, but a reduction in dopamine transporter (DAT) expression and a higher levels of oxidative stress were observed. We found that these disturbances are age-related characteristics that this APP/PS1 mice develops spontaneously much later. Therefore, MDMA administration seems to anticipate the striatal dopaminergic dysfunction in this FAD model. The most important outcome lies in a potentiation, by MDMA, of the amyloid beta deposition in the striatum. PMID:27344237

  19. Franklin: User Experiences

    SciTech Connect

    National Energy Research Supercomputing Center; He, Yun; Kramer, William T.C.; Carter, Jonathan; Cardo, Nicholas

    2008-05-07

    The newest workhorse of the National Energy Research Scientific Computing Center is a Cray XT4 with 9,736 dual core nodes. This paper summarizes Franklin user experiences from friendly early user period to production period. Selected successful user stories along with top issues affecting user experiences are presented.

  20. The User Experience

    ERIC Educational Resources Information Center

    Schmidt, Aaron

    2010-01-01

    User experience (UX) is about arranging the elements of a product or service to optimize how people will interact with it. In this article, the author talks about the importance of user experience and discusses the design of user experiences in libraries. He first looks at what UX is. Then he describes three kinds of user experience design: (1)…

  1. Prevalence of use study for amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxy-amphetamine (MDA), 3,4-methylenedioxy-methamphetamine (MDMA), and 3,4-methylenedioxy-ethylamphetamine (MDEA) in military entrance processing stations (MEPS) specimens.

    PubMed

    Klette, Kevin L; Kettle, Aaron R; Jamerson, Matthew H

    2006-06-01

    The Roche Abuscreen Onlinetrade mark Amphetamine immunoassay (IA), modified to include sodium periodate, and the Microgenics DRI Ecstasy IA were used to determine the prevalence of amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) in urine specimens from applicants seeking to join the United States Armed Forces. Over a 4-month period, a total of 85,658 specimens were IA screened using the Department of Defense 500 ng/mL administrative cutoff level for AMP and MDMA. All presumptively positive specimens were confirmed using a solid-phase extraction procedure coupled with simultaneous analysis of AMP, MAMP, MDA, MDMA, and MDEA by fast gas chromatography-mass spectrometry using the same cutoff levels as the IA. The Roche Online Amphetamine IA identified 216 specimens as presumptively positive; of these, 70 specimens confirmed positive for AMP and 87 specimens confirmed positive for AMP and/or MAMP, resulting in a confirmation rate of 73%. The Microgenics DRI Ecstasy IA identified eight specimens as presumptively positive; of these, five specimens confirmed positive for MDMA and/or MDA, resulting in a confirmation rate of 63%. The total use prevalence for AMP, MAMP, MDA, MDMA, and/or MDEA in military entrance processing stations specimens over the testing period was determined to be 0.19%.

  2. Nearly Two-Thirds of E-Cigarette Users Also Smoke: CDC

    MedlinePlus

    ... news/fullstory_161764.html Nearly Two-Thirds of E-Cigarette Users Also Smoke: CDC Survey also found ... that in 2015, 59 percent of all adult e-cigarette users were also current cigarette smokers. The ...

  3. The Student Drug User and His Family

    ERIC Educational Resources Information Center

    Kuehn, John L.

    1970-01-01

    Despite the misery and hostility of young drug users, they still seem to be searching for honest, receiving, confirming adults. The presence of adequately staffed college mental health units as well as trained and concerned professionals in the private sector to supply consultation and education to faculty and administrators are no longer a luxury…

  4. User Working Group Charter

    Atmospheric Science Data Center

    2014-04-29

    ... Program through the EOS Data Information System (EOSDIS) Project and the Langley ASDC, located at NASA Langley Research Center, Hampton, ... of the ASDC user interface, development of the Information Management System (IMS), and ASDC user conferences requirements for and ...

  5. 77 FR 16239 - Medical Device User Fee Act; Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-20

    ... MDUFA reauthorization process with a public meeting held on September 14, 2010 (75 FR 49502, August 13...); the Medical Device Manufacturers Association (MDMA); the Medical Imaging and Technology Alliance...

  6. NASCAP user's manual, 1978

    NASA Technical Reports Server (NTRS)

    Cassidy, J. J., III

    1978-01-01

    NASCAP simulates the charging process for a complex object in either tenuous plasma (geosynchronous orbit) or ground test (electron gun source) environment. Program control words, the structure of user input files, and various user options available are described in this computer programmer's user manual.

  7. Atmoshperic Science User Forum

    Atmospheric Science Data Center

    2016-02-26

    article title:  Atmospheric Science User Forum     View Larger Image ... ASDC is pleased to announce the release of the Atmospheric Science User Forum. The purpose of this forum is to improve user service, quality, and efficiency of NASA atmospheric science data by providing a quick and easy way to facilitate scientific ...

  8. Helping Users Help Themselves.

    ERIC Educational Resources Information Center

    O'Malley, Claire E.

    This discussion of the design of user-initiated help systems in computers focuses on the information that users actively seek to help them with their tasks, with emphasis on how to help users ask the questions that will bridge the gap between the initial internal (mental) form of the query and their information need as expressed by the system.…

  9. DOSFAC2 user`s guide

    SciTech Connect

    Young, M.L.; Chanin, D.

    1997-12-01

    This document describes the DOSFAC2 code, which is used for generating dose-to-source conversion factors for the MACCS2 code. DOSFAC2 is a revised and updated version of the DOSFAC code that was distributed with version 1.5.11 of the MACCS code. included are (1) an overview and background of DOSFAC2, (2) a summary of two new functional capabilities, and (3) a user`s guide. 20 refs., 5 tabs.

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

    PubMed

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

    2016-06-01

    Ecstasy/3,4-methylenedioxymethamphetamine (MDMA) use is proposed to cause damage to serotonergic (5-HT) axons in humans. Therefore, users should show deficits in cognitive processes that rely on serotonin-rich, prefrontal areas of the brain. However, there is inconsistency in findings to support this hypothesis. The aim of the current study was to examine deficits in executive functioning in ecstasy users compared with controls using meta-analysis. We identified k = 39 studies, contributing 89 effect sizes, investigating executive functioning in ecstasy users and polydrug-using controls. We compared function-specific task performance in 1221 current ecstasy users and 1242 drug-using controls, from tasks tapping the executive functions - updating, switching, inhibition and access to long-term memory. The significant main effect demonstrated overall executive dysfunction in ecstasy users [standardized mean difference (SMD) = -0.18, 95% confidence interval (CI) -0.26 to -0.11, Z = 5.05, p < 0.001, I 2 = 82%], with a significant subgroup effect (χ 2 = 22.06, degrees of freedom = 3, p < 0.001, I 2 = 86.4%) demonstrating differential effects across executive functions. Ecstasy users showed significant performance deficits in access (SMD = -0.33, 95% CI -0.46 to -0.19, Z = 4.72, p < 0.001, I 2 = 74%), switching (SMD = -0.19, 95% CI -0.36 to -0.02, Z = 2.16, p < 0.05, I 2 = 85%) and updating (SMD = -0.26, 95% CI -0.37 to -0.15, Z = 4.49, p < 0.001, I 2 = 82%). No differences were observed in inhibitory control. We conclude that this is the most comprehensive analysis of executive function in ecstasy users to date and provides a behavioural correlate of potential serotonergic neurotoxicity. PMID:26966023

  11. Study of the Hepatoprotective Activity of Methanolic Extract of Feijoa sellowiana Fruits Against MDMA using the Isolated Rat Liver Perfusion System

    PubMed Central

    Karami, Mohammad; Saeidnia, Sodabah; Nosrati, Anahita

    2013-01-01

    liver injury induced by viruses, chemicals and drugs can be protected by different medicinal plants. Feijoa sellowiana (Myrtaceae) is an evergreen bush native to southern areas of South America, as well as Iran where the fruits are very popular. Feijoa has shown a potent antimicrobial effect. Morever, the antioxidant activity of total Feijoa extract has also been reported. MDMA or ecstasy is a ring-substituted amphetamine derivative which has been abused as a widespread recreational drug by the young generation. Liver is a target organ for MDMA toxicity. In fact, this sense MDMA is metabolized by cytochromes P4502D, 2B and 3Aand reactive metabolites are readily oxidized to the corresponding o-qiuinones and reactive oxygen species (ROS). This study investigated whether methanilic Feijoa sellowiana fruits can produce biochemical changes using the Isolated Rat Liver Perfusion (IRLP) system. The, the liver was perfused with different concentrations of the extract (10, 20, 40, 50,100 mg/kg), added to the buffer and perfused within 2 h. During the perfusion we tried to find out the antioxidant activity or liver protective effect of Feijoa, by determinining amino-transferases activities (SGOT and SGPT ) and glutathione reductase (GSH) level in comparison with the positive and negative controls. Subsequently, sections of liver tissue were examined for any histopathological changes. The results revealed that the activities of SGOT and SGPT were seriously decreased and GSH level was significantly increased by the Feijoa extract. Overall, necrosis in the liver parenchyma was decreased. These findings revealed that Feijoa sellowiana is an effective hepatoprotective plant. PMID:24250575

  12. Study of the Hepatoprotective Activity of Methanolic Extract of Feijoa sellowiana Fruits Against MDMA using the Isolated Rat Liver Perfusion System.

    PubMed

    Karami, Mohammad; Saeidnia, Sodabah; Nosrati, Anahita

    2013-01-01

    liver injury induced by viruses, chemicals and drugs can be protected by different medicinal plants. Feijoa sellowiana (Myrtaceae) is an evergreen bush native to southern areas of South America, as well as Iran where the fruits are very popular. Feijoa has shown a potent antimicrobial effect. Morever, the antioxidant activity of total Feijoa extract has also been reported. MDMA or ecstasy is a ring-substituted amphetamine derivative which has been abused as a widespread recreational drug by the young generation. Liver is a target organ for MDMA toxicity. In fact, this sense MDMA is metabolized by cytochromes P4502D, 2B and 3Aand reactive metabolites are readily oxidized to the corresponding o-qiuinones and reactive oxygen species (ROS). This study investigated whether methanilic Feijoa sellowiana fruits can produce biochemical changes using the Isolated Rat Liver Perfusion (IRLP) system. The, the liver was perfused with different concentrations of the extract (10, 20, 40, 50,100 mg/kg), added to the buffer and perfused within 2 h. During the perfusion we tried to find out the antioxidant activity or liver protective effect of Feijoa, by determinining amino-transferases activities (SGOT and SGPT ) and glutathione reductase (GSH) level in comparison with the positive and negative controls. Subsequently, sections of liver tissue were examined for any histopathological changes. The results revealed that the activities of SGOT and SGPT were seriously decreased and GSH level was significantly increased by the Feijoa extract. Overall, necrosis in the liver parenchyma was decreased. These findings revealed that Feijoa sellowiana is an effective hepatoprotective plant. PMID:24250575

  13. Male sex work and HIV risk among young heroin users in Hanoi, Vietnam.

    PubMed

    Clatts, Michael C; Giang, Le M; Goldsamt, Lloyd A; Yi, Huso

    2007-12-01

    The present study describes complex drug and sexual risk in a group of male sex workers (n = 79) who were recruited in the context of a larger study of young heroin users in Hanoi, Vietnam (n = 1270). Male sex workers were significantly more likely than male non-sex workers to be migrants (P < 0.001) and to have unstable housing (P < 0.001), to have lifetime exposure to marijuana (P < 0.001), 3,4 methylenedioxymethamphetamine (MDMA, ecstasy) (P < 0.01), amphetamines (P < 0.05), cocaine (P < 0.01) and morphine (P < 0.001). Male sex workers are more likely to currently use MDMA (P < 0.05), amphetamines (P < 0.001), morphine (P < 0.05) and to 'smoke' as their most frequent mode of heroin administration (P < 0.01). Male sex workers are more likely to have both male and female concurrent sex partners (P < 0.001), to have a history of sexual victimisation (P < 0.001), to have had more than three different sex partners in the past 30 days (P < 0.001), and to have had partners who injected drugs before sex (P < 0.001) or who used drugs during sex (P < 0.01). In their last sexual encounter with a client partner, approximately one-third (31.1%) reported having had receptive anal sex. In nearly three-quarters of these exchanges (71.4%), no condom was used. Similarly, in their last sexual encounter with a client partner, 42.2% reported having had insertive anal sex and in nearly half (47.4%) of these encounters no condom was used. Consistent with recent data from elsewhere in the region, there is an urgent need for additional research on male sex work in South-east Asia in order to properly situate behavioural interventions for male sex workers in this region.

  14. Identification and quantitation of amphetamine, methamphetamine, MDMA, pseudoephedrine, and ephedrine in blood, plasma, and serum using gas chromatography-mass spectrometry (GC/MS).

    PubMed

    Gunn, Josh; Kriger, Scott; Terrell, Andrea R

    2010-01-01

    Amphetamine, methamphetamine, MDMA, pseudoephedrine, and ephedrine are measured in blood, serum, and plasma using gas chromatography coupled to mass spectrometry (GC/MS). Following a simple liquid-liquid extraction, analytes are derivatized with heptafluorobutyric anhydride (HFBA) and 1 microL injected onto a HP-5MS 15-meter capillary column. Quantitation of each analyte is accomplished using a multi-point calibration curve and deuterated internal standards. The method provides a simple, robust, and reliable means to identify and measure these analytes.

  15. MADS Users' Guide

    NASA Technical Reports Server (NTRS)

    Moerder, Daniel D.

    2014-01-01

    MADS (Minimization Assistant for Dynamical Systems) is a trajectory optimization code in which a user-specified performance measure is directly minimized, subject to constraints placed on a low-order discretization of user-supplied plant ordinary differential equations. This document describes the mathematical formulation of the set of trajectory optimization problems for which MADS is suitable, and describes the user interface. Usage examples are provided.

  16. Adult Books for Young Adults.

    ERIC Educational Resources Information Center

    Carter, Betty

    1997-01-01

    Considers the differences between young adult and adult books and maintains that teachers must be familiar with young adults' tastes for both. Suggests that traffic between these publishing divisions is a two-way street, with young adults reading adult books and adults reading young adult books. (TB)

  17. User Registration in EOSDIS

    NASA Astrophysics Data System (ADS)

    Murphy, K. J.; Mitchell, A. E.

    2009-12-01

    Throughout the lifetime of EOSDIS the topic of user registration has received varied attention. Initially, for example, users ordering data from the Earth Science Data Gateway were required to register for delivery of media orders, to check order status and save profile information for future interactions. As EOSDIS embraced evolution of its data systems, the mostly centralized search and order system was replaced with a more diverse set of interfaces allowing (mostly) anonymous online access to data, tools and services. The changes to EOSDIS were embraced by users but the anonymous nature of the interaction made it more difficult to characterize users, capture metrics and provide customized services that benefit users. Additionally, new tools and interfaces have been developed without a centralized registration system. Currently a patchwork of independent registration systems exists throughout EOSDIS for ordering data and interacting with online tools and services. Each requires a separate username and password that must be managed by users. A consolidation of registration systems presents an opportunity to improve not only the user experience through tool customization and simplification of password management, but the understanding of users. This work discusses the options for implementing a common user registration for the EOSDIS, anticipated benefits and pitfalls.

  18. Preliminary ISIS users manual

    NASA Technical Reports Server (NTRS)

    Grantham, C.

    1979-01-01

    The Interactive Software Invocation (ISIS), an interactive data management system, was developed to act as a buffer between the user and host computer system. The user is provided by ISIS with a powerful system for developing software or systems in the interactive environment. The user is protected from the idiosyncracies of the host computer system by providing such a complete range of capabilities that the user should have no need for direct access to the host computer. These capabilities are divided into four areas: desk top calculator, data editor, file manager, and tool invoker.

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

    PubMed

    Davis, Alan K; Rosenberg, Harold

    2015-01-01

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

  20. ELISA Detection of 30 New Amphetamine Designer Drugs in Whole Blood, Urine and Oral Fluid using Neogen® "Amphetamine" and "Methamphetamine/MDMA" Kits.

    PubMed

    Nieddu, Maria; Burrai, Lucia; Baralla, Elena; Pasciu, Valeria; Varoni, Maria Vittoria; Briguglio, Irene; Demontis, Maria Piera; Boatto, Gianpiero

    2016-09-01

    Amphetamine designer drugs are central nervous system stimulants that are widely disseminated in the illegal market. Generally, in forensic laboratories, immunoassay methods are the first line of screening for these types of drugs in a biological specimen (typically blood, urine or oral fluid). In this article, we describe the cross-reactivity profiles of 30 new amphetamine designer drugs, using the Neogen(®) [Amphetamine Specific and Methamphetamine/3,4-Methylenedioxymethamphetamine (MDMA) assays] drug tests. To assess the potential matrix influence on the response, each assay was tested on whole blood, urine and oral fluid. Concentrations of 10,000 ng/mL were not sufficient to produce a positive response for the majority of the analyzed amphetamines. This clearly demonstrates that, although these kits are extremely effective for the target drugs for which they are intended (amphetamine, methamphetamine and MDMA), they cannot be used to reliably identify the tested designer drugs in real cases, as these concentrations greatly exceed those expected to be found in forensic samples. PMID:27405364

  1. Online User Group Directory

    ERIC Educational Resources Information Center

    Berger, Mary

    1978-01-01

    This list of U.S. and international online user groups includes contact persons and their addresses. The U.S. regions are divided according to the Medlars regional geographical breakdown. The user groups were formed so that data base producers or search service vendors could be invited to do training or give educational programs. (JPF)

  2. User's Guide for SKETCH

    NASA Technical Reports Server (NTRS)

    Hedgley, David R., Jr.

    2000-01-01

    A user's guide for the computer program SKETCH is presented on this disk. SKETCH solves a popular problem in computer graphics-the removal of hidden lines from images of solid objects. Examples and illustrations are included in the guide. Also included is the SKETCH program, so a user can incorporate the information into a particular software system.

  3. MIRADS-2 user's manual

    NASA Technical Reports Server (NTRS)

    1975-01-01

    An on-line data storage and retrieval system which allows the user to extract and process information from stored data bases is described. The capabilities of the system are provided by a general purpose computer program containing several functional modules. The modules contained in MIRADS are briefly described along with user terminal operation procedures and MIRADS commands.

  4. NASTRAN: Users' experiences

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The proceedings of a conference on NASA Structural Analysis (NASTRAN) to analyze the experiences of users of the program are presented. The subjects discussed include the following: (1) statics and buckling, (2) vibrations and dynamics, (3) substructing, (4) new capability, (5) user's experience, and (6) system experience. Specific applications of NASTRAN to spacecraft, aircraft, nuclear power plants, and materials tests are reported.

  5. LANES 1 Users' Guide

    NASA Technical Reports Server (NTRS)

    Jordan, J.

    1985-01-01

    This document is intended for users of the Local Area Network Extensible Simulator, version I. This simulator models the performance of a Fiber Optic network under a variety of loading conditions and network characteristics. The options available to the user for defining the network conditions are described in this document. Computer hardware and software requirements are also defined.

  6. KDYNA user's manual

    SciTech Connect

    Levatin, J.A.L.; Attia, A.V.; Hallquist, J.O.

    1990-09-28

    This report is a complete user's manual for KDYNA, the Earth Sciences version of DYNA2D. Because most features of DYNA2D have been retained in KDYNA much of this manual is identical to the DYNA2D user's manual.

  7. SOSS User Guide

    NASA Technical Reports Server (NTRS)

    Zhu, Zhifan; Gridnev, Sergei; Windhorst, Robert D.

    2015-01-01

    This User Guide describes SOSS (Surface Operations Simulator and Scheduler) software build and graphic user interface. SOSS is a desktop application that simulates airport surface operations in fast time using traffic management algorithms. It moves aircraft on the airport surface based on information provided by scheduling algorithm prototypes, monitors separation violation and scheduling conformance, and produces scheduling algorithm performance data.

  8. Crack/cocaine users show more family problems than other substance users

    PubMed Central

    Moura, Helena Ferreira; Benzano, Daniela; Pechansky, Flavio; Kessler, Felix Henrique Paim

    2014-01-01

    OBJECTIVES: To evaluate family problems among crack/cocaine users compared with alcohol and other substance users. METHODS: A cross-sectional multi-center study selected 741 current adult substance users from outpatient and inpatient Brazilian specialized clinics. Subjects were evaluated with the sixth version of the Addiction Severity Index, and 293 crack users were compared with 126 cocaine snorters and 322 alcohol and other drug users. RESULTS: Cocaine users showed more family problems when compared with other drug users, with no significant difference between routes of administration. These problems included arguing (crack 66.5%, powder cocaine 63.3%, other drugs 50.3%, p = 0.004), having trouble getting along with partners (61.5%×64.6%×48.7%, p = 0.013), and the need for additional childcare services in order to attend treatment (13.3%×10.3%×5.1%, p = 0.002). Additionally, the majority of crack/cocaine users had spent time with relatives in the last month (84.6%×86.5%×76.6%, p = 0.011). CONCLUSIONS: Brazilian treatment programs should enhance family treatment strategies, and childcare services need to be included. PMID:25029583

  9. The PANTHER User Experience

    SciTech Connect

    Coram, Jamie L.; Morrow, James D.; Perkins, David Nikolaus

    2015-09-01

    This document describes the PANTHER R&D Application, a proof-of-concept user interface application developed under the PANTHER Grand Challenge LDRD. The purpose of the application is to explore interaction models for graph analytics, drive algorithmic improvements from an end-user point of view, and support demonstration of PANTHER technologies to potential customers. The R&D Application implements a graph-centric interaction model that exposes analysts to the algorithms contained within the GeoGraphy graph analytics library. Users define geospatial-temporal semantic graph queries by constructing search templates based on nodes, edges, and the constraints among them. Users then analyze the results of the queries using both geo-spatial and temporal visualizations. Development of this application has made user experience an explicit driver for project and algorithmic level decisions that will affect how analysts one day make use of PANTHER technologies.

  10. User`s guide to MIDAS

    SciTech Connect

    Tisue, S.A.; Williams, N.B.; Huber, C.C.; Chun, K.C.

    1995-12-01

    Welcome to the MIDAS User`s Guide. This document describes the goals of the Munitions Items Disposition Action System (MIDAS) program and documents the MIDAS software. The main text first describes the equipment and software you need to run MIDAS and tells how to install and start it. It lists the contents of the database and explains how it is organized. Finally, it tells how to perform various functions, such as locating, entering, viewing, deleting, changing, transferring, and printing both textual and graphical data. Images of the actual computer screens accompany these explanations and guidelines. Appendix A contains a glossary of names for the various abbreviations, codes, and chemicals; Appendix B is a list of modem names; Appendix C provides a database dictionary and rules for entering data; and Appendix D describes procedures for troubleshooting problems associated with connecting to the MIDAS server and using MIDAS.

  11. Aztec user`s guide. Version 1

    SciTech Connect

    Hutchinson, S.A.; Shadid, J.N.; Tuminaro, R.S.

    1995-10-01

    Aztec is an iterative library that greatly simplifies the parallelization process when solving the linear systems of equations Ax = b where A is a user supplied n x n sparse matrix, b is a user supplied vector of length n and x is a vector of length n to be computed. Aztec is intended as a software tool for users who want to avoid cumbersome parallel programming details but who have large sparse linear systems which require an efficiently utilized parallel processing system. A collection of data transformation tools are provided that allow for easy creation of distributed sparse unstructured matrices for parallel solution. Once the distributed matrix is created, computation can be performed on any of the parallel machines running Aztec: nCUBE 2, IBM SP2 and Intel Paragon, MPI platforms as well as standard serial and vector platforms. Aztec includes a number of Krylov iterative methods such as conjugate gradient (CG), generalized minimum residual (GMRES) and stabilized biconjugate gradient (BICGSTAB) to solve systems of equations. These Krylov methods are used in conjunction with various preconditioners such as polynomial or domain decomposition methods using LU or incomplete LU factorizations within subdomains. Although the matrix A can be general, the package has been designed for matrices arising from the approximation of partial differential equations (PDEs). In particular, the Aztec package is oriented toward systems arising from PDE applications.

  12. Quality user support: Supporting quality users

    SciTech Connect

    Woolley, T.C.

    1994-12-31

    During the past decade, fundamental changes have occurred in technical computing in the oil industry. Technical computing systems have moved from local, fragmented quantity, to global, integrated, quality. The compute power available to the average geoscientist at his desktop has grown exponentially. Technical computing applications have increased in integration and complexity. At the same time, there has been a significant change in the work force due to the pressures of restructuring, and the increased focus on international opportunities. The profile of the user of technical computing resources has changed. Users are generally more mature, knowledgeable, and team oriented than their predecessors. In the 1990s, computer literacy is a requirement. This paper describes the steps taken by Oryx Energy Company to address the problems and opportunities created by the explosive growth in computing power and needs, coupled with the contraction of the business. A successful user support strategy will be described. Characteristics of the program include: (1) Client driven support; (2) Empowerment of highly skilled professionals to fill the support role; (3) Routine and ongoing modification to the support plan; (4) Utilization of the support assignment to create highly trained advocates on the line; (5) Integration of the support role to the reservoir management team. Results of the plan include a highly trained work force, stakeholder teams that include support personnel, and global support from a centralized support organization.

  13. Radiological Toolbox User's Manual

    SciTech Connect

    Eckerman, KF

    2004-07-01

    A toolbox of radiological data has been assembled to provide users access to the physical, chemical, anatomical, physiological and mathematical data relevant to the radiation protection of workers and member of the public. The software runs on a PC and provides users, through a single graphical interface, quick access to contemporary data and the means to extract these data for further computations and analysis. The numerical data, for the most part, are stored within databases in SI units. However, the user can display and extract values using non-SI units. This is the first release of the toolbox which was developed for the U.S. Nuclear Regulatory Commission.

  14. Reconceptualizing Early and Late Onset: A Life Course Analysis of Older Heroin Users

    ERIC Educational Resources Information Center

    Boeri, Miriam Williams; Sterk, Claire E.; Elifson, Kirk W.

    2008-01-01

    Purpose: Researchers' knowledge regarding older users of illicit drugs is limited despite the increasing numbers of users. In this article, we apply a life course perspective to gain a further understanding of older adult drug use, specifically contrasting early- and late-onset heroin users. Design and Methods: We collected qualitative data from…

  15. Bevalac user's handbook

    SciTech Connect

    Not Available

    1990-04-01

    This report is a users manual on the Bevalac accelerator facility. This paper discuses: general information; the Bevalac and its operation; major facilities and experimental areas; and experimental equipment.

  16. ARM User Survey Report

    SciTech Connect

    Roeder, LR

    2010-06-22

    The objective of this survey was to obtain user feedback to, among other things, determine how to organize the exponentially growing data within the Atmospheric Radiation Measurement (ARM) Climate Research Facility, and identify users’ preferred data analysis system. The survey findings appear to have met this objective, having received approximately 300 responses that give insight into the type of work users perform, usage of the data, percentage of data analysis users might perform on an ARM-hosted computing resource, downloading volume level where users begin having reservations, opinion about usage if given more powerful computing resources (including ability to manipulate data), types of tools that would be most beneficial to them, preferred programming language and data analysis system, level of importance for certain types of capabilities, and finally, level of interest in participating in a code-sharing community.

  17. Interactive Office user's manual

    NASA Technical Reports Server (NTRS)

    Montgomery, Edward E.; Lowers, Benjamin; Nabors, Terri L.

    1990-01-01

    Given here is a user's manual for Interactive Office (IO), an executive office tool for organization and planning, written specifically for Macintosh. IO is a paperless management tool to automate a related group of individuals into one productive system.

  18. ULDA user's guide

    NASA Technical Reports Server (NTRS)

    Perry, Charleen; Driessen, Cornelius; Pasian, Fabio

    1989-01-01

    The Uniform Low Dispersion Archive (ULDA) is a software system which, in one sitting, allows one to obtain copies on one's personal computer of those International Ultraviolet Explorer (IUE) low dispersion spectra that are of interest to the user. Overviews and use instructions are given for two programs, one to search for and select spectra, and the other to convert those spectra into a form suitable for the user's image processing system.

  19. FAST User Guide

    NASA Technical Reports Server (NTRS)

    Walatka, Pamela P.; Clucas, Jean; McCabe, R. Kevin; Plessel, Todd; Potter, R.; Cooper, D. M. (Technical Monitor)

    1994-01-01

    The Flow Analysis Software Toolkit, FAST, is a software environment for visualizing data. FAST is a collection of separate programs (modules) that run simultaneously and allow the user to examine the results of numerical and experimental simulations. The user can load data files, perform calculations on the data, visualize the results of these calculations, construct scenes of 3D graphical objects, and plot, animate and record the scenes. Computational Fluid Dynamics (CFD) visualization is the primary intended use of FAST, but FAST can also assist in the analysis of other types of data. FAST combines the capabilities of such programs as PLOT3D, RIP, SURF, and GAS into one environment with modules that share data. Sharing data between modules eliminates the drudgery of transferring data between programs. All the modules in the FAST environment have a consistent, highly interactive graphical user interface. Most commands are entered by pointing and'clicking. The modular construction of FAST makes it flexible and extensible. The environment can be custom configured and new modules can be developed and added as needed. The following modules have been developed for FAST: VIEWER, FILE IO, CALCULATOR, SURFER, TOPOLOGY, PLOTTER, TITLER, TRACER, ARCGRAPH, GQ, SURFERU, SHOTET, and ISOLEVU. A utility is also included to make the inclusion of user defined modules in the FAST environment easy. The VIEWER module is the central control for the FAST environment. From VIEWER, the user can-change object attributes, interactively position objects in three-dimensional space, define and save scenes, create animations, spawn new FAST modules, add additional view windows, and save and execute command scripts. The FAST User Guide uses text and FAST MAPS (graphical representations of the entire user interface) to guide the user through the use of FAST. Chapters include: Maps, Overview, Tips, Getting Started Tutorial, a separate chapter for each module, file formats, and system

  20. VOLTTRON: User Guide

    SciTech Connect

    Lutes, Robert G.; Katipamula, Srinivas; Akyol, Bora A.; Tenney, Nathan D.; Haack, Jereme N.; Monson, Kyle E.; Carpenter, Brandon J.

    2014-04-24

    This document is a user guide for the deployment of the Transactional Network platform and agent/application development within the VOLTTRON. The intent of this user guide is to provide a description of the functionality of the Transactional Network Platform. This document describes how to deploy the platform, including installation, use, guidance, and limitations. It also describes how additional features can be added to enhance its current functionality.

  1. Metadata: A user`s view

    SciTech Connect

    Bretherton, F.P.; Singley, P.T.

    1994-12-31

    An analysis is presented of the uses of metadata from four aspects of database operations: (1) search, query, retrieval, (2) ingest, quality control, processing, (3) application to application transfer; (4) storage, archive. Typical degrees of database functionality ranging from simple file retrieval to interdisciplinary global query with metadatabase-user dialog and involving many distributed autonomous databases, are ranked in approximate order of increasing sophistication of the required knowledge representation. An architecture is outlined for implementing such functionality in many different disciplinary domains utilizing a variety of off the shelf database management subsystems and processor software, each specialized to a different abstract data model.

  2. Hanford inventory program user`s manual

    SciTech Connect

    Hinkelman, K.C.

    1994-09-12

    Provides users with instructions and information about accessing and operating the Hanford Inventory Program (HIP) system. The Hanford Inventory Program is an integrated control system that provides a single source for the management and control of equipment, parts, and material warehoused by Westinghouse Hanford Company in various site-wide locations. The inventory is comprised of spare parts and equipment, shop stock, special tools, essential materials, and convenience storage items. The HIP replaced the following systems; ACA, ASP, PICS, FSP, WSR, STP, and RBO. In addition, HIP manages the catalog maintenance function for the General Supplies inventory stocked in the 1164 building and managed by WIMS.

  3. User Localization During Human-Robot Interaction

    PubMed Central

    Alonso-Martín, F.; Gorostiza, Javi F.; Malfaz, María; Salichs, Miguel A.

    2012-01-01

    This paper presents a user localization system based on the fusion of visual information and sound source localization, implemented on a social robot called Maggie. One of the main requisites to obtain a natural interaction between human-human and human-robot is an adequate spatial situation between the interlocutors, that is, to be orientated and situated at the right distance during the conversation in order to have a satisfactory communicative process. Our social robot uses a complete multimodal dialog system which manages the user-robot interaction during the communicative process. One of its main components is the presented user localization system. To determine the most suitable allocation of the robot in relation to the user, a proxemic study of the human-robot interaction is required, which is described in this paper. The study has been made with two groups of users: children, aged between 8 and 17, and adults. Finally, at the end of the paper, experimental results with the proposed multimodal dialog system are presented. PMID:23012577

  4. User localization during human-robot interaction.

    PubMed

    Alonso-Martín, F; Gorostiza, Javi F; Malfaz, María; Salichs, Miguel A

    2012-01-01

    This paper presents a user localization system based on the fusion of visual information and sound source localization, implemented on a social robot called Maggie. One of the main requisites to obtain a natural interaction between human-human and human-robot is an adequate spatial situation between the interlocutors, that is, to be orientated and situated at the right distance during the conversation in order to have a satisfactory communicative process. Our social robot uses a complete multimodal dialog system which manages the user-robot interaction during the communicative process. One of its main components is the presented user localization system. To determine the most suitable allocation of the robot in relation to the user, a proxemic study of the human-robot interaction is required, which is described in this paper. The study has been made with two groups of users: children, aged between 8 and 17, and adults. Finally, at the end of the paper, experimental results with the proposed multimodal dialog system are presented.

  5. Ethylenedioxy homologs of N-methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) and its corresponding cathinone analog methylenedioxymethcathinone: Interactions with transporters for serotonin, dopamine, and norepinephrine.

    PubMed

    Del Bello, Fabio; Sakloth, Farhana; Partilla, John S; Baumann, Michael H; Glennon, Richard A

    2015-09-01

    N-Methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA; 'Ecstasy'; 1) and its β-keto analog methylone (MDMC; 2) are popular drugs of abuse. Little is known about their ring-expanded ethylenedioxy homologs. Here, we prepared N-methyl-(3,4-ethylenedioxyphenyl)-2-aminopropane (EDMA; 3), both of its optical isomers, and β-keto EDMA (i.e., EDMC; 4) to examine their effects at transporters for serotonin (SERT), dopamine (DAT), and norepinephrine (NET). In general, ring-expansion of the methylenedioxy group led to a several-fold reduction in potency at all three transporters. With respect to EDMA (3), S(+)3 was 6-fold, 50-fold, and 8-fold more potent than its R(-) enantiomer at SERT, DAT, and NET, respectively. Overall, in the absence of a β-carbonyl group, the ethylenedioxy (i.e., 1,4-dioxane) substituent seems better accommodated at SERT than at DAT and NET.

  6. Altered energy production, lowered antioxidant potential, and inflammatory processes mediate CNS damage associated with abuse of the psychostimulants MDMA and methamphetamine.

    PubMed

    Downey, Luke A; Loftis, Jennifer M

    2014-03-15

    Central nervous system (CNS) damage associated with psychostimulant dependence may be an ongoing, degenerative process with adverse effects on neuropsychiatric function. However, the molecular mechanisms regarding how altered energy regulation affects immune response in the context of substance use disorders are not fully understood. This review summarizes the current evidence regarding the effects of psychostimulant [particularly 3,4-methylenedioxy-N-methylamphetamine (MDMA) and methamphetamine] exposure on brain energy regulation, immune response, and neuropsychiatric function. Importantly, the neuropsychiatric impairments (e.g., cognitive deficits, depression, and anxiety) that persist following abstinence are associated with poorer treatment outcomes - increased relapse rates, lower treatment retention rates, and reduced daily functioning. Qualifying the molecular changes within the CNS according to the exposure and use patterns of specifically abused substances should inform the development of new therapeutic approaches for addiction treatment. PMID:24485894

  7. Ethylenedioxy Homologs of N-Methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) and its Corresponding Cathinone Analog Methylenedioxymethcathinone: Interactions with Transporters for Serotonin, Dopamine, and Norepinephrine

    PubMed Central

    Del Bello, Fabio; Sakloth, Farhana; Partilla, John S.; Baumann, Michael H.; Glennon, Richard A.

    2015-01-01

    N -Methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA; ‘Ecstasy’; 1) and its β-keto analog methylone (MDMC; 2) are popular drugs of abuse. Little is known about their ring-expanded ethylenedioxy homologs. Here, we prepared N-methyl-(3,4-ethylenedioxyphenyl)-2-aminopropane (EDMA; 3), both of its optical isomers, and β-keto EDMA (i.e., EDMC; 4) to examine their effects at transporters for serotonin (SERT), dopamine (DAT), and norepinephrine (NET). In general, ring-expansion of the methylenedioxy group led to a several-fold reduction in potency at all three transporters. With respect to EDMA (3), S(+)3 was 6-fold, 50-fold, and 8-fold more potent than its R(−) enantiomer at SERT, DAT, and NET, respectively. Overall, in the absence of a β-carbonyl group, the ethylenedioxy (i.e., 1,4-dioxane) substituent seems better accommodated at SERT than at DAT and NET. PMID:26233799

  8. Altered energy production, lowered antioxidant potential, and inflammatory processes mediate CNS damage associated with abuse of the psychostimulants MDMA and methamphetamine

    PubMed Central

    Downey, Luke A.; Loftis, Jennifer M.

    2014-01-01

    Central nervous system (CNS) damage associated with psychostimulant dependence may be an ongoing, degenerative process with adverse effects on neuropsychiatric function. However, the molecular mechanisms regarding how altered energy regulation affects immune response in the context of substance use disorders are not fully understood. This review summarizes the current evidence regarding the effects of psychostimulant [particularly 3,4-methylenedioxy-N-methylamphetamine (MDMA) and methamphetamine] exposure on brain energy regulation, immune response, and neuropsychiatric function. Importantly, the neuropsychiatric impairments (e.g., cognitive deficits, depression, and anxiety) that persist following abstinence are associated with poorer treatment outcomes – increased relapse rates, lower treatment retention rates, and reduced daily functioning. Qualifying the molecular changes within the CNS according to the exposure and use patterns of specifically abused substances should inform the development of new therapeutic approaches for addiction treatment. PMID:24485894

  9. TWEAT `95: User`s documentation update

    SciTech Connect

    Robertus, B.; Lambert, R.

    1996-03-01

    This report is designed to be a supplement to TWEAT`94 (PVTD-C94-05.01K Rev.1). It is intended to describe the primary features of the Ternary Waste Envelope Assessment Tool software package that have been added in FY`95 and how to use them. It contains only minimal duplication of information found in TWEAT`94 even though all features of TWEAT`94 will still be available. Emphasis on this Update is the binary plotting capability and the OWL Import modifications. Like it`s predecessors, this manual does not provide instructions for modifying the program code itself. The user of TWEAT`95 is expected to be familiar with the basic concepts and operation of the TWEAT software as discussed in TWEAT`94. Software and hardware requirements have not changed since TWEAT`94. TWEAT has now been tested using Macintosh System software versions 6.05 through 7.5.

  10. Evaluating User Participation and User Influence in an Enterprise System

    ERIC Educational Resources Information Center

    Gibbs, Martin D.

    2010-01-01

    Does user influence have an impact on the data quality of an information systems development project? What decision making should users have? How can users effectively be engaged in the process? What is success? User participation is considered to be a critical success factor for Enterprise Resource Planning (ERP) projects, yet there is little…

  11. GRSAC Users Manual

    SciTech Connect

    Ball, S.J.; Nypaver, D.J.

    1999-02-01

    An interactive workstation-based simulation code (GRSAC) for studying postulated severe accidents in gas-cooled reactors has been developed to accommodate user-generated input with ''smart front-end'' checking. Code features includes on- and off-line plotting, on-line help and documentation, and an automated sensitivity study option. The code and its predecessors have been validated using comparisons with a variety of experimental data and similar codes. GRSAC model features include a three-dimensional representation of the core thermal hydraulics, and optional ATWS (anticipated transients without scram) capabilities. The user manual includes a detailed description of the code features, and includes four case studies which guide the user through four different examples of the major uses of GRSAC: an accident case; an initial conditions setup and run; a sensitivity study; and the setup of a new reactor model.

  12. Computer acceptance of older adults.

    PubMed

    Nägle, Sibylle; Schmidt, Ludger

    2012-01-01

    Even though computers play a massive role in everyday life of modern societies, older adults, and especially older women, are less likely to use a computer, and they perform fewer activities on it than younger adults. To get a better understanding of the factors affecting older adults' intention towards and usage of computers, the Unified Theory of Acceptance and Usage of Technology (UTAUT) was applied as part of a more extensive study with 52 users and non-users of computers, ranging in age from 50 to 90 years. The model covers various aspects of computer usage in old age via four key constructs, namely performance expectancy, effort expectancy, social influences, and facilitating conditions, as well as the variables gender, age, experience, and voluntariness it. Interestingly, next to performance expectancy, facilitating conditions showed the strongest correlation with use as well as with intention. Effort expectancy showed no significant correlation with the intention of older adults to use a computer.

  13. TIA Software User's Manual

    NASA Technical Reports Server (NTRS)

    Cramer, K. Elliott; Syed, Hazari I.

    1995-01-01

    This user's manual describes the installation and operation of TIA, the Thermal-Imaging acquisition and processing Application, developed by the Nondestructive Evaluation Sciences Branch at NASA Langley Research Center, Hampton, Virginia. TIA is a user friendly graphical interface application for the Macintosh 2 and higher series computers. The software has been developed to interface with the Perceptics/Westinghouse Pixelpipe(TM) and PixelStore(TM) NuBus cards and the GW Instruments MacADIOS(TM) input-output (I/O) card for the Macintosh for imaging thermal data. The software is also capable of performing generic image-processing functions.

  14. CARE 3 User's Workshop

    NASA Technical Reports Server (NTRS)

    1988-01-01

    A user's workshop for CARE 3, a reliability assessment tool designed and developed especially for the evaluation of high reliability fault tolerant digital systems, was held at NASA Langley Research Center on October 6 to 7, 1987. The main purpose of the workshop was to assess the evolutionary status of CARE 3. The activities of the workshop are documented and papers are included by user's of CARE 3 and NASA. Features and limitations of CARE 3 and comparisons to other tools are presented. The conclusions to a workshop questionaire are also discussed.

  15. GLAST User Support

    NASA Astrophysics Data System (ADS)

    Band, David L.; Science Support Center, GLAST

    2006-12-01

    The Gamma-ray Large Area Space Telescope (GLAST) mission will provide the user community with many scientific opportunities. The mission's interface with the user community is the GLAST Science Support Center (GSSC). Yearly guest investigator (GI) cycles will support research related to GLAST. After the first year GIs may propose pointed observations; however, as a consequence of the large field-of-view of GLAST's instruments, pointed observations will rarely have an advantage over the default survey mode. Data, analysis software and documentation will be provided through the GSSC website (http://glast.gsfc.nasa.gov/ssc/); the website also includes a library of scientific results, and a helpdesk.

  16. RADTRAN 5 user guide.

    SciTech Connect

    Kanipe, Frances L.; Neuhauser, Karen Sieglinde

    2003-07-01

    This User Guide for the RADTRAN 5 computer code for transportation risk analysis describes basic risk concepts and provides the user with step-by-step directions for creating input files by means of either the RADDOG input file generator software or a text editor. It also contains information on how to interpret RADTRAN 5 output, how to obtain and use several types of important input data, and how to select appropriate analysis methods. Appendices include a glossary of terms, a listing of error messages, data-plotting information, images of RADDOG screens, and a table of all data in the internal radionuclide library.

  17. Perspectives on User Satisfaction Surveys.

    ERIC Educational Resources Information Center

    Cullen, Rowena

    2001-01-01

    Discusses academic libraries, digital environments, increasing competition, the relationship between service quality and user satisfaction, and user surveys. Describes the SERVQUAL model that measures service quality and user satisfaction in academic libraries; considers gaps between user expectations and managers' perceptions of user…

  18. Hostel User Study.

    ERIC Educational Resources Information Center

    Allen, Phyllis

    Findings from a study of living accommodations for young people are given in the first part. Features are identified that are regarded as important by management and residents. Suggestions are made as to how user response may be predicted and the responses of the residents to eight schemes are examined in detail. Also considered are--(1) the…

  19. User Oriented Product Evaluation.

    ERIC Educational Resources Information Center

    Alkin, Marvin C.; Wingard, Joseph

    While the educational product development field has expanded tremendously over the last 15 years, there is a paucity of conveniently assembled and readily interpretable information that would enable users to make accurate and informed evaluations of different, but comparable, instructional products. Minimum types of validation data which should be…

  20. Educating the Music User

    ERIC Educational Resources Information Center

    Adams, Mark C.

    2016-01-01

    To better serve students' evolving needs in music, music educators must connect classroom learning with how students use and interact with music in their daily lives. One way to accomplish this is by approaching classrooms with the music user in mind, which can open new possibilities for meaningful music making and remove students from the…

  1. User Authentication. SPEC Kit.

    ERIC Educational Resources Information Center

    Plum, Terry, Comp.; Bleiler, Richard, Comp.

    2001-01-01

    This SPEC (Systems and Procedures Exchange Center) Kit presents the results of a survey of Association of Research Libraries (ARL) member libraries designed to examine the systems research libraries use to authenticate and authorize the users of their online networked information resources. A total of 52 of 121 ARL member libraries responded to…

  2. TOTAL user manual

    NASA Technical Reports Server (NTRS)

    Johnson, Sally C.; Boerschlein, David P.

    1994-01-01

    Semi-Markov models can be used to analyze the reliability of virtually any fault-tolerant system. However, the process of delineating all of the states and transitions in the model of a complex system can be devastatingly tedious and error-prone. Even with tools such as the Abstract Semi-Markov Specification Interface to the SURE Tool (ASSIST), the user must describe a system by specifying the rules governing the behavior of the system in order to generate the model. With the Table Oriented Translator to the ASSIST Language (TOTAL), the user can specify the components of a typical system and their attributes in the form of a table. The conditions that lead to system failure are also listed in a tabular form. The user can also abstractly specify dependencies with causes and effects. The level of information required is appropriate for system designers with little or no background in the details of reliability calculations. A menu-driven interface guides the user through the system description process, and the program updates the tables as new information is entered. The TOTAL program automatically generates an ASSIST input description to match the system description.

  3. The User Interface.

    ERIC Educational Resources Information Center

    Lindeman, Martha J.; And Others

    1989-01-01

    The first of three articles on the design of user interfaces for information retrieval systems discusses the need to examine types of display, prompting, and input as separate entities. The second examines the use of artificial intelligence in creating natural language interfaces, and the third outlines standards for case studies in human computer…

  4. Our Deming Users' Group.

    ERIC Educational Resources Information Center

    Dinklocker, Christina

    1992-01-01

    After training in the Total Quality Management concept, a suburban Ohio school district created a Deming Users' Group to link agencies, individuals, and ideas. The group has facilitated ongoing school/business collaboration, networking among individuals from diverse school systems, mentoring and cooperative learning activities, and resource…

  5. Power User Interface

    NASA Technical Reports Server (NTRS)

    Pfister, Robin; McMahon, Joe

    2006-01-01

    Power User Interface 5.0 (PUI) is a system of middleware, written for expert users in the Earth-science community, PUI enables expedited ordering of data granules on the basis of specific granule-identifying information that the users already know or can assemble. PUI also enables expert users to perform quick searches for orderablegranule information for use in preparing orders. PUI 5.0 is available in two versions (note: PUI 6.0 has command-line mode only): a Web-based application program and a UNIX command-line- mode client program. Both versions include modules that perform data-granule-ordering functions in conjunction with external systems. The Web-based version works with Earth Observing System Clearing House (ECHO) metadata catalog and order-entry services and with an open-source order-service broker server component, called the Mercury Shopping Cart, that is provided separately by Oak Ridge National Laboratory through the Department of Energy. The command-line version works with the ECHO metadata and order-entry process service. Both versions of PUI ultimately use ECHO to process an order to be sent to a data provider. Ordered data are provided through means outside the PUI software system.

  6. User's guide to SSARRMENU

    USGS Publications Warehouse

    Mastin, M.C.; Le, Thanh

    2001-01-01

    The U.S. Geological Survey, in cooperation with Pierce County Department of Public Works, Washington, has developed an operational tool called the Puyallup Flood-Alert System to alert users of impending floods in the Puyallup River Basin. The system acquires and incorporates meteorological and hydrological data into the Streamflow Synthesis and Reservoir Regulation (SSARR) hydrologic flow-routing model to simulate floods in the Puyallup River Basin. SSARRMENU is the user-interactive graphical interface between the user, the input and output data, and the SSARR model. In a companion cooperative project with Pierce County, the SSARR model for the Puyallup River Basin was calibrated and validated. The calibrated model is accessed through SSARRMENU, which has been specifically programed for the Puyallup River and the needs of Pierce County. SSARRMENU automates the retrieval of data from ADAPS (Automated DAta Processing System, the U.S. Geological Survey?s real-time hydrologic database), formats the data for use with SSARR, initiates SSARR model runs, displays alerts for impending floods, and provides utilities to display the simulated and observed data. An on-screen map of the basin and a series of menu items provide the user wi

  7. HEMPDS user's manual

    SciTech Connect

    Warren, K.H.

    1983-02-01

    HEMPDS, the double-slide version of two-dimensional HEMP, allows the intersection of slide lines and slide lines in any direction, thus making use of triangular zones. this revised user's manual aids the physicist, computer scientist, and computer technician in using, maintaining, and coverting HEMPDS. Equations, EOS models, and sample problems are included.

  8. EREP users handbook

    NASA Technical Reports Server (NTRS)

    1971-01-01

    Revised Skylab spacecraft, experiments, and mission planning information is presented for the Earth Resources Experiment Package (EREP) users. The major hardware elements and the medical, scientific, engineering, technology and earth resources experiments are described. Ground truth measurements and EREP data handling procedures are discussed. The mission profile, flight planning, crew activities, and aircraft support are also outlined.

  9. User Centric Policy Management

    ERIC Educational Resources Information Center

    Cheek, Gorrell P.

    2013-01-01

    Internet use, in general, and online social networking sites, in particular, are experiencing tremendous growth with hundreds of millions of active users. As a result, there is a tremendous amount of privacy information and content online. Protecting this information is a challenge. Access control policy composition is complex, laborious and…

  10. Older Adults' Knowledge of Internet Hazards

    ERIC Educational Resources Information Center

    Grimes, Galen A.; Hough, Michelle G.; Mazur, Elizabeth; Signorella, Margaret L.

    2010-01-01

    Older adults are less likely to be using computers and less knowledgeable about Internet security than are younger users. The two groups do not differ on trust of Internet information. The younger group shows no age or gender differences. Within the older group, computer users are more trusting of Internet information, and along with those with…

  11. Stigma towards Marijuana Users and Heroin Users.

    PubMed

    Brown, Seth A

    2015-01-01

    Despite high levels of stigmatizing attitudes and behaviors toward individuals with substance use problems, there is surprisingly limited research on understanding the contributors to such high levels. College students with no history of marijuana or heroin use (N=250) completed self-report measures to examine the level of substance use stigma towards individuals using two illicit substances (marijuana and heroin) and the contribution of three perceiver characteristics (sex, previous contact with substance users, and five beliefs about substance use) to three dimensions of stigma (social distance, negative emotions, and forcing treatment). Greater levels of internalized stigma were noted towards individuals who use heroin (versus marijuana). For marijuana use, those who had less previous contact and higher endorsement of certain beliefs (rarity, severity, and less controllability) were associated with greater stigmatizing attitudes. For heroin use, the associations were weak or non-existent. The findings strengthen the argument that substance use stigma needs to be examined and perhaps addressed substance by substance, rather than as a group. Further, contact interventions may be a particularly effective strategy for altering substance use stigma. PMID:26148124

  12. MDMA (Ecstasy or Molly)

    MedlinePlus

    ... neurotransmitters (the chemical messengers of brain cells): serotonin , dopamine , and norepinephrine . Serotonin —plays a role in controlling ... a heightened sense of emotional closeness and empathy. Dopamine —helps to control movement, motivation, emotions, and sensations ...

  13. Enabling User to User Interactions in Web Lectures with History-Aware User Awareness

    ERIC Educational Resources Information Center

    Ketterl, Markus; Mertens, Robert; Wiesen, Christoph; Vornberger, Oliver

    2011-01-01

    Purpose: The purpose of this paper is to present a user interface for web lectures for engaging with other users while working with video based learning content. The application allows its users to ask questions about the content and to get answers from those users that currently online are more familiar with it. The filtering is based on the…

  14. Little Cigars and Cigarillos: Users, Perceptions, and Reasons for Use

    PubMed Central

    Nyman, Amy L.; Sterling, Kymberle L.; Weaver, Scott R.; Majeed, Ban A.; Eriksen, Michael P.

    2016-01-01

    Objective This study examines little cigar and cigarillo (LCC) adult user characteristics, perceived addictiveness, use and importance of flavors, intentions to continue use, and reasons for use to inform prevention efforts and regulatory policy. Methods Data come from the 2014 Tobacco Products and Risk Perceptions Survey of a national probability sample of 5717 US adults, conducted online, June–November, 2014. The analytic sample consisted of 141 current LCC users. Results Current LCC smokers were more likely to be male, younger, black or Hispanic, lower SES, current cigarette smokers, and to report poorer health than non-smokers. Perceived addictiveness was low overall, with 73.6% considering themselves “not at all” addicted, although female LCC users and dual users of cigarettes were more likely to consider themselves addicted to LCCs. Use of flavored LCCs was widespread. Flavors were cited as important reasons for use, especially among younger users, as were favorable comparisons with affordability and burn time of cigarettes. Conclusions Most LCC users do not perceive themselves addicted to LCCs. Users report being influenced most by flavorings and affordability, indicating that appropriate regulations and education to improve health perceptions could help reduce use of these harmful products. PMID:27413772

  15. Wheelchair Use among Community-Dwelling Older Adults: Prevalence and Risk Factors in a National Sample

    ERIC Educational Resources Information Center

    Clarke, Philippa; Colantonio, Angela

    2005-01-01

    Older adults are the largest group of wheelchair users yet there are no peer-reviewed studies on the national profile of older wheelchair users in Canada. We investigated the characteristics of wheelchair users in a national sample of community-dwelling older adults from the Canadian Study of Health and Aging (CSHA-2). Questions on the use of…

  16. Designing a Facebook interface for senior users.

    PubMed

    Gomes, Gonçalo; Duarte, Carlos; Coelho, José; Matos, Eduardo

    2014-01-01

    The adoption of social networks by older adults has increased in recent years. However, many still cannot make use of social networks as these are simply not adapted to them. Through a series of direct observations, interviews, and focus groups, we identified recommendations for the design of social networks targeting seniors. Based on these, we developed a prototype for tablet devices, supporting sharing and viewing Facebook content. We then conducted a user study comparing our prototype with Facebook's native mobile application. We have found that Facebook's native application does not meet senior users concerns, like privacy and family focus, while our prototype, designed in accordance with the collected recommendations, supported relevant use cases in a usable and accessible manner. PMID:24672361

  17. Designing a Facebook Interface for Senior Users

    PubMed Central

    Coelho, José

    2014-01-01

    The adoption of social networks by older adults has increased in recent years. However, many still cannot make use of social networks as these are simply not adapted to them. Through a series of direct observations, interviews, and focus groups, we identified recommendations for the design of social networks targeting seniors. Based on these, we developed a prototype for tablet devices, supporting sharing and viewing Facebook content. We then conducted a user study comparing our prototype with Facebook's native mobile application. We have found that Facebook's native application does not meet senior users concerns, like privacy and family focus, while our prototype, designed in accordance with the collected recommendations, supported relevant use cases in a usable and accessible manner. PMID:24672361

  18. CSTEM User Manual

    NASA Technical Reports Server (NTRS)

    Hartle, M.; McKnight, R. L.

    2000-01-01

    This manual is a combination of a user manual, theory manual, and programmer manual. The reader is assumed to have some previous exposure to the finite element method. This manual is written with the idea that the CSTEM (Coupled Structural Thermal Electromagnetic-Computer Code) user needs to have a basic understanding of what the code is actually doing in order to properly use the code. For that reason, the underlying theory and methods used in the code are described to a basic level of detail. The manual gives an overview of the CSTEM code: how the code came into existence, a basic description of what the code does, and the order in which it happens (a flowchart). Appendices provide a listing and very brief description of every file used by the CSTEM code, including the type of file it is, what routine regularly accesses the file, and what routine opens the file, as well as special features included in CSTEM.

  19. ASSIST user manual

    NASA Technical Reports Server (NTRS)

    Johnson, Sally C.; Boerschlein, David P.

    1995-01-01

    Semi-Markov models can be used to analyze the reliability of virtually any fault-tolerant system. However, the process of delineating all the states and transitions in a complex system model can be devastatingly tedious and error prone. The Abstract Semi-Markov Specification Interface to the SURE Tool (ASSIST) computer program allows the user to describe the semi-Markov model in a high-level language. Instead of listing the individual model states, the user specifies the rules governing the behavior of the system, and these are used to generate the model automatically. A few statements in the abstract language can describe a very large, complex model. Because no assumptions are made about the system being modeled, ASSIST can be used to generate models describing the behavior of any system. The ASSIST program and its input language are described and illustrated by examples.

  20. Trilinos users guide.

    SciTech Connect

    Willenbring, James M.; Heroux, Michael Allen

    2003-08-01

    The Trilinos Project is an effort to facilitate the design, development, integration and ongoing support of mathematical software libraries. A new software capability is introduced into Trilinos as a package. A Trilinos package is an integral unit usually developed by a small team of experts in a particular algorithms area such as algebraic preconditioners, nonlinear solvers, etc. The Trilinos Users Guide is a resource for new and existing Trilinos users. Topics covered include how to configure and build Trilinos, what is required to integrate an existing package into Trilinos and examples of how those requirements can be met, as well as what tools and services are available to Trilinos packages. Also discussed are some common practices that are followed by many Trilinos package developers. Finally, a snapshot of current Trilinos packages and their interoperability status is provided, along with a list of supported computer platforms.

  1. RELAP-7 User's Guide

    SciTech Connect

    Zhang, Hongbin; Zhao, Haihua; Zou, Ling; Andrs, David; Berry, Ray Alden; Martineau, Richard Charles

    2014-12-01

    The document contains a user's guide on how to run the RELAP-7 code. The RELAP-7 code is the next generation nuclear reactor system safety analysis code being developed at the Idaho National Laboratory. RELAP-7 will become the main reactor systems simulation toolkit for the LWRS (Light Water Reactor Sustainability) program’s RISMC (Risk Informed Safety Margin Characterization) effort and the next generation tool in the RELAP reactor safety/systems analysis application series. RELAP-7 is written with object oriented programming language C++. A number of example problems and their associated input files are presented in this document to guide users to run the RELAP-7 code starting with simple pipe problems to problems with increasing complexity.

  2. Outside users payload model

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The outside users payload model which is a continuation of documents and replaces and supersedes the July 1984 edition is presented. The time period covered by this model is 1985 through 2000. The following sections are included: (1) definition of the scope of the model; (2) discussion of the methodology used; (3) overview of total demand; (4) summary of the estimated market segmentation by launch vehicle; (5) summary of the estimated market segmentation by user type; (6) details of the STS market forecast; (7) summary of transponder trends; (8) model overview by mission category; and (9) detailed mission models. All known non-NASA, non-DOD reimbursable payloads forecast to be flown by non-Soviet-block countries are included in this model with the exception of Spacelab payloads and small self contained payloads. Certain DOD-sponsored or cosponsored payloads are included if they are reimbursable launches.

  3. IAC user manual

    NASA Technical Reports Server (NTRS)

    Vos, R. G.; Beste, D. L.; Gregg, J.

    1984-01-01

    The User Manual for the Integrated Analysis Capability (IAC) Level 1 system is presented. The IAC system currently supports the thermal, structures, controls and system dynamics technologies, and its development is influenced by the requirements for design/analysis of large space systems. The system has many features which make it applicable to general problems in engineering, and to management of data and software. Information includes basic IAC operation, executive commands, modules, solution paths, data organization and storage, IAC utilities, and module implementation.

  4. Magnetic tape user guide

    NASA Technical Reports Server (NTRS)

    Evans, A. B.; Lee, L. L.

    1985-01-01

    This User Guide provides a general introduction to the structure, use, and handling of magnetic tapes at Langley Research Center (LaRC). The topics covered are tape terminology, physical characteristics, error prevention and detection, and creating, using, and maintaining tapes. Supplementary documentation is referenced where it might be helpful. The documentation is included for the tape utility programs, BLOCK, UNBLOCK, and TAPEDMP, which are available at the Central Scientific Computing Complex at LaRC.

  5. Salinas - User's Notes

    SciTech Connect

    ALVIN,KENNETH F.; BHARDWAJ,MANOJ K.; DRIESSEN,BRIAN; REESE,GARTH M.; SEGALMAN,DANIEL J.

    1999-11-01

    Salinas provides a massively parallel implementation of structural dynamics finite element analysis, required for high fidelity, validated models used in modal, vibration, static and shock analysis of weapons systems. This document provides a users guide to the input for Salinas. Details of input specifications for the different solution types, output options, element types and parameters are included. The appendices contain detailed examples, and instructions for running the software on parallel platforms.

  6. PISCES 2 users manual

    NASA Technical Reports Server (NTRS)

    Pratt, Terrence W.

    1987-01-01

    PISCES 2 is a programming environment and set of extensions to Fortran 77 for parallel programming. It is intended to provide a basis for writing programs for scientific and engineering applications on parallel computers in a way that is relatively independent of the particular details of the underlying computer architecture. This user's manual provides a complete description of the PISCES 2 system as it is currently implemented on the 20 processor Flexible FLEX/32 at NASA Langley Research Center.

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

    ERIC Educational Resources Information Center

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

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

  8. Dyslexics as Library Users.

    ERIC Educational Resources Information Center

    Bliss, Barbara A.

    1986-01-01

    Describes characteristics of dyslexics and contributions to understanding their special needs provided by Orton's research. Insights into needs of adult dyslexics based on classroom experiences are summarized, their implications for librarians are suggested, and provision of special training for tutors in Dane County (Wisconsin) public library…

  9. AVRAM user's manual

    SciTech Connect

    McGrady, P.W.

    1988-02-01

    This document details the use of the reliability code for the Atomic Vapor Laser Isotope Separation (AVLIS) project. This code was designed by Tom Anklam and John Harris. In late 1984 Patrick McGrady and Elena Koontz of C and TD/TA were assigned the task of improving the code and converting it for use on the DEC-10 system. In early 1986, Patric McGrady converted it to the CRAY. The AVRAM code is divided into distinct parts (often referred to as programs in this document). There is a COSMOS file that controls the execution of the FORTRAN code and controls the naming of output datasets and the deletion of temporary datasets created by the code. The FORTRAN code consists of a main program as a driver and of three main subroutines: EDIT, PARAM, and AVRAM. The EDIT program allows the user to create a new user defined system or add to an existing system or to change certain parameters. The PARAM program allows the user to alter system parameters and to select options such as economics run, criticality analysis or sensitivity studies. The AVRAM program does a reliability analysis of the system.

  10. PARFUME User's Guide

    SciTech Connect

    Kurt Hamman

    2010-09-01

    PARFUME, a fuel performance analysis and modeling code, is being developed at the Idaho National Laboratory for evaluating gas reactor coated particle fuel assemblies for prismatic, pebble bed, and plate type fuel geometries. The code is an integrated mechanistic analysis tool that evaluates the thermal, mechanical, and physico-chemical behavior of coated fuel particles (TRISO) and the probability for fuel failure given the particle-to-particle statistical variations in physical dimensions and material properties that arise during the fuel fabrication process. Using a robust finite difference numerical scheme, PARFUME is capable of performing steady state and transient heat transfer and fission product diffusion analyses for the fuel. Written in FORTRAN 90, PARFUME is easy to read, maintain, and modify. Currently, PARFUME is supported only on MS Windows platforms. This document represents the initial version of the PARFUME User Guide, a supplement to the PARFUME Theory and Model Basis Report which describes the theoretical aspects of the code. User information is provided including: 1) code development, 2) capabilities and limitations, 3) installation and execution, 4) user input and output, 5) sample problems, and 6) error messages. In the near future, the INL plans to release a fully benchmarked and validated beta version of PARFUME.

  11. Ximconv User`s Guide Version 1.0.1

    SciTech Connect

    McClurg, F.R.

    1992-06-01

    This user`s guide is the documentation for ximconv: a motif interface to the Image Tools developed by the San Diego Supercomputer Center (SDSC). The ximconv utility offers the user a point and click interface for converting from one file format to another.

  12. Managing End User Computing for Users with Disabilities.

    ERIC Educational Resources Information Center

    General Services Administration, Washington, DC. Clearinghouse on Computer Accommodation.

    This handbook presents guidelines to assist federal Information Resources Managers in applying computer and related information technology to accommodate users with disabilities. It discusses managing the end user environment, assessing accommodation requirements, and providing end user tools and support. The major portion of the document consists…

  13. Deinstitutionalization in the UK and Ireland: Outcomes for Service Users.

    ERIC Educational Resources Information Center

    Emerson, Eric; Hatton, Chris

    1996-01-01

    The United Kingdom literature on effects of deinstitutionalization of adults with developmental disabilities from 1980 to 1994 was reviewed. Analysis generally associated smaller, community-based residential services with improvements in user engagement, adaptive behaviors and challenging behaviors, community acceptance and integration,…

  14. Website Physical Activity Interventions: Preferences of Potential Users

    ERIC Educational Resources Information Center

    Ferney, Shannon L.; Marshall, Alison L.

    2006-01-01

    Information and communication technologies (particularly websites and e-mail) have the potential to deliver health behavior change programs to large numbers of adults at low cost. Controlled trials using these new media to promote physical activity have produced mixed results. User-centered development methods can assist in understanding the…

  15. Profiles of Adolescent Substance Abstainers, Users, and Abusers.

    ERIC Educational Resources Information Center

    Hillman, Stephen B.; Sawilowsky, Shlomo S.

    Psychoactive drugs are widely available in the United States. Many, such as coffee, cigarettes, and alcohol, are used commonly and acceptably by adults. For children and adolescents sorting through the complex messages about both licit and illicit drugs is difficult. Previous research examined differences between substance users and abusers with…

  16. Adult immunization

    PubMed Central

    Mehta, Bharti; Chawla, Sumit; Kumar Dharma, Vijay; Jindal, Harashish; Bhatt, Bhumika

    2014-01-01

    Vaccination is recommended throughout life to prevent vaccine-preventable diseases and their sequel. The primary focus of vaccination programs has historically been directed to childhood immunizations. For adults, chronic diseases have been the primary focus of preventive and medical health care, though there has been increased emphasis on preventing infectious diseases. Adult vaccination coverage, however, remains low for most of the routinely recommended vaccines. Though adults are less susceptible to fall prey to traditional infectious agents, the probability of exposure to infectious agents has increased manifold owing to globalization and increasing travel opportunities both within and across the countries. Thus, there is an urgent need to address the problem of adult immunization. The adult immunization enterprise is more complex, encompassing a wide variety of vaccines and a very diverse target population. There is no coordinated public health infrastructure to support an adult immunization program as there is for children. Moreover, there is little coordination among adult healthcare providers in terms of vaccine provision. Substantial improvement in adult vaccination is needed to reduce the health consequences of vaccine-preventable diseases among adults. Routine assessment of adult patient vaccination needs, recommendation, and offer of needed vaccines for adults should be incorporated into routine clinical care of adults. PMID:24128707

  17. Distributed user services for supercomputers

    NASA Technical Reports Server (NTRS)

    Sowizral, Henry A.

    1989-01-01

    User-service operations at supercomputer facilities are examined. The question is whether a single, possibly distributed, user-services organization could be shared by NASA's supercomputer sites in support of a diverse, geographically dispersed, user community. A possible structure for such an organization is identified as well as some of the technologies needed in operating such an organization.

  18. User computer system pilot project

    SciTech Connect

    Eimutis, E.C.

    1989-09-06

    The User Computer System (UCS) is a general purpose unclassified, nonproduction system for Mound users. The UCS pilot project was successfully completed, and the system currently has more than 250 users. Over 100 tables were installed on the UCS for use by subscribers, including tables containing data on employees, budgets, and purchasing. In addition, a UCS training course was developed and implemented.

  19. User Program Performance Monitor

    1983-09-30

    PROGLOOK makes it possible to monitor the execution of virtually any OS/MVT or OS/VS2 Release 1.6 load module. The main reason for using PROGLOOK is to find out which portions of a code use most of the CPU time so that those parts of the program can be rewritten to reduce CPU time. For large production programs, users have typically found it possible to reduce CPU time by 10 to 30 percent without changing themore » program''s function.« less

  20. XTV users guide

    SciTech Connect

    Dearing, J.F.; Johns, R.C.

    1996-09-01

    XTV is an X-Windows based Graphical User Interface for viewing results of Transient Reactor Analysis Code (TRAC) calculations. It provides static and animated color mapped visualizations of both thermal-hydraulic and heat conduction components in a TRAC model of a nuclear power plant, as well as both on-screen and hard copy two-dimensional plot capabilities. XTV is the successor to TRAP, the former TRAC postprocessor using the proprietary DISSPLA graphics library. This manual describes Version 2.0, which requires TRAC version 5.4.20 or later for full visualization capabilities.

  1. XMGR5 users manual

    SciTech Connect

    Jones, K.R.; Fisher, J.E.

    1997-03-01

    ACE/gr is XY plotting tool for workstations or X-terminals using X. A few of its features are: User defined scaling, tick marks, labels, symbols, line styles, colors. Batch mode for unattended plotting. Read and write parameters used during a session. Polynomial regression, splines, running averages, DFT/FFT, cross/auto-correlation. Hardcopy support for PostScript, HP-GL, and FrameMaker.mif format. While ACE/gr has a convenient point-and-click interface, most parameter settings and operations are available through a command line interface (found in Files/Commands).

  2. SHAFT79 user's manual

    SciTech Connect

    Pruess, K.; Schroeder, R.C.

    1980-03-01

    SHAFT79 (Simultaneous Heat And Fluid Transport) is an integrated finite difference program for computing two-phase non-isothermal flow in porous media. The principal application for which SHAFT79 is designed is in geothermal reservoir simulation. SHAFT79 solves the same equations as an earlier version, called SHAFT78, but uses much more efficient mathematical and numerical methods. The present SHAFT79 user's manual gives a brief account of equations and numerical methods and then describes in detail how to set up input decks for running the program. The application of SHAFT79 is illustrated by means of a few sample problems. (MHR)

  3. User and technical documentation

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The program LP1 calculates outbound and return trajectories between low earth orbit (LEO) and libration point no. 1 (L1). Libration points (LP) are defined as locations in space that orbit the Earth such that they are always stationary with respect to the Earth-Moon line. L1 is located behind the Moon such that the pull of the Earth and Moon together just cancel the centrifugal acceleration associated with the libration point's orbit. The input required from the user to define the flight is described. The contents of the six reports produced as outputs are presented. Also included are the instructions needed to execute the program.

  4. Prism users guide.

    SciTech Connect

    Weirs, V. Gregory

    2012-03-01

    Prism is a ParaView plugin that simultaneously displays simulation data and material model data. This document describes its capabilities and how to use them. A demonstration of Prism is given in the first section. The second section contains more detailed notes on less obvious behavior. The third and fourth sections are specifically for Alegra and CTH users. They tell how to generate the simulation data and SESAME files and how to handle aspects of Prism use particular to each of these codes.

  5. BLOCKAGE 2.5 user`s manual

    SciTech Connect

    Rao, D.V.; Brideau, J.; Shaffer, C.; Souto, F.; Bernahl, W.

    1996-12-01

    The BLOCKAGE 2.5 code described in this User`s Manual was developed by the US Nuclear Regulatory Commission (NRC) as a tool to evaluate licensee compliance with NRC Bulletin 96-03, ``Potential Plugging of Emergency Core Cooling Suction Strainers by Debris in Boiling Water Reactors.`` As such, BLOCKAGE 2.5 provides a generalized framework into which a user can input plant-specific and insulation-specific data for performing analyses in accordance with Regulatory Guide 1.82, Rev. 2. This user`s manual describes the capabilities of BLOCKAGE 2.5 along with a description of the graphics user`s interface provided for data entry. Each input/output dialog is described in detail along with special considerations related to developing and executing BLOCKAGE. Also, several sample problems are provided such that user can easily modify them to suit a particular plant of interest. The models used in BLOCKAGE 2.5 and their validation are presented in the accompanying NUREG/CR-6371. The BLOCKAGE models were designed to be parametric in nature, allowing the user flexibility to examine the impact of several modeling assumptions and to conduct sensitivity analyses. As a result, BLOCKAGE 2.5 results are known to be very sensitive to the user provided input. It is therefore strongly recommended that users become thoroughly familiar with BLOCKAGE models and their limitations as described in NUREG/CR-6224.

  6. High antibiotic consumption: a characterization of heavy users in Spain.

    PubMed

    Malo, Sara; José Rabanaque, María; Feja, Cristina; Jesús Lallana, María; Aguilar, Isabel; Bjerrum, Lars

    2014-09-01

    Heavy antibiotic users are those individuals with the highest exposure to antibiotics. They play an important role as contributors to the increasing risk of antimicrobial resistance. We applied different methods to identify and characterize the group of heavy antibiotic users in Spain as well as their exposure to antibiotics. Data on outpatient prescribing of antimicrobials (ATC J01) in 2010 were obtained from a prescription database covering Aragón (northeastern Spain). The antimicrobial consumption at the individual level was analysed both according to the volume of DDD and the number of packages purchased per year. Heavy antibiotic users were identified according to Lorenz curves and characterized by age, gender, and their antimicrobial prescription profile. Lorenz curves demonstrated substantial differences in the individual use of an