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Sample records for abstinent mdma users

  1. 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

  2. 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. PMID:25014666

  3. Neuroimaging in human MDMA (Ecstasy) users.

    PubMed

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

    2008-10-01

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

  4. Sleep deprivation differentially impairs cognitive performance in abstinent methylenedioxymethamphetamine ("Ecstasy") users.

    PubMed

    McCann, Una D; Wilson, Michael J; Sgambati, Francis P; Ricaurte, George A

    2009-11-01

    Methylenedioxymethamphetamine (MDMA; "Ecstasy") is a popular recreational drug and brain serotonin (5-HT) neurotoxin. Neuroimaging data indicate that some human MDMA users develop persistent deficits in brain 5-HT neuronal markers. Although the consequences of MDMA-induced 5-HT neurotoxicity are not fully understood, abstinent MDMA users have been found to have subtle cognitive deficits and altered sleep architecture. The present study sought to test the hypothesis that sleep disturbance plays a role in cognitive deficits in MDMA users. Nineteen abstinent MDMA users and 21 control subjects participated in a 5 d inpatient study in a clinical research unit. Baseline sleep quality was measured using the Pittsburgh Sleep Quality Inventory. Cognitive performance was tested three times daily using a computerized cognitive battery. On the third day of admission, subjects began a 40 h sleep deprivation period and continued cognitive testing using the same daily schedule. At baseline, MDMA users performed less accurately than controls on a task of working memory and more impulsively on four of the seven computerized tests. During sleep deprivation, MDMA users, but not controls, became increasingly impulsive, performing more rapidly at the expense of accuracy on tasks of working and short-term memory. Tests of mediation implicated baseline sleep disturbance in the cognitive decline seen during sleep deprivation. These findings are the first to demonstrate that memory problems in MDMA users may be related, at least in part, to sleep disturbance and suggest that cognitive deficits in MDMA users may become more prominent in situations associated with sleep deprivation. PMID:19890014

  5. 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. PMID:24333019

  6. Cannabis and Ecstasy/ MDMA: empirical measures of creativity in recreational users.

    PubMed

    Jones, Katy A; Blagrove, M; Parrott, A C

    2009-12-01

    This study investigated the associations between chronic cannabis and Ecstasy/MDMA use and one objective and two subjective measure of creativity. Fifteen abstinent Ecstasy users, 15 abstinent cannabis users, and 15 nondrug-user controls, completed three measures of creativity: the Consequences behavioral test of creativity, self-assessed performance on the Consequences test, and Gough's Trait Self-Report Creative Adjective Checklist. The Consequences test involved five scenarios where possible consequences had to be devised; scoring was conducted by the standard blind rating (by two independent judges) for "remoteness" and "rarity," and by a frequency and rarity of responses method. Cannabis users had significantly more "rare-creative" responses than controls (Tukey, p < 0.05); this effect remained significant with gender as a covariate. There were no significant differences between the groups on the number of standard scoring "remote-creative" ideas or for fluency of responses. On self-rated creativity, there was a significant ANOVA group difference (p < 0.05), with Ecstasy users tending to rate their answers as more creative than controls (Tukey comparison; p = 0.058, two-tailed). Ecstasy users did not differ from controls on the behavioral measures of creativity, although there was a borderline trend for self-assessment of greater creativity. Cannabis users produced significantly more "rare-creative" responses, but did not rate themselves as more creative. PMID:20235438

  7. 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

  8. 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

  9. 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

  10. Abstinence

    MedlinePlus

    ... opportunity for sperm to fertilize an egg. continue Protection Against STDs Abstinence protects people against STDs. Some STDs spread through oral-genital sex, anal sex, or even intimate skin-to-skin ...

  11. Gender difference in hippocampal volume reduction among abstinent methamphetamine users

    PubMed Central

    Du, Jiang; Quan, Meina; Zhuang, Wenxu; Zong, Na; Jiang, Haifeng; Kennedy, David N.; Harrington, Amy; Ziedonis, Douglas; Fan, Xiaoduo; Zhao, Min

    2015-01-01

    Background and Aims Growing evidence suggests abnormalities in brain morphology including hippocampal structure in patients with methamphetamine (MA) dependence. Yet little is known about the possible gender difference. This study was performed to examine hippocampal volume in abstinent male and female MA users, and to further explore its relationship with cognitive function. Methods 27 abstinent MA users (19 males and 8 females) with average 5.75 months of duration and 29 healthy controls (19 males and 10 females) age 18 to 45 years old were recruited for clinical assessment and imaging scan. FreeSurfer was used to segment the hippocampus bilaterally, and hippocampal volumes were extracted for group and gender comparisons. Cognitive function was measured using the CogState Battery Chinese language version (CSB-C). Results Analysis of covariance (ANCOVA) controlling for education showed a significant group by gender interaction for right hippocampal relative volume adjusted for total brain size (p=0.002). Female patients showed significantly less volume compared with female healthy controls; there was no significant difference in volume between male patients and male healthy controls. Within female patients, there were significant negative relationships between right hippocampal volume and average dose of MA use (p=0.001), as well as the total error scores on the Continuous Paired Association Learning Task (CPAL) in CSB-C (p=0.013). Conclusions There seems to be a gender difference in how MA affects hippocampal volume and cognitive function in abstinent MA users. Hippocampus might be an important treatment target for cognitive improvement and functional recovery in this patient population, especially in females. PMID:25920682

  12. EMPLOYMENT-BASED ABSTINENCE REINFORCEMENT PROMOTES OPIATE AND COCAINE ABSTINENCE IN OUT-OF-TREATMENT INJECTION DRUG USERS

    PubMed Central

    Holtyn, August F.; Koffarnus, Mikhail N.; DeFulio, Anthony; Sigurdsson, Sigurdur O.; Strain, Eric C.; Schwartz, Robert P.; Silverman, Kenneth

    2016-01-01

    We examined the use of employment-based abstinence reinforcement in out-of-treatment injection drug users, in this secondary analysis of a previously reported trial. Participants (N = 33) could work in the therapeutic workplace, a model employment-based program for drug addiction, for 30 weeks and could earn approximately $10 per hr. During a 4-week induction, participants only had to work to earn pay. After induction, access to the workplace was contingent on enrollment in methadone treatment. After participants met the methadone contingency for 3 weeks, they had to provide opiate-negative urine samples to maintain maximum pay. After participants met those contingencies for 3 weeks, they had to provide opiate- and cocaine-negative urine samples to maintain maximum pay. The percentage of drug-negative urine samples remained stable until the abstinence reinforcement contingency for each drug was applied. The percentage of opiate- and cocaine-negative urine samples increased abruptly and significantly after the opiate- and cocaine-abstinence contingencies, respectively, were applied. These results demonstrate that the sequential administration of employment-based abstinence reinforcement can increase opiate and cocaine abstinence among out-of-treatment injection drug users. PMID:25292399

  13. Dissociated Grey Matter Changes with Prolonged Addiction and Extended Abstinence in Cocaine Users

    PubMed Central

    Connolly, Colm G.; Bell, Ryan P.; Foxe, John J.; Garavan, Hugh

    2013-01-01

    Extensive evidence indicates that current and recently abstinent cocaine abusers compared to drug-naïve controls have decreased grey matter in regions such as the anterior cingulate, lateral prefrontal and insular cortex. Relatively little is known, however, about the persistence of these deficits in long-term abstinence despite the implications this has for recovery and relapse. Optimized voxel based morphometry was used to assess how local grey matter volume varies with years of drug use and length of abstinence in a cross-sectional study of cocaine users with various durations of abstinence (1–102 weeks) and years of use (0.3–24 years). Lower grey matter volume associated with years of use was observed for several regions including anterior cingulate, inferior frontal gyrus and insular cortex. Conversely, higher grey matter volumes associated with abstinence duration were seen in non-overlapping regions that included the anterior and posterior cingulate, insular, right ventral and left dorsal prefrontal cortex. Grey matter volumes in cocaine dependent individuals crossed those of drug-naïve controls after 35 weeks of abstinence, with greater than normal volumes in users with longer abstinence. The brains of abstinent users are characterized by regional grey matter volumes, which on average, exceed drug-naïve volumes in those users who have maintained abstinence for more than 35 weeks. The asymmetry between the regions showing alterations with extended years of use and prolonged abstinence suggest that recovery involves distinct neurobiological processes rather than being a reversal of disease-related changes. Specifically, the results suggest that regions critical to behavioral control may be important to prolonged, successful, abstinence. PMID:23527239

  14. A qualitative study of methamphetamine users' perspectives on barriers and facilitators of drug abstinence.

    PubMed

    Herbeck, Diane M; Brecht, Mary-Lynn; Christou, Dayna; Lovinger, Katherine

    2014-01-01

    To better understand methamphetamine (MA) use patterns and the process of recovery, qualitative interviews were conducted with adult MA users (n = 20), comparing a sample that received substance abuse treatment with those who had not received treatment. Respondents provided detailed information on why and how they changed from use to abstinence and factors they considered to be barriers to abstinence. Audio recordings and transcripts were reviewed for common themes. Participants reported a range of mild/moderate to intensely destructive problems, including loss of important relationships and profound changes to who they felt they were at their core; e.g., "I didn't realize how dark and mean I was … I was like a different person." Initial abstinence was often facilitated by multiple external forces (e.g., drug testing, child custody issues, prison, relocation), but sustained abstinence was attributed to shifts in thinking and salient realizations about using. The treatment group reported using more and different resources to maintain their abstinence than the no-treatment group. Findings indicate individualized interventions and multiple, simultaneous approaches and resources were essential in reaching stable abstinence. Understanding long-term users' experiences with MA use, addiction, and abstinence can inform strategies for engaging and sustaining MA users in treatment and recovery. PMID:25052880

  15. What is the role of harm reduction when drug users say they want abstinence?

    PubMed

    Neale, Joanne; Nettleton, Sarah; Pickering, Lucy

    2011-05-01

    Quantitative survey data indicate that most drug users starting treatment want abstinence rather than harm reduction (McKeganey et al., 2004). This finding has been seized upon by those seeking 'evidence' that abstinence is the bedrock of recovery and harm reduction is a negative and oppositional philosophy. However, all research involves questions of meaning, definition and value and an alternative research paradigm and different study design can provide important additional insights into treatment aspirations, including the desire for abstinence. Qualitative interviews conducted with 30 recovering heroin users (15 males and 15 females) in Southern England in 2009 confirm that those starting treatment often report a desire for abstinence. Nonetheless, drug users are frequently uncertain about their ability to achieve this and can have very different and inconsistent understandings of what being abstinent means. We suggest that the work of the critical theorist Habermas (1970, 1991) could improve our understanding of abstinence and is consistent with recent efforts to achieve a working definition of recovery. Importantly, our qualitative data also reveal that drug users have treatment aspirations that extend far beyond their drug consumption. They additionally want to improve relationships, engage in meaningful activities, acquire material possessions, and achieve better mental and physical health. Moreover, these broader life goals are often inextricably linked to their drug taking. From this, we conclude that both abstinence and harm reduction discourses should more routinely prioritise the many diverse 'wellness' goals that so clearly motivate treatment clients. The harm reduction field will then likely find that it has more in common with abstinence-oriented services and the broader recovery agenda than it might otherwise have imagined. PMID:21055914

  16. 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.

  17. Acute, sub-acute and long-term subjective consequences of 'ecstasy' (MDMA) consumption in 430 regular users.

    PubMed

    Verheyden, Suzanne L; Henry, John A; Curran, H Valerie

    2003-10-01

    This study examined the reported psychological effects of different patterns of MDMA use in men and women, and how they are modified by use of other psychoactive substances. A semi-structured interview was conducted with 466 regular MDMA users, exploring the perceived acute, sub-acute and long-term subjective effects of this drug. Factor analysis established three main categories of acute effects of MDMA: (i) positive and (ii) negative effects on mental health, and (iii) physical effects. In terms of subacute effects, 83% of participants reported experiencing low mood and 80% reported impaired concentration between ecstasy-taking sessions. Factors affecting these effects included age, gender, extent of MDMA use and concomitant use of cocaine or amphetamine. The long-term effects most frequently reported included the development of tolerance to MDMA (59%), impaired ability to concentrate (38%), depression (37%) and 'feeling more open towards people' (31%). In terms of what might persuade users to stop using MDMA, their most prominent concern was the drug's long-term effects on mental health. PMID:14533132

  18. Rapid Recovery of Vesicular Dopamine Levels in Methamphetamine Users in Early Abstinence.

    PubMed

    Boileau, Isabelle; McCluskey, Tina; Tong, Junchao; Furukawa, Yoshiaki; Houle, Sylvain; Kish, Stephen J

    2016-03-01

    We previously reported very low levels of dopamine in post-mortem striatum of chronic methamphetamine users, raising the possibility that restoration of normal dopamine levels could help in this addiction and perhaps prevent early relapse. To establish relevance of this finding to the living brain, we tested whether striatal [(11)C]-(+)-dihydrotetrabenazine binding, a vesicular monoamine transporter probe sensitive to changes in (stored) vesicular dopamine, is elevated in methamphetamine users. Chronic methamphetamine users underwent [(11)C]-(+)-dihydrotetrabenazine positron emission tomography scans during early (mean 2.6 days) and later (~10 days) abstinence. Striatal [(11)C]-(+)-dihydrotetrabenazine binding was elevated (suggesting low stored dopamine) in methamphetamine users (n=28; 2.6 days after last use) relative to controls (n=22) (+28%, p<0.0001) and correlated with severity and recency of drug use and with cognitive impairment and withdrawal symptoms. Mean [(11)C]-(+)-dihydrotetrabenazine binding levels in the subgroup of methamphetamine users who could remain abstinent ~10 days following last use (n=17) were normal at the follow-up scan. Our imaging data support post-mortem findings and suggest that chronic methamphetamine users have low brain levels of stored dopamine during very early abstinence from MA, which could contribute to behavioral and cognitive deficits. Findings also suggest a rapid recovery of stored dopamine in some methamphetamine users who become abstinent and who therefore might not benefit from dopamine replacement medication (eg, levodopa). Further study is necessary to establish whether those users who could not maintain abstinence for the second scan might have a more severe and persistent dopamine deficiency and who could benefit from this medication. PMID:26321315

  19. 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 ...

  20. Hippocampal volume reduction in female but not male recent abstinent methamphetamine users.

    PubMed

    Du, Jiang; Quan, Meina; Zhuang, Wenxu; Zhong, Na; Jiang, Haifeng; Kennedy, David N; Harrington, Amy; Ziedonis, Douglas; Fan, Xiaoduo; Zhao, Min

    2015-08-01

    Growing evidence suggests abnormalities in brain morphology including hippocampal structure in patients with methamphetamine (MA) dependence. This study was performed to examine hippocampal volume in abstinent MA users, and to further explore its relationship with cognitive function. 30 abstinent MA users (20 males and 10 females) with average 5.52 months of duration of abstinence and 29 healthy controls (19 males and 10 females) age 18-45 years old were recruited for clinical assessment and imaging scan. FreeSurfer was used to segment the hippocampus bilaterally, and hippocampal volumes were extracted for group and gender comparisons. Cognitive function was measured using the CogState Battery Chinese language version (CSB-C). Analysis of covariance (ANCOVA) controlling for education showed a significant group by gender interaction for the right hippocampal relative volume adjusted for total brain size (p = 0.020); there was a significant difference between male controls and female controls (p < 0.001), but such a difference did not exist between male patients and female patients (p = 0.203). No significant correlations were found between hippocampal volume and cognitive measures. There seems to be a gender difference in how MA affects hippocampal volume in abstinent MA users. Hippocampus might be an important treatment target for cognitive improvement and functional recovery in this patient population, especially in females. PMID:25920682

  1. Mismatch Negativity and P50 Sensory Gating in Abstinent Former Cannabis Users

    PubMed Central

    Broyd, Samantha J.; Greenwood, Lisa-marie; van Hell, Hendrika H.; Croft, Rodney J.; Coyle, Hannah; Lee-Bates, Ben; Todd, Juanita; Johnstone, Stuart J.; Michie, Patricia T.; Solowij, Nadia

    2016-01-01

    Prolonged heavy exposure to cannabis is associated with impaired cognition and brain functional and structural alterations. We recently reported attenuated mismatch negativity (MMN) and altered P50 sensory gating in chronic cannabis users. This study investigated the extent of brain functional recovery (indexed by MMN and P50) in chronic users after cessation of use. Eighteen ex-users (median 13.5 years prior regular use; median 3.5 years abstinence) and 18 nonusers completed (1) a multifeature oddball task with duration, frequency, and intensity deviants and (2) a P50 paired-click paradigm. Trend level smaller duration MMN amplitude and larger P50 ratios (indicative of poorer sensory gating) were observed in ex-users compared to controls. Poorer P50 gating correlated with prior duration of cannabis use. Duration of abstinence was positively correlated with duration MMN amplitude, even after controlling for age and duration of cannabis use. Impaired sensory gating and attenuated MMN amplitude tended to persist in ex-users after prolonged cessation of use, suggesting a lack of full recovery. An association with prolonged duration of prior cannabis use may indicate persistent cannabis-related alterations to P50 sensory gating. Greater reductions in MMN amplitude with increasing abstinence (positive correlation) may be related to either self-medication or an accelerated aging process. PMID:27019754

  2. Mismatch Negativity and P50 Sensory Gating in Abstinent Former Cannabis Users.

    PubMed

    Broyd, Samantha J; Greenwood, Lisa-marie; van Hell, Hendrika H; Croft, Rodney J; Coyle, Hannah; Lee-Bates, Ben; Todd, Juanita; Johnstone, Stuart J; Michie, Patricia T; Solowij, Nadia

    2016-01-01

    Prolonged heavy exposure to cannabis is associated with impaired cognition and brain functional and structural alterations. We recently reported attenuated mismatch negativity (MMN) and altered P50 sensory gating in chronic cannabis users. This study investigated the extent of brain functional recovery (indexed by MMN and P50) in chronic users after cessation of use. Eighteen ex-users (median 13.5 years prior regular use; median 3.5 years abstinence) and 18 nonusers completed (1) a multifeature oddball task with duration, frequency, and intensity deviants and (2) a P50 paired-click paradigm. Trend level smaller duration MMN amplitude and larger P50 ratios (indicative of poorer sensory gating) were observed in ex-users compared to controls. Poorer P50 gating correlated with prior duration of cannabis use. Duration of abstinence was positively correlated with duration MMN amplitude, even after controlling for age and duration of cannabis use. Impaired sensory gating and attenuated MMN amplitude tended to persist in ex-users after prolonged cessation of use, suggesting a lack of full recovery. An association with prolonged duration of prior cannabis use may indicate persistent cannabis-related alterations to P50 sensory gating. Greater reductions in MMN amplitude with increasing abstinence (positive correlation) may be related to either self-medication or an accelerated aging process. PMID:27019754

  3. Dysregulated responses to emotions among abstinent heroin users: correlation with childhood neglect and addiction severity.

    PubMed

    Gerra, G; Somaini, L; Manfredini, M; Raggi, M A; Saracino, M A; Amore, M; Leonardi, C; Cortese, E; Donnini, C

    2014-01-01

    The aim of this paper was to investigate the subjective responses of abstinent heroin users to both neutral and negative stimuli and the related hypothalamus-pituitary-adrenal reactions to emotional experience in relationship to their perception of childhood adverse experiences. Thirty male abstinent heroin dependents were included in the study. Emotional responses and childhood neglect perception were measured utilizing the State-Trait Anxiety Inventory Y-1 and the Child Experience of Care and Abuse Questionnaire. Neutral and unpleasant pictures selected from the International Affective Picture System and the Self-Assessment Manikin procedure have been used to determine ratings of pleasure and arousal. These ratings were compared with normative values obtained from healthy volunteers used as control. Blood samples were collected before and after the experimental sessions to determine both adrenocorticotropic hormone and cortisol plasma levels. Basal anxiety scores, cortisol and adrenocorticotropic hormone levels were higher in abstinent heroin users than in controls. Tests showed that anxiety scores did not change in controls after the vision of neutral slides, whilst they did in abstinent heroin addicts, increasing significantly; and increased less significantly after the unpleasant task, in comparison to controls. Abstinent heroin users showed significantly higher levels of parent antipathy and childhood emotional neglect perception than controls for both the father and the mother. Plasma adrenocorticotropic hormone and cortisol levels did not significantly increase after unpleasant slide set viewing among addicted individuals, because of the significantly higher basal levels characterizing the addicted subjects in comparison with controls. Multiple regression correlation showed a significant relationship between childhood neglect perception, arousal reaction, impaired hypothalamus-pituitary-adrenal axis response and addiction severity. Early adverse experiences

  4. 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…

  5. A Randomized Trial of Employment-Based Reinforcement of Cocaine Abstinence in Injection Drug Users

    ERIC Educational Resources Information Center

    Silverman, Kenneth; Wong, Conrad J.; Needham, Mick; Diemer, Karly N.; Knealing, Todd; Crone-Todd, Darlene; Fingerhood, Michael; Nuzzo, Paul; Kolodner, Kenneth

    2007-01-01

    High-magnitude and long-duration abstinence reinforcement can promote drug abstinence but can be difficult to finance. Employment may be a vehicle for arranging high-magnitude and long-duration abstinence reinforcement. This study determined if employment-based abstinence reinforcement could increase cocaine abstinence in adults who inject drugs…

  6. From Abstinence to Relapse: A Preliminary Qualitative Study of Drug Users in a Compulsory Drug Rehabilitation Center in Changsha, China

    PubMed Central

    Yang, Mei; Mamy, Jules; Gao, Pengcheng; Xiao, Shuiyuan

    2015-01-01

    Background Relapse among abstinent drug users is normal. Several factors are related to relapse, but it remains unclear what individuals’ actual life circumstances are during periods of abstinence, and how these circumstances facilitate or prevent relapse. Objective To illuminate drug users’ experiences during abstinence periods and explore the real-life catalysts and inhibitors contributing to drug use relapse. Method Qualitative in-depth interviews were conducted with 20 drug users recruited from a compulsory isolated drug rehabilitation center in Changsha. The interviews were guided by open-ended questions on individuals’ experiences in drug use initiation, getting addicted, treatment history, social environment, abstinence, and relapse. Participants were also encouraged to share their own stories. Interviews were digitally recorded and fully transcribed. The data of 18 participants who reported abstinence experiences before admission were included in the analyses. The data were analyzed using a thematic analysis with inductive hand coding to derive themes. Results Most drug users were able to successfully abstain from drugs. During abstinence, their lives were congested with challenges, such as adverse socioeconomic conditions, poor family/social support, interpersonal conflicts, and stigma and discrimination, all of which kept them excluded from mainstream society. Furthermore, the police’s system of ID card registration, which identifies individuals as drug users, worsened already grave situations. Relapse triggers reported by the participants focused mainly on negative feelings, interpersonal conflicts, and stressful events. Craving was experienced but not perceived as a relapse trigger by most participants. Conclusions This study of in-depth interview with drug users found evidence of situations and environments they live during abstinence appear rather disadvantaged, making it extremely difficult for them to remain abstinent. Comprehensive programs

  7. Effect of Abstinence on Depression, Anxiety, and Quality of Life in Chronic Methamphetamine Users in a Therapeutic Community

    PubMed Central

    Bagheri, Maryam; Mokri, Azarakhsh; Khosravi, Aliakbar; Kabir, Kourosh

    2015-01-01

    Background: During withdrawal, patients experience different symptoms. These symptoms are associated with relapse. Understanding different outcomes of methamphetamine abstinence is useful for finding better treatments for dependence. Objectives: This study aimed to show the effects of abstinence on depression, anxiety, and quality of life in methamphetamine users. Patients and Methods: A prospective quasi-experimental (before and after study) method was used to show the effect of 3 weeks abstinence on depression, anxiety, and quality of life. A convenient sample of addicted people entered into the study and 34 people completed the study. Beck Depression Scale, Cattell Anxiety Inventory and Short Form Health Survey (SF-36) (for assessing quality of life), were used for outcome assessments. Results: The mean depression score after abstinence decreased significantly (P < 0.001). Both hidden and obvious anxiety and total anxiety had a high level at admission and after 3 weeks of abstinence, the mean level of anxiety did not change significantly (P < 0.096). However, the quality of life increased after 3 weeks of abstinence (P < 0.001). Conclusions: Depression and anxiety are prevalent in methamphetamine users. Short-term abstinence improves depression and quality of life but does not improve anxiety in methamphetamine abusers. During follow up of these patients, addressing depression and anxiety is important to achieve better results. PMID:26495258

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

    PubMed Central

    Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

    2009-01-01

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

  9. Motivated Attention to Cocaine and Emotional Cues in Abstinent and Current Cocaine Users: An ERP Study

    PubMed Central

    Dunning, Jonathan P.; Parvaz, Muhammad A.; Hajcak, Greg; Maloney, Thomas; Alia-Klein, Nelly; Woicik, Patricia A.; Telang, Frank; Wang, Gene-Jack; Volkow, Nora D.; Goldstein, Rita Z.

    2011-01-01

    Event-related potentials (ERPs) are a direct measure of neural activity and are ideally suited to study the time-course of attentional engagement with emotional and drug-related stimuli in addiction. In particular, the late positive potential (LPP) appears enhanced following cocaine-related compared to neutral stimuli in individuals with cocaine use disorders (CUD). However, previous studies have not directly compared cocaine-related to emotional stimuli while examining potential differences between abstinent and current cocaine users. The present study examined ERPs in 55 CUD (27 abstinent and 28 current users) and 29 matched healthy controls while they passively viewed pleasant, unpleasant, neutral, and cocaine-related pictures. To examine the time-course of attention to these stimuli, we analyzed both an early and later window in the LPP as well as the early posterior negativity (EPN), established in assessing motivated attention. Cocaine pictures elicited increased electrocortical measures of motivated attention in ways similar to affectively pleasant and unpleasant pictures in all CUD, an effect that was no longer discernible during the late LPP window for the current users. This group also exhibited deficient processing of the other emotional stimuli (early LPP window: pleasant pictures; late LPP window: pleasant and unpleasant pictures). Results were unique to the LPP and not EPN. Taken together, results support a relatively early attention bias to cocaine stimuli in cocaine addicted individuals further suggesting that recent cocaine use decreases such attention bias during later stages of processing but at the expense of deficient processing of other emotional stimuli. PMID:21450043

  10. Glycemic Allostasis during Mental Activities on Fasting in Non-alcohol Users and Alcohol Users with Different Durations of Abstinence.

    PubMed

    Welcome, Mo; Pereverzev, Va

    2014-09-01

    Glycemic allostasis is the process by which blood glucose stabilization is achieved through the balancing of glucose consumption rate and release into the blood stream under a variety of stressors. This paper reviews findings on the dynamics of glycemic levels during mental activities on fasting in non-alcohol users and alcohol users with different periods of abstinence. Referred articles for this review were searched in the databases of PubMed, Scopus, DOAJ and AJOL. The search was conducted in 2013 between January 20 and July 31. The following keywords were used in the search: alcohol action on glycemia OR brain glucose OR cognitive functions; dynamics of glycemia, dynamics of glycemia during mental activities; dynamics of glycemia on fasting; dynamics of glycemia in non-alcohol users OR alcohol users; glycemic regulation during sobriety. Analysis of the selected articles showed that glycemic allostasis during mental activities on fasting is poorly regulated in alcohol users even after a long duration of sobriety (1-4 weeks after alcohol consumption), compared to non-alcohol users. The major contributor to the maintenance of euglycemia during mental activities after the night's rest (during continuing fast) is gluconeogenesis. PMID:25364589

  11. Glycemic Allostasis during Mental Activities on Fasting in Non-alcohol Users and Alcohol Users with Different Durations of Abstinence

    PubMed Central

    Welcome, MO; Pereverzev, VA

    2014-01-01

    Glycemic allostasis is the process by which blood glucose stabilization is achieved through the balancing of glucose consumption rate and release into the blood stream under a variety of stressors. This paper reviews findings on the dynamics of glycemic levels during mental activities on fasting in non-alcohol users and alcohol users with different periods of abstinence. Referred articles for this review were searched in the databases of PubMed, Scopus, DOAJ and AJOL. The search was conducted in 2013 between January 20 and July 31. The following keywords were used in the search: alcohol action on glycemia OR brain glucose OR cognitive functions; dynamics of glycemia, dynamics of glycemia during mental activities; dynamics of glycemia on fasting; dynamics of glycemia in non-alcohol users OR alcohol users; glycemic regulation during sobriety. Analysis of the selected articles showed that glycemic allostasis during mental activities on fasting is poorly regulated in alcohol users even after a long duration of sobriety (1-4 weeks after alcohol consumption), compared to non-alcohol users. The major contributor to the maintenance of euglycemia during mental activities after the night's rest (during continuing fast) is gluconeogenesis. PMID:25364589

  12. Persistent Microstructural Deficits of Internal Capsule in One-Year Abstinent Male Methamphetamine Users: a Longitudinal Diffusion Tensor Imaging Study.

    PubMed

    Zhuang, Wenxu; Tang, Yingying; Zhong, Na; Jiang, Haifeng; Du, Jiang; Wang, Jijun; Zhao, Min

    2016-09-01

    White matter (WM) alterations have been reported in methamphetamine (MA) users. However, knowledge about longitudinal changes in WM during abstinence from MA remains unknown. The present study aimed to examine how WM changes in long-term MA abstinent, in particular, whether the WM deficits would recover as the duration of abstinence extended. Twenty male MA dependent individuals and 19 healthy controls (HCs) were recruited and participated in both clinical assessments and diffusion tensor imaging (DTI) scans. The MA group underwent two DTI scans, a baseline scan with a duration of abstinence of 6.4 months and and a follow-up scan with a duration of abstinence of 13.0 months. Tract-Based Spatial Statistics was utilized to conduct baseline DTI analysis of MA group compared with HCs. The clusters with significant group differences of factional anisotropy (FA) were extracted as region of interests (ROIs). Mean values of DTI measurements (FA, mean diffusivity, axial diffusivity and radial diffusivity) were calculated within the ROIs in each subject's native space at baseline and follow-up. The MA group showed significant lower FA in the right internal capsule and superior corona radiate than HCs. The deficits did not recover when the duration of abstinence from MA reached 13 months. No significant correlations were found between FA and clinical measurements. Our results suggested persistent microstructure deficits of WM tracts surrounding the basal ganglia in MA dependent individuals. PMID:27115910

  13. EEG of Chronic Marijuana Users during Abstinence: Relationship to Years of Marijuana Use, Cerebral Blood Flow and Thyroid Function

    PubMed Central

    Herning, Ronald I.; Better, Warren; Cadet, Jean L.

    2008-01-01

    Objective Marijuana abuse is associated with neurological changes including increases in frontal EEG alpha during abstinence. Research is needed to assess to what extent these EEG patterns are indicative of cerebral perfusion deficits. Methods We recorded the resting eyes closed EEG of 75 abstinent marijuana users and 33 control subjects. Fifty-six marijuana users used marijuana for less than eight years and 19 used for eight years or more. The EEG evaluation occurred within 72 hours of admission to an inpatient unit. Fifty-nine marijuana users remained abstinent for a month and were tested twice. Supplemental psychological and physiological data were also collected. Results Log alpha2 and beta2 power at posterior sites were significantly lower for the marijuana abusers that used eight years or more than the other marijuana abusers and the control subjects. These EEG changes continued for the month of abstinence. The marijuana users who used marijuana for more than eight years, also, had lower heart rates and thyroid function (T4) compared to the other marijuana users and the control subjects. Conclusions Chronic marijuana use was also associated with reduced EEG power in alpha and beta bands at posterior sites. These reductions in EEG power appear to be related to cerebral perfusion deficits and/or thyroid function in marijuana abusers. Significance Our results suggest EEG, cerebral blood flow velocity, cardiovascular and thyroid function alterations in marijuana abuser with an extended period of use. These alterations reflect under arousal in these systems. PMID:18065267

  14. Immune Function Alterations during 12 Weeks of Abstinence in Heroin Users.

    PubMed

    Wang, Z; Yang, X-R; Song, H; Cao, B-R; Yin, F; An, Z-M; Kang, L; Li, J

    2015-01-01

    The intent of the study was to evaluate immune system changes during 12 weeks of abstinence in heroin users. We recruited men (N = 65) aged 18-45 years and collected demographic and heroin use pattern data. Serum blood levels of total interleukin 2 (IL-2), interferon γ (IFN-γ), immunoglobulin (Ig) A, IgG, and IgM were assessed at five time points. The IL-2 level was increased on day 84 as compared to that in healthy controls. The IFN-γ level was higher in heroin users than in healthy controls between days 0 and 28, and was decreased on day 84. IgG and IgM levels in heroin users were higher than those in healthy controls in our 12-week study, and were in positive correlation with the way of using the drug, duration of heroin dependence, and daily heroin intake. Our data revealed that the immune system was not restored during the 12 weeks of heroin withdrawal. PMID:26789146

  15. Personality Measures In Former Heroin Users Receiving Methadone or in Protracted Abstinence from Opiates

    PubMed Central

    Cohen, Lisa J.; Gertmenian-King, Enid; Kunik, Lauren; Weaver, Carrie; London, Edythe D.; Galynker, Igor

    2007-01-01

    Objective Methadone Maintenance Therapy (MMT) and detoxification to abstinence are among the most common treatment options for opiate-dependent patients. This paper compares personality traits in detoxified former heroin users and those on MMT in order to assess their relevance to treatment selection. Methods Twenty-six formerly heroin-dependent subjects receiving MMT (MM), 33 formerly heroin-dependent subjects withdrawn from MMT (MW), and 43 healthy controls were compared on the Millon Clinical Multiaxial Inventory-II (MCMI-II) and the Temperament and Character Inventory (TCI). Results On the TCI, MM patients had higher Novelty Seeking and lower Self Directedness scores than controls. Both MM and MW subjects scored higher than controls on multiple MCMI-II scales. MW but not MM subjects scored higher than controls on 2 Cluster A scales and the Delusional Disorder scale. Conclusions Schizophrenia-spectrum pathology in former opiate users may be greater than previously recognized and could potentially be relevant to treatment selection. PMID:15992397

  16. 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

  17. Predictors of Smokeless Tobacco Abstinence

    ERIC Educational Resources Information Center

    Ebbert, Jon O.; Glover, Elbert D.; Shinozaki, Eri; Schroeder, Darrell R.; Dale, Lowell C.

    2008-01-01

    Objectives: To investigate predictors of tobacco abstinence among smokeless tobacco (ST) users. Methods: Logistic regression analyses assessed characteristics associated with tobacco abstinence among ST users receiving bupropion SR. Results: Older age was associated with increased tobacco abstinence in both placebo and bupropion SR groups at end…

  18. 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

  19. Decision-making in stimulant and opiate addicts in protracted abstinence: evidence from computational modeling with pure users

    PubMed Central

    Ahn, Woo-Young; Vasilev, Georgi; Lee, Sung-Ha; Busemeyer, Jerome R.; Kruschke, John K.; Bechara, Antoine; Vassileva, Jasmin

    2014-01-01

    Substance dependent individuals (SDI) often exhibit decision-making deficits; however, it remains unclear whether the nature of the underlying decision-making processes is the same in users of different classes of drugs and whether these deficits persist after discontinuation of drug use. We used computational modeling to address these questions in a unique sample of relatively “pure” amphetamine-dependent (N = 38) and heroin-dependent individuals (N = 43) who were currently in protracted abstinence, and in 48 healthy controls (HC). A Bayesian model comparison technique, a simulation method, and parameter recovery tests were used to compare three cognitive models: (1) Prospect Valence Learning with decay reinforcement learning rule (PVL-DecayRI), (2) PVL with delta learning rule (PVL-Delta), and (3) Value-Plus-Perseverance (VPP) model based on Win-Stay-Lose-Switch (WSLS) strategy. The model comparison results indicated that the VPP model, a hybrid model of reinforcement learning (RL) and a heuristic strategy of perseverance had the best post-hoc model fit, but the two PVL models showed better simulation and parameter recovery performance. Computational modeling results suggested that overall all three groups relied more on RL than on a WSLS strategy. Heroin users displayed reduced loss aversion relative to HC across all three models, which suggests that their decision-making deficits are longstanding (or pre-existing) and may be driven by reduced sensitivity to loss. In contrast, amphetamine users showed comparable cognitive functions to HC with the VPP model, whereas the second best-fitting model with relatively good simulation performance (PVL-DecayRI) revealed increased reward sensitivity relative to HC. These results suggest that some decision-making deficits persist in protracted abstinence and may be mediated by different mechanisms in opiate and stimulant users. PMID:25161631

  20. Correlations between compulsory drug abstinence treatments and HIV risk behaviors among injection drug users in a border city of South China.

    PubMed

    Chen, Huey T; Tuner, Nannette; Chen, Charlene J; Lin, Hui-yi; Liang, Shaoling; Wang, Siven

    2013-08-01

    Compulsory drug abstinence treatments (CAT) provided by the public security system have been one of the predominant methods of addressing drug abuse and HIV risks in China. This study assessed the association between CAT and HIV risk behaviors by surveying a community sample of 613 injection drug users (IDUs) at a city located in South China. The data indicated that the great majority of the participants (89.6%) had received the institutionalized treatments an average of 4.5 times. The study found that the number of compulsory drug abstinence treatments increased IDUs' HIV/AIDS knowledge. However, other HIV-related outcomes were not encouraging. The study found that the number of compulsory drug abstinence treatments was not related to an increase in condom use. Furthermore, the frequency of compulsory drug abstinence treatments was not related to needle/syringe sharing, but was positively associated with cooker/cotton/rinse water sharing and drug solution sharing. The number of compulsory drug abstinence treatments was positively associated with HIV status. In general, this study found little support that CAT has accomplished its goal in reducing HIV risks among injection drug users in the sample. Policy implications for reforming CAT are suggested. PMID:23837811

  1. MDMA: interactions with other psychoactive drugs.

    PubMed

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

    2011-10-01

    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is one of the most widely abused illegal drugs. Some users self-report euphoria and an increased perception and feeling of closeness to others. When taken in warm environments, MDMA users may develop acute complications with potential fatal consequences. In rodents, MDMA increases locomotor activity and, depending on ambient temperature, may produce a dose-dependent, potentially lethal hyperthermia. Like most other recreational drugs, MDMA is frequently taken in combination with other substances including tobacco, EtOH, marijuana, amphetamines, cocaine and, caffeine. Although polydrug use is very common, the understanding of the effects of this multiple substance use, as well as the analysis of consequences of different drug-drug associations, received rather little attention. The purpose of this review is to summarize our current knowledge about the changes on MDMA-related behavior, pharmacology, and neurotoxicity associated with co-consumption of other drugs of abuse and psychoactive agents. PMID:21756931

  2. Attentional dysfunction in abstinent long-term cannabis users with and without schizophrenia.

    PubMed

    Rentzsch, Johannes; Stadtmann, Ada; Montag, Christiane; Kunte, Hagen; Plöckl, Doris; Hellweg, Rainer; Gallinat, Jürgen; Kronenberg, Golo; Jockers-Scherübl, Maria Christiane

    2016-08-01

    Long-term cannabis use may confer cognitive deficits and increased risk of psychosis. However, the relationship between cannabis use and schizophrenia is complex. In particular, little is known about the effects of chronic cannabis use on the attention-related electric brain response in schizophrenia. We investigated auditory novelty and oddball P300 evoked potentials in a mixed sample of first-episode and chronic schizophrenic patients and healthy controls with (SZCA, n = 20; COCA, n = 20, abstinence ≥28 days) or without (SZ, n = 20; CO, n = 20) chronic cannabis use. Duration of regular cannabis use was 8.3 ± 5.6 (SZCA) and 9.1 ± 7.1 (COCA) years. In general, schizophrenic patients showed reduced P300 amplitudes. Cannabis use was associated with both a reduced early and late left-hemispheric novelty P300. There was a significant 'diagnosis × cannabis' interaction for the left-hemispheric late novelty P300 in that cannabis use was associated with a reduced amplitude in the otherwise healthy but not in the schizophrenic group compared with their relative control groups (corrected p < 0.02; p > 0.9, respectively). The left-hemispheric late novelty P300 in the otherwise healthy cannabis group correlated inversely with amount and duration of cannabis use (r = -0.50, p = 0.024; r = -0.57, p = 0.009, respectively). Our study confirms attentional deficits with chronic cannabis use. However, cannabis use may lead to different cognitive sequelae in patients with schizophrenia and in healthy controls, possibly reflecting preexisting alterations in the endocannabinoid system in schizophrenia. PMID:26182894

  3. Abnormal frontostriatal activity in recently abstinent cocaine users during implicit moral processing.

    PubMed

    Caldwell, Brendan M; Harenski, Carla L; Harenski, Keith A; Fede, Samantha J; Steele, Vaughn R; Koenigs, Michael R; Kiehl, Kent A

    2015-01-01

    Investigations into the neurobiology of moral cognition are often done by examining clinical populations characterized by diminished moral emotions and a proclivity toward immoral behavior. Psychopathy is the most common disorder studied for this purpose. Although cocaine abuse is highly co-morbid with psychopathy and cocaine-dependent individuals exhibit many of the same abnormalities in socio-affective processing as psychopaths, this population has received relatively little attention in moral psychology. To address this issue, the authors used functional magnetic resonance imaging (fMRI) to record hemodynamic activity in 306 incarcerated male adults, stratified into regular cocaine users (n = 87) and a matched sample of non-cocaine users (n = 87), while viewing pictures that did or did not depict immoral actions and determining whether each depicted scenario occurred indoors or outdoors. Consistent with expectations, cocaine users showed abnormal neural activity in several frontostriatial regions during implicit moral picture processing compared to their non-cocaine using peers. This included reduced moral/non-moral picture discrimination in the vACC, vmPFC, lOFC, and left vSTR. Additionally, psychopathy was negatively correlated with activity in an overlapping region of the ACC and right lateralized vSTR. These results suggest that regular cocaine abuse may be associated with affective deficits which can impact relatively high-level processes like moral cognition. PMID:26528169

  4. Abnormal frontostriatal activity in recently abstinent cocaine users during implicit moral processing

    PubMed Central

    Caldwell, Brendan M.; Harenski, Carla L.; Harenski, Keith A.; Fede, Samantha J.; Steele, Vaughn R.; Koenigs, Michael R.; Kiehl, Kent A.

    2015-01-01

    Investigations into the neurobiology of moral cognition are often done by examining clinical populations characterized by diminished moral emotions and a proclivity toward immoral behavior. Psychopathy is the most common disorder studied for this purpose. Although cocaine abuse is highly co-morbid with psychopathy and cocaine-dependent individuals exhibit many of the same abnormalities in socio-affective processing as psychopaths, this population has received relatively little attention in moral psychology. To address this issue, the authors used functional magnetic resonance imaging (fMRI) to record hemodynamic activity in 306 incarcerated male adults, stratified into regular cocaine users (n = 87) and a matched sample of non-cocaine users (n = 87), while viewing pictures that did or did not depict immoral actions and determining whether each depicted scenario occurred indoors or outdoors. Consistent with expectations, cocaine users showed abnormal neural activity in several frontostriatial regions during implicit moral picture processing compared to their non-cocaine using peers. This included reduced moral/non-moral picture discrimination in the vACC, vmPFC, lOFC, and left vSTR. Additionally, psychopathy was negatively correlated with activity in an overlapping region of the ACC and right lateralized vSTR. These results suggest that regular cocaine abuse may be associated with affective deficits which can impact relatively high-level processes like moral cognition. PMID:26528169

  5. 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. PMID:26241170

  6. Neural and cardiac toxicities associated with 3,4-methylenedioxymethamphetamine (MDMA).

    PubMed

    Baumann, Michael H; Rothman, Richard B

    2009-01-01

    (+/-)-3,4-Methylenedioxymethamphetamine (MDMA) is a commonly abused illicit drug which affects multiple organ systems. In animals, high-dose administration of MDMA produces deficits in serotonin (5-HT) neurons (e.g., depletion of forebrain 5-HT) that have been viewed as neurotoxicity. Recent data implicate MDMA in the development of valvular heart disease (VHD). The present paper reviews several issues related to MDMA-associated neural and cardiac toxicities. The hypothesis of MDMA neurotoxicity in rats is evaluated in terms of the effects of MDMA on monoamine neurons, the use of scaling methods to extrapolate MDMA doses across species, and functional consequences of MDMA exposure. A potential treatment regimen (l-5-hydroxytryptophan plus carbidopa) for MDMA-associated neural deficits is discussed. The pathogenesis of MDMA-associated VHD is reviewed with specific reference to the role of valvular 5-HT(2B) receptors. We conclude that pharmacological effects of MDMA occur at the same doses in rats and humans. High doses of MDMA that produce 5-HT depletions in rats are associated with tolerance and impaired 5-HT release. Doses of MDMA that fail to deplete 5-HT in rats can cause persistent behavioral dysfunction, suggesting even moderate doses may pose risks. Finally, the MDMA metabolite, 3,4-methylenedioxyamphetamine (MDA), is a potent 5-HT(2B) agonist which could contribute to the increased risk of VHD observed in heavy MDMA users. PMID:19897081

  7. [Periodic abstinence: its possibilities].

    PubMed

    1981-05-01

    Experience with family planning mehods requiring periodic sexual abstinence has been varied. During the last decade interest has centered on 2 methods, the cervical mucus and the sympto-thermal, which are based on identifying the onset of the fertile period. During the 1970s, the Australian physicians John and Evelyn Billings developed the cervical mucus method, in which changes in the quanitity and characteristics of cervical mucus are used to determine the moment of ovulation. The sympto-thermal method depends on identification of the slight rise in basal body temperature that occurs in the latter part of the menstrual cycle as well as cervical mucus changes and sometimes the calendar to determine the fertile period. The Catholic Church has been the main proponent of periodic abstinence methods, but since 1973 the World Health Organization has invested US$3.3 million on research in such methods. The Billings method requires differentiating between dry, wet, and very wet mucus in the vagina and between different consistencies of mucus. The method ususally requires 1-3 months for instruction and sexual abstinence is usually recommended for the 1st month. The average number of days of required abstinence was 9 in a study of 66 women and 15-18 in a study of 870 women. Many women with short menstrual cycles do not experience postmenstrual dry days, in which case abstinence may be required as many as 13 days out of 23. 18.8% of users of periodic abstinence methods in 1 North American study became pregnant in the 1st year, but most were using the calendar method. Women who desired to terminate childbearing had only about 1/2 as many failures with periodic abstinence methods as did women wishing to postpone a birth. PMID:12311397

  8. Ecstasy (MDMA) exposure and neuropsychological functioning: a polydrug perspective.

    PubMed

    Medina, Krista Lisdahl; Shear, Paula K; Corcoran, Kevin

    2005-10-01

    Ecstasy (MDMA) is a popular drug that can act as a selective serotonin neurotoxin in several species. The goal of the present study was to examine the relationship between ecstasy exposure and cognitive functioning after controlling for other drug use and demographic variables. Furthermore, we assessed whether gender was a moderator of the relationship between cognitive functioning and ecstasy use. Data were collected from 31 men and 34 women with a wide range of ecstasy use (17 marijuana users with no ecstasy use and 48 ecstasy users ranging from low to heavy use). Participants were interviewed and administered a battery of neuropsychological tests. The primary finding was that ecstasy exposure was significantly related to poorer verbal learning and memory ability in a dose-dependent manner, while no such relationship was observed between ecstasy exposure and executive functioning or attentional ability. Gender was found to significantly moderate the relationship between ecstasy consumption and design fluency. These results suggest primary memory dysfunction among abstinent recreational ecstasy users. This finding is consistent with reports of hippocampal vulnerability, particularly among heavy users. PMID:16248911

  9. 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

  10. Plasma concentrations of BDNF and IGF-1 in abstinent cocaine users with high prevalence of substance use disorders: relationship to psychiatric comorbidity.

    PubMed

    Pedraz, María; Martín-Velasco, Ana Isabel; García-Marchena, Nuria; Araos, Pedro; Serrano, Antonia; Romero-Sanchiz, Pablo; Suárez, Juan; Castilla-Ortega, Estela; Barrios, Vicente; Campos-Cloute, Rafael; Ruiz, Juan Jesús; Torrens, Marta; Chowen, Julie Ann; Argente, Jesús; de la Torre, Rafael; Santín, Luis Javier; Villanúa, María Ángeles; Rodríguez de Fonseca, Fernando; Pavón, Francisco Javier

    2015-01-01

    Recent studies have identified biomarkers related to the severity and pathogenesis of cocaine addiction and common comorbid psychiatric disorders. Monitoring these plasma mediators may improve the stratification of cocaine users seeking treatment. Because the neurotrophic factors are involved in neural plasticity, neurogenesis and neuronal survival, we have determined plasma concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1) and IGF-1 binding protein 3 (IGFBP-3) in a cross-sectional study with abstinent cocaine users who sought outpatient treatment for cocaine (n = 100) and age/body mass matched controls (n = 85). Participants were assessed with the diagnostic interview 'Psychiatric Research Interview for Substance and Mental Disorders'. Plasma concentrations of these peptides were not different in cocaine users and controls. They were not associated with length of abstinence, duration of cocaine use or cocaine symptom severity. The pathological use of cocaine did not influence the association of IGF-1 with age observed in healthy subjects, but the correlation between IGF-1 and IGFBP-3 was not significantly detected. Correlation analyses were performed between these peptides and other molecules sensitive to addiction: BDNF concentrations were not associated with inflammatory mediators, lipid derivatives or IGF-1 in cocaine users, but correlated with chemokines (fractalkine/CX3CL1 and SDF-1/CXCL12) and N-acyl-ethanolamines (N-palmitoyl-, N-oleoyl-, N-arachidonoyl-, N-linoleoyl- and N-dihomo-γ-linolenoyl-ethanolamine) in controls; IGF-1 concentrations only showed association with IGFBP-3 concentrations in controls; and IGFBP-3 was only correlated with N-stearoyl-ethanolamine concentrations in cocaine users. Multiple substance use disorders and life-time comorbid psychopathologies were common in abstinent cocaine users. Interestingly, plasma BDNF concentrations were exclusively found to be decreased in users diagnosed

  11. Plasma Concentrations of BDNF and IGF-1 in Abstinent Cocaine Users with High Prevalence of Substance Use Disorders: Relationship to Psychiatric Comorbidity

    PubMed Central

    Araos, Pedro; Serrano, Antonia; Romero-Sanchiz, Pablo; Suárez, Juan; Castilla-Ortega, Estela; Barrios, Vicente; Campos-Cloute, Rafael; Ruiz, Juan Jesús; Torrens, Marta; Chowen, Julie Ann; Argente, Jesús; de la Torre, Rafael; Santín, Luis Javier; Villanúa, María Ángeles; Rodríguez de Fonseca, Fernando; Pavón, Francisco Javier

    2015-01-01

    Recent studies have identified biomarkers related to the severity and pathogenesis of cocaine addiction and common comorbid psychiatric disorders. Monitoring these plasma mediators may improve the stratification of cocaine users seeking treatment. Because the neurotrophic factors are involved in neural plasticity, neurogenesis and neuronal survival, we have determined plasma concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1) and IGF-1 binding protein 3 (IGFBP-3) in a cross-sectional study with abstinent cocaine users who sought outpatient treatment for cocaine (n = 100) and age/body mass matched controls (n = 85). Participants were assessed with the diagnostic interview ‘Psychiatric Research Interview for Substance and Mental Disorders’. Plasma concentrations of these peptides were not different in cocaine users and controls. They were not associated with length of abstinence, duration of cocaine use or cocaine symptom severity. The pathological use of cocaine did not influence the association of IGF-1 with age observed in healthy subjects, but the correlation between IGF-1 and IGFBP-3 was not significantly detected. Correlation analyses were performed between these peptides and other molecules sensitive to addiction: BDNF concentrations were not associated with inflammatory mediators, lipid derivatives or IGF-1 in cocaine users, but correlated with chemokines (fractalkine/CX3CL1 and SDF-1/CXCL12) and N-acyl-ethanolamines (N-palmitoyl-, N-oleoyl-, N-arachidonoyl-, N-linoleoyl- and N-dihomo-γ-linolenoyl-ethanolamine) in controls; IGF-1 concentrations only showed association with IGFBP-3 concentrations in controls; and IGFBP-3 was only correlated with N-stearoyl-ethanolamine concentrations in cocaine users. Multiple substance use disorders and life-time comorbid psychopathologies were common in abstinent cocaine users. Interestingly, plasma BDNF concentrations were exclusively found to be decreased in users diagnosed

  12. Attributions for Abstinence from Illicit Drugs by University Students

    ERIC Educational Resources Information Center

    Rosenberg, Harold; Baylen, Chelsea; Murray, Shanna; Phillips, Kristina; Tisak, Marie S.; Versland, Amelia; Pristas, Erica

    2008-01-01

    Aim: To assess college students' attributions for abstinence from alcohol and illicit drugs. Method: We recruited 125 undergraduates to rate the degree to which each of 41 listed reasons influenced their abstention from six specific substances (alcohol, MDMA/ecstasy, inhalants, cocaine, marijuana, and hallucinogens). Findings: Internal consistency…

  13. Abstinence education*

    PubMed Central

    Zeiler, Alean

    2014-01-01

    The American College of Pediatricians strongly endorses abstinence-until-marriage sex education and recommends adoption by all school systems in lieu of “comprehensive sex education.” This position is based on “the public health principle of primary prevention—risk avoidance in lieu of risk reduction,” upholding the “human right to the highest attainable standard of health” (Freedman 1995). PMID:25473134

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

    PubMed Central

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

    2014-01-01

    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 prosocial 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 1.5 mg/kg), intranasal oxytocin (20 IU or 40 IU), and placebo. Plasma oxytocin concentrations, as well as cardiovascular and subjective effects were assessed before and at several time points after drug administration. MDMA (1.5 mg/kg only) increased plasma oxytocin levels to a mean peak of 83.7 pg/ml at approximately 90–120 minutes, compared to 18.6 pg/ml after placebo. Intranasal oxytocin (40 IU, but not 20 IU) increased plasma oxytocin levels to 48.0 pg/ml, 30–60 min 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. PMID:24882155

  15. 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

  16. 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 ...

  17. Modulation of Risky Choices in Recently Abstinent Dependent Cocaine Users: A Transcranial Direct-Current Stimulation Study

    PubMed Central

    Gorini, Alessandra; Lucchiari, Claudio; Russell-Edu, William; Pravettoni, Gabriella

    2014-01-01

    Previous neurobiological and neuropsychological investigations have shown that risk-taking behaviors and addictions share many structural and functional aspects. In particular, both are characterized by an irresistible need to obtain immediate rewards and by specific alterations in brain circuits responsible for such behaviors. In this study, we used transcranial direct-current stimulation over the dorsolateral prefrontal cortex (DLPFC) of two samples of subjects (18 dependent cocaine users and 18 control subjects) to investigate the effects of left and right cortical excitability on two risk tasks: (1) the balloon analog risk task (BART) and (2) the game of dice task (GDT). All subjects randomly received a left anodal/right cathodal stimulation (LAn+), a right anodal/left cathodal stimulation (RAn+), and a sham (placebo) stimulation each run at least 48 h apart. Participants were asked to perform the BART and the GDT immediately before and after each stimulation. Our results reveal that the activation of the DLPFC (left and right) results in a reduction of risky behaviors at the BART task both in controls subjects and cocaine dependent users. The effect of tDCS on GDT, instead, is more complex. Cocaine users increased safe behavior after right DLPFC anodal stimulation, while risk-taking behavior increased after left DLPFC anodal stimulation. Control subjects’ performance was only affected by the anodal stimulation of the right DLPFC, resulting in an increase of safe bets. These results support the hypothesis that excessive risk propensity in dependent cocaine users might be due to a hypoactivation of the right DLPFC and an unbalance interhemispheric interaction. In conclusion, since risky decision-making seems to be, at least in part, responsible for maintenance and relapse of addiction, we argue that a neuromodulation-based approach could represent a valuable adjunct in the clinical treatment of addiction. PMID:25221496

  18. 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. PMID:25974188

  19. Associations between University Students' Reported Reasons for Abstinence from Illicit Substances and Type of Drug

    ERIC Educational Resources Information Center

    Rosenberg, Harold; Bonar, Erin E.; Pavlick, Michelle; Jones, Lance D.; Hoffmann, Erica; Murray, Shanna; Faigin, Carol Ann; Cabral, Kyle; Baylen, Chelsea

    2012-01-01

    We recruited 211 undergraduates to rate the degree to which each of 34 listed reasons for not taking drugs had influenced their abstinence from MDMA/ecstasy, cocaine, marijuana, and hallucinogens. Participants rated reasons such as personal and family medical histories, religion, and physiological consequences of drug use as having little or no…

  20. 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…

  1. '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

  2. Making Sense of Abstinence

    ERIC Educational Resources Information Center

    Taverner, Bill; Montfort, Sue

    2011-01-01

    Young people need to know that abstinence is a far more complex, difficult concept than it is often portrayed. Abstinence is a decision about sexual behaviors that a person may make throughout his or her life. It is a choice made at a specific time in a specific situation, for a specific period of time, whether one is in a partnered relationship…

  3. 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

  4. 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

  5. The neurobiology of cognitive control in successful cocaine abstinence

    PubMed Central

    Connolly, Colm G.; Foxe, John J.; Nierenberg, Jay; Shpaner, Marina; Garavan, Hugh

    2011-01-01

    Introduction Extensive evidence demonstrates that current cocaine abusers show hypoactivity in anterior cingulate and dorsolateral prefrontal cortex and respond poorly relative to drug-naïve controls on tests of executive function. Relatively little is known about the cognitive sequalae of long-term abstinence in cocaine addicts. Methods Here, we use a GO-NOGO task in which successful performance necessitated withholding a prepotent response to assay cognitive control in short-and long-term abstinent cocaine users (1-5 weeks and 40-102 weeks, respectively). Results We report significantly greater activity in prefrontal, cingulate, cerebellar and inferior frontal gyrii in abstinent cocaine users for both successful response inhibitions and errors of commission. Moreover, this relative hyperactivity was present in both abstinent groups, which, in the presence of comparable behavioral performance, suggests a functional compensation. Conclusions Differences between the short- and long-abstinence groups in the patterns of functional recruitment suggest different cognitive control demands at different stages in abstinence. Short-term abstinence showed increased inhibition-related dorsolateral and inferior frontal activity indicative of the need for increased inhibitory control while long-term abstinence showed increased error-related ACC activity indicative of heightened behavioral monitoring. The results suggest that the integrity of prefrontal systems that underlie cognitive control functions may be an important characteristic of successful long-term abstinence. PMID:21885214

  6. MDMA: a social drug in a social context

    PubMed Central

    Kirkpatrick, Matthew G.; de Wit, Harriet

    2014-01-01

    Rationale The drug ±3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”, “molly”) is thought to produce pro-social effects and enhance social interaction. However, in most laboratory studies to date, the participants have been tested under non-social conditions, which may not simulate the effects the drug produces in more naturalistic social settings. Methods Healthy experienced MDMA users participated in three laboratory sessions in which they received MDMA (0.5 or 1.0 mg/kg or placebo; double blind). They were randomly assigned to one of three social conditions, in which they were tested alone (SOL; N=10), in the presence of a research assistant (RAP; N=11) or in the presence of another participant who also received the drug (OPP; N=11). Results As expected, MDMA increased heart rate and blood pressure, and produced positive subjective effects in all three groups. It also increased ratings of attractiveness of another person and increased social interaction in RAP and OPP. The social context affected certain responses to the drug. The effects of MDMA were greater in the OPP condition, compared to the SOL or RAP conditions, on measures of “feel drug”, “dizzy” and on cardiovascular measures. But responses to the drug on other measures, including social behavior, did not differ across the conditions. Conclusions These findings provide some support for the idea that drugs produce greater effects when they are used in the presence of other drug users. However, the influence of the social context was modest, and it remains to be determined whether other variables related to social context would substantially alter the effects of MDMA or other drugs. PMID:25281223

  7. MDMA (Ecstasy) association with impaired fMRI BOLD thalamic coherence and functional connectivity*

    PubMed Central

    Salomon, Ronald M.; Karageorgiou, John; Dietrich, Mary S.; McLellan, Jessica Y.; Charboneau, Evonne J.; Blackford, Jennifer U.; Cowan, Ronald L.

    2011-01-01

    Background MDMA exposure is associated with chronic serotonergic dysfunction in preclinical and clinical studies. A recent functional magnetic resonance imaging (fMRI) comparison of past MDMA users to non-MDMA-using controls revealed increased spatial extent and amplitude of activation in the supplementary motor area during motor tasks (Karageorgiou et al., 2009). Blood oxygenation level dependent (BOLD) data from that study were reanalyzed for intraregional coherence and for inter-regional temporal correlations between time series, as functional connectivity. Methods Fourteen MDMA users and ten controls reporting similar non-MDMA abuse performed finger taps during fMRI. Fourteen motor pathway regions plus a pontine raphé region were examined. Coherence was expressed as percent of voxels positively correlated with an intraregional index voxel. Functional connectivity was determined using wavelet correlations. Results Intraregional thalamic coherence was significantly diminished at low frequencies in MDMA users compared to controls (p=0.009). Inter-regional functional connectivity was significantly weaker for right thalamo - left caudate (p=0.002), right thalamo - left thalamus (p=0.007), right caudate - right postcentral (p=0.007) and right supplementary motor area - right precentral gyrus (p=0.011) region pairs compared to controls. When stratified by lifetime exposure, significant negative associations were observed between cumulative MDMA use and functional connectivity in seven other region-pairs, while only one region-pair showed a positive association. Conclusions Reported prior MDMA use was associated with deficits in BOLD intraregional coherence and inter-regional functional connectivity, even among functionally robust pathways involving motor regions. This suggests that MDMA use is associated with long-lasting effects on brain neurophysiology beyond the cognitive domain. PMID:21807471

  8. Neonatal abstinence syndrome

    MedlinePlus

    NAS; Neonatal abstinence symptoms ... may contribute to the severity of a baby's NAS symptoms. ... symptoms of withdrawal. Even after medical treatment for NAS is over and babies leave the hospital, they ...

  9. MDMA administration decreases serotonin but not N-acetylaspartate in the rat brain

    PubMed Central

    Perrine, Shane A.; Ghoddoussi, Farhad; Michaels, Mark S.; Hyde, Elisabeth M.; Kuhn, Donald M.; Galloway, Matthew P.

    2010-01-01

    In animals, repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) reduces markers of serotonergic activity and studies show similar serotonergic deficits in human MDMA users. Using proton magnetic resonance spectroscopy (1H-MRS) at 11.7 Tesla, we measured the metabolic neurochemical profile in intact, discrete tissue punches taken from prefrontal cortex, anterior striatum, and hippocampus of rats administered MDMA (5 mg/kg IP, 4× q 2 h) or saline and euthanized 7 days after the last injection. Monoamine content was measured with HPLC in contralateral punches from striatum and hippocampus to compare the MDMA-induced loss of 5HT innervation with constituents in the 1H-MRS profile. When assessed 7 days after the last MDMA injection, levels of hippocampal and striatal serotonin (5HT) were significantly reduced, consistent with published animal studies. N-acetylaspartate (NAA) levels were significantly increased in prefrontal cortex and not affected in anterior striatum or hippocampus; myo-inositol (INS) levels were increased in prefrontal cortex and hippocampus but not anterior striatum. Glutamate levels were increased in prefrontal cortex and decreased in hippocampus, while GABA levels were decreased only in hippocampus. The data suggest that NAA may not reliably reflect MDMA-induced 5HT neurotoxicity. However, the collective pattern of changes in 5HT, INS, glutamate and GABA is consistent with persistent hippocampal neuroadaptations caused by MDMA. PMID:20800616

  10. 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…

  11. Acute effects of MDMA (3,4-methylenedioxymethamphetamine) on EEG oscillations: alone and in combination with ethanol or THC (delta-9-tetrahydrocannabinol)

    PubMed Central

    Dumont, Glenn J. H.; van Gerven, Joop M. A.; Buitelaar, Jan K.; Verkes, Robbert-Jan

    2010-01-01

    Rationale Typical users of 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”) are polydrug users, combining MDMA with alcohol or cannabis [most active compound: delta-9-tetrahydrocannabinol (THC)]. Objectives The aim of the present study was to investigate whether co-administration of alcohol or THC with MDMA differentially affects ongoing electroencephalogram (EEG) oscillations compared to the administration of each drug alone. Methods In two separate experiments, 16 volunteers received four different drug conditions: (1) MDMA (100 mg); (2) alcohol clamp (blood alcohol concentration = 0.6‰) or THC (inhalation of 4, 6 and 6 mg, interval of 1.5 h); (3) MDMA in combination with alcohol or THC; and (4) placebo. Before and after drug administration, electroencephalography was recorded during an eyes closed resting state. Results Theta and alpha power increased after alcohol intake compared to placebo and reduced after MDMA intake. No interaction between alcohol and MDMA was found. Significant MDMA × THC effects for theta and lower-1-alpha power indicated that the power attenuation after the combined intake of MDMA and THC was less than the sum of each drug alone. For the lower-2-alpha band, the intake of MDMA or THC alone did not significantly affect power, but the intake of combined MDMA and THC significantly decreased lower-2-alpha power. Conclusions The present findings indicate that the combined intake of MDMA and THC, but not of MDMA and alcohol, affects ongoing EEG oscillations differently than the sum of either one drug alone. Changes in ongoing EEG oscillations may be related to the impaired task performance that has often been reported after drug intake. PMID:20924751

  12. 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

  13. 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

  14. Behavioural and neurotoxic long-lasting effects of MDMA plus cocaine in adolescent mice.

    PubMed

    Daza-Losada, M; Rodríguez-Arias, M; Maldonado, C; Aguilar, M A; Miñarro, J

    2008-08-20

    The poly-drug pattern is the most common among MDMA users, with cocaine being a frequently associated drug. The aim of the present work was to evaluate the behavioural and neurotoxic long-term effects of exposure during adolescence to MDMA alone or plus cocaine. Mice of 28 to 30 days of age received a treatment of two daily injections of an identical dose of MDMA (5, 10 or 20 mg/kg), alone or plus cocaine (25 mg/kg), for 3 days (6 administrations). Three weeks after receiving MDMA, an increase in the time dedicated by the animals to social contacts with their conspecifics was observed, whilst their behaviour in the elevated plus maze showed no differences from that of non-treated mice. After being exposed to MDMA plus cocaine, mice spent more time in social contacts during the interaction test, as well as exhibiting an anxiolytic profile in the elevated plus maze, with an increase in the time and number of entries in the open arms. The activity of mice treated with cocaine alone or plus MDMA remained constant; the decrease observed among the rest of the animals after the second hour was absent in their case. The level of dopamine in the striatum was diminished in mice treated with 20 mg/kg of MDMA, but this neurotransmitter was not affected in animals exposed to the same dose plus cocaine. The present results highlight pronounced alterations in the behaviour of adult mice after exposure to MDMA and cocaine during adolescence, and demonstrate that these long-term effects can occur without the dopaminergic system becoming affected. PMID:18585379

  15. 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. PMID:24752593

  16. Characterizing Smoking and Drinking Abstinence from Social Media

    PubMed Central

    Tamersoy, Acar; De Choudhury, Munmun; Chau, Duen Horng

    2015-01-01

    Social media has been established to bear signals relating to health and well-being states. In this paper, we investigate the potential of social media in characterizing and understanding abstinence from tobacco or alcohol use. While the link between behavior and addiction has been explored in psychology literature, the lack of longitudinal self-reported data on long-term abstinence has challenged addiction research. We leverage the activity spanning almost eight years on two prominent communities on Reddit: StopSmoking and StopDrinking. We use the self-reported “badge” information of nearly a thousand users as gold standard information on their abstinence status to characterize long-term abstinence. We build supervised learning based statistical models that use the linguistic features of the content shared by the users as well as the network structure of their social interactions. Our findings indicate that long-term abstinence from smoking or drinking (~one year) can be distinguished from short-term abstinence (~40 days) with 85% accuracy. We further show that language and interaction on social media offer powerful cues towards characterizing these addiction-related health outcomes. We discuss the implications of our findings in social media and health research, and in the role of social media as a platform for positive behavior change and therapy. PMID:26640831

  17. 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.…

  18. Ecstasy (MDMA) and oral health.

    PubMed

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

    2008-01-26

    3,4-methylenedioxymethamphetamine (MDMA), more commonly known as 'ecstasy' or XTC, is frequently used by young adults in the major cities. Therefore, it is likely that dentists might be confronted with individuals who use ecstasy. This review describes systemic and oral effects of ecstasy. Life-threatening complications include hyperthermia, hyponatraemia and liver failure. In addition, psychotic episodes, depression, panic disorders and impulsive behaviour have been reported. Oral effects include xerostomia, bruxism, and an increased risk of developing dental erosion. Mucosal changes have also been reported. Recent use of ecstasy may interfere with dental treatment. Finally, the potential use of saliva for non-invasive detection of ecstasy is discussed. PMID:18268544

  19. Randomized Trial of Prize-Based Reinforcement Density for Simultaneous Abstinence from Cocaine and Heroin

    ERIC Educational Resources Information Center

    Ghitza, Udi E.; Epstein, David H.; Schmittner, John; Vahabzadeh, Massoud; Lin, Jia-Ling; Preston, Kenzie L.

    2007-01-01

    To examine the effect of reinforcer density in prize-based abstinence reinforcement, heroin/cocaine users (N = 116) in methadone maintenance (100 mg/day) were randomly assigned to a noncontingent control group (NonC) or to 1 of 3 groups that earned prize draws for abstinence: manual drawing with standard prize density (MS) or computerized drawing…

  20. 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

  1. MDMA & cannabis: a mini-review of cognitive, behavioral, and neurobiological effects of co-consumption.

    PubMed

    Schulz, Sybille

    2011-06-01

    Although the prevalence of co-use of cannabis and 3,4 methylenedioxymethamphetamine (MDMA) is very common among polydrug users in western societies, few studies have tested the consequences on behavior, cognition or neurobiology. This review examines 23 articles published between 2002 and 2010 with an explicit focus on the combination, or administration, of MDMA and cannabis or cannabinoid agents. The aim was to provide a short overview on the latest human research concerning cognitive effects of co-consumption of MDMA and cannabis, and a more elaborate picture of the state of knowledge about the interaction of cannabinoid agents and MDMA from animal studies. It was found that recent retrospective studies on cognitive functions in long-term drug abusers point to an additive negative effect on different types of memory, as well as a cannabis-independent decrease in learning and decision-making in MDMA users. Behavioral experiments in rodents and in vitro studies investigating the combined effect of MDMA and cannabinoid agents demonstrate modulator effects of acute co-administration on measures like body temperature, conditioned reinforcement, and presumed neurotoxicity. As neural mechanism underlying these changes, an interaction between the cannabinoid system, especially cannabinoid receptor 1, and the serotonergic and dopaminergic system in the prefrontal cortex, nucleus accumbens, and hippocampus is suggested. In conclusion, there are few and somewhat contradictory studies examining the effects of co-use of these drugs on cognitive measures like impulsivity, memory and executive functions or underlying neurobiological alterations, and a shortage of animal studies examining long-term effects of chronic co-administration. PMID:21696342

  2. Response inhibition and addiction medicine: from use to abstinence.

    PubMed

    Spechler, Philip A; Chaarani, Bader; Hudson, Kelsey E; Potter, Alexandra; Foxe, John J; Garavan, Hugh

    2016-01-01

    Historically, neuroscientific research into addiction has emphasized affective and reinforcement mechanisms as the essential elements underlying the pursuit of drugs, their abuse, and difficulties associated with abstinence. However, research over the last decade or so has shown that cognitive control systems, associated largely but not exclusively with the frontal lobes, are also important contributors to drug use behaviors. Here, we focus on inhibitory control and its contribution to both current use and abstinence. A body of evidence points to impaired inhibitory abilities across a range of drugs of abuse. Typically, studies suggest that substance-abusing individuals are characterized by relative hypoactivity in brain systems underlying inhibitory control. In contrast, abstinent users tend to show either normal or supernormal levels of activity in the same systems attesting to the importance of inhibitory control in suppressing the drug use urges that plague attempts at abstinence. In this chapter, the brain and behavioral basis of response inhibition will be reviewed, with a focus on neuroimaging studies of response inhibition in current and abstinent drug abusers. PMID:26806775

  3. MDMA (ecstasy) modulates locomotor and prefrontal cortex sensory evoked activity.

    PubMed

    Atkins, Kristal; Burks, Tilithia; Swann, Alan C; Dafny, Nachum

    2009-12-11

    Ingestion of 3, 4-methylenedioxymethamphetamine (MDMA) leads to heightened response to sensory stimulation; thus, MDMA is referred to as "ecstasy" because it produces pleasurable enhancement of such sensation. There have been no electrophysiological studies that report the consequences of MDMA on sensory input. The present study was initiated to study the effects of acute and chronic MDMA on locomotor activity and sensory evoked field potential from freely behaving rats previously implanted with permanent electrodes in the prefrontal cortex (PFC). The main findings of this study are that: (1) acute MDMA augments locomotor behavior and attenuates the incoming sensory input, (2) chronic treatment of MDMA elicits behavioral sensitization, (3) chronic administration of MDMA results in attenuation of the baseline activity of the sensory evoked field potential, and (4) administration of rechallenge MDMA result in enhancement of the PFC sensory evoked field potential. PMID:19769950

  4. Assessing White Matter Integrity as a Function of Abstinence Duration in Former Cocaine-Dependent Individuals

    PubMed Central

    Bell, Ryan P.; Foxe, John J.; Nierenberg, Jay; Hoptman, Matthew J.; Garavan, Hugh

    2010-01-01

    Current cocaine-dependent users show reductions in white matter (WM) integrity, especially in cortical regions associated with cognitive control that have been associated with inhibitory dysfunction. A key question is whether these white matter differences are present following abstinence from drug use. To address this, WM integrity was examined using diffusion tensor imaging (DTI) obtained on 43 cocaine abstinent patients (abstinence duration ranged between five days and 102 weeks) and 43 non-using controls. Additionally, a cross-sectional comparison separated the patients into three groups (short-term, mid-term and long-term) based upon duration of cocaine abstinence. The 43 cocaine abstinent patients showed lower fractional anisotropy (FA) in the left anterior callosal fibers, left genu of the corpus callosum, right superior longitudinal fasciculus, right callosal fibers and the superior corona radiata bilaterally when compared against non-using controls. Higher FA in the cocaine abstinent patients was observed in the splenium of the corpus callosum and right superior longitudinal fasciculus. Differences between the cocaine abstinent groups were observed bilaterally in the inferior longitudinal fasciculus, right anterior thalamic radiation, right ventral posterolateral nucleus of the thalamus, left superior corona radiata, superior longitudinal fasciculus bilaterally, right cingulum and the WM of the right precentral gyrus. The results identified WM differences between cocaine abstinent patients and controls as well as distinct differences between abstinent subgroups. The findings suggest that specific white matter differences persist throughout abstinence while other, spatially distinct, differences discriminate as a function of abstinence duration. These differences may, therefore, represent brain changes that mark recovery from addiction. PMID:21075564

  5. The Ethics of Abstinence-Only and Abstinence-Plus Sexuality Education.

    ERIC Educational Resources Information Center

    Wiley, David C.

    2002-01-01

    Highlights some of the ethical dilemmas present in the debate over abstinence-only and abstinence-plus sexuality education in the schools, discussing issues related to: morality, ethics, and values; limitations to codes of ethics; questions about abstinence-only sexuality education; ethics and abstinence- only sexuality education; and sexuality…

  6. Differences in the acceptability of non-abstinence goals by type of drug among American substance abuse clinicians.

    PubMed

    Rosenberg, Harold; Davis, Alan K

    2014-02-01

    To assess whether acceptability of non-abstinence outcome goals varied depending on the specific drug a client consumes (alcohol, cannabis, amphetamine, heroin, cocaine, MDMA/ecstasy, polydrug), severity of diagnosis (DSM-IV Abuse vs. Dependence), and finality of outcome goal (intermediate vs. final), we recruited 432 clinicians to complete a web-based questionnaire. More respondents rated non-abstinence acceptable as an intermediate goal for clients diagnosed with alcohol abuse (44%) or cannabis abuse (43%) than for clients diagnosed as abusing the other listed drugs (23 to 31%). Similarly, larger proportions of respondents rated non-abstinence as acceptable as a final goal for clients diagnosed with alcohol abuse (30%) or cannabis abuse (24%) than for clients diagnosed as abusing the other drugs (11 to 13%). Only 9 to 13% of respondents rated non-abstinence as an acceptable final goal for clients diagnosed with dependence, but 20% to 30% rated non-abstinence as acceptable as an intermediate goal for clients diagnosed as dependent. PMID:23953169

  7. Smoking Abstinence, Eating Style, and Food Intake.

    ERIC Educational Resources Information Center

    Duffy, Joanne; Hall, Sharon M.

    1988-01-01

    Administered the Eating Inventory and the Profile of Mood States (POMS) to smoking subjects assigned to cigarette abstinence or to continued smoking. Found abstinent smokers with high Disinhibition Scale scores overate more than did nonabstinent smokers or abstinent smokers with lower scores when participating in a subsequent ice cream tasting…

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

    PubMed Central

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

    2014-01-01

    Background: Adenosine is an endogenous purine nucleoside that has a neuromodulatory role in the central nervous system. The amphetamine derivative (±)-3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a synthetic amphetamine analogue used recreationally to obtain an enhanced affiliated emotional response. MDMA is a potent monoaminergic neurotoxin with the potential of damage to brain neurons. The NF-kB family of proteins are ubiquitously expressed and are inducible transcription factors that regulate the expression of genes involved in disparate processes such as immunity and ingrowth, development and cell-death regulation. In this study we investigated the effects of the A2a adenosine receptor (A2a-R) agonist (CGS) and antagonist (SCH) on NF-kB expression after MDMA administration. Methods: Sixty three male Sprague–Dawley rats were injected to MDMA (10 and 20mg/kg) followed by intraperitoneal CGS (0.03 mg/kg) or SCH (0.03mg/kg) injection. The cerebellum were then removed forcresylviolet staining, western blot and RT- PCR analyses. MDMA significantly elevated NF-kB expression. Our results showed that MDMA increased the number of cerebellar dark neurons. Results: We observed that administration of CGS following MDMA, significantly elevated the NF-kB expression both at mRNA and protein levels. By contrast, administration of the A2a-R antagonist SCH resulted in a decrease in the NF-kB levels. Conclusion: These results indicated that, co-administration of A2a agonist (CGS) can protect against MDMA neurotoxic effects by increasing NF-kB expression levels; suggesting a potential application for protection against the neurotoxic effects observed in MDMA users. PMID:25678999

  9. Maintenance Sessions Prolong Cigarette Abstinence.

    ERIC Educational Resources Information Center

    Brandon, Thomas H.; And Others

    Recent smoking treatment programs have shifted emphasis from initial cessation rates to long-term abstinence, with aversion therapy and coping response training having had the most success. A smoking cessation treatment consisting of rapid smoking and behavioral counseling was supplemented with two maintenance treatments. After completing the…

  10. [Maintaining abstinence after alcohol detoxification].

    PubMed

    Batel, Philippe; Balester-Mouret, Sylvain

    2006-05-31

    "To quit drinking" is not the panacea of alcohol dependence treatment; it is only its first step. Abstinence should be considered more as a mean than a purpose of the after-withdrawal cares. The frequent resistance of the alcoholic patient to undertake in a long term abstinence can be by-passed by suggesting to fix himself renewable terms for periods during which he feels rather confident to raise the bet of a "most accomplished possible" abstinence. To facilitate the realization and the preservation of this abstinence in the best conditions (potentiation of the profits and minimization of the difficulties), a "therapeutic menu" will be proposed to the patient besides a "minimum plan" containing a medical follow-up over one year, with variable frequency of visits according to the evolution and the prescription of one or two anti-craving drugs registered. Psychotherapies using different techniques as Cognitive Behavioural Therapy, group therapy or psychoanalysis could be proposed after a necessary clarification to the patients of the mechanism of action of each and the waited profits. In the final, two thirds of the patients with alcohol dependence fire in one year a profit of their treatments; the practitioner takes, actually, no risk and should propose systematically a project to the only 20% of them who come to consult him. PMID:16836206

  11. Associations between Sexual Abstinence Ideals, Religiosity, and Alcohol Abstinence: A Longitudinal Study of Finnish Twins

    PubMed Central

    Winter, Torsten; Karvonen, Sakari; Rose, Richard J.

    2016-01-01

    We analyzed prevalence and stability of attitudes endorsing sexual abstinence ideals from late adolescence into early adulthood and studied associations of these attitudes with religiosity and alcohol abstinence in a sexually liberal Nordic society. Our population-based sample of Finnish twins permitted comparisons of co-twins concordant for religiosity but discordant for drinking to evaluate the association of sexual abstinence ideals with alcohol abstinence, controlling for household environment. From age 17 to 24, endorsement of sexual abstinence as a romantic ideal declined from 25% to 15%. Religiosity and alcohol abstinence correlated, both separately and together, with endorsing sexual abstinence. Abstinence ideals were associated with literal belief in fundamental tenets of the Bible. The association of sexual abstinence ideals with alcohol abstinence was confirmed in within-family comparisons of co-twins discordant for drinking but concordant for religiosity. Alcohol-abstinent twins were significantly more likely than their non-alcohol-abstinent twin siblings to endorse sexual abstinence ideals; that result suggests the association of sexual abstinence ideals with abstaining from alcohol is not explained by unmeasured confounds in familial background and structure. Our longitudinal results and analyses of discordant twins suggest that attitudes toward sexual abstinence ideals are embedded within other conservative attitudes and behaviors. PMID:23301620

  12. Effects of Stress and MDMA on Hippocampal Gene Expression

    PubMed Central

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

    2014-01-01

    MDMA (3,4-methylenedioxymethamphetamine) is a substituted amphetamine and popular drug of abuse. Its mood-enhancing short-term effects may prompt its consumption under stress. Clinical studies indicate that MDMA treatment may mitigate the symptoms of stress disorders such as posttraumatic stress syndrome (PTSD). On the other hand, repeated administration of MDMA results in persistent deficits in markers of serotonergic (5-HT) nerve terminals that have been viewed as indicative of 5-HT neurotoxicity. Exposure to chronic stress has been shown to augment MDMA-induced 5-HT neurotoxicity. Here, we examine the transcriptional responses in the hippocampus to MDMA treatment of control rats and rats exposed to chronic stress. MDMA altered the expression of genes that regulate unfolded protein binding, protein folding, calmodulin-dependent protein kinase activity, and neuropeptide signaling. In stressed rats, the gene expression profile in response to MDMA was altered to affect sensory processing and responses to tissue damage in nerve sheaths. Subsequent treatment with MDMA also markedly altered the genetic responses to stress such that the stress-induced downregulation of genes related to the circadian rhythm was reversed. The data support the view that MDMA-induced transcriptional responses accompany the persistent effects of this drug on neuronal structure/function. In addition, MDMA treatment alters the stress-induced transcriptional signature. PMID:24511526

  13. 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

  14. 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

  15. 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. PMID:24972084

  16. Breastfeeding and abstinence among the Yoruba.

    PubMed

    Dow, T E

    1977-08-01

    Contemporary patterns of breastfeeding and postpartum abstinence among the Yoruba of Nigera are examined. Quite extensive periods of postpartum abstinence are still observed by most rural and poorer urban women to prolong breastfeeding and increase child survivorship. Differentials in duration of breastfeeding and abstinence relate to both socioeconomic factors and age, suggesting the likelihood of large future reductions. Implications for family planning prospects and policies are noted. PMID:888163

  17. 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. PMID:24418707

  18. Discriminative stimulus effects of psychostimulants and hallucinogens in S(+)-3,4-methylenedioxymethamphetamine (MDMA) and R(-)-MDMA trained mice.

    PubMed

    Murnane, K S; Murai, N; Howell, L L; Fantegrossi, W E

    2009-11-01

    3,4-Methylenedioxymethamphetamine (MDMA) is a substituted phenethylamine more commonly known as the drug of abuse "ecstasy." The acute and persistent neurochemical effects of MDMA in the mice are distinct from those in other species. MDMA shares biological effects with both amphetamine-type stimulants and mescaline-type hallucinogens, which may be attributable to distinct effects of its two enantiomers, both of which are active in vivo. In this regard, among the substituted phenethylamines, R(-)-enantiomers tend to have hallucinogen-like effects, whereas S(+)-enantiomers tend to have stimulant-like effects. In the present study, mice were trained to discriminate S(+)- or R(-)-MDMA from vehicle. Drug substitution tests were then undertaken with the structurally similar phenethylamine dopamine/norepinephrine releaser S(+)-amphetamine, the structurally dissimilar tropane nonselective monoamine reuptake inhibitor cocaine, the structurally similar phenethylamine 5-hydroxytryptamine (5-HT)(2A) agonist 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7), and the structurally dissimilar mixed action tryptamine 5-HT(2A) agonist/monoamine reuptake inhibitor N,N-dipropyltryptamine (DPT). S(+)-amphetamine fully substituted in the S(+)-MDMA-treated animals but did not substitute for the R(-)-MDMA cue. 2C-T-7 fully substituted in the R(-)-MDMA-trained animals but did not substitute for the S(+)-MDMA cue. Cocaine and DPT substituted for both training drugs, but whereas cocaine was more potent in S(+)-MDMA-trained mice, DPT was more potent in R(-)-MDMA-trained mice. These data suggest that qualitative differences in the discriminative stimulus effects of each stereoisomer of MDMA exist in mice and further our understanding of the complex nature of the interoceptive effects of MDMA. PMID:19684254

  19. The Controversy between Abstinence-Only and Abstinence- Plus Approaches to Sexuality Education.

    ERIC Educational Resources Information Center

    Fisher, Jamie L.

    2002-01-01

    Asserts that the debate over abstinence-only versus abstinence-plus sexuality education has shifted from what best serves students to what best suits adults' beliefs. Though research suggests comprehensive approaches to sexuality education are the most effective in reducing risk, government funding supports abstinence-only programs, which have…

  20. Texas Abstinence Educators' Self-Efficacy to Motivate Youth Sexual Abstinence

    ERIC Educational Resources Information Center

    Rasberry, Catherine N.; Goodson, Patricia; Buhi, Eric R.; Pruitt, B. E.; Wilson, Kelly; Suther, Sandra

    2007-01-01

    Authors examined self-efficacy to motivate abstinent behavior (among youth) in a sample of instructors teaching abstinence-only-until-marriage education in Texas (N = 104). Sixty-one percent of the sample had been trained/certified to teach abstinence education. Instructors (mostly female and White) were more confident motivating students to…

  1. Duration of detection of methamphetamine in hair after abstinence.

    PubMed

    Suwannachom, Natiprada; Thananchai, Thiwaphorn; Junkuy, Anongphan; O'Brien, Timothy E; Sribanditmongkol, Pongruk

    2015-09-01

    Researchers in the field of hair analysis have known for at least two decades that test results for many chemical compounds remain positive for a considerable period of time after subjects have reported cessation of use. These findings were generally based on small sample populations or individual case studies. Within the last decade, hair analyses of larger populations have investigated the phenomenon of residual positives in abstinent individuals in order to determine the period of time required for various compounds to present negative hair test results at internationally accepted cutoff levels. Such data has primarily been used to establish guidelines for retesting former abusers of illicit drugs in order to evaluate claims of abstinence. To date, research has focused on cocaine and opiates. The present study is the first to examine the duration of detection of methamphetamine (MA) and its metabolite amphetamine (AP) in the hair of chronic MA users who recently ceased their consumption of the drug. The study population (n=63) consisted of inpatients at a hospital drug rehabilitation program in Chiang Mai, Thailand. Drug taking behavior was collected by personal interview at the time of enrollment. Subjects provided hair samples at approximately monthly intervals for MA and AP analysis by gas chromatography-mass spectrometry at 0.2ng/mg cutoff levels. The correlation of baseline MA and AP concentrations in hair at the beginning of abstinence with corresponding duration of detection indicated great individual variability for the rate of clearance of MA and AP from hair. In regard to duration of detection, the majority of chronic MA users remained MA positive for up to about 90 days of reported abstinence, but by 120 days, the detection rate had fallen to about 16%. All subjects tested negative for MA after 153 days of abstinence. For AP, the limit of the duration of detection was reached at 106 days. With the adoption of a margin of safety to compensate for

  2. 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

  3. 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. PMID:24403876

  4. MDMA DECREASES THE EFFECTS OF SIMULATED SOCIAL REJECTION

    PubMed Central

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

    2014-01-01

    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. PMID

  5. Abstinence-Only Debate Heating Up

    ERIC Educational Resources Information Center

    Bowman, Darcia Harris

    2004-01-01

    President Bush's proposal to almost double the amount of money the federal government spends on abstinence education to $273 million in fiscal 2005 has raised the stakes in the battle over what to teach children and adolescents about sex. Only a small percentage of Americans believe abstinence-only programs are the best form of sex education for…

  6. 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

  7. 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

  8. Long-term behavioral consequences of prenatal MDMA exposure.

    PubMed

    Thompson, Valerie B; Heiman, Justin; Chambers, James B; Benoit, Stephen C; Buesing, William R; Norman, Mantana K; Norman, Andrew B; Lipton, Jack W

    2009-03-23

    The current study sought to determine whether prenatal 3,4-methylenedioxy-N-methamphetamine (MDMA) exposure from E14-20 in the rat resulted in behavioral sequelae in adult offspring. Prenatal MDMA exposure results in increased dopaminergic fiber density in the prefrontal cortex, striatum and nucleus accumbens of young rats. Since these areas are critical in response to novelty, reward, attention and locomotor activity, we hypothesized that prenatal MDMA exposure would produce significant changes in the performance of tasks that examine such behaviors in adult rats. Adult rats prenatally exposed to MDMA exhibited greater activity and spent more time in the center during a novel open field test as compared to controls. This increased activity was not reflected in normal home cage activity. Prenatal exposure to MDMA did not affect feeding or food reward. It did not alter cocaine self-administration behaviors, nor did it have an effect on the locomotor response to amphetamine challenge. Finally, while prenatal MDMA did not affect performance in the radial arm maze or the Morris water maze (MWM), these animals demonstrated altered performance in a cued MWM paradigm. Prenatal MDMA exposure resulted in perseverative attendance to a hanging cue when the platform in the MWM was removed as compared to controls. Together, these data demonstrate that prenatal exposure to MDMA results in a behavioral phenotype in adult rats characterized by reduced anxiety, a heightened response to novelty, and "hyperattentiveness" to environmental cues during spatial learning. PMID:19162054

  9. Predictors of motivation for abstinence at the end of outpatient substance abuse treatment.

    PubMed

    Laudet, Alexandre B; Stanick, Virginia

    2010-06-01

    Commitment to abstinence, a motivational construct, is a strong predictor of reductions in drug and alcohol use. Level of commitment to abstinence at treatment end predicts sustained abstinence, a requirement for recovery. This study sought to identify predictors of commitment to abstinence at treatment end to guide clinical practice and to inform the conceptualization of motivational constructs. Polysubstance users (N = 250) recruited at the start of outpatient treatment were reinterviewed at the end of services. Based on the extant literature, potential predictors were during treatment measures of substance use and related cognitions, psychological functioning, recovery supports, stress, quality of life satisfaction, and treatment experiences. In multivariate analyses, perceived harm of future drug use, abstinence self-efficacy, quality of life satisfaction, and number of network members in 12-step recovery contributed 26.6% of the variance explained in the dependent variable, a total of 49.6% when combined with the control variables (demographics and baseline level of the outcome). Gender subgroup analyses yielded largely similar results. Clinical implications of findings for maximizing commitment to abstinence when clients leave treatment are discussed as are future research directions. PMID:20185267

  10. A Multistudy Analysis of the Effects of Early Cocaine Abstinence on Sleep

    PubMed Central

    Matuskey, D; Pittman, B; Forselius, E; Malison, RT; Morgan, PT

    2010-01-01

    Objective To describe the sleep patterns of early cocaine abstinence in chronic users by polysomnographic and subjective measures. Methods 28 cocaine-dependent participants (ages 24-55) underwent polysomnographic sleep (PSG) recording on the 1st, 2nd and 3rd weeks of abstinence on a research dedicated inpatient facility. Objective measures of total sleep time, total REM time, slow wave sleep, sleep efficiency and a subjective measure (sleep quality) along with demographic data were collected from three different long term research studies over a five year period. Data were reanalyzed to allow greater statistical power for comparisons. Results Progressive weeks of abstinence had main effects on all assessed PSG sleep measures showing decreased total sleep time, REM sleep, stage 1 and 2 sleep, and sleep efficiency; increases in sleep onset and REM latencies and a slight increase in slow-wave sleep time were also present. Total sleep time and slow wave sleep were negatively associated with years of cocaine use. Total sleep time was positively associated with the amount of current ethanol use. Sex differences were found with females having more total REM time and an increase at a near significance level in slow wave sleep. Subjective measures were reported as improving with increasing abstinence over the same time period. Conclusions Chronic cocaine users show a general deterioration in objective sleep measures over a three-week period despite an increase in subjective overall sleep quality providing further evidence for “occult insomnia” during early cocaine abstinence. PMID:21144676

  11. 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.

  12. How could MDMA (ecstasy) help anxiety disorders? A neurobiological rationale.

    PubMed

    Johansen, P Ø; Krebs, T S

    2009-06-01

    Exposure therapy is known to be an effective treatment for anxiety disorders. Nevertheless, exposure is not used as much as it should be, and instead patients are often given supportive medications such as serotonin reuptake inhibitors (SSRIs) and benzodiazepines, which may even interfere with the extinction learning that is the aim of treatment. Given that randomized controlled trials are now investigating a few doses of +/-3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') in combination with psychotherapy for treatment-resistant anxiety disorders, we would like to suggest the following three mechanisms for this potentially important new approach: 1) MDMA increases oxytocin levels, which may strengthen the therapeutic alliance; 2) MDMA increases ventromedial prefrontal activity and decreases amygdala activity, which may improve emotional regulation and decrease avoidance and 3) MDMA increases norepinephrine release and circulating cortisol levels, which may facilitate emotional engagement and enhance extinction of learned fear associations. Thus, MDMA has a combination of pharmacological effects that, in a therapeutic setting, could provide a balance of activating emotions while feeling safe and in control, as described in case reports of MDMA-augmented psychotherapy. Further clinical and preclinical studies of the therapeutic value of MDMA are indicated. PMID:19273493

  13. 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. PMID:26073279

  14. [Entactogenic drugs "ecstasy" (MDMA), "eve" (MDE) and other ring-substituted methamphetamine derivatives. A new class of substances among illegal designer drugs?].

    PubMed

    Gouzoulis-Mayfrank, E; Hermle, L; Kovar, K A; Sass, H

    1996-05-01

    The widely used recreational drugs 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) and 3,4-methylenedioxyethamphetamine (MDE, Eve) occupy an intermediate position between stimulants and hallucinogens. Besides stimulation similar to that caused by amphetamines, they usually induce a pleasant, easily controllable emotional state with relaxation, fearlessness and feelings of happiness, but they sometimes also have stronger, hallucinogenic, effects. A number of pharmacological studies support the hypothesis that these drugs make up a distinct class of psychoactive substances, which have been designated "entactogens." On the drug scene, MDMA and MDE are considered "safe." However, this view must be corrected. Complications are rare, but potentially devastating ([long-lasting anxiety and depressive syndromes in chronic users, fatalities with hyperpyrexia, rhabdomyolysis and DIC syndrome (disseminated instravascular coagulation), possible hepatotoxicity]. Moreover, the clinical relevance of animal studies showing neurotoxic effects of MDMA on central serotonergic pathways is still not clear. PMID:9005345

  15. Auditory stimuli enhance MDMA-conditioned reward and MDMA-induced nucleus accumbens dopamine, serotonin and locomotor responses

    PubMed Central

    Feduccia, Allison A.; Duvauchelle, Christine L.

    2016-01-01

    MDMA (3,4-methylenedioxymethamphetamine), also known as ecstasy, is a popular drug often taken in environments rich in audio and visual stimulation, such as clubs and dance parties. The present experiments were conducted to test the notion that auditory stimulation influences the rewarding effects of MDMA. In Experiment 1, a conditioned place preference (CPP) procedure was conducted in which rats received MDMA (1.5 mg/kg, s.c.) in a distinctive environment accompanied by music (65–75 dB), white noise (70 dB), or no added sound. Animals were pretreated with saline on alternating days in an alternate environment. Results revealed CPP in animals exposed to white noise during MDMA trials. For Experiment 2, rats from Experiment 1 had access to operant levers that delivered intravenous MDMA (0.5 mg/kg/inj) or saline (0.1 ml) on alternate days in the presence or absence of the same types of auditory stimuli as previously experienced. After three each of MDMA and non-reinforced (saline) sessions, animals were tested for NAcc DA and 5-HT responses to MDMA (1.5 mg/kg) or saline under the same stimulus conditions. Findings revealed that NAcc DA and 5-HT increased after an MDMA injection, and both DA and 5-HT were significantly highest in animals exposed to music during the test session. These results indicate that paired sensorial stimuli can engage the same systems activated during drug use and enhance neurochemical and behavioral responses to MDMA administration. PMID:18722516

  16. Understanding Sexual Abstinence in Urban Adolescent Girls

    PubMed Central

    Morrison-Beedy, Dianne; Carey, Michael P.; Côté-Arsenault, Denise; Seibold-Simpson, Susan; Robinson, Kerry Anne

    2008-01-01

    Objectives To gain insight into the context of sexual abstinence and identify potential determinants of abstinence in this population. Design Four focus groups. Participants and Setting Twenty-four, predominantly African American (88%) girls aged 14 to 19 years were recruited from urban health centers and youth development programs in Rochester, New York, between September and December 2006. Data Analysis Content analysis was used to analyze the four verbatim transcripts. Using analytic induction, groups were compared and contrasted at the micro (within-group) and macro (between-group) levels to identify themes. Results Four themes were identified that provided insight into how and why these girls remain abstinent despite being in sexually active social climates. They focused on the following: self-respect (I'm worth it), impact of mothers (Mama says … think before you let it go), influence of boys and other peers (Boys will be boys), and potential negative consequences of sex (Hold on, there's a catch). Conclusions Developing interventions to maintain abstinence, delay onset of sexual activity, and promote protected first and subsequent sexual contact in abstinent girls are key to decreasing future sexual risk. These findings suggest opportunities to develop HIV prevention strategies tailored to the needs of abstinent girls. PMID:18336442

  17. How MDMA's pharmacology and pharmacokinetics drive desired effects and harms.

    PubMed

    Michael White, C

    2014-03-01

    3,4-Methylenedioxymethamphetamine (MDMA) is an agent of abuse that has been used by over 16 million Americans. Increased energy, elevated mood, bonding with others, and psychedelic effects are desired effects while liver damage, extended depressed mood, sexual assault, rhabdomyolysis, serotonin syndrome, multiorgan failure, cardiovascular events, arrhythmias, and death are possible adverse effects. These desirable and adverse effects of MDMA are extensions of its fascinating pharmacologic and pharmacokinetic profile. In addition to methamphatemine like effects, MDMA also has mescaline like effects and increases the release of cortisol, oxytocin, and antidiuretic hormone. The desirable effects of MDMA are accentuated by the rave or electronic dance music scene where warm temperatures, vigorous dancing, loud music, and light shows accentuate some of the responses. However, the same environment increases the risk of certain harms. Knowledge of the constellation of these factors is needed for education, prevention of harm, and treatment. PMID:24431106

  18. 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

  19. Beyond Abstinence-Only: Relationships between Abstinence Education and Comprehensive Topic Instruction

    ERIC Educational Resources Information Center

    Jeffries, William L., IV; Dodge, Brian; Bandiera, Frank C.; Reece, Michael

    2010-01-01

    In the United States, a debate exists as to whether abstinence-only or comprehensive sexuality education strategies are most beneficial for school-age youth. Despite abstinence being a fundamental component of comprehensive education, the two are often characterized as polar opposites. Few studies have examined overlaps between the approaches. The…

  20. Abstinence-Related Word Associations and Definitions of Abstinence and Virginity among Missouri High School Freshmen

    ERIC Educational Resources Information Center

    Wilson, Kelly L.; Smith, Matthew Lee; Menn, Mindy

    2013-01-01

    Background: The ways in which adolescents define and view sex, abstinence, and virginity impact the efforts of sexuality educators and sexual health professionals. This study examined terminology used by nonsexually active high school students to define abstinence and virginity and identified words students associate with these terms. Purposes…

  1. Abstinence Self-Efficacy and Abstinence 1 Year After Substance Use Disorder Treatment

    ERIC Educational Resources Information Center

    Ilgen, Mark; McKellar, John; Tiet, Quyen

    2005-01-01

    To better understand the relationship between abstinence self-efficacy and treatment outcomes in substance use disorder patients, experts in the field need more information about the levels of abstinence self-efficacy most predictive of treatment outcomes. Participants (N = 2,967) from 15 residential substance use disorder treatment programs were…

  2. 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

  3. Abstinence-Conflict Model: Toward an Optimal Animal Model for Screening Medications Promoting Drug Abstinence.

    PubMed

    Peck, J A

    2016-01-01

    Drug addiction is a significant health and societal problem for which there is no highly effective long-term behavioral or pharmacological treatment. A rising concern are the use of illegal opiate drugs such as heroin and the misuse of legally available pain relievers that have led to serious deleterious health effects or even death. Therefore, treatment strategies that prolong opiate abstinence should be the primary focus of opiate treatment. Further, because the factors that support abstinence in humans and laboratory animals are similar, several animal models of abstinence and relapse have been developed. Here, we review a few animal models of abstinence and relapse and evaluate their validity and utility in addressing human behavior that leads to long-term drug abstinence. Then, a novel abstinence "conflict" model that more closely mimics human drug-seeking episodes by incorporating negative consequences for drug seeking (as are typical in humans, eg, incarceration and job loss) and while the drug remains readily available is discussed. Additionally, recent research investigating both cocaine and heroin seeking in rats using the animal conflict model is presented and the implications for heroin treatments are examined. Finally, it is argued that the use of animal abstinence/relapse models that more closely approximate human drug addiction, such as the abstinence-conflict model, could lead to a better understanding of the neurobiological and environmental factors that support long-term drug abstinence. In turn, this will lead to the development of more effective environmental and pharmacotherapeutic interventions to treat opiate addiction and addiction to other drugs of abuse. PMID:27055619

  4. 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

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

    PubMed Central

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

    2015-01-01

    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

  6. Abstinence-Only Sex Education: College Students' Evaluations and Responses

    ERIC Educational Resources Information Center

    Gardner, Emily A.

    2015-01-01

    This qualitative study explores the abstinence-only sex education experiences of a small group of young adults in the southeastern USA. Most participants felt that their abstinence-only sex education had mixed value and low overall impact in their lives. Perceptions about abstinence, virginity, and marriage varied significantly from those stressed…

  7. The Impact of Abstinence Education: What Does the Research Say?

    ERIC Educational Resources Information Center

    Young, Michael; Penhollow, Tina

    2006-01-01

    There has long been controversy in this country about the implementation of school-based sexuality education. In recent years, however, the controversy has centered on abstinence education. Critics of abstinence education programs seem to have three major concerns relative to abstinence education programming: (1) promotion of religion; (2)…

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

    PubMed

    Schenk, Susan

    2011-04-01

    A number of reviews have focused on the short- and long-term effects of MDMA and, in particular, on the persistent deficits in serotonin neurotransmission that accompany some exposure regimens. The mechanisms underlying the serotonin deficits and their relevance to various behavioral and cognitive consequences of MDMA use are still being debated. It has become clear, however, that some individuals develop compulsive and uncontrolled drug-taking that is consistent with abuse. For other drugs of abuse, this transition has been attributed to neuroadaptations in central dopamine mechanisms that occur as a function of repeated drug exposure. A question remains as to whether similar neuroadaptations occur as a function of exposure to MDMA and the impact of serotonin neurotoxicity in the transition from use to abuse. This review focuses specifically on this issue by first providing an overview of human studies and then reviewing the animal literature with specific emphasis on paradigms that measure subjective effects of drugs and self-administration as indices of abuse liability. It is suggested that serotonin deficits resulting from repeated exposure to MDMA self-administration lead to a sensitized dopaminergic response to the drug and that this sensitized response renders MDMA comparable to other drugs of abuse. PMID:21184779

  9. Animal models of drug relapse and craving: From drug priming-induced reinstatement to incubation of craving after voluntary abstinence.

    PubMed

    Venniro, Marco; Caprioli, Daniele; Shaham, Yavin

    2016-01-01

    High rates of relapse to drug use during abstinence is a defining feature of drug addiction. In abstinent drug users, drug relapse is often precipitated by acute exposure to the self-administered drug, drug-associated cues, stress, as well as by short-term and protracted withdrawal symptoms. In this review, we discuss different animal models that have been used to study behavioral and neuropharmacological mechanisms of these relapse-related phenomena. In the first part, we discuss relapse models in which abstinence is achieved through extinction training, including the established reinstatement model, as well as the reacquisition and resurgence models. In the second part, we discuss recent animal models in which drug relapse is assessed after either forced abstinence (e.g., the incubation of drug craving model) or voluntary (self-imposed) abstinence achieved either by introducing adverse consequences to ongoing drug self-administration (e.g., punishment) or by an alternative nondrug reward using a discrete choice (drug vs. palatable food) procedure. We conclude by briefly discussing the potential implications of the recent developments of animal models of drug relapse after voluntary abstinence to the development of medications for relapse prevention. PMID:26822352

  10. 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

  11. Health Education Curriculum Content--Abstinence

    ERIC Educational Resources Information Center

    North Dakota Department of Public Instruction, 2011

    2011-01-01

    As a result of House Bill 1229, introduced and passed during the 2011 North Dakota legislative session, every school district, both public and nonpublic, must expand health education to include abstinence education, if teaching sexuality education as part of the general health curriculum. This fact sheet provides guidance for districts in meeting…

  12. A Test of the Abstinence Violation Effect.

    ERIC Educational Resources Information Center

    Ruderman, Audrey J.

    According to the abstinence violation effect, highly controlled drinkers tend to overindulge following an initial slip. To investigate this relapse model, 47 male college students, ranging in age from 21 to 46, were assigned either to an unrestrained or a restrained drinker group according to their scores on the Restrained Drinking Scale. Subjects…

  13. Current preclinical studies on neuroinflammation and changes in blood-brain barrier integrity by MDMA and methamphetamine.

    PubMed

    O'Shea, Esther; Urrutia, Andrés; Green, A Richard; Colado, M Isabel

    2014-12-01

    The blood-brain barrier (BBB) is essential in the maintenance of brain homeostasis both by preserving normal brain functioning and also by protecting the brain from exposure to a range of potentially harmful substances. This review presents some of the evidence of BBB disruption following exposure to the substituted amphetamines 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and methamphetamine (METH), two drugs of abuse which are widely consumed recreationally by younger sectors of the population. Both MDMA and METH have been shown to produce disruption of the BBB as reflected by IgG extravasation and Evans Blue leakage. In particular, METH decreases the expression of basal lamina proteins associated with an increase in matrix metalloproteinase activity. These changes in BBB integrity appear to be related to MDMA-induced activation of the mitogen-activated protein kinase (MAPK) JNK1/2. The consequences of the disruption in the BBB by these two drugs remain to be established, but there is evidence in the literature that, at least in the case of METH, increased matrix metalloproteinase (MMP) activity may be related to increased behavioural sensitization and reward perhaps because of the modification of the passage of the drug into the CNS. In addition, the high incidence of AIDS-related neurologic disease in METH users may also be related to increased entry into the brain of virally derived neurotoxic products. This article is part of the Special Issue entitled 'CNS Stimulants'. PMID:24594477

  14. Motives for khat use and abstinence in Yemen - a gender perspective

    PubMed Central

    2010-01-01

    Background Khat consumption is widespread in Yemeni society and causes problems both in economic development and public health. Preventive measures have been largely unsuccessful and the cultivation continues to proliferate. The gender-specific motives for khat use and abstinence were studied to create a toe-hold for more specific interventions. Methods In a quota sample with equal numbers of males, females, abstainers and consumers, 320 subjects were interviewed on their specific opinions about khat and its impact on subjective and public health, and on social and community functioning. Strata were compared in their acceptance and denial of opinions. Notions that could predict abstinence status or gender were identified with multivariate logistic regression analysis. Results Male khat users had a strong identification with khat use, while females were more ambivalent. The notion that khat consumption is a bad habit (odds ratio (OR) 3.4; p < 0.001) and consumers are malnuorished (OR 2.2; p = 0.046) were associated with female gender among khat users. Among the females worries about health impact (OR 3.2; p = 0.040) and loss of esteem in the family (OR 3.1; p = 0.048) when using khat predicted abstinence. Male abstainers opposed khat users in the belief that khat is the cause of social problems (OR 5.1, p < 0.001). Logistic regression reached an accuracy of 75 and 73% for the prediction of abstinence and 71% for gender among consumers. (All models p < 0.001.) Conclusions Distinct beliefs allow a differentiation between males, females, khat users and abstainers when targeting preventive measures. In accordance to their specific values female khat users are most ambivalent towards their habit. Positive opinions scored lower than expected in the consumers. This finding creates a strong toe-hold for gender-specific public health interventions. PMID:21110889

  15. 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

  16. Online Community Use Predicts Abstinence in Combined Internet/Phone Intervention for Smoking Cessation

    PubMed Central

    Papandonatos, George D.; Erar, Bahar; Stanton, Cassandra A.; Graham, Amanda L.

    2016-01-01

    Objective To estimate the causal effects of online community use on 30-day point prevalence abstinence at 3 months among smokers randomized to combined Internet+Phone intervention for smoking cessation. Method Participants were N=399 adult smokers in the Internet+Phone arm of The iQUITT Study, a randomized trial of Internet and proactive telephone counseling for smoking cessation. All participants accessed a web-based smoking-cessation program with an established online community and received telephone counseling. Automated tracking metrics of passive (e.g., reading posts, viewing profiles) and active (e.g., writing posts, sending messages) community use were extracted at 3 months. Self-selected community use defines the groups of interest: None, Passive, and Both (passive+active). Inverse probability of treatment weighting corrected for baseline imbalances on demographic, smoking, and psychosocial variables. Propensity weights estimated via generalized boosted models were used to calculate Average Treatment Effects (ATE) and Average Treatment effects on the Treated (ATT). Results Patterns of community use were: None=145 (36.3%), Passive=82 (20.6%), and Both=172 (43.1%). ATE-weighted abstinence rates were: None=12.2% (95% CI=6.7–17.7); Passive=25.2% (95% CI=15.1–35.2); Both=35.5% (95% CI=28.1–42.9). ATT-weighted abstinence rates indicated even greater benefits of passive community use by non-users. Conclusions More than one third of participants who received telephone counseling and used the community both passively and actively achieved abstinence. Participation in an established online community as part of a combined Internet+phone intervention has the potential to promote short-term abstinence. Results also demonstrated that information and support that originate in the community can serve as a resource for all users. PMID:27100127

  17. Use of an Online Smoking Cessation Community Promotes Abstinence: Results of Propensity Score Weighting

    PubMed Central

    Graham, Amanda L.; Papandonatos, George D.; Erar, Bahar; Stanton, Cassandra A.

    2015-01-01

    Objective To estimate the causal effects of use of an online smoking cessation community on 30-day point prevalence abstinence at 3 months. Methods Participants were N=492 adult current smokers in the enhanced Internet arm of The iQUITT Study, a randomized trial of Internet and telephone treatment for smoking cessation. All participants accessed a web-based smoking-cessation program that included a large, established online community. Automated tracking metrics of passive (e.g., reading forum posts, viewing member profiles) and active (e.g., writing forum posts, sending private messages) community use were extracted from the site at 3 months. Self-selected community use defines the groups of interest: “None”, “Passive”, and “Both” (passive+active). Inverse probability of treatment weighting corrected for baseline imbalances on demographic, smoking, psychosocial, and medical history variables. Propensity weights estimated via generalized boosted models were used to calculate Average Treatment Effects (ATE) and Average Treatment effects on the Treated (ATT). Results Patterns of community use were: None=198 (40.2%), Passive=110 (22.4%), and Both=184 (37.4%). ATE-weighted abstinence rates were: None=4.2% (95% CI=1.5–6.9); Passive=15.1% (95% CI=8.4–21.9); Both=20.4% (95% CI=13.9–26.8). ATT-weighted abstinence rates indicated even greater benefits of community use. Conclusions Community users were more likely to quit smoking at 3 months than nonusers. The estimated benefit from use of online community resources was even larger among subjects with high propensity to use them. No differences in abstinence emerged between passive and passive/active users. Results suggest that lurking in online communities confers specific abstinence benefits. Implications of these findings for online cessation communities are discussed. PMID:26651470

  18. 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

  19. Dramatic Increases in Maternal Opioid Use and Neonatal Abstinence Syndrome

    MedlinePlus

    ... Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA ( ... Monitoring the Future 2015 Survey Results Drug and Alcohol Use in College-Age Adults in 2014 View ...

  20. 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

  1. Neonatal Abstinence Syndrome: Presentation and Treatment Considerations.

    PubMed

    Jones, Hendrée E; Kaltenbach, Karol; Johnson, Elisabeth; Seashore, Carl; Freeman, Emily; Malloy, Erin

    2016-01-01

    This clinical case conference discusses the treatment of a pregnant woman with opioid use disorder in a comprehensive care program that includes buprenorphine pharmacotherapy. The presentation summarizes common experiences that pregnant women who receive buprenorphine pharmacotherapy face, and also what their prenatally opioid-exposed children confront in the immediate postpartum period. It describes the elements of a successful comprehensive care model and corollary neonatal abstinence syndrome treatment regimen. Expert commentary is included on issues that arise in the buprenorphine induction and maintenance throughout the prenatal and postpartum periods and in the treatment of co-occurring mental health problems during both the prenatal and postpartum periods, particularly the treatment of depression. There is also expert commentary on the care of opioid-exposed neonates, with attention to the treatment for neonatal abstinence syndrome. PMID:27244045

  2. Development of a high-speed MALDI-triple quadrupole mass spectrometric method for the determination of 3,4-methylenedioxymethamphetamine (MDMA) in oral fluid.

    PubMed

    Poetzsch, Michael; Steuer, Andrea E; Hysek, Cedric M; Liechti, Matthias E; Kraemer, Thomas

    2016-02-01

    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is still a widely used illicit designer drug and its detection in different matrices is of major importance for forensic purposes (e.g. driving under the influence) as well as for workplace drug testing or abstinence control. Established analytical methods for the determination of MDMA are mainly employing high performance liquid chromatography (HPLC) or gas chromatography (GC) coupled to mass spectrometric detection. Matrix assisted laser desorption/ionization-triple quadrupole-tandem mass spectrometry (MALDI-QqQ-MS/MS) is so far rarely used in forensics and offers an ultrafast high-throughput platform. The Quantisal™ Oral Fluid Collection Device was used for sample collection. After addition of the deuterated internal standard and a carbonate buffer (0.75 M Na2 CO3 ), oral fluid samples were liquid-liquid extracted (ButOAc/EtOAc, 1:1). As little as 1 microlitre of a mixture of this extract and the MALDI matrix (alpha-cyano-4-hydroxycinnamic acid) was spotted onto the MALDI plate and could directly be analyzed. With MALDI omitting chromatographic separation, very short analysis times of about 10 s per sample were possible. The method was developed and validated according to international guidelines including specificity, recovery, matrix effects, accuracy and precision, stabilities and limit of quantification. All validation criteria were fulfilled except for ion suppression/enhancement. Comparison with a routine liquid chromatography-tandem mass spectrometry (LC-MS/MS) method showed good agreement of the results. Applicability of the method was shown by analyzing about 250 oral fluid samples collected after controlled administration of 125 mg MDMA in a pharmacokinetic study. The whole lot of samples could be analyzed in less than 1 h, proving the ultra-high-speed of the method. PMID:25990956

  3. 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

  4. Effect of repeated ('binge') dosing of MDMA to rats housed at normal and high temperature on neurotoxic damage to cerebral 5-HT and dopamine neurones.

    PubMed

    Sanchez, Veronica; O'shea, Esther; Saadat, Kathryn S; Elliott, J Martin; Colado, M Isabel; Green, A Richard

    2004-09-01

    The technique of 'binge' dosing (several doses in one session) by recreational users of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) requires evaluation in terms of its consequences on the acute hyperthermic response and long-term neurotoxicity. We examined the neurotoxic effects of this dosing schedule on 5-HT and dopamine neurones in the rat brain. When repeated (three) doses of MDMA (2, 4 and 6 mg/kg i.p.) were given 3 h apart to rats housed at 19 degrees C, a dose-dependent acute hyperthermia and long-term loss of 5-HT was observed in several brain regions (hippocampus, cortex and striatum), with an approximate 50% loss following 3 x 4 mg/kg and 65% decrease following 3 x 6 mg/kg. No decrease in striatal dopamine content was detected. When MDMA (4 mg/kg i.p.) was given repeatedly to rats housed at 30 degrees C, a larger acute hyperthermic response than that observed in rats treated at 19 degrees C environment was seen (maximum response 2.6 +/- 0.1 degrees C versus 1.3 +/- 0.2 degrees C). A long-term cerebral 5-HT loss of approximately 65% was also detected in both the cortex and hippocampus, but no loss in striatal dopamine content occurred. These data emphasize the increased acute hyperthermic response and neurotoxicity which occurs when MDMA is administered in a hot room environment compared to normal room temperature conditions, and support the view that MDMA is a selective 5-HT neurotoxin, even when a binge dosing schedule is employed and the rats are present in a hot environment. PMID:15358986

  5. 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. PMID:24141857

  6. The Influence of Recency of Use on fMRI Response During Spatial Working Memory in Adolescent Marijuana Users

    PubMed Central

    Schweinsburg, Alecia D.; Schweinsburg, Brian C.; Medina, Krista Lisdahl; McQueeny, Tim; Brown, Sandra A.; Tapert, Susan F.

    2010-01-01

    Some neurocognitive recovery occurs within a month of abstinence from heavy marijuana use, yet functional magnetic resonance imaging (fMRI) has revealed altered activation among recent and abstinent adult users. Here, we compared fMRI response during a spatial working memory (SWM) task between adolescent marijuana users with brief and sustained durations of abstinence. Participants were 13 recent users (2 – 7 days abstinent), 13 abstinent users (27 – 60 days abstinent), and 18 non-using controls, all ages 15 – 18. Groups were similar on demographics, had no psychiatric or medical disorders, and user groups were similar on substance histories. Teens performed a 2-back SWM task during fMRI. Groups performed similarly on the task, but recent users showed greater fMRI response in medial and left superior prefrontal cortices, as well as bilateral insula. Abstinent users had increased response in the right precentral gyrus (clusters ≥1328 μl, p<.05). This cross-sectional study did not examine changes in brain response among the same participants over time. Yet results suggests that adolescents who recently used marijuana show increased brain activity in regions associated with working memory updating and inhibition, compared to users with weeks to months of abstinence. This study preliminarily suggests that (1) recent marijuana use may disrupt neural connections associated with SWM and result in compensatory brain response, and (2) sustained abstinence from marijuana may be associated with improvements in SWM response among adolescents. PMID:21053763

  7. Neighborhood Vigilance, Health Locus of Control, and Smoking Abstinence

    PubMed Central

    Reitzel, Lorraine R.; Lahoti, Sejal; Li, Yisheng; Cao, Yumei; Wetter, David W.; Waters, Andrew J.; Vidrine, Jennifer Irvin

    2012-01-01

    Objectives To examine whether health locus of control mediated relations of self-reported neighborhood vigilance and biochemically verified, continuous short-term smoking abstinence among 200 smokers enrolled in a cohort study. Methods A nonparametric bootstrapping procedure was used to assess mediation. Results Health locus of control-chance mediated relations between neighborhood vigilance and smoking abstinence in analyses adjusted for sociodemographics and tobacco dependence (p < .05). Greater vigilance was associated with greater attributions that health was affected by chance, which was associated with a lower likelihood of smoking abstinence. Conclusions Results suggest that neighborhood perceptions influence residents’ attributions for health outcomes, which can affect smoking abstinence. PMID:23985180

  8. Active and passive MDMA ('ecstasy') intake induces differential transcriptional changes in the mouse brain.

    PubMed

    Fernàndez-Castillo, N; Orejarena, M J; Ribasés, M; Blanco, E; Casas, M; Robledo, P; Maldonado, R; Cormand, B

    2012-02-01

    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is a recreational drug widely used by adolescents and young adults. Although its rewarding effects are well established, there is controversy on its addictive potential. We aimed to compare the consequences of active and passive MDMA administration on gene expression in the mouse brain since all previous studies were based on passive MDMA administration. We used a yoked-control operant intravenous self-administration paradigm combined with microarray technology. Transcriptomic profiles of ventral striatum, frontal cortex, dorsal raphe nucleus and hippocampus were analysed in mice divided in contingent MDMA, yoked MDMA and yoked saline groups, and several changes were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The comparison of contingent MDMA and yoked MDMA vs. yoked saline mice allowed the identification of differential expression in several genes, most of them with immunological and inflammatory functions, but others being involved in neuroadaptation. In the comparison of contingent MDMA vs. yoked MDMA administration, hippocampus and the dorsal raphe nucleus showed statistically significant changes. The altered expression of several genes involved in neuroadaptative changes and synapse function, which may be related to learning self-administration behaviour, could be validated in these two brain structures. In conclusion, our study shows a strong effect of MDMA administration on the expression of immunological and inflammatory genes in all the four brain regions studied. In addition, experiments on MDMA self-administration suggest that the dorsal raphe nucleus and hippocampus may be involved in active MDMA-seeking behaviour, and show specific alterations on gene expression that support the addictive potential of this drug. PMID:21951708

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

    PubMed

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

    2009-11-01

    Serotonin (5-HT) release is the primary pharmacological mechanism of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') action in the primate brain. Dopamine release and direct stimulation of dopamine D2 and serotonin 5-HT2A receptors also contributes to the overall action of MDMA. The role of 5-HT1A receptors in the human psychopharmacology of MDMA, however, has not yet been elucidated. In order to reveal the consequences of manipulation at the 5-HT1A receptor system on cognitive and subjective effects of MDMA, a receptor blocking study using the mixed beta-adrenoreceptor blocker/5-HT1A antagonist pindolol was performed. Using a double-blind, placebo-controlled within-subject design, 15 healthy male subjects were examined under placebo (PL), 20 mg pindolol (PIN), MDMA (1.6 mg/kg b.wt.), MDMA following pre-treatment with pindolol (PIN-MDMA). Tasks from the Cambridge Neuropsychological Test Automated Battery were used for the assessment of cognitive performance. Psychometric questionnaires were applied to measure effects of treatment on core dimensions of Altered States of Consciousness, mood and state anxiety. Compared with PL, MDMA significantly impaired sustained attention and visual-spatial memory, but did not affect executive functions. Pre-treatment with PIN did not significantly alter MDMA-induced impairment of cognitive performance and only exerted a minor modulating effect on two psychometric scales affected by MDMA treatment ('positive derealization' and 'dreaminess'). Our findings suggest that MDMA differentially affects higher cognitive functions, but does not support the hypothesis from animal studies, that some of the MDMA effects are causally mediated through action at the 5-HT1A receptor system. PMID:18635693

  10. Is Abstinence Education Theory Based? The Underlying Logic of Abstinence Education Programs in Texas

    ERIC Educational Resources Information Center

    Goodson, Patricia; Pruitt, B. E.; Suther, Sandy; Wilson, Kelly; Buhi, Eric

    2006-01-01

    Authors examined the logic (or the implicit theory) underlying 16 abstinence-only-until-marriage programs in Texas (50% of all programs funded under the federal welfare reform legislation during 2001 and 2002). Defined as a set of propositions regarding the relationship between program activities and their intended outcomes, program staff's…

  11. 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. PMID:25863258

  12. MDMA pretreatment leads to mild chronic unpredictable stress-induced impairments in spatial learning.

    PubMed

    Cunningham, Jacobi I; Raudensky, Jamie; Tonkiss, John; Yamamoto, Bryan K

    2009-10-01

    3,4-Methylenedioxymethamphetamine (MDMA) is a drug of abuse worldwide and a selective serotonin (5-HT) neurotoxin. An important factor in the risk of drug abuse and relapse is stress. Although multiple parallels exist between MDMA abuse and stress, including effects on 5-HTergic neurotransmission, few studies have investigated the consequences of combined exposure to MDMA and chronic stress. Therefore, rats were pretreated with MDMA and exposed 7 days later to 10 days of mild chronic unpredictable stress (CUS). MDMA pretreatment was hypothesized to enhance the effects of CUS leading to enhanced 5-HT transporter (SERT) depletion in the hippocampus and increased anxiety and cognitive impairment. Whereas MDMA alone increased anxiety-like behavior on the elevated plus maze, CUS alone or in combination with MDMA pretreatment did not increase anxiety-like behavior. In contrast, MDMA pretreatment led to CUS-induced learning impairment in the Morris water maze but not an enhanced depletion of hippocampal SERT protein. These results show that prior exposure to MDMA leads to stress-induced impairments in learning behavior that is not otherwise observed with stress alone and appear unrelated to an enhanced depletion of SERT. PMID:19824774

  13. 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

  14. 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

  15. Methamphetamine and MDMA (ecstasy) neurotoxicity: 'of mice and men'.

    PubMed

    Itzhak, Yossef; Achat-Mendes, Cindy

    2004-05-01

    Methamphetamine (METH) and 3,4-meythylenedioxymethamphetamine (MDMA; 'ecstasy') are currently major drugs of abuse. One of the major concerns of amphetamines abuse is their potential neurotoxic effect on dopaminergic and serotonergic neurons. Although data from human studies are somewhat limited, compelling evidence suggests that these drugs cause neurotoxicity in rodents and primates. Recent studies in transgenic and knockout mice identified the role of dopamine transporters, nitric oxide, apoptotic proteins, and inflammatory cytokines in amphetamines neurotoxicity. Further research into the mechanisms underlying the dopaminergic and serotonergic neurotoxicity and the behavioral corollaries of these neuronal insults could facilitate our understanding of the consequences of human abuse of METH and MDMA on cognition, drug-seeking behavior, extinction and relapse. PMID:15370888

  16. Feeling Abstinent? Feeling Comprehensive? Touching the Affects of Sexuality Curricula

    ERIC Educational Resources Information Center

    Lesko, Nancy

    2010-01-01

    This interpretive study draws on interdisciplinary scholarship on affect and knowledge to ask: toward what feelings do abstinence-only and comprehensive sexuality education curricula direct us? A methodology that is attuned to double exposures is discussed, and one abstinence-only sexuality education curriculum and one comprehensive sexuality…

  17. Evaluation of an Abstinence Based Intervention for Middle School Students

    ERIC Educational Resources Information Center

    Rue, Lisa; Chandran, Raj; Pannu, Aman; Bruce, David; Singh, Rana; Traxler, Karen

    2012-01-01

    Outcomes associated with an abstinence education intervention were evaluated using a single group design with a 12-month longitudinal follow-up. The intervention group of adolescents ages 12-14 years (N = 427) were enrolled in an 11.5-hour abstinence education intervention offered during the school day. Significant differences were found in the…

  18. Should We Be Teaching Sex Education or Sexual Abstinence?

    ERIC Educational Resources Information Center

    Stover, Del

    2007-01-01

    In this article, the author examines the controversial issue whether to teach sex education or sexual abstinence. Sex education has always been fraught with controversy. The discord in Westbrook, Maine, school district is noteworthy because of the vocal support for an abstinence-only curriculum approach to sex education that has reshaped the…

  19. Effectiveness of Abstinence-Only Intervention in Middle School Teens

    ERIC Educational Resources Information Center

    Borawski, Elaine A.; Trapl, Erika S.; Lovegreen, Loren D.; Colabianchi, Natalie; Block, Tonya

    2005-01-01

    Objectives: To examine effectiveness of abstinence-until-marriage curriculum on knowledge, beliefs, efficacy, intentions, and behavior. Methods: Nonrandomized control trial involving 2069 middle school students with a 5-month follow-up. Results: Intervention students reported increases in knowledge and abstinence beliefs, but decreases in…

  20. Implementing the Abstinence Education Provision of the Welfare Reform Legislation.

    ERIC Educational Resources Information Center

    Haskins, Ron; Bevan, Carol Statuto

    As part of its 1996 welfare reform bill, the U.S. Congress enacted a $50 million per year program to fund abstinence education. The welfare reform law addresses the problem of births to single adolescents by enforcing child support payments, giving states financial incentives to reduce nonmarital births, and creating the abstinence education…

  1. Citizenship Lessons in Abstinence-Only Sexuality Education

    ERIC Educational Resources Information Center

    Fields, Jessica; Hirschman, Celeste

    2007-01-01

    We examine abstinence-only-until-marriage education as part of a broad effort to reassert the primacy of conventional (hetero) sexual norms. While all sexuality education offers students lessons in "good sexual citizenship," abstinence-only-until-marriage education reserves the rights and responsibilities of membership and belonging for those who…

  2. Defining Sex and Abstinence: Dialogue Is the Key

    ERIC Educational Resources Information Center

    Hamill, Shelley D.; Chepko, Stevie

    2005-01-01

    When does abstinence end and sexual activity begin? In previous generations, the continuum of sexual activity was well-defined in the old baseball analogy. Teens, parents, and teachers knew what going to first, second, or third base involved. For the current generation of young people, sex and abstinence are not so well-defined. As parents and…

  3. Factors Affecting Long-Term Abstinence from Substances Use

    ERIC Educational Resources Information Center

    Elsheikh, Salah Elgaily

    2008-01-01

    Objective: The purpose of this study is to explore the attitudes of abstainers from drug use that relate to the factors leading to long-term abstinence. Materials and Methods: Cross-sectional study was carried out in Al-Amal Hospital to examine, which attitudes of abstainers related to long-term abstinence. A random survey was conducted on 62…

  4. Cocaine Abstinence and Reduced Use Associated With Lowered Marker of Endothelial Dysfunction in African Americans: A Preliminary Study

    PubMed Central

    Lai, Hong; Stitzer, Maxine; Treisman, Glenn; Moore, Richard; Brinker, Jeffrey; Gerstenblith, Gary; Kickler, Thomas S.; Li, Ji; Chen, Shaoguang; Fishman, Elliot; Lai, Shenghan

    2016-01-01

    Objectives Clinical and epidemiological evidence suggests that cocaine use is associated with an increased risk of premature atherosclerosis. The objectives of this study were to explore (1) whether cocaine abstinence is associated with a reduced marker of endothelial dysfunction, (2) whether cocaine abstinence is associated with a slower coronary plaque progression, and (3) whether reduction in cocaine use is associated with a reduced marker of endothelial dysfunction in African American chronic cocaine users with contrast-enhanced coronary CT angiography-confirmed less than 50% coronary stenosis. Methods Between March and June 2014, a total of 57 African American cocaine users with contrast-enhanced CT angiography-confirmed less than 50% coronary stenosis in Baltimore, Maryland, were enrolled in a 6-month follow-up study to investigate whether cocaine abstinence or reduction in cocaine use is associated with decreased endothelin-1 (ET-1) levels and coronary plaque progression at the 6-month follow-up. A voucher-based incentive approach was used to systematically reinforce cocaine abstinence, and urine benzoylecgonine test was implemented to confirm cocaine use. Results Among the 57 participants, 44 were HIV-infected. The median of duration of cocaine use was 18 (interquartile range, 7–30) years. According to generalized estimating equation analyses, both cocaine abstinence and reduction in cocaine use in the 6 months were independently associated with decreased ET-1. The incidence of coronary plaque progression was 7.4/100 person-years and 23.1/100 person-years in those who were totally abstinent from cocaine and those who continued to use cocaine, respectively. However, the difference in the incidence between these 2 groups was not significant (exact P = 0.30). Conclusions The findings of this study revealed a possible association of cocaine abstinence/reduction with lowered ET levels, which suggests that such changes in cocaine use might be beneficial for

  5. 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

  6. Intact inhibitory control processes in abstinent drug abusers (II): a high-density electrical mapping study in former cocaine and heroin addicts.

    PubMed

    Morie, Kristen P; Garavan, Hugh; Bell, Ryan P; De Sanctis, Pierfilippo; Krakowski, Menachem I; Foxe, John J

    2014-07-01

    Response inhibition deficits are well-documented in drug users, and are related to the impulsive tendencies characteristic of the addictive phenotype. Addicts also show significant motivational issues that may accentuate these inhibitory deficits. We investigated the extent to which these inhibitory deficits are present in abstinence. Salience of the task stimuli was also manipulated on the premise that emotionally-valenced inputs might impact inhibitory efficacy by overcoming the blunted responses to everyday environmental inputs characteristic of this population. Participants performed response inhibition tasks consisting of both neutral and emotionally valenced stimuli while high-density event-related potentials (ERPs) were recorded. Electrophysiological responses (N2/P3 components) to successful inhibitions in abstinent abusers (N = 20) and non-using participants (N = 21) were compared. In contrast to previous work in current users, our abstinent cohort showed no detectable behavioral or electrophysiological differences in their inhibitory responses, and no differences on self-reports of impulsivity, despite their long histories of chronic use (mean = 10.3 years). The current findings are consistent with a recovery of inhibitory control processes as a function of abstinence. Abstinent former users, however, did show a reduced modulation, relative to controls, of their ERPs to valenced input while performing successful inhibitions, although contrary to our hypothesis, the use of valenced inputs had no impact on inhibitory performance. Reduced ERP modulation to emotionally valenced inputs may have implications for relapse in emotional contexts outside the treatment center. PMID:23507565

  7. 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. PMID:24491919

  8. The Role of The A2A Receptor in Cell Apoptosis Caused by MDMA

    PubMed Central

    Soleimani, Mansooreh; Katebi, Majid; Alizadeh, Akram; Mohammadzadeh, Farzaneh; Mehdizadeh, Mehdi

    2012-01-01

    Objective: Ecstasy, also known as 3, 4-methylenedioxymethamphetamine (MDMA), is a psychoactive recreational hallucinogenic substance and a major worldwide recreational drug. There are neurotoxic effects observed in laboratory animals and humans following MDMA use. MDMA causes apoptosis in neurons of the central nervous system (CNS). Withdrawal signs are attenuated by treatment with the adenosine receptor (A2A receptor). This study reports the effects of glutamyl cysteine synthetase (GCS), as an A2A receptor agonist, and succinylcholine (SCH), as an A2A receptor antagonist, on Sprague Dawley rats, both in the presence and absence of MDMA. Materials and Methods: In this experimental study, we used seven groups of Sprague Dawley rats (200-250 g each). Each group was treated with daily intraperitoneal (IP) injections for a period of one week, as follows: i. MDMA (10 mg/kg); ii. GCS (0.3 mg/kg); iii. SCH (0.3 mg/kg); iv. GCS + SCH (0.3 mg/kg each); v. MDMA (10 mg/kg) + GCS (0.3 mg/kg); vi. MDMA (10 mg/kg) + SCH (0.3 mg/kg); and vi. normal saline (1 cc/kg) as the sham group. Bax (apoptotic protein) and Bcl-2 (anti-apoptotic protein) expressions were evaluated by striatum using RT-PCR and Western blot analysis. Results: There was a significant increase in Bax protein expression in the MDMA+SCH group and a significant decrease in Bcl-2 protein expression in the MDMA+SCH group (p<0.05). Conclusion: A2A receptors have a role in the apoptotic effects of MDMA via the Bax and Bcl-2 pathways. An agonist of this receptor (GCS) decreases the cytotoxcity of MDMA, while the antagonist of this receptor (SCH) increases its cytotoxcity. PMID:23508639

  9. A Cautionary Tale About Conducting Research on Abstinence Education: How Do State Abstinence Coordinators Define "Sexual Activity?"

    ERIC Educational Resources Information Center

    Bailey, William; Young, Michael; Knickerbocker, Cliff; Doan, Tam

    2002-01-01

    Investigated how state coordinators of abstinence education programs defined "sexual activity." Researchers surveyed Title V abstinence education coordinators from the 50 states, the District of Columbia, and three territories. Of the 17 coordinators providing at least partial responses, none reported having a definition of sexual activity. The…

  10. MDMA administration to pregnant Sprague-Dawley rats results in its passage to the fetal compartment.

    PubMed

    Campbell, Nicholas G; Koprich, James B; Kanaan, Nicholas M; Lipton, Jack W

    2006-01-01

    Recent investigations have demonstrated that prenatal 3,4-methylenedeoxymethamphetamine (MDMA; ecstasy) exposure in rats results in significant and persistent changes in the developing brain. However, no published pharmacokinetic studies exist demonstrating that MDMA administered during pregnancy passes to the fetal compartment. This leaves open the question whether MDMA is directly acting on the fetal brain to produce the observed changes in previous studies, or whether such effects are an indirect result of MDMA administration to the pregnant dam. Therefore, pregnant rats were administered a single dose of MDMA (15 mg/kg, subcutaneous) at embryonic day 14 (E14) and the levels of MDMA and its metabolite 3,4-methylenedioxyamphetamine (MDA) were quantified in maternal plasma, amniotic fluid, and fetal brain over 8 h by HPLC. The time course of MDMA and MDA metabolism was reliable and reproducible in all tissues. There was a strong correlation between fetal amniotic fluid and fetal brain suggesting that amniotic fluid could be used to reliably estimate fetal brain levels without directly utilizing fetal brain tissue. These data also provide a framework for subsequent in vitro cell culture studies using biologically relevant MDMA doses. PMID:16905291

  11. 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

  12. 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. PMID:25818246

  13. Neonatal Abstinence Syndrome: Essentials for the Practitioner

    PubMed Central

    Robinson, Christine A.

    2014-01-01

    The incidence of neonatal abstinence syndrome (NAS) has increased dramatically during the past 15 years, likely due to an increase in antepartum maternal opiate use. Optimal care of these patients is still controversial because of the available published literature lacking sufficient sample size, placebo control, and comparative pharmacologic trials. Primary treatment for NAS consists of opioid replacement therapy with either morphine or methadone. Paregoric and tincture of opium have been abandoned because of relative safety concerns. Buprenorphine is emerging as a treatment option with promising initial experience. Adjunctive agents should be considered for infants failing treatment with opioid monotherapy. Traditionally, phenobarbital has been used as adjunctive therapy; however, results of clonidine as adjunctive therapy for NAS appear to be beneficial. Future directions for research in NAS should include validating a simplified scoring tool, conducting comparative studies, exploring home management options, and optimizing management through pharmacogenomics. PMID:25309144

  14. Neonatal abstinence syndrome: essentials for the practitioner.

    PubMed

    Siu, Anita; Robinson, Christine A

    2014-07-01

    The incidence of neonatal abstinence syndrome (NAS) has increased dramatically during the past 15 years, likely due to an increase in antepartum maternal opiate use. Optimal care of these patients is still controversial because of the available published literature lacking sufficient sample size, placebo control, and comparative pharmacologic trials. Primary treatment for NAS consists of opioid replacement therapy with either morphine or methadone. Paregoric and tincture of opium have been abandoned because of relative safety concerns. Buprenorphine is emerging as a treatment option with promising initial experience. Adjunctive agents should be considered for infants failing treatment with opioid monotherapy. Traditionally, phenobarbital has been used as adjunctive therapy; however, results of clonidine as adjunctive therapy for NAS appear to be beneficial. Future directions for research in NAS should include validating a simplified scoring tool, conducting comparative studies, exploring home management options, and optimizing management through pharmacogenomics. PMID:25309144

  15. Methamphetamine Dependence and Neuropsychological Functioning: Evaluating Change During Early Abstinence*

    PubMed Central

    Simon, Sara L.; Dean, Andy C.; Cordova, Xochitl; Monterosso, John R.; London, Edythe D.

    2010-01-01

    Objective: The purpose of this work was to assess neuropsychological functioning of individuals in early abstinence from methamphetamine dependence and to test for cognitive change over the first month of abstinence. Method: Methamphetamine-dependent subjects in very early abstinence from methamphetamine (4–9 days; n = 27) were compared with healthy comparison subjects (n = 28) on a test battery that evaluated five cognitive domains (attention/processing speed, learning/memory, working memory, timed executive functioning, and untimed executive functioning). A subsample of the methamphetamine-dependent subjects (n = 18), who maintained abstinence for 1 month, as well as a subsample of the comparison subjects (n = 21), were retested. Results: At the first assessment, the methamphetamine-dependent subjects showed significantly worse performance than the comparison group on a test of processing speed; they also performed 0.31 SDs worse than the control group on a global battery composite score (p < .05). After a month of abstinence, methamphetamine-dependent subjects demonstrated slightly more cognitive improvement than healthy control subjects on the entire cognitive battery, but this difference did not approach statistical significance (p = .33). Conclusions: Our findings suggest that methamphetamine-dependent subjects do not show considerable cognitive gains in the first month of abstinence. A greater length of abstinence may be needed for cognitive improvement. PMID:20409426

  16. Investigating Group Contingencies to Promote Brief Abstinence from Cigarette Smoking

    PubMed Central

    Meredith, Steven E.; Dallery, Jesse

    2013-01-01

    In contingency management (CM), monetary incentives are contingent on evidence of drug abstinence. Typically, incentives (e.g., “vouchers” exchangeable for goods or services) are contingent on individual performance. We programmed vouchers contingent on group performance to investigate whether these contingencies would promote brief abstinence from cigarette smoking. Thirty-two participants were divided into small teams (n = 3 per team). During three 5-day within-subject experimental conditions, participants submitted video recordings of breath carbon monoxide (CO) measures twice daily via Mōtiv8 Systems™, an Internet-based remote monitoring application. During the interdependent contingency condition, participants earned vouchers each time they and their teammates submitted breath CO samples indicative of abstinence (i.e., negative samples). During the independent contingency condition, participants earned vouchers each time they submitted negative samples, regardless of their teammates' performance. During the no vouchers condition, no monetary incentives were contingent on abstinence. In addition, half of the participants (n = 16) could communicate with their teammates through an online peer support forum. Although forum access did not appear to promote smoking abstinence, monetary incentives did promote brief abstinence. Significantly more negative samples were submitted when vouchers were contingent on individual performance (56%) or team performance (53%) relative to when no vouchers were available (35%; F = 6.9, p = 0.002). The results show that interdependent contingencies can promote brief abstinence from cigarette smoking. Moreover, the results suggest that these contingencies may help lower treatment costs and promote social support. PMID:23421358

  17. ESTIMATES OF PRENATAL ABSTINENCE FROM ALCOHOL: A MATTER OF PERSPECTIVE

    PubMed Central

    Chang, Grace; McNamara, Tay K.; Wilkins-Haug, Louise; Orav, E. John

    2007-01-01

    Abstinence from alcohol has been recommended for both pregnant and pre-conceptional women. The purpose of this study is to compare self and partner reports of abstinence from alcohol in a sample of 253 pregnant women who were T-ACE (Tolerance, Annoy, Cut-down, Eye-opener) alcohol screen positive. Dyads’ reports of the women’s abstinence from alcohol before, during, and after pregnancy were compared. Based on their own self-report, less than 20% of the pregnant women were abstinent in their first trimester and about half were abstinent for the rest of their pregnancy. Partners significantly over-estimated the women’s abstinence from alcohol at all points except in the post-partum period when the dyad had the highest rate of agreement (85.4%). Reasons for the discrepancies in the self and partner reports of prenatal abstinence, and how partners might influence such behavior remain speculative, but identify areas for future research and prevention. PMID:17187936

  18. 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. PMID:23457892

  19. 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

  20. MDMA toxicity and pathological consequences: a review about experimental data and autopsy findings.

    PubMed

    Turillazzi, Emanuela; Riezzo, Irene; Neri, Margherita; Bello, Stefania; Fineschi, Vittorio

    2010-08-01

    Studies conducted in humans or in animals explored the presence, nature and potential causes of 3,4-methylenedioxymethamphetamine (MDMA) toxicity. According to literature, there are four principal types of such serious toxicity: hepatic, cardiovascular, cerebral and hyperpyrexic. The molecular mechanisms involved in the genesis of these toxic effects are not yet fully clarified, but the oxidative stress, excitotoxicity, and mitochondrial dysfunction appear to be causal events that converge to mediate MDMA-induced toxicity. Studies conducted on animals demonstrated that the acute administration of MDMA elicits cardiovascular responses that are similar to those elicited by d-amphetamine, and that these responses appear to involve catecholaminergic and non-catecholaminergic-dependent mechanisms. Although there is undeniable evidence of MDMA-induced cardiac toxicity, the mechanism responsible remains to be clarified. While many reports both in humans and in animals have demonstrated MDMA-induced liver damage, the underlying mechanism accounting for hepatic toxicity is poorly understood. Various mechanisms may contribute to MDMA-induced liver toxicity, including the metabolism of MDMA, the increased efflux of neurotransmitters, the oxidation of biogenic amines, and hyperthermia. The molecular mechanisms involved in the genesis of these toxic effects are not yet fully clarified, but the oxidative stress, excitotoxicity, and mitochondrial dysfunction appear to be causal events that converge to mediate MDMA-induced neurotoxicity, as measured by loss of various markers of dopaminergic and serotonergic terminals. The evidence is overwhelming that MDMA produces acute and long-lasting toxic anatomic effects in animals and humans. Anatomical and functional MDMA consequences must be better understood. PMID:20420577

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

    PubMed Central

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

    2014-01-01

    3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug that can cause severe and even fatal adverse effects. However, interest remains for its possible clinical applications in posttraumatic stress disorder and anxiety treatment. Preclinical studies to determine MDMA’s safety are needed. We evaluated MDMA’s pharmacokinetics and metabolism in male rats receiving 2.5, 5, and 10 mg/kg s.c. MDMA, and the associated pharmacodynamic consequences. Blood was collected via jugular catheter at 0, 0.5, 1, 2, 4, 6, 8, 16, and 24 hours, with simultaneous serotonin (5-HT) behavioral syndrome and core temperature monitoring. Plasma specimens were analyzed for MDMA and the metabolites (±)-3,4-dihydroxymethamphetamine (HHMA), (±)-4-hydroxy-3-methoxymethamphetamine (HMMA), and (±)-3,4-methylenedioxyamphetamine (MDA) by liquid chromatography–tandem mass spectrometry. After 2.5 mg/kg MDMA, mean MDMA Cmax was 164 ± 47.1 ng/ml, HHMA and HMMA were major metabolites, and <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. PMID:24141857

  2. One day access to a running wheel reduces self-administration of d-methamphetamine, MDMA and Methylone

    PubMed Central

    Aarde, Shawn M.; Miller, Michelle L.; Creehan, Kevin M.; Vandewater, Sophia A.; Taffe, Michael A.

    2015-01-01

    Background Exercise influences drug craving and consumption in humans and drug self-administration in laboratory animals, but the effects can be variable. Improved understanding of how exercise affects drug intake or craving would enhance applications of exercise programs to human drug users attempting cessation. Methods Rats were trained in the intravenous self-administration (IVSA) of d-methamphetamine (METH; 0.05 mg/kg/inf), 3,4-methylenedioxymethamphetamine (MDMA; 0.5 mg/kg/inf) or methylone (0.5 mg/kg/inf). Once IVSA was established, the effect of ~22 hrs of wheel access in the home cage on subsequent drug taking was assessed in a two cohort crossover design. Results Provision of home cage wheel access during the day prior to IVSA sessions significantly decreased the self-administration of METH, MDMA and methylone. At the individual level, there was no correlation between the amount a rat used the wheel and the size of the individual’s decrease in drug intake. Conclusions Wheel access can reduce self-administration of a variety of psychomotor stimulants. It does so immediately, i.e., without a need for weeks of exercise prior to drug access. This study therefore indicates that future mechanistic investigations should focus on acute effects of exercise. In sum, the results predict that exercise programs can be used to decrease stimulant drug use in individuals even with no exercise history and an established drug taking pattern. PMID:25863714

  3. 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

  4. Exposure to and Views of Information about Sexual Abstinence among Older Teens

    ERIC Educational Resources Information Center

    Jones, Rachel K.; Biddlecom, Ann E.

    2011-01-01

    There is scant research of adolescents' understanding of abstinence. We conducted interviews with a sample of 58 teens to find out their exposure to abstinence information from a range of sources. Most teens had received abstinence information or messages from school, family members, and friends. For many teens, information about abstinence, or…

  5. Hold the Sex, Please: The Discursive Politics between National and Local Abstinence Education Providers

    ERIC Educational Resources Information Center

    Hess, Amie

    2010-01-01

    There are many assumptions made about the beliefs behind abstinence-only until marriage (AOUM) sex education, yet comparatively little research examining the views of abstinence education providers. Drawing on in-depth interviews with 21 abstinence grantees throughout New York State, I examine how individuals working in abstinence organizations…

  6. Blue-yellow colour vision impairment and cognitive deficits in occasional and dependent stimulant users.

    PubMed

    Hulka, Lea M; Wagner, Michael; Preller, Katrin H; Jenni, Daniela; Quednow, Boris B

    2013-04-01

    Specific blue-yellow colour vision impairment has been reported in dependent cocaine users and it was postulated that drug-induced changes in retinal dopamine neurotransmission are responsible. However, it is unclear whether these changes are confined to chronic cocaine users, whether they are specific for dopaminergic stimulants such as cocaine and amphetamine and whether they are related to cognitive functions such as working memory, encoding and consolidation. In 47 occasional and 29 dependent cocaine users, 23 MDMA (commonly known as 'ecstasy') users and 47 stimulant-naive controls, colour vision discrimination was measured with the Lanthony Desaturated Panel D-15 Test and memory performance with the Auditory Verbal Learning Test. Both occasional and dependent cocaine users showed higher colour confusion indices than controls. Users of the serotonergic stimulant MDMA (26%), occasional (30%) and dependent cocaine users (34%) exhibited more frequent blue-yellow colour vision disorders compared to controls (9%). Inferior performance of MDMA users was caused by a subgroup with high amphetamine co-use (55%), while MDMA use alone was not associated with decreased blue-yellow discrimination (0%). Cognitive performance was worse in cocaine users with colour vision disorder compared to users and controls with intact colour vision and both colour vision impairment and cognitive deficits were related to cocaine use. Occasional cocaine and amphetamine use might induce blue-yellow colour vision impairment, whereas the serotonergic stimulant MDMA does not impair colour vision. The association between colour vision impairment and cognitive deficits in cocaine users may reflect that retinal and cerebral dopamine alterations are linked to a certain degree. PMID:22704223

  7. 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

  8. 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. PMID:21074589

  9. 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

  10. 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

  11. Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction, and organ damage.

    PubMed

    Song, Byoung-Joon; Moon, Kwan-Hoon; Upreti, Vijay V; Eddington, Natalie D; Lee, Insong J

    2010-08-01

    Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage. PMID:20420575

  12. Altered Functional Connectivity Strength in Abstinent Chronic Cocaine Smokers Compared to Healthy Controls.

    PubMed

    Ray, Suchismita; Gohel, Suril; Biswal, Bharat B

    2015-10-01

    Past research involving cocaine and resting-state functional connectivity (RSFC) has shown altered functional connectivity within the frontal and between the frontal and other cortical and subcortical brain regions in chronic users of cocaine. However, there have been discrepancies in literature regarding the relationship between RSFC between brain regions and cocaine use behavior. This study explored the RSFC between brain regions in cocaine smokers abstinent from cocaine use for 72 h and healthy controls. Also, the relationship between RSFC between brain regions and various cocaine use measures (cocaine use duration; frequency, and money spent on cocaine/week) was examined. Twenty chronic cocaine users and 17 controls completed a resting-state scan and an anatomical MPRAGE scan. Group independent component analysis performed on functional magnetic resonance imaging data identified 13 ICs pertaining to distinct resting-state networks, and group-level differences were examined. To examine inter-network functional connectivity between brain regions, these 13 ICs were divided into 61 distinct regions of interest (ROIs). Correlations were calculated between 61 ROI time series. For the ROI pairs that significantly differed from controls in connectivity strength, correlations were computed between connectivity strength and cocaine use measures. Results showed an enhanced RSFC within the sensory motor cortex and the left frontal-parietal network in cocaine users than controls. An increased inter-network RSFC between frontal-temporal and frontal-parietal brain regions, and a decreased RSFC between parietal-parietal, occipital-limbic, occipital-occipital, and occipital-parietal brain regions was found in cocaine users. This study demonstrated that intra-network connectivity strength of sensory motor cortex was negatively correlated with years of cocaine use. Inter-network connectivity strength between occipital-limbic brain regions was positively correlated with years of

  13. Intolerance for Smoking Abstinence Questionnaire: Psychometric Properties and Relationship to Tobacco Dependence and Abstinence

    PubMed Central

    Sirota, Alan D.; Rohsenow, Damaris J.; MacKinnon, Selene V.; Martin, Rosemarie A.; Eaton, Cheryl A.; Kaplan, Gary B.; Monti, Peter M.; Tidey, Jennifer W.; Swift, Robert M.

    2013-01-01

    While smokers’ ability to tolerate emotional or physical distress has been associated with length of smoking cessation, there is no measure of ability to tolerate smoking abstinence discomfort specifically, which may be more heuristic than a measure of tolerance of general emotional stress or physical discomfort. Methods Questionnaires completed by 300 smokers assessed inability to tolerate smoking abstinence discomfort (IDQ-S), general physical discomfort (IDQ-P), and general emotional discomfort (IDQ-E), so that shared variance among these measures could be assessed. Results The IDQ-S has three reliable components: Withdrawal Intolerance, Lack of Cognitive Coping, and Pain Intolerance. The 14-item IDQ-P and 9-item IDQ-E each consist of one reliable component. Intercorrelations suggest only modest shared variance. Support for construct and discriminant validity was seen. Two scales of the IDQ-S showed excellent convergent validity, correlating with smoking use, dependence, motivation, and length of past smoking cessation, while IDQ-P and IDQ-E correlated with few indices of use or dependence and not with smoking cessation. Conclusions The final 17-item IDQ-S with two scales is reliable and valid, and more heuristic than measures of general physical or emotional discomfort intolerance as a correlate of motivation and past success with smoking cessation. PMID:20381260

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

    PubMed

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

    2009-05-01

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

  15. 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. PMID:26251327

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

    PubMed Central

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

    2010-01-01

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

  17. Tobacco withdrawal symptoms mediate motivation to reinstate smoking during abstinence.

    PubMed

    Aguirre, Claudia G; Madrid, Jillian; Leventhal, Adam M

    2015-08-01

    Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and 3 unique withdrawal components (i.e., low positive affect, negative affect, and urge to smoke) mediated the effect of smoking abstinence on motivation to reinstate smoking. Smokers (≥10 cigarettes per day; N = 286) attended 2 counterbalanced sessions at which abstinence duration was differentially manipulated (1 hr vs. 17 hr). At both sessions, participants reported current withdrawal symptoms and subsequently completed a task in which they were monetarily rewarded proportional to the length of time they delayed initiating smoking, with shorter latency reflecting stronger motivation to reinstate smoking. Abstinence reduced latency to smoking initiation and positive affect and increased composite withdrawal symptom level, urge, and negative affect. Abstinence-induced reductions in latency to initiating smoking were mediated by each withdrawal component, with stronger effects operating through urge. Combined analyses suggested that urge, negative affect, and low positive affect operate through empirically unique mediational pathways. Secondary analyses suggested similar effects on smoking quantity, few differences among specific urge and affect subtypes, and that dependence amplifies some abstinence effects. This study provides the first experimental evidence that within-person variation in abstinence impacts motivation to reinstate drug use through withdrawal. Urge, negative affect, and low positive affect may reflect unique withdrawal-mediated mechanisms underlying tobacco addiction. PMID:25961814

  18. Sex Differences in Time Perception During Smoking Abstinence

    PubMed Central

    Kable, Joseph W.

    2015-01-01

    Introduction: Nicotine withdrawal leads to impulsive decision-making, which reflects a preference for smaller, immediate rewards and often prompts a relapse to smoking. The mechanism by which nicotine withdrawal leads to impulsive decision-making is not well known. An essential dimension of decision-making is time perception. Impulsive decisions reflect intolerance of temporal delays and the perception that time is passing more slowly. Sex may be an important factor in impulsive decision-making and time perception, but no studies have investigated whether sex moderates the effects of nicotine withdrawal on impulsive decision-making and time perception. Methods: Thirty-three (12 female) adult smokers completed 2 laboratory sessions: following 24-hr abstinence and once smoking-as-usual (order counterbalanced, abstinence biochemically verified). Participants completed 2 time perception tasks, a decision-making task, and self-report measures of craving, withdrawal, and mood. Results: During time reproduction, males overestimated time during abstinence compared to smoking, whereas there was no session effect for females. On the time discrimination task, smokers were less accurate during abstinence, and this effect tended to be stronger among females. In general, males had higher discounting rates compared with females, but there was no effect of abstinence. Conclusions: The current data suggest that the effect of abstinence on time perception may be stronger in males and that males generally exhibit steeper delay discounting rates. Time perception may be an important mechanism in smoking abstinence. Our future work will investigate the role of time perception in smoking relapse and whether this is moderated by sex. PMID:25762755

  19. Food addiction: detox and abstinence reinterpreted?

    PubMed

    Shriner, Richard L

    2013-10-01

    The senior patient and/or the geriatrician are confronted with a confusing literature describing how patients interested in combating metabolic syndrome, diabesity (diabetes plus obesity) or simple obesity might best proceed. The present paper gives a brief outline of the basic disease processes that underlie metabolic pro-inflammation, including how one might go about devising the most potent and practical detoxification from such metabolic compromise. The role that dietary restriction plays in pro-inflammatory detoxification (detox), including how a modified fast (selective food abstinence) is incorporated into this process, is developed. The unique aspects of geriatric bariatric medicine are elucidated, including the concepts of sarcopenia and the obesity paradox. Important caveats involving the senior seeking weight loss are offered. By the end of the paper, the reader will have a greater appreciation for the challenges and opportunities that lie ahead for geriatric patients who wish to overcome food addiction and reverse pro-inflammatory states of ill-heath. This includes the toxic metabolic processes that create obesity complicated by type 2 diabetes mellitus (T2DM) which collectively we call diabesity. In that regard, diabesity is often the central pathology that leads to the evolution of the metabolic syndrome. The paper also affords the reader a solid review of the neurometabolic processes that effectuate anorexigenic versus orexigenic inputs to obesity that drive food addiction. We argue that these processes lead to either weight gain or weight loss by a tripartite system involving metabolic, addictive and relational levels of organismal functioning. Recalibrating the way we negotiate these three levels of daily functioning often determines success or failure in terms of overcoming metabolic syndrome and food addiction. PMID:23267844

  20. Abnormal gray matter volume and resting-state functional connectivity in former heroin-dependent individuals abstinent for multiple years.

    PubMed

    Wang, Lubin; Zou, Feng; Zhai, Tianye; Lei, Yu; Tan, Shuwen; Jin, Xiao; Ye, Enmao; Shao, Yongcong; Yang, Yihong; Yang, Zheng

    2016-05-01

    Previous studies have suggested that heroin addiction is associated with structural and functional brain abnormalities. However, it is largely unknown whether these characteristics of brain abnormalities would be persistent or restored after long periods of abstinence. Considering the very high rates of relapse, we hypothesized that there may exist some latent neural vulnerabilities in abstinent heroin users. In this study, structural and resting-state functional magnetic resonance imaging data were collected from 30 former heroin-dependent (FHD) subjects who were drug free for more than 3 years and 30 non-addicted control (CN) volunteers. Voxel-based morphometry was used to identify possible gray matter volume differences between the FHD and CN groups. Alterations in resting-state functional connectivity in FHD were examined using brain areas with gray matter deficits as seed regions. Significantly reduced gray matter volume was observed in FHD in an area surrounding the parieto-occipital sulcus, which included the precuneus and cuneus. Functional connectivity analyses revealed that the FHD subjects showed reduced positive correlation within the default mode network and visual network and decreased negative correlation between the default mode network, visual network and task positive network. Moreover, the altered functional connectivity was correlated with self-reported impulsivity scores in the FHD subjects. Our findings suggest that disruption of large-scale brain systems is present in former heroin users even after multi-year abstinence, which could serve as system-level neural underpinnings for behavioral dysfunctions associated with addiction. PMID:25727574

  1. Synthetic studies and pharmacological evaluations on the MDMA (“Ecstasy”) antagonist Nantenine

    PubMed Central

    LeGendre, Onica; Pecic, Stevan; Chaudhary, Sandeep; Zimmerman, Sarah M.; Fantegrossi, William E.; Harding, Wayne W.

    2009-01-01

    The naturally occurring aporphine alkaloid nantenine, has been shown to antagonize behavioral and physiological effects of MDMA in mice. We have synthesized (±)-nantenine via an oxidative cyclization reaction with PIFA and evaluated its binding profile against a panel of CNS targets. To begin to understand the importance of the chiral center of nantenine with regards to its capacity to antagonize the effects of MDMA in vivo, (R)- and (S)-nantenine were prepared and evaluated in a food-reinforced operant task in rats. Pretreatment with either nantenine enantiomer (0.3 mg/kg i.p.) completely blocked the behavioral suppression induced upon administration of 3.0 mg/kg MDMA. (±)-Nantenine displayed high affinity and selectivity for the α1A adrenergic receptor among several other receptors suggesting that this α1 subtype may be significantly involved in the anti-MDMA effects of the enantiomers. PMID:19963380

  2. 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.

  3. MDMA (ecstasy) effects in pubescent rats: Males are more sensitive than females.

    PubMed

    Koenig, Julie; Lazarus, Christine; Jeltsch, Hélène; Ben Hamida, Sami; Riegert, Céline; Kelche, Christian; Jones, Byron C; Cassel, Jean-Christophe

    2005-07-01

    In Experiment 1, we assessed the effects of 3,4-methylenedioxymethamphetamine (MDMA) on locomotor activity in pubescent male and female Long-Evans rats. Thirty-nine day old rats were injected ip with 10 mg/kg of MDMA (ambient temperature 25 degrees C) three times at 2 h intervals. Initially, females showed greater locomotor activation by the drug than males, however after the second injection, males showed greater hyperlocomotion. After the third injection, 3 of 10 females and all of the males died. In the surviving females, we observed serotonin depletion in cortex and hippocampus, but catecholaminergic markers were unaltered. In Experiment 2, male and female rats were repeatedly injected with saline or 2, 5 or 10 mg/kg MDMA and body temperature was measured (ambient temperature 21.5 degrees C). After the third injection of 10 mg/kg MDMA, the MDMA-induced hyperthermia was greater in males than in females (about +0.8 degrees C); at the lower dose, no difference was observed. Probably because of the lower ambient temperature, only 1 female and 2 males succumbed to the MDMA treatment, and MDMA induced less serotonin depletion than in the first experiment, with no difference between females and males. Thus, pubescent males appear to be more sensitive than females to locomotor and hyperpyretic effects of MDMA. This sex-dependent effect, which is at variance with previously reported dimorphisms in psychostimulant effects, is discussed in terms of possible differences in dopamine D1 and D2 receptors at pubescence, or other factors related to drug metabolism. PMID:15951008

  4. 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

  5. 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

  6. 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.

  7. 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. PMID:19024211

  8. 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.

  9. 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

  10. Glutamatergic Neurometabolites during Early Abstinence from Chronic Methamphetamine Abuse

    PubMed Central

    Tobias, Marc C.; Hudkins, Matthew; London, Edythe D.

    2015-01-01

    Background: The acute phase of abstinence from methamphetamine abuse is critical for rehabilitation success. Proton magnetic resonance spectroscopy has detected below-normal levels of glutamate+glutamine in anterior middle cingulate of chronic methamphetamine abusers during early abstinence, attributed to abstinence-induced downregulation of the glutamatergic systems in the brain. This study further explored this phenomenon. Methods: We measured glutamate+glutamine in additional cortical regions (midline posterior cingulate, midline precuneus, and bilateral inferior frontal cortex) putatively affected by methamphetamine. We examined the relationship between glutamate+glutamine in each region with duration of methamphetamine abuse as well as the depressive symptoms of early abstinence. Magnetic resonance spectroscopic imaging was acquired at 1.5 T from a methamphetamine group of 44 adults who had chronically abused methamphetamine and a control group of 23 age-, sex-, and tobacco smoking-matched healthy volunteers. Participants in the methamphetamine group were studied as inpatients during the first week of abstinence from the drug and were not receiving treatment. Results: In the methamphetamine group, small but significant (5–15%, P<.05) decrements (vs control) in glutamate+glutamine were observed in posterior cingulate, precuneus, and right inferior frontal cortex; glutamate+glutamine in posterior cingulate was negatively correlated (P<.05) with years of methamphetamine abuse. The Beck Depression Inventory score was negatively correlated (P<.005) with glutamate+glutamine in right inferior frontal cortex. Conclusions: Our findings support the idea that glutamatergic metabolism is downregulated in early abstinence in multiple cortical regions. The extent of downregulation may vary with length of abuse and may be associated with severity of depressive symptoms emergent in early recovery. PMID:25522400

  11. 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

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

    PubMed

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

    2009-07-01

    The delta opioid system is involved in the behavioral effects of various drugs of abuse. However, only a few studies have focused on the possible interactions between the opioid system and the effects of 3,4-methylenedioxymethamphetamine (MDMA). In order to examine the possible role of the delta opioid system in MDMA-induced behaviors in mice, locomotor activity and conditioned place preference (CPP) were investigated in the presence of naltrindole (NTI), a selective delta opioid antagonist. Moreover, the consequences of acute and chronic MDMA administration on pro-enkephalin (Penk) and pro-opiomelanocortin (Pomc) gene expression were assessed by real-time quantitative polymerase chain reaction (QPCR). The results showed that, after acute MDMA administration (9 mg/kg; i.p.), NTI (5 mg/kg, s.c.) was able to totally block MDMA-induced hyperlocomotion. Penk gene expression was not modulated by acute MDMA, but a decrease of Pomc gene expression was observed, which was not antagonized by NTI. Administration of the antagonist prevented the acquisition of MDMA-induced CPP, suggesting an implication of the delta opioid receptors in this behavior. Following chronic MDMA treatment, only the level of Pomc was modulated. The observed increase was totally blocked by NTI pre-treatment. All these results confirm the interactions between the delta opioid system (receptors and peptides) and the effects of MDMA. PMID:19523041

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

    PubMed Central

    Modi, Gunjan M; Yang, Pamela B; Swann, Alan C; Dafny, Nachum

    2006-01-01

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

  14. Subjective Social Status Predicts Smoking Abstinence Among Light Smokers

    PubMed Central

    Whembolua, Guy-Lucien; Davis, Julia T.; Reitzel, Lorraine R.; Guo, Hongfei; Thomas, Janet L.; Goldade, Kate R.; Okuyemi, Kola S.; Ahluwalia, Jasjit S.

    2015-01-01

    Objectives To determine if community subjective social status (SSS) predicted smoking abstinence through 26 weeks postrandomization among 755 African American light smokers of low SES (socioeconomic status). Methods Participants were enrolled in a double-blind, placebo-controlled, randomized clinical trial, which examined the efficacy of nicotine gum and counseling for smoking cessation. Results Results indicated that SSS predicted smoking abstinence over time [P=.046; odds ratio (OR) =1.075 (1.001–1.155)] after adjusting for covariates. Conclusions Further research is needed to understand the effects of community SSS on smoking cessation among heavy smokers and other ethnic groups. PMID:22584091

  15. Adolescent Heavy Drinkers’ Amplified Brain Responses to Alcohol Cues Decrease Over One Month of Abstinence

    PubMed Central

    Brumback, Ty; Squeglia, Lindsay M.; Jacobus, Joanna; Pulido, Carmen; Tapert, Susan F.; Brown, Sandra A.

    2015-01-01

    heavy drinking adolescents prior to the onset of any alcohol use diagnosis. Across the majority of these brain regions, differences in BOLD response were no longer apparent following a month of abstinence, suggesting a decrease in alcohol cue reactivity among adolescent non-dependent heavy drinkers as a consequence of abstaining from alcohol. These results highlight the malleability of adolescent brain function despite no formal intervention targeting cue reactivity. Increased understanding of the neural underpinnings of cue reactivity could have implications for prevention and intervention strategies in adolescent heavy alcohol users. PMID:25796007

  16. Initial Abstinence Status and Contingency Management Treatment Outcomes: Does Race Matter?

    PubMed Central

    Montgomery, LaTrice; Carroll, Kathleen M.; Petry, Nancy M.

    2015-01-01

    Objective Limited research has evaluated African American substance users’ response to evidence-based treatments. This study examined the efficacy of contingency management (CM) in African American and White cocaine users. Method A secondary analysis evaluated effects of race, treatment condition, and baseline cocaine urine sample results on treatment outcomes of African American (n = 444) and White (n = 403) cocaine abusers participating in one of six randomized clinical trials comparing CM to standard care. Results African American and White patients who initiated treatment with a cocaine-negative urine sample remained in treatment for similar durations and submitted a comparable proportion of negative samples during treatment regardless of treatment type; CM was efficacious in both races in terms of engendering longer durations of abstinence in patients who began treatment abstinent. Whites who began treatment with a cocaine positive sample remained in treatment longer and submitted a higher proportion of negative samples when assigned to CM than standard care. African Americans who initiated treatment with a cocaine positive sample, however, did not remain in treatment longer with CM compared with standard care, and gains in terms of drug use outcomes were muted in nature relative to Whites. This interaction effect persisted through the 9-month follow-up period. Conclusions CM is not equally effective in reducing drug use among all subgroups, specifically African American patients who are using cocaine upon treatment entry. Future research on improving treatment outcomes in this population is needed. PMID:25798729

  17. Abstinence Programs Don't Work, Largest Study to Date Concludes

    ERIC Educational Resources Information Center

    Freking, Kevin

    2007-01-01

    This article reports on a study conducted by Mathematica Policy Research Inc. of students in four abstinence programs, as well as peers from the same communities who did not participate in the abstinence programs. A federally mandated report said that students who participated in sexual-abstinence education programs partially funded by the federal…

  18. 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

  19. Serotonergic Neurotoxic Thioether Metabolites of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”): Synthesis, Isolation and Characterization of Diastereoisomers

    PubMed Central

    Pizarro, Nieves; de la Torre, Rafael; Joglar, Jesús; Okumura, Noriko; Perfetti, Ximena; Lau, Serrine S.; Monks, Terrence J.

    2014-01-01

    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a synthetic recreational drug of abuse that produces long-term toxicity associated with the degeneration of serotonergic nerve terminals. In various animal models direct administration of MDMA into the brain fails to reproduce the serotonergic neurotoxicity, implying a requirement for the systemic metabolism and bioactivation of MDMA. Catechol-thioether metabolites of MDMA, formed via oxidation of 3,4-dihydroxymetamphetamine and 3,4-dihydroxyamphetamine (HHMA and HHA) and subsequent conjugation with glutathione (GSH), are selective serotonergic neurotoxicants when administered directly into brain. Moreover, following systemic administration of MDMA, the thioether adducts are present in rat brain dialysate. MDMA contains a stereogenic center, and is consumed as a racemate. Interestingly, different pharmacological properties have been attributed to the two enantiomers, (S)-MDMA being the most active in the central nervous system and responsible for the entactogenic effects, and most likely also for the neurodegeneration. The present study focused on the synthesis and stereochemical analysis of the neurotoxic MDMA thioether metabolites, 5-(glutathion-S-yl)-HHMA, 5-(N-acetylcysteine-S-yl)-HHMA, 2,5-bis-(glutathion-S-yl)-HHMA and 2,5-bis-(N-acetylcysteine-S-yl)-HHMA. Both enzymatic and electrochemical syntheses were explored, and methodologies for analytical and semi-preparative diastereoisomeric separation of MDMA thioether conjugates by HPLC-CEAS and HPLC-UV respectively were developed. Synthesis, diastereoisomeric separation, and unequivocal identification of the thioether conjugates of MDMA provide the chemical tools necessary for appropriate toxicological and metabolic studies on MDMA metabolites contributing to its neurotoxicity. PMID:19548351

  20. Alcoholic abstinence in elderly subjects with misuse of alcohol.

    PubMed

    Menecier, Pascal; Verny, Marc; Fernandez, Lydia; Ploton, Louis

    2016-06-01

    Alcohol use disorder does not disappear with aging, neither the associated induced-suffering. While the prevalence of alcohol use disorder still remains around 10% in the subjects over 65 year old age, and daily encountered by hospital or nursing-home caregivers. Alcohol misuse is often overlooked in elderly people, which then obtain lesser care than younger adults although the care prognosis remains as good as or better than before the age of 65, alcoholic abstinence gets always a place among care offers to elders suffering of alcohol use disorders and dependence. However abstinence is a complex notion gathering various representations or meanings, and induces necessary psychological changes. Alcoholic abstinence seems thus to be feared by families or caregivers, because of lack of knowledge about the addictive dimension of the disorder. On behalf of ultimate freedom, and allowing a last pleasure, alcohol use disorders and its associated suffering can be neglected because abstinence is considered as aggressive and harmful. However, modalities of reduction of alcohol consumption as well as access control or regulated supply of alcoholic beverages, keep having a place in graduate care offers. Beyond the choice of decreasing or suppress drinking alcohol beverages, which only are terms or conditions of improvement, the main point remains the improvement of well-fare, quality of life and elders' health. PMID:27277151

  1. Smokers’ Expectancies for Abstinence: Preliminary Results from Focus Groups

    PubMed Central

    Hendricks, Peter S.; Wood, Sabrina B.; Hall, Sharon M.

    2010-01-01

    Smokers’ expectancies regarding the effects of cigarette use are powerful predictors of smoking motivation and behavior. However, studies have not investigated the consequences that smokers expect when they attempt to quit smoking: abstinence-related expectancies. The primary goal of this qualitative study was to gain initial insight into smokers’ expectancies for abstinence. Eight focus groups were conducted with 30 smokers diverse with respect to age, gender, and ethnoracial background. Content analyses indicated that smokers anticipate a variety of outcomes from abstinence. The most frequently reported expectancies included pharmacologic withdrawal symptoms, behavioral withdrawal symptoms, decreased monetary expense, and immediate improvement of certain aspects of physical functioning and health. Additional expectancies concerned weight gain, improved attractiveness, enhanced social functioning/self-esteem, long-term health outcomes, and loss of relationships. Finally, a number of relatively unheralded expectancies were revealed. These involved NRT effectiveness, alcohol and other drug use, vigilance to cue reactivity, cessation-related social support, aversion to smoking, and “political process” implications. This study provides a preliminary step in understanding smokers’ expectancies for abstinence from cigarettes. PMID:19586157

  2. Adolescent Heavy Episodic Drinking: Neurocognitive Functioning during Early Abstinence

    PubMed Central

    Winward, Jennifer L.; Hanson, Karen L.; Bekman, Nicole M.; Tapert, Susan F.; Brown, Sandra A.

    2014-01-01

    Introduction The present study investigated the rate and pattern of neuropsychological recovery in heavy episodic drinking teens during the initial days to weeks of abstinence from alcohol. Method Adolescents (ages 16–18) with histories of heavy episodic drinking (HED; N=39) and socio-demographically similar control teens (CON; N=26) were recruited from San Diego area schools. HED and CON were comparable on 5th grade standardized math and language arts test performance to ensure similar functioning prior to onset of substance use. Participants were administered three neuropsychological test batteries with 2-week intervals during a 4-week monitored abstinence period. Results HED teens performed worse overall than CON on tests of prospective memory (p=.005), cognitive switching (p=.039), inhibition task accuracy (p=.001), verbal memory (p's<.045), visuospatial construction (p’s<.043), and language and achievement (p’s<.008). The statistically significant group × time interaction for block design demonstrated normalization within the four weeks of abstinence for the HED (p=.009). Discussion This study identified cognitive performance deficits associated with heavy episodic drinking in adolescence during early abstinence and with sustained 4-week abstention. These findings suggest alcohol-related influences on several underlying brain systems that may predate the onset of alcohol abuse or dependence or take longer than four weeks to recover. PMID:24512674

  3. "Sex Respect": Abstinence Education and Other Deployments for Sexual "Freedom"

    ERIC Educational Resources Information Center

    Jackson, Liz

    2006-01-01

    Those who view the right to a religiously neutral, empirically-based public education as fundamental have been able to do little more than watch in terror as abstinence-only sex education, which excludes information on either safe sex or birth control, has come to prevail in United States (US) schools. Among causes for concern are abstinence…

  4. Sexually Abstinent Adolescents: An 18-Month Follow-Up

    ERIC Educational Resources Information Center

    Blinn-Pike, Lynn; Berger, Thomas J.; Hewett, John; Oleson, Jacob

    2004-01-01

    This study was a longitudinal follow-up of 697 early adolescents from 20 schools in Missouri, investigating students who, in 1997, indicated on a survey of sexual attitudes and behaviors that they had not had sexual intercourse. They completed the Reasons for Abstinence Scale (RAS) by identifying those items that were reasons why they had not had…

  5. Opioid Abstinence Reinforcement Delays Heroin Lapse during Buprenorphine Dose Tapering

    ERIC Educational Resources Information Center

    Greenwald, Mark K.

    2008-01-01

    A positive reinforcement contingency increased opioid abstinence during outpatient dose tapering (4, 2, then 0 mg/day during Weeks 1 through 3) in non-treatment-seeking heroin-dependent volunteers who had been maintained on buprenorphine (8 mg/day) during an inpatient research protocol. The control group (n = 12) received $4.00 for completing…

  6. Internet-based group contingency management to promote smoking abstinence

    PubMed Central

    Dallery, Jesse; Meredith, Steven; Jarvis, Brantley; Nuzzo, Paul A.

    2015-01-01

    Internet-based group contingencies have been shown to promote brief periods of abstinence from cigarette smoking. Under a group contingency, small teams of smokers must collectively meet abstinence goals to receive monetary consequences. The present study investigated two arrangements, one in which all team members had to meet group treatment goals to receive monetary consequences (Full Group), and one in which team members had to meet some group goals and some individual goals to receive these consequences (Mixed Group). Mōtiv8 Systems, an Internet-based remote monitoring platform, was used to collect video-recorded breath carbon monoxide (CO) samples. All team members could communicate with each other via an online discussion forum. During baseline conditions, only 3.3% of CO samples were negative for smoking, which suggests that self-monitoring and access to the online discussion forum were insufficient to initiate abstinence. When the group contingencies were instituted 41.3% of CO samples were negative. There were no statistically significant differences between the two arrangements in the percentage of negative CO samples or point prevalence at the end of treatment or at the 3-month follow-up. Participants posted an average of 25 comments on the discussion forum, most of which were rated as positive by independent observers. The mean cost of vouchers per participant was lower in the Full Group ($33) relative to the Mixed group ($190). The present results replicate and extend previous findings on group contingencies to promote abstinence and social support. PMID:25821915

  7. Plasma lipoprotein changes during abstinence in chronic alcoholics.

    PubMed

    Weidman, S W; Beard, J D; Sabesin, S M

    1984-08-01

    Plasma lipoprotein changes during a 2-week period of abstinence were followed in 6 male, chronic alcoholics without evidence of severe liver disease and with initial HDL cholesterol (HDL-CH) greater than 60 mg/dl. Fasting blood samples were obtained on days 1, 3, 7 and 14 of the study. Reference data were obtained from healthy non-alcoholic normolipidemic men who had abstained from alcohol for 10 days. At day 1, plasma- and HDL-CH (by the heparin-Mn2+ technique) were 17 and 69% higher, respectively, than those of controls. During abstinence, VLDL-CH increased 52% whereas HDL-CH decreased 30% compared to day 1 values. (IDL + LDL)-CH increased during abstinence to levels 33% higher than that of controls. Plasma, SF greater than 400, VLDL- and d greater than 1.006 g/ml-triglycerides (TG) were not significantly different from those of the control group. Only the d greater than 1.006 g/ml-TG showed a significant effect of abstinence, increasing by 37%. Initial plasma and d greater than 1.006 g/ml-phospholipid (PL) concentrations were 17 and 31% higher, respectively, than those of controls; and the latter was the only fraction to change significantly with abstinence, decreasing by 13%. Density gradient ultracentrifugation was employed to further resolve the d greater than 1.006 g/ml fraction into IDL, LDL, HDL and VHDL subfractions. Initial levels of IDL- and LDL-CH and -PL in the alcoholic group did not differ from those of controls. IDL-CH and -PL were invariant during abstinence, whereas LDL-CH and -PL levels increased 38 and 28%, during this period. Apo A-I, CH and PL contained in the 'lighter' density HDL region of the gradient (d = 1.063-1.125 g/ml) were 70-108% increased over the corresponding parameters for controls; and with abstinence decreased 30-40% between days 1 and 14. CH and PL in the 'heavier' density HDL region (d = 1.125-1.21 g/ml) were 30% increased over those of controls, while apo A-I levels were similar to controls. During abstinence, 'heavy' HDL

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

    PubMed Central

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

    2015-01-01

    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 (80 pmol/100nl) or artificial CSF followed by a systemic dose of either MDMA (7.5 mg/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 (10 m/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. PMID:25725382

  9. The rewarding properties of MDMA are preserved in mice lacking mu-opioid receptors.

    PubMed

    Robledo, Patricia; Mendizabal, Victoria; Ortuño, Jordi; de la Torre, Rafael; Kieffer, Brigitte L; Maldonado, Rafael

    2004-08-01

    The involvement of mu-opioid receptors in the rewarding properties of MDMA was explored in mu-opioid receptor knockout mice using the conditioning place preference paradigm. The associated release of dopamine in the nucleus accumbens was investigated by in vivo microdialysis. A significant rewarding effect of MDMA (10 mg/kg, i.p.) was observed in both wild-type and mu-opioid receptor knockout mice. MDMA (10 mg/kg, i.p.) also induced similar increases in dopamine and decreases in 3,4-dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens dialysates of both wild-type and mu-opioid receptor knockout mice. No significant differences in basal levels of dopamine, 3,4-dihydroxyphenylacetic or homovanillic acids between wild-type and mu-opioid receptor knockout mice were observed. In summary, the present results suggest that, in contrast to what has been reported for other drugs of abuse such as opioids, ethanol, nicotine and Delta(9)-tetrahydrocannabinol, mu-opioid receptors do not play a major role in the rewarding properties of MDMA. These differences could be due to distinct mechanisms controlling dopamine release in the nucleus accumbens and suggest that the effects of MDMA on dopaminergic neurons are independent of micro -opioid receptors. PMID:15255997

  10. 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

  11. 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

  12. 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

  13. Locomotor and pyretic effects of MDMA-ethanol associations in rats.

    PubMed

    Cassel, Jean-Christophe; Jeltsch, Hélène; Koenig, Julie; Jones, Byron C

    2004-01-01

    3,4-Methylenedioxymethamphetamine [(MDMA) or ecstasy] is a popular club drug often used in combination with ethanol. In the current study, we investigated the effects of MDMA and ethanol combinations on locomotor activity and body temperature of rats. For four consecutive days, male Long-Evans rats were treated daily with a 10-mg/kg dose of MDMA with or without a 1.5-g/kg dose of ethanol. 3,4-Methylenedioxymethamphetamine increased spontaneous activity (on average +1,140%), and this increase was potentiated by ethanol on all days (on average +1,710%). Moreover, ethanol inhibited the MDMA-induced hyperthermia (on average -1.3 degrees C) by the first day of treatment, but not on subsequent treatment days, supporting the suggestion that this effect may undergo tolerance. These observations seem to indicate that combined ethanol-MDMA may induce effects on locomotor activity and thermoregulation that involve separate mechanisms, the first one being less sensitive to tolerance than the second one might be. Results of our study have important implications for understanding the motivation and the health risks of polydrug abusers combining ecstasy and ethanol. PMID:15902924

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

    PubMed

    Skrinska, Victor A; Gock, Susan B

    2005-01-01

    The phenylalkylamine derivatives, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy, XTC, Adam), 3,4-methylenedioxyethamphetamine (MDEA, MDE, Eve), and 3,4-methylenedioxyamphetamine (MDA), are psychostimulants with hallucinogenic properties. MDA is also a metabolite of both MDMA and MDEA. These drugs are ring-substituted amphetamine derivatives that produce hallucinogenic, entactogenic ('love drug'), and stimulating effects. MDMA was initially developed as an appetite suppressant, however, its use as a therapeutic drug has been very limited. Because of its effects as a hallucinogenic psychostimulant with relatively low toxicity, it has emerged over the last two decades as a common recreational psychostimulant or 'club drug' at 'raves'. MDMA, MDEA, and MDA are often referred to as 'rave' or 'designer' drugs. They are produced in clandestine laboratories and have an increasing presence on the illicit drug market worldwide. Significant adverse health effects have been reported that include: serotonin neurotoxicity, severe psychiatric disorders, renal failure, malignant hyperthermia, hepatitis, rhabdomyolysis, and disseminated intravascular coagulation. A number of fatal outcomes associated with severe MDMA intoxication have been reported. PMID:15916245

  15. 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. PMID:24290437

  16. Reasons for not drinking and perceived injunctive norms as predictors of alcohol abstinence among college students.

    PubMed

    Rinker, Dipali Venkataraman; Neighbors, Clayton

    2013-07-01

    Few studies have examined the association between reasons for not drinking and social norms among abstinent college students. Research suggests that drinking motives are associated with perceived injunctive norms and drinking. Therefore, it seems likely that reasons for not drinking may also be associated with perceived injunctive norms and abstinence. The aim of this study was to examine the relationship between reasons for not drinking and perceived injunctive norms on alcohol abstinence. Participants were 423 light-drinking and abstinent college students from a public northwestern university who completed online surveys at baseline, 3-, and 6-month follow-up. We examined abstinence as a function of all subscales of the Reasons for Not Drinking scale using logistic regression, as well as conducted two mediational analyses indicating: (1) perceived injunctive norms as a mediator of the relationship between reasons for not drinking and abstinence, and (2) reasons for not drinking as a mediator of the relationship between perceived injunctive norms and abstinence. The Disapproval/Lack of Interest subscale was the only subscale of the Reasons for Not Drinking scale that was significantly associated with 6-month abstinence. Further, Disapproval/Lack of Interest both directly predicted abstinence and indirectly predicted abstinence via perceived injunctive norms. Perceived injunctive norms indirectly predicted abstinence via Disapproval/Lack of Interest, but did not directly predict abstinence. Results suggest that self-defining personal values are an important component of keeping abstaining college students abstinent. These results are discussed with regard to implications for interventions designed specifically for maintaining abstinence throughout college. PMID:23578745

  17. 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

  18. 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

  19. Determination of MDMA, MDEA and MDA in urine by high performance liquid chromatography with fluorescence detection.

    PubMed

    da Costa, José Luiz; da Matta Chasin, Alice Aparecida

    2004-11-01

    This paper describes the development and validation of analytical methodology for the determination of the use of MDMA, MDEA and MDA in urine. After a simple liquid extraction, the analyses were carried out on a high performance liquid chromatography (HPLC) in an octadecyl column, with fluorescence detection. The mobile phase using a sodium dodecyl sulfate ion-pairing reagent allows good separation and efficiency. The method showed good linearity and precision. Recovery was between 85 and 102% and detection limits were 10, 15 and 20 ng/ml for MDA, MDMA and MDEA, respectively. No interfering substances were detected with fluorescence detection. PMID:15458720

  20. Student evaluation of sex education programs advocating abstinence.

    PubMed

    Olsen, J; Weed, S; Nielsen, A; Jensen, L

    1992-01-01

    This research examined the attitudes of students who were enrolled in three different sex education programs that emphasize abstinence. Data were examined to determine whether secondary school students responded positively to the programs. The programs examined were Values and Choices, Teen Aid, and Sex Respect. Results of the study indicated that all three programs were rated positively, with female, younger (junior high school age), and virgin-naive students rating the programs more highly. PMID:1621567

  1. Internet-based group contingency management to promote smoking abstinence.

    PubMed

    Dallery, Jesse; Meredith, Steven; Jarvis, Brantley; Nuzzo, Paul A

    2015-06-01

    Internet-based group contingencies have been shown to promote brief periods of abstinence from cigarette smoking. Under a group contingency, small teams of smokers must collectively meet abstinence goals to receive monetary consequences. The present study investigated 2 arrangements, 1 in which all team members had to meet group treatment goals to receive monetary consequences (full group), and 1 in which team members had to meet some group goals and some individual goals to receive these consequences (mixed group). Mo̅tiv8 Systems, an Internet-based remote monitoring platform, was used to collect video-recorded breath carbon monoxide (CO) samples. All team members could communicate with each other via an online discussion forum. During baseline conditions, only 3.3% of CO samples were negative for smoking, which suggests that self-monitoring and access to the online discussion forum were insufficient to initiate abstinence. When the group contingencies were instituted 41.3% of CO samples were negative. There were no statistically significant differences between the 2 arrangements in the percentage of negative CO samples or point prevalence at the end of treatment or at the 3-month follow-up. Participants posted an average of 25 comments on the discussion forum, most of which were rated as positive by independent observers. The mean cost of vouchers per participant was lower in the full group ($33) relative to the mixed group ($190). The present results replicate and extend previous findings on group contingencies to promote abstinence and social support. PMID:25821915

  2. 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

  3. A study on the mechanisms by which minocycline protects against MDMA ('ecstasy')-induced neurotoxicity of 5-HT cortical neurons.

    PubMed

    Orio, Laura; Llopis, Noemi; Torres, Elisa; Izco, Maria; O'Shea, Esther; Colado, M Isabel

    2010-08-01

    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is a selective 5-HT neurotoxin in rat brain which has been shown to produce acute neuroinflammation characterized by activation of microglia and release of interleukin-1beta (IL-1beta). We aimed to determine whether or not minocycline, a semi-synthetic tetracycline antibiotic capable of inhibiting microglial activation, could prevent the inflammatory response and reduce the toxicity induced by MDMA. Adult male Dark Agouti rats were given minocycline twice a day for 2 days (45 mg/kg on the first day and 90 mg/kg on the second day; 12-h apart, i.p.). MDMA (12.5 mg/kg; i.p.) was given after the third minocycline injection and animals were killed either 1 h later for the determination of NFkappaB binding activity, 3 h later for the determination of IL-1beta, 24 h later for the determination of microglial activation or 7 days later for the determination of [(3)H]-paroxetine binding as a measure of 5-HT neurotoxicity. MDMA increased NFkappaB activation, IL-1beta release and microglial activation both in the frontal cortex and in the hypothalamus and 7 days later produced a reduction in the density of 5-HT uptake sites in both these brain areas. Minocycline prevented the MDMA-induced increase in NFkappaB activation, IL-1beta release and microglial activation in the frontal cortex and prevented the 5-HT neurotoxicity 7 days later. However, in the hypothalamus, in spite of preventing MDMA-induced microglial activation, minocycline failed to prevent MDMA-induced NFkappaB activation, IL-1beta release and neurotoxicity. This suggests that the protective mechanism of minocycline against MDMA-induced neurotoxicity in frontal cortex involves inhibition of MDMA-induced NFkappaB activation possibly through a reduction in IL-1beta signalling. PMID:19777321

  4. Cigarette abstinence impairs memory and metacognition despite administration of 2 mg nicotine gum.

    PubMed

    Kelemen, William L; Fulton, Erika K

    2008-12-01

    The authors assessed the effects of cigarette abstinence (nonabstinent vs. minimum 8 hours abstinent) and nicotine gum (0 mg vs. 2 mg nicotine) on sustained attention, free recall, and metacognition using a within-subjects design. Moderate smokers (10 women and 22 men) received one training session followed by four test sessions on consecutive days. Nicotine gum improved sustained attention in both abstinent and nonabstinent states, but had no significant effect on predicted or actual recall levels. Cigarette abstinence significantly impaired free recall and reduced the magnitude of participants' predictions of their own performance. In addition, participants were significantly more overconfident about their future memory when abstinent. Thus, nicotine gum can improve smokers' performance in basic aspects of cognition (e.g., sustained attention) but may not alleviate the detrimental effects of cigarette abstinence on higher-level processes such memory and metacognition. PMID:19086773

  5. 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. PMID:18353576

  6. 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.

  7. 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

  8. [Evaluation of educational effects on drug dependence abstinence for convicts].

    PubMed

    Sakurai, Tomoko; Nishikawa, Kyoko; Tanaka, Takanori

    2011-06-01

    The object of this study is to evaluate the educational effects of group work sessions on drug dependence abstinence for convicts in Fukui Prison. Questionnaire surveys were conducted among participants on the first and last session. The results of surveys were analyzed quantitatively. The average ages of 50 respondents were 39 years. 95.9% of them used methamphetamine among drugs and the majority has used drugs for the past 5 years. 93.9% of respondents had no medical treatment histories and 95.8% of them have not used any formal consultations. The survey result before the sessions showed that 75.5% of respondents showed positive stances towards participations on educational group work sessions. The survey after the sessions showed 67.4% of respondents were able to talk their drug problems in group meetings and 87.0% responded that group work sessions were helpful for solving drug problems. Also, 80.0% responded that they can stop using drugs and the percentage dropped by 11.0% from the first session. In terms of the participation in self-help groups after releases from the prison, the majority responded negatively, although 78.0% showed positive responses to using consultation services. The outcomes by means of evaluation scale also showed a significant improvement on denial and no relevant change on interpersonal trusts. This study revealed that it was possible to confirm the effectiveness of drug abstinence education through group work. It is important to consider three points in further studies; 1) cooperation between judicial and medical institutions for introducing consultation and medical treatments among convicts; 2) follow-up programs for reinforcing education on drug abstinence; 3) social welfare services in cooperation with educational effects to prevent repeated offences. PMID:21861335

  9. Manifestations of early brain recovery associated with abstinence from alcoholism.

    PubMed

    Bartsch, Andreas J; Homola, György; Biller, Armin; Smith, Stephen M; Weijers, Heinz-Gerd; Wiesbeck, Gerhard A; Jenkinson, Mark; De Stefano, Nicola; Solymosi, László; Bendszus, Martin

    2007-01-01

    Chronic alcohol abuse results in morphological, metabolic, and functional brain damage which may, to some extent, be reversible with early effects upon abstinence. Although morphometric, spectroscopic, and neuropsychological indicators of cerebral regeneration have been described previously, the overall amount and spatial preference of early brain recovery attained by abstinence and its associations with other indicators of regeneration are not well established. We investigated global and local brain volume changes in a longitudinal two-timepoint study with T1-weighted MRI at admission and after short-term (6-7 weeks) sobriety follow-up in 15 uncomplicated, recently detoxified alcoholics. Volumetric brain gain was related to metabolic and neuropsychological recovery. On admission and after short-term abstinence, structural image evaluation using normalization of atrophy (SIENA), its voxelwise statistical extension to multiple subjects, proton MR spectroscopy (1H-MRS), and neuropsychological tests were applied. Upon short-term sobriety, 1H-MRS levels of cerebellar choline and frontomesial N-acetylaspartate (NAA) were significantly augmented. Automatically detected global brain volume gain amounted to nearly two per cent on average and was spatially significant around the superior vermis, perimesencephalic, periventricular and frontal brain edges. It correlated positively with the percentages of cerebellar and frontomesial choline increase, as detected by 1H-MRS. Moreover, frontomesial NAA gains were associated with improved performance on the d2-test of attention. In 10 age- and gender-matched healthy control subjects, no significant brain volume or metabolite changes were observed. Although cerebral osmotic regulations may occur initially upon sobriety, significant increases of cerebellar choline and frontomesial NAA levels detected at stable brain water integrals and creatine concentrations, serum electrolytes and red blood cell indices in our patient sample

  10. Weighing the Evidence: A Systematic Review on Long-Term Neurocognitive Effects of Cannabis Use in Abstinent Adolescents and Adults.

    PubMed

    Ganzer, Florian; Bröning, Sonja; Kraft, Stefanie; Sack, Peter-Michael; Thomasius, Rainer

    2016-06-01

    Findings on neurocognitive effects of sustained cannabis use are heterogeneous. Previous work has rarely taken time of abstinence into account. In this review, we focus on understanding sustained effects of cannabis, which begin when clinical symptoms of the drug have worn off after at least 14 days. We conducted a search between 2004 and 2015 and found 38 studies with such a prolonged abstinence phase. Study-design quality in terms of evidence-based medicine is similar among studies. Studies found some attention or concentration deficits in cannabis users (CU). There is evidence that chronic CU might experience sustained deficits in memory function. Findings are mixed regarding impairments in inhibition, impulsivity and decision making for CU, but there is a trend towards worse performance. Three out of four studies found evidence that motor function remains impaired even after a time of abstinence, while no impairments in visual spatial functioning can be concluded. Functional imaging demonstrates clear differences in activation patterns between CU and controls especially in hippocampal, prefrontal and cerebellar areas. Structural differences are found in cortical areas, especially the orbitofrontal region and the hippocampus. Twenty studies (57 %) reported data on outcome effects, leading to an overall effect size of r mean = .378 (CI 95 % = [.342; .453]). Heavy use is found to be more consistently associated with effects in diverse domains than early age of onset. Questions of causality-in view of scarce longitudinal studies, especially those targeting co-occurring psychiatric disorders-are discussed. PMID:27125202

  11. Exercise during early, but not late abstinence, attenuates subsequent relapse vulnerability in a rat model.

    PubMed

    Beiter, R M; Peterson, A B; Abel, J; Lynch, W J

    2016-01-01

    Exercise has shown promise as a nonpharmacological intervention for addiction, with evidence suggesting a potential utility for relapse prevention. In humans, exercise as an intervention is typically introduced well after the initiation of abstinence, yet neurobiological data from preclinical studies suggest that it may be more effective if initiated during early abstinence. Here, using rat models, we determined whether the beneficial effects of exercise on relapse vulnerability depends on when exercise is first initiated, during early versus late abstinence. Once rats (n=47) acquired cocaine self-administration, they were given 24-h access to cocaine (1.5 mg/kg per infusion) under a discrete trial procedure (four infusions per hour) for 10 days. The rats then began a 14-day abstinence period in which they had access (2 h per day) to a locked wheel throughout abstinence (sedentary) or an unlocked wheel during early (days 1-7), late (days 8-14) or throughout (days 1-14) abstinence (n=10-14 per group). Cocaine seeking, as assessed under an extinction/cued-induced reinstatement procedure, was examined on day 15 of abstinence. Exercise beginning during early abstinence robustly attenuated subsequent cocaine seeking, and this effect persisted even when exercise ended on the seventh day of abstinence. In contrast, exercise during late abstinence was not effective and these animals displayed high levels of cocaine seeking similar to those observed in sedentary animals. These results indicate that the timing of exercise availability differentially impacts cocaine seeking with results suggesting that exercise during early, but not late, abstinence may provide long-term protection against cocaine relapse. PMID:27115123

  12. Exercise during early, but not late abstinence, attenuates subsequent relapse vulnerability in a rat model

    PubMed Central

    Beiter, R M; Peterson, A B; Abel, J; Lynch, W J

    2016-01-01

    Exercise has shown promise as a nonpharmacological intervention for addiction, with evidence suggesting a potential utility for relapse prevention. In humans, exercise as an intervention is typically introduced well after the initiation of abstinence, yet neurobiological data from preclinical studies suggest that it may be more effective if initiated during early abstinence. Here, using rat models, we determined whether the beneficial effects of exercise on relapse vulnerability depends on when exercise is first initiated, during early versus late abstinence. Once rats (n=47) acquired cocaine self-administration, they were given 24-h access to cocaine (1.5 mg/kg per infusion) under a discrete trial procedure (four infusions per hour) for 10 days. The rats then began a 14-day abstinence period in which they had access (2 h per day) to a locked wheel throughout abstinence (sedentary) or an unlocked wheel during early (days 1–7), late (days 8–14) or throughout (days 1–14) abstinence (n=10–14 per group). Cocaine seeking, as assessed under an extinction/cued-induced reinstatement procedure, was examined on day 15 of abstinence. Exercise beginning during early abstinence robustly attenuated subsequent cocaine seeking, and this effect persisted even when exercise ended on the seventh day of abstinence. In contrast, exercise during late abstinence was not effective and these animals displayed high levels of cocaine seeking similar to those observed in sedentary animals. These results indicate that the timing of exercise availability differentially impacts cocaine seeking with results suggesting that exercise during early, but not late, abstinence may provide long-term protection against cocaine relapse. PMID:27115123

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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. PMID:23775255

  18. A Guided Abstinence Experience to Illustrate Addiction Recovery Principles

    PubMed Central

    2008-01-01

    Objectives To develop and implement an elective pharmacy course that included a guided abstinence experience to illustrate addiction recovery principles. Design A 1-credit elective course to illustrate addiction recovery principles was developed and implemented. The course required students to give up a habit for 6 weeks that was causing them problems, meet weekly to discuss addiction recovery processes, and relate their experiences in a journal. Course grades were determined by class participation, submitted worksheets, and submission of the journal and a paper concerning their role as a pharmacist in dealing with those with addictions and in recovery. Pre- and posttests consisting of addiction case scenarios were used to assess students' application of course material. Assessment Graded course elements, pretesting and posttesting, and student course evaluations indicated that course objectives were met. Over the past 15 years, student enrollment has grown from approximately 10% of pharmacy classes to approximately 50% (average 31 students). Conclusion A guided abstinence experience was an effective tool for teaching pharmacy students the concepts of addiction and recovery. PMID:19002278

  19. Cue reactivity in active pathological, abstinent pathological, and regular gamblers.

    PubMed

    Sodano, Ruthlyn; Wulfert, Edelgard

    2010-03-01

    Twenty-one treatment-seeking pathological gamblers, 21 pathological gamblers in recovery, and 21 recreational gamblers watched two video-taped exciting gambling scenarios and an exciting roller-coaster control scenario while their arousal (heart rate and subjective excitement) and urge to gamble were being measured. The gamblers did not differ significantly in cue-elicited heart rate elevations or excitement. However, the active pathological gamblers reported significantly greater urges to gamble across all cues compared to the abstinent pathological gamblers and, with marginal significance (p = 0.06), also compared to the social gamblers. Further exploration of these findings revealed that active pathological gamblers experience urges to gamble in response to exciting situations, whether or not they are gambling related, whereas abstinent and social gamblers only report urges to an exciting gambling-related cue. This suggests that for pathological gamblers excitement itself, irrespective of its source, may become a conditioned stimulus capable of triggering gambling behavior. Implications for treatment and future research are discussed. PMID:19662519

  20. Biased Perception of Mean Emotion in Abstinent Heroin Abusers.

    PubMed

    Zhang, Meng; Wang, Xuan; Hu, Chun; Liao, Huayu; Yang, Tong; Shen, Mowei

    2015-01-01

    Although evidence suggests that drug abusers exhibit biases when coding individual emotional facial expressions, little is known about how they process multiple expressions simultaneously. The present study evaluated the mean emotions perceived by abstinent heroin abusers. Male abstinent heroin abusers (AHs) and healthy controls (HCs) were randomly assigned into three emotional conditions (happy, sad, or angry), viewed sets of four faces (Experiment 1) or individual faces (Experiment 2) that varied in emotionality (neutral to happy/sad/angry), and judged whether a test face presented later was more/less emotional than the preceding stimuli. Average points of subjective equality were calculated to reflect participants' biases in perceiving emotions of sets or single faces. Relative to HCs, AHs overestimated mean emotions for sad and angry faces in Experiment 1; however, no such biases were found in Experiment 2. This suggests biased ensemble coding towards negative emotional facial expressions in AHs. Furthermore, when controlling for depression and anxiety, AHs' enhanced perception of mean emotion for angry or sad faces in Experiment 1 decreased, indicating a possible mediating effect of these psychopathological variables in the relationship between drug addiction history and abnormal ensemble processing for sets of emotional expressions. PMID:26595559

  1. Effects of an Internet-Based Voucher Reinforcement Program for Smoking Abstinence: A Feasibility Study

    ERIC Educational Resources Information Center

    Dallery, Jesse; Glenn, Irene M.

    2005-01-01

    The present study tested the feasibility of an Internet-based method to obtain objective evidence of smoking abstinence and to deliver vouchers for evidence of abstinence. Four heavy smokers participated in this 4-week study. Twice daily, participants made video recordings of themselves providing a breath carbon monoxide (CO) sample with a Web…

  2. Attitudes toward Sexual Abstinence among Black Seventh-Day Adventist College Students

    ERIC Educational Resources Information Center

    Ashley, George; Ramirez, Octavio; Cort, Malcolm

    2013-01-01

    The purpose of this study was to identify Black Seventh-Day Adventist (SDA) college students' attitudes toward the concept of sexual abstinence. Attitude toward abstinence was operationalized as a dichotomy of acceptance or rejection of the concept as a way to order sexual behavior. The study utilized a convenience sample ("N" =…

  3. Abstinence Violation Effect: Validation of an Attributional Construct with Smoking Cessation.

    ERIC Educational Resources Information Center

    Curry, Susan; And Others

    1987-01-01

    The abstinence violation effect (AVE) proposed in Marlatt and Gordon's model of smoking relapse was operationalized as a combination of internal, stable, and global causal attributions for smoking following the attainment of abstinence from smoking. Smoking cessation program participants who relapsed following a slip reported significantly higher…

  4. Abstinence, Sex, and Virginity: Do They Mean What We Think They Mean?

    ERIC Educational Resources Information Center

    Hans, Jason D.; Kimberly, Claire

    2011-01-01

    Ambiguous definitions concerning which behaviors constitute sex, abstinence, and virginity may lead to arbitrary interpretations of meaning or miscommunication, which could be particularly problematic in health care, educational, and research contexts. The purpose of this study was to examine and compare definitions of sex, abstinence, and…

  5. Clinical Trial of Abstinence-Based Vouchers and Cognitive-Behavioral Therapy for Cannabis Dependence

    ERIC Educational Resources Information Center

    Budney, Alan J.; Moore, Brent A.; Rocha, Heath L.; Higgins, Stephen T.

    2006-01-01

    Ninety cannabis-dependent adults seeking treatment were randomly assigned to receive cognitive-behavioral therapy, abstinence-based voucher incentives, or their combination. Treatment duration was 14 weeks, and outcomes were assessed for 12 months post treatment. Findings suggest that (a) abstinence-based vouchers were effective for engendering…

  6. Influence of Materials on Teacher Adoption of Abstinence-Only-Until-Marriage Programs

    ERIC Educational Resources Information Center

    Wilson, Kelly L.; Wiley, David C.

    2009-01-01

    Background: Given the growing scientific evidence against abstinence-only-until-marriage education, health educators are supporting an evidence-based approach to teaching sexuality education. However, there is still an abundance of federal support and funding streams allocated to sustain abstinence-only programs. This study assessed indicators…

  7. 77 FR 42768 - Leadership Meeting on Maternal, Fetal, and Infant Opioid Exposure and Neonatal Abstinence Syndrome

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-20

    ... CONTROL POLICY Leadership Meeting on Maternal, Fetal, and Infant Opioid Exposure and Neonatal Abstinence... Meeting on Maternal, Fetal and Infant Opioid Exposure and Neonatal Abstinence Syndrome (NAS) will bring together leaders in the field of policy, opioid exposed infants, pain treatment during pregnancy,...

  8. Comprehensive Sexuality Education or Abstinence-Only Education: Which Is More Effective?

    ERIC Educational Resources Information Center

    Pittman, Vicki; Gahungu, Athanase

    2006-01-01

    The purpose of this study was to examine the difference in effectiveness between comprehensive sexuality abstinence-based education and abstinence-only education. A survey was developed and distributed to over 140 individuals via a variety of sources such as: (1) the researcher's e-mail lists; (2) a group of City Core/City Year volunteers; (3) a…

  9. A Qualitative Evaluation of the Students of Service (SOS) Program for Sexual Abstinence in Louisiana

    ERIC Educational Resources Information Center

    Yoo, Seunghyun; Johnson, Carolyn C.; Rice, Janet; Manuel, Powlin

    2004-01-01

    Abstinence-only programs for preventing teen pregnancy are the only options in some states but are the programs of choice in others. Effectiveness data, however, are lacking. The SOS Adolescent Family Life Program (SOS), an abstinence-only teen pregnancy prevention program, was implemented in south central Louisiana. Peer mentoring with an…

  10. A Review of 21 Curricula for Abstinence-Only-until-Marriage Programs.

    ERIC Educational Resources Information Center

    Wilson, Kelly L.; Goodson, Patricia; Pruitt, B.E.; Buhi, Eric; Davis-Gunnels, Emily

    2005-01-01

    The authors reviewed the content, methods, and overall quality of 21 curricula used in abstinence-only-until-marriage programs. Only materials designed for use in middle school grades (fifth to eighth) or with middle school-aged audiences (9-13 years of age), which presented the abstinence message in at least 40% of their content, were included. A…

  11. Emotional reactivity to emotional and smoking cues during smoking abstinence: Potentiated startle and P300 suppression

    PubMed Central

    Engelmann, Jeffrey M.; Gewirtz, Jonathan C.; Cuthbert, Bruce N.

    2012-01-01

    Negative affect is thought to be an important factor in the maintenance of cigarette smoking, and thus it is important to further develop objective measures of smoking-related emotional responses. Nonsmokers, nonabstinent smokers, and abstinent smokers participated in a cue reactivity task where eyeblink startle amplitude and startle probe P300 (P3) suppression were measured during the presentation of emotional pictures. During unpleasant pictures, the amplitude of both measures was smaller in nonabstinent smokers than in nonsmokers or abstinent smokers. P3 suppression, but not startle amplitude, was larger in abstinent smokers than in nonsmokers. Abstinence-induced increases in cigarette craving were associated with P3 suppression during tobacco-related pictures. Results suggest that tobacco abstinence increases emotional reactivity to unpleasant stimuli, which is consistent with negative reinforcement models of tobacco addiction. PMID:24015407

  12. The Relationship of Self-Control and Abstinence Maintenance: An Exploratory Analysis of Self-Regulation

    PubMed Central

    Ferrari, Joseph R.; Stevens, Edward B.; Jason, Leonard A.

    2010-01-01

    Studies of self-regulation suggested that self-control requires finite resources which, in turn, may present a significant challenge for those trying to recover from or control addictive behaviors. The present study examined the relationships between self-regulation and abstinence maintenance among adults in recovery (n = 606: 407 men, 199 women; M age = 38.5 years) residing in self-governed, communal living, abstinent homes across the United States. Self-regulation scores (controlling for sex and age) were positively related to length of abstinence. In addition, a factor analysis of self-regulation scores resulted in some differentiation between general self-discipline and impulsivity in self-control related to addiction. The relationship between impulsivity and length of abstinence was stronger than the relationship derived between general self-regulation and length of abstinence. PMID:20689650

  13. 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. PMID:21194370

  14. Acute administration of 3,4-methylenedioxymethamphetamine (MDMA) induces oxidative stress, lipoperoxidation and TNFα-mediated apoptosis in rat liver.

    PubMed

    Cerretani, D; Bello, S; Cantatore, S; Fiaschi, A I; Montefrancesco, G; Neri, M; Pomara, C; Riezzo, I; Fiore, C; Bonsignore, A; Turillazzi, E; Fineschi, V

    2011-11-01

    Liver toxicity is one of the consequences of ecstasy (3,4-methylenedioxymethamphetamine MDMA) abuse and hepatocellular damage is reported after MDMA consumption. Various factors probably play a role in ecstasy-induced hepatotoxicity, namely its metabolism, the increased efflux of neurotransmitters, the oxidation of biogenic amines, and hyperthermia. MDMA undergoes extensive hepatic metabolism that involves the production of reactive metabolites which form adducts with intracellular nucleophilic sites. MDMA-induced-TNF-α can promote multiple mechanisms to initiate apoptosis in hepatocytes, activation of pro-apoptotic (BID, SMAC/DIABLO) and inhibition of anti-apoptotic (NF-κB, Bcl-2) proteins. The aim of the present study was to obtain evidence for the oxidative stress mechanism and apoptosis involved in ecstasy-induced hepatotoxicity in rat liver after a single 20 mg/kg, i.p. MDMA administration. Reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA), an indicator of lipid peroxidation, were determined in rat liver after 3 and 6h after MDMA treatment. The effect of a single MDMA treatment included decrease of GR and GPx activities (29% and 25%, respectively) and GSH/GSSG ratio (32%) with an increase of MDA (119%) after 3h from ecstasy administration compared to control rats. Liver cytosolic level of AA was increased (32%) after 6 h MDMA treatment. Our results demonstrate a strong positive reaction for TNFα (p<0.001) in hepatocytes and a diffuse apoptotic process in the liver specimens (p<0.001). There was correlation between immunohistochemical results and Western blotting which were quantitatively measured by densitometry, confirming the strong positivity for TNF-α (p<0.001) and NF-κB (p<0.001); weak and intense positivity reactions was confirmed for Bcl-2, SMAC/DIABLO (p<0.001) and BID reactions (p<0.001). The results obtained in the

  15. A Randomized Trial of Long-Term Reinforcement of Cocaine Abstinence in Methadone-Maintained Patients Who Inject Drugs

    ERIC Educational Resources Information Center

    Silverman, Kenneth; Robles, Elias; Mudric, Timothy; Bigelow, George E.; Stitzer, Maxine L.

    2004-01-01

    This study determined whether long-term abstinence reinforcement could maintain cocaine abstinence throughout a yearlong period. Patients who injected drugs and used cocaine during methadone treatment (n = 78) were randomly assigned to 1 of 2 abstinence-reinforcement groups or to a usual care control group. Participants in the 2…

  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. 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

  18. 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

  19. 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

  20. 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

  1. An extended nondrug MDMA-like experience evoked through posthypnotic suggestion.

    PubMed

    Hastings, Arthur

    2006-09-01

    This research explored whether hypnotic suggestion could produce a subjective mindbody condition similar to that produced by the psychoactive drug methylenedioxy methamphetamine (MDMA, Ecstasy). Twelve participants received posthypnotic instructions to re-experience an MDMA-like state posthypnotically, similar to one in their prior experience, for one hour. Three separate self report measures and qualitative self reports showed that the posthypnotic condition effectively mimicked an MDMA-like experience, lasting an hour at a stable level. Participant ratings in real time and in retrospect ranged from 36% to 100% similarity to a drug-induced experience. The qualitative reports and rating scales enabled a phenomenological description of the subjective experience. Scores on the Tellegen Absorption Scale correlated significantly with the strength of the posthypnotic condition (Spearman rho .87, p = .0003). The participants successfully carried out various intentional activities during this time (e.g., self reflection, talking with partners about relationships, artwork, walking in nature). Applications for this technique as an adjunct to therapy and health treatments are discussed. PMID:17165370

  2. Emotional intelligence, risk perception in abstinent cocaine dependent individuals.

    PubMed

    Romero-Ayuso, Dulce; Mayoral-Gontán, Yolanda; Triviño-Juárez, José-Matías

    2016-01-01

    Cocaine is now responsible for the second-highest number of cessation intervention requests. In this study we analyze the different skills of emotional intelligence in cocaine- dependent patients maintaining abstinence. The Mayer- Salovey-Caruso Emotional Intelligence Test (MSCEIT) and the Balloon Analogue Risk Task (BART) were administered to 50 subjects (25 individuals with no history of drug use and 25 individuals in treatment at the Addictive Behaviors Unit in a state of withdrawal at the time of evaluation). The results showed differences between these groups in overall emotional intelligence quotient, strategic emotional intelligence, understanding emotions and emotional management. Cocaine-addicted participants showed difficulties in analyzing complex emotions and regulating their emotional response, aspects that can interfere with interactions in daily life. PMID:27099213

  3. 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

  4. 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

  5. Differential contributions of dopamine D1, D2, and D3 receptors to MDMA-induced effects on locomotor behavior patterns in mice.

    PubMed

    Risbrough, Victoria B; Masten, Virginia L; Caldwell, Sorana; Paulus, Martin P; Low, Malcolm J; Geyer, Mark A

    2006-11-01

    MDMA or 'ecstasy' (3,4-methylenedioxymethamphetamine) is a commonly used psychoactive drug that has unusual and distinctive behavioral effects in both humans and animals. In rodents, MDMA administration produces a unique locomotor activity pattern, with high activity characterized by smooth locomotor paths and perseverative thigmotaxis. Although considerable evidence supports a major role for serotonin release in MDMA-induced locomotor activity, dopamine (DA) receptor antagonists have recently been shown to attenuate these effects. Here, we tested the hypothesis that DA D1, D2, and D3 receptors contribute to MDMA-induced alterations in locomotor activity and motor patterns. DA D1, D2, or D3 receptor knockout (KO) and wild-type (WT) mice received vehicle or (+/-)-MDMA and were tested for 60 min in the behavioral pattern monitor (BPM). D1 KO mice exhibited significant increases in MDMA-induced hyperactivity in the late testing phase as well as an overall increase in straight path movements. In contrast, D2 KO mice exhibited reductions in MDMA-induced hyperactivity in the late testing phase, and exhibited significantly less sensitivity to MDMA-induced perseverative thigmotaxis. At baseline, D2 KO mice also exhibited reduced activity and more circumscribed movements compared to WT mice. Female D3 KO mice showed a slight reduction in MDMA-induced hyperactivity. These results confirm differential modulatory roles for D1 and D2 and perhaps D3 receptors in MDMA-induced hyperactivity. More specifically, D1 receptor activation appears to modify the type of activity (linear vs circumscribed), whereas D2 receptor activation appears to contribute to the repetitive circling behavior produced by MDMA. PMID:16855533

  6. Attributes that Differentiate Children Who Sip Alcohol from Abstinent Peers

    PubMed Central

    Jackson, Christine; Ennett, Susan T.; Dickinson, Denise M.; Bowling, J. Michael

    2012-01-01

    Sipping alcohol during childhood may be a marker of differentiation as regards children’s future risk of underage drinking; yet very little is known about alcohol use when it occurs among elementary school-aged children. The purpose of the present study is to examine alcohol sipping behavior in a sample of third-grade school children to learn whether sipping is associated with attributes that could increase children’s likelihood of further underage drinking. We collected telephone interview data from 1050 mothers and their third grade children (mean age 9.2 years; 48.2% male) residing in the Southeastern United States. The majority of mothers were White non-Hispanic (69.02%) or Black non-Hispanic (21.3%); most (85%) lived in households shared with fathers or other adult caretakers. We hypothesized that children who sip alcohol would score lower than abstinent peers on indicators of competence and score higher on indicators of exposure to alcohol-specific socialization by parents and peers. A multivariate model controlling for frequency of parent alcohol use and demographic covariates showed that children who had sipped alcohol were significantly less likely than abstinent peers to affirm indicators of competence and significantly more likely to affirm indicators of exposure to alcohol specific socialization by parents and by same age peers. These preliminary findings suggest that developmental attributes associated with risk of underage drinking begin to differentiate at least as young as middle childhood. Research is needed to test prospectively for continuity between alcohol risk attributes present in middle childhood and future alcohol use. PMID:23224982

  7. Systematic Review of Abstinence-Plus HIV Prevention Programs in High-Income Countries

    PubMed Central

    Underhill, Kristen; Operario, Don; Montgomery, Paul

    2007-01-01

    Background Abstinence-plus (comprehensive) interventions promote sexual abstinence as the best means of preventing HIV, but also encourage condom use and other safer-sex practices. Some critics of abstinence-plus programs have suggested that promoting safer sex along with abstinence may undermine abstinence messages or confuse program participants; conversely, others have suggested that promoting abstinence might undermine safer-sex messages. We conducted a systematic review to investigate the effectiveness of abstinence-plus interventions for HIV prevention among any participants in high-income countries as defined by the World Bank. Methods and Findings Cochrane Collaboration systematic review methods were used. We included randomized and quasi-randomized controlled trials of abstinence-plus programs for HIV prevention among any participants in any high-income country; trials were included if they reported behavioural or biological outcomes. We searched 30 electronic databases without linguistic or geographical restrictions to February 2007, in addition to contacting experts, hand-searching conference abstracts, and cross-referencing papers. After screening 20,070 abstracts and 325 full published and unpublished papers, we included 39 trials that included approximately 37,724 North American youth. Programs were based in schools (10), community facilities (24), both schools and community facilities (2), health care facilities (2), and family homes (1). Control groups varied. All outcomes were self-reported. Quantitative synthesis was not possible because of heterogeneity across trials in programs and evaluation designs. Results suggested that many abstinence-plus programs can reduce HIV risk as indicated by self-reported sexual behaviours. Of 39 trials, 23 found a protective program effect on at least one sexual behaviour, including abstinence, condom use, and unprotected sex (baseline n = 19,819). No trial found adverse program effects on any behavioural outcome

  8. Brain Activity in Cigarette Smokers Performing a Working Memory Task: Effect of Smoking Abstinence

    PubMed Central

    Xu, Jiansong; Mendrek, Adrianna; Cohen, Mark S.; Monterosso, John; Rodriguez, Paul; Simon, Sara L.; Brody, Arthur; Jarvik, Murray; Domier, Catherine P.; Olmstead, Richard; Ernst, Monique; London, Edythe D.

    2009-01-01

    Background When nicotine-dependent human subjects abstain from cigarette smoking, they exhibit deficits in working memory. An understanding of the neural substrates of such impairments may help to understand how nicotine affects cognition. Our aim, therefore, was to identify abnormalities in the circuitry that mediates working memory in nicotine-dependent subjects after they initiate abstinence from smoking. Methods We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study eight smokers while they performed a letter version of the N-Back working memory task under satiety (≤1.5 hours abstinence) and abstinence (≥14 hours abstinence) conditions. Results Task-related activity in the left dorsal lateral prefrontal cortex (DLPFC) showed a significant interaction between test session (satiety, abstinence) and task load (1-back, 2-back, and 3-back). This interaction reflected the fact that task-related activity in the satiety condition was relatively low during performance of the 1-back task but greater at the more difficult task levels, whereas task-related activity in the abstinence condition was relatively high at the 1-back level and did not increase at the more difficult task levels. Conclusions We conclude that neural processing related to working memory in the left DLPFC is less efficient during acute abstinence from smoking than at smoking satiety. PMID:16038685

  9. Predictors of Abstinence Self-Efficacy: Examining the role of HIV-risk Sexual Behavior

    PubMed Central

    Majer, John M.; Glantsman, Olya; Palmer, John S.; Jason, Leonard A.

    2016-01-01

    Abstinence self-efficacy, or the confidence in ones’ beliefs in one’s ability to effectively engage in behaviors to maintain substance use abstinence, is a crucial recovery resource. However, little research has been conducted on what predicts increases in this recovery resource. Understanding predictors of abstinence self-efficacy could help social service practitioners in creating effective treatment plans/interventions while extending what is presently known in this small body of research. Predictors of abstinence self-efficacy were analyzed among a sample of ex-offenders (224 men and 46 women) who were completing inpatient treatment for substance use disorders. Hierarchical linear regression was conducted to examine changes in participants’ abstinence self-efficacy in relation to factors directly related (HIV-risk drug use behaviors, substance use, 12-step meeting attendance) and indirectly related (HIV-risk sexual behaviors, incarceration histories) to substance use. HIV-risk sexual behaviors and substance use predicted significant decreases in abstinence self-efficacy whereas 12-step meeting attendance predicted significant increases. However, incarceration histories and HIV-risk drug use behaviors were not significant predictors of abstinence self-efficacy. Findings suggest HIV-risk sexual behavior should be considered when assessing relapse prevention for persons with substance use disorders, and that researchers should examine behaviors that are not directly related to substance use when investigating recovery resources.

  10. Repeated episodes of heroin cause enduring alterations of circadian activity in protracted abstinence.

    PubMed

    Stinus, Luis; Cador, Martine; Caille, Stephanie

    2012-01-01

    Opiate withdrawal is followed by a protracted abstinence syndrome consisting of craving and physiological changes. However, few studies have been dedicated to both the characterization and understanding of these long-term alterations in post-dependent subjects. The aim of the present study was to develop an opiate dependence model, which induces long-lasting behavioral changes in abstinent rats. Here, we first compared the effects of several protocols for the induction of opiate dependence (morphine pellets, repeated morphine or heroin injections) on the subsequent response to heroin challenges (0.25 mg/kg) at different time points during abstinence (3, 6, 9 and 18 weeks). In a second set of experiments, rats were exposed to increasing doses of heroin and subsequently monitored for general circadian activity up to 20 weeks of abstinence. Results show that heroin injections rather than the other methods of opiate administration have long-term consequences on rats' sensitivity to heroin with its psychostimulant effects persisting up to 18 weeks of abstinence. Moreover, intermittent episodes of heroin dependence rather than a single exposure produce enduring alteration of the basal circadian activity both upon heroin cessation and protracted abstinence. Altogether, these findings suggest that the induction of heroin dependence through intermittent increasing heroin injections is the optimal method to model long-term behavioral alterations during protracted abstinence in rats. This animal model would be useful in further characterizing long-lasting changes in post-dependent subjects to help understand the prolonged vulnerability to relapse. PMID:24961201

  11. Repeated Episodes of Heroin Cause Enduring Alterations of Circadian Activity in Protracted Abstinence

    PubMed Central

    Stinus, Luis; Cador, Martine; Caille, Stephanie

    2012-01-01

    Opiate withdrawal is followed by a protracted abstinence syndrome consisting of craving and physiological changes. However, few studies have been dedicated to both the characterization and understanding of these long-term alterations in post-dependent subjects. The aim of the present study was to develop an opiate dependence model, which induces long-lasting behavioral changes in abstinent rats. Here, we first compared the effects of several protocols for the induction of opiate dependence (morphine pellets, repeated morphine or heroin injections) on the subsequent response to heroin challenges (0.25 mg/kg) at different time points during abstinence (3, 6, 9 and 18 weeks). In a second set of experiments, rats were exposed to increasing doses of heroin and subsequently monitored for general circadian activity up to 20 weeks of abstinence. Results show that heroin injections rather than the other methods of opiate administration have long-term consequences on rats’ sensitivity to heroin with its psychostimulant effects persisting up to 18 weeks of abstinence. Moreover, intermittent episodes of heroin dependence rather than a single exposure produce enduring alteration of the basal circadian activity both upon heroin cessation and protracted abstinence. Altogether, these findings suggest that the induction of heroin dependence through intermittent increasing heroin injections is the optimal method to model long-term behavioral alterations during protracted abstinence in rats. This animal model would be useful in further characterizing long-lasting changes in post-dependent subjects to help understand the prolonged vulnerability to relapse. PMID:24961201

  12. Genetic markers associated with abstinence length in alcohol-dependent subjects treated with acamprosate.

    PubMed

    Karpyak, V M; Biernacka, J M; Geske, J R; Jenkins, G D; Cunningham, J M; Rüegg, J; Kononenko, O; Leontovich, A A; Abulseoud, O A; Hall-Flavin, D K; Loukianova, L L; Schneekloth, T D; Skime, M K; Frank, J; Nöthen, M M; Rietschel, M; Kiefer, F; Mann, K F; Weinshilboum, R M; Frye, M A; Choi, D S

    2014-01-01

    Acamprosate supports abstinence in some alcohol-dependent subjects, yet predictors of response are unknown. To identify response biomarkers, we investigated associations of abstinence length with polymorphisms in candidate genes in glycine and glutamate neurotransmission pathways and genes previously implicated in acamprosate response. Association analyses were conducted in the discovery sample of 225 alcohol-dependent subjects treated with acamprosate for 3 months in community-based treatment programs in the United States. Data from 110 alcohol-dependent males treated with acamprosate in the study PREDICT were used for replication of the top association findings. Statistical models were adjusted for relevant covariates, including recruitment site and baseline clinical variables associated with response. In the discovery sample, shorter abstinence was associated with increased intensity of alcohol craving and lower number of days between the last drink and initiation of acamprosate treatment. After adjustment for covariates, length of abstinence was associated with the GRIN2B rs2058878 (P=4.6 × 10(-5)). In the replication sample, shorter abstinence was associated with increased craving, increased depressive mood score and higher alcohol consumption. Association of abstinence length with GRIN2B rs2058878 was marginally significant (P=0.0675); as in the discovery sample, the minor A allele was associated with longer abstinence. Furthermore, rs2300272, which is in strong linkage disequilibrium with rs2058878, was also associated with abstinence length (P=0.049). This is the first report of a replicated association of genetic markers with the length of abstinence in acamprosate-treated alcoholics. Investigation of the underlying mechanisms of this association and its usefulness for individualized treatment selection should follow. PMID:25290263

  13. 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

  14. The application of Bandura's self-efficacy theory to abstinence-oriented alcoholism treatment.

    PubMed

    Rollnick, S; Heather, N

    1982-01-01

    This paper explores the relevance of self-efficacy theory (Bandura, 1977b) to the process of abstinence treatment and the phenomenon of relapse. By distinguishing between the particular efficacy and outcome expectations created in treatment it is possible to clarify some of the problems encountered between clinicians and alcoholics. Bandura's theory also explains why some treatment methods might be more effective than others. Analysis of relapse suggests that while some of the expectations created in treatment might serve to promote abstinence, others might unwittingly precipitate relapse. The understanding of abstinence treatment could be enhanced by the testing of hypotheses which emerge from this analysis. PMID:7180618

  15. Neurotrophic factors in women with crack cocaine dependence during early abstinence: the role of early life stress

    PubMed Central

    Viola, Thiago Wendt; Tractenberg, Saulo Gantes; Levandowski, Mateus Luz; Pezzi, Júlio Carlos; Bauer, Moisés Evandro; Teixeira, Antonio Lúcio; Grassi-Oliveira, Rodrigo

    2014-01-01

    Background Neurotrophic factors have been investigated in the pathophysiology of alcohol and drug dependence and have been related to early life stress driving developmental programming of neuroendocrine systems. Methods We conducted a follow-up study that aimed to assess the plasma levels of glial cell line–derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT3) and neurotrophin-4/5 (NT4/5) in crack users during 3 weeks of early abstinence in comparison with healthy controls. We performed a comprehensive clinical assessment in female inpatients with crack cocaine dependence (separated into 2 groups: participants with (CSA+) and without (CSA−) a history of childhood sexual abuse) and a group of nonuser control participants. Results Our sample included 104 women with crack cocaine dependence and 22 controls; of the women who used crack cocaine, 22 had a history of childhood sexual abuse and 82 did not. The GDNF plasma levels in the CSA+ group increased dramatically during 3 weeks of detoxification. In contrast, those in the CSA− group showed lower and stable levels of GDNF under the same conditions. Compared with the control group, BDNF plasma levels remained elevated and NGF levels were reduced during early abstinence. We found no differences in NT3 and NT4/5 between the patients and controls. However, within-group analyses showed that the CSA+ group exhibited higher levels of NT4/5 than the CSA− group at the end of detoxification. Limitations Some of the participants were using neuroleptics, mood stabilizers or antidepressants; our sample included only women; memory bias could not be controlled; and we did not investigate the possible confounding effects of other forms of stress during childhood. Conclusion This study supports the association between early life stress and peripheral neurotrophic factor levels in crack cocaine users. During early abstinence, plasmastic GDNF and NT4/5 were

  16. Could MDMA Promote Stemness Characteristics in Mouse Embryonic Stem Cells via mGlu5 Metabotropic Glutamate Receptors?

    PubMed Central

    Meamar, Rokhsareh; Karamali, Fereshte; Mousavi, Seyed Ali; Baharvand, Hossein; Nasr-Esfahani, Mohammad Hossein

    2012-01-01

    Objective: Ecstasy, or 3, 4 (±) methylenedioxymethamphetamine (MDMA), is a potent neurotoxic drug. One of the mechanisms for its toxicity is the secondary release of glutamate. Mouse embryonic stem cells (mESCs) express only one glutamate receptor, the metabotropic glutamate receptor 5 (mGlu5), which is involved in the maintenance and self-renewal of mESCs. This study aims to investigate whether MDMA could influence self-renewal via the mGlu5 receptor in mESCs. Materials and Methods: In this expremental study, we used immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to determine the presence of the mGlu5 receptor in mESCs. The expression of mGlu5 was evaluated after MDMA was added to mESCs throughout neural precursor cell formation as group 1 and during neural precursor cell differentiation as group 2. The stemness characteristic in treated mESCs by immunofluorescence and flow cytometry was studied. Finally, caspase activity was evaluated by fluorescence staining in the treated group. One-way ANOVA or repeated measure of ANOVA according to the experimental design was used for statistical analyses. Results: In this study mGlu5 expression was shown in mESCs. In terms of neuronal differentiation, MDMA affected mGlu5 expression during neural precursor cell formation (group 1) and not during neural precursor differentiation (group 2). MDMA (450 µM) induced a significant increment in self-renewal properties in mESCs but did not reverse 2-methyl-6(phenylethynyl) pyridine (MPEP, 1 µM), a non-competitive selective mGlu5 antagonist. Fluorescence staining with anti-caspase 3 showed a significant increase in the number of apoptotic cells in the MDMA group. Conclusion: We observed a dual role for MDMA on mESCs: reduced proliferation and maintenance of self-renewal. The lack of decreasing stemness characteristic in presence of MPEP suggests that MDMA mediates its role through a different mechanism that requires further investigation. In

  17. Increases in use of novel synthetic stimulant are not directly linked to decreased use of 3,4-methylenedioxy-N-methylamphetamine (MDMA).

    PubMed

    Chen, Chang; Kostakis, Chris; Irvine, Rodney J; White, Jason M

    2013-09-10

    A decline in 3,4-methylenedioxy-N-methylamphetamine (MDMA) use in Adelaide, Australia from 2009 to 2010 was confirmed by us previously. Reports suggested that the shortage in MDMA supply was associated with an increased prevalence of other synthetic stimulants, but quantitative measurements were unavailable. To obtain objective data on the community use of synthetic stimulants, we collected wastewater samples from multiple treatment plants in Adelaide, Australia from 2009 to 2011 and analysed them using solid-phase extraction/liquid chromatography/tandem mass spectrometry (SPE-LC-MS/MS), targeting MDMA and some of the most reported synthetic cathinones and piperazines. Data were temporally compared. MDMA and six other synthetic stimulants were detected and quantified in wastewater samples. While MDMA level decreased markedly from 2009 to 2010 and remained low in 2011, localized increased use of mephedrone, methylone, methylenedioxypyrovalerone (MDPV), benzylpiperazine (BZP), 3-trifluoromethylphenylpiperazine (TFMPP), but not methcathinone, was observed in 2010 and 2011. This suggested that the decline in MDMA use was associated with an increase in the use of a number of other synthetic stimulants. However, the lag time from the decrease in MDMA to the increase in use of a number of these stimulants, together with the highly regionalized use of all synthetic stimulants except methcathinone indicates that there was no direct population wide substitution in response to the reduction in MDMA. PMID:23890650

  18. 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. PMID:25936514

  19. 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

  20. 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. PMID:25343292

  1. Evidence that MDMA ('ecstasy') increases cannabinoid CB2 receptor expression in microglial cells: role in the neuroinflammatory response in rat brain.

    PubMed

    Torres, Elisa; Gutierrez-Lopez, Maria Dolores; Borcel, Erika; Peraile, Ines; Mayado, Andrea; O'Shea, Esther; Colado, Maria Isabel

    2010-04-01

    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') produces selective long-lasting serotonergic neurotoxicity in rats. The drug also produces acute hyperthermia which modulates the severity of the neurotoxic response. In addition, MDMA produces signs of neuroinflammation reflected as microglial activation and an increase in the release of interleukin-1beta, the latter of which appears to be a consequence of the hyperthermic response and to be implicated in the neurotoxicity induced by the drug. Over-expression of the cannabinoid CB2 receptor in microglia during non-immune and immune pathological conditions is thought to be aimed at controlling the production of neurotoxic factors such as proinflammatory cytokines. Our objective was to study the pattern of CB2 receptor expression following MDMA and to examine the effect of JWH-015 (a CB2 agonist) on the MDMA-induced neuroinflammatory response as well as 5-hydroxytryptamine (5-HT) neurotoxicity. Adult Dark Agouti rats were given MDMA (12.5 mg/kg, i.p.) and killed 3 h or 24 h later for the determination of CB2 receptor expression. JWH-015 was given 48 h, 24 h and 0.5 h before MDMA and 1 h and/or 6 h later and animals were killed for the determination of microglial activation (3 h and 24 h) and 5-HT neurotoxicity (7 days). MDMA increased CB2 receptor expression shortly after administration and these receptors were found in microglia. JWH-015 decreased MDMA-induced microglial activation and interleukin-1beta release and slightly decreased MDMA-induced 5-HT neurotoxicity. In conclusion, CB2 receptor activation reduces the neuroinflammatory response following MDMA and provides partial neuroprotection against the drug. PMID:20067581

  2. Basic and neutral route specific impurities in MDMA prepared by different synthesis methods. Comparison of impurity profiles.

    PubMed

    Swist, M; Wilamowski, J; Parczewski, A

    2005-12-20

    In this work, the neutral and basic impurities found in the precipitate of MDMA(*)HCl are presented. MDMA.HCl was prepared by the most popular synthesis methods used in clandestine manufacture, i.e. safrole bromination, Leuckart method and reductive amination with various reducing agents: Al/Hg, NaBH(4), NaBH(3)CN. 3,4-Methylenedioxyphenyl-2-propanone (MDP-2-P), the starting material in Leuckart reaction and reductive amination, was prepared by two different synthesis methods, i.e. by isosafrole oxidation and MDP-2-nitropropene reduction. The extraction of impurities was performed under alkaline and neutral conditions. Impurity profiles were obtained using GC/MS. Each synthesis method is characterised by its own route specific impurities. The influence of pH on the extraction of synthesis markers from 3,4-methylenedioxymethamphetamine (MDMA) samples is discussed and comparison of the profiles of basic and neutral impurities is presented. PMID:16226147

  3. “That's Nasty” to Curiosity: Early Adolescent Cognitions about Sexual Abstinence

    PubMed Central

    Ott, Mary A.; Pfeiffer, Elizabeth J.

    2010-01-01

    Purpose Effective sex education for early adolescents should make use of age-appropriate cultural models about sexual abstinence. However, little is known about how early adolescents view this topic. We describe developmental differences in cognitions about sexual abstinence among high risk early adolescents. Methods After IRB approval and informed consent, we interviewed twenty-two 11-14 year-olds, using a qualitative, two-stage interview. Participants were first asked a series of open-ended questions about sexual abstinence, and then asked to explain their answers. Interviews were transcribed, organized by age, and read in their entirety. Codes were developed from the literature, field notes, and transcripts. Key concepts were identified and models were developed with a focus on developmental change. Results We observed three distinct views of sexual abstinence, “That's Nasty,” “Curious,” and Normative. All viewed abstinence as a starting point and sex as a transition to adulthood. “That's Nasty” participants identified sex as distasteful, displayed limited understanding of sex, and viewed abstinence as appropriate for kids like themselves. Curious participants expressed a desire for information about sex, and a sense of missing something important. Normative participants viewed the transition from abstinence to sexual experience as part of a normal, albeit challenging, transition to adulthood. Conclusions Participants demonstrated differences in cognitions about sexual abstinence, related to age and development. The transition from viewing sex as distasteful to curiosity appears to be a time of both vulnerability and openness, and may provide an opportunity for intervention. PMID:19465322

  4. Abstinence from chronic cocaine self-administration alters striatal dopamine systems in rhesus monkeys.

    PubMed

    Beveridge, Thomas J R; Smith, Hilary R; Nader, Michael A; Porrino, Linda J

    2009-04-01

    Although dysregulation within the dopamine (DA) system is a hallmark feature of chronic cocaine exposure, the question of whether these alterations persist into abstinence remains largely unanswered. Nonhuman primates represent an ideal model in which to assess the effects of abstinence on the DA system following chronic cocaine exposure. In this study, male rhesus monkeys self-administered cocaine (0.3 mg/kg per injection, 30 reinforcers per session) under a fixed-interval 3-min schedule for 100 days followed by either 30 or 90 days abstinence. This duration of cocaine self-administration has been previously shown to decrease DA D2-like receptor densities and increase levels of D1-like receptors and DA transporters (DAT). Responding by control monkeys was maintained by food presentation under an identical protocol and the same abstinence periods. [(3)H]SCH 23390 binding to DA D1 receptors following 30 days of abstinence was significantly higher in all portions of the striatum, compared to control animals, whereas [(3)H]raclopride binding to DA D2 receptors was not different between groups. [(3)H]WIN 35 428 binding to DAT was also significantly higher throughout virtually all portions of the dorsal and ventral striatum following 30 days of abstinence. Following 90 days of abstinence, however, levels of DA D1 receptors and DAT were not different from control values. Although these results indicate that there is eventual recovery of the separate elements of the DA system, they also highlight the dynamic nature of these components during the initial phases of abstinence from chronic cocaine self-administration. PMID:18769473

  5. Abstinence from Chronic Cocaine Self-Administration Alters Striatal Dopamine Systems in Rhesus Monkeys

    PubMed Central

    Beveridge, Thomas JR; Smith, Hilary R; Nader, Michael A; Porrino, Linda J

    2013-01-01

    Although dysregulation within the dopamine (DA) system is a hallmark feature of chronic cocaine exposure, the question of whether these alterations persist into abstinence remains largely unanswered. Nonhuman primates represent an ideal model in which to assess the effects of abstinence on the DA system following chronic cocaine exposure. In this study, male rhesus monkeys self-administered cocaine (0.3 mg/kg per injection, 30 reinforcers per session) under a fixed-interval 3-min schedule for 100 days followed by either 30 or 90 days abstinence. This duration of cocaine self-administration has been previously shown to decrease DA D2-like receptor densities and increase levels of D1-like receptors and DA transporters (DAT). Responding by control monkeys was maintained by food presentation under an identical protocol and the same abstinence periods. [3H]SCH 23390 binding to DA D1 receptors following 30 days of abstinence was significantly higher in all portions of the striatum, compared to control animals, whereas [3H]raclopride binding to DA D2 receptors was not different between groups. [3H]WIN 35 428 binding to DAT was also significantly higher throughout virtually all portions of the dorsal and ventral striatum following 30 days of abstinence. Following 90 days of abstinence, however, levels of DA D1 receptors and DAT were not different from control values. Although these results indicate that there is eventual recovery of the separate elements of the DA system, they also highlight the dynamic nature of these components during the initial phases of abstinence from chronic cocaine self-administration. PMID:18769473

  6. Incentive Learning for Morphine-Associated Stimuli During Protracted Abstinence Increases Conditioned Drug Preference

    PubMed Central

    Smith, Rachel J; Aston-Jones, Gary

    2014-01-01

    Previous studies from our laboratory found that rats express increased preference for drug-paired stimuli following 2 or 5 weeks of protracted abstinence from chronic drug exposure as compared with naive animals. Here, we show that this increased morphine place preference depends upon experiencing drug-stimulus pairings specifically in the abstinent state, indicating a critical role for incentive learning. Male Sprague Dawley rats were initially conditioned for morphine place preference (8 mg/kg) and then made dependent on morphine (by subcutaneous morphine pellets) and subjected to forced abstinence. Place preference was tested every 1–2 weeks with no additional drug-cue conditioning. In this paradigm, there was no difference between morphine-pelleted (dependent) and placebo-pelleted (non-dependent) rats in place preference at any time during abstinence (up to 6 weeks). However, these same morphine-pelleted rats expressed significantly increased preference when they were subsequently re-conditioned for morphine place preference during protracted abstinence. Placebo-pelleted rats did not show enhanced preference after re-conditioning. These findings reveal that incentive learning has a key role in increased morphine place preference when drug is experienced during protracted abstinence. This indicates that incentive learning is involved not only in instrumental responding (as previously reported), but also in updating Pavlovian-conditioned responses to morphine-associated stimuli. Therefore, enhanced morphine preference is not a direct consequence of the negative affective state of abstinence, but instead reflects increased acquisition of morphine-stimulus associations during abstinence. These results indicate that, during the development of addiction in humans, drug-associated stimuli acquire increasingly stronger incentive properties each time they are re-experienced. PMID:23942418

  7. 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

  8. A direct comparison of the behavioral and physiological effects of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in humans

    PubMed Central

    Kirkpatrick, Matthew G.; Gunderson, Erik W.; Perez, Audrey Y.; Haney, Margaret; Foltin, Richard W.

    2015-01-01

    Rationale Despite their chemical similarities, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) produce differing neurochemical and behavioral responses in animals. In humans, individual studies of methamphetamine and MDMA indicate that the drugs engender overlapping and divergent effects; there are only limited data comparing the two drugs in the same individuals. Objectives This study examined the effects of methamphetamine and MDMA using a within-subject design. Methods Eleven adult volunteers completed this 13-day residential laboratory study, which consisted of four 3-day blocks of sessions. On the first day of each block, participants received oral methamphetamine (20, 40 mg), MDMA (100 mg), or placebo. Drug plasma concentrations, cardiovascular, subjective, and cognitive/psychomotor performance effects were assessed before drug administration and after. Food intake and sleep were also assessed. On subsequent days of each block, placebo was administered and residual effects were assessed. Results Acutely, both drugs increased cardiovascular measures and “positive” subjective effects and decreased food intake. In addition, when asked to identify each drug, participants had difficulty distinguishing between the amphetamines. The drugs also produced divergent effects: methamphetamine improved performance and disrupted sleep, while MDMA increased “negative” subjective-effect ratings. Few residual drug effects were noted for either drug. Conclusions It is possible that the differences observed could explain the differential public perception and abuse potential associated with these amphetamines. Alternatively, the route of administration by which the drugs are used recreationally might account for the many of the effects attributed to these drugs (i.e., MDMA is primarily used orally, whereas methamphetamine is used by routes associated with higher abuse potential). PMID:21713605

  9. 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

  10. 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. PMID:26093344

  11. Subjective Social Status Affects Smoking Abstinence During Acute Withdrawal Through Affective Mediators

    PubMed Central

    Reitzel, Lorraine R.; Mazas, Carlos A.; Cofta-Woerpel, Ludmila; Li, Yisheng; Cao, Yumei; Businelle, Michael S.; Cinciripini, Paul M.; Wetter, David W.

    2010-01-01

    Objectives Direct and mediated associations between subjective social status (SSS), a subjective measure of socioeconomic status, and smoking abstinence were examined during the period of acute withdrawal among a diverse sample of 421 smokers (33% Caucasian, 34% African-American, 33% Latino) undergoing a quit attempt. Methods Logistic regressions examined relations between SSS and abstinence, controlling for sociodemographic variables. Depression, stress, positive affect, and negative affect on the quit day were examined as potential affective mediators of the SSS-abstinence association, with and without adjusting for pre-quit mediator scores. Results SSS predicted abstinence through 2 weeks post-quit. Abstinence rates were approximately 2.5 times higher in the highest versus the lowest SSS quartile. Depression and positive affect mediated the SSS-abstinence relationships, but only depression maintained significance when adjusting for the baseline mediator score. Conclusions Among a diverse sample of quitting smokers, low SSS predicted relapse during acute withdrawal after controlling for numerous covariates, an effect partially accounted for by quit day affective symptomatology. Smokers endorsing lower SSS face significant hurdles in achieving cessation, highlighting the need for targeted interventions encompassing attention to quit day mood reactivity. PMID:20219054

  12. Cortical activation during delay discounting in abstinent methamphetamine dependent individuals

    PubMed Central

    Schwartz, Daniel L.; Huckans, Marilyn S.; McFarland, Bentson H.; Meiri, Gal; Stevens, Alexander A.; Mitchell, Suzanne H.

    2010-01-01

    Background Methamphetamine (MA)-dependent individuals prefer smaller immediate over larger delayed rewards in delay discounting (DD) tasks. Human and animal data implicate ventral (amygdala, ventral striatum, ventrolateral prefrontal cortex insula) and dorsal (dorsolateral prefrontal cortex, dorsal anterior cingulate cortex and posterior parietal cortex) systems in DD decisions. The ventral system is hypothesized to respond to the salience and immediacy of rewards while the dorsal system is implicated in the process of comparison and choice. Methods We used functional Magnetic Resonance Imaging to probe the neural correlates of DD in 19 recently abstinent MA-dependent patients and 17 age- and gender-matched controls. Results Hard DD choices were associated with greatest activation in bilateral middle cingulate, posterior parietal cortex (PPC), and the right rostral insula. Control subjects showed more activation than MA patients bilaterally in the precuneus and in the right caudate nucleus, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). Magnitude of discounting was correlated with activity in the amygdala, DLPFC, posterior cingulate cortex and PPC. Conclusions Our findings were consistent with a model wherein dorsal cognitive systems modulate the neural response of ventral regions. Patients addicted to MA, who strongly prefer smaller immediate over larger delayed rewards, activate the dorsal cognitive control system in order to overcome their preference. Activation of the amygdala during choice of delayed rewards was associated with a greater degree of discounting, suggesting that heavily discounting MA-dependent individuals may be more responsive to the negative salience of delayed rewards than controls. PMID:18685833

  13. The Effects of E-Cigarette Visual Appearance on Craving and Withdrawal Symptoms in Abstinent Smokers

    PubMed Central

    Dawkins, Lynne; Munafò, Marcus; Christoforou, Gina; Olumegbon, Naomi; Soar, Kirstie

    2016-01-01

    Introduction Electronic cigarette (e-cigarette) use is becoming increasing popular among smokers and there is a plethora of devices available. Nicotine delivery is clearly important for reducing tobacco craving and withdrawal symptoms, but other sensor-motor aspects of e-cigarettes (such as visual appearance) may contribute to this effect. This study explored whether it is important for an e-cigarette to visually resemble a tobacco cigarette in order to reduce craving and withdrawal symptoms. Methods Sixty-three abstinent smokers (40% female, aged 18-65 years) who were not current e-cigarette users were randomly allocated to take ten 3-second puffs from either a white or a red first generation e-cigarette. Current craving (urge to smoke) and nicotine withdrawal symptoms (using the Mood and Physical Symptoms Scale; MPSS) were measured before and ten minutes after use. Results Linear regression revealed higher craving and withdrawal symptoms in the red versus the white condition but only among those who were e-cigarette naive (craving: B = .76, p = .009; withdrawal symptoms: B = 2.18, p = 0.009), not among those with e-cigarette experience (craving: B = −.08, p = 0.89; withdrawal symptoms: B = .24, p = .81), and these effects differed between groups (p = 0.04 and 0.01 for craving and withdrawal symptoms respectively). Conclusion Cigarette-like appearance was associated with a greater reduction in craving and withdrawal symptoms but only for those with no prior e-cigarette experience. This effect, putatively mediated via classical conditioning or expectancies, may aid understanding of smokers’ initial preferences for ‘cigalike’ e-cigarette devices. PMID:26415054

  14. Examining the role of oxytocin in the interoceptive effects of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') using a drug discrimination paradigm in the rat.

    PubMed

    Broadbear, Jillian H; Tunstall, Brendan; Beringer, Katherine

    2011-04-01

    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') use results in distinctive mood changes of a prosocial nature, most likely through its enhancement of serotonin (5HT) neurotransmission. Activation of 5HT-1A postsynaptic receptors has been shown to stimulate the release of oxytocin in the central nervous system where it regulates aspects of mood and behavior. Using a drug discrimination paradigm, we examined whether modulation of oxytocin receptor activity would affect conditioned behavioral responses to MDMA. Male and female Sprague Dawley rats (n=24) were trained to reliably differentiate between MDMA and a related stimulant, amphetamine (AMP), and saline using a three-lever drug discrimination paradigm. The extent to which substitution with carbetocin (an oxytocin analog) or co-administration with atosiban (an oxytocin receptor antagonist) affected drug-appropriate responding was evaluated. The tricyclic antidepressant imipramine was included as a negative control. The results supported the hypotheses that substitution with an oxytocin analog (carbetocin) would partially generalize to the MDMA training cue, whereas blocking oxytocin receptors with atosiban would result in a selective disruption of MDMA--but not AMP-appropriate responding. These findings were specific to the oxytocin receptor ligands as imipramine pre-treatment did not affect drug-appropriate responding. The results of this study implicate oxytocin receptor activation as a key MDMA-specific interoceptive cue in male and female rats and support the conclusion that this is one of the features of MDMA's subjective effects that distinguishes it from AMP. PMID:21070509

  15. Impulsivity, inhibition and negative priming in ecstasy users.

    PubMed

    Dafters, Richard I

    2006-08-01

    A modified Stroop color-word interference paradigm was used to investigate the effects of recreational ecstasy (MDMA) use on central executive inhibitory processes. Ecstasy users who also used cannabis were compared with non-users matched for cannabis consumption and with non-drug users on a Stroop task in which standard color-word interference trials were interspersed with trials in which the target color was the same as the distractor word on the immediately preceding trial. Ecstasy's effects on standard inhibition (conscious suppression of a prepotent response pattern--responsible for Stroop interference) could thus be contrasted with its effect on the short-term, unconscious, inhibitory process responsible for suppression of the preceding distractor word (negative priming). Neither drug group differed from the non-drug users in level of Stroop interference but ecstasy users showed reduced negative priming compared to the cannabis users and non-drug users. The loss of inhibition in the ecstasy users was not related to impulsivity assessed by two standard scales since these were similar in both drug-user groups and raised relative to the non-drug users. It is argued that previous failures to demonstrate loss of inhibition could be partly due to the fact that standard executive function tests, such as the Stroop, are unable to differentiate between sub-types of inhibition, only some of which may be affected by ecstasy use. PMID:16242244

  16. Large-Scale Brain Network Coupling Predicts Acute Nicotine Abstinence Effects on Craving and Cognitive Function

    PubMed Central

    Lerman, Caryn; Gu, Hong; Loughead, James; Ruparel, Kosha; Yang, Yihong; Stein, Elliot A.

    2014-01-01

    IMPORTANCE Interactions of large-scale brain networks may underlie cognitive dysfunctions in psychiatric and addictive disorders. OBJECTIVES To test the hypothesis that the strength of coupling among 3 large-scale brain networks–salience, executive control, and default mode–will reflect the state of nicotine withdrawal (vs smoking satiety) and will predict abstinence-induced craving and cognitive deficits and to develop a resource allocation index (RAI) that reflects the combined strength of interactions among the 3 large-scale networks. DESIGN, SETTING, AND PARTICIPANTS A within-subject functional magnetic resonance imaging study in an academic medical center compared resting-state functional connectivity coherence strength after 24 hours of abstinence and after smoking satiety. We examined the relationship of abstinence-induced changes in the RAI with alterations in subjective, behavioral, and neural functions. We included 37 healthy smoking volunteers, aged 19 to 61 years, for analyses. INTERVENTIONS Twenty-four hours of abstinence vs smoking satiety. MAIN OUTCOMES AND MEASURES Inter-network connectivity strength (primary) and the relationship with subjective, behavioral, and neural measures of nicotine withdrawal during abstinence vs smoking satiety states (secondary). RESULTS The RAI was significantly lower in the abstinent compared with the smoking satiety states (left RAI, P = .002; right RAI, P = .04), suggesting weaker inhibition between the default mode and salience networks. Weaker inter-network connectivity (reduced RAI) predicted abstinence-induced cravings to smoke (r = −0.59; P = .007) and less suppression of default mode activity during performance of a subsequent working memory task (ventromedial prefrontal cortex, r = −0.66, P = .003; posterior cingulate cortex, r = −0.65, P = .001). CONCLUSIONS AND RELEVANCE Alterations in coupling of the salience and default mode networks and the inability to disengage from the default mode network may

  17. Prenatal Methadone Exposure, Meconium Biomarker Concentrations and Neonatal Abstinence Syndrome

    PubMed Central

    Gray, Teresa R.; Choo, Robin E.; Concheiro, Marta; Williams, Erica; Elko, Andrea; Jansson, Lauren M.; Jones, Hendrée E.; Huestis, Marilyn A.

    2010-01-01

    Aims Methadone is standard pharmacotherapy for opioid-dependent pregnant women, yet the relationship between maternal methadone dose and neonatal abstinence syndrome (NAS) severity is still unclear. This research evaluated whether quantification of fetal methadone and drug exposure via meconium would reflect maternal dose and predict neonatal outcomes. Design Prospective clinical study Setting An urban drug treatment facility treating pregnant and post-partum women and their children Participants Forty-nine opioid-dependent pregnant women received 30–110 mg methadone daily. Measurements Maternal methadone dose, infant birth parameters and NAS assessments were extracted from medical records. Thrice-weekly urine specimens were screened for opioids and cocaine. Newborn meconium specimens were quantified for methadone, opioid, cocaine and tobacco biomarkers. Findings There was no relationship between meconium methadone concentrations, presence of opioids, cocaine and/or tobacco in meconium, maternal methadone dose or NAS severity. Opioid, cocaine and tobacco biomarkers also were found in 36.7, 38.7 and 81.1% of meconium specimens, respectively, and were associated with positive urine specimens in the third trimester. The presence of opioids other than methadone in meconium correlated with increased rates of preterm birth, longer infant hospital stays and decreased maternal time in drug treatment. Conclusions Methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) concentrations in meconium did not predict infant birth parameters or NAS severity. Prospective urine testing defined meconium drug detection windows for opiates and cocaine as three months, rather than the currently accepted six months. The presence of opioids in meconium could be used as a biomarker for infants at elevated risk in the newborn period. PMID:20854338

  18. Incidence of Neonatal Abstinence Syndrome - 28 States, 1999-2013.

    PubMed

    Ko, Jean Y; Patrick, Stephen W; Tong, Van T; Patel, Roshni; Lind, Jennifer N; Barfield, Wanda D

    2016-01-01

    Neonatal abstinence syndrome (NAS) is a postnatal drug withdrawal syndrome that occurs primarily among opioid-exposed infants shortly after birth, often manifested by central nervous system irritability, autonomic overreactivity, and gastrointestinal tract dysfunction (1). During 2000-2012, the incidence of NAS in the United States significantly increased (2,3). Several recent publications have provided national estimates of NAS (2,3); however, data describing incidence at the state level are limited. CDC examined state trends in NAS incidence using all-payer, hospital inpatient delivery discharges compiled in the State Inpatient Databases of the Healthcare Cost and Utilization Project (HCUP) during 1999-2013. Among 28 states with publicly available data in HCUP during 1999-2013, the overall NAS incidence increased 300%, from 1.5 per 1,000 hospital births in 1999, to 6.0 per 1,000 hospital births in 2013. During the study period, significant increases in NAS incidence occurred in 25 of 27 states with at least 3 years of data, with annual incidence rate changes ranging from 0.05 (Hawaii) to 3.6 (Vermont) per 1,000 births. In 2013, NAS incidence ranged from 0.7 cases per 1,000 hospital births (Hawaii) to 33.4 cases per 1,000 hospital births (West Virginia). The findings underscore the importance of state-based public health programs to prevent unnecessary opioid use and to treat substance use disorders during pregnancy, as well as decrease the incidence of NAS. PMID:27513154

  19. Potential reduced exposure products (PREPs) for smokeless tobacco users: Clinical evaluation methodology

    PubMed Central

    Gray, Jennifer N.; Breland, Alison B.; Weaver, Michael; Eissenberg, Thomas

    2011-01-01

    Several potential reduced exposure products (PREPs) for smokeless tobacco (SLT) users are marketed in the United States, though their effects are largely unknown. These products include some that are low in tobacco-specific nitrosamines (TSNs), like Stonewall, a pressed tobacco tablet, and General snus, a moist snuff product produced in Sweden. Methodology assessing the toxicant exposure and effects of cigarette-like PREPs for smokers has been developed, and might be modified for use in evaluating PREPs for SLT users. This report describes two studies examining the toxicant exposure and effects of two PREPs for SLT users. Study 1 (n = 13) consisted of four 4.5-hr laboratory sessions where SLT products (own brand, Stonewall, General snus, and tobacco-free placebo) were used for four 30-min episodes and nicotine exposure and tobacco/nicotine abstinence symptoms were measured. Study 2 (n = 19) consisted of four 5-day ad libitum use periods when participants used own brand, Stonewall, General snus, or no SLT and urinary levels of metabolites of nicotine (cotinine) and the TSN 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNAL) and abstinence symptoms were measured. Compared with own brand, Stonewall was associated with lower levels of cotinine and NNAL, while General snus was associated with similar levels of cotinine and lower levels of NNAL. Abstinence symptoms generally did not differ across tobacco conditions. These results show that clinical laboratory methods can be used to evaluate the toxicant exposure and abstinence symptom suppression associated with PREPs for SLT users. PMID:19023835

  20. Relations between in-treatment and follow-up abstinence among cocaine-dependent homeless persons in three clinical trials.

    PubMed

    Vuchinich, Rudy; Wallace, Dennis; Milby, Jesse B; Schumacher, Joseph E; Mennemeyer, Stephen; Kertesz, Stefan

    2009-06-01

    Clinical trials with cocaine-dependent outpatients have found a strong relation between in-treatment and follow-up abstinence, and the strength of this relation is constant across treatment conditions with variable efficacy in generating abstinence. The authors conducted secondary analyses of data from 3 clinical trials to determine whether this relation generalizes to cocaine-dependent homeless persons. The 3 trials (total N = 543) were conducted in a community health care facility for homeless people. The 7 treatment arms across the 3 trials were combinations of day treatment, abstinence-contingent housing, and vocational training. Drug use was measured with urine toxicology testing. Consecutive weeks of abstinence during treatment were strongly related to abstinence at the 12-month follow-up, whether or not missing 12-month data were included in the analysis. The treatment arms differed in their efficacy in generating abstinence, but the relation between in-treatment and follow-up abstinence did not differ across treatment arms. These results replicate earlier reports of these relations and extend them to a population of homeless people. The lack of differences between treatment arms in the in-treatment-follow-up abstinence relation implies that that relation is independent of the treatment-specific intervention components that generate group differences in abstinence. PMID:19586231

  1. Sailing against the tide? Sustaining sexual abstinence among Christian youth in a university setting in South Africa.

    PubMed

    Mbotho, Mbali; Cilliers, Michelle; Akintola, Olagoke

    2013-03-01

    This qualitative study sought to understand the perceptions and experiences of abstinence among young Christians in a University in South Africa. Willingness to adhere to Christian teachings of sexual chastity is the primary motivation for sexual abstinence while spiritual, mental and physical health benefits of abstinence as well as enforcement of Christian teachings by members and peers are secondary motivations that help sustain sexual abstinence. Sexual pressures come from desire to satisfy sexual urge, subtle coercion, peer pressure, momentary loss of self-control. There is need for multi-pronged interventions aimed at empowering Christian youth to deal with sources of sexual pressures. PMID:21253847

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

    PubMed

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

    2012-11-01

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

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

    PubMed Central

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

    2012-01-01

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

  4. Provider views of harm reduction versus abstinence policies within homeless services for dually diagnosed adults

    PubMed Central

    Padgett, Deborah K.; Tiderington, Emmy

    2013-01-01

    Harm reduction is considered by many to be a legitimate alternative to abstinence-based services for dually diagnosed individuals, yet there is limited understanding of how varying approaches affect front-line practice within supportive housing services for homeless adults. This paper examines how front-line providers working with individuals who have experienced homelessness, serious mental illness, and addiction view policies of harm reduction versus abstinence within two distinctly different approaches to homeless services: the traditional or ‘treatment first’ (TF) approach that requires abstinence and the more recent Housing First (HF) approach that incorporates harm reduction. As part of a federally-funded qualitative study, 129 in-depth interviews conducted with 41 providers were thematically analyzed to understand how providers view a harm reduction versus abstinence approach. Themes included: (a) harm reduction as a welcomed alternative; (b) working with ambiguity; and (c) accommodating abstinence. Drawing on recovery principles, we consider the broader implications of the findings for behavioral health care with this population. PMID:23404076

  5. Cocaine abstinence following chronic treatment alters cerebral metabolism in dopaminergic reward regions. Bromocriptine enhances recovery

    SciTech Connect

    Clow, D.W.; Hammer, R.P. Jr. )

    1991-01-01

    2-(14C)deoxyglucose autoradiography was used to determine local cerebral glucose utilization (lCGU) in rats following chronic cocaine treatment and subsequent abstinence. lCGU was examined in 43 discrete brain regions in animals which had received daily injections of cocaine for 14 days (10 mg/kg) followed by 3 days of saline or bromocriptine (10 mg/kg) treatment. Cocaine abstinence following chronic treatment significantly reduced lCGU in several regions including mesocorticolimbic structures such as ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc). Within the NAc, however, only the rostral pole showed significant reduction. In contrast, when bromocriptine treatment accompanied abstinence, lCGU was no longer reduced in mesocorticolimbic and most other regions, implying that metabolic recovery was enhanced by bromocriptine treatment during early abstinence following chronic cocaine treatment. These data suggest that cerebral metabolism is decreased during cocaine abstinence following chronic treatment in critical brain regions, and that this alteration can be prevented by treatment with direct-acting dopamine agonists such as bromocriptine.

  6. Surviving Drug Addiction: The Effect of Treatment and Abstinence on Mortality

    PubMed Central

    Dennis, Michael L.; Laudet, Alexandre; Funk, Rodney R.; Simeone, Ronald S.

    2011-01-01

    Objectives. We examined the relationships between substance abuse treatment, abstinence, and mortality in a sample of individuals entering treatment. We also estimated overall mortality rates and the extent to which they varied according to demographic, clinical severity, and treatment variables. Methods. We used data from a 9-year longitudinal study of 1326 adults entering substance abuse treatment on the west side of Chicago, of whom 131 died (11.0 per 1000 person-years). Baseline predictors, initial and long-term treatment response, and substance use patterns were used to predict mortality rates and time to mortality. Results. Older age, health problems, and substance use were associated with an increased risk of mortality, and higher percentages of time abstinent and longer durations of continuous abstinence were associated with a reduced risk of mortality. Treatment readmission in the first 6 months after baseline was related to an increased likelihood of abstinence, whereas readmission after 6 months was related to a decreased likelihood of abstinence, suggesting that treatment timing is significant. Conclusions. Our findings suggest the need to shift the addiction treatment field from an acute care model to a chronic disease management paradigm and the need for more aggressive screening, intervention, and addiction management over time. PMID:21330586

  7. Predictors of tobacco smoking abstinence among tuberculosis patients in South Africa.

    PubMed

    Louwagie, Goedele M C; Ayo-Yusuf, Olalekan A

    2015-06-01

    This study examines predictors of smoking cessation in tuberculosis patients with high HIV co-infection rates in a South African primary care setting. Current smokers were randomly allocated to brief motivational interviewing (n = 205) or receipt of a brief message (n = 204). Multi-level logistic regression was performed to identify predictors of sustained 3- and 6-month abstinence and 7-day point prevalence abstinence (PPA) at 1 month, with the facility as a random effect. The intervention was ineffective among smokers with high nicotine-dependence at 1 month, but was effective for all smokers over longer periods. Higher baseline self-efficacy predicted the 1-month 7-day PPA, but not sustained abstinence. HIV-positive participants' odds of sustained abstinence were about three times higher than those of their HIV-negative counterparts. Results support a more intensive motivational intervention and/or coping skills' training to increase self-efficacy and abstinence rates. Tobacco cessation services can be introduced in tuberculosis services where high HIV co-infection rates occur. PMID:25655663

  8. A model to examine the validity of the 6-month abstinence criterion for liver transplantation.

    PubMed

    Yates, W R; Martin, M; LaBrecque, D; Hillebrand, D; Voigt, M; Pfab, D

    1998-04-01

    Six months of abstinence from alcohol is a commonly used criterion for liver transplantation eligibility for patients with alcoholic cirrhosis. There is limited evidence to document the validity of this criterion with regard to risk of alcoholism relapse. Ninety-one patients with alcoholic cirrhosis were interviewed for relapse risk using the High Risk Alcoholism Relapse (HRAR) Scale. The HRAR model can be used to predict relapse risk independent of duration of sobriety and therefore can be used to examine the validity of the 6 months of abstinence criteria in this clinical population. The two methods demonstrated poor to fair agreement. Agreement was highest with a cutoff allowing a 5% 6-month relapse risk when 79% agreement (c = 0.56) was demonstrated between the two methods. Using the 6-month abstinence criterion alone disallows a significant number of candidates who have a low relapse risk based on their HRAR score. The validity of the 6-month abstinence criterion is supported somewhat by comparison with the HRAR model. However, use of the 6-month abstinence criterion alone forces a significant number of patients with a low relapse risk by HRAR to wait for transplant listing. A relapse risk model based on an estimate of alcoholism severity in addition to duration of sobriety may more accurately select patients who are most likely to benefit from liver transplantation. PMID:9581661

  9. Amount of earnings during prize contingency management treatment is associated with post-treatment abstinence outcomes

    PubMed Central

    Petry, Nancy M.; Roll, John M.

    2012-01-01

    Contingency management (CM) treatments that provide patients with the opportunity to earn chances of winning prizes of varying magnitudes are becoming increasingly popular. In the CM literature, magnitude of reinforcement is linked with effect sizes, such that CM treatments that provide larger magnitude reinforcement are more efficacious than those that provide lower magnitude reinforcement. With prize CM, even when magnitudes of overall expected prize earnings are constant, some patients win more prizes than others. Thus, patients who win larger overall amounts of prizes during treatment may have better outcomes than those who win fewer prizes. This study evaluated the impact of overall amounts of prizes won on long-term abstinence outcomes. The dollar amount of prizes won during prize CM treatments was determined from 78 cocaine abusing methadone maintenance patients who were randomized to prize CM treatments in three clinical trials. Abstinence three months following the end of the CM intervention was the primary dependent variable. The dollar amount of prizes won during CM treatment was a significant predictor of submission of cocaine-negative urine samples and self reports of cocaine abstinence at the follow-up evaluation, even after controlling for other variables associated with long-term abstinence such as pre-treatment urinalysis results and longest duration of abstinence achieved during treatment. These results suggest that magnitudes of earnings during prize CM may impact outcomes and call for further experimentation of parameters related to the efficacy of prize CM. PMID:21707189

  10. Human Ecstasy use is associated with increased cortical excitability: an fMRI study.

    PubMed

    Bauernfeind, Amy L; Dietrich, Mary S; Blackford, Jennifer U; Charboneau, Evonne J; Lillevig, James G; Cannistraci, Christopher J; Woodward, Neil D; Cao, Aize; Watkins, Tristan; Di Iorio, Christina R; Cascio, Carissa; Salomon, Ronald M; Cowan, Ronald L

    2011-05-01

    The serotonergic neurotoxin, 3,4-methylenedioxymethamphetamine (MDMA/Ecstasy), is a highly popular recreational drug. Human recreational MDMA users have neurocognitive and neuropsychiatric impairments, and human neuroimaging data are consistent with animal reports of serotonin neurotoxicity. However, functional neuroimaging studies have not found consistent effects of MDMA on brain neurophysiology in human users. Several lines of evidence suggest that studying MDMA effects in visual system might reveal the general cortical and subcortical neurophysiological consequences of MDMA use. We used 3 T functional magnetic resonance imaging during visual stimulation to compare visual system lateral geniculate nucleus (LGN) and Brodmann Area (BA) 17 and BA 18 activation in 20 long abstinent (479.95±580.65 days) MDMA users and 20 non-MDMA user controls. Lifetime quantity of MDMA use was strongly positively correlated with blood oxygenation level-dependent (BOLD) signal intensity in bilateral LGN (r(s)=0.59; p=0.007), BA 17 (r(s)=0.50; p=0.027), and BA 18 (r(s)=0.48; p=0.031), and with the spatial extent of activation in BA 17 (r(s)=0.059; p=0.007) and BA 18 (r(s)=0.55; p=0.013). There were no between-group differences in brain activation in any region, but the heaviest MDMA users showed a significantly greater spatial extent of activation than controls in BA 17 (p=0.031) and BA 18 (p=0.049). These results suggest that human recreational MDMA use may be associated with a long-lasting increase in cortical excitability, possibly through loss of serotonin input to cortical and subcortical regions. When considered in the context of previous results, cortical hyper-excitability may be a biomarker for MDMA-induced serotonin neurotoxicity. PMID:21326196

  11. 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

  12. Effectiveness of abstinence-based incentives: interaction with intake stimulant test results.

    PubMed

    Stitzer, Maxine L; Petry, Nancy; Peirce, Jessica; Kirby, Kimberly; Killeen, Therese; Roll, John; Hamilton, John; Stabile, Patricia Q; Sterling, Robert; Brown, Chanda; Kolodner, Ken; Li, Rui

    2007-10-01

    Intake urinalysis test result (drug positive vs. negative) has been previously identified as a strong predictor of drug abuse treatment outcome, but there is little information about how this prognostic factor may interact with the type of treatment delivered. The authors used data from a multisite study of abstinence incentives for stimulant abusers enrolled in outpatient counseling treatment (N. M. Petry, J. M. Peirce, et al., 2005) to examine this question. The first study urine was used to stratify participants into stimulant negative (n = 306) versus positive (n = 108) subgroups. Abstinence incentives significantly improved retention in those testing negative but not in those testing positive. Findings suggest that stimulant abusers presenting to treatment with a stimulant-negative urine benefit from abstinence incentives, but alternative treatment approaches are needed for those who test stimulant positive at intake. PMID:17907862

  13. Alcohol liver disease: A review of current therapeutic approaches to achieve long-term abstinence

    PubMed Central

    García, María Luisa Gutiérrez; Blasco-Algora, Sara; Fernández-Rodríguez, Conrado M

    2015-01-01

    Harmful alcohol drinking may lead to significant damage on any organ or system of the body. Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease in Europe. In ALD, only alcohol abstinence was associated with a better long-term survival. Therefore, current effective therapeutic strategy should be oriented towards achieving alcohol abstinence or a significant reduction in alcohol consumption. Screening all primary care patients to detect those cases with alcohol abuse has been proposed as population-wide preventive intervention in primary care. It has been suggested that in patients with mild alcohol use disorder the best approach is brief intervention in the primary care setting with the ultimate goal being abstinence, whereas patients with moderate-to-severe alcohol use disorder must be referred to specialized care where detoxification and medical treatment of alcohol dependence must be undertaken. PMID:26229395

  14. A Deposit Contract Method to Deliver Abstinence Reinforcement for Cigarette Smoking

    PubMed Central

    Dallery, Jesse; Meredith, Steven; Glenn, Irene M

    2008-01-01

    Eight smokers were randomly assigned to a deposit contract ($50.00) or to a no-deposit group. Using a reversal design, participants could recoup their deposit (deposit group) or earn vouchers (no-deposit group) for smoking reductions and abstinence (breath carbon monoxide [CO] ≤ 4 parts per million) during treatment phases. Treatment was delivered via a novel Internet-based method to monitor smoking status. Although equivalent decreases in breath CO and abstinence were observed during treatment in both groups, $178.50 in vouchers were distributed to participants in the no-deposit group, whereas a small surplus remained in the deposit group. A deposit contract method may represent a cost-effective model to deliver abstinence reinforcement for cigarette smoking. PMID:19192864

  15. Alcohol liver disease: A review of current therapeutic approaches to achieve long-term abstinence.

    PubMed

    García, María Luisa Gutiérrez; Blasco-Algora, Sara; Fernández-Rodríguez, Conrado M

    2015-07-28

    Harmful alcohol drinking may lead to significant damage on any organ or system of the body. Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease in Europe. In ALD, only alcohol abstinence was associated with a better long-term survival. Therefore, current effective therapeutic strategy should be oriented towards achieving alcohol abstinence or a significant reduction in alcohol consumption. Screening all primary care patients to detect those cases with alcohol abuse has been proposed as population-wide preventive intervention in primary care. It has been suggested that in patients with mild alcohol use disorder the best approach is brief intervention in the primary care setting with the ultimate goal being abstinence, whereas patients with moderate-to-severe alcohol use disorder must be referred to specialized care where detoxification and medical treatment of alcohol dependence must be undertaken. PMID:26229395

  16. Convergent evidence from alcohol-dependent humans and rats for a hyperdopaminergic state in protracted abstinence.

    PubMed

    Hirth, Natalie; Meinhardt, Marcus W; Noori, Hamid R; Salgado, Humberto; Torres-Ramirez, Oswaldo; Uhrig, Stefanie; Broccoli, Laura; Vengeliene, Valentina; Roßmanith, Martin; Perreau-Lenz, Stéphanie; Köhr, Georg; Sommer, Wolfgang H; Spanagel, Rainer; Hansson, Anita C

    2016-03-15

    A major hypothesis in addiction research is that alcohol induces neuroadaptations in the mesolimbic dopamine (DA) system and that these neuroadaptations represent a key neurochemical event in compulsive drug use and relapse. Whether these neuroadaptations lead to a hypo- or hyperdopaminergic state during abstinence is a long-standing, unresolved debate among addiction researchers. The answer is of critical importance for understanding the neurobiological mechanism of addictive behavior. Here we set out to study systematically the neuroadaptive changes in the DA system during the addiction cycle in alcohol-dependent patients and rats. In postmortem brain samples from human alcoholics we found a strong down-regulation of the D1 receptor- and DA transporter (DAT)-binding sites, but D2-like receptor binding was unaffected. To gain insight into the time course of these neuroadaptations, we compared the human data with that from alcohol-dependent rats at several time points during abstinence. We found a dynamic regulation of D1 and DAT during 3 wk of abstinence. After the third week the rat data mirrored our human data. This time point was characterized by elevated extracellular DA levels, lack of synaptic response to D1 stimulation, and augmented motor activity. Further functional evidence is given by a genetic rat model for hyperdopaminergia that resembles a phenocopy of alcohol-dependent rats during protracted abstinence. In summary, we provide a new dynamic model of abstinence-related changes in the striatal DA system; in this model a hyperdopaminergic state during protracted abstinence is associated with vulnerability for relapse. PMID:26903621

  17. Psychological symptoms are associated with both abstinence and risky sex among men with HIV.

    PubMed

    Miller, Carol T; Solomon, Sondra E; Bunn, Janice Y; Varni, Susan E; Hodge, James J

    2015-02-01

    Sexual abstinence is often deemed the "safest behavior" in HIV prevention, but is sometimes associated with psychological symptoms (e.g., depression) just as sexually risky behavior is. This study explored whether sexual abstinence and risky sexual behavior among men with HIV were associated with similar constellations of psychological symptoms. Prior research has not addressed this issue because abstinent people often are not included in the sample or, when data are analyzed, researchers combine abstinent people with sexually active people who practice safer sex. Past research also neglects the co-morbidity of psychological symptoms. A latent class analysis of the psychological symptoms (assessed with the Symptom Check List 90-R; Derogatis, 1994) of 140 men with HIV, mostly from rural New England, revealed three latent classes: men who were asymptomatic on all symptom domains (28.8 %), men who were symptomatic on all domains (34.1 %), and men who were symptomatic on internalizing domains (37.1 %), but were asymptomatic on the externalizing symptoms of hostility and paranoid ideation. Logistic regression showed that sexual behavior during the past 90 days of men in the all symptom class and the internalizing symptoms class was similar, with abstinence and risky sex predominating, and safer sex being relatively uncommon for both classes. The sexual behavior of men in the asymptomatic class differed, with safer sex being relatively more likely to occur compared to the symptomatic classes. These findings suggest that the psychological symptom profile of sexually abstinent people places them at risk for inconsistent condom use should they engage in sexual behavior. PMID:25614050

  18. Psychological Symptoms are Associated with Both Abstinence and Risky Sex among Men with HIV

    PubMed Central

    Miller, Carol T.; Solomon, Sondra E.; Bunn, Janice Y.; Varni, Susan E.; Hodge, James J.

    2015-01-01

    Sexual abstinence is often deemed the “safest behavior” in HIV prevention, but is sometimes associated with psychological symptoms (e.g., depression) just as sexually risky behavior is. This study explored whether sexual abstinence and risky sexual behavior among men with HIV are associated with similar constellations of psychological symptoms. Prior research has not addressed this issue because abstinent people often are not included in the sample, or when data are analyzed, researchers combine abstinent people with sexually active people who practice safer sex. Past research also neglects the co-morbidity of psychological symptoms. A latent class analysis of the psychological symptoms (assessed with the Symptom Check List 90-R; Derogatis, 1994) of 140 men with HIV, mostly from rural New England, revealed three latent classes; men who were asymptomatic on all symptom domains (28.8%), men who were symptomatic on all domains (34.1%), and men who were symptomatic on internalizing domains (37.1%), but were asymptomatic on the externalizing symptoms of hostility and paranoid ideation. Logistic regression showed that sexual behavior during the past 90 days of men in the all symptom class and the internalizing symptoms class was similar, with abstinence and risky sex predominating, and safer sex being relatively uncommon for both classes. The sexual behavior of men in the asymptomatic class differed, with safer sex being relatively more likely to occur compared to the symptomatic classes. These findings suggest that the psychological symptom profile of sexually abstinent people places them at risk for inconsistent condom use should they engage in sexual behavior. PMID:25614050

  19. Acceptability of OCT and Abstinence Requirements among Women Participating in Microbicide Safety Trials

    PubMed Central

    Breitkopf, Carmen Radecki; Loza, Melissa; Vincent, Kathleen; Moench, Thomas; Stanberry, Lawrence R.; Rosenthal, Susan L.

    2011-01-01

    Background Developing effective and safe microbicides requires study procedures (e.g. technology used, abstinence requirements, and product use) that are acceptable to participants. Methods Thirty women completed 4 study visits including pelvic examination, colposcopy, optical coherence tomography (OCT), and semi-structured, qualitative interviews. Additional requirements included abstinence (for approximately 16 days) and twice daily vaginal product use (for 5.5 days). Interviews were audio-recorded, transcribed, and analyzed using framework analysis. Themes addressing OCT experiences, acceptability of abstinence, and vaginal product use were examined. Results OCT was viewed favorably as an imaging technology. Some women reported feeling the fiber-optic probe “poking” them and over one-third spontaneously reported feeling pressure or pinching upon rotation of the speculum in connection with the OCT evaluation. Compliance with vaginal gel use was high, but for many women assigned to use a product containing nonoxynol-9 (versus placebo), the post-product use exam was more uncomfortable, relative to the initial exam or one week following product discontinuation. Nearly all women experienced product leakage; acceptability of leakage varied. Two women were not abstinent and several more found abstinence challenging. Some women involved their partner in decision making regarding trial enrollment. Strategies to remain abstinent included participating when the partner was away, avoiding early intimacy, and engaging in alternative sexual activities. Conclusions Qualitative interviews in early-phase studies provide insights and capture information that would be missed by behavioral inference alone. Understanding participant’s experiences is important in order to provide anticipatory guidance and plan future microbicide studies that facilitate adherence with trial requirements. PMID:22183842

  20. Learning To Speak Out in an Abstinence Based Sex Education Group: Gender and Race Work in an Urban Magnet School.

    ERIC Educational Resources Information Center

    Weis, Lois

    This paper describes an abstinence-based sex education group for diverse girls in grades 7-12 in an urban magnet school. Data were gathered from a within-school program, My Bottom Line, which was designed to prevent or delay the onset of sexual activity, build self-esteem, and increase young women's self-sufficiency through an abstinence based,…

  1. Adult Discrimination against Children: The Case of Abstinence-Only Education in Twenty-First-Century USA

    ERIC Educational Resources Information Center

    Greslé-Favier, Claire

    2013-01-01

    This paper analyses abstinence-only education programmes and discourses within the frame of theories of adult discrimination against children. To begin with, a definition of abstinence-only programmes and of the political context in which they were created will be provided. These programmes will then be analysed through the lens of children's…

  2. Developmental 3,4-methylenedioxymethamphetamine (MDMA) impairs sequential and spatial but not cued learning independent of growth, litter effects or injection stress.

    PubMed

    Williams, Michael T; Morford, LaRonda L; Wood, Sandra L; Rock, Stephanie L; McCrea, Anne E; Fukumura, Masao; Wallace, Tanya L; Broening, Harry W; Moran, Mary S; Vorhees, Charles V

    2003-04-01

    Previously, we have shown that rats administered MDMA from postnatal (P) days 11-20 had reductions in body weight during the period of treatment and as adults they had deficits in sequential and spatial learning and memory. In the present study, to control for weight reductions, we used litters with double the number of offspring to induce growth restriction comparable to that of standard size litters treated with MDMA. Litters were treated twice daily from P11 to 20 with vehicle or MDMA (20 mg/kg) or only weighed. Males, but not females, exposed to MDMA had longer latencies and more errors in the Cincinnati water maze compared to males of the other treatments. In the Morris water maze (210 cm pool, 10x10 cm platform), the MDMA animals were impaired relative to all other treatments during acquisition. Only the MDMA females showed deficits when the platform was shifted to a new location, however, both MDMA males and females were impaired when the location of the platform was again shifted and a reduced platform (5x5 cm) used. No differences were observed in the ability to swim a straight channel, locate a platform with a cue, or the endocrine response to forced swim among the treatment groups. No differences were seen between animals injected with saline and those only weighed. The data suggest that factors, such as growth retardation, multiple injections, or the composition of the litter, do not affect the development of learning and memory impairments resulting from P11 to 20 MDMA exposure. The large litter approach offers a novel method to control for undernutrition during the preweaning period in rodents. PMID:12644267

  3. MDMA increases glutamate release and reduces parvalbumin-positive GABAergic cells in the dorsal hippocampus of the rat: role of cyclooxygenase

    PubMed Central

    Anneken, John H.; Cunningham, Jacobi I.; Collins, Stuart A.; Yamamoto, Bryan K.; Gudelsky, Gary A.

    2012-01-01

    3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a popular drug of abuse with well-documented acute effects on serotonergic, dopaminergic, and cholinergic transmitter systems, as well as evidence of long-term disruption of serotoninergic systems in the rat brain. Recently, it was demonstrated that MDMA evokes a delayed and sustained increase in glutamate release in the hippocampus. The purpose of the present study was to determine the role of inflammatory mediators in the MDMA-induced increase in glutamate release, as well as the contribution of inflammatory pathways in the persistent neurochemical toxicity associated with repeated MDMA treatment. Treatment with the non-selective cyclooxygenase (COX) inhibitor ketoprofen and the COX-2 selective inhibitor nimesulide attenuated the increase in extracellular glutamate in the hippocampus evoked by repeated MDMA exposure (10 mg/kg, i.p., every 2 h); no attenuation was observed in rats treated with the COX-1 selective inhibitor piroxicam. Reverse dialysis of a major product of COX activity, prostaglandin E2, also resulted in a significant increase in extracellular glutamate in the hippocampus. Repeated exposure to MDMA diminished the number of parvalbumin-positive GABA interneurons in the dentate gyrus of the hippocampus, an effect that was attenuated by ketoprofen treatment. However, COX inhibition with ketoprofen did not prevent the long-term depletion of 5-HT in the hippocampus evoked by MDMA treatment. These data are supportive of the view that cyclooxygenase activity contributes to the mechanism underlying both the increased release of glutamate and decreased number of GABA interneurons in the rat hippocampus produced by repeated MDMA exposure. PMID:23179355

  4. The mechanisms involved in the long-lasting neuroprotective effect of fluoxetine against MDMA (‘ecstasy')-induced degeneration of 5-HT nerve endings in rat brain

    PubMed Central

    Sanchez, V; Camarero, J; Esteban, B; Peter, M J; Green, A R; Colado, M I

    2001-01-01

    It has been reported that co-administration of fluoxetine with 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy') prevents MDMA-induced degeneration of 5-HT nerve endings in rat brain. The mechanisms involved have now been investigated. MDMA (15 mg kg−1, i.p.) administration produced a neurotoxic loss of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in cortex, hippocampus and striatum and a reduction in cortical [3H]-paroxetine binding 7 days later. Fluoxetine (10 mg kg−1, i.p., ×2, 60 min apart) administered concurrently with MDMA or given 2 and 4 days earlier provided complete protection, and significant protection when given 7 days earlier. Fluvoxamine (15 mg kg−1, i.p., ×2, 60 min apart) only produced neuroprotection when administered concurrently. Fluoxetine (10 mg kg−1, ×2) markedly increased the KD and reduced the Bmax of cortical [3H]-paroxetine binding 2 and 4 days later. The Bmax was still decreased 7 days later, but the KD was unchanged. [3H]-Paroxetine binding characteristics were unchanged 24 h after fluvoxamine (15 mg kg−1, ×2). A significant cerebral concentration of fluoxetine plus norfluoxetine was detected over the 7 days following fluoxetine administration. The fluvoxamine concentration had decreased markedly by 24 h. Pretreatment with fluoxetine (10 mg kg−1, ×2) failed to alter cerebral MDMA accumulation compared to saline pretreated controls. Neither fluoxetine or fluvoxamine altered MDMA-induced acute hyperthermia. These data demonstrate that fluoxetine produces long-lasting protection against MDMA-induced neurodegeneration, an effect apparently related to the presence of the drug and its active metabolite inhibiting the 5-HT transporter. Fluoxetine does not alter the metabolism of MDMA or its rate of cerebral accumulation. PMID:11522596

  5. A study of the mechanisms involved in the neurotoxic action of 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy') on dopamine neurones in mouse brain

    PubMed Central

    Colado, M Isabel; Camarero, Jorge; Mechan, Annis O; Sanchez, Veronica; Esteban, Blanca; Elliott, J Martin; Green, A Richard

    2001-01-01

    Administration of 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy') to mice produces acute hyperthermia and long-term degeneration of striatal dopamine nerve terminals. Attenuation of the hyperthermia decreases the neurodegeneration. We have investigated the mechanisms involved in producing the neurotoxic loss of striatal dopamine. MDMA produced a dose-dependent loss in striatal dopamine concentration 7 days later with 3 doses of 25 mg kg−1 (3 h apart) producing a 70% loss. Pretreatment 30 min before each MDMA dose with either of the N-methyl-D-aspartate antagonists AR-R15896AR (20, 5, 5 mg kg−1) or MK-801 (0.5 mg kg−1×3) failed to provide neuroprotection. Pretreatment with clomethiazole (50 mg kg−1×3) was similarly ineffective in protecting against MDMA-induced dopamine loss. The free radical trapping compound PBN (150 mg kg−1×3) was neuroprotective, but it proved impossible to separate neuroprotection from a hypothermic effect on body temperature. Pretreatment with the nitric oxide synthase (NOS) inhibitor 7-NI (50 mg kg−1×3) produced neuroprotection, but also significant hypothermia. Two other NOS inhibitors, S-methyl-L-thiocitrulline (10 mg kg−1×3) and AR-R17477AR (5 mg kg−1×3), provided significant neuroprotection and had little effect on MDMA-induced hyperthermia. MDMA (20 mg kg−1) increased 2,3-dihydroxybenzoic acid formation from salicylic acid perfused through a microdialysis tube implanted in the striatum, indicating increased free radical formation. This increase was prevented by AR-R17477AR administration. Since AR-R17477AR was also found to have no radical trapping activity this result suggests that MDMA-induced neurotoxicity results from MDMA or dopamine metabolites producing radicals that combine with NO to form tissue-damaging peroxynitrites. PMID:11739248

  6. 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

  7. Interaction between Dysfunctional Connectivity at Rest and Heroin Cues-Induced Brain Responses in Male Abstinent Heroin-Dependent Individuals

    PubMed Central

    Liu, Jixin; Qin, Wei; Yuan, Kai; Li, Jing; Wang, Wei; Li, Qiang; Wang, Yarong; Sun, Jinbo; von Deneen, Karen M.; Liu, Yijun; Tian, Jie

    2011-01-01

    Background The majority of previous heroin cue-reactivity functional magnetic resonance imaging (fMRI) studies focused on local function impairments, such as inhibitory control, decision-making and stress regulation. Our previous studies have demonstrated that these brain circuits also presented dysfunctional connectivity during the resting state. Yet few studies considered the relevance of resting state dysfunctional connectivity to task-related neural activity in the same chronic heroin user (CHU). Methodology/Principal Findings We employed the method of graph theory analysis, which detected the abnormality of brain regions and dysregulation of brain connections at rest between 16 male abstinent chronic heroin users (CHUs) and 16 non-drug users (NDUs). Using a cue-reactivity task, we assessed the relationship between drug-related cue-induced craving activity and the abnormal topological properties of the CHUs' resting networks. Comparing NDUs' brain activity to that of CHUs, the intensity of functional connectivity of the medial frontal gyrus (meFG) in patients' resting state networks was prominently greater and positively correlated with the same region's neural activity in the heroin-related task; decreased functional connectivity intensity of the anterior cingulate cortex (ACC) in CHUs at rest was associated with more drug-related cue-induced craving activities. Conclusions These results may indicate that there exist two brain systems interacting simultaneously in the heroin-addicted brain with regards to a cue-reactivity task. The current study may shed further light on the neural architecture that supports craving responses in heroin dependence. PMID:22028765

  8. Implementation of a statewide surveillance system for neonatal abstinence syndrome - Tennessee, 2013.

    PubMed

    Warren, Michael D; Miller, Angela M; Traylor, Julie; Bauer, Audrey; Patrick, Stephen W

    2015-02-13

    Over the last decade, rates of opioid pain reliever prescribing grew substantially in the United States, affecting many segments of the population, including pregnant women. Nationally, Tennessee ranks second in the rate of prescriptions written for opioid pain relievers, with 1.4 per person in 2012. The rising prevalence of opioid pain reliever use and misuse in Tennessee led to an increase in adverse outcomes in the state, including neonatal abstinence syndrome (NAS). NAS is a withdrawal syndrome experienced by infants shortly after birth. The syndrome most commonly occurs after antenatal exposure to opioids, although other medications have also been implicated. From 2000 to 2009, the incidence rate of NAS in Tennessee increased from 0.7 to 5.1 per 1,000 births, exceeding the national average, which increased from 1.2 to 3.4 per 1,000 births. NAS is associated with numerous morbidities for the infant, including low birth weight, poor feeding, and respiratory problems. Previous population-based analyses of NAS relied on hospital discharge data, which typically become available for analysis only after substantial delay. In Tennessee, the rising incidence of NAS and its associated public health burden created an urgent need for timelier incidence figures to drive policy and prevention efforts. Beginning January 1, 2013, the Tennessee Department of Health (TDH) made NAS reporting mandatory. A total of 921 cases were reported in 2013 (among 79,954 births), with the most cases clustered in eastern Tennessee; 63% of cases occurred to mothers who were reported to be using at least one substance prescribed by a health care provider (e.g., opioid pain relievers or maintenance medications for opioid dependency), and 33% of cases occurred among women using illicit or diverted substances (e.g., heroin or medications prescribed for someone else). The first year's surveillance results highlight the need for primary prevention activities focused on reducing dependence

  9. Abstinence-based incentives in methadone maintenance: interaction with intake stimulant test results.

    PubMed

    Stitzer, Maxine L; Peirce, Jessica; Petry, Nancy M; Kirby, Kimberly; Roll, John; Krasnansky, Joseph; Cohen, Allan; Blaine, Jack; Vandrey, Ryan; Kolodner, Ken; Li, Rui

    2007-08-01

    Baseline drug use detected in urine toxicology has been shown to predict drug abuse treatment outcome, including response to contingency management interventions with drug abstinence as their target. This study examined the association between baseline urine test result and treatment outcome in stabilized methadone maintenance patients with ongoing stimulant use to determine whether abstinence incentives were differentially effective in those testing stimulant negative versus positive at study entry. Participants were 386 methadone-maintained patients who took part in a National Drug Abuse Treatment Clinical Trials Network multisite study aimed at reducing stimulant abuse during treatment (J. M. Peirce et al., 2006). At study intake, 24% of participants tested stimulant negative and 76% tested positive. Those testing negative at entry submitted 82% negative urines during the study versus 36% for those testing positive at entry (odds ratio [OR] = 8.67; confidence interval [CI] = 5.81-12.94). Compared with those receiving usual care, the addition of abstinence incentives resulted in a significant increase in stimulant-negative urine samples submitted during the study both for those testing negative at study entry (OR = 2.27; CI = 1.13- 4.75) and for those testing positive (OR = 1.84; CI = 1.25-2.71). These findings suggest that abstinence incentives have significant clinical benefits independent of initial drug use severity among methadone maintenance patients with ongoing stimulant drug use. PMID:17696681

  10. A Deposit Contract Method to Deliver Abstinence Reinforcement for Cigarette Smoking

    ERIC Educational Resources Information Center

    Dallery, Jesse; Meredith, Steven; Glenn, Irene M.

    2008-01-01

    Eight smokers were randomly assigned to a deposit contract ($50.00) or to a no-deposit group. Using a reversal design, participants could recoup their deposit (deposit group) or earn vouchers (no-deposit group) for smoking reductions and abstinence (breath carbon monoxide [CO] less than or equal to 4 parts per million) during treatment phases.…

  11. Government Influence and Community Involvement on Abstinence-Only Programs in 1999 and 2003

    ERIC Educational Resources Information Center

    Gusrang, Jamie L.; Cheng, Simon

    2010-01-01

    In this study, we compare federal government influence on abstinence-only programs in 1999 and 2003 to better see how shifts in the federal government's sex education polices impacted other government and community actors. Using data from the Sex Education in America Surveys (SEAS), we find that changes in federal policy, particularly after the…

  12. Teacher Perspectives on Abstinence and Safe Sex Education in South Africa

    ERIC Educational Resources Information Center

    Francis, Dennis A.; DePalma, Renée

    2014-01-01

    The stakes are high for sex education in South Africa: it has been estimated that 8.7% of young people live with HIV. Within primarily US and UK contexts, there has been much debate over the relative merits of abstinence-only and comprehensive sexual education programmes. These perspectives have largely been presented as irreconcilable, but…

  13. Group-Based Randomized Trial of Contingencies for Health and Abstinence in HIV Patients

    ERIC Educational Resources Information Center

    Petry, Nancy M.; Weinstock, Jeremiah; Alessi, Sheila M.; Lewis, Marilyn W.; Dieckhaus, Kevin

    2010-01-01

    Objective: Contingency management (CM) treatments are usually applied individually for drug abstinence, but CM can also be targeted toward health behaviors and implemented in groups. This study evaluated effects of a group-based CM intervention that focused on reinforcing health behaviors. Method: HIV-positive patients with cocaine or opioid use…

  14. Effectiveness of Abstinence-Based Incentives: Interaction with Intake Stimulant Test Results

    ERIC Educational Resources Information Center

    Stitzer, Maxine L.; Petry, Nancy; Peirce, Jessica; Kirby, Kimberly; Killeen, Therese; Roll, John; Hamilton, John; Stabile, Patricia Q.; Sterling, Robert; Brown, Chanda; Kolodner, Ken; Li, Rui

    2007-01-01

    Intake urinalysis test result (drug positive vs. negative) has been previously identified as a strong predictor of drug abuse treatment outcome, but there is little information about how this prognostic factor may interact with the type of treatment delivered. The authors used data from a multisite study of abstinence incentives for stimulant…

  15. Attacking the Personal Fable: Role-Play and Its Effect on Teen Attitudes toward Sexual Abstinence.

    ERIC Educational Resources Information Center

    Saltz, Eli; And Others

    1994-01-01

    Examines role playing as a tool for changing teenagers' attitudes about sex behavior and the consequences of teen pregnancy. A sample of 267 ninth-grade students attending a high-risk urban school participated. Role playing and watching videos of friends' role playing significantly increased favorable attitudes toward abstinence in girls but not…

  16. Making sense of abstinence: social representations in young Africans' HIV-related narratives from six countries.

    PubMed

    Winskell, Kate; Beres, Laura K; Hill, Elizabeth; Mbakwem, Benjamin Chigozie; Obyerodhyambo, Oby

    2011-09-01

    Despite the prominence of abstinence promotion in HIV prevention for young Africans, there is little documentation concerning its reception and interpretation. With the purpose of informing programmatic practice, we examined how young Africans from six countries with contrasting HIV prevalence rates make sense of abstinence. 'Scenarios from Africa' scriptwriting contests invite young people to contribute ideas for short films about HIV. Using thematic narrative-based approaches, we analyzed a stratified random sample of these narratives written in 2005 by young women and men aged 10-24 years from Senegal, Burkina Faso, South-East Nigeria, Kenya, Namibia and Swaziland. Abstinence was considerably more prominent as a theme in the samples from SE Nigeria, Kenya and Swaziland. It was articulated in relation to conservative Christian sexual morality and in opposition to condom use with particular intensity in SE Nigeria, with stigmatising implications for non-abstainers. However, cross-national commonalities were more striking than differences. Examples of non-stigmatising pro-abstinence messaging highlighted the appeal of discourses of romantic love and future plans across countries and demographic characteristics. The analysis yielded contextual understanding, youth-driven ideas and recommendations to inform comprehensive HIV-prevention efforts. PMID:21787256

  17. Sexual Partners and Contraceptive Use: A 16-Year Prospective Study Predicting Abstinence and Risk Behavior

    ERIC Educational Resources Information Center

    Siebenbruner, Jessica; Zimmer-Gembeck, Melanie J.; Egeland, Byron

    2007-01-01

    Antecedents and correlates of sexual behavior among 167 (46 female) adolescents were examined in this multi-informant longitudinal study. Data were collected at birth through middle adolescence. Data on number of sexual partners and contraception use at age 16 defined sexual abstinence (SAs, n = 73), high-risk sexual behavior (HRTs, n = 45) and…

  18. Resting state synchrony in long-term abstinent alcoholics with versus without comorbid drug dependence☆

    PubMed Central

    Camchong, Jazmin; Stenger, Victor Andrew; Fein, George

    2013-01-01

    Background We previously reported that when long-term abstinent alcoholics (LTAA; with no drug comorbidity) are compared to controls, they show increased resting state synchrony (RSS) in the executive control network and reduced RSS in the appetitive drive network suggestive of compensatory mechanisms that may facilitate abstinence. The aim of the present study was to investigate whether long-term abstinent alcoholics with comorbid stimulants dependence (LTAAS) show similar RSS mechanisms. Methods Resting-state functional MRI data were collected on 36 LTAAS (20 females, age: 47.85 ± 7.30), 23 LTAA (8 females, age: M = 47.91 ± 6.76), and 23 non-substance abusing controls (NSAC; 8 females, age: M = 47.99 ± 6.70). Using seed-based measures, we examined RSS with the nucleus accumbens (NAcc) and the subgenual anterior cingulate cortex (sgACC). Results Results showed commonalities in LTAA and LTAAS RSS (similar enhanced executive control RSS and left insula RSS) as well as differences (no attenuation of appetitive drive RSS in LTAAS and no enhancement of RSS in right insula in LTAA). Conclusions We believe these differences are adaptive mechanisms that support abstinence. These findings suggest common as well as specific targets for treatment in chronic alcoholics with vs without comorbid stimulant dependence. PMID:23639390

  19. Impacts of Four Title V, Section 510 Abstinence Education Programs. Final Report

    ERIC Educational Resources Information Center

    Trenholm, Christopher; Devaney, Barbara; Fortson, Ken; Quay, Ken; Wheeler, Justin; Clark, Melissa

    2007-01-01

    Since fiscal year 1998, the Title V, Section 510 program has allocated $50 million annually in federal funding for programs that teach abstinence form sexual activity outside of marriage as the expected standard for school-age children. A new impact report from Mathematica's congressionally mandated multi-year evaluation of four abstinence…

  20. Implementing and Evaluating a Rural Community-Based Sexual Abstinence Program: Challenges and Solutions

    ERIC Educational Resources Information Center

    Stauss, Kimberly; Boyas, Javier; Murphy-Erby, Yvette

    2012-01-01

    Informing both program evaluation and practice research, this paper describes lessons learned during the planning, implementation, and pilot phases of an abstinence education program based in a rural community in a southern state in the USA. Although a number of challenges can emerge in successfully implementing and evaluating such a program in a…

  1. An Evaluation of an Abstinence-Only Sex Education Curriculum: An 18-Month Follow-Up

    ERIC Educational Resources Information Center

    Denny, George; Young, Michael

    2006-01-01

    The article examines the results from an 18-month follow-up evaluation of an abstinence education curriculum series. Participants were students from 15 school districts recruited to participate in the project. The intervention was the Sex Can Wait curriculum series, consisting of upper elementary, middle school, and high school components. The…

  2. Evaluation of an Abstinence-Only Adolescent Pregnancy Prevention Program: A Replication.

    ERIC Educational Resources Information Center

    Roosa, Mark W.; Christopher, F. Scott

    1990-01-01

    Second evaluation of abstinence-only adolescent pregnancy prevention program included 528 subjects. None of desired changes in attitudes or behavior (premarital sexual attitudes, sexual behaviors, self-esteem, family communication) occurred for total sample or for virgins in sample. Findings question federal policy of relying exclusively on…

  3. Differential Transitions between Cocaine Use and Abstinence for Men and Women

    ERIC Educational Resources Information Center

    Gallop, Robert J.; Crits-Christoph, Paul; Ten Have, Thomas R.; Barber, Jacques P.; Frank, Arlene; Griffin, Margaret L.; Thase, Michael E.

    2007-01-01

    The longitudinal course of cocaine dependence is characterized by alternating periods of abstinence and relapse. Although gender has emerged as an important predictor of relapse, previous studies have examined mean differences in use by gender. Focusing strictly on differences in averages between men and women does not address potential gender…

  4. Spinal cord thyrotropin releasing hormone receptors of morphine tolerant-dependent and abstinent rats

    SciTech Connect

    Rahmani, N.H.; Gulati, A.; Bhargava, H.N. )

    1990-07-01

    The effect of chronic administration of morphine and its withdrawal on the binding of 3H-(3-MeHis2)thyrotropin releasing hormone (3H-MeTRH) to membranes of the spinal cord of the rat was determined. Male Sprague-Dawley rats were implanted with either 6 placebo or 6 morphine pellets (each containing 75-mg morphine base) during a 7-day period. Two sets of animals were used. In one, the pellets were left intact at the time of sacrificing (tolerant-dependent) and in the other, the pellets were removed 16 hours prior to sacrificing (abstinent rats). In placebo-pellet-implanted rats, 3H-MeTRH bound to the spinal cord membranes at a single high affinity binding site with a Bmax of 21.3 +/- 1.6 fmol/mg protein, and an apparent dissociation constant Kd of 4.7 +/- 0.8 nM. In morphine tolerant-dependent or abstinent rats, the binding constants of 3H-MeTRH to spinal cord membranes were unaffected. Previous studies from this laboratory indicate that TRH can inhibit morphine tolerance-dependence and abstinence processes without modifying brain TRH receptors. Together with the present results, it appears that the inhibitory effect of TRH on morphine tolerance-dependence and abstinence is probably not mediated via central TRH receptors but may be due to its interaction with other neurotransmitter systems.

  5. Motivational interviewing group at inpatient detoxification, its influence in maintaining abstinence and treatment retention after discharge.

    PubMed

    Bachiller, Diana; Grau-López, Lara; Barral, Carmen; Daigre, Constanza; Alberich, Cristina; Rodríguez-Cintas, Laia; Valero, Sergi; Casas, Miquel; Roncero, Carlos

    2015-01-01

    The relapse rate after discharge from inpatient detoxification is high. The objective of this pilot study is to assess the sociodemographic, clinical and therapeutic factors associated with maintaining abstinence in patients who participated in a brief motivational interviewing group during admission for detoxification. A total of 46 patients, diagnosed substance dependent according to DSM -IV, and admitted to the Hospital Detoxification Unit, participated in a brief motivational interviewing group. Sociodemographic, clinical, motivation to change (University of Rhode Island Change Assessment, URICA) and satisfaction with the treatment group (Treatment Perceptions Questionnaire, CPT) data were collected. Abstinence and treatment retention two months after discharge were assessed by weekly telephone calls. A survival analysis was performed. Being male, having more cognitions of the maintenance stage of change at discharge, being satisfied with group therapy and therapist during hospitalization are associated with longer abstinence after discharge. The brief motivational interviewing group approach with patients admitted for detoxification is related to greater likelihood of maintaining abstinence and subsequent treatment retention. PMID:26132300

  6. Sex Can Wait: An Abstinence-Based Sexuality Curriculum for Upper Elementary School.

    ERIC Educational Resources Information Center

    Young, Michael; Young, Tamera

    This curriculum, directed primarily to students in grades five and six, is a 5-week sexuality education program designed to promote sexual abstinence as the best decision young people can make for themselves. The guide is divided into three general areas of emphasis: Knowing Myself, Reltating to Others, and Planning My Future. These sections are…

  7. Sex Can Wait: An Abstinence-Based Sexuality Curriculum for High School.

    ERIC Educational Resources Information Center

    Core-Gebhart, Pennie; And Others

    This curriculum, directed primarily to students in grades nine and ten, is a 5-week sexuality education program designed to promote sexual abstinence as the best decision young people can make for themselves. The guide is divided into four general areas of emphasis. Section one, "Knowing Myself," helps students feel good about who they are as…

  8. The Evaluation of Abstinence Education Programs Funded Under Title V Section 510: Interim Report.

    ERIC Educational Resources Information Center

    Devaney, Barbara; Johnson, Amy; Maynard, Rebecca; Trenholm, Chris

    This report presents interim findings from an independent, federally funded evaluation of the abstinence education programs authorized under the Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA) and defined under Title V, Section 510 (b)(2)(A-H) of the Social Security Act. The report draws heavily on 4 years of…

  9. Adolescents' Thoughts about Abstinence Curb the Return of Marijuana Use during and after Treatment

    ERIC Educational Resources Information Center

    King, Kevin M.; Chung, Tammy; Maisto, Stephen A.

    2009-01-01

    Despite evidence showing that readiness to change substance use predicts reductions in substance use among treated adolescents, there is little research on changes in thoughts about abstinence and marijuana use during and after treatment. The current study tested whether time-varying changes in adolescents' motivation to abstain and perceived…

  10. Six month abstinence rule for liver transplantation in severe alcoholic liver disease patients

    PubMed Central

    Obed, Aiman; Stern, Steffen; Jarrad, Anwar; Lorf, Thomas

    2015-01-01

    Alcoholic liver disease (ALD) is the second most common diagnosis among patients undergoing liver transplantation (LT). The recovery results of patients transplanted for ALD are often at least as good as those of patients transplanted for other diagnoses and better than those suffering from hepatitis C virus, cryptogenic cirrhosis, or hepatocellular carcinoma. In the case of medically non-responding patients with severe acute alcoholic hepatitis or acute-on chronic liver failure, the refusal of LT is often based on the lack of the required alcohol abstinence period of six months. The obligatory abidance of a period of abstinence as a transplant eligibility requirement for medically non-responding patients seems unfair and inhumane, since the majority of these patients will not survive the six-month abstinence period. Data from various studies have challenged the 6-mo rule, while excellent survival results of LT have been observed in selected patients with severe alcoholic hepatitis not responding to medical therapy. Patients with severe advanced ALD should have legal access to LT. The mere lack of pre-LT abstinence should not be an obstacle for being listed. PMID:25892898

  11. Effects of Initial Abstinence and Programmed Lapses on the Relative Reinforcing Effects of Cigarette Smoking

    ERIC Educational Resources Information Center

    Chivers, Laura L.; Higgins, Stephen T.; Heil, Sarah H.; Proskin, Rebecca W.; Thomas, Colleen S.

    2008-01-01

    Fifty-eight smokers received abstinence-contingent monetary payments for 1 (n = 15) or 14 (n = 43) days. Those who received contingent payments for 14 days also received 0, 1, or 8 experimenter-delivered cigarette puffs on 5 evenings. The relative reinforcing effects of smoking were assessed in a 3-hr session on the final study day, when…

  12. Experiences of violence and association with decreased drug abstinence among women in Cape Town, South Africa.

    PubMed

    Reed, Elizabeth; Myers, Bronwyn; Novak, Scott P; Browne, Felicia A; Wechsberg, Wendee M

    2015-01-01

    Drug abuse is a contributing factor in women's HIV risk in low-income communities in Cape Town, South Africa. This study assessed whether experiencing violence is associated with reduced drug abstinence among adult women (n = 603) participating in a randomized field trial for an HIV prevention study in Cape Town. In relation to drug abstinence at 12-month follow-up, multivariable regression models were used to assess (1) baseline partner and non-partner victimization, and (2) victimization at 12-month follow-up among participants reporting baseline victimization. Baseline partner (AOR = 0.6; 95 % CI 0.4-0.9) and non-partner victimization (AOR = 0.6; 95 % CI 0.4-0.9) were associated with a reduced likelihood of drug abstinence at follow-up. Among participants who reported victimization at baseline, those no longer reporting victimization at follow-up did not differ significantly in drug abstinence compared with those who reported victimization at follow-up. The study findings highlight the lasting impact of victimization on women's drug use outcomes, persisting regardless of whether violence was no longer reported at follow-up. Overall, the findings support the need for the primary prevention of violence to address the cycle of violence, drug use, and HIV among women in this setting. PMID:24934652

  13. Sex Can Wait: An Abstinence-Based Sexuality Curriculum for Middle School.

    ERIC Educational Resources Information Center

    Core-Gebhart, Pennie; And Others

    This curriculum, directed primarily to students in grades seven and eight, is a five-week sexuality education program designed to promote sexual abstinence as the best decision young people can make for themselves. The guide is divided into three general areas of emphasis. These sections are divided into six units that focus the content of the…

  14. Remaining Off Alcohol and Drugs: A Self-Management Skills Program for Abstinence.

    ERIC Educational Resources Information Center

    Dunphy, Peter Hughes

    The Remaining Off Alcohol and Drugs Program (ROAD) was developed to teach newly abstinent chemical misusing clients how to remain alcohol and drug free. It provides its participants with a repertoire of knowledge, skills and behaviors that they can use in dealing with the most common problems caused by discontinuing chemical use and which can be…

  15. Evidence on the Effectiveness of Abstinence Education: An Update. No. 2372

    ERIC Educational Resources Information Center

    Kim, Christine C.; Rector, Robert

    2010-01-01

    Teen sexual activity is costly, not just for teens, but also for society. Teens who engage in sexual activity risk a host of negative outcomes including STD infection, emotional and psychological harm, and out-of-wedlock childbearing. Genuine abstinence education is therefore crucial to the physical and psycho-emotional well-being of the nation's…

  16. Experiences of Violence and Association with Decreased Drug Abstinence Among Women in Cape Town, South Africa

    PubMed Central

    Reed, Elizabeth; Myers, Bronwyn; Novak, Scott P.; Browne, Felicia A.; Wechsberg, Wendee M.

    2015-01-01

    Drug abuse is a contributing factor in women’s HIV risk in low-income communities in Cape Town, South Africa. This study assessed whether experiencing violence is associated with reduced drug abstinence among adult women (n = 603) participating in a randomized field trial for an HIV prevention study in Cape Town. In relation to drug abstinence at 12-month follow-up, multivariable regression models were used to assess (1) baseline partner and non-partner victimization, and (2) victimization at 12-month follow-up among participants reporting baseline victimization. Baseline partner (AOR = 0.6; 95 % CI 0.4–0.9) and non-partner victimization (AOR = 0.6; 95 % CI 0.4–0.9) were associated with a reduced likelihood of drug abstinence at follow-up. Among participants who reported victimization at baseline, those no longer reporting victimization at follow-up did not differ significantly in drug abstinence compared with those who reported victimization at follow-up. The study findings highlight the lasting impact of victimization on women’s drug use outcomes, persisting regardless of whether violence was no longer reported at follow-up. Overall, the findings support the need for the primary prevention of violence to address the cycle of violence, drug use, and HIV among women in this setting. PMID:24934652

  17. Voucher-Based Contingent Reinforcement of Smoking Abstinence among Methadone-Maintained Patients: A Pilot Study

    ERIC Educational Resources Information Center

    Dunn, Kelly E.; Sigmon, Stacey C.; Thomas, Colleen S.; Heil, Sarah H.; Higgins, Stephen T.

    2008-01-01

    This study evaluated the efficacy of a contingency management (CM) intervention to promote smoking cessation in methadone-maintained patients. Twenty participants, randomized into contingent (n = 10) or noncontingent (n = 10) experimental conditions, completed the 14-day study. Abstinence was determined using breath carbon monoxide and urine…

  18. 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. PMID:16226151

  19. 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

  20. Stress enhances retrieval of drug-related memories in abstinent heroin addicts.

    PubMed

    Zhao, Li-Yan; Shi, Jie; Zhang, Xiao-Li; Epstein, David H; Zhang, Xiang-Yang; Liu, Yu; Kosten, Thomas R; Lu, Lin

    2010-02-01

    Stress is associated with relapse to drugs after abstinence, but the mechanisms for this association are unclear. One mechanism may be that stress enhances abstinent addicts' recall of memories of drugs as stress relievers. This study assessed the effects of stress on free recall and cued recall of 10 heroin-related and 10 neutral words learned 24 h earlier by 102 abstinent heroin addicts. These participants were randomly assigned to three experiments that also assessed attention and working memory. Experiment 1 used a psychosocial stressor (Trier social stress test (TSST)) before testing for recall of heroin-related words. Experiment 2 added administration of the beta-adrenoceptor antagonist propranolol 1 h before the psychosocial stressor. Experiment 3 added administration of either cortisol with propranolol, cortisol alone, or propranolol alone 1 h before word recall to determine whether stress enhancement of heroin-related word recall required noradrenergic-glucocorticoid interactions. We found that free recall of heroin-related words in abstinent addicts was enhanced after stress or cortisol administration when compared with a non-stress condition or placebo, respectively, whereas these interventions had no effect on neutral word recall. beta-adrenergic blockade blocked the enhancing effect of stress or cortisol on free recall of heroin-related words. Neither stress nor cortisol affected cued recall, attention, or working memory. The potential of beta-adrenergic blockade to reduce or block stress-induced enhancement of drug-related memory retrieval may be relevant to preventing stress-induced relapse in abstinent heroin addicts. PMID:19890257

  1. Internet and Telephone Treatment for Smoking Cessation: Mediators and Moderators of Short-Term Abstinence

    PubMed Central

    Papandonatos, George D.; Cobb, Caroline O.; Cobb, Nathan K.; Niaura, Raymond S.; Abrams, David B.; Tinkelman, David G.

    2015-01-01

    Introduction: This study examined mediators and moderators of short-term treatment effectiveness from the iQUITT Study (Quit Using Internet and Telephone Treatment), a 3-arm randomized trial that compared an interactive smoking cessation Web site with an online social network (enhanced Internet) alone and in conjunction with proactive telephone counseling (enhanced Internet plus phone) to a static Internet comparison condition (basic Internet). Methods: The analytic sample was N = 1,236 participants with complete 3-month data on all mediating variables. The primary outcome was 30-day point prevalence abstinence (ppa) at 3 months. Recognizing the importance of temporal precedence in mediation analyses, we also present findings for 6-month outcomes. Purported mediators were treatment utilization and changes in psychosocial constructs. Proposed moderators included baseline demographic, smoking, and psychosocial variables. Mediation analyses examined the extent to which between-arm differences in 30-day ppa could be attributed to differential Web site utilization, telephone counseling, and associated changes in smoking self-efficacy and social support for quitting. Effect modification analyses fitted interactions between treatment and prespecified moderators on abstinence. Results: Significant mediators of 30-day ppa were changes in smoking temptations, quitting confidence, and positive and negative partner support, which were strongly associated with increased Web site utilization. The addition of telephone counseling to an enhanced Web site further improved abstinence rates, partly via an association with increased quitting confidence. Baseline smoking rate was the only significant moderator. Conclusions: Increased treatment utilization and associated changes in several psychosocial measures yielded higher abstinence rates. Findings validate the importance of treatment utilization, smoking self-efficacy, and social support to promote abstinence. PMID:25156528

  2. Changes in cerebral CB1 receptor availability after acute and chronic alcohol abuse and monitored abstinence.

    PubMed

    Ceccarini, Jenny; Hompes, Titia; Verhaeghen, Anne; Casteels, Cindy; Peuskens, Hendrik; Bormans, Guy; Claes, Stephan; Van Laere, Koen

    2014-02-19

    Involvement of the type 1 cannabinoid receptor (CB1R) in the effects of alcohol on the brain is supported by animal experiments, but how in vivo CB1R levels are altered in alcoholic patients is still unclear. To assess the short-time effects of a binge drinking episode on CB1R availability, 20 healthy social drinkers underwent [(18)F]MK-9470-positron emission tomography (PET) at baseline and after intravenous ethanol administration (ALC ACU). Moreover, 26 alcoholic patients underwent sequential CB1R PET after chronic heavy drinking (ALC CHR) and after 1 month of abstinence (ALC ABST). Seventeen healthy subjects served as controls. Compared with baseline, ALC ACU resulted in a global increase of CB1R availability (+15.8%). In contrast, a global decreased CB1R availability was found in ALC CHR patients (-16.1%) compared with controls, which remained unaltered after abstinence (-17.0%). Voxel-based analysis showed that ALC CHR patients had reduced CB1R availability, especially in the cerebellum and parieto-occipital cortex. After abstinence, reduced CB1R availability extended also to other areas such as the ventral striatum and mesotemporal lobe. In conclusion, whereas the acute alcohol effect is an increase in CB1R availability, chronic heavy drinking leads to reduced CB1R availability that is not reversible after 1 month of abstinence. Longer follow-up is required to differentiate whether this is a compensatory effect of repeated endocannabinoid overstimulation or an enduring trait-like feature. An enhanced CB1R signaling may offer a new therapeutic direction for treatment of the negative affective state produced by alcohol withdrawal and abstinence, which is critical for the maintenance of alcohol addiction. PMID:24553924

  3. 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

  4. 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

  5. Effects of naltrexone on post-abstinence alcohol drinking in C57BL/6NCRL and DBA/2J mice.

    PubMed

    Tomie, Arthur; Azogu, Idu; Yu, Lei

    2013-07-01

    The present experiment evaluated the effects of naltrexone, a non-selective opioid receptor antagonist, on post-abstinence alcohol drinking in C57BL/6NCRL and DBA/2J male mice. Home cage 2-bottle (alcohol vs. water) free-choice procedures were employed. During the pre-abstinence period, alcohol intake was much lower for the DBA/2J mice relative to the C57BL/6NCRL mice, and this strain difference was observed for groups receiving either 3% or 10% alcohol concentrations. The four-day abstinence period effectively reduced alcohol intakes (i.e., a negative alcohol deprivation effect, negative ADE) in both groups of DBA/2J mice, but had no effect on alcohol intakes in either group of C57BL/6NCRL mice. Both groups trained with 3% alcohol received the second four-day abstinence period, where the effects of acute administration of either naltrexone or saline on post-abstinence alcohol drinking were assessed. Naltrexone was more effective in reducing post-abstinence drinking of 3% alcohol in the DBA/2J mice than in the C57BL/6NCRL mice. In the DBA/2J mice, naltrexone further reduced, relative to saline-injected controls, the low levels of post-abstinence alcohol intake. Thus, the low baseline levels of alcohol drinking in DBA/2J mice were further diminished by the four-day abstinence period (negative ADE), and this suppressed post-abstinence level of alcohol drinking was still further reduced by acute administration of naltrexone. The results indicate that naltrexone is effective in reducing further the low levels of alcohol drinking induced by the negative ADE. PMID:23499782

  6. 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

  7. 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

  8. Employment-Based Abstinence Reinforcement as a Maintenance Intervention for the Treatment of Cocaine Dependence: A Randomized Controlled Trial

    PubMed Central

    DeFulio, Anthony; Donlin, Wendy D.; Wong, Conrad J.; Silverman, Kenneth

    2009-01-01

    Context: Due to the chronic nature of cocaine dependence, long-term maintenance treatments may be required to sustain abstinence. Abstinence reinforcement is among the most effective means of initiating cocaine abstinence. Practical and effective means of maintaining abstinence reinforcement programs over time are needed. Objective: Determine whether employment-based abstinence reinforcement can be an effective long-term maintenance intervention for cocaine dependence. Design: Participants (N=128) were enrolled in a 6-month job skills training and abstinence initiation program. Participants who initiated abstinence, attended regularly, and developed needed job skills during the first six months were hired as operators in a data entry business and randomly assigned to an employment only (Control, n = 24) or abstinence-contingent employment (n = 27) group. Setting: A nonprofit data entry business. Participants: Unemployed welfare recipients who persistently used cocaine while enrolled in methadone treatment in Baltimore. Intervention: Abstinence-contingent employment participants received one year of employment-based contingency management, in which access to employment was contingent on provision drug-free urine samples under routine and then random drug testing. If a participant provided drug-positive urine or failed to provide a mandatory sample, then that participant received a temporary reduction in pay and could not work until urinalysis confirmed recent abstinence. Main Outcome Measure: Cocaine-negative urine samples at monthly assessments across one year of employment. Results: During the one-year of employment, abstinence-contingent employment participants provided significantly more cocaine-negative urine samples than employment only participants (79.3% and 50.7%, respectively; p = 0.004, OR = 3.73, 95% CI = 1.60 – 8.69). Conclusions: Employment-based abstinence reinforcement that includes random drug testing is effective as a long-term maintenance

  9. 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

  10. 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

  11. 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

  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. The Knowledge Gap Versus the Belief Gap and Abstinence-Only Sex Education.

    PubMed

    Hindman, Douglas Blanks; Yan, Changmin

    2015-08-01

    The knowledge gap hypothesis predicts widening disparities in knowledge of heavily publicized public affairs issues among socioeconomic status groups. The belief gap hypothesis extends the knowledge gap hypothesis to account for knowledge and beliefs about politically contested issues based on empirically verifiable information. This analysis of 3 national surveys shows belief gaps developed between liberals and conservatives regarding abstinence-only sex education; socioeconomic status-based knowledge gaps did not widen. The findings partially support both belief gap and knowledge gap hypotheses. In addition, the unique contributions of exposure to Fox News, CNN, and MSNBC in this process were investigated. Only exposure to Fox News was linked to beliefs about abstinence-only sex education directly and indirectly through the cultivation of conservative ideology. PMID:25950234

  14. Factors Associated with Sexual Abstinence among Adolescents in Four Sub-Saharan African Countries

    PubMed Central

    Kabiru, Caroline W.; Ezeh, Alex

    2008-01-01

    Drawing on nationally representative data collected from Burkinabé, Ghanaian, Malawian, and Ugandan adolescents, this study examines differences among four groups of never married, 15–19 year olds: primary abstainers (sexually inexperienced), secondary abstainers (last sex more than 12 months prior to the survey), recent abstainers (sexually active in last year but not in the last 3 months), and sexually active (had sexual intercourse in the last 3 months). The percentage of primary abstinent adolescents ranged from 42% (Malawian males) to 85% (Ghanaian males). In general, a greater proportion of females than males were primary abstainers. Primary abstainers were younger than sexually experienced adolescents. Current involvement in a romantic relationship was a significant predictor of sexual status with primary abstainers being the least likely to be romantically involved. Overall, findings suggest that adolescents’ gender, prior sexual experiences and contextual circumstances, such as romantic partnerships, should be considered when designing abstinence promotion programs. PMID:19122794

  15. I want to hold your hand: abstinence curricula, bioethics, and the silencing of desire.

    PubMed

    Wilkerson, Abby

    2013-06-01

    The abstinence approach to sex education remains influential despite its demonstrated ineffectiveness. One bill forbids the "promotion" of "gateway sexual activity," while requiring outright condemnation of "non-abstinence," defined so loosely as to plausibly include handholding. Bioethics seldom (if ever) contributes to sex-ed debates, yet exploring the pivotal role of medical discourse reveals the need for bioethical intervention. Sex-ed debates revolve around a theory of human flourishing based on heteronormative temporality, a developmental teleology ensuring the transmission of various supposed social goods through heterosexual marriage (Halberstam, 2005). Heteronormative temporality also constitutes a moralized discourse in which the values of health and presumed certainties of medicine serve to justify conservative religious dictates that otherwise would appear controversial as the basis for public policy. Overall, this analysis explores how moralized medical discourses compound existing injustices, while suggesting bioethics' potential contributions to moral and political analysis of sex-ed policies. PMID:23468394

  16. Nigerian secondary school adolescents' perspective on abstinence-only sexual education as an effective tool for promotion of sexual health.

    PubMed

    Inyang, Mfrekemfon P; Inyang, Obonganyie P

    2013-01-01

    The success of any type of sexual education programme depends on the knowledge and preparedness for practice by adolescents. A recent study has found that an 'abstinence-only' sexual education programme is effective in reducing sexual activity among adolescents. Knowledge of abstinence-only sexual education and preparedness for practice as an effective tool for promotion of sexual health among Nigerian secondary school adolescents was studied. An analytic descriptive survey design was used for the study. The research population comprised of all public secondary schools in three southern geopolitical zones of the Niger Delta Region of Nigeria. A multistage sampling technique was used to select 2020 senior secondary school (SS1-SS3) students as sample for the study. A partially self-designed and partially adapted questionnaire from an 'abstinence-only versus comprehensive sex education' debate, from debatepedia (http://wiki.idebate.org/), entitled 'Questionnaire on Nigerian Secondary School Adolescents' Perspective on Abstinence-Only Sexual Education (QNSSAPAOSE)' was used in eliciting information from respondents. Hypotheses were formulated and tested. Frequency counts, percentage and Pearson Product Moment Correlation were used in analysing data. A greater proportion of secondary school adolescents in this study lacked knowledge of sexual education. About 80% of the respondents could not define sexual education. The general perspective on abstinence-only sexual education was negative, as revealed by the larger number of respondents who demonstrated unwillingness to practice abstinence-only sexual education. Specifically, of those who responded in favour of abstinence-only sexual education, the youngest group of adolescents (11-13 years) and the male respondents were more likely to accept this type of education than the other groups. Poor knowledge of sexual education could be responsible for unwillingness to practice abstinence-only sexual education. Sexual

  17. Telling true from false: cannabis users show increased susceptibility to false memories.

    PubMed

    Riba, J; Valle, M; Sampedro, F; Rodríguez-Pujadas, A; Martínez-Horta, S; Kulisevsky, J; Rodríguez-Fornells, A

    2015-06-01

    Previous studies on the neurocognitive impact of cannabis use have found working and declarative memory deficits that tend to normalize with abstinence. An unexplored aspect of cognitive function in chronic cannabis users is the ability to distinguish between veridical and illusory memories, a crucial aspect of reality monitoring that relies on adequate memory function and cognitive control. Using functional magnetic resonance imaging, we show that abstinent cannabis users have an increased susceptibility to false memories, failing to identify lure stimuli as events that never occurred. In addition to impaired performance, cannabis users display reduced activation in areas associated with memory processing within the lateral and medial temporal lobe (MTL), and in parietal and frontal brain regions involved in attention and performance monitoring. Furthermore, cannabis consumption was inversely correlated with MTL activity, suggesting that the drug is especially detrimental to the episodic aspects of memory. These findings indicate that cannabis users have an increased susceptibility to memory distortions even when abstinent and drug-free, suggesting a long-lasting compromise of memory and cognitive control mechanisms involved in reality monitoring. PMID:25824306

  18. Rapid elimination of Carboxy-THC in a cohort of chronic cannabis users.

    PubMed

    Lewis, John; Molnar, Anna; Allsop, David; Copeland, Jan; Fu, Shanlin

    2016-01-01

    Urinary 11-nor-Δ(9)-tetrahydrocannabinol-9-carboxylic acid (Carboxy-THC) concentrations, normalised to creatinine output, have been demonstrated to be a useful tool in the interpretation of the results of a series of urine tests for cannabis. These tests, often termed historical data, can be used to identify potential chronic cannabis users who may present occupational health and safety risks within the workplace. Conversely, the data can also be used to support employee claims of previous regular, rather than recent, cannabis use. This study aimed at examining the mean elimination of Carboxy-THC in 37 chronic users undergoing voluntary abstinence over a 2-week period. Urine specimens were collected prior to the study and after 1 and 2 weeks of abstinence. Carboxy-THC levels in urine were measured by gas chromatography-mass spectrometry (GC-MS) following alkaline hydrolysis, organic solvent extraction and derivatisation to form its pentafluoropropionic derivative. The creatinine-normalised Carboxy-THC concentrations declined rapidly over the 2 weeks of abstinence period and the majority of chronic cannabis users (73%) reduced their urinary Carboxy-THC levels to below the 15-μg/L confirmatory cutoff within that time. The study further highlights the value of historical urinary Carboxy-THC data as a means of identifying potential occupational health and safety risks among chronic cannabis users. PMID:26233612

  19. Telling true from false: cannabis users show increased susceptibility to false memories

    PubMed Central

    Riba, J; Valle, M; Sampedro, F; Rodríguez-Pujadas, A; Martínez-Horta, S; Kulisevsky, J; Rodríguez-Fornells, A

    2015-01-01

    Previous studies on the neurocognitive impact of cannabis use have found working and declarative memory deficits that tend to normalize with abstinence. An unexplored aspect of cognitive function in chronic cannabis users is the ability to distinguish between veridical and illusory memories, a crucial aspect of reality monitoring that relies on adequate memory function and cognitive control. Using functional magnetic resonance imaging, we show that abstinent cannabis users have an increased susceptibility to false memories, failing to identify lure stimuli as events that never occurred. In addition to impaired performance, cannabis users display reduced activation in areas associated with memory processing within the lateral and medial temporal lobe (MTL), and in parietal and frontal brain regions involved in attention and performance monitoring. Furthermore, cannabis consumption was inversely correlated with MTL activity, suggesting that the drug is especially detrimental to the episodic aspects of memory. These findings indicate that cannabis users have an increased susceptibility to memory distortions even when abstinent and drug-free, suggesting a long-lasting compromise of memory and cognitive control mechanisms involved in reality monitoring. PMID:25824306

  20. Abstinence duration modulates striatal functioning during monetary reward processing in cocaine patients.

    PubMed

    Bustamante, Juan-Carlos; Barrós-Loscertales, Alfonso; Costumero, Víctor; Fuentes-Claramonte, Paola; Rosell-Negre, Patricia; Ventura-Campos, Noelia; Llopis, Juan-José; Ávila, César

    2014-09-01

    Pre-clinical and clinical studies in cocaine addiction highlight alterations in the striatal dopaminergic reward system that subserve maintenance of cocaine use. Using an instrumental conditioning paradigm with monetary reinforcement, we studied striatal functional alterations in long-term abstinent cocaine-dependent patients and striatal functioning as a function of abstinence and treatment duration. Eighteen patients and 20 controls underwent functional magnetic resonance imaging during a Monetary Incentive Delay task. Region of interest analyses based on masks of the dorsal and ventral striatum were conducted to test between-group differences and the functional effects in the cocaine group of time (in months) with no more than two lapses from the first time patients visited the clinical service to seek treatment at the scanning time (duration of treatment), and the functional effects of the number of months with no lapses or relapses at the scanning session time (length of abstinence). We applied a voxel-wise and a cluster-wise FWE-corrected level (pFWE) at a threshold of P < 0.05. The patient group showed lower activation in the right caudate during reward anticipation than the control group. The regression analyses in the patients group revealed a positive correlation between duration of treatment and brain activity in the left caudate during reward anticipation. Likewise, length of abstinence negatively correlated with brain activity in the bilateral nucleus accumbens during monetary outcome processing. In conclusion, caudate and nucleus accumbens show a different brain response pattern to non-drug rewards during cocaine addiction, which can be modulated by treatment success. PMID:23445167

  1. Drug Metabolizing Enzyme and Transporter Gene Variation, Nicotine Metabolism, Prospective Abstinence, and Cigarette Consumption.

    PubMed

    Bergen, Andrew W; Michel, Martha; Nishita, Denise; Krasnow, Ruth; Javitz, Harold S; Conneely, Karen N; Lessov-Schlaggar, Christina N; Hops, Hyman; Zhu, Andy Z X; Baurley, James W; McClure, Jennifer B; Hall, Sharon M; Baker, Timothy B; Conti, David V; Benowitz, Neal L; Lerman, Caryn; Tyndale, Rachel F; Swan, Gary E

    2015-01-01

    The Nicotine Metabolite Ratio (NMR, ratio of trans-3'-hydroxycotinine and cotinine), has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. We searched for drug metabolizing enzyme and transporter (DMET) gene variation associated with the NMR and prospective abstinence in 2,946 participants of laboratory studies of nicotine metabolism and of clinical trials of smoking cessation therapies. Stage I was a meta-analysis of the association of 507 common single nucleotide polymorphisms (SNPs) at 173 DMET genes with the NMR in 449 participants of two laboratory studies. Nominally significant associations were identified in ten genes after adjustment for intragenic SNPs; CYP2A6 and two CYP2A6 SNPs attained experiment-wide significance adjusted for correlated SNPs (CYP2A6 PACT=4.1E-7, rs4803381 PACT=4.5E-5, rs1137115, PACT=1.2E-3). Stage II was mega-regression analyses of 10 DMET SNPs with pretreatment NMR and prospective abstinence in up to 2,497 participants from eight trials. rs4803381 and rs1137115 SNPs were associated with pretreatment NMR at genome-wide significance. In post-hoc analyses of CYP2A6 SNPs, we observed nominally significant association with: abstinence in one pharmacotherapy arm; cigarette consumption among all trial participants; and lung cancer in four case:control studies. CYP2A6 minor alleles were associated with reduced NMR, CPD, and lung cancer risk. We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk. Additional multivariate analyses with patient variables and genetic modeling will improve prediction of nicotine metabolism, disease risk and smoking cessation treatment prognosis. PMID:26132489

  2. Drug Metabolizing Enzyme and Transporter Gene Variation, Nicotine Metabolism, Prospective Abstinence, and Cigarette Consumption

    PubMed Central

    Bergen, Andrew W.; Michel, Martha; Nishita, Denise; Krasnow, Ruth; Javitz, Harold S.; Conneely, Karen N.; Lessov-Schlaggar, Christina N.; Hops, Hyman; Zhu, Andy Z. X.; Baurley, James W.; McClure, Jennifer B.; Hall, Sharon M.; Baker, Timothy B.; Conti, David V.; Benowitz, Neal L.; Lerman, Caryn; Tyndale, Rachel F.; Swan, Gary E.

    2015-01-01

    The Nicotine Metabolite Ratio (NMR, ratio of trans-3’-hydroxycotinine and cotinine), has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. We searched for drug metabolizing enzyme and transporter (DMET) gene variation associated with the NMR and prospective abstinence in 2,946 participants of laboratory studies of nicotine metabolism and of clinical trials of smoking cessation therapies. Stage I was a meta-analysis of the association of 507 common single nucleotide polymorphisms (SNPs) at 173 DMET genes with the NMR in 449 participants of two laboratory studies. Nominally significant associations were identified in ten genes after adjustment for intragenic SNPs; CYP2A6 and two CYP2A6 SNPs attained experiment-wide significance adjusted for correlated SNPs (CYP2A6 PACT=4.1E-7, rs4803381 PACT=4.5E-5, rs1137115, PACT=1.2E-3). Stage II was mega-regression analyses of 10 DMET SNPs with pretreatment NMR and prospective abstinence in up to 2,497 participants from eight trials. rs4803381 and rs1137115 SNPs were associated with pretreatment NMR at genome-wide significance. In post-hoc analyses of CYP2A6 SNPs, we observed nominally significant association with: abstinence in one pharmacotherapy arm; cigarette consumption among all trial participants; and lung cancer in four case:control studies. CYP2A6 minor alleles were associated with reduced NMR, CPD, and lung cancer risk. We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk. Additional multivariate analyses with patient variables and genetic modeling will improve prediction of nicotine metabolism, disease risk and smoking cessation treatment prognosis. PMID:26132489

  3. Investigation of the neuroanatomical substrates of reward seeking following protracted abstinence in mice

    PubMed Central

    Madsen, Heather B; Brown, Robyn M; Short, Jennifer L; Lawrence, Andrew J

    2012-01-01

    Persistent vulnerability to relapse represents a major challenge in the treatment of drug addiction. The brain circuitry that underlies relapse-like behaviour can be investigated using animal models of drug seeking. As yet there have been no comprehensive brain mapping studies that have specifically examined the neuroanatomical substrates of cue-induced opiate seeking following abstinence in a mouse operant paradigm. The aim of this study was to compare the brain regions involved in sucrose vs. morphine seeking following protracted abstinence in mice. Male CD1 mice were trained to respond for either sucrose (10% w/v) or intravenous morphine (0.1 mg kg−1 per infusion) in an operant paradigm in the presence of a discrete cue. Once stable responding was established, mice were subjected to abstinence in their home cages for 3 weeks and then perfused for tissue collection, or returned to the operant chambers to assess cue-induced reward seeking before being perfused for tissue collection. Brain tissue was processed for Fos immunohistochemistry and Fos expression was quantified in a range of brain nuclei. We identified unique patterns of neuronal activation for sucrose and morphine seeking mice as well as some overlap. Structures activated in both ‘relapse’ groups included the anterior cingulate and orbitofrontal cortex, nucleus accumbens shell, bed nucleus of the stria terminalis, substantia nigra pars compacta, ventral tegmental area, hippocampus, periaqueductal grey, locus coeruleus and lateral habenula. Structures that were more activated in morphine seeking mice included the nucleus accumbens core, basolateral amygdala, substantia nigra pars reticulata, and the central nucleus of the amygdala. The dorsal raphe was the only structure examined that was specifically activated in sucrose seeking mice. Overall our findings support a cortico-striatal limbic circuit driving opiate seeking, and we have identified some additional circuitry potentially relevant to

  4. 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

  5. Prolonged sexual abstinence after childbirth: gendered norms and perceived family health risks. Focus group discussions in a Tanzanian suburb

    PubMed Central

    2013-01-01

    Background Prolonged sexual abstinence after childbirth is a socio-cultural practice with health implications, and is described in several African countries, including Tanzania. This study explored discourses on prolonged postpartum sexual abstinence in relation to family health after childbirth in low-income suburbs of Dar es Salaam, Tanzania. Methods Data for the discourse analysis were collected through focus group discussions with first-time mothers and fathers and their support people in Ilala, Dar es Salaam, Tanzania. Results In this setting, prolonged sexual abstinence intended at promoting child health was the dominant discourse in the period after childbirth. Sexual relations after childbirth involved the control of sexuality for ensuring family health and avoiding the social implications of non-adherence to sexual abstinence norms. Both abstinence and control were emphasised more with regard to women than to men. Although the traditional discourse on prolonged sexual abstinence for protecting child health was reproduced in Ilala, some modern aspects such as the use of condoms and other contraceptives prevailed in the discussion. Conclusion Discourses on sexuality after childbirth are instrumental in reproducing gender-power inequalities, with women being subjected to more restrictions and control than men are. Thus, interventions that create openness in discussing sexual relations and health-related matters after childbirth and mitigate gendered norms suppressing women and perpetuating harmful behaviours are needed. The involvement of males in the interventions would benefit men, women, and children through improving the gender relations that promote family health. PMID:23316932

  6. Longitudinal Mapping of Gyral and Sulcal Patterns of Cortical Thickness and Brain Volume Regain during Early Alcohol Abstinence.

    PubMed

    Wang, Guo-Ying; Demirakca, Traute; van Eijk, Julia; Frischknecht, Ulrich; Ruf, Matthias; Ucar, Serhat; Hermann, Derik; Mann, Karl; Kiefer, Falk; Ende, Gabriele

    2016-01-01

    We explored brain volume recovery in terms of cortical thickness (CTh; gyral, sulcal pattern) and surface area (SA), as well as subcortical volume recovery in the first 2 weeks of abstinence in 49 alcohol-dependent patients (ADPs). A widespread reduction of CTh in ADPs at day 1 of abstinence compared to healthy controls, with more pronounced differences in sulci relative to gyri was found. After 2 weeks of abstinence, partial recovery to varying degrees of CTh loss in ADPs was observed for several regions. The longitudinal CTh changes were greater in sulci than in gyri of affected regions. No longitudinal change in SAs and subcortical volumes was found. Alterations of CTh contribute to brain volume loss in alcoholism and recovery during early abstinence. Sulci seem to be more vulnerable to excessive alcohol consumption and to drive abstinence-induced volume recovery. During the initial 2 weeks of abstinence no subcortical volume regain was observed. Either the time span was too short or the lower subcortical volume could represent a predisposing trait marker. PMID:26343988

  7. Abnormal resting-state functional connectivity of the nucleus accumbens in multi-year abstinent heroin addicts.

    PubMed

    Zou, Feng; Wu, Xinhuai; Zhai, Tianye; Lei, Yu; Shao, Yongcong; Jin, Xiao; Tan, Shuwen; Wu, Bing; Wang, Lubin; Yang, Zheng

    2015-11-01

    Functional neuroimaging studies suggest that abnormal brain functional connectivity may be the neural underpinning of addiction to illicit drugs and of relapse after successful cessation therapy. Aberrant brain networks have been demonstrated in addicted patients and in newly abstinent addicts. However, it is not known whether abnormal brain connectivity patterns persist after prolonged abstinence. In this cross-sectional study, whole-brain resting-state functional magnetic resonance images (8 min) were collected from 30 heroin-addicted individuals after a long period of abstinence (more than 3 years) and from 30 healthy controls. We first examined the group differences in the resting-state functional connectivity of the nucleus accumbens (NAc), a brain region implicated in relapse-related processes, including craving and reactivity to stress following acute and protracted withdrawal from heroin. We then examined the relation between the duration of abstinence and the altered NAc functional connectivity in the heroin group. We found that, compared with controls, heroin-dependent participants exhibited significantly greater functional connectivity between the right ventromedial prefrontal cortex and the NAc and weaker functional connectivity between the NAc and the left putamen, left precuneus, and supplementary motor area. However, with longer abstinence time, the strength of NAc functional connectivity with the left putamen increased. These results indicate that dysfunction of the NAc functional network is still present in long-term-abstinent heroin-dependent individuals. PMID:26280556

  8. Comparison of expired carbon monoxide and plasma cotinine as markers of cigarette abstinence.

    PubMed

    Jatlow, Peter; Toll, Benjamin A; Leary, Vanessa; Krishnan-Sarin, Suchitra; O'Malley, Stephanie S

    2008-12-01

    The clinical pharmacology of biochemical measures of nicotine exposure has been thoroughly reviewed with regard to usefulness and limitations in detecting abstinence from cigarette smoking. While plasma nicotine concentration measures only acute nicotine exposure, plasma, salivary, and urine cotinine concentrations reflect exposure over an extended period of time. Although, expired carbon monoxide (CO) is frequently used to confirm self reports, it has a relatively short half life, calling into question whether this measure might provide misleading information by exaggerating smoking cessation success rates. To examine this question, we analyzed expired CO, plasma cotinine and self report data collected in a clinical trial in which subjects (N=207) were randomly assigned to gain- or loss-framed messages for smoking cessation in combination with open label sustained-release bupropion (300 mg/day). In examining measurements collected at 6 weeks, 3 and 6 months, results showed that CO significantly overestimated abstinence rates as compared with cotinine, although the discrepancy was less at the later time points. These data suggest that while expired CO is a useful and well-established marker in certain contexts, when testing extended abstinence from smoking with non-nicotine medications, cotinine measurements should be preferred. PMID:18650033

  9. Impact of a brief telephone referral on quitline use, quit attempts and abstinence

    PubMed Central

    Mathew, Amanda R.; Burris, Jessica L.; Alberg, Anthony J.; Cummings, K. Michael; Carpenter, Matthew J.

    2015-01-01

    Quitline use can prompt quit attempts and promote abstinence among smokers, but rates of use are low and outcomes of brief quitline referrals unclear. In this study, a brief intervention was delivered to smokers who expressed motivation to quit in the next 30 days (N = 221) to encourage use of their state quitline. Correlates of quitline use were examined, and quitline callers versus non-callers were compared on the following outcomes at 2-month follow-up: cessation medication use, quit attempts and abstinence. Of the 221 smokers given a quitline referral, 34% called the quitline. Baseline motivation alone distinguished quitline callers from non-callers. Quitline use was positively associated with use of cessation medication, an association that remained robust even after adjusting for baseline motivation to quit. A trend was observed in which callers were marginally more likely than non-callers to report both a 24-h quit attempt and 7-day point prevalence abstinence. Relative to non-callers, callers also endorsed greater confidence to quit and increased self-efficacy to resist smoking temptations at follow-up. This study demonstrates a minimal intervention can promote acceptance of quitlines and favorable cessation outcomes among smokers motivated to quit. PMID:25092882

  10. An endocannabinoid signal associated with desire for alcohol is suppressed in recently abstinent alcoholics

    PubMed Central

    Mangieri, Regina A.; Hong, Kwang-Ik A.

    2009-01-01

    Background Alcoholics report persistent alcohol craving that is heightened by cognitive cues, stressful situations, and abstinence. The role of endogenous cannabinoids in human alcohol craving—though long suspected—remains elusive. Materials and methods We employed laboratory exposure to stress, alcohol cue, and neutral relaxed situations through guided imagery procedures to evoke alcohol desire and craving in healthy social drinkers (n=11) and in treatment-engaged, recently abstinent alcoholic subjects (n=12) and assessed alcohol craving, heart rate, and changes in circulating endocannabinoid levels. Subjective anxiety was also measured as a manipulation check for the procedures. Results In healthy social drinkers, alcohol cue imagery increased circulating levels of the endocannabinoid anandamide, whereas neutral and stress-related imagery had no such effect. Notably, baseline and response anandamide levels in these subjects were negatively and positively correlated with self-reported alcohol craving scores, respectively. Cue-induced increases in heart rate were also correlated with anandamide responses. By contrast, no imagery-induced anandamide mobilization was observed in alcoholics, whose baseline anandamide levels were markedly reduced compared to healthy drinkers and were uncorrelated to either alcohol craving or heart rate. Conclusions The results suggest that plasma anandamide levels provide a marker of the desire for alcohol in social drinkers, which is suppressed in recently abstinent alcoholics. PMID:19343330

  11. Alcohol abstinence or harm-reduction? Parental messages for college-bound light drinkers.

    PubMed

    LaBrie, Joseph W; Boyle, Sarah C; Napper, Lucy E

    2015-07-01

    Parental communications about alcohol can have a significant impact on college students' alcohol use; however, it is unclear what types of communication may be most beneficial for reducing alcohol risk, particularly among students who have already initiated alcohol use. The present research examines differences in alcohol use and employment of drinking protective behavioral strategies between pre-college matriculation high school seniors receiving predominantly abstinence parent messaging and students primarily receiving harm-reduction parent messaging. Students who identified as light drinkers were recruited during their last month in high school and completed an online assessment of alcohol use and parent alcohol communication. Analyses revealed that, in comparison to light drinkers who primarily received harm-reduction messaging from parents, light drinkers who received more abstinence messaging reported less frequent alcohol use, lower peak alcohol consumption, and greater use of protective drinking strategies aimed at changing the way they drank and avoiding serious hazards associated with drinking. Findings from this study underscore the utility of messages related to abstinence even for parents who are aware that their children have had previous experiences with alcohol and highlight the need for longitudinal research assessing additional mechanisms associated with message efficacy among light, moderate and heavy drinking students transitioning to college. PMID:25753930

  12. Effects of DA-Phen, a dopamine-aminoacidic conjugate, on alcohol intake and forced abstinence.

    PubMed

    Sutera, Flavia Maria; De Caro, Viviana; Cannizzaro, Carla; Giannola, Libero Italo; Lavanco, Gianluca; Plescia, Fulvio

    2016-09-01

    The mesolimbic dopamine (DA) system plays a key role in drug reinforcement and is involved in the development of alcohol addiction. Manipulation of the DAergic system represents a promising strategy to control drug-seeking behavior. Previous studies on 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) showed in vivo effects as a DA-ergic modulator. This study was aimed at investigate DA-Phen effects on operant behavior for alcohol seeking behavior, during reinstatement following subsequent periods of alcohol deprivation. For this purpose, male Wistar rats were tested in an operant paradigm of self-administration; behavioral reactivity and anxiety like-behavior during acute abstinence were evaluated. A characterization of DA-Phen CNS targeting by its quantification in the brain was also carried out. Our findings showed that DA-Phen administration was able to reduce relapse in alcohol drinking by 50% and reversed the alterations in behavioral reactivity and emotionality observed during acute abstinence. In conclusion, DA-Phen can reduce reinstatement of alcohol drinking in an operant-drinking paradigm following deprivation periods and reverse abstinence-induced behavioral phenotype. DA-Phen activity seems to be mediated by the modulation of the DAergic transmission. However further studies are needed to characterize DA-Phen pharmacodynamic and pharmacokinetic properties, and its potential therapeutic profile in alcohol addiction. PMID:27155501

  13. Relations among Affect, Abstinence Motivation and Confidence, and Daily Smoking Lapse Risk

    PubMed Central

    Minami, Haruka; Yeh, Vivian M.; Bold, Krysten W.; Chapman, Gretchen B.; McCarthy, Danielle E.

    2016-01-01

    Aims This study tested the hypothesis that changes in momentary affect, abstinence motivation, and confidence would predict lapse risk over the next 12–24 hours using Ecological Momentary Assessment (EMA) data from smokers attempting to quit smoking. Method 103 adult, daily, treatment-seeking smokers recorded their momentary affect, motivation to quit, abstinence confidence, and smoking behaviors in near real time with multiple EMA reports per day using electronic diaries post-quit. Results Multilevel models indicated that initial levels of negative affect were associated with smoking, even after controlling for earlier smoking status, and that short-term increases in negative affect predicted lapses up to 12, but not 24, hours later. Positive affect had significant effects on subsequent abstinence confidence, but not motivation to quit. High levels of motivation appeared to reduce increases in lapse risk that occur over hours while momentary changes in confidence did not predict lapse risk over 12 hours. Conclusion Negative affect had short-lived effects on lapse risk, whereas higher levels of motivation protected against the risk of lapsing that accumulates over hours. An increase in positive affect was associated with greater confidence to quit, but such changes in confidence did not reduce short-term lapse risk, contrary to expectations. Relations observed among affect, cognitions, and lapse seem to depend critically on the timing of assessments. PMID:24955665

  14. The role of BMI change on smoking abstinence in a sample of HIV-infected smokers.

    PubMed

    Buchberg, Meredith K; Gritz, Ellen R; Kypriotakis, George; Arduino, Roberto C; Vidrine, Damon J

    2016-01-01

    The prevalence of cigarette smoking among persons living with HIV/AIDS (PLWHA) is approximately 40%, significantly higher than that of the general population. Identifying predictors of successful smoking cessation for PLWHA is necessary to alleviate the morbidity and mortality associated with smoking in this population. Weight gain has been associated with smoking relapse in the general population, but has not been studied among PLWHA. Data from 474 PLWHA enrolled in a smoking cessation randomized clinical trial were analyzed to examine the effect of BMI change, from baseline to 3-month follow-up, on smoking outcomes using multiple logistic regression. The odds of 7-day smoking abstinence at 3-month follow-up were 4.22 (95% CI = 1.65, 10.82) times higher for participants classified as BMI decrease and 4.22 (95% CI = 1.62, 11.01) times higher for participants classified as BMI increase as compared to participants with a minimal increase or decrease in BMI. In this sample, both weight gain and loss following smoking cessation were significantly associated with abstinence at 3-month follow-up among HIV-infected smokers. Further research and a better understanding of predictors of abstinence will encourage more tailored interventions, with the potential to reduce morbidity and mortality. PMID:26666313

  15. GLOBAL AND LOCAL MORPHOMETRIC DIFFERENCES IN RECENTLY ABSTINENT METHAMPHETAMINE-DEPENDENT INDIVIDUALS

    PubMed Central

    Schwartz, Daniel L.; Mitchell, Alex D.; Lahna, David L.; Luber, Hannah S.; Huckans, Marilyn S.; Mitchell, Suzanne H.; Hoffman, William F.

    2010-01-01

    Methamphetamine (MA) is associated with behavioral and cognitive deficits that may be related to macrostructural abnormalities. Quantitative anatomical comparisons between controls and methamphetamine-dependent individuals have produced conflicting results. We examined local and global differences in brain structure in 61 abstinent methamphetamine-dependent individuals and 44 controls with voxel-based morphometry and tissue segmentation. We related regional differences in gray matter density and whole brain segmentation volumes to performance on a behavioral measure of impulsivity and group membership using multiple linear regression. Within the MA group, we related cortical and subcortical gray matter density to MA use history, length of abstinence and age of first use. Controls had greater density relative to MA in bilateral insula and left middle frontal gyrus. Impulsivity was higher in the MA group and, within all subjects, impulsivity was positively correlated with gray matter density in posterior cingulate cortex and ventral striatum and negatively correlated in left superior frontal gyrus. Length of abstinence from MA was associated with greater amygdalar density. Earlier age of first use of MA (in subjects who initiated use before age 21) was associated with smaller intracranial volume. The findings are consistent with multiple possible mechanisms including neuroadaptations due to addictive behavior, neuroinflammation as well as dopaminergic and serotonergic neurotoxicity. PMID:20096794

  16. Relations among affect, abstinence motivation and confidence, and daily smoking lapse risk.

    PubMed

    Minami, Haruka; Yeh, Vivian M; Bold, Krysten W; Chapman, Gretchen B; McCarthy, Danielle E

    2014-06-01

    This study tested the hypothesis that changes in momentary affect, abstinence motivation, and confidence would predict lapse risk over the next 12-24 hr using Ecological Momentary Assessment (EMA) data from smokers attempting to quit smoking. One hundred and three adult, daily, treatment-seeking smokers recorded their momentary affect, motivation to quit, abstinence confidence, and smoking behaviors in near real time with multiple EMA reports per day using electronic diaries postquit. Multilevel models indicated that initial levels of negative affect were associated with smoking, even after controlling for earlier smoking status, and that short-term increases in negative affect predicted lapses up to 12, but not 24, hr later. Positive affect had significant effects on subsequent abstinence confidence, but not motivation to quit. High levels of motivation appeared to reduce increases in lapse risk that occur over hours although momentary changes in confidence did not predict lapse risk over 12 hr. Negative affect had short-lived effects on lapse risk, whereas higher levels of motivation protected against the risk of lapsing that accumulates over hours. An increase in positive affect was associated with greater confidence to quit, but such changes in confidence did not reduce short-term lapse risk, contrary to expectations. Relations observed among affect, cognitions, and lapse seem to depend critically on the timing of assessments. PMID:24955665

  17. Abstinence Funding Was Not Associated With Reductions In HIV Risk Behavior In Sub-Saharan Africa.

    PubMed

    Lo, Nathan C; Lowe, Anita; Bendavid, Eran

    2016-05-01

    The President's Emergency Plan for AIDS Relief (PEPFAR) has been the largest funder of abstinence and faithfulness programming in sub-Saharan Africa, with a cumulative investment of over US $1.4 billion in the period 2004-13. We examined whether PEPFAR funding for abstinence and faithfulness programs, which aimed to reduce the risk of HIV transmission, was associated with a relative change in five outcomes indicative of high-risk sexual behavior: number of sexual partners in the past twelve months for men and for women, age at first sexual intercourse for men and for women, and teenage pregnancies. Using nationally representative surveys from twenty-two sub-Saharan African countries, we compared trends between people living in countries that received PEPFAR abstinence and faithfulness funding and those living in countries that did not in the period 1998-2013. We found no evidence to suggest that PEPFAR funding was associated with population-level reductions in any of the five outcomes. These results suggest that alternative funding priorities for HIV prevention may yield greater health benefits. PMID:27140992

  18. Distinct periods of developmental sensitivity to the effects of 3,4-(±)-methylenedioxymethamphetamine (MDMA) on behaviour and monoamines in rats.

    PubMed

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

    2012-07-01

    Previous findings showed allocentric and egocentric learning deficits in rats after MDMA treatment from postnatal days (PD) 11-20 but not after treatment from PD 1-10. Shorter treatment periods (PD 1-5, 6-10, 11-15, or 16-20) resulted in allocentric learning deficits averaged across intervals but not for any interval individually and no egocentric learning deficits individually or collectively. Whether this difference was attributable to treatment length or age at the start of treatment was unclear. In the present experiment rat litters were treated on PD 1-10, 6-15, or 11-20 with 0, 10, or 15 mg/kg MDMA q.i.d. at 2-h intervals. Two male/female pairs/litter received each treatment. One pair/litter received acoustic startle with prepulse inhibition, straight channel swimming, Cincinnati water maze (CWM), and conditioned fear in a latent inhibition paradigm. The other pair/litter received locomotor activity, straight channel swimming, Morris water maze (MWM), and locomotor activity retest with MK-801 challenge. MDMA impaired CWM learning following PD 6-15 or 11-20 exposure. In MWM acquisition, all MDMA-treated groups showed impairment. During reversal and shift, the PD 6-15 and PD 11-20 MDMA-treated groups were significantly impaired. Reductions in locomotor activity were most evident after PD 6-15 treatment while increases in acoustic startle were most evident after PD 1-10 treatment. After MK-801 challenge, MDMA-treated offspring showed less locomotion compared to controls. Region-specific changes in brain monoamines were also observed but were not significantly correlated with behavioural changes. The results show that PD 11-20 exposure to MDMA caused the largest long-term cognitive deficits followed by PD 6-15 exposure with PD 1-10 exposure least affected. Other effects, such as those upon MK-801-stimulated locomotion showed greatest effects after PD 1-10 MDMA exposure. Hence, each effect has a different window of developmental susceptibility. PMID:21733225

  19. 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

  20. 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

  1. Cerebral white matter recovery in abstinent alcoholics—a multimodality magnetic resonance study

    PubMed Central

    Durazzo, Timothy C.; Mon, Anderson; Yeh, Ping-Hong; Meyerhoff, Dieter J.

    2010-01-01

    Most previous neuroimaging studies of alcohol-induced brain injury and recovery thereof during abstinence from alcohol used a single imaging modality. They have demonstrated widespread microstructural, macrostructural or metabolite abnormalities that were partially reversible with abstinence, with the cigarette smoking potentially modulating these processes. The goals of this study were to evaluate white matter injury and recovery thereof, simultaneously with diffusion tensor imaging, magnetic resonance imaging and spectroscopy in the same cohort; and to evaluate the relationships between outcome measures of similar regions. We scanned 16 non-smoking and 20 smoking alcohol-dependent individuals at 1 week of abstinence from alcohol and 22 non-smoking light drinkers using a 1.5 T magnetic resonance scanner. Ten non-smoking alcohol-dependent individuals and 11 smoking alcohol-dependent individuals were re-scanned at 1 month of abstinence. All regional diffusion tensor imaging, magnetic resonance imaging and spectroscopic outcome measures were calculated over comparable volumes of frontal, temporal, parietal and occipital white matter. At 1 week of abstinence and relative to non-smoking light drinkers, non-smoking alcohol-dependent individuals had higher mean diffusivity in frontal, temporal and parietal white matter (all P < 0.008), whereas smoking alcohol-dependent individuals had elevated mean diffusivity only in frontal white matter (P = 0.03). Smoking alcohol-dependent individuals demonstrated lower concentrations of N-acetyl-aspartate (a marker of neuronal viability) in frontal white matter (P = 0.03), whereas non-smoking alcohol-dependent individuals had lower N-acetyl-aspartate in parietal white matter (P = 0.05). These abnormalities were not accompanied by detectable white matter atrophy. However, the patterns of white matter recovery were different between non-smoking alcohol-dependent individuals and smoking alcohol-dependent individuals. In non

  2. Randomized Trial Comparing Two Treatment Strategies Using Prize-Based Reinforcement of Abstinence in Cocaine and Opiate Users

    ERIC Educational Resources Information Center

    Preston, Kenzie L.; Ghitza, Udi E.; Schmittner, John P.; Schroeder, Jennifer R.; Epstein, David H.

    2008-01-01

    We compared two strategies of prize-based contingency management (CM) in methadone-maintained outpatients. Urine was tested thrice weekly for 5 weeks pre-CM, 12 weeks CM, and 8 weeks post-CM. Participants were randomly assigned to a cocaine contingency (four prize draws for each cocaine-negative urine, N = 29) or an opiate-cocaine contingency (one…

  3. Nicotine content and abstinence state have different effects on subjective ratings of positive versus negative reinforcement from smoking

    PubMed Central

    Lindsey, Kimberly P.; Bracken, Bethany K.; MacLean, Robert R.; Ryan, Elizabeth T.; Lukas, Scott E.; Frederick, Blaise deB.

    2012-01-01

    Despite the well-known adverse health consequences of smoking, approximately 20% of US adults smoke tobacco cigarettes. Much of the research on smoking reinforcement and the maintenance of tobacco smoking behavior has focused on nicotine; however, a number of other non-nicotine factors are likely to influence the reinforcing effects of smoked tobacco. A growing number of studies suggest that non-nicotine factors, through many pairings with nicotine, are partially responsible for the reinforcing effect of smoking. Additionally, both clinical studies and preclinical advances in our understanding of nicotinic receptor regulation suggest that abstinence from smoking may influence smoking reinforcement. These experiments were conducted for 2 reasons: to validate a MRI-compatible cigarette smoking device; and to simultaneously investigate the impact of nicotine, smoking-associated conditioned reinforcers, and smoking abstinence state on subjective ratings of smoking reinforcement. Participants smoked nicotine and placebo cigarettes through an fMRI compatible device in an overnight-abstinent state or in a nonabstinent state, after having smoked a cigarette 25 minutes prior. Outcome measures were within-subject changes in physiology and subjective ratings of craving and drug effect during the smoking of nicotine or placebo cigarettes on different days in both abstinence states. Cigarette type (nicotine vs. placebo) had a significant effect on positive subjective ratings of smoking reinforcement (“High”, “Like Drug”, “Feel Drug”; nicotine>placebo). In contrast, abstinence state was found to have significant effects on both positive and negative ratings of smoking reinforcement (“Crave”, “Anxiety”, “Irritability”; abstinence > nonabstinence). Interaction effects between abstinence and nicotine provide clues about the importance of neuroadaptive mechanisms operating in dependence, as well as the impact of conditioned reinforcement on subjective ratings

  4. Effects of abstinence from chronic cocaine self-administration on nonhuman primate dorsal and ventral noradrenergic bundle terminal field structures.

    PubMed

    Smith, Hilary R; Beveridge, Thomas J R; Nader, Michael A; Porrino, Linda J

    2016-06-01

    Repeated exposure to cocaine is known to dysregulate the norepinephrine system, and norepinephrine has also been implicated as having a role in abstinence and withdrawal. The goal of this study was to determine the effects of exposure to cocaine self-administration and subsequent abstinence on regulatory elements of the norepinephrine system in the nonhuman primate brain. Rhesus monkeys self-administered cocaine (0.3 mg/kg/injection, 30 reinforcers/session) under a fixed-interval 3-min schedule of reinforcement for 100 sessions. Animals in the abstinence group then underwent a 30-day period during which no operant responding was conducted, followed by a final session of operant responding. Control animals underwent identical schedules of food reinforcement and abstinence. This duration of cocaine self-administration has been shown previously to increase levels of norepinephrine transporters (NET) in the ventral noradrenergic bundle terminal fields. In contrast, in the current study, abstinence from chronic cocaine self-administration resulted in elevated levels of [(3)H]nisoxetine binding to the NET primarily in dorsal noradrenergic bundle terminal field structures. As compared to food reinforcement, chronic cocaine self-administration resulted in decreased binding of [(3)H]RX821002 to α2-adrenoceptors primarily in limbic-related structures innervated by both dorsal and ventral bundles, as well as elevated binding in the striatum. However, following abstinence from responding for cocaine binding to α2-adrenoceptors was not different than in control animals. These data demonstrate the dynamic nature of the regulation of norepinephrine during cocaine use and abstinence, and provide further evidence that the norepinephrine system should not be overlooked in the search for effective pharmacotherapies for cocaine dependence. PMID:26013302

  5. (+/-)3,4-Methylenedioxymethamphetamine (MDMA) dose-dependently impairs spatial learning in the morris water maze after exposure of rats to different five-day intervals from birth to postnatal day twenty.

    PubMed

    Vorhees, Charles V; Schaefer, Tori L; Skelton, Matthew R; Grace, Curtis E; Herring, Nicole R; Williams, Michael T

    2009-01-01

    During postnatal days (PD) 11-20, (+/-)3,4-methylenedioxymethamphetamine (MDMA) treatment impairs egocentric and allocentric learning, and reduces spontaneous locomotor activity; however, it does not have these effects during PD 1-10. How the learning impairments relate to the stress hyporesponsive period (SHRP) is unknown. To test this association, the preweaning period was subdivided into 5-day periods from PD 1-20. Separate pups within each litter were injected subcutaneously with 0, 10, 15, 20, or 25 mg/kg MDMA x4/day on PD 1-5, 6-10, 11-15, or 16-20, and tested as adults. The 3 highest MDMA dose groups showed reduced locomotor activity during the first 10 min (of 60 min), especially in the PD 1-5 and 6-10 dosing regimens. MDMA groups in all dosing regimens showed impaired allocentric learning in the Morris water maze (on acquisition and reversal, all MDMA groups were affected; on the small platform phase, the 2 high-dose groups were affected). No effects of MDMA were found on anxiety (elevated zero maze), novel object recognition, or egocentric learning (although a nonsignificant trend was observed). The Morris maze results did not support the idea that the SHRP is critical to the effects of MDMA on allocentric learning. However, since no effects on egocentric learning were found, but were apparent after PD 11-20 treatment, the results show that these 2 forms of learning have different exposure-duration sensitivities. PMID:19372692

  6. The acute effect in rats of 3,4-methylenedioxyethamphetamine (MDEA, "eve") on body temperature and long term degeneration of 5-HT neurones in brain: a comparison with MDMA ("ecstasy").

    PubMed

    Colado, M I; Granados, R; O'Shea, E; Esteban, B; Green, A R

    1999-06-01

    Administration of a single dose of the recreationally used drug 3,4-methylenedioxyethamphetamine (MDEA or "eve") to Dark Agouti rats resulted in an acute dose-dependent hyperthermic response. The peak effect and duration of hyperthermia of a dose of MDEA of 35 mg/kg intraperitoneally was similar to a dose of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") of 15 mg/kg intraperitoneally. Seven days later this dose of MDMA produced a marked (approximately 50%) loss of 5-HT and its metabolite 5-HIAA in cortex, hippocampus and striatum and a similar loss of [3H]-paroxetine binding in cortex: these losses reflecting the MDMA-induced neurotoxic degeneration of 5-HT nerve endings. In contrast, administration of MDEA (15, 25 or 35 mg/kg), even at the highest dose, produced only a 20% loss in cortex and hippocampus and no decrease in striatum. The neurotoxic effect of MDEA was only weakly dose-dependent. Neither MDEA (35 mg/kg) nor MDMA (15 mg/kg) altered striatal dopamine content 7 days later. MDEA appeared to have about half the potency of MDMA in inducing acute hyperthermia and 25% of the potency in inducing degeneration of cerebral 5-HT neurones. However since higher doses of MDEA (compared to MDMA) are probably necessary to induce mood changing effects, these data do not support any contention that this compound is a "safer" recreational drug than MDMA in terms of either acute toxicity or long term neurodegeneration. PMID:10401727

  7. Exposure to 3,4-methylenedioxymethamphetamine (MDMA) on postnatal days 11-20 induces reference but not working memory deficits in the Morris water maze in rats: implications of prior learning.

    PubMed

    Vorhees, Charles V; Reed, Tracy M; Skelton, Matthew R; Williams, Michael T

    2004-01-01

    3,4-methylenedioxymethamphetamine (MDMA) in previous experiments has been shown to induce long-term spatial and sequential learning and memory deficits in adult offspring after exposure to the drug on postnatal (P) days 11-20, but not after exposure on P1-10. Herein we further tested for the effects of MDMA (0, 5, 10 or 20 mg/kg x 2/day) after exposure on P11-20 on reference and working memory in the Morris water maze (MWM), on reference memory in the Barnes maze, and on cued learning in the visible platform version of the MWM. The MWM and Barnes mazes were counterbalanced such that half the litters received the MWM-first and the other half received the Barnes maze first. Effects on MWM performance as a function of test order were observed. For animals that received the Barnes maze first, spatial MWM learning and memory trends were seen but they were not significantly different between MDMA groups and saline controls. For those receiving the MWM-first, there are consistent impairments on all measures in the MDMA groups compared to controls on MWM performance (latency, path length, and cumulative distance from the goal). On probe trials, MDMA animals receiving the MWM-first showed increased distance from the target site compared to controls. There were no MDMA effects seen on cued trials in the MWM or on straight channel swimming trials regardless of test order, indicating that MDMA had no effects on swimming ability or on the skills needed to learn the MWM. Similarly, there were no effects of MDMA on MWM working memory regardless of test order. No MDMA effects on the Barnes maze were found regardless of test order, however, the interpretation of this finding was compromised by the poor performance of the animals on this task. PMID:15380825

  8. 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

  9. 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

  10. The antecedents and benefits of achieving abstinence in opioid addicts: a 2.5-year follow-up study.

    PubMed

    Rounsaville, B J; Kosten, T R; Kleber, H D

    1987-01-01

    This report examines long-term and short-term benefits of achieving abstinence from opioids in a sample of opioid addicts who were reevaluated 2.5 years following seeking treatment. Extensive assessment of drug use history and drug-associated problems had been obtained when the subjects applied for treatment. At follow-up evaluations, detailed information was obtained on intervening course of drug use, treatment, legal problems, psychological problems, social functioning, occupational functioning, and medical status. The results were as follows: (1) Achieving abstinence from illicit opioids was associated with concurrent improvement in other aspects of functioning including reduction of criminal activity, improved medical status, improved social functioning, and reduced abuse of other psychoactive substances. However, many of these improvements were reversed immediately if relapse to opioid use occurred. (2) Achieving abstinence was associated with being in drug treatment, especially treatment in a methadone maintenance program. (3) Achievement of abstinence was not successfully predicted by client characteristics measured at entrance into treatment. (4) Long-range benefits of abstinence were detectable in social functioning even for those who had relapsed at the time of follow-up reevaluation. PMID:3687888

  11. Cognitive function during early abstinence from opioid dependence: a comparison to age, gender, and verbal intelligence matched controls

    PubMed Central

    Rapeli, Pekka; Kivisaari, Reetta; Autti, Taina; Kähkönen, Seppo; Puuskari, Varpu; Jokela, Olga; Kalska, Hely

    2006-01-01

    Background Individuals with opioid dependence have cognitive deficits during abuse period in attention, working memory, episodic memory, and executive function. After protracted abstinence consistent cognitive deficit has been found only in executive function. However, few studies have explored cognitive function during first weeks of abstinence. The purpose of this study was to study cognitive function of individuals with opioid dependence during early abstinence. It was hypothesized that cognitive deficits are pronounced immediately after peak withdrawal symptoms have passed and then partially recover. Methods Fifteen patients with opioid dependence and fifteen controls matched for, age, gender, and verbal intelligence were tested with a cognitive test battery When patients performed worse than controls correlations between cognitive performance and days of withdrawal, duration of opioid abuse, duration of any substance abuse, or opioid withdrawal symptom inventory score (Short Opiate Withdrawal Scale) were analyzed. Results Early abstinent opioid dependent patients performed statistically significantly worse than controls in tests measuring complex working memory, executive function, and fluid intelligence. Their complex working memory and fluid intelligence performances correlated statistically significantly with days of withdrawal. Conclusion The results indicate a rather general neurocognitive deficit in higher order cognition. It is suggested that cognitive deficit during early abstinence from opioid dependence is related to withdrawal induced neural dysregulation in the prefrontal cortex and is partly transient. PMID:16504127

  12. Influence of abstinence and conditions of cocaine access on the reinforcing strength of cocaine in nonhuman primates.

    PubMed

    Czoty, Paul W; Martelle, Jennifer L; Nader, Michael A

    2006-12-01

    The development of addiction is marked by a transition from recreational to uncontrolled drug use. Investigators modeling this phenomenon in rodents observed increases in cocaine self-administration when conditions of drug access were altered as well as after abstinence. The present studies were designed to extend this research to nonhuman primates by examining whether the reinforcing strength of cocaine could be altered by changing conditions of cocaine availability or by introducing abstinence periods. Rhesus monkeys self-administered cocaine (0.03-0.3 mg/kg per injection) under a progressive-ratio (PR) schedule of reinforcement in evening sessions, with the number of injections earned serving as a measure of reinforcing strength. Alterations in the reinforcing strength of cocaine were assessed after additional access to cocaine under a fixed-ratio (FR) schedule was provided in morning sessions and following various periods of abstinence (3, 7 and 14 days) from regimens of self-administration that resulted in a range of cocaine intakes. Under baseline PR conditions, the maximum number of cocaine injections increased dose-dependently, peaking when 0.3 mg/kg per injection cocaine was available. No increases in the reinforcing strength of cocaine were observed under any condition. In contrast, a statistically significant decrease in the reinforcing strength of cocaine was observed following 14 days of abstinence under one condition. These results fail to support the views that increasing access to cocaine or abstinence enhances the reinforcing strength of cocaine. PMID:16730922

  13. Smoking Abstinence-related Expectancies among American Indians, African Americans, and Women: Potential Mechanisms of Tobacco-related Disparities

    PubMed Central

    Hendricks, Peter S.; Westmaas, J. Lee; Park, Van M. Ta; Thorne, Christopher B.; Wood, Sabrina B.; Baker, Majel R.; Lawler, R. Marsh; Hooper, Monica Webb; Delucchi, Kevin L.; Hall, Sharon M.

    2014-01-01

    Research has documented tobacco-related health disparities by race and gender. Prior research, however, has not examined expectancies about the smoking cessation process (i.e., abstinence-related expectancies) as potential contributors to tobacco-related disparities in special populations. This cross-sectional study compared abstinence-related expectancies between American Indian (n = 87), African American (n = 151), and White (n = 185) smokers, and between women (n = 231) and men (n = 270) smokers. Abstinence-related expectancies also were examined as mediators of race and gender relationships with motivation to quit and abstinence self-efficacy. Results indicated that American Indians and African Americans were less likely than Whites to expect withdrawal effects, and more likely to expect that quitting would be unproblematic. African Americans also were less likely than Whites to expect smoking cessation interventions to be effective. Compared to men, women were more likely to expect withdrawal effects and weight gain.These expectancy differences mediated race and gender relationships with motivation to quit and abstinence self-efficacy. Findings emphasize potential mechanisms underlying tobacco-related health disparities among American Indians, African Americans, and women, and suggest a number of specific approaches for targeting tobacco dependence interventions to these populations. PMID:23528192

  14. Mediators of the relationship between nicotine replacement therapy and smoking abstinence among people living with HIV/AIDS.

    PubMed

    Stanton, Cassandra A; Lloyd-Richardson, Elizabeth E; Papandonatos, George D; de Dios, Marcel A; Niaura, Raymond

    2009-06-01

    Cigarette smoking is highly prevalent among people living with HIV/AIDS and poses unique health risks. Smoking cessation programs tailored to this population have documented improved smoking outcomes with nicotine replacement therapy (NRT). The current study examined 6-month abstinence rates from a randomized clinical trial targeting 412 HIV-positive adult current smokers (51% European American, 19% African American, and 17% Hispanic American) and tested whether psychosocial variables, such as self-efficacy and decisional balance, mediated the relationship between NRT and long-term abstinence. Meeting criteria for complete mediation, 6-month smoking abstinence rates improved significantly with increases in these mediators, and the association of NRT and smoking abstinence was no longer significant once changes in self-efficacy and decisional balance were taken into account . Failure to translate gains in self-efficacy among African Americans into improved abstinence rates accounted for racial/ethnic differences among participants. Specific psychosocial factors, such as self-efficacy, may be particularly amenable to change in cessation interventions and should be addressed with greater awareness of how cultural and social contextual factors impact treatment response among people living with HIV/AIDS. PMID:19537955

  15. Addiction: From Context-Induced Hedonia to Appetite, Based on Transition of Micro-behaviors in Morphine Abstinent Tree Shrews.

    PubMed

    Duan, Ying; Shen, Fang; Gu, Tingting; Sui, Nan

    2016-01-01

    Drug addiction is viewed as a maladaptive memory induced by contextual cues even in the abstinent state. However, the variations of hedonia and appetite induced by the context during the abstinence have been neglected. To distinguish the representative behaviors between hedonia and appetite, micro-behaviors in abstinent animal such as psycho-activity and drug seeking behaviors were observed in morphine conditioned place preference (CPP). To confirm the different effects of reward between drug and natural reward, a palatable food CPP paradigm was compared in current work. After a 10-day training in CPP with morphine or food, the preference was tested on day 1, 14, 28, and the changes of micro-behaviors were analyzed further. Our data showed that tree shrews treated with morphine performed more jumps on day 1 and more visits to saline paired side on day 28, which indicated a featured behavioral transition from psycho-activity to seeking behavior during drug abstinence. Meanwhile, food-conditioned animals only displayed obvious seeking behaviors in the three tests. The results suggest that the variations of micro-behaviors could imply such a transition from hedonic response to appetitive behaviors during morphine abstinence, which provided a potential behavioral basis for further neural mechanism studies. PMID:27375516

  16. Addiction: From Context-Induced Hedonia to Appetite, Based on Transition of Micro-behaviors in Morphine Abstinent Tree Shrews

    PubMed Central

    Duan, Ying; Shen, Fang; Gu, Tingting; Sui, Nan

    2016-01-01

    Drug addiction is viewed as a maladaptive memory induced by contextual cues even in the abstinent state. However, the variations of hedonia and appetite induced by the context during the abstinence have been neglected. To distinguish the representative behaviors between hedonia and appetite, micro-behaviors in abstinent animal such as psycho-activity and drug seeking behaviors were observed in morphine conditioned place preference (CPP). To confirm the different effects of reward between drug and natural reward, a palatable food CPP paradigm was compared in current work. After a 10-day training in CPP with morphine or food, the preference was tested on day 1, 14, 28, and the changes of micro-behaviors were analyzed further. Our data showed that tree shrews treated with morphine performed more jumps on day 1 and more visits to saline paired side on day 28, which indicated a featured behavioral transition from psycho-activity to seeking behavior during drug abstinence. Meanwhile, food-conditioned animals only displayed obvious seeking behaviors in the three tests. The results suggest that the variations of micro-behaviors could imply such a transition from hedonic response to appetitive behaviors during morphine abstinence, which provided a potential behavioral basis for further neural mechanism studies. PMID:27375516

  17. Baclofen promotes alcohol abstinence in alcohol dependent cirrhotic patients with hepatitis C virus (HCV) infection

    PubMed Central

    Leggio, L.; Ferrulli, A.; Zambon, A.; Caputo, F.; Kenna, G.A.; Swift, R.M.; Addolorato, G.

    2016-01-01

    Hepatitis C virus (HCV) and alcoholic liver disease (ALD), either alone or in combination, count for more than two thirds of all liver diseases in the Western world. There is no safe level of drinking in HCV-infected patients and the most effective goal for these patients is total abstinence. Baclofen, a GABAB receptor agonist, represents a promising pharmacotherapy for alcohol dependence (AD). Previously, we performed a randomized clinical trial (RCT), which demonstrated the safety and efficacy of baclofen in patients affected by AD and cirrhosis. The goal of this post-hoc analysis was to explore baclofen's effect in a subgroup of alcohol-dependent HCV-infected cirrhotic patients. Any patient with HCV infection was selected for this analysis. Among the 84 subjects randomized in the main trial, 24 alcohol-dependent cirrhotic patients had a HCV infection; 12 received baclofen 10mg t.i.d. and 12 received placebo for 12-weeks. With respect to the placebo group (3/12, 25.0%), a significantly higher number of patients who achieved and maintained total alcohol abstinence was found in the baclofen group (10/12, 83.3%; p=0.0123). Furthermore, in the baclofen group, compared to placebo, there was a significantly higher increase in albumin values from baseline (p=0.0132) and a trend toward a significant reduction in INR levels from baseline (p=0.0716). In conclusion, baclofen was safe and significantly more effective than placebo in promoting alcohol abstinence, and improving some LFTs (i.e. albumin, INR) in alcohol-dependent HCV-infected cirrhotic patients. Baclofen may represent a clinically relevant alcohol pharmacotherapy for these patients. PMID:22244707

  18. Emotion-word Processing Difficulties in Abstinent Alcoholics with and without Lifetime Externalizing Disorders

    PubMed Central

    Endres, Michael J.; Fein, George

    2015-01-01

    Background Evidence suggests that abstinent alcoholics have difficulties processing a variety of emotion-laden stimuli, and some of these difficulties may not fully resolve with long-term abstinence. The current study examined whether emotion-word processing difficulties were present in long-term abstinent alcoholics (LTAA; 18+ months of sobriety) with and without a previously diagnosed externalizing (EXT; ASPD and/or ADHD diagnosis) disorder. Method Subjects (N=121) completed an affective go/no-go (AGNG) task with positive, negative, and neutral emotion-word stimuli, and a lexical decision-making (LDM) task with non-emotion word and non-word stimuli. Non-substance abusing controls (NSAC; n=38, 50.0 % Female, mean age=48±7.8), LTAA with EXT (n=32, 41% Female, mean age=47.1±6.6 years), and LTAA without EXT (n=51, 47% Female, mean age=49.7±6.5 years) were compared on signal discriminability (d’) and mean RT for correct responses (mcRT). Results In the LDM task, LTAA had lower (d’) values and slower mcRT than NSAC. In the AGNG task, LTAA and NSAC did not differ in AGNG task mcRT. LTAA had lower (d’) values than NSAC, and this effect was partially associated with group differences in LDM task (d’) values. In LTAA, lower AGNG (d’) values also were associated with an earlier age of first drink, greater lifetime alcohol use, and a history of externalizing disorder. Conclusions Our findings suggest that detecting the emotional content of words is impaired in LTAA, and this impairment is over and above LTAA’s more general lexical processing difficulties. Results also suggest that specific emotion processing impairments in LTAA may be exacerbated by greater lifetime alcohol use burden and other comorbid EXT diagnoses. PMID:23278634

  19. Sublingual Buprenorphine for Treatment of the Neonatal Abstinence Syndrome: A Randomized Trial

    PubMed Central

    Kraft, Walter K.; Gibson, Eric; Dysart, Kevin; Damle, Vidula S.; LaRusso, Jennifer L.; Greenspan, Jay S.; Moody, David E.; Kaltenbach, Karol; Ehrlich, Michelle E.

    2008-01-01

    Objective In utero exposure to drugs of abuse can lead to the Neonatal Abstinence Syndrome (NAS), a condition that is associated with prolonged hospitalization. Buprenorphine is a partial mu opioid agonist used for treatment of adult detoxification and maintenance, but has never been administered to neonates with opioid abstinence. The primary objective of this study was to demonstrate the feasibility and to the extent possible in this sized study, the safety of sublingual buprenorphine in the treatment of NAS. Secondary goals were to evaluate efficacy relative to standard therapy and to characterize buprenorphine pharmacokinetics when sublingually administered. Methods We conducted a randomized, open-label, active control study of sublingual buprenorphine for the treatment of opiate withdrawal. Thirteen term infants were allocated to sublingual buprenorphine 13.2–39 mcg/kg/day administered in three divided doses and thirteen to standard of care oral neonatal opium solution (NOS). Dose decisions were made using a modified Finnegan scoring system. Results Sublingual buprenorphine was largely effective in controlling NAS. Greater than 98% of plasma concentrations ranged from undetectable to approximately 0.60 ng/ml, which is less than needed to control abstinence symptoms in adults. The ratio of buprenorphine to norbuprenorphine was larger than that seen in adults, suggesting a relative impairment of N-dealkylation. Three infants receiving buprenorphine and one infant receiving standard of care reached protocol-specified maximum doses and required adjuvant therapy with phenobarbital. The mean length of treatment for the NOS group was 32 compared to 22 days for the buprenorphine group. The mean length of stay for the NOS group was 38 days compared to 27 days for the buprenorphine group. Treatment with buprenorphine was well tolerated. Conclusions Buprenorphine administered via the sublingual route is feasible and apparently safe, and may represent a novel treatment

  20. MISH publishes new framework for fear-based, abstinence-only education.

    PubMed

    Mayer, R

    1997-01-01

    The US Medical Institute for Sexual Health (MISH) "National Guidelines for Sexuality and Character Education" is a fear-based, abstinence-only framework for sexuality education. This document is virtually identical in format, conceptual framework, and typeface to that produced by the Sexuality Information and Education Council of the United States (SIECUS) and adopts SIECUS language in many sections. SIECUS agrees with approximately 60% of the MISH messages and finds it noteworthy that the MISH guidelines provide a blueprint for sex education from elementary school through high school. However, MISH and SIECUS follow very different approaches to sex education. SIECUS seeks to help young people acquire the necessary information to safeguard their sexual health and make proper decisions, while the single goal of MISH is to promote abstinence until marriage (avoiding sexual intercourse and any activity involving genital contact or stimulation). MISH promotes this view with fear-based messages, uses only negative terms to describe adolescent sexual relations, and provides scant and misleading information about contraception (including the assertion that adolescent use of birth control is often ineffective). The MISH curriculum also promotes the anti-abortion viewpoint that life begins at conception. While acknowledging the changing composition of the US family, MISH promotes a view of the nuclear family as the "best" type of family in which to rear children. MISH skirts the issue of sexual orientation and avoids giving information about ways to seek treatment for sexually transmitted diseases or prenatal care. MISH guidelines make unsubstantiated statements about the value of abstinence, provide almost no information about how to adapt their framework to various communities, discuss contraceptives and condoms only in terms of failures, and suggest that all adolescent sexual relations have negative consequences. PMID:12319710

  1. Sperm Chromatin Immaturity Observed in Short Abstinence Ejaculates Affects DNA Integrity and Longevity In Vitro

    PubMed Central

    Salian, Sujith Raj; Kumar, Dayanidhi; Singh, Vikram Jeet; D’Souza, Fiona; Kalthur, Guruprasad; Kamath, Asha; Adiga, Satish Kumar

    2016-01-01

    Background The influence of ejaculatory abstinence (EA) on semen parameters and subsequent reproductive outcome is still debatable; hence understanding the impact of EA on sperm structural and functional integrity may provide a valuable information on predicting successful clinical outcome. Objective To understand the influence of EA on sperm chromatin maturity, integrity, longevity and global methylation status. Methods This experimental prospective study included 76 ejaculates from 19 healthy volunteers who provided ejaculates after observing 1, 3, 5 and 7 days of abstinence. Sperm chromatin maturity, DNA integrity and global methylation status were assessed in the neat ejaculate. Sperm motility, DNA integrity and longevity were assessed in the processed fraction of the fresh and frozen-thawed ejaculates to determine their association with the length of EA. Results Spermatozoa from 1 day ejaculatory abstinence (EA-1) displayed significantly higher level of sperm chromatin immaturity in comparison to EA-3 (P < 0.05) and EA-5 (P < 0.01) whereas; the number of 5-methyl cytosine immunostained spermatozoa did not vary significantly across groups. On the other hand, in vitro incubation of processed ejaculate from EA-1 resulted in approximately 20 and 40 fold increase in the DNA fragmented spermatozoa at the end of 6 and 24h respectively (P < 0.01–0.001). Conclusion Use of short-term EA for therapeutic fertilization would be a clinically valuable strategy to improve the DNA quality. However, use of such spermatozoa after prolonged incubation in vitro should be avoided as it can carry a substantial risk of transmitting DNA fragmentation to the oocytes. PMID:27043437

  2. Abstinence versus Moderation Goals in Brief Motivational Treatment for Pathological Gambling.

    PubMed

    Stea, Jonathan N; Hodgins, David C; Fung, Tak

    2015-09-01

    The present study examined the nature and impact of participant goal selection (abstinence versus moderation) in brief motivational treatment for pathological gambling via secondary analyses from a randomized controlled trial. The results demonstrated that the pattern of goal selection over time could be characterized by both fluidity and stability, whereby almost half of participants switched their goal at least one time, over 25% of participants selected an unchanging goal of 'quit most problematic type of gambling', almost 20% selected an unchanging goal of 'quit all types of gambling', and approximately 10% selected an unchanging goal of 'gamble in a controlled manner.' The results also demonstrated that pretreatment goal selection was uniquely associated with three variables, whereby compared to participants who selected the goal to 'cut back on problem gambling', those who selected the goal to 'quit problem gambling' were more likely to have greater gambling problem severity, to have identified video lottery terminal play as problematic, and to have greater motivation to overcome their gambling problem. Finally, the results demonstrated that goal selection over time had an impact on the average number of days gambled over the course of treatment, whereby those with abstinence-based goals gambled significantly fewer days than those with moderation-based goals. Nevertheless, goal selection over time was not related to dollars gambled, dollars per day gambled, or perceived goal achievement. The findings do not support the contention that abstinence-based goals are more advantageous than moderation goals and are discussed in relation to the broader alcohol treatment literature. PMID:24748014

  3. 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

  4. 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

  5. Application of ORAL.screen saliva drug test for the screening of methamphetamine, MDMA, and MDEA incorporated in hair.

    PubMed

    Miki, Akihiro; Katagi, Munehiro; Shima, Noriaki; Tsuchihashi, Hitoshi

    2004-03-01

    By the use of a one-step immunoassay drug test for oral fluid, a convenient and fairly sensitive screening method has been devised for methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) incorporated in hair. These drugs, in a 10-mg portion of hair, were extracted into 5M HCl/methanol (1:20, v/v), and the extract reconstituted in 100 micro L water was assayed with the saliva drug test ORAL.screen trade mark. The limits of detection were 0.5 ng/mg hair for d-MA, 0.8 ng/mg for dl-MDMA, and 1.0 ng/mg for dl-MDEA. The results are in good agreement with those of gas chromatography-mass spectrometry (GC-MS) determination. Although all positive results must be confirmed by either GC-MS or a specific alternative methodology, this method provided a simple screening, suitable for drug enforcement purposes, while requiring only a 10-mg hair specimen. PMID:15068568

  6. 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

  7. Predictors of sexual abstinence among Wolaita Sodo University Students, South Ethiopia

    PubMed Central

    2013-01-01

    Background It is over 30 years since the first case of AIDS [Acquired Immune Deficiency Syndrome] was identified. Attention has been focused recently on the promotion of the “ABCs” of HIV prevention (being abstinent or delaying sex, remaining faithful to one sexual partner, and using condoms consistently during sexual intercourse). As programs that focus on ABCs to prevent heterosexual transmission HIV are rolled out, questions of how well university students who come from varied cultural contexts actually understand the terms and address challenges to adopt behaviors is unanswered. In Ethiopia, despite the mushrooming number of students in the higher learning institutions with the current figure being 210,000 students accommodated in 33 public and 72 private higher learning institutions, sexual and reproductive health services, are not delivered in an organized way. The objective of this study is to identify factors associated with Sexual abstinence among Wolaita Sodo University students to provide evidence for designing appropriate interventions. Methods A Cross-Sectional study was conducted among 750 undergraduate students selected from Wolaita Sodo University using a stratified simple random sampling technique during the academic year. Data were collected using structured self administered questionnaire, focus group discussion and in depth interview guides as tools for data collection. Ethical clearance was obtained from Jimma University and informed consent was obtained from the participants after explaining purpose of study. Statistical tests were employed wherever necessary at the significance level of 0.05. Results All of the participants had heard about HIV/AIDS of which 97.3% had good knowledge. Higher proportions of male students were sexually active than their counter parts. Students with better knowledge on HIV AIDS were 6.6 (95%CI=1.6, 12.9) times more likely to abstain from sexual intercourse than their counter parts. Conclusions Knowledge of

  8. Cardiac autonomic function during sleep: effects of alcohol dependence and evidence of partial recovery with abstinence

    PubMed Central

    de Zambotti, Massimiliano; Willoughby, Adrian R.; Baker, Fiona C.; Sugarbaker, David S.; Colrain, Ian M.

    2015-01-01

    Chronic alcoholism is associated with the development of cardiac and peripheral autonomic nervous system (ANS) pathology. The aim of the present study was to evaluate the extent to which recovery in ANS function could be demonstrated over the first 4 months of abstinence. Fifteen alcoholics (7 women) were studied on three occasions: within a month of detoxification, at approximately 2 months post-detox, and at 4 months post-detox. Thirteen control subjects (6 women) were also studied on three occasions with inter-study intervals matching those of the alcoholics. Six alcoholics relapsed, 48.7 ± 27.9 days following the initial PSG session. ANS function was assessed in the first part of stable non-rapid eye movement sleep. Frequency-domain power spectral analysis of heart rate variability (HRV) produced variables including: heart rate (HR), total power (TP; an index representing total HR variability), High Frequency power (HFa; an index reflecting cardiac vagal modulation), HF proportion of total power (HFprop sympathovagal balance), and HF peak frequency (HFpf; an index reflecting respiration rate). Overall, high total and high frequency variability and low sympathovagal balance and myocardial contractility are considered as desired conditions to promote cardiovascular health. At initial assessment, alcoholics had a higher HR (p < 0.001) and respiratory rate (p < 0.01), and lower vagal activity (HFa; p < 0.01) than controls. Alcoholics showed evidence of recovery in HR (p = 0.039) and HFa (p = 0.031) with 4 months of abstinence. Alcoholics with higher TP at the initial visit showed a greater improvement in TP from the initial to the 4-month follow-up session (r = 0.75, p < 0.05). Alcoholics showed substantial recovery in HR and vagal modulation of HRV with 4 months of abstinence, with evidence that the extent of recovery in HRV may be partially determined by the extent of alcohol dependence-related insult to the cardiac ANS system. These data support other studies

  9. Physicians' views of periodic abstinence methods: a study in four countries.

    PubMed

    Snowden, R; Kennedy, K I; Leon, F; Orense, V C; Perera, H W; Phillips, R; Askew, I; Flynn, A; Severy, L J

    1988-01-01

    A study of the knowledge, perceptions, and behavioral intentions of physicians regarding periodic abstinence (PA) methods was undertaken in Mauritius, Peru, the Philippines, and Sri Lanka. Most respondents considered PA to be useful, although even the PA providers prescribed mainly non-PA methods. Detailed knowledge of PA methods was not evident, but most physicians were willing to initiate general discussion about PA with patients. Physicians favored methods perceived as "scientific" and "modern," which primarily prevent pregnancy and secondarily avoid other health risks. When carefully presented as "scientific" and "modern," methods presented to medical audiences may find acceptance and be more likely to result in referral. PMID:3176094

  10. Cardiac autonomic function during sleep: effects of alcohol dependence and evidence of partial recovery with abstinence.

    PubMed

    de Zambotti, Massimiliano; Willoughby, Adrian R; Baker, Fiona C; Sugarbaker, David S; Colrain, Ian M

    2015-06-01

    Chronic alcoholism is associated with the development of cardiac and peripheral autonomic nervous system (ANS) pathology. The aim of the present study was to evaluate the extent to which recovery in ANS function could be demonstrated over the first 4 months of abstinence. Fifteen alcoholics (7 women) were studied on three occasions: within a month of detoxification, at approximately 2 months post-detox, and at 4 months post-detox. Thirteen control subjects (6 women) were also studied on three occasions with inter-study intervals matching those of the alcoholics. Six alcoholics relapsed, 48.7 ± 27.9 days following the initial PSG session. ANS function was assessed in the first part of stable non-rapid eye movement sleep. Frequency-domain power spectral analysis of heart rate variability (HRV) produced variables including: heart rate (HR), total power (TP; an index representing total HR variability), High Frequency power (HFa; an index reflecting cardiac vagal modulation), HF proportion of total power (HFprop sympathovagal balance), and HF peak frequency (HFpf; an index reflecting respiration rate). Overall, high total and high frequency variability and low sympathovagal balance and myocardial contractility are considered as desired conditions to promote cardiovascular health. At initial assessment, alcoholics had a higher HR (p < 0.001) and respiratory rate (p < 0.01), and lower vagal activity (HFa; p < 0.01) than controls. Alcoholics showed evidence of recovery in HR (p = 0.039) and HFa (p = 0.031) with 4 months of abstinence. Alcoholics with higher TP at the initial visit showed a greater improvement in TP from the initial to the 4 month follow-up session (r = 0.75, p < 0.05). Alcoholics showed substantial recovery in HR and vagal modulation of HRV with 4 months of abstinence, with evidence that the extent of recovery in HRV may be partially determined by the extent of alcohol dependence-related insult to the cardiac ANS system. These data support other studies

  11. Orexin-A level elevation in recently abstinent male methamphetamine abusers.

    PubMed

    Chen, Wen-Yin; Kao, Chung-Feng; Chen, Po-Yu; Lin, Shih-Ku; Huang, Ming-Chyi

    2016-05-30

    Research has suggested that methamphetamine (METH) use influences orexin regulation. We examined the difference in orexin-A levels between METH abusers and healthy controls. Fasting serum orexin-A levels were measured in 35 participants who used METH in the preceding 3 weeks and 36 healthy controls. We found METH abusers had significantly higher orexin-A levels. No association was observed between orexin-A levels and METH use variables. Our results, consistent with prior preclinical evidence, showed that recent METH exposure is associated with increased orexin-A expression. Further investigation is required to determine whether orexin-A levels normalize after a longer term of abstinence. PMID:27137956

  12. Changes in leptin, ghrelin, growth hormone and neuropeptide-Y after an acute model of MDMA and methamphetamine exposure in rats.

    PubMed

    Kobeissy, Firas H; Jeung, Jennifer A; Warren, Matthew W; Geier, Jacqueline E; Gold, Mark S

    2008-03-01

    Club drug abuse is a growing problem in the United States. Beyond addiction and toxicity are endocrine effects which are not well characterized. Specifically, the changes in appetite following exposure to drugs of abuse are an interesting but poorly understood phenomenon. Serum hormones such as leptin, ghrelin, growth hormone (GH), and neuropeptide-Y (NP-Y) are known to affect appetite, but have not been studied extensively with drugs of abuse. In this work, we examine the effects of club drugs 3,4-methylenedioxymethamphetamine (MDMA) (ecstasy) and methamphetamine (METH) (doses of 5, 20 and 40 mg/kg) on serum concentrations of these hormones in adult male Sprague-Dawley rats 6, 12, 24 and 48 hours after drug administration. In a dose-dependent manner, MDMA was shown to cause transient significant decreases in serum leptin and GH followed by a base line recovery after 24 hours. Conversely, serum ghrelin increased and normalized after 24 hours. Interestingly, serum NP-Y showed a steady decrease in both treatment of MDMA and METH at different time points and dosages. In humans, abuse of these drugs reduces eating. As evident from these data, acute administration of METH and MDMA had significant effects on different serum hormone levels involved in appetite regulation. Future studies should be performed to see how chronic, low dose drug administration would affect hormone levels and try to answer questions about the physiological mechanisms involved in the anorexic paradigm observed in drug use. PMID:17910739

  13. 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

  14. Decision-making in polydrug amphetamine-type stimulant users: an fMRI study.

    PubMed

    Koester, Philip; Volz, Kirsten G; Tittgemeyer, Marc; Wagner, Daniel; Becker, Benjamin; Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

    2013-07-01

    Qualitative poor decision-making and associated altered neuronal activation patterns have been described for the users of several drugs, amongst others for stimulants like amphetamine and MDMA. Deficits in decision-making might be caused by an augmented attraction to short-term rewarding properties despite negative long-term consequences, leading to rigid stimulus-response patterns. In the present imaging study, we investigated decision-making and associated neuronal activation in three groups differing in their exposure to amphetamine and MDMA. An established paradigm on risky choices was used to evaluate decision-making performance and corresponding functional magnet resonance imaging (fMRI) activation. Subjects could choose between a low-risk control gamble and an experimental gamble, which always differed in the probability of winning or losing, as well as the magnitudes of monetary gain or loss. Experienced users (EU), users with low exposure to stimulants and drug-naive controls, did not differ from each other in behavioral performance. In accordance with our hypotheses, the anticipation of reward led to an activation of primarily the frontal cortex and the striatum in low-exposure users and drug-naive controls. In contrast, frontal and parietal activation was observed in all groups when the actual outcome of an experimental gamble was presented. EU displayed more activation compared to both control groups when there was a high probability of winning. The study at hand supports the hypothesis that neuronal activation patterns might even differ between drug users and healthy controls when no behavioral deficits are apparent. In EU, the probability of the occurrence of an event has more influence on neuronal activation than on the actual magnitude of reinforcing properties of this event. PMID:23392532

  15. A reinforcement-based therapeutic workplace for the treatment of drug abuse: six-month abstinence outcomes.

    PubMed

    Silverman, K; Svikis, D; Robles, E; Stitzer, M L; Bigelow, G E

    2001-02-01

    This study evaluated a novel drug abuse treatment, the Therapeutic Workplace. In this treatment, patients are paid to perform jobs or to participate in job training. Salary is linked to abstinence by requiring patients to provide drug-free urine samples to gain access to the workplace. Pregnant and postpartum drug abuse patients (N = 40) were randomly assigned to a Therapeutic Workplace or usual care control group. Therapeutic Workplace participants were invited to work 3 hr every weekday for 6 months and could earn up to $4,030 in vouchers for abstinence, workplace attendance, and performance. On average, 45% of participants attended the workplace per day. Relative to controls, the Therapeutic Workplace nearly doubled patients' abstinence from opiates and cocaine (33% vs. 59% of thrice-weekly urine samples drug negative, respectively, p < .05). The Therapeutic Workplace can effectively treat heroin and cocaine abuse in pregnant and postpartum women. PMID:11519628

  16. 5-HT loss in rat brain following 3,4-methylenedioxymethamphetamine (MDMA), p-chloroamphetamine and fenfluramine administration and effects of chlormethiazole and dizocilpine.

    PubMed Central

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

    1993-01-01

    1. The present study has investigated whether the neurotoxic effects of the relatively selective 5-hydroxytryptamine (5-HT) neurotoxins, 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy'), p-chloroamphetamine (PCA) and fenfluramine on hippocampal and cortical 5-HT terminals in rat brain could be prevented by administration of either chlormethiazole or dizocilpine. 2. Administration of MDMA (20 mg kg-1, i.p.) resulted in an approximate 30% loss of cortical and hippocampal 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) content 4 days later. Injection of chlormethiazole (50 mg kg-1) 5 min before and 55 min after the MDMA provided complete protection in both regions, while dizocilpine (1 mg kg-1, i.p.) protected only the hippocampus. 3. Administration of a single dose of chlormethiazole (100 mg kg-1) 20 min after the MDMA also provided complete protection to the hippocampus but not the cortex. This regime also attenuated the sustained hyperthermia (approx +2.5 degrees C) induced by the MDMA injection. 4. Injection of PCA (5 mg kg-1, i.p.) resulted in a 70% loss of 5-HT and 5-HIAA content in hippocampus and cortex 4 days later. Injection of chlormethiazole (100 mg kg-1, i.p.) or dizocilpine (1 mg kg-1, i.p.) 5 min before and 55 min after the PCA failed to protect against the neurotoxicity, nor was protection afforded by chlormethiazole when a lower dose of PCA (2.5 mg kg-1, i.p.) was given which produced only a 30% loss of 5-HT content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7682129

  17. Abstinence from cocaine self-administration heightens neural encoding of goal-directed behaviors in the accumbens.

    PubMed

    Hollander, Jonathan A; Carelli, Regina M

    2005-08-01

    Cocaine addiction in humans is characterized by cycles of abstinence from drug-taking and relapse. Here, electrophysiological recording procedures were used to determine whether nucleus accumbens (Acb) neuronal firing properties are altered following interruption and resumption of cocaine self-administration. Rats (n = 12) were trained to self-administer cocaine (2 h daily sessions) then divided into two groups. Acb activity was recorded for Group 1 (controls) during two additional self-administration sessions completed over the next 2 days (test sessions 1 and 2). Acb activity was recorded for Group 2 (1-month) during one self-administration session completed the next day (test 1), and during a second self-administration session 1 month later (test 2). As in prior reports, a subset of Acb neurons exhibited patterned discharges (short duration and/or long-term cyclic alterations, termed 'phasically active') relative to cocaine-reinforced responding during test session 1. Remarkably, the percentage of phasically active cells dramatically increased (nearly two-fold) following 1-month abstinence, in the core but not the shell of the Acb. Likewise, the strength of the neural correlates (determined via signal-to-baseline ratios) also increased as a function of abstinence. Extinction experiments in another set of rats (n = 12) revealed an increased motivational state for the drug following abstinence. The results show that abstinence from cocaine self-administration causes a dramatic increase in the number and strength of Acb neurons that encode cocaine-related information, thus representing the first neurophysiological correlate of heightened activation of the 'brain reward system' following abstinence and resumption (relapse) of cocaine consumption. PMID:15856078

  18. A Critical Role of Lateral Hypothalamus in Context-Induced Relapse to Alcohol Seeking after Punishment-Imposed Abstinence

    PubMed Central

    Rabei, Rana; Kaganovsky, Konstantin; Caprioli, Daniele; Bossert, Jennifer M.; Bonci, Antonello

    2014-01-01

    In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA + GABAB receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse. PMID:24872550

  19. A critical role of lateral hypothalamus in context-induced relapse to alcohol seeking after punishment-imposed abstinence.

    PubMed

    Marchant, Nathan J; Rabei, Rana; Kaganovsky, Konstantin; Caprioli, Daniele; Bossert, Jennifer M; Bonci, Antonello; Shaham, Yavin

    2014-05-28

    In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA + GABAB receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse. PMID:24872550

  20. Alterations in mesolimbic dopamine function during the abstinence period following chronic ethanol consumption.

    PubMed

    Bailey, C P; O'Callaghan, M J; Croft, A P; Manley, S J; Little, H J

    2001-12-01

    Previous work demonstrated that the locomotor stimulant actions of amphetamine, cocaine and nicotine were increased when these drugs were given during the abstinence phase after chronic ethanol consumption. These changes were seen at 6 days and at 2 months after cessation of alcohol. The present study examined neuronal alterations which might be related to these changes in behaviour. Markedly reduced spontaneous firing rates of dopaminergic cells in the ventral tegmental area (VTA) in midbrain slices were seen 6 days into the abstinence period after cessation of chronic ethanol consumption, but by 2 months the firing rates had returned to control values. Increased affinity of striatal receptors for the D1-like receptor ligand 3H-SCH23390, but no change in the receptor density, was found both at the 6 day and the 2 month intervals. The binding properties of striatal D2-like receptors, of D1-like and D2-like receptors in the frontal cerebral cortex, and the release of tritiated dopamine from slices of striatum or frontal cerebral cortex, were unchanged at 6 days and 2 months. It is suggested that the decreased neuronal firing leads to a persistent increase in sensitivity of D1-like receptors and that these changes could explain the increased effects of the other drugs of abuse. PMID:11747903

  1. Frontostriatal Circuit Dynamics Correlate with Cocaine Cue-Evoked Behavioral Arousal during Early Abstinence.

    PubMed

    Smith, Wesley C; Rosenberg, Matthew H; Claar, Leslie D; Chang, Victoria; Shah, Sagar N; Walwyn, Wendy M; Evans, Christopher J; Masmanidis, Sotiris C

    2016-01-01

    It is thought that frontostriatal circuits play an important role in mediating conditioned behavioral responses to environmental stimuli that were previously encountered during drug administration. However, the neural correlates of conditioned responses to drug-associated cues are not well understood at the level of large populations of simultaneously recorded neurons, or at the level of local field potential (LFP) synchrony in the frontostriatal network. Here we introduce a behavioral assay of conditioned arousal to cocaine cues involving pupillometry in awake head-restrained mice. After just 24 h of drug abstinence, brief exposures to olfactory stimuli previously paired with cocaine injections led to a transient dilation of the pupil, which was greater than the dilation effect to neutral cues. In contrast, there was no cue-selective change in locomotion, as measured by the rotation of a circular treadmill. The behavioral assay was combined with simultaneous recordings from dozens of electrophysiologically identified units in the medial prefrontal cortex (mPFC) and ventral striatum (VS). We found significant relationships between cocaine cue-evoked pupil dilation and the proportion of inhibited principal cells in the mPFC and VS. Additionally, LFP coherence analysis revealed a significant correlation between pupillary response and synchrony in the 25-45 Hz frequency band. Together, these results show that pupil dilation is sensitive to drug-associated cues during acute stages of abstinence, and that individual animal differences in this behavioral arousal response can be explained by two complementary measures of frontostriatal network activity. PMID:27390774

  2. Proteomic profiling of human sera for discovery of potential biomarkers to monitor abstinence from alcohol abuse

    PubMed Central

    Lai, Xianyin; Liangpunsakul, Suthat; Li, Kaigang; Witzmann, Frank A.

    2015-01-01

    Although numerous biomarkers or biomarker candidates have been discovered to detect levels of drinking and intervals of time after last drinking episode, only a few biomarkers have been applied to monitor abstinence in a longer interval (≥ 6 weeks) from alcohol abuse. Considering sample sources, sensitivity, and specificity, new biomarkers from blood with better accuracy are needed. To address this, serum proteomic profiles were compared between pre- and post- treatment samples from subjects seeking treatment for alcohol abuse and dependence in an intensive 6-week daily outpatient program using high-abundance plasma protein immunodepletion and LC-MS/MS techniques. Protein identification, quantification, candidate biomarker selection, and prioritization analyses were carried out. Among the 246 quantified serum proteins, abundance of 13 and 45 proteins in female and male subjects were significantly changed (p ≤ 0.05), respectively. Of these biomarker candidate proteins, 2 (female) and 8 (male) proteins were listed in category 1, with high area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, and fold change. In summary, several new biomarker candidates have been identified to monitor abstinence from alcohol abuse. PMID:25475211

  3. Emotion differentiation and intensity during acute tobacco abstinence: A comparison of heavy and light smokers.

    PubMed

    Sheets, Erin S; Bujarski, Spencer; Leventhal, Adam M; Ray, Lara A

    2015-08-01

    The ability to recognize and label discrete emotions, termed emotion differentiation, is particularly pertinent to overall emotion regulation abilities. Patterns of deficient emotion differentiation have been associated with mood and anxiety disorders but have yet to be examined in relation to nicotine dependence. This study employed ecological momentary assessment to examine smokers' subjective experience of discrete emotions during 24-h of forced tobacco abstinence. Thirty daily smokers rated their emotions up to 23 times over the 24-hour period, and smoking abstinence was biologically verified. From these data, we computed individual difference measures of emotion differentiation, overall emotion intensity, and emotional variability. As hypothesized, heavy smokers reported poorer negative emotion differentiation than light smokers (d=0.55), along with more intense negative emotion (d=0.97) and greater negative emotion variability (d=0.97). No differences were observed in positive emotion differentiation. Across the sample, poorer negative emotion differentiation was associated with greater endorsement of psychological motives to smoke, including negative and positive reinforcement motives, while positive emotion differentiation was not. PMID:25885662

  4. Guanfacine enhances inhibitory control and attentional shifting in early abstinent cocaine-dependent individuals

    PubMed Central

    Fox, Helen; Sofuoglu, Mehmet; Sinha, Rajita

    2015-01-01

    Objectives Attenuation of adrenergic drive and cognitive enhancement, via stimulation of alpha2 pre- and post-synaptic receptors, may selectively enhance executive performance in early abstinent cocaine-dependent individuals. As these cognitive processes underpin important treatment-related behaviors, the alpha2 agonist, guanfacine HCl, may represent an effective pharmaco-therapeutic intervention. Methods Twenty-five early abstinent cocaine-dependent individuals were administered a battery of neurocognitive tasks on entry into treatment (baseline) and again following 3 weeks of either placebo or guanfacine treatment (up to 3 mg). Tasks included: Stop Signal, Stroop, 3-Dimentional Intra-dimensional/Extra-dimensional (IDED) task, Spatial Working Memory (SWM), Paired Associates Learning (PAL), Verbal Fluency and the Rey Auditory Verbal Learning Test (RAVLT). Results Compared with placebo, the guanfacine group demonstrated attenuated anxiety and negative affect as well as improved performance on selective executive tests. This included fewer directional errors on the stop signal task, fewer errors on the extra-dimensional shift component of the IDED task and better attentional switching during verbal fluency. Guanfacine did not improve strategic working memory or peripheral memory. Conclusion Guanfacine improves selective cognitive processes which may underlie salient treatment-related regulatory behaviors. Alpha2 agonists may therefore represent important agents for cocaine dependence. PMID:25567555

  5. PROOF-OF-CONCEPT HUMAN LABORATORY STUDY FOR PROTRACTED ABSTINENCE IN ALCOHOL DEPENDENCE: EFFECTS OF GABAPENTIN

    PubMed Central

    Mason, Barbara J.; Light, John M.; Williams, Lauren D.; Drobes, David J.

    2009-01-01

    There is a need for safe medications that can effectively support recovery by treating symptoms of protracted abstinence in alcoholics that may precipitate relapse e.g., craving and disturbances in sleep and mood. This proof-of-concept study reports on the effectiveness of gabapentin 1200 mg for attenuating these symptoms in a non treatment-seeking sample of cue-reactive, alcohol-dependent individuals. Subjects were 33 paid volunteers with current DSM-IV alcohol dependence and a strength of craving rating 1σ or greater for alcohol than water cues. Subjects were randomly assigned to gabapentin or placebo for 1-week and then participated in a within-subjects trial where each was exposed to standardized sets of pleasant, neutral, and unpleasant visual stimuli followed by alcohol or water cues. We found a significant attenuating effect of gabapentin (vs. placebo) on several measures of subjective craving for alcohol as well as for affectively-evoked craving. Gabapentin was also found to significantly improve several measures of sleep quality. Side effects were minimal, and gabapentin effects were not found to resemble any major classes of abused drugs. Results suggest that gabapentin may be effective for treating the protracted abstinence phase in alcohol dependence and, hence, that a randomized clinical trial would be an appropriate next step. The study also suggests the value of cue reactivity studies as proof-of-concept screens for potential anti relapse drugs. PMID:18855801

  6. Experiences of food abstinence in patients with type 2 diabetes: a qualitative study

    PubMed Central

    Buchmann, Maike; Wermeling, Matthias; Lucius-Hoene, Gabriele; Himmel, Wolfgang

    2016-01-01

    Objective People with type 2 diabetes often report pressure to abstain from many of life's pleasures. We tried to reconstruct these patients’ sense of pressure to better understand how people with diabetes make sense of, and integrate, these feelings into their life. Design, setting and participants A secondary analysis of narrative interviews with 14 patients with type 2 diabetes who are part of a website project. Main outcome measures Grounded theory-based analysis of narrative interviews, consisting of open, axial and selective coding. Results People with type 2 diabetes felt obliged to give up many pleasures and live a life of abstinence. They perceived a pressure to display a modest culinary lifestyle via improved laboratory test results and weight. Their verbal efforts to reassure and distance themselves from excessiveness indicate a high moral pressure. With regard to the question of how to abstain, food and behaviour were classified into healthy and unhealthy. Personal rules sometimes led to surprising experiences of freedom. Conclusions People with diabetes have internalised that their behaviour is a barrier to successful treatment. They experience an intensive pressure to show abstinence and feel misjudged when their efforts have no visible effect. Taking into account this moral pressure, and listening to patients’ personal efforts and strategies to establish healthy behaviours, might help to build a trusting relationship with healthcare providers. PMID:26739724

  7. Frontostriatal Circuit Dynamics Correlate with Cocaine Cue-Evoked Behavioral Arousal during Early Abstinence123

    PubMed Central

    Shah, Sagar N.; Evans, Christopher J.

    2016-01-01

    It is thought that frontostriatal circuits play an important role in mediating conditioned behavioral responses to environmental stimuli that were previously encountered during drug administration. However, the neural correlates of conditioned responses to drug-associated cues are not well understood at the level of large populations of simultaneously recorded neurons, or at the level of local field potential (LFP) synchrony in the frontostriatal network. Here we introduce a behavioral assay of conditioned arousal to cocaine cues involving pupillometry in awake head-restrained mice. After just 24 h of drug abstinence, brief exposures to olfactory stimuli previously paired with cocaine injections led to a transient dilation of the pupil, which was greater than the dilation effect to neutral cues. In contrast, there was no cue-selective change in locomotion, as measured by the rotation of a circular treadmill. The behavioral assay was combined with simultaneous recordings from dozens of electrophysiologically identified units in the medial prefrontal cortex (mPFC) and ventral striatum (VS). We found significant relationships between cocaine cue-evoked pupil dilation and the proportion of inhibited principal cells in the mPFC and VS. Additionally, LFP coherence analysis revealed a significant correlation between pupillary response and synchrony in the 25–45 Hz frequency band. Together, these results show that pupil dilation is sensitive to drug-associated cues during acute stages of abstinence, and that individual animal differences in this behavioral arousal response can be explained by two complementary measures of frontostriatal network activity. PMID:27390774

  8. Effects of fluvoxamine and citalopram in maintaining abstinence in a sample of Italian detoxified alcoholics.

    PubMed

    Angelone, S M; Bellini, L; Di Bella, D; Catalano, M

    1998-01-01

    A 16-week, randomized study was performed to test the efficacy of two selective serotonin reuptake inhibitors (SSRIs) fluvoxamine and citalopram, in decreasing relapse and craving in alcoholics, and to investigate possible differences in their clinical profile. After detoxification, each of the 81 patients (55 males and 26 females) was randomly assigned to one of three groups: 23 subjects did not receive any pharmacological treatment, 25 were treated with fluvoxamine, 150mg/day, and 33 with citalopram, 20 mg/day. All patients received standard cognitive-behavioural therapy. Craving was assessed twice a month using a 10-step scale. Every intake of alcohol was considered a relapse and the subject was taken out of the study. At the end of the study, both the fluvoxamine and citalopram groups showed a statistically higher rate of continuous abstinence (63.6 and 60.7%, respectively) compared to the group without pharmacological treatment (30.4%). Relapse severity did not differ among the three groups. Only citalopram showed a significant effect on craving throughout the study period. This study confirmed the efficacy of SSRIs as an adjunct to psychotherapy to prevent relapse in alcoholics. The relationship between the effects of these SSRIs on abstinence and craving, as well as the differences between their profiles, are discussed. PMID:9566477

  9. Social stress, economic hardship, and psychological distress as predictors of sustained abstinence from substance use after treatment.

    PubMed

    Wahler, Elizabeth A; Otis, Melanie D

    2014-11-01

    Social characteristics associated with disadvantage, such as racial/ethnic minority status, female gender, and low socioeconomic status (SES), are often associated with increased psychological distress and substance use disorders. This project tests a conceptual model derived from Pearlin's social stress theory for predicting abstinence from substance use between baseline and 1-year follow-up in secondary data from a large statewide sample of Kentucky substance abuse treatment participants (N = 1,123). Racial minority status, employment, and higher education level were predictive of substance use at follow-up, while female gender was predictive of abstinence. Limitations, implications for practice, and suggestions for future research are discussed. PMID:25050587

  10. "If I Could Really Say that and Get Away with It!" Accountability and Ambivalence in American Parents' Sexuality Lessons in the Age of Abstinence

    ERIC Educational Resources Information Center

    Elliott, Sinikka

    2010-01-01

    Based on in-depth interviews with 64 American parents of teenagers, I examine how parents navigate the complex landscape of abstinence, personal responsibility, and sexual well-being in their sexuality lessons to their children. Reflecting the dominance of the abstinence-only discourse, many parents expressed a sense of accountability to promote…

  11. Queer Youth Experiences with Abstinence-Only-until-Marriage Sexuality Education: "I Can't Get Married so where Does that Leave Me?"

    ERIC Educational Resources Information Center

    Fisher, Christopher Micheal

    2009-01-01

    Abstinence-only-until-marriage sexuality education has received increasing attention vis-a-vis policy, funding, and research. Despite large sums of federal money to develop, implement, and to some extent, assess abstinence-only education, virtually no studies have looked to assess the experiences of such a curriculum for gay and bisexual male…

  12. The drug-of-choice phenomenon psychological differences among drug users who preferred different drugs.

    PubMed

    O'Connor, L E; Berry, J W; Morrison, A; Brown, S

    1995-04-01

    The Eysenck Personality Questionnaire, the Sensation Seeking Scale, and the Brief Symptom Inventory were administered to 125 recovering drug users with three or more months abstinent from drugs. Subjects were divided according to drug preference: opiates, stimulants, marijuana, alcohol, and a polydrug preference. Opiate users were significantly higher in Susceptibility to Boredom. Alcohol misusers compared to a combined stimulant, opiate, and polydrug group were significantly lower in Extroversion and Susceptibility to Boredom. Subjects raised in drug/alcohol-using families scored significantly higher on Neuroticism and on the Positive Symptom Total of the BSI, and had a higher rate of suicidality. PMID:7601576

  13. [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

  14. Using incentives to encourage smoking abstinence among pregnant indigenous women? A feasibility study.

    PubMed

    Glover, Marewa; Kira, Anette; Walker, Natalie; Bauld, Linda

    2015-06-01

    Smoking during pregnancy increases the risk of many adverse health outcomes for both the mother and the unborn child (Morton et al. 2010). Indigenous people often have a higher smoking prevalence during pregnancy than non-Indigenous populations. In New Zealand (NZ), the smoking rates among Indigenous Māori women who are pregnant have reduced since 1991 (68 %) but still remains high in 2007 (34 %) (Morton et al. 2010). The success rate of most smoking cessation interventions for pregnant smokers is low at <6 % (Lumley et al. 2009). In other populations of pregnant women, financial incentives have been shown to increase the attractiveness of smoking cessation programs and increase the number of quit attempts. A feasibility study was undertaken to determine the likely effectiveness of an incentives-based cessation trial among pregnant Māori women that smoked. Pregnant smokers, aged 16 years and older, who self-identified as Māori, were 2-30 weeks pregnant, and currently smoked, were recruited through health practitioners, print media, and radio adverts in Auckland, NZ. Participants were randomised to (1) usual cessation support, including information about different cessation products and services, and access to nicotine replacement therapy (control), (2) usual cessation support plus a retail voucher to the value of NZ$25 for each 'abstinent from smoking' week for 8 weeks (voucher), or (3) usual cessation support plus product to the value of NZ$25 for each 'abstinent from smoking' week for 8 weeks (product). Outcomes measures included weekly self-reported and monthly biochemically verified smoking status, and acceptability. Of the 74 referred women, 50 declined involvement in the study and 24 consented and were randomised (eight control, eight voucher and eight to product). The mean age of participants was 25 years old (±2.25). Overall 21 % (n = 5) of the women were abstinent from smoking for at least 6 weeks of the eight, one from the control, six from the

  15. Relapse prevention and maintaining abstinence in older adults with alcohol-use disorders.

    PubMed

    Barrick, Christopher; Connors, Gerard J

    2002-01-01

    Although older adults are sometimes believed to have the lowest rates of alcohol abuse as an age cohort, the prevalence of alcohol use and abuse in this group is clearly underestimated. The under-diagnosis of alcohol abuse is due, in part, to the facts that the effects of alcohol use among older adults tend to be less clearly visible than among other age groups and that older adults are less likely to seek treatment than younger age groups. An additional challenge to diagnosis may be a lack of previous alcohol abuse by the patient, as approximately one-third of older adults with alcohol-use problems first develop their drinking problem after the age of 60 years. With a demographic shift that is expected to increase the number of older adults with alcohol problems, the awareness and understanding of this problem becomes increasingly important. Under-diagnosis of problem drinking in older adults is particularly unfortunate because the risks associated with alcohol abuse and relapse for the elderly are significant. Relapse, or the return to drinking following abstinence, may follow situations that are of particularly high risk for older adults. These include situations related to anxiety, interpersonal conflict, depression, loneliness, loss or social isolation. By helping patients to monitor these high-risk situations, to identify strategies that have been successful in promoting abstinence in the past, and to become engaged in treatment, relapse may be avoided and abstinence maintained. Treatments such as cognitive-behavioural therapy, group and family therapies and self-help groups are just as effective for older adults as they are for other age groups. In fact, group and family therapies and self-help groups may be of particular benefit to older adults because of the emphasis on social support. Medicinal adjuncts are also equally effective in the elderly, but strict compliance and careful monitoring of adverse effects are especially important in patients who take

  16. Abstinence-What?: A Critical Look at the Language of Educational Approaches to Adolescent Sexual Risk Reduction

    ERIC Educational Resources Information Center

    Beshers, Sarah

    2007-01-01

    Twenty-six years ago, Ronald Reagan signed the Adolescent Family Life Act, and the abstinence education movement began its rapid ascendancy to political dominance, a process marked by increasingly generous federal funding, which reached a peak of $176 million in FY 2006. Throughout this period, a debate ensued over the appropriate approach to…

  17. Sodium oxybate: a review of its use in alcohol withdrawal syndrome and in the maintenance of abstinence in alcohol dependence.

    PubMed

    Keating, Gillian M

    2014-01-01

    A liquid formulation of sodium oxybate (Alcover(®)), the sodium salt of γ-hydroxybutyric acid (GHB), is approved in Italy and Austria for use in alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence. This article reviews the efficacy and tolerability of sodium oxybate in alcohol withdraw