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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. Risky car following in abstinent users of MDMA.

    PubMed

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

    2010-05-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2006-07-01

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

  6. 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.

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

    PubMed Central

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

    2012-01-01

    Context MDMA (ecstasy) is a popular recreational drug that produces loss of serotonin (5-HT) axons in animal models. Whether MDMA produces chronic reductions in 5-HT signaling in humans remains controversial. Objective To determine if MDMA use is associated with chronic reductions in serotonin signaling in female human cerebral cortex as reflected by increased 5-HT2A receptors. Design Cross sectional case-control study comparing 5-HT2A receptor levels in abstinent female MDMA polydrug users to MDMA-naive females; within-group design assessing the association of lifetime MDMA use and 5-HT2A receptors. Subjects had at least 90 days abstinence from MDMA use as verified by hair sampling. Cortical 5-HT2A receptor levels were assayed with the 5HT2A-specific Positron Emission Tomography (PET) radioligand [18F]setoperone. Setting Academic Medical Center Research Laboratory. Participants Volunteer female MDMA users (N=14) and MDMA-naive controls (N=10). Main exclusion criteria were non-drug-related DSM-IV axis I psychiatric disorders and general medical illness. Main Outcome Measure Cortical 5-HT2A receptor non-displaceable binding potential (5-HT2ABPND). Results MDMA users had increased 5-HT2ABPND in occipital-parietal (19.7%), temporal (20.5%), occipito-temporal-parietal (18.3%), frontal (16.6%), and fronto-parietal (18.5%) regions (p<0.05; corrected). Lifetime MDMA use associated positively with 5-HT2ABPND in fronto-parietal (β=0.665;p=0.007), occipito-temporal (β=0.798;p=0.002), fronto-limbic (β=0.634;p=0.024), and frontal (β=0.691;p=0.008) regions. In contrast, there were no regions in which MDMA use was inversely associated with receptor levels. There were no statistically significant effects of the duration of MDMA abstinence on 5-HT2ABPND. Conclusions Human recreational MDMA use is associated with long-lasting increases in 5-HT2A receptor density. 5-HT2A receptor levels correlate positively with lifetime MDMA use and do not decrease with abstinence. These

  8. 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.

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

    PubMed

    Parrott, Andrew C

    2013-09-01

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

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

    PubMed Central

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

    2012-01-01

    Rationale Ecstasy (MDMA) polydrug users have verbal memory performance that is statistically significantly lower than comparison control subjects. Studies have correlated long-term MDMA use with altered brain activation in regions that play a role in verbal memory. Objectives The aim of our study was to examine the association of lifetime ecstasy use with semantic memory performance and brain activation in ecstasy polydrug users. Methods 23 abstinent ecstasy polydrug users (age=24.57) and 11 controls (age=22.36) performed a two-part fMRI semantic encoding and recognition task. To isolate brain regions activated during each semantic task, we created statistical activation maps in which brain activation was greater for word stimuli than for non-word stimuli (corrected p<0.05). Results During the encoding phase, ecstasy polydrug users had greater activation during semantic encoding bilaterally in language processing regions, including Brodmann Areas 7, 39, and 40. Of this bilateral activation, signal intensity with a peak T in the right superior parietal lobe was correlated with lifetime ecstasy use (rs=0.43, p=0.042). Behavioral performance did not differ between groups. Conclusions These findings demonstrate that ecstasy polydrug users have increased brain activation during semantic processing. This increase in brain activation in the absence of behavioral deficits suggests that ecstasy polydrug users have reduced cortical efficiency during semantic encoding, possibly secondary to MDMA-induced 5-HT neurotoxicity. Although pre-existing differences cannot be ruled out, this suggests the possibility of a compensatory mechanism allowing ecstasy polydrug users to perform equivalently to controls, providing additional support for an association of altered cerebral neurophysiology with MDMA exposure. PMID:23241648

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

    PubMed Central

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

    2009-01-01

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

  12. 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

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

    PubMed Central

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

    2013-01-01

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

  14. 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

  15. 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

  16. Abnormal cerebellar morphometry in abstinent adolescent marijuana users

    PubMed Central

    Medina, Krista Lisdahl; Nagel, Bonnie J.; Tapert, Susan F.

    2010-01-01

    Background Functional neuroimaging data from adults have, in general, found frontocerebellar dysfunction associated with acute and chronic marijuana (MJ) use (Loeber & Yurgelun-Todd, 1999). One structural neuroimaging study found reduced cerebellar vermis volume in young adult MJ users with a history of heavy polysubstance use (Aasly et al., 1993). The goal of this study was to characterize cerebellar volume in adolescent chronic MJ users following one month of monitored abstinence. Method Participants were MJ users (n=16) and controls (n=16) aged 16-18 years. Extensive exclusionary criteria included history of psychiatric or neurologic disorders. Drug use history, neuropsychological data, and structural brain scans were collected after 28 days of monitored abstinence. Trained research staff defined cerebellar volumes (including three cerebellar vermis lobes and both cerebellar hemispheres) on high-resolution T1-weighted magnetic resonance images. Results Adolescent MJ users demonstrated significantly larger inferior posterior (lobules VIII-X) vermis volume (p<.009) than controls, above and beyond effects of lifetime alcohol and other drug use, gender, and intracranial volume. Larger vermis volumes were associated with poorer executive functioning (p’s<.05). Conclusions Following one month of abstinence, adolescent MJ users had significantly larger posterior cerebellar vermis volumes than non-using controls. These greater volumes are suggested to be pathological based on linkage to poorer executive functioning. Longitudinal studies are needed to examine typical cerebellar development during adolescence and the influence of marijuana use. PMID:20413277

  17. 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 ...

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

    PubMed

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

    2014-12-01

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

  19. Employment-based abstinence reinforcement promotes opiate and cocaine abstinence in out-of-treatment injection drug users.

    PubMed

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

    2014-01-01

    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.

  20. Employment-based abstinence reinforcement promotes opiate and cocaine abstinence in out-of-treatment injection drug users.

    PubMed

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

    2014-01-01

    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

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

    PubMed

    Davis, Alan K; Rosenberg, Harold

    2014-01-01

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

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

    PubMed

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

    2005-07-01

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

  3. 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

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

    PubMed Central

    Parrott, Andrew C; Young, Lucy

    2014-01-01

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

  5. Daily marijuana users with past alcohol problems increase alcohol consumption during marijuana abstinence.

    PubMed

    Peters, Erica N; Hughes, John R

    2010-01-15

    Drug abuse treatment programs typically recommend complete abstinence because of a fear that clients who stop use of one drug will substitute another. A within-subjects study investigated whether consumption of alcohol and other substances changes during marijuana abstinence. Twenty-eight daily marijuana users who were not trying to stop or reduce their marijuana consumption completed an 8-day baseline period in which they used marijuana and other drugs as usual, a 13-day marijuana abstinence period, and a 7-day return-to-baseline period. Participants provided self-report of substance use daily and submitted urine samples twice weekly to verify marijuana abstinence. A diagnosis of past alcohol abuse or dependence significantly moderated the alcohol increase from baseline to marijuana abstinence (p<0.01), such that individuals with this diagnosis significantly increased alcohol use (52% increase) but those without this history did not (3% increase). Increases in marijuana withdrawal discomfort scores and alcohol craving scores from baseline to marijuana abstinence significantly and positively correlated with increases in alcohol use. Increases in cigarettes, caffeine, and non-marijuana illicit drugs did not occur. This study provides empirical validation of drug substitution in a subgroup of daily marijuana users, but results need to be replicated in individuals who seek treatment for marijuana problems.

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

    PubMed

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

    2004-06-01

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

  7. Neural correlates of craving and impulsivity in abstinent former cocaine users: Towards biomarkers of relapse risk.

    PubMed

    Bell, Ryan P; Garavan, Hugh; Foxe, John J

    2014-10-01

    A significant hindrance to effective treatment of addiction is identifying those most likely to relapse. Cocaine addiction is characterized by deficits in inhibitory control and elevated reactivity to cocaine cues, both hypothesized to be integral to development of addiction and propensity to relapse. It follows that reduction of both impulsivity and cue-reactivity following abstinence is protective against relapse, and that persistence of these factors increases vulnerability. Using functional magnetic resonance imaging, we examined neural activation patterns in dorsal and ventral striatum in abstinent cocaine dependent (CD) individuals (N=20) and non-using controls (N=19) as they performed a cocaine craving task. We also examined activations in nodes of the response inhibition circuit (RIC) as they performed an inhibition task. At the between-groups level, no differences in RIC or striatal activation were seen in former users, in contrast to previous investigations in current users, suggesting large-scale functional recovery with abstinence. However, at the individual participant-level, abstinent CD individuals displayed an association between cocaine cue-related neural activations in the right ventral striatum and compulsive cocaine craving scores. Compulsive craving scores were also negatively correlated with duration of abstinence. Further, there was an association between motor impulsivity scores and inhibition-related activations in the right inferior frontal gyrus and pre-supplementary motor area in abstinent CD individuals. Thus, while former users as a group did not show deficits in inhibitory function or cocaine-cue reactivity, participant-level results pointed to activation patterns in a minority of these individuals that likely contributes to enduring relapse vulnerability. PMID:24951856

  8. Neural substrates of faulty decision-making in abstinent marijuana users.

    PubMed

    Bolla, Karen I; Eldreth, Dana A; Matochik, John A; Cadet, Jean L

    2005-06-01

    Persistent dose-related cognitive decrements have been reported in 28-day abstinent heavy marijuana (MJ) users. However, the neural substrates of these decrements in cognitive performance are not known. This study aimed to determine if 25-day abstinent MJ users show persistent dose-related alterations in performance and brain activity using PET H(2)(15)O during the Iowa Gambling Task-IGT (a decision-making task). Eleven heavy MJ users and 11 non-drug users participated. The MJ group resided in an inpatient research unit at the NIH/NIDA-IRP for 25 days prior to testing to ensure abstinence. A dose-related association was found between increased MJ use and lower IGT performance and alterations in brain activity. The MJ group showed greater activation in the left cerebellum and less activation in the right lateral orbitofrontal cortex (OFC) and the right dorsolateral prefrontal cortex (DLPFC) than the Control group. When the MJ group was divided into Moderate (8-35 joints/week) and Heavy users (53-84 joints/week), the Heavy MJ group showed less activation in the left medial OFC and greater activation in the left cerebellum than the Moderate group. However, brain activity and task performance were similar between the Moderate MJ users and the Control group, suggesting a "threshold effect". These preliminary findings indicate that very heavy users of MJ have persistent decision-making deficits and alterations in brain activity. Specifically, the Heavy MJ users may focus on only the immediate reinforcing aspects of a situation (i.e., getting high) while ignoring the negative consequences. Thus, faulty decision-making could make an individual more prone to addictive behavior and more resistant to treatment. Finally, it is unclear if these neurologic findings will become progressively worse with continued heavy MJ use or if they will resolve with abstinence from MJ use.

  9. 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 ...

  10. 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

  11. 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

  12. 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

  13. 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…

  14. 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…

  15. 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

  16. 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

  17. 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

  18. 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

  19. A randomized trial of employment-based reinforcement of cocaine abstinence in injection drug users.

    PubMed

    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 and use cocaine during methadone treatment. Participants could work 4 hr every weekday in a workplace where they could earn about $10.00 per hour in vouchers; they were required to provide routine urine samples. Participants who attended the workplace and provided cocaine-positive urine samples during the initial 4 weeks were invited to work 26 weeks and were randomly assigned to an abstinence-and-work (n = 28) or work-only (n = 28) group. Abstinence-and-work participants had to provide urine samples showing cocaine abstinence to work and maintain maximum pay. Work-only participants could work independent of their urinalysis results. Abstinence-and-work participants provided more (p = .004; OR = 5.80, 95% CI = 2.03-16.56) cocaine-negative urine samples (29%) than did work-only participants (10%). Employment-based abstinence reinforcement can increase cocaine abstinence.

  20. A randomized trial of employment-based reinforcement of cocaine abstinence in injection drug users.

    PubMed

    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 and use cocaine during methadone treatment. Participants could work 4 hr every weekday in a workplace where they could earn about $10.00 per hour in vouchers; they were required to provide routine urine samples. Participants who attended the workplace and provided cocaine-positive urine samples during the initial 4 weeks were invited to work 26 weeks and were randomly assigned to an abstinence-and-work (n = 28) or work-only (n = 28) group. Abstinence-and-work participants had to provide urine samples showing cocaine abstinence to work and maintain maximum pay. Work-only participants could work independent of their urinalysis results. Abstinence-and-work participants provided more (p = .004; OR = 5.80, 95% CI = 2.03-16.56) cocaine-negative urine samples (29%) than did work-only participants (10%). Employment-based abstinence reinforcement can increase cocaine abstinence. PMID:17970256

  1. 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

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

    PubMed Central

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

    2011-01-01

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

  3. 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

  4. 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…

  5. 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

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

    PubMed

    Parrott, A. C.

    2001-12-01

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

  7. Metabolic Abnormalities in Lobar and Subcortical Brain Regions of Abstinent Polysubstance Users: Magnetic Resonance Spectroscopic Imaging

    PubMed Central

    Abé, Christoph; Mon, Anderson; Hoefer, Michael E.; Durazzo, Timothy C.; Pennington, David L.; Schmidt, Thomas P.; Meyerhoff, Dieter J.

    2013-01-01

    Aims: The aim of the study was to explore neurometabolic and associated cognitive characteristics of patients with polysubstance use (PSU) in comparison with patients with predominant alcohol use using proton magnetic resonance spectroscopy. Methods: Brain metabolite concentrations were examined in lobar and subcortical brain regions of three age-matched groups: 1-month-abstinent alcohol-dependent PSU, 1-month-abstinent individuals dependent on alcohol alone (ALC) and light drinking controls (CON). Neuropsychological testing assessed cognitive function. Results: While CON and ALC had similar metabolite levels, persistent metabolic abnormalities (primarily higher myo-inositol) were present in temporal gray matter, cerebellar vermis and lenticular nuclei of PSU. Moreover, lower cortical gray matter concentration of the neuronal marker N-acetylaspartate within PSU correlated with higher cocaine (but not alcohol) use quantities and with a reduced cognitive processing speed. Conclusions: These metabolite group differences reflect cellular/astroglial injury and/or dysfunction in alcohol-dependent PSU. Associations of other metabolite concentrations with neurocognitive performance suggest their functional relevance. The metabolic alterations in PSU may represent polydrug abuse biomarkers and/or potential targets for pharmacological and behavioral PSU-specific treatment. PMID:23797281

  8. The case for MDMA (ecstasy) regulation.

    PubMed

    Donelly, Joshua

    2015-06-01

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

  9. The case for MDMA (ecstasy) regulation.

    PubMed

    Donelly, Joshua

    2015-06-01

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

  10. 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

  11. 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.

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

    PubMed

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

    2009-09-01

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

  13. MDMA and the "ecstasy paradigm".

    PubMed

    Cole, Jon C

    2014-01-01

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

  14. Biochemical Validation of Self-Reported Smokeless Tobacco Abstinence among Smokeless Tobacco Users: Results from a Clinical Trial of Varenicline in India.

    PubMed

    Jain, Raka; Jhanjee, Sonali; Jain, Veena; Gupta, Tina; Mittal, Swati; Chauhan, Prashant; Raghav, Rahul; Goelz, Patricia; Schnoll, Robert A

    2015-01-01

    The validity of self-reported tobacco use is often questioned given the potential for underestimation of use. This study used data from a double-blind, placebo-controlled clinical trial of varenicline for smokeless tobacco dependence in India to evaluate the accuracy of self-reported smokeless tobacco cessation using biochemical validation procedures and to evaluate correlates of reporting inaccuracy. Smokeless tobacco users attending a dental clinic at AIIMS were randomized to placebo or varenicline; all participants received counseling. Detailed smokeless tobacco use was recorded and abstinence was defined as cotinine-verified 7-day point prevalence cessation (cotinine < 50 ng/ml) and breath CO > 10 ppm at the end of 12 weeks of treatment. One-half of study completers (82/165) self-reported abstinence. Biochemical verification confirmed that (65.9%) subjects provided accurate self-reports while (34.1%) participants underreported tobacco use. These data indicate poor agreement between self-reported and biochemically confirmed abstinence (κ = -0.191). Underreporters of tobacco use had significantly higher baseline cotinine (p < 0.05), total craving (p < 0.012), and negative reinforcement craving (p < 0.001) vs. those whose self-reports were correctly verified. These findings provide evidence to support the need for biochemical validation of self-reported abstinence outcomes among smokeless tobacco users in cessation programs in India and identify high levels of pretreatment cotinine and craving levels as potential correlates of false reporting.

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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…

  20. Abstinence education.

    PubMed

    Zeiler, Alean

    2014-11-01

    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).

  1. 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

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

    NASA Astrophysics Data System (ADS)

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

    2002-09-01

    The prevailing view is that the popular recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, or ``ecstasy'') is a selective serotonin neurotoxin in animals and possibly in humans. Nonhuman primates exposed to several sequential doses of MDMA, a regimen modeled after one used by humans, developed severe brain dopaminergic neurotoxicity, in addition to less pronounced serotonergic neurotoxicity. MDMA neurotoxicity was associated with increased vulnerability to motor dysfunction secondary to dopamine depletion. These results have implications for mechanisms of MDMA neurotoxicity and suggest that recreational MDMA users may unwittingly be putting themselves at risk, either as young adults or later in life, for developing neuropsychiatric disorders related to brain dopamine and/or serotonin deficiency.

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

    PubMed

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

    2014-08-01

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

  4. 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

  5. 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 ...

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2015-08-01

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

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

    PubMed

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

    2014-03-01

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

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

    PubMed

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

    2014-06-01

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

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

    PubMed

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

    2011-12-01

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

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

    PubMed

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

    2003-12-01

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

  13. 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…

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

    ERIC Educational Resources Information Center

    Elk, Carrie

    1996-01-01

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

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

    PubMed Central

    Puerta, Elena; Aguirre, Norberto

    2011-01-01

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

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

    PubMed

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

    2007-01-01

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

  17. Human Pharmacology of Mephedrone in Comparison with MDMA.

    PubMed

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

    2016-10-01

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

  18. Human Pharmacology of Mephedrone in Comparison with MDMA.

    PubMed

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

    2016-10-01

    Mephedrone (4-methylmethcathinone) is a novel psychoactive substance popular among drug users because it displays similar effects to MDMA (3,4-methylenedioxymethamphetamine, ecstasy). Mephedrone consumption has been associated with undesirable effects and fatal intoxications. At present, there is no research available on its pharmacological effects in humans under controlled and experimental administration. This study aims to evaluate the clinical pharmacology of mephedrone and its relative abuse liability compared with MDMA. Twelve male volunteers participated in a randomized, double-blind, crossover, and placebo-controlled trial. The single oral dose conditions were: mephedrone 200 mg, MDMA 100 mg, and placebo. Outcome variables included physiological, subjective, and psychomotor effects, and pharmacokinetic parameters. The protocol was registered in ClinicalTrials.gov (NCT02232789). Mephedrone produced a significant increase in systolic and diastolic blood pressure, heart rate, and pupillary diameter. It elicited stimulant-like effects, euphoria, and well-being, and induced mild changes in perceptions with similar ratings to those observed after MDMA administration although effects peaked earlier and were shorter in duration. Maximal plasma concentration values for mephedrone and MDMA peaked at 1.25 h and 2.00 h, respectively. The elimination half-life for mephedrone was 2.15 h and 7.89 h for MDMA. In a similar manner to MDMA, mephedrone exhibits high abuse liability. Its earlier onset and shorter duration of effects, probably related to its short elimination half-life, could explain a more compulsive pattern of use as described by the users. PMID:27206266

  19. '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.

  20. '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

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

    PubMed

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

    2008-10-30

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

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

    PubMed

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

    2015-04-01

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

  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. 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…

  5. 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.

  6. 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

  7. Relationship between intravenous use and achieving initial cocaine abstinence.

    PubMed

    Budney, A J; Higgins, S T; Bickel, W; Kent, L

    1993-04-01

    This study assessed whether route of cocaine administration (intravenous vs. intranasal) influences cocaine abstinence during the first 6 weeks of outpatient treatment. Fifty-nine persons received behavioral treatment or standard drug counselling in an outpatient clinic. Based on information collected at intake, intravenous users had fewer years of education, were employed in less skilled jobs, were less likely to be married, reported more negative consequences from cocaine use, reported using more cocaine per occasion and spent more money on cocaine per week than intranasal users. Intravenous and intranasal users did not differ significantly in the average duration of continuous cocaine abstinence (mean = 2.6 vs. mean = 3.3 weeks achieved during 6 weeks of treatment). The duration of abstinence between intravenous and intranasal users was equal in the behavioral treatment (mean = 4.2). In standard treatment the average duration was less among intravenous than intranasal users (mean = 0.9 vs. mean = 2.4), but that difference did not achieve statistical significance. Hepatitis and employment instability were associated with shorter periods of cocaine abstinence among intravenous users, whereas employment instability, lower job skill level, drug use severity and reports of memory loss were associated with shorter periods of cocaine abstinence among intranasal users. These results indicate that i.v. cocaine users can achieve a period of initial abstinence in an outpatient setting comparable to the duration of typical inpatient hospitalizations, although special types of outpatient treatment may be necessary to obtain a positive outcome.

  8. Relationship between intravenous use and achieving initial cocaine abstinence.

    PubMed

    Budney, A J; Higgins, S T; Bickel, W; Kent, L

    1993-04-01

    This study assessed whether route of cocaine administration (intravenous vs. intranasal) influences cocaine abstinence during the first 6 weeks of outpatient treatment. Fifty-nine persons received behavioral treatment or standard drug counselling in an outpatient clinic. Based on information collected at intake, intravenous users had fewer years of education, were employed in less skilled jobs, were less likely to be married, reported more negative consequences from cocaine use, reported using more cocaine per occasion and spent more money on cocaine per week than intranasal users. Intravenous and intranasal users did not differ significantly in the average duration of continuous cocaine abstinence (mean = 2.6 vs. mean = 3.3 weeks achieved during 6 weeks of treatment). The duration of abstinence between intravenous and intranasal users was equal in the behavioral treatment (mean = 4.2). In standard treatment the average duration was less among intravenous than intranasal users (mean = 0.9 vs. mean = 2.4), but that difference did not achieve statistical significance. Hepatitis and employment instability were associated with shorter periods of cocaine abstinence among intravenous users, whereas employment instability, lower job skill level, drug use severity and reports of memory loss were associated with shorter periods of cocaine abstinence among intranasal users. These results indicate that i.v. cocaine users can achieve a period of initial abstinence in an outpatient setting comparable to the duration of typical inpatient hospitalizations, although special types of outpatient treatment may be necessary to obtain a positive outcome. PMID:8508724

  9. 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…

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

    PubMed

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

    2011-08-01

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

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

    PubMed

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

    2014-05-01

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

  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. MDMA enhances emotional empathy and prosocial behavior.

    PubMed

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

    2014-11-01

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

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

    PubMed

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

    2011-07-01

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

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

    PubMed

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

    2014-09-01

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

  17. 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

  18. 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.

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

    PubMed Central

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

    2009-01-01

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

  20. 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.…

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

    PubMed

    Docherty, J R; Green, A R

    2010-07-01

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

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

    PubMed Central

    Docherty, JR; Green, AR

    2010-01-01

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

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

    PubMed

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

    2013-09-01

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

  4. 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…

  5. 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

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

    PubMed Central

    Kamilar-Britt, Philip; Bedi, Gillinder

    2015-01-01

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

  7. 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.

  8. 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

  9. 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

  10. 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…

  11. 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…

  12. A Qualitative Study of Methamphetamine Users’ Perspectives on Barriers and Facilitators of Drug Abstinence

    PubMed Central

    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

  13. Making a medicine out of MDMA.

    PubMed

    Sessa, Ben; Nutt, David

    2015-01-01

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

  14. 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

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

    PubMed

    Ball, Kevin T; Slane, Mylissa

    2014-11-01

    Pre-clinical studies of individual differences in addiction vulnerability have been increasing over recent years, but the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) has received relatively little attention in this regard. Previously, we reported large individual differences both in rats' initial behavioral response to experimenter-administered MDMA and their degree of behavioral sensitization to repeated administration. To determine whether these differences could predict subsequent patterns of MDMA-taking or -seeking behaviors we used the self-administration-extinction-reinstatement model to examine addiction-like behavior (i.e., escalation of MDMA self-administration and cue-induced reinstatement of MDMA seeking) in rats a priori characterized for either locomotor sensitization or tolerance to MDMA. Rats that developed tolerance to the locomotor-activating effects of MDMA had a significantly larger locomotor response to the first MDMA injection relative to rats that developed sensitization. Importantly, rats that developed tolerance subsequently displayed an escalation of MDMA self-administration over days, as well as clear cue-induced reinstatement of MDMA seeking following extinction. Conversely, rats that developed locomotor sensitization to MDMA subsequently maintained relatively stable levels of MDMA self-administration over days and showed no cue-induced reinstatement of MDMA seeking. These results show that differences in the level of psychomotor activation following acute and repeated MDMA administration can reliably predict two important addiction-like behaviors in rats, which may have implications in the prediction of compulsive MDMA use in humans.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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…

  4. 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.

  5. 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

  6. MDMA decreases the effects of simulated social rejection.

    PubMed

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

    2014-02-01

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

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

    SciTech Connect

    Chen, Da-Ren; Cheng, Mengdawn

    2007-01-01

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

  8. 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…

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

    PubMed

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

    2011-08-01

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

  10. The potential dangers of using MDMA for psychotherapy.

    PubMed

    Parrott, Andrew C

    2014-01-01

    MDMA has properties that may make it attractive for psychotherapy, although many of its effects are potentially problematic. These contrasting effects will be critically reviewed in order to assess whether MDMA could be safe for clinical usage. Early studies from the 1980s noted that MDMA was an entactogen, engendering feelings of love and warmth. However, negative experiences can also occur with MDMA since it is not selective in the thoughts or emotions it releases. This unpredictability in the psychological material released is similar to another serotonergic drug, LSD. Acute MDMA has powerful neurohormonal effects, increasing cortisol, oxytocin, testosterone, and other hormone levels. The release of oxytocin may facilitate psychotherapy, whereas cortisol may increase stress and be counterproductive. MDMA administration is followed by a period of neurochemical recovery, when low serotonin levels are often accompanied by lethargy and depression. Regular usage can also lead to serotonergic neurotoxicity, memory problems, and other psychobiological problems. Proponents of MDMA-assisted therapy state that it should only be used for reactive disorders (such as PTSD) since it can exacerbate distress in those with a prior psychiatric history. Overall, many issues need to be considered when debating the relative benefits and dangers of using MDMA for psychotherapy. PMID:24830184

  11. 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

  12. The potential dangers of using MDMA for psychotherapy.

    PubMed

    Parrott, Andrew C

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

  14. 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

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

    PubMed Central

    Parrott, A.C.

    2009-01-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2013-01-01

    Background and Purpose Recreational users report that mephedrone has similar psychoactive effects to 3,4-methylenedioxymethamphetamine (MDMA). MDMA induces well-characterized changes in body temperature due to complex monoaminergic effects on central thermoregulation, peripheral blood flow and thermogenesis, but there are little preclinical data on the acute effects of mephedrone or other synthetic cathinones. Experimental Approach The acute effects of cathinone, methcathinone and mephedrone on rectal and tail temperature were examined in individually housed rats, with MDMA included for comparison. Rats were killed 2 h post-injection and brain regions were collected for quantification of 5-HT, dopamine and major metabolites. Further studies examined the impact of selected α-adrenoceptor and dopamine receptor antagonists on mephedrone-induced changes in rectal temperature and plasma catecholamines. Key Results At normal room temperature, MDMA caused sustained decreases in rectal and tail temperature. Mephedrone caused a transient decrease in rectal temperature, which was enhanced by α1-adrenoceptor and dopamine D1 receptor blockade, and a prolonged decrease in tail temperature. Cathinone and methcathinone caused sustained increases in rectal temperature. MDMA decreased 5-HT and/or 5-hydroxyindoleacetic acid (5-HIAA) content in several brain regions and reduced striatal homovanillic acid (HVA) levels, whereas cathinone and methcathinone increased striatal HVA and 5-HIAA. Cathinone elevated striatal and hypothalamic 5-HT. Mephedrone elevated plasma noradrenaline levels, an effect prevented by α-adrenoceptor and dopamine receptor antagonists. Conclusions and Implications MDMA and cathinones have different effects on thermoregulation, and their acute effects on brain monoamines also differ. These findings suggest that the adverse effects of cathinones in humans cannot be extrapolated from previous observations on MDMA. PMID:23043631

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

    PubMed

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

    2014-03-01

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

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

    PubMed

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

    2014-03-01

    Methylphenidate and 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') are widely misused psychoactive drugs. Methylphenidate increases brain dopamine and norepinephrine levels by blocking the presynaptic reuptake transporters. MDMA releases serotonin, dopamine and norepinephrine through the same transporters. Pharmacodynamic interactions of methylphenidate and MDMA are likely. This study compared the pharmacodynamic and pharmacokinetic effects of methylphenidate and MDMA administered alone or in combination in healthy subjects using a double-blind, placebo-controlled, crossover design. Methylphenidate did not enhance the psychotropic effects of MDMA, although it produced psychostimulant effects on its own. The haemodynamic and adverse effects of co-administration of methylphenidate and MDMA were significantly higher compared with MDMA or methylphenidate alone. Methylphenidate did not change the pharmacokinetics of MDMA and vice versa. Methylphenidate and MDMA shared some subjective amphetamine-type effects; however, 125 mg of MDMA increased positive mood more than 60 mg of methylphenidate, and methylphenidate enhanced activity and concentration more than MDMA. Methylphenidate and MDMA differentially altered facial emotion recognition. Methylphenidate enhanced the recognition of sad and fearful faces, whereas MDMA reduced the recognition of negative emotions. Additionally, the present study found acute pharmacodynamic tolerance to MDMA but not methylphenidate. In conclusion, the combined use of methylphenidate and MDMA does not produce more psychoactive effects compared with either drug alone, but potentially enhances cardiovascular and adverse effects. The findings may be of clinical importance for assessing the risks of combined psychostimulant misuse. Trial registration identification number: NCT01465685 (http://clinicaltrials.gov/ct2/show/NCT01465685). PMID:24103254

  20. 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

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

    PubMed Central

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

    2009-01-01

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

  2. 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.

  3. Effects of MDMA on body temperature in humans

    PubMed Central

    Liechti, Matthias E

    2014-01-01

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

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

    PubMed

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

    2014-09-01

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

  5. Differences between abstinent and non-abstinent individuals in recovery from alcohol use disorders

    PubMed Central

    Subbaraman, Meenakshi Sabina; Witbrodt, Jane

    2014-01-01

    Objective Non-abstinent goals can improve quality of life (QOL) among individuals with alcohol use disorders (AUD). However, prior studies have defined “recovery” based on DSM criteria, and thus may have excluded individuals using non-abstinent techniques that do not involve reduced drinking. Furthermore, no prior study has considered length of time in recovery when comparing QOL between abstinent and non-abstinent individuals. The current aims are to identify correlates of non-abstinent recovery and examine differences in QOL between abstainers and non-abstainers accounting for length of time in recovery. Sample A large (N=5,380) national sample of individuals who self-describe as “in recovery” from alcohol problems recruited in the context of the What Is Recovery? (WIR) study. Method Multivariable stepwise regressions estimating the probability of non-abstinent recovery and average quality of life. Results Younger age (OR = 0.72), no prior treatment (OR = 0.63) or AA (OR = 0.32), fewer dependence symptoms (OR = 0.17) and less time in recovery all significantly (P < 0.05) related to non-abstinent recovery. Abstainers reported significantly (P < 0.05) higher QOL than non-abstainers (B = 0.39 for abstinence vs. non-abstinence), and abstinence was one of the strongest correlates of QOL, even beyond sociodemographics variables like education. Conclusions Non-abstainers are younger with less time in recovery and less problem severity but worse QOL than abstainers. Clinically, individuals considering non-abstinent goals should be aware that abstinence may be best for optimal QOL in the long run. Furthermore, time in recovery should be accounted for when examining correlates of recovery. PMID:25117850

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

    PubMed

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

    2012-05-01

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

  7. 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.

  8. 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…

  9. 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…

  10. 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

  11. Stereoselective effects of MDMA on inhibition of monoamine uptake

    SciTech Connect

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

    1986-03-05

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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. MDMA alters emotional processing and facilitates positive social interaction

    PubMed Central

    Wardle, Margaret C.; de Wit, Harriet

    2014-01-01

    Background ±3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) produces “prosocial” effects, such as feelings of empathy and closeness, thought to be important to its abuse and its value in psychotherapy. However, it is not fully understood how MDMA alters basic emotional processes to produce these effects, or whether it produces corresponding changes in actual social behavior. Here we examined how MDMA affects perceptions of and responses to emotional expressions, and tested its effects on behavior during a social interaction. We also examined whether MDMA’s prosocial effects related to a measure of abuse liability. Methods Over three sessions 36 healthy volunteers with previous ecstasy use received MDMA (0.75mg/kg, 1.5mg/kg) and placebo under double-blind conditions. We measured i) mood and cardiovascular effects, ii) perception of and psychophysiological responses to emotional expressions iii) use of positive and negative words in a social interaction and iv) perceptions of an interaction partner. We then tested whether these effects predicted desire to take the drug again. Results MDMA slowed perception of angry expressions, increased psychophysiological responses to happy expressions, and increased positive word use and perceptions of partner empathy and regard in a social interaction. These effects were not strongly related to desire to take the drug again. Conclusions MDMA alters basic emotional processes by slowing identification of negative emotions and increasing responses to positive emotions in others. Further, it positively affects behavior and perceptions during actual social interaction. These effects may contribute to the efficacy of MDMA in psychotherapy, but appear less closely related to its abuse potential. PMID:24728603

  17. 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…

  18. 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)…

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

    PubMed

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

    2006-07-01

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

  20. 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

  1. 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.

  2. 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

  3. 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…

  4. 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…

  5. 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

  6. 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

  7. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  10. 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

  11. 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 ...

  12. 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

  13. Altered energy production, lowered antioxidant potential, and inflammatory processes mediate CNS damage associated with abuse of the psychostimulants MDMA and methamphetamine

    PubMed Central

    Downey, Luke A.; Loftis, Jennifer M.

    2014-01-01

    Central nervous system (CNS) damage associated with psychostimulant dependence may be an ongoing, degenerative process with adverse effects on neuropsychiatric function. However, the molecular mechanisms regarding how altered energy regulation affects immune response in the context of substance use disorders are not fully understood. This review summarizes the current evidence regarding the effects of psychostimulant [particularly 3,4-methylenedioxy-N-methylamphetamine (MDMA) and methamphetamine] exposure on brain energy regulation, immune response, and neuropsychiatric function. Importantly, the neuropsychiatric impairments (e.g., cognitive deficits, depression, and anxiety) that persist following abstinence are associated with poorer treatment outcomes – increased relapse rates, lower treatment retention rates, and reduced daily functioning. Qualifying the molecular changes within the CNS according to the exposure and use patterns of specifically abused substances should inform the development of new therapeutic approaches for addiction treatment. PMID:24485894

  14. 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

  15. 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.

  16. Employment-based abstinence reinforcement following inpatient detoxification in HIV-positive opioid and/or cocaine-dependent patients.

    PubMed

    Dunn, Kelly E; Fingerhood, Michael; Wong, Conrad J; Svikis, Dace S; Nuzzo, Paul; Silverman, Kenneth

    2014-02-01

    Employment-based reinforcement interventions have been used to promote abstinence from drugs among chronically unemployed injection drug users. The current study used an employment-based reinforcement intervention to promote opioid and cocaine abstinence among opioid and/or cocaine-dependent, HIV-positive participants who had recently completed a brief inpatient detoxification. Participants (n = 46) were randomly assigned to an abstinence and work group that was required to provide negative urine samples in order to enter the workplace and to earn incentives for work (n = 16), a work-only group that was permitted to enter the workplace and to earn incentives independent of drug use (n = 15), and a no-voucher control group that did not receive any incentives for working (n = 15) over a 26-week period. The primary outcome was urinalysis-confirmed opioid, cocaine, and combined opioid/cocaine abstinence. Participants were 78% male and 89% African American. Results showed no significant between-groups differences in urinalysis-verified drug abstinence or HIV risk behaviors during the 6-month intervention. The work-only group had significantly greater workplace attendance, and worked more minutes per day when compared to the no-voucher group. Several features of the study design, including the lack of an induction period, setting the threshold for entering the workplace too high by requiring immediate abstinence from several drugs, and increasing the risk of relapse by providing a brief detoxification that was not supported by any continued pharmacological intervention, likely prevented the workplace from becoming established as a reinforcer that could be used to promote drug abstinence. However, increases in workplace attendance have important implications for adult training programs. PMID:24490712

  17. Employment-based abstinence reinforcement following inpatient detoxification in HIV-positive opioid and/or cocaine-dependent patients.

    PubMed

    Dunn, Kelly E; Fingerhood, Michael; Wong, Conrad J; Svikis, Dace S; Nuzzo, Paul; Silverman, Kenneth

    2014-02-01

    Employment-based reinforcement interventions have been used to promote abstinence from drugs among chronically unemployed injection drug users. The current study used an employment-based reinforcement intervention to promote opioid and cocaine abstinence among opioid and/or cocaine-dependent, HIV-positive participants who had recently completed a brief inpatient detoxification. Participants (n = 46) were randomly assigned to an abstinence and work group that was required to provide negative urine samples in order to enter the workplace and to earn incentives for work (n = 16), a work-only group that was permitted to enter the workplace and to earn incentives independent of drug use (n = 15), and a no-voucher control group that did not receive any incentives for working (n = 15) over a 26-week period. The primary outcome was urinalysis-confirmed opioid, cocaine, and combined opioid/cocaine abstinence. Participants were 78% male and 89% African American. Results showed no significant between-groups differences in urinalysis-verified drug abstinence or HIV risk behaviors during the 6-month intervention. The work-only group had significantly greater workplace attendance, and worked more minutes per day when compared to the no-voucher group. Several features of the study design, including the lack of an induction period, setting the threshold for entering the workplace too high by requiring immediate abstinence from several drugs, and increasing the risk of relapse by providing a brief detoxification that was not supported by any continued pharmacological intervention, likely prevented the workplace from becoming established as a reinforcer that could be used to promote drug abstinence. However, increases in workplace attendance have important implications for adult training programs.

  18. 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

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

    PubMed

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

    2015-03-15

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

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

    PubMed

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

    2013-06-01

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

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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…

  6. 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…

  7. 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…

  8. 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…

  9. 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

  10. 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

  11. 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.

  12. Smoking Cessation Abstinence Goal in Treatment-Seeking Smokers

    PubMed Central

    Hall, Sharon M.; Shi, Yanling; Humfleet, Gary L.; Munoz, Ricardo F.; Reus, Victor I.; Prochaska, Judith J.

    2014-01-01

    Introduction Baseline abstinence goal is a robust predictor of cigarette abstinence. However, important questions about goal remain unanswered. These include variables correlating with goal, changes in goal, the relationship of goal and abstinence status over time, and predictors of change. The current study aimed to address these questions. Method Participants were treatment-seeking volunteers in two clinical trials. In Clinical Trial 1 (N=402), participants smoked ≥10 cigarettes per day (CPD) and were ≥50 years of age. In Clinical Trial 2 (N=406), participants smoked ≥10 CPD, smoked within 30 minutes of arising, and were ≥18 years of age. The outcome variables were biochemically verified 7-day abstinence from cigarettes at weeks 12, 24, 52, and 104. Abstinence goal, demographic, psychological, and smoking related variables were assessed via standard instruments. Results At baseline, the greater the desire to quit and one’s expectations of success, and the lesser the educational level, the more likely participants were to have a quit forever goal. Throughout the two-year study, abstinence from cigarettes and a lower educational level were correlated with a goal of quit forever; 37% of participants changed goal. There were no predictors of goal change. Abstinence goal was related to abstinence status across the study period. Goal predicted abstinence status at subsequent assessments, even when status was controlled. Conclusion Lesser educational levels were consistent predictors of a more stringent goal. Abstinence goal changes over time. These findings suggest that repeated counseling about goal is advisable and participants would benefit from such counseling, independent of demographic characteristics and smoking status. PMID:25462664

  13. 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

  14. Stress, religiosity, and abstinence from alcohol.

    PubMed

    Krause, N

    1991-03-01

    The purpose of this study was to test a conceptual model that attempts to identify psychosocial factors associated with the avoidance of alcohol in later life. This model is based on the life stress literature. Although most researchers maintain that life events are associated with greater alcohol consumption, a basic premise of this study is that certain stressors may be related to abstinence from alcohol in later life. In examining this relationship, the effects of a potentially important coping resource (religiosity) were also considered. Findings from a nationwide survey suggest that although greater health problems are associated with a greater probability that elderly people will abstain from using alcohol, financial difficulties had the opposite effect and were instead related to a lesser probability that older adults would avoid drinking alcoholic beverages. Finally, gender and race were found to exert important effects throughout the model.

  15. 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

  16. 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

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

    PubMed

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

    2016-01-01

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

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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

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

    PubMed

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

    1999-11-26

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

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

    PubMed

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

    2014-12-01

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

  5. 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

  6. 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…

  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.

  9. Cognitive functions in abstinent alcohol-dependent patients.

    PubMed

    Kopera, Maciej; Wojnar, Marcin; Brower, Kirk; Glass, Jennifer; Nowosad, Izabela; Gmaj, Bartłomiej; Szelenberger, Waldemar

    2012-11-01

    The objective of this cross-sectional study was to compare cognitive functioning of abstaining alcohol-dependent (AD) male patients and healthy controls as well as to investigate whether their cognitive performance varied by abstinence length. Forty-two maintaining abstinent (AD) patients and 34 healthy controls were examined. Tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to assess cognitive functions. Differences in cognitive performance were found between AD patients and healthy controls. Nonverbal tasks in cognitive domains such as attention, visual memory and working memory were impaired in AD patients who presented deficits in visual episodic memory, had slower reaction time and reduced working memory span. Patients who were abstinent for less than one year made more errors in both attentional set shifting and working memory tests than healthy controls and patients with longer durations of abstinence. Impairments identified in multiple cognitive domains in abstinent alcohol-dependent subjects suggest functional deficits in extensive brain networks connecting interrelated brain structures. Attentional control and spatial working memory were less impaired in those AD patients who maintained abstinence for at least one year.

  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. 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.

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

    PubMed

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

    2014-10-01

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

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

    PubMed

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

    2015-03-01

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

  14. 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

  15. The abstinence violation effect in child molesters.

    PubMed

    Ward, T; Hudson, S M; Marshall, W L

    1994-05-01

    The reformulation of the abstinence violation effect (AVE) is briefly described together with the empirical support for the construct. Twenty-six incarcerated male child molesters were assessed, using the Differential Emotions Scale and the Attributional Dimension Scale, at three points (high-risk, lapse, and relapse) while they listened to an audiotaped recording of a description of their most typical offense chain. Eighteen Ss experienced an AVE at the point of relapse and 7 as a result of lapse. There were significant increases in most negative emotions and decreases in interest over the relapse chain. There were significantly higher disgust, contempt, hostility, fear, shame, shyness and anger scores reported by those showing an AVE. Conversely, the AVE group showed significantly lower scores for joy and surprise. There were no significant differences on any of the 4 attributional dimensions across the relapse process but those showing an AVE reported significantly more uncontrollability and higher stability scores. The significance of these results for clinical practice are discussed.

  16. Neonatal Abstinence Syndrome: Presentation and Treatment Considerations.

    PubMed

    Kaltenbach, Karol; Jones, Hendree E

    2016-01-01

    The increase in opioid use among the general population is reflected in pregnant women and neonatal abstinence syndrome (NAS) statistics. This increase has produced an unprecedented focus on NAS from both the political-judicial sphere and the medical community. Under the banner of fetal protection, judges and prosecutors have implemented punitive approaches against women who use prescribed and nonprescribed opioids during pregnancy, including arrest, civil commitment, detention, prosecution, and loss of custody or termination of parental rights. Within the medical community, questions have been raised regarding protocols to detect prenatal drug exposure at delivery, NAS treatment protocols, the need for quality-improvement strategies to standardize care and reduce length of stay for mother and infant, and the benefits of engaging the mother in the care of her infant. It is not uncommon for the expression of strong discordant views on these issues both between and among these political-judicial and medical constituencies. Closely examining the issues often reveal a lack of understanding of substance use disorders, their treatment, and the occurrence and treatment of NAS. This study provides an in-depth examination of NAS, including variations in presentation and factors that impact the efficacy of treatment, and also identifying questions that remain unanswered. Finally, 4 key areas on which future research should focus to guide both medical care and public policy are discussed. PMID:26974659

  17. Modafinil and nicotine interactions in abstinent smokers.

    PubMed

    Sofuoglu, Mehmet; Waters, Andrew J; Mooney, Marc

    2008-01-01

    In this study, we examined the effects of a wakefulness-promoting medication, modafinil, alone and with the nicotine lozenge, on subjective, physiological and cognitive measures as well as on nicotine withdrawal in overnight abstinent cigarette smokers. Nineteen smokers, 13 male and 6 female, participated in a double-blind, placebo-controlled, crossover study. In each of three experimental sessions, subjects were treated orally with a single 200 mg or 400 mg dose of modafinil or placebo. Two hours and 10 min following the medication treatment, subjects received a single 2 mg nicotine lozenge. Both doses of modafinil alone increased the rating of elated-depressed on the Profile of Mood States (POMS) subscale in the direction of depressed and increased ratings of negative affect on the Positive and Negative Affect Schedule (PANAS). In contrast, the 200 mg modafinil dose combined with a 2 mg nicotine lozenge, increased the rating of energetic-tired in the direction of energetic on the POMS subscale. Modafinil attenuated self-reported rating of 'drug strength' in response to the nicotine lozenge. Modafinil, alone or in combination with the nicotine lozenge, did not affect tobacco withdrawal symptoms. There was an increase in baseline heart rate and systolic blood pressure under modafinil treatment. In addition, modafinil speeded reaction times on a modified Stroop task. The clinical utility of modafinil for smoking cessation needs to be determined in future studies. PMID:17868195

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

    PubMed

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

    2008-11-01

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

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

    PubMed

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

    2006-06-01

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

  20. Methamphetamine use parameters do not predict neuropsychological impairment in currently abstinent dependent adults.

    PubMed

    Cherner, Mariana; Suarez, Paola; Casey, Corinna; Deiss, Robert; Letendre, Scott; Marcotte, Thomas; Vaida, Florin; Atkinson, J Hampton; Grant, Igor; Heaton, Robert K

    2010-01-15

    Methamphetamine (meth) abuse is increasingly of public health concern and has been associated with neurocognitive dysfunction. Some previous studies have been hampered by background differences between meth users and comparison subjects, as well as unknown HIV and hepatitis C (HCV) status, which can also affect brain functioning. We compared the neurocognitive functioning of 54 meth dependent (METH+) study participants who had been abstinent for an average of 129 days, to that of 46 demographically comparable control subjects (METH-) with similar level of education and reading ability. All participants were free of HIV and HCV infection. The METH+ group exhibited higher rates of neuropsychological impairment in most areas tested. Among meth users, neuropsychologically normal (n=32) and impaired (n=22) subjects did not differ with respect to self-reported age at first use, total years of use, route of consumption, or length of abstinence. Those with motor impairment had significantly greater meth use in the past year, but impairment in cognitive domains was unrelated to meth exposure. The apparent lack of correspondence between substance use parameters and cognitive impairment suggests the need for further study of individual differences in vulnerability to the neurotoxic effects of methamphetamine.

  1. 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

  2. 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.

  3. Tobacco Withdrawal Symptoms Mediate Motivation to Reinstate Smoking During Abstinence

    PubMed Central

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

    2015-01-01

    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 three 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≥cig/day; N=286) attended two counterbalanced sessions at which abstinence duration was differentially manipulated (1-hour vs. 17-hours). 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

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

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

    PubMed

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

    1993-01-01

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

  10. 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

  11. 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

  12. 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.

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

    PubMed

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

    2002-07-12

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

  14. 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.

  15. 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.

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

    PubMed

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

    2010-01-01

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

  17. 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.

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

    PubMed Central

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

    2008-01-01

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

  19. 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

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

    PubMed

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

    2014-01-01

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

  1. 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.

  2. Postpartum smoking abstinence and smoke-free environments.

    PubMed

    Ashford, Kristin; Hahn, Ellen; Hall, Lynne; Peden, Ann R; Rayens, Mary Kay

    2011-01-01

    The purpose of this exploratory study was to describe factors that contribute to successful postpartum smoking abstinence among women who quit smoking during pregnancy. Research questions addressed the primary motivators and lifestyle characteristics of women who do not return to postpartum smoking. Participants were recruited from a feasibility study (N = 16) based on their ability to remain smoke free for at least 6 months following delivery. Individual interviews were analyzed using content analysis strategies. Women's narratives described the process of postpartum smoking abstinence. Four themes emerged: (a) child's health as the primary motivator, (b) demanding a smoke-free home or environment, (c) smoking perception changes from one of primarily comfort to one of disgust, and (d) viewing abstinence as a lifelong change. Clinical implications include educating families about the effects of smoke-free environments on the health of their children while redirecting smoking habits with healthy behaviors.

  3. Paths to tobacco abstinence: A repeated measures latent class analysis

    PubMed Central

    McCarthy, Danielle E.; Ebssa, Lemma; Witkiewitz, Katie; Shiffman, Saul

    2015-01-01

    Objective Knowledge of smoking change processes may be enhanced by identifying pathways to stable abstinence. We sought to identify latent classes of smokers based on their day-to-day smoking status in the first weeks of a cessation attempt. We examined treatment effects on class membership and compared classes on baseline individual differences and 6-month abstinence rates. Method In this secondary analysis of a double-blind randomized placebo-controlled clinical trial (N=1433) of 5 smoking cessation pharmacotherapies (nicotine patch, nicotine lozenge, bupropion SR, patch and lozenge, or bupropion SR and lozenge), we conducted repeated measures latent class analysis of daily smoking status (any smoking vs. none) for the first 27 days of a quit attempt. Treatment and covariate relations with latent class membership were examined. Distal outcome analysis compared confirmed 6-month abstinence rates among the latent classes. Results A 5-class solution was selected. Three-quarters of smokers were in stable smoking or abstinent classes, but 25% were in classes with unstable abstinence probabilities over time. Active treatment (compared to placebo), and particularly the patch and lozenge combination, promoted early quitting. Latent classes differed in 6-month abstinence rates and on several baseline variables, including nicotine dependence, quitting history, self-efficacy, sleep disturbance, and minority status. Conclusions Repeated measures latent class analysis identified latent classes of smoking change patterns affected by treatment, related to known risk factors, and predictive of distal outcomes. Tracking behavior early in a change attempt may identify prognostic patterns of change and facilitate adaptive treatment planning. PMID:25867447

  4. 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

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

    PubMed

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

    2014-04-01

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

  6. 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

  7. PROGNOSTIC SIGNIFICANCE OF PSYCHOPATHOLOGY IN THE ABSTINENCE FROM OPIATE ADDICTION

    PubMed Central

    Satija, D.C.; Sharma, D.K.; Gaur, Arun; Nathawat, S.S.

    1989-01-01

    SUMMARY The aim of the present study was to find out the influence of psychopathology on abstinence from opiate addiction. A group of 54 opiate addicts with psychopathology was compared with another group of 55 opiate addicts without psychopathology. Both the groups were detoxified and followed up for a period of 12 months. Common psychopathology in opiate addicts consisted of psychopathic personality disorder, manic depressive psychosis, schizophrenia and psychosomatic and neurotic disorders. Abstinence rate was 18.8% in opiate addicts with psychopathology in contrast to 60.8% in addicts without psychopathology. The implications of the findings have been discussed. PMID:21927375

  8. 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

  9. 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

  10. 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…

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2010-02-01

    In Western societies, a considerable percentage of young people use 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy'). The use of alcohol (ethanol) in combination with ecstasy is common. The aim of the present study was to assess the acute psychomotor and subjective effects of (co-) administration of MDMA and ethanol over time and in relation to the pharmacokinetics. We performed a four-way, double blind, randomized, crossover, placebo-controlled study in 16 healthy volunteers (nine men, seven women) between the ages of 18 and 29. MDMA (100 mg) was given orally while blood alcohol concentration was maintained at pseudo-steady state levels of approximately 0.6 per thousand for 3 h by a 10% intravenous ethanol clamp. MDMA significantly increased psychomotor speed but did not affect psychomotor accuracy and induced subjective arousal. Ethanol impaired both psychomotor speed and accuracy and induced sedation. Coadministration of ethanol and MDMA improved psychomotor speed but impaired psychomotor accuracy compared with placebo and reversed ethanol-induced sedation. Pharmacokinetics and pharmacodynamics showed maximal effects at 90-150 min after MDMA administration after which drug effects declined in spite of persisting MDMA plasma concentration, with the exception of ethanol-induced sedation, which manifested itself fully only after the infusion was stopped. In conclusion, results show that subjects were more aroused when intoxicated with both substances combined compared with placebo, but psychomotor accuracy was significantly impaired. These findings may have implications for general neuropsychological functioning as this may provide a sense of adequate performance that does not agree with a significant reduction in psychomotor accuracy.

  13. 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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

  16. Abstinence, Social Norms, and Drink Responsibly Messages: A Comparison Study

    ERIC Educational Resources Information Center

    Glassman, Tavis J.; Kruger, Jessica Sloan; Deakins, Bethany A.; Paprzycki, Peter; Blavos, Alexis A.; Hutzelman, Erin N.; Diehr, Aaron

    2016-01-01

    Objective: The purpose of this study was to determine which type of prevention message (abstinence, social norms, or responsible drinking) was most effective at reducing alcohol consumption. Participants: The subjects from this study included 194 college students from a public university. Methods: Researchers employed a quasi-experimental design,…

  17. Smoking topography and abstinence in adult female smokers.

    PubMed

    McClure, Erin A; Saladin, Michael E; Baker, Nathaniel L; Carpenter, Matthew J; Gray, Kevin M

    2013-12-01

    Preliminary evidence, within both adults and adolescents, suggests that the intensity with which cigarettes are smoked (i.e., smoking topography) is predictive of success during a cessation attempt. These reports have also shown topography to be superior compared to other variables, such as cigarettes per day, in the prediction of abstinence. The possibility that gender may influence this predictive relationship has not been evaluated but may be clinically useful in tailoring gender-specific interventions. Within the context of a clinical trial for smoking cessation among women, adult daily smokers completed a laboratory session that included a 1-hour ad libitum smoking period in which measures of topography were collected (N=135). Participants were then randomized to active medication (nicotine patch vs. varenicline) and abstinence was monitored for 4weeks. Among all smoking topography measures and all abstinence outcomes, a moderate association was found between longer puff duration and greater puff volume and continued smoking during the active 4-week treatment phase, but only within the nicotine patch group. Based on the weak topography-abstinence relationship among female smokers found in the current study, future studies should focus on explicit gender comparisons to examine if these associations are specific to or more robust in male smokers.

  18. Smoking topography and abstinence in adult female smokers

    PubMed Central

    McClure, Erin A.; Saladin, Michael E.; Baker, Nathaniel L.; Carpenter, Matthew J.; Gray, Kevin M.

    2013-01-01

    Preliminary evidence, within both adults and adolescents, suggests that the intensity with which cigarettes are smoked (i.e. smoking topography) is predictive of success during a cessation attempt. These reports have also shown topography to be superior compared to other variables, such as cigarettes per day, in the prediction of abstinence. The possibility that gender may influence this predictive relationship has not been evaluated, but may be clinically useful in tailoring gender-specific interventions. Within the context of a clinical trial for smoking cessation among women, adult daily smokers completed a laboratory session that included a 1-hour ad-libitum smoking period in which measures of topography were collected (N=135). Participants were then randomized to active medication (nicotine patch vs. varenicline) and abstinence was monitored for 4 weeks. Among all smoking topography measures and all abstinence outcomes, a moderate association was found between longer puff duration and greater puff volume and continued smoking during the active 4-week treatment phase, but only within the nicotine patch group. Based on the weak topography-abstinence relationship among female smokers found in the current study, future studies should focus on explicit gender comparisons to examine if these associations are specific to or more robust in male smokers. PMID:24018226

  19. 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…

  20. 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.

  1. 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

  2. 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…

  3. Smokers' expectancies for abstinence: preliminary results from focus groups.

    PubMed

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

    2009-06-01

    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 nicotine replacement therapy effectiveness, alcohol and other drug use, 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

  4. 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

  5. "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…

  6. Time dependency of craving and response inhibition during nicotine abstinence

    PubMed Central

    Tsaur, Stephen; Strasser, Andrew A.; Souprountchouk, Valentina; Evans, Gretchen C.; Ashare, Rebecca L.

    2015-01-01

    Background Nicotine withdrawal produces increased craving for cigarettes and deficits in response inhibition, and these withdrawal symptoms are predictive of relapse. Although it is well-established that these symptoms emerge early during abstinence, there is mixed evidence regarding whether they occur simultaneously. Given the importance of the early withdrawal period, this study examined craving and response inhibition at 24h and 72h abstinence. Methods Twenty-one non-treatment seeking adult smokers were evaluated at baseline, 24h, and 72h abstinence for craving (Questionnaire on Smoking Urges – Brief) and response inhibition (Stop Signal Task, Stroop Task, Continuous Performance Task). Generalized linear regression models were used for primary outcomes, and Pearson correlations for examining the association between craving and response inhibition. Results Factor 2 craving (anticipated relief of negative affect) increased from baseline to 24h abstinent (p=0.004), which subsided by 72h (p=0.08). Deficits in response inhibition measured by the Stop Signal Task were observed at 72h (p=0.046), but not 24h (p=0.318). No correlation was found between response inhibition and craving at any time point (p-values>0.19), except between the Stroop Task and factor 1 craving at baseline (p=0.025). Conclusions Factor 2 craving peaked at 24h, whereas deficits in response inhibition did not emerge until 72h, indicating that need to target craving and cognitive function during early abstinence may not occur simultaneously. Further characterizing the time course of withdrawal symptoms may guide development of targeted treatments for smoking cessation. PMID:26052265

  7. Elevated Plasma Prolactin in Abstinent Methamphetamine-Dependent Subjects

    PubMed Central

    Zorick, Todd; Mandelkern, Mark A.; Lee, Buyean; Wong, Ma-Li; Miotto, Karen; Shabazian, Jon; London, Edythe D.

    2011-01-01

    Background Methamphetamine use disorders are pervasive global social problems that produce large medical and public health burdens. Abnormalities in pituitary hormonal regulation have been observed in preclinical models of substance abuse and in human substance abusers. They have not been studied before, however, in methamphetamine-dependent human subjects. Objectives To determine if methamphetamine-dependent research volunteers differ from healthy control subjects in plasma levels of adrenocorticotropic hormone (ACTH), cortisol, or prolactin, or in pituitary dopamine D2 receptor availability during early abstinence from methamphetamine. Methods Methamphetamine-dependent subjects (N=31), who were not seeking treatment, resided on an inpatient ward for up to 5 weeks. Abstinence was confirmed by daily urine drug screening. Venous blood was sampled for plasma hormone levels, and positron emission tomography with [18F]fallypride was performed to determine dopamine D2 receptor availability during the first week of abstinence. Venous blood was sampled again for hormone levels during the fourth week of abstinence. Matched healthy volunteers (N=23) participated as a comparison group. Results Methamphetamine-dependent and healthy comparison subjects did not differ in plasma ACTH or cortisol levels, but had an elevated plasma prolactin at both the first week and fourth week of abstinence. There was no group difference in pituitary dopamine D2 receptor availability. Conclusion Methamphetamine-dependent individuals have abnormalities in prolactin regulation, which is not likely due to alterations in pituitary dopamine D2 receptor availability. Scientific Significance Methamphetamine dependence is associated with elevated prolactin levels, which may contribute to medical co-morbidity in afflicted individuals. PMID:21142706

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

    PubMed

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

    2013-12-01

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

  9. 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

  10. 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

  11. 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.

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

    PubMed

    Kuteykin-Teplyakov, Konstantin; Maldonado, Rafael

    2014-11-01

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

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

    PubMed

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

    2015-05-22

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

  14. 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

  15. 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.

  16. Physical Activity as a Strategy for Maintaining Tobacco Abstinence

    PubMed Central

    Prochaska, Judith J.; Hall, Sharon M.; Humfleet, Gary; Muňoz, Ricardo F.; Reus, Victor; Gorecki, Julie; Hu, Dixie

    2008-01-01

    Objectives For smoking cessation, physical activity (PA) may help manage withdrawal symptoms, mood, stress, and weight; yet studies of PA as an aid for smoking cessation have been mixed. This study examined: (1) the impact of an extended relapse prevention program on increasing moderate to vigorous PA (MVPA) in adults enrolled in a tobacco cessation treatment trial; (2) whether changes in MVPA were associated with sustained abstinence from smoking; and (3) mechanisms by which MVPA may support sustained abstinence from smoking. Method In a randomized controlled trial conducted from 2003-2006 in San Francisco, California, 407 adult smokers received a 12 week group-based smoking cessation treatment with bupropion and nicotine patch with the quit date set at week 3. At week 12, participants were randomized to no further treatment or to 40 weeks of bupropion or placebo with or without an 11-session relapse prevention intervention of which 2 sessions (held at weeks 16 and 20) focused on PA. Participants receiving the PA intervention (n=163) received a pedometer, counseling to increase steps 10% biweekly towards a 10,000 steps/day goal, and personalized reports graphing progress with individualized goals. The International Physical Activity Questionnaire assessed weekly minutes of MVPA at baseline and weeks 12 and 24. Sustained abstinence from tobacco at week 24 was validated with expired carbon monoxide. Results In a repeated mixed model analysis, intervention participants significantly increased their MVPA relative to control participants, F(1,475)=3.95, p=.047. Pedometer step counts also increased significantly, t(23)=2.36, p=.027, though only 15% of intervention participants provided 6 weeks of pedometer monitoring. Controlling for treatment condition, increased MVPA predicted sustained smoking abstinence at week 24, odds ratio=1.84 (95% CI: 1.07, 3.05). Among participants with sustained abstinence, increased MVPA was associated with increased vigor (r=0.23, p=.025

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

    PubMed

    Johnson, Bethann N; Yamamoto, Bryan K

    2010-10-01

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

  18. 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

  19. 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

  20. Craving among long-abstinent smokers: An Internet survey

    PubMed Central

    2010-01-01

    Introduction: This survey estimated the prevalence and correlates of craving among long-abstinent smokers. Methods: We surveyed 403 former smokers (abstinent 1–10 years) via an Internet consumer sample (www.zoomerang.com). Results: Although the majority (59%) of former smokers reported a desire to smoke in the last year, this desire appeared to be clinically significant in only 11%. Those with significant prolonged craving were more nicotine dependent and appeared to have more mental health problems but did differ from other former smokers on demographics or family history of smoking. Discussion: A minority of smokers appears to continue to struggle with cravings long after cessation. Replications in larger more generalizable surveys are needed. In addition, whether prolonged craving indicates risk for relapse needs to be determined. PMID:20164170

  1. Comparison of urine and hair testing for drugs of abuse in the control of abstinence in driver's license re-granting.

    PubMed

    Dufaux, Bertin; Agius, Ronald; Nadulski, Thomas; Kahl, Hans-Gerhard

    2012-06-01

    The purpose of the study was to compare the detection rate of illicit drugs in urine and hair specimens. The samples were taken from subjects trying to regain their revoked driver's license after a drug- or alcohol-related traffic offence. In 2010, we screened 14 000 urine and 3900 hair samples for amphetamines, methamphetamines, cannabinoids, cocaine, opiates, methadone, and benzodiazepines as well as for ethylglucuronide. We used the low threshold values of the new German guidelines for Medical Psychological Assessment (MPA). Positive screening tests were confirmed with gas chromatography-mass spectrometry (GC-MS), gas chromatography-tandem mass spectrometry (GC-MS/MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results show that positivity rates for methamphetamines, MDMA, cocaine, and monoacetylmorphine were 1.7-, 5.7-, 3.8- and 9.3-fold higher in hair than in urine. In contrast, the detection rate for benzodiazepines was higher in urine than in hair (oxazepam, 0.21% versus 0%, nordiazepam 0.10% versus 0.03%). The positivity rate in hair for ethylglucuronide was 6-fold (12.7%) that for urine testing (2.1%). The study reveals that in the control of abstinence in the context of driving license re-granting there are in part large differences of positivity rates for some drugs or metabolites between hair and urine samples. These differences should be kept in mind by physicians and psychologists in traffic medicine who are ordering the drug testing.

  2. The Effects of Acute Abstinence from Smoking and Performance-Based Rewards on Performance Monitoring

    PubMed Central

    Schlienz, Nicolas J.; Hawk, Larry W.; Rosch, Keri S.

    2013-01-01

    Rationale Abstinence from smoking disrupts performance in multiple cognitive domains, and such cognitive effects may serve to maintain smoking behavior. Rather than having specific effects on a narrow domain of processing, abstinence may disrupt more general cognitive control processes and/or motivation. Objectives The present study tested the prediction that overnight abstinence from smoking would disrupt a general performance monitoring system indexed via the error-related negativity (ERN). A secondary aim was to determine the extent to which performance-based monetary rewards improved the ERN among smokers and whether the effect of reward was diminished during abstinence. Methods The ERN was assessed during a flanker task among 25 heavy, non-treatment-seeking smokers both when smoking as usual and after overnight abstinence; reward and no-reward trial blocks occurred within each session. Results As predicted, mean ERN amplitude was reduced during abstinence. The ERN was enhanced by reward; this effect did not vary with smoking abstinence. Conclusion This study provides novel data that suggest acute abstinence from smoking disrupts a neurophysiological index of a general performance monitoring system that is involved in a range of cognitive functions. The ERN may be a useful complement to narrow-band cognitive studies of abstinence and interventions designed to target cognition in addiction. Because the ERN was concurrently sensitive to abstinence and performance-based incentives, it may be particular useful for examining the interplay of cognition and motivation in smoking and smoking cessation. PMID:23681159

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

    PubMed Central

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

    2010-01-01

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

  4. 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

  5. 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.

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

    PubMed

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

    2014-09-01

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

  7. Top-Down Network Effective Connectivity in Abstinent Substance Dependent Individuals

    PubMed Central

    Regner, Michael F.; Saenz, Naomi; Maharajh, Keeran; Yamamoto, Dorothy J.; Mohl, Brianne; Wylie, Korey; Tregellas, Jason; Tanabe, Jody

    2016-01-01

    Objective We hypothesized that compared to healthy controls, long-term abstinent substance dependent individuals (SDI) will differ in their effective connectivity between large-scale brain networks and demonstrate increased directional information from executive control to interoception-, reward-, and habit-related networks. In addition, using graph theory to compare network efficiencies we predicted decreased small-worldness in SDI compared to controls. Methods 50 SDI and 50 controls of similar sex and age completed psychological surveys and resting state fMRI. fMRI results were analyzed using group independent component analysis; 14 networks-of-interest (NOI) were selected using template matching to a canonical set of resting state networks. The number, direction, and strength of connections between NOI were analyzed with Granger Causality. Within-group thresholds were p<0.005 using a bootstrap permutation. Between group thresholds were p<0.05, FDR-corrected for multiple comparisons. NOI were correlated with behavioral measures, and group-level graph theory measures were compared. Results Compared to controls, SDI showed significantly greater Granger causal connectivity from right executive control network (RECN) to dorsal default mode network (dDMN) and from dDMN to basal ganglia network (BGN). RECN was negatively correlated with impulsivity, behavioral approach, and negative affect; dDMN was positively correlated with impulsivity. Among the 14 NOI, SDI showed greater bidirectional connectivity; controls showed more unidirectional connectivity. SDI demonstrated greater global efficiency and lower local efficiency. Conclusions Increased effective connectivity in long-term abstinent drug users may reflect improved cognitive control over habit and reward processes. Higher global and lower local efficiency across all networks in SDI compared to controls may reflect connectivity changes associated with drug dependence or remission and requires future, longitudinal

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

    PubMed

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

    2001-11-01

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

  9. 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.

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

    PubMed Central

    Vijay, Nisha; Morris, Marilyn E.

    2014-01-01

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

  11. 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

  12. 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.

  13. Abstinence Rates among College Cigarette Smokers Enrolled in A Randomized Clinical Trial Evaluating Quit and Win Contests: The Impact of Concurrent Hookah Use

    PubMed Central

    Bengtson, J.E.; Wang, Q.; Luo, X.; Marigi, Erick; Winta, Ghidei; Ahluwalia, J.S.

    2015-01-01

    Objective To examine baseline characteristics and biochemically verified 1-, 4-, and 6-month tobacco quit rates among college students enrolled in a Quit and Win cessation trial, comparing those who concurrently smoke both hookah and cigarettes with those who deny hookah use. Methods Analyses were conducted on data from 1,217 college students enrolled in a Quit and Win tobacco cessation randomized clinical trial from 2010–2012. Multivariable logistic regression (MLR) analyses examined group differences in baseline characteristics and cotinine verified 30-day abstinence at 1, 4, and 6-month follow-up, adjusting for baseline covariates. Results Participants smoked 11.5(±8.1) cigarettes per day on 28.5(±3.8) days/month, and 22% smoked hookah in the past 30 days. Hookah smokers (n=270) were more likely to be male (p<0.0001), younger (p<0.0001), report more binge drinking (p<0.0001) and score higher on impulsivity (p<0.001). MLR results indicate that hookah users, when compared to non-users, had a 36% decrease in odds of self-reported 30-day abstinence at 4-months (OR= 0.64, 95% CI=0.45–0.93, p=0.02) and a 63% decrease in odds in biochemically verified continuous abstinence at 6-months (OR = 0.37, CI=0.14–0.99, p=0.05). Conclusion College cigarette smokers who concurrently use hookah display several health risk factors and demonstrate lower short and long-term tobacco abstinence rates. PMID:25773472

  14. If at First You Don’t Succeed: Characterization of Smokers with Late Smoking Abstinence Onset

    PubMed Central

    Leyro, Teresa M.; Hendricks, Peter S.; Hall, Sharon M.

    2015-01-01

    Most cigarette smoking cessation research has aimed to clarify characteristics associated with initial and sustained abstinence, with less attention paid to predictors of gaining abstinence following an initial failure. The current investigation explored pre-treatment demographic, smoking, and psychiatric characteristics related to gaining abstinence among smokers who failed to attain initial abstinence. Participants were 809 individuals enrolled in extended, 52-week, smoking cessation interventions. Of these, 287 (62.4%) failed to achieve initial abstinence. Gaining abstinence following initial abstinence failure was defined as achieving seven-day point prevalent abstinence at any post-initial abstinence assessment. Compared to those who failed to achieved abstinence during treatment (Treatment Failures), those who gained abstinence (Gainers) were more likely to be abstinent at post-treatment follow-up assessments conducted at weeks 64 (χ2 (1, N=268)=56.3, p<.01) and 104 (χ2 (1, N=231)=37.0, p<.01). With regard to correlates of gaining abstinence, Gainers were more likely to have a live-in partner (χ2(1, N=283)=3.8, p=.05, Cramér’s V = .12), identify as Hispanic (χ2(1, N=281)=7.8, p<.01, Cramér’s V = .17), evidence lower baseline expired breath carbon monoxide (F(1, 284)=5.7, p=.02, η2 = .02), report less cigarette dependence (F(1, 278)=7.1, p<.01, η2=.03), and report past week cannabis use (χ2(1, N=284)=5.6, p=.02, Cramér’s V=.14). A logistic regression model suggested having a live-in partner (OR=5.14, 95% CI=1.09–3.02, p=.02) and identifying as Hispanic (OR=4.93, 95% CI=1.20–18.77, p=.03) increased the odds of gaining abstinence. These findings provide insight into an understudied area, contributing an initial framework toward understanding gaining abstinence following initial failure. PMID:25637886

  15. 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

  16. 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

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

    PubMed Central

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

    2015-01-01

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

  18. 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

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

    PubMed

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

    2014-06-01

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

  20. 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

  1. 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

  2. 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.

  3. 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

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

    PubMed Central

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

    2014-01-01

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

  5. 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

  6. 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

  7. Opioid neonatal abstinence syndrome: controversies and implications for practice.

    PubMed

    Wolff, Kim; Perez-Montejano, Raul

    2014-01-01

    The Opioid Neonatal Abstinence Syndrome (NAS) is a term used to describe a cluster of signs and symptoms seen in infants experiencing withdrawal from opioid drugs. Despite a substantial literature the relationship between maternal methadone dose, NAS and the method of assessment of NAS symptoms has not been agreed. The following review will address current and historical controversies surrounding these issues and will examine the evidence concerned with the evaluation of neonates exposed to methadone in utero. The key findings are as follows: A variety of NAS scales are used to assess the severity of neonatal withdrawal symptoms including locally adapted validated tools. Inconsistencies in the use of NAS scales have included the timing, duration and frequency of administration; the degree to which observers were trained to reliability; the use of NAS scales designed for term neonates to assess pre-term neonates who may have a qualitatively different expression of abstinence symptoms and; the research setting in which the tool was administered. There is a lack of research investigating the observant bias' effect upon scoring NAS, the basis for treatment decisions and the influence of concomitant maternal use of non-opioid drugs late in pregnancy. We also discuss the implications of the lack of recognition of NAS symptoms leading to possible under reporting and inappropriate, early neonatal discharge from hospital. In addition, this paper also discusses the merits and problems of conducting research in this area and highlights gaps in our knowledge and areas for further research.

  8. 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.

  9. 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.

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

    PubMed

    Górska, A M; Gołembiowska, K

    2015-04-01

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

  11. 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…

  12. The Effect of Contracted Abstinence on College Students' Behavior toward Alcohol Use.

    ERIC Educational Resources Information Center

    Blum, Steven B.; And Others

    1980-01-01

    Assessed the relative effects of contracted abstinence and a class in alcoholism on college students' attitudes and behavior toward alcohol use. The alcohol class was effective in modifying self-reported drinking behavior,while contracted abstinence was an effective tool when used in the context of an alcohol class. (Author)

  13. 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…

  14. 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…

  15. 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" =…

  16. 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…

  17. 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…

  18. 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.

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

    PubMed

    Henwood, Benjamin F; Padgett, Deborah K; Tiderington, Emmy

    2014-01-01

    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 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 different approaches to homeless services: the traditional or "treatment first" approach that requires abstinence, and the more recent housing first 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 harm reduction versus abstinence approaches. Themes included the following: (a) harm reduction as a welcomed alternative, (b) working with ambiguity, and (c) accommodating abstinence. Drawing on recovery principles, the authors consider the broader implications of the findings for behavioral health care with this population.

  20. Abstinence Memorable Message Narratives: A New Exploratory Research Study Into Young Adult Sexual Narratives.

    PubMed

    Cooke-Jackson, Angela; Orbe, Mark P; Johnson, Amber L; Kauffman, Lydia

    2015-01-01

    Abstinence for most adolescent-aged college students relates to several factors, including strong religious beliefs, an aversion to taking risks, high career expectations, or limited attractiveness. Young adults receive hundreds of messages from various sources; therefore, understanding their memorable sexual messages is essential. This exploratory research uses an interpretive method to unravel the memorable sexual narratives of 65 virgin respondents. Findings yield two primary themes: involuntary abstinence, and conscious abstinence, which demonstrate that messages of abstinence are important yet often imbue punitive internal attitudes and beliefs derived from mainstream media and peer relationships. The article concludes with a recommendation for health practitioners and communication scholars to create positive open spaces where young adults can discuss sexuality, sexual relationships, and sexual behaviors. Additionally, understanding stigmas related to abstinence helps reframe normative sex communication messages and promote constructive short- and long-term sexual health behaviors.

  1. Neuroplasticity in Human Alcoholism: Studies of Extended Abstinence with Potential Treatment Implications.

    PubMed

    Fein, George; Cardenas, Valerie A

    2015-01-01

    Alcoholism is characterized by a lack of control over excessive alcohol consumption despite significant negative consequences. This impulsive and compulsive behavior may be related to functional abnormalities within networks of brain regions responsible for how we make decisions. The abnormalities may result in strengthened networks related to appetitive drive-or the need to fulfill desires-and simultaneously weakened networks that exercise control over behaviors. Studies using functional magnetic resonance imaging (fMRI) in abstinent alcoholics suggest that abstinence is associated with changes in the tone of such networks, decreasing resting tone in appetitive drive networks, and increasing resting tone in inhibitory control networks to support continued abstinence. Identifying electroencephalographic (EEG) measures of resting tone in these networks initially identified using fMRI, and establishing in longitudinal studies that these abstinence-related changes in network tone are progressive would motivate treatment initiatives to facilitate these changes in network tone, thereby supporting successful ongoing abstinence. PMID:26259093

  2. 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…

  3. 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

  4. Altered cerebral blood flow and neurocognitive correlates in adolescent cannabis users

    PubMed Central

    Jacobus, Joanna; Goldenberg, Diane; Wierenga, Christina E.; Tolentino, Neil J.; Liu, Thomas T.

    2012-01-01

    Rationale The effects of adolescent marijuana use on the developing brain remain unclear, despite its prevalence. Arterial spin labeling (ASL) is a noninvasive imaging technique that characterizes neurovascular status and cerebral blood flow (CBF), potentially revealing contributors to neuropathological alterations. No studies to date have looked at CBF in adolescent marijuana users. Objectives This study examined CBF in adolescent marijuana users and matched healthy controls at baseline and after 4 weeks of monitored abstinence. Methods Heavy adolescent marijuana users (n=23, >200 lifetime marijuana use days) and demographically matched controls (n=23) with limited substance exposure underwent an ASL brain scan at an initial session and after 4 weeks of sequential urine toxicology to confirm abstinence. Results Marijuana users showed reduced CBF in four cortical regions including the left superior and middle temporal gyri, left insula, left and right medial frontal gyrus, and left supramarginal gyrus at baseline; users showed increased CBF in the right precuneus at baseline, as compared to controls (corrected p values<0.05). No between group differences were found at follow-up. Conclusions Marijuana use may influence CBF in otherwise healthy adolescents acutely; however, group differences were not observed after several weeks of abstinence. Neurovascular alterations may contribute to or underlie changes in brain activation, neuropsychological performance, and mood observed in young cannabis users with less than a month of abstinence. PMID:22395430

  5. 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.

  6. Alcohol and pregnancy: do abstinence policies have unintended consequences?

    PubMed

    O'Leary, Colleen M

    2012-01-01

    Most policies and guidelines recommend that women abstain from alcohol during pregnancy. This can be difficult to achieve in developed nations where the majority of women consume alcohol and almost half of pregnancies are unplanned, leading to many pregnancies being exposed to alcohol prior to pregnancy awareness. Concerns have been raised that abstinence policies may lead women in this situation to terminate their pregnancy out of fear that they have harmed their baby; however, the evidence is limited. A recent study found that while few women reported alcohol as the reason for seeking an abortion, in almost all cases where alcohol was the reason, the women were either binge drinking or reported alcohol-related problems and the pregnancy was unplanned.

  7. Nonpharmacologic Management of Neonatal Abstinence Syndrome: An Integrative Review.

    PubMed

    Edwards, Lindy; Brown, Lisa F

    2016-01-01

    Neonatal abstinence syndrome (NAS) affects 3.39 in every 1,000 live births. A literature review was conducted to determine the varying types of nonpharmacologic management being used currently and its effect on the treatment of NAS symptoms. Fourteen articles were found that used nonpharmacologic management in the treatment of NAS. Therapies included breastfeeding, positioning, rooming-in, acupuncture/acupressure, and beds. Each of the nonpharmacologic therapies in these articles, with the exception of rocking beds, was shown to have a positive effect on the newborn with NAS. These effects include a shorter length of stay, a decrease in NAS scores, a decrease need for pharmacologic treatment, less agitation, a better quality of sleep, and a decrease in the severity of NAS symptoms. This review article shows that nonpharmacologic management is an effective tool for NAS symptom treatment. PMID:27636695

  8. The abstinence violation effect and very low calorie diet success.

    PubMed

    Mooney, J P; Burling, T A; Hartman, W M; Brenner-Liss, D

    1992-01-01

    This study evaluated the relationship between Marlatt and Gordon's (1985) Abstinence Violation Effect (AVE) and fasting outcomes of patients enrolled in a Very Low Calorie Diet (VLCD) and behavior education program. Within the first 11 weeks of the VLCD, 41 of 76 patients reported a fasting lapse and rated this lapse on an attribution scale. Patients reporting greater characterological attributions for their first lapse (i.e., a higher AVE) lost a smaller percentage of their excess weight during active fasting than patients reporting more situational attributions r(39) = -.36, p less than .025. First lapse AVE ratings did not distinguish between program dropout versus completer status, but high AVE dropouts did spend fewer weeks in the VLCD program than low AVE dropouts, r(12) = -.54, p less than .05. Although a faster's initial level of obesity accounted for the largest portion of weight loss outcome variance, the AVE accounted for a significant additional portion of outcome.

  9. Long-Term Outcomes of Infants with Neonatal Abstinence Syndrome.

    PubMed

    Maguire, Denise J; Taylor, Susan; Armstrong, Kathleen; Shaffer-Hudkins, Emily; Germain, Aaron M; Brooks, Sandra S; Cline, Genieveve J; Clark, Leah

    2016-01-01

    Parents of infants with neonatal abstinence syndrome (NAS) in the NICU may have questions about the long-term consequences of prenatal exposure to methadone, both asked and unasked. Although the signs of withdrawal will abate relatively quickly, parents should be aware of potential vision, motor, and behavioral/cognitive problems, as well as sleeping disturbances and ear infections so their infants can be followed closely and monitored by their pediatrician with appropriate referrals made. Furthermore, this knowledge may inspire parents to enroll their infants in an early intervention program to help optimize their outcomes. There are still many unanswered questions about epigenetic consequences, risk for child abuse/neglect, and risk of future substance abuse in this population. PMID:27636691

  10. 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

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

    PubMed

    Jansen, Karl L R; Theron, Lynn

    2006-03-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2012-01-01

    In vitro human studies show that the metabolism of most amphetamine-like psychostimulants is regulated by the polymorphic cytochrome P450 isozyme CYP2D6. Two compounds, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA), were selected as archetypes to discuss the translation and clinical significance of in vitro to in vivo findings. Both compounds were chosen based on their differential interaction with CYP2D6 and their high abuse prevalence in society. Methamphetamine behaves as both a weak substrate and competitive inhibitor of CYP2D6, while MDMA acts as a high affinity substrate and potent mechanism-based inhibitor (MBI) of the enzyme. The MBI behavior of MDMA on CYP2D6 implies that subjects, irrespective of their genotype/phenotype, are phenocopied to the poor metabolizer (PM) phenotype. The fraction of metabolic clearance regulated by CYP2D6 for both drugs is substantially lower than expected from in vitro studies. Other isoenzymes of cytochrome P450 and a relevant contribution of renal excretion play a part in their clearance. These facts tune down the potential contribution of CYP2D6 polymorphism in the clinical outcomes of both substances. Globally, the clinical relevance of CYP2D6 polymorphism is lower than that predicted by in vitro studies. PMID:23162568

  15. 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

  16. 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.

  17. 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

  18. 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

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

    SciTech Connect

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

    2008-07-01

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

  20. 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

  1. Effect of abstinence on left ventricular performance in asymptomatic chronic alcoholics

    SciTech Connect

    Slutsky, R.; Berger, F.; Garver, P.

    1983-08-01

    Twelve asymptomatic men who were chronic alcoholics (42.3+-10.7 years, mean age +- 1 SD) underwent supine bicycle exercise and gated cardiac blood pool imaging 4-7 days after alcohol withdrawal and then again 32-65 days after abstinence (42.2+-15.0 days). Workloads and exercise stages were identical during both exercise studies. Rest and exercise heart rates, blood pressures, cardiac outputs, double products, and systemic vascular resistances were similar in both studies. Ejection fraction (EF) was higher after abstinence at peak exercise (0,68+-0,07 vs. 0.61+-0.08 P<0.05); end-systolic volume (ESV) was smaller at rest and at peak exercise after abstinence (P<0.05). During the first exercise study, 6 of 12 (50%) subjects did not increase their EF by 0.05 units and 4 of 12 (33%) had no EF increase after abstinence. Even the original ''normal'' responders had greater rest and exercise EFs after abstinence. In the first exercise study end diastolic volume (EDV) rose during exercise (P<0.05) while ESV did not change. After abstinence, EDV did not change during exercise, while ESV declined (P<0.05). These results show that latent cardiac dysfunction exists in asymptomatic chronic alcoholics, which is partially although not completely resolved by abstinence of brief periods.

  2. Reduced Influence of Monetary Incentives on Go/NoGo Performance During Smoking Abstinence

    PubMed Central

    Roberts, Nicole J.; Geier, Charles F.

    2015-01-01

    Introduction: Smokers may experience decreased sensitivity to nondrug incentives during acute smoking deprivation. This decreased sensitivity may undermine attempts to encourage continued abstinence by enhancing cognitive processes through the use of monetary incentives. This study assessed whether the capacity for monetary incentives to enhance cognitive performance was compromised in nicotine-deprived smokers. Method: Eighteen smokers performed an incentivized Go/NoGo task on 2 occasions, once after smoking as usual prior to the session, and once after undergoing 12-hr abstinence. Participants could earn up to $5.00 ($2.50 per session) based on their performance on reward blocks of the Go/NoGo task. Results: Performance was significantly more accurate on incentivized NoGo, frequent-Go, and infrequent-Go trials relative to neutral trials during the smoke as usual session. Participants also produced fewer premature, impulsive responses on rewarded versus neutral blocks during the smoke as usual session. No significant difference between reward and neutral blocks was observed on any of the 4 performance indices during the abstinent session. Conclusions: The ability for monetary incentives to enhance inhibitory control may be compromised during acute abstinence in smokers. These findings may have implications for contingency management treatment programs which are thought to promote continued abstinence partly by facilitating the allocation of cognitive resources to processes that encourage continued abstinence by increasing the value associated with continued abstinence. PMID:25542919

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

    PubMed Central

    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

  4. 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

  5. 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

  6. 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

  7. The effects of moderate drinking and abstinence on serum and urinary beta-hexosaminidase levels.

    PubMed

    Kärkkäinen, P; Jokelainen, K; Roine, R; Suokas, A; Salaspuro, M

    1990-02-01

    The effects of moderate alcohol intake on serum (SHEX)- and urinary beta-hexosaminidase (UHEX) were studied in ten healthy volunteers, who ingested 60 g of 100% ethanol daily for 10 days. The drinking period was preceded and followed by an abstinence period. Moderate drinking and abstinence were rapidly and significantly reflected on SHEX, while UHEX levels did not change significantly during the study. Gramma-glutamyl transpeptidase (GGT), aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) decreased during the first abstinence period (P less than 0.05), but stayed thereafter at a constant level. It is concluded that SHEX may better reflect recent alcohol consumption than UHEX, GGT, ASAT or ALAT.

  8. 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.

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

    PubMed

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

    2014-01-01

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

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

    PubMed

    Milliet, Quentin; Weyermann, Céline; Esseiva, Pierre

    2009-05-30

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

  11. Effects of Smoking Abstinence, Smoking Cues and Nicotine Replacement in Smokers with Schizophrenia and Controls

    PubMed Central

    Tidey, Jennifer W.; Rohsenow, Damaris J.; Kaplan, Gary B.; Swift, Robert M.; Adolfo, Amy B.

    2010-01-01

    The mechanisms underlying the low smoking cessation rates among smokers with schizophrenia (SS) are unknown. In this laboratory study, we compared the responses of 21 SS and 21 non-psychiatric controls (CS) to manipulations of 5-hour smoking abstinence, transdermal nicotine replacement (0, 21 and 42 mg), and in vivo smoking cues. Results indicate that SS were more sensitive than CS to the effects of acute abstinence on CO boost, but not more sensitive to the effects of abstinence on urge levels or withdrawal symptoms. SS and CS did not differ in urge response to in vivo smoking cues, but SS were less consistent in their reactions. These findings suggest that heightened sensitivity to the effects of abstinence on smoke intake may partially account for the low cessation rates experienced by SS, but other potential mechanisms should be explored using behavioral laboratory models. PMID:18584468

  12. 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

  13. 3,4-methylenedioxymethamphetamine (MDMA--Ecstasy) decreases neutrophil activity through the glucocorticoid pathway and impairs host resistance to Listeria monocytogenes infection in mice.

    PubMed

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

    2014-12-01

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

  14. 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.

  15. Sustained Recreational Use of Ecstasy Is Associated with Altered Pre and Postsynaptic Markers of Serotonin Transmission in Neocortical Areas: A PET Study with [11C]DASB and [11C]MDL 100907

    PubMed Central

    Urban, Nina BL; Girgis, Ragy R; Talbot, Peter S; Kegeles, Lawrence S; Xu, X; Frankle, W Gordon; Hart, Carl L; Slifstein, Mark; Abi-Dargham, Anissa; Laruelle, Marc

    2012-01-01

    3,4-Methylenedioxymethamphetamine (MDMA), the main psychoactive component of the recreational drug ecstasy, is a potent serotonin (5-HT) releaser. In animals, MDMA induces 5-HT depletion and toxicity in 5-HT neurons. The aim of this study was to investigate both presynaptic (5-HT transporter, SERT) and postsynaptic (5-HT2A receptor) markers of 5-HT transmission in recently abstinent chronic MDMA users compared with matched healthy controls. We hypothesized that MDMA use is associated with lower SERT density and concomitant upregulation of 5-HT2A receptors. Positron emission tomography studies using the SERT ligand [11C]DASB and the 5-HT2A receptor ligand [11C]MDL 100907 were evaluated in 13 current and recently detoxified MDMA users and 13 matched healthy controls. MDMA users reported a mean duration of ecstasy use of 8 years, regular exposure, and at least 2 weeks of abstinence before the scans. SERT and 5-HT2A receptor availability (binding potential, BPND) were analyzed with a two-tissue compartment model with arterial input function. Current recreational MDMA use was significantly associated with lower SERT BPND and higher 5-HT2A receptor BPND in cortical, but not subcortical regions. Decreased SERT BPND was regionally associated with upregulated 5-HT2A receptor BPND. In light of the animal literature, the most parsimonious interpretation is that repeated exposure to MDMA in humans, even in moderate amounts, leads to damage in 5-HT neuron terminals innervating the cortex. Alterations in mood, cognition, and impulse control associated with these changes might contribute to sustain MDMA use. The reversibility of these changes upon abstinence remains to be firmly established. PMID:22353758

  16. Incentive learning for morphine-associated stimuli during protracted abstinence increases conditioned drug preference.

    PubMed

    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.

  17. “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

  18. 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

  19. Genetic and behavioral determinants of hippocampal volume recovery during abstinence from alcohol.

    PubMed

    Hoefer, Michael E; Pennington, David L; Durazzo, Timothy C; Mon, Anderson; Abé, Christoph; Truran, Diana; Hutchison, Kent E; Meyerhoff, Dieter J

    2014-11-01

    Alcohol-dependent individuals (ALC) have smaller hippocampi and poorer neurocognition than healthy controls. Results from studies on the association between alcohol consumption and hippocampal volume have been mixed, suggesting that comorbid or premorbid factors (i.e., those present prior to the initiation of alcohol dependence) determine hippocampal volume in ALC. We aimed to characterize the effects of select comorbid (i.e., cigarette smoking) and premorbid factors (brain-derived neurotrophic factor [BDNF] genotype [Val66Met rs6265]) on hippocampal volume in an ALC cohort followed longitudinally into extended abstinence. One hundred twenty-one adult ALC in treatment (76 smokers, 45 non-smokers) and 35 non-smoking light-drinking controls underwent quantitative magnetic resonance imaging, BDNF genotyping, and neurocognitive assessments. Representative subgroups were studied at 1 week, 1 month, and at an average of 7 months of abstinence. ALC had smaller hippocampi than healthy controls at all time points. Hippocampal volume at 1 month of abstinence correlated with lower visuospatial function. Smoking status did not influence hippocampal volume or hippocampal volume recovery during abstinence. However, only BDNF Val homozygotes tended to have hippocampal volume increases over 7 months of abstinence, and Val homozygotes had significantly larger hippocampi than Met carriers at 7 months of abstinence. These findings suggest that BDNF genotype, but not smoking status or measures of drinking severity, regulate functionally relevant hippocampal volume recovery in abstinent ALC. Future studies aimed at exploring genetic determinants of brain morphometry in ALC may need to evaluate individuals during extended abstinence after the acute environmental effects of chronic alcohol consumption have waned.

  20. 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.

  1. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2011-05-01

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

  4. 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

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

    PubMed

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

    2013-01-01

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

  6. Incubation of alcohol craving during abstinence in patients with alcohol dependence.

    PubMed

    Li, Peng; Wu, Ping; Xin, Xue; Fan, Yun-Li; Wang, Gui-Bin; Wang, Fan; Ma, Meng-Ying; Xue, Ming-Ming; Luo, Yi-Xiao; Yang, Fu-De; Bao, Yan-Ping; Shi, Jie; Sun, Hong-Qiang; Lu, Lin

    2015-05-01

    Time-dependent increases in cue-induced nicotine and methamphetamine craving during abstinence were recently reported in human drug-dependent individuals. In the present study, we sought to determine whether this 'incubation of craving' phenomenon also occurs in alcoholics. Four groups of 80 inpatient adult male alcoholics were assessed in a single session (between-group design) for cue-induced alcohol craving at 7, 14, 30 and 60 days of abstinence. Another group that included 19 patients was repeatedly tested for cue-induced alcohol craving at the same abstinence days as above. Other psychological and physiological measures were assessed at the four abstinence timepoints. Cue-induced alcohol craving measured with visual analogue scales was the highest at 60 days of abstinence both between and within groups. However, heart rate, blood pressure and skin conductance responses did not differ between abstinent groups. These results provide evidence of the incubation of alcohol craving in humans, extending previous reports with smokers and methamphetamine addicts. PMID:24698092

  7. Environmental enrichment and abstinence attenuate ketamine-induced cardiac and renal toxicity.

    PubMed

    Li, Xingxing; Li, Shuangyan; Zheng, Wenhui; Pan, Jian; Huang, Kunyu; Chen, Rong; Pan, Tonghe; Liao, Guorong; Chen, Zhongming; Zhou, Dongsheng; Shen, Wenwen; Zhou, Wenhua; Liu, Yu

    2015-06-26

    The current study was designed to investigate the effect of abstinence in combination with environmental enrichment (EE) on cardiac and renal toxicity induced by 2 weeks of ketamine self-administration (SA) in rodents. In Experiment 1, one group of rats underwent ketamine SA for 14 days. In Experiment 2, the animals completed 2 weeks of ketamine SA followed by 2 and 4 weeks of abstinence. In Experiment 3, animals underwent 14 days of ketamine SA and 4 weeks of abstinence in which isolated environment (IE) and EE was introduced. The corresponding control groups were included for each experiment. Two weeks of ketamine SA caused significant increases in organ weight, Apoptosis Stimulating Fragment/Kidney Injury Molecule-1, and apoptotic level of heart and kidney. The extended length of withdrawal from ketamine SA partially reduced toxicity on the heart and kidney. Finally, introduction of EE during the period of abstinence greatly promoted the effect of abstinence on ketamine-induced cardiac and renal toxicity. The interactive effect of EE and abstinence was promising to promote the recovery of cardiac and renal toxicity of ketamine.

  8. Transdermal nicotine patch enhances type I collagen synthesis in abstinent smokers.

    PubMed

    Sørensen, Lars T; Jorgensen, Lars N; Zillmer, Rikke; Vange, Jakob; Hemmingsen, Ulla; Gottrup, Finn

    2006-01-01

    Cigarette smokers deposit less collagen, expressed as hydroxyproline, in granulation tissue than nonsmokers. We studied the effect of abstinence from smoking and transdermal nicotine patches on deposition of hydroxyproline, proline, type I procollagen, and total proteins. Fifty-four healthy smokers were studied during 10 days of smoking and again from days 10 to 20 following smoking cessation. After the first 10 days of abstinence they were randomized to double-blind treatment with transdermal nicotine patches of 25 mg/day or placebo for a period of 10 days. During this period and during smoking, an expanded polytetrafluoroethylene tube was implanted into the subcutis. Following removal of the implant, total amino acids and peptides were extracted. Hydroxyproline and proline were analyzed by high-pressure liquid chromatography, type I procollagen was analyzed by enzyme-linked immunoassay, and total proteins were determined colorimetrically. In the 39 subjects who complied with the study protocol, abstinence from smoking did not affect the deposition of hydroxyproline, proline, type I procollagen, or total protein in the implants. During abstinence, the type I procollagen level increased by 18% in the transdermal nicotine patches group and decreased by 10% in the placebo group (p<0.05). We conclude that 20 days of abstinence from smoking does not affect collagen deposition in granulation tissue. However, in abstinent smokers, transdermal nicotine patches appears to increase type I collagen synthesis.

  9. Acute withdrawal, protracted abstinence and negative affect in alcoholism: Are they linked?

    PubMed Central

    Heilig, M.; Egli, M.; Crabbe, J.C.; Becker, H.C.

    2012-01-01

    The role of withdrawal-related phenomena in development and maintenance of alcohol addiction remains under debate. A “self-medication” framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that, in most patients, these symptoms abate over 3 – 6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: 1) Are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence? 2) Is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal? 3) To what extent is susceptibility to negative affect that persists into protracted abstinence heritable? PMID:20148778

  10. Internet-based group contingency management to promote abstinence from cigarette smoking: A feasibility study

    PubMed Central

    Meredith, Steven E.; Grabinski, Michael J.; Dallery, Jesse

    2011-01-01

    Background In contingency management (CM) interventions, monetary consequences are contingent on evidence of drug abstinence. Typically, these consequences are contingent on individual performance. Consequences contingent on group performance may promote social support (e.g., praise). Methods Thus, to combine social support with the monetary incentives of CM, we integrated independent and interdependent group contingencies of reinforcement into an Internet-based intervention to promote smoking abstinence. Breath carbon monoxide (CO) measures were compared between treatment conditions and a baseline control condition. Thirteen participants were divided into 5 groups or “teams” (n = 2–3 per team). Each participant submitted video recordings of CO measurement twice daily via the Internet. Teammates could monitor each other’s progress and communicate with one another through an online peer support forum. During a 4-day tapering condition, vouchers exchangeable for goods were contingent on gradual reductions in breath CO. During a 10-day abstinence induction condition, vouchers were contingent on abstinence (CO ≤4 ppm). In both treatment conditions, concurrent independent and interdependent group contingencies were arranged (i.e., a mixed contingency arrangement). Results Less than 1% of CO samples submitted during baseline were ≤4 ppm, compared to 57% submitted during abstinence induction. Sixty-five percent of participants’ comments on the online peer support forum were rated as positive by independent observers. Participants rated the intervention favorably on a treatment acceptability questionnaire. Conclusion The results suggest that the intervention is feasible and acceptable for promoting abstinence from cigarette smoking. PMID:21414733

  11. Incubation of alcohol craving during abstinence in patients with alcohol dependence.

    PubMed

    Li, Peng; Wu, Ping; Xin, Xue; Fan, Yun-Li; Wang, Gui-Bin; Wang, Fan; Ma, Meng-Ying; Xue, Ming-Ming; Luo, Yi-Xiao; Yang, Fu-De; Bao, Yan-Ping; Shi, Jie; Sun, Hong-Qiang; Lu, Lin

    2015-05-01

    Time-dependent increases in cue-induced nicotine and methamphetamine craving during abstinence were recently reported in human drug-dependent individuals. In the present study, we sought to determine whether this 'incubation of craving' phenomenon also occurs in alcoholics. Four groups of 80 inpatient adult male alcoholics were assessed in a single session (between-group design) for cue-induced alcohol craving at 7, 14, 30 and 60 days of abstinence. Another group that included 19 patients was repeatedly tested for cue-induced alcohol craving at the same abstinence days as above. Other psychological and physiological measures were assessed at the four abstinence timepoints. Cue-induced alcohol craving measured with visual analogue scales was the highest at 60 days of abstinence both between and within groups. However, heart rate, blood pressure and skin conductance responses did not differ between abstinent groups. These results provide evidence of the incubation of alcohol craving in humans, extending previous reports with smokers and methamphetamine addicts.

  12. Recovery of sexual function in abstinent alcoholic men.

    PubMed

    Van Thiel, D H; Gavaler, J S; Sanghvi, A

    1983-04-01

    Sixty chronically alcoholic men who were impotent and known to have abstained from alcohol were followed prospectively to determine (a) the frequency of spontaneous recovery of normal sexual functioning, (b) indicators of spontaneous recovery, and (c) the response of those who did not achieve a spontaneous recovery to agents known to interact with the hypothalamic-pituitary-gonadal axis. Twenty-five percent of the men studied experienced a spontaneous recovery. Indicators of a spontaneous recovery were absence of testicular atrophy and normal gonadotropin responses to luteinizing hormone releasing factor or clomiphene, or both. Interestingly, the severity of the biochemical or histologic liver disease at admission to study did not have value in predicting endocrine responses or recovery of sexual functioning with continued abstinence. Those not recovering spontaneously were treated sequentially with clomiphene, human chorionic gonadotropin, and an oral exogenous androgen, fluoxymesterone. Only the androgen produced acceptable results and then only at unusually high doses, suggesting some degree of androgen insensitivity in such men.

  13. Is resilience relevant to smoking abstinence for Indigenous Australians?

    PubMed

    Tsourtos, George; Ward, Paul R; Lawn, Sharon; Winefield, Anthony H; Hersh, Deborah; Coveney, John

    2015-03-01

    The prevalence rate of tobacco smoking remains high for Australian Indigenous people despite declining rates in other Australian populations. Given many Indigenous Australians continue to experience a range of social and economic structural problems, stress could be a significant contributing factor to preventing smoking abstinence. The reasons why some Indigenous people have remained resilient to stressful adverse conditions, and not rely on smoking to cope as a consequence, may provide important insights and lessons for health promotion policy and practice. In-depth interviews were employed to collect oral histories from 31 Indigenous adults who live in metropolitan Adelaide. Participants were recruited according to smoking status (non-smokers were compared with current smokers to gain a greater depth of understanding of how some participants have abstained from smoking). Perceived levels of stress were associated with encouraging smoking behaviour. Many participants reported having different stresses compared with non-Indigenous Australians, with some participants reporting having additional stressors such as constantly experiencing racism. Resilience often occurred when participants reported drawing upon internal psychological assets such as being motivated to quit and where external social support was available. These findings are discussed in relation to a recently developed psycho-social interactive model of resilience, and how this resilience model can be improved regarding the historical and cultural context of Indigenous Australians' experience of smoking.

  14. Neonatal Abstinence Syndrome Following Tianeptine Dependence During Pregnancy.

    PubMed

    Bence, Camille; Bonord, Alexandre; Rebillard, Camille; Vaast, Pascal; Alexandre, Charlotte; Jardri, Renaud; Rolland, Benjamin

    2016-01-01

    Tianeptine, an atypical antidepressant, has been found to exhibit a potential for abuse. The use of therapeutic doses of tianeptine during pregnancy has never raised safety concerns. However, the impact of tianeptine abuse on the mother-child dyad has never been assessed. We report herein the case of a female patient who presented with dependence on tianeptine, with the use of >650 mg of the drug per day. She had 2 successive pregnancies with similar doses. The state of dependence remained unidentified throughout the first pregnancy, but just after delivery, her full-term newborn exhibited unexpected neonatal abstinence syndrome (NAS). The NAS was successfully treated with morphine, although both the mother's and newborn's urine drug screen was negative. The causality of tianeptine in inducing NAS was retrospectively assessed as "probable" by using a validated causality algorithm. During the second pregnancy, this patient sought addiction treatment and was admitted for residential detoxification treatment in her seventh month of pregnancy. Delivery occurred at full term with a low birth weight neonate. No further developmental insults or medical problems were subsequently identified in the 2 children. Maternal tianeptine dependence during pregnancy may induce a type of NAS that mimics opiate NAS. This finding appears to be consistent with a recent finding of the agonist action of tianeptine on the opiate μ-receptor. PMID:26659818

  15. Neonatal Abstinence Syndrome Following Tianeptine Dependence During Pregnancy.

    PubMed

    Bence, Camille; Bonord, Alexandre; Rebillard, Camille; Vaast, Pascal; Alexandre, Charlotte; Jardri, Renaud; Rolland, Benjamin

    2016-01-01

    Tianeptine, an atypical antidepressant, has been found to exhibit a potential for abuse. The use of therapeutic doses of tianeptine during pregnancy has never raised safety concerns. However, the impact of tianeptine abuse on the mother-child dyad has never been assessed. We report herein the case of a female patient who presented with dependence on tianeptine, with the use of >650 mg of the drug per day. She had 2 successive pregnancies with similar doses. The state of dependence remained unidentified throughout the first pregnancy, but just after delivery, her full-term newborn exhibited unexpected neonatal abstinence syndrome (NAS). The NAS was successfully treated with morphine, although both the mother's and newborn's urine drug screen was negative. The causality of tianeptine in inducing NAS was retrospectively assessed as "probable" by using a validated causality algorithm. During the second pregnancy, this patient sought addiction treatment and was admitted for residential detoxification treatment in her seventh month of pregnancy. Delivery occurred at full term with a low birth weight neonate. No further developmental insults or medical problems were subsequently identified in the 2 children. Maternal tianeptine dependence during pregnancy may induce a type of NAS that mimics opiate NAS. This finding appears to be consistent with a recent finding of the agonist action of tianeptine on the opiate μ-receptor.

  16. 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

  17. Extended-release naltrexone modulates brain response to drug cues in abstinent heroin-dependent patients.

    PubMed

    Langleben, Daniel D; Ruparel, Kosha; Elman, Igor; Loughead, James W; Busch, Elliot L; Cornish, James; Lynch, Kevin G; Nuwayser, Elie S; Childress, Anna R; O'Brien, Charles P

    2014-03-01

    Drug cues play an important role in relapse to drug use. Naltrexone is an opioid antagonist that is used to prevent relapse in opioid dependence. Central opioidergic pathways may be implicated in the heightened drug cue-reactivity, but the effects of the opioid receptors' blockade on the brain responses to drug cues in opioid dependence are unknown. To pursue this question, we studied 17 abstinent i.v. heroin users with brain functional magnetic resonance imaging (fMRI) during exposure to visual heroin-related cues and matched neutral images before and 10-14 days after an injection of extended-release naltrexone (XRNTX). Whole brain analysis of variance of fMRI data showed main effect of XRNTX in the medial frontal gyrus, precentral gyrus, cuneus, precuneus, caudate and the amygdala. fMRI response was decreased in the amygdala, cuneus, caudate and the precentral gyrus and increased in the medial frontal gyrus and the precuneus. Higher plasma levels of naltrexone's major metabolite, 6-beta-naltrexol, were associated with larger reduction in the fMRI response to drug cues after XRNTX in the precentral, caudate and amygdala clusters. The present data suggest that XRNTX pharmacotherapy of opioid-dependent patients may, respectively, decrease and potentiate prefrontal and limbic cortical responses to drug cues and that this effect might be related to the XRNTX metabolism. Our findings call for further evaluation of the brain fMRI response to drug-related cues and of the 6-beta-naltrexol levels as potential biomarkers of XRNTX therapeutic effects in patients with opioid dependence.

  18. The effects of e-cigarette visual appearance on craving and withdrawal symptoms in abstinent smokers.

    PubMed

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

    2016-02-01

    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 sensorimotor 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. Sixty-three cigarette smokers (40% female, aged 18-65 years) who were not current e-cigarette users were randomly allocated to take ten 3-s puffs from either a white or a red first-generation e-cigarette following overnight abstinence. Current craving (urge to smoke) and nicotine withdrawal symptoms (using the Mood and Physical Symptoms Scale [MPSS]) were measured before and 10 min after use. Linear regression revealed higher craving and withdrawal symptoms in the red condition versus the white condition, but only among those who were e-cigarette naive (craving: B = .76, p = .009; withdrawal symptoms: B = 2.18, p = .009), not among those with e-cigarette experience (craving: B = -.08, p = .89; withdrawal symptoms: B = .24, p = .81), and these effects differed between groups (p = .04 and 0.01 for craving and withdrawal symptoms, respectively). In conclusion, cigarette-like appearance was associated with lower 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.

  19. Modeling naturalistic craving, withdrawal, and affect during early nicotine abstinence: a pilot EMA study

    PubMed Central

    Bujarski, Spencer; Roche, Daniel J.O.; Sheets, Erin S.; Krull, Jennifer L.; Guzman, Iris; Ray, Lara A.

    2015-01-01

    Despite the critical role of withdrawal, craving, and positive (PA) and negative affect (NA) in smoking relapse, relatively little is known about the temporal and predictive relationship between these constructs within the first day of abstinence. This pilot study aims to characterize dynamic changes in withdrawal, craving and affect over the course of early abstinence using ecological momentary assessment. Beginning immediately after smoking, moderate and heavy smoking participants (n = 15 per group) responded to hourly surveys assessing craving, withdrawal, NA, and PA. Univariate and multivariate multilevel random coefficient modeling was used to describe the progression of craving, withdrawal/NA and PA and to test correlations between these constructs at the subject-level over the course of early abstinence. Heavy smokers reported greater craving from 1–4 hours of abstinence and greater withdrawal/NA after 3 or more hours as compared to moderate smokers. Level of withdrawal/NA was strongly positively associated with craving, and PA was negatively correlated with craving, however the temporal dynamics of these correlations differed substantially. The association between withdrawal/NA and craving decreased over early abstinence, whereas the reverse was observed for PA. These findings can inform experimental studies of nicotine abstinence as well as their clinical applications to smoking cessation efforts. In particular, these results help to elucidate the role of PA in nicotine abstinence by demonstrating its independent association with nicotine craving over and above withdrawal/NA. If supported by future studies, these findings can refine experimental methods and clinical approaches for smoking cessation. PMID:25844632

  20. Borderline Personality Symptoms in Short-Term and Long-Term Abstinent Alcohol Dependence

    PubMed Central

    Fein, George; Nip, Vincent

    2011-01-01

    Background Comorbidity of Borderline Personality Disorder (BPD) and Substance and Alcohol Use Disorders (SUDs and AUDs is very high. The literature suggests a negative synergy between BPD and SUDs, which may impact an individual’s ability to achieve and maintain remission of either disorder in the face of the other. Methods We examined lifetime and current (past year) BPD symptom counts in three gender- and age-comparable groups: short-term abstinent alcoholics (STA, 6–15 weeks abstinent), long-term abstinent alcoholics (LTA, more than 18 months abstinent), and non-substance-abusing controls (NSAC). Abstinent individuals were recruited primarily from mutual-help recovery networks and about half had comorbid drug dependence. BPD symptoms were obtained using the SCID-II, followed up with questions regarding currency, but did not require that BPD symptoms represent persistent or pervasive behavior such as would meet criteria for BPD diagnosis. Thus our study dealt only with BPD symptoms, not BPD diagnoses. Results Alcoholics had more lifetime and current symptoms for most all BPD criteria than NSAC. In general, STA and LTA did not differ in BPD symptoms, except for a group-by-gender effect for both lifetime and current anger-associated symptoms and for lifetime abandonment-avoidance symptoms. For these cases, there were much higher symptom counts for STA women vs. men, with comparable symptom counts for LTA women vs. men. Conclusions Our results suggest for the most part that BPD symptoms do not prevent the maintenance of recovery in AUD and SUD individuals who have established at least six weeks abstinence within the mutual-help recovery network – in fact the presence of BPD symptoms is the norm. However, we did find difficulty in establishing longer-term abstinence in women with anger-associated symptoms and abandonment avoidance symptoms. PMID:22309234

  1. Smoking Abstinence and Depressive Symptoms Modulate the Executive Control System During Emotional Information Processing

    PubMed Central

    Froeliger, Brett; Modlin, Leslie A.; Kozink, Rachel V.; Wang, Lihong; McClernon, F. Joseph

    2011-01-01

    Background Smoking abstinence disrupts affective and cognitive processes. In this study, functional magnetic resonance imaging (fMRI) was used to investigate the effects of smoking abstinence on emotional information processing (EIP). Methods Smokers (n=17) and nonsmokers (n=18) underwent fMRI while performing an emotional distractor oddball task in which rare targets were presented following negative and neutral task-irrelevant distractors. Smokers completed two sessions: once following 24-hr abstinence and once while satiated. The abstinent versus satiated states were compared by evaluating responses to distractor images and to targets following each distractor valence within frontal executive and limbic brain regions. Regression analyses were done to investigate whether self-reported negative affect influences brain response to images and targets. Exploratory regression analyses examined relations between baseline depressive symptoms and smoking state on brain function. Results Smoking state affected response to target detection in the right inferior frontal gyrus (IFG). During satiety, activation was greater in response to targets following negative versus neutral distractors; following abstinence, the reverse was observed. Withdrawal-related negative affect was associated with right insula activation to negative images. Finally, depression symptoms were associated with abstinence-induced hypoactive response to negative emotional distractors and task-relevant targets following negative distractors in frontal brain regions. Conclusions Neural processes related to novelty detection/attention in the right IFG may be disrupted by smoking abstinence and negative stimuli. Reactivity to emotional stimuli and the interfering effects on cognition are moderated by the magnitude of smoking state-dependent negative affect and baseline depressive symptoms. PMID:22081878

  2. Increased impulsivity in rats as a result of repeated cycles of alcohol intoxication and abstinence

    PubMed Central

    Irimia, Cristina; Wiskerke, Joost; Natividad, Luis A.; Polis, Ilham Y.; de Vries, Taco J.; Pattij, Tommy; Parsons, Loren H.

    2014-01-01

    Impulsivity is a risk factor for alcoholism and long-term alcohol exposure may further impair impulse control in a manner that propels problematic alcohol use. The present study employed the rat 5-Choice Serial Reaction Time Task (5-CSRTT) to measure behavioral inhibition and attentional capacity during abstinence from repeated 5d cycles of alcohol liquid diet consumption. Task performance was not disrupted following the first cycle of alcohol exposure, however, evidence of impaired behavioral inhibition emerged following the third cycle of alcohol exposure. In comparison with controls, alcohol rats exhibited deficits in inhibitory control during cognitively challenging 5-CSRTT tests employing variable inter-trial intervals (varITI). This behavioral disruption was not present during early abstinence (3d) but was evident by 7d abstinence and persisted for at least 34d. Interestingly, renewed alcohol consumption ameliorated these disruptions in impulse control, though deficient behavioral inhibition re-emerged during subsequent abstinence. Indices of increased impulsivity were no longer present in tests conducted after 49 days of abstinence. Alcohol-related impairments in impulse control were not evident in sessions employing highly familiar task parameters regardless of abstinence period and control experiments confirmed that performance deficits during the challenge sessions were unlikely to result from alcohol-related disruption in the adaptation to repeated varITI testing. Together, the current findings demonstrate that chronic intermittent alcohol consumption results in decreased behavioral inhibition in rats that is temporally similar to clinical observations of disrupted impulsive control in abstinent alcoholics performing tasks of behavioral inhibition. PMID:24341858

  3. Modeling naturalistic craving, withdrawal, and affect during early nicotine abstinence: A pilot ecological momentary assessment study.

    PubMed

    Bujarski, Spencer; Roche, Daniel J O; Sheets, Erin S; Krull, Jennifer L; Guzman, Iris; Ray, Lara A

    2015-04-01

    Despite the critical role of withdrawal, craving, and positive affect (PA) and negative affect (NA) in smoking relapse, relatively little is known about the temporal and predictive relationship between these constructs within the first day of abstinence. This pilot study aims to characterize dynamic changes in withdrawal, craving, and affect over the course of early abstinence using ecological momentary assessment. Beginning immediately after smoking, moderate and heavy smoking participants (n = 15 per group) responded to hourly surveys assessing craving, withdrawal, NA, and PA. Univariate and multivariate multilevel random coefficient modeling was used to describe the progression of craving, withdrawal/NA, and PA and to test correlations between these constructs at the subject level over the course of early abstinence. Heavy smokers reported greater craving from 1-4 hr of abstinence and greater withdrawal/NA after 3 or more hours as compared with moderate smokers. Level of withdrawal/NA was strongly positively associated with craving, and PA was negatively correlated with craving; however, the temporal dynamics of these correlations differed substantially. The association between withdrawal/NA and craving decreased over early abstinence, whereas the reverse was observed for PA. These findings can inform experimental studies of nicotine abstinence as well as their clinical applications to smoking cessation efforts. In particular, these results help to elucidate the role of PA in nicotine abstinence by demonstrating its independent association with nicotine craving over and above withdrawal/NA. If supported by future studies, these findings can refine experimental methods and clinical approaches for smoking cessation.

  4. Resurgence of instrumental behavior after an abstinence contingency.

    PubMed

    Bouton, Mark E; Schepers, Scott T

    2014-06-01

    In resurgence, an extinguished instrumental behavior (R1) recovers when a behavior that has replaced it (R2) is also extinguished. The phenomenon may be relevant to understanding relapse that can occur after the termination of "contingency management" treatments, in which an unwanted behavior (e.g., substance abuse) is reduced by reinforcing an alternative behavior. When reinforcement is discontinued, the unwanted behavior might resurge. However, unlike most resurgence experiments, contingency management treatments also introduce a negative contingency, in which reinforcers are not delivered unless the client has abstained from the unwanted behavior. In two experiments with rats, we therefore examined the effects of adding a negative "abstinence" contingency to the resurgence design. During response elimination, R2 was not reinforced unless R1 had not been emitted for a minimum period of time (45, 90, or 135 s). In both experiments, adding such a contingency to simple R1 extinction reduced, but did not eliminate, resurgence. In Experiment 2, we found the same effect in a yoked group that could earn reinforcers for R2 at the same points in time as the negative-contingency group, but without the requirement to abstain from R1. Thus, the negative contingency per se did not contribute to the reduction in resurgence. These results suggest that the contingency reduced resurgence by making reinforcers more difficult to earn and more widely spaced in time. This could have allowed the animal to learn that R1 was extinguished in the "context" of infrequent reinforcement-a context more like that of resurgence testing. The results are thus consistent with a contextual (renewal) account of resurgence. The method might provide a better model of relapse after termination of a contingency management treatment. PMID:24366673

  5. Variations in Opioid Receptor Genes in Neonatal Abstinence Syndrome*

    PubMed Central

    Wachman, Elisha M; Hayes, Marie J; Sherva, Richard; Brown, Mark S; Davis, Jonathan M; Farrer, Lindsay A; Nielsen, David A

    2015-01-01

    Background There is significant variability in the severity of neonatal abstinence syndrome (NAS) due to in-utero opioid exposure. We wanted to determine if single nucleotide polymorphisms (SNPs) in key candidate genes contribute to this variability. Methods Full-term opioid-exposed newborns and their mothers (n=86 pairs) were studied. DNA was genotyped for 80 SNPs from 14 genes utilizing a custom designed microarray. The association of each SNP with NAS outcomes was evaluated. Results SNPs in two opioid receptor genes in the infants were associated with worse NAS severity: 1) The PNOC rs732636 A allele (OR=3.8, p=0.004) for treatment with 2 medications and a longer hospital stay (LOS) of 5.8 days (p=0.01), and 2) The OPRK1 rs702764 C allele (OR=4.1, p=0.003) for treatment with 2 medications. The OPRM1 rs1799971 G allele (β= −6.9 days, p=0.02) and COMT rs740603 A allele (β= −5.3 days, p=0.01) were associated with shorter LOS. The OPRD1 rs204076 A allele in the mothers was associated with a longer LOS by 6.6 days (p=0.008). Results were significant point-wise but did not meet the experiment-wide significance level. Conclusions These findings suggest that SNPs in opioid receptor and the PNOC genes are associated with NAS severity. However, further testing in a large sample is warranted. This has important implications for prenatal prediction and personalized treatment regimens for infants at highest risk for severe NAS. PMID:26233486

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

    PubMed

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

    2003-07-01

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

  7. Human Ecstasy Use is Associated with Increased Cortical Excitability: An fMRI Study

    PubMed Central

    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

    2011-01-01

    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 (rs=0.59; p=0.007), BA 17 (rs=0.50; p=0.027), and BA 18 (rs=0.48; p=0.031), and with the spatial extent of activation in BA 17 (rs=0.059; p=0.007) and BA 18 (rs=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

  8. Factors influencing abstinence, anticipation, and delay of sex among adolescent boys in high-STI prevalence communities

    PubMed Central

    Cummings, Teresa; Auerswald, Colette L.; Ott, Mary A.

    2013-01-01

    Purpose Abstinence is a core pregnancy and STI prevention strategy. We explore the attitudinal, behavioral, and family contexts relating to abstinence and the decision to delay sex among adolescent boys. Methods Adolescent boys ages 14–17 were recruited from community sites using a venue-based sampling method. All eligible boys at venues were invited to participate in an electronic survey. Question items included sexual behaviors, attitudes related to sex, relationships, masculine values, and family contextual items. Results We enrolled 667 participants, age 15.7 years, of diverse ethnicity. 252 (38%) were abstinent. Abstinent participants were younger, less likely to report non-coital behaviors, and reported lower conventional masculine values. Among abstinent participants, 62% planned to delay sex, while 38% anticipated sex in the next year. Participants with lower conventional masculine values, and more religious or moral motivations for abstinence were more likely to plan to delay sex. Discussion Abstinence among boys is common, even in high STI risk communities. For these boys, abstinence appears to be a complex behavioral decision, influenced by demographic, behavioral, attitudinal and contextual factors such as age, race, non-coital sexual behaviors and masculine values. Understanding the attitudes and contexts of abstinence, including plans to delay sex, can inform the development of public health programs for early fatherhood and STI prevention. PMID:24355627

  9. 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.

  10. Effects of Smoking Abstinence on Cigarette Craving, Nicotine Withdrawal, and Nicotine Reinforcement in Smokers With and Without Schizophrenia

    PubMed Central

    2014-01-01

    Introduction: Schizophrenia is associated with a high prevalence of cigarette smoking. The aims of this study were to compare smokers with schizophrenia (SS) and control smokers without psychiatric illness (CS) on (a) cigarette craving and nicotine withdrawal symptom severity during a 72-hr smoking abstinence period; (b) nicotine reinforcement, before and after abstinence; and (c) latency to smoking lapse following abstinence. We also explored mediators of smoking lapse in SS and CS. Methods: SS (n = 28) and CS (n = 27) underwent a nicotine versus denicotinized cigarette puff choice task before and after a 72-hr period of smoking abstinence that was experimentally controlled by providing cash reinforcement contingent on biochemical verification of abstinence. Twenty-four hours after the second choice task, participants could receive a low-value reinforcer if they had continued to abstain since the previous day. Those who remained abstinent were recontacted a week later to determine time of their smoking lapse. Results: SS reported more severe cigarette craving and nicotine withdrawal symptoms throughout the 72-hr abstinence period, had greater nicotine preference after abstinence, and lapsed back to smoking significantly sooner than CS. The relationship between group and smoking lapse latency was mediated by baseline depression and nicotine withdrawal symptom severity but not by effects of abstinence on craving or nicotine reinforcement. Conclusions: Overall, these results indicate that negative affect is a key contributor to poor smoking cessation outcomes among those with schizophrenia. PMID:24113929

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

    PubMed

    Doblin, Rick

    2002-01-01

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2014-08-01

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

  14. Understanding Motivations for Abstinence among Adolescent Young Women: Insights into Effective Sexual Risk Reduction Strategies

    PubMed Central

    Long-Middleton, Ellen R.; Burke, Pamela J.; Lawrence, Cheryl A. Cahill; Blanchard, Lauren B.; Amudala, Naomi H.; Rankin, Sally H.

    2012-01-01

    Introduction Pregnancy and sexually transmitted infections pose a significant threat to the health and wellbeing of adolescent young women. Abstinence when practiced provides the most effective means in preventing these problems, yet the perspective of abstinent young women is not well understood. The purpose of the investigation was to characterize female adolescents’ motivations for abstinence. Method As part of a larger, cross-sectional quantitative study investigating predictors of HIV risk reduction behaviors, qualitative responses from study participants who never had intercourse were analyzed in a consensus-based process using content analysis and frequency counts. An urban primary care site in a tertiary care center served as the setting, with adolescent young women ages 15–19 years included in the sample. Results Five broad topic categories emerged from the data that characterized motivations for abstinence in this sample: 1) Personal Readiness, 2) Fear, 3) Beliefs and Values, 4) Partner Worthiness and 5) Lack of Opportunity. Discussion A better understanding of the motivations for abstinence may serve to guide the development of interventions to delay intercourse. PMID:22525893

  15. 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

  16. Belief about drug assignment and abstinence in treatment of cigarette smoking using nortriptyline.

    PubMed

    Hall, Sharon M; Gorecki, Julie A; Reus, Victor I; Humfleet, Gary L; Muñoz, Ricardo F

    2007-04-01

    This study assessed the relationship between beliefs about drug assignment and abstinence status in two treatment studies using nortriptyline hydrochloride as an adjunct to smoking cessation. Smokers (N = 345) drawn from two clinical trials were asked at the final follow-up (FFU) at 52 or 64 weeks whether they believed they had received active or placebo drug. Responses were obtained from 262 participants, or 76% of the sample. Biochemically verified abstinence was collected at end of treatment (EOT) and FFU. In both studies, participants were correct in guessing drug assignment. At FFU, belief about drug assignment was not related to abstinence for either active or placebo participants. Participants who received active drug and who were smoking at EOT were more likely to believe they had received placebo than active drug participants who were abstinent at EOT. We found no significant relationship between belief about drug and abstinence status for placebo participants at EOT. Baseline variables did not significantly predict correctness of drug identification. Participants who experienced drug side-effects not easily attributable to nicotine withdrawal were more likely to identify their drug assignment as nortriptyline. We conclude that experience during the active treatment period, including side-effects and treatment success, may be related to belief about drug assignment, that the field would be well served by at least two assessments of blindness in clinical trials, and that discrepancy between these findings and those regarding nicotine replacement therapy may be related to differences in dependent variables. PMID:17454701

  17. 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.

  18. The link between postnatal abstinence and extramarital sex in Côte d'Ivoire.

    PubMed

    Ali, M M; Cleland, J G

    2001-09-01

    Whether the link, found in Benin, between postnatal abstinence and husbands' extramarital contacts can be generalized to other West African countries is assessed in this study. Data from the 1994 Demographic and Health Survey, Côte d'Ivoire, obtained from monogamous husbands concerning their extramarital sexual behavior in the two months preceding the survey were linked to data reported by wives concerning postnatal abstinence over the same time period. Logistic regression was applied to assess the link between these two factors, net of the effects of possible confounders. A significant effect of postnatal abstinence on the probability that the husband reported at least one extramarital partner was found. Unprotected extramarital sex was two times more common among men who observed conjugal abstinence than it was among other men. Other predictors of extramarital sex were urban-rural residence, region, education, and whether or not husband and wife had the same religious affiliation. Because condom use is low in this population, the protective effect of marital abstinence is offset by an increased probability that husbands will seek extramarital partners during the postpartum period. The results confirm the earlier findings for Benin and can likely be generalized to most of West Africa.

  19. Amount of earnings during prize contingency management treatment is associated with posttreatment abstinence outcomes.

    PubMed

    Petry, Nancy M; Roll, John M

    2011-12-01

    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 pretreatment 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. The human startle reflex and alcohol cue reactivity: effects of early versus late abstinence.

    PubMed

    Saladin, Michael E; Drobes, David J; Coffey, Scott F; Libet, Julian M

    2002-06-01

    This study investigated the human eyeblink startle reflex as a measure of alcohol cue reactivity. Alcohol-dependent participants early (n = 36) and late (n = 34) in abstinence received presentations of alcohol and water cues. Consistent with previous research, greater salivation and higher ratings of urge to drink occurred in response to the alcohol cues. Differential salivary and urge responding to alcohol versus water cues did not vary as a function of abstinence duration. Of special interest was the finding that startle response magnitudes were relatively elevated to alcohol cues, but only in individuals early in abstinence. Affective ratings of alcohol cues suggested that alcohol cues were perceived as aversive. Methodological and theoretical implications of the findings are discussed.

  5. 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

  6. 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

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

    NASA Astrophysics Data System (ADS)

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

    2004-01-01

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

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

    PubMed

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

    1997-05-01

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

  9. 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

  10. Brain-derived neurotrophic factor serum levels in cocaine-dependent patients during early abstinence.

    PubMed

    Corominas-Roso, Margarida; Roncero, Carlos; Eiroa-Orosa, Francisco Jose; Gonzalvo, Begoña; Grau-Lopez, Lara; Ribases, Marta; Rodriguez-Cintas, Laia; Sánchez-Mora, Cristina; Ramos-Quiroga, Josep-Antoni; Casas, Miguel

    2013-09-01

    Preclinical studies indicate that brain-derived neurotrophic factor (BDNF) is involved in neuroplastic changes underlying enduring cocaine-seeking following withdrawal. However, little is known about temporal changes in serum BDNF levels or the involvement of BDNF in craving and abstinence in early-abstinent cocaine-dependent patients. Twenty-three cocaine-dependent individuals (aged 33.65 ± 6.85 years) completed a two-week detoxification program at an inpatient facility. Two serum samples were collected for each patient at baseline and at the end of the protocol. Serum samples were also collected for 46 healthy controls (aged 35.52 ± 9.37 years). Demographic, consumption and clinical data were recorded for all patients. Significantly lower serum BDNF levels (p<.0001) were observed for cocaine-dependent patients at baseline compared to healthy controls. Serum BDNF levels increased significantly across 12 days of early abstinence (p=.030). Baseline BDNF levels correlated with craving (p=.034). Post-detoxification BDNF levels correlated with craving (p=.018), loss of control (p<.000), abstinence measures (p=0.031), depression (p=0.036), and anxiety (p=0.036). Post-detoxification BDNF levels also had predictive value for the loss of control measure of craving. Chronic cocaine use is associated with decreased serum BDNF. A progressive increase in serum BDNF levels during early abstinence correlates with cocaine craving and abstinence symptoms and may reflect increasing BDNF levels in different brain regions. These findings suggest that serum BDNF may be a biomarker for cocaine addiction. PMID:23021567

  11. 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.

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

    PubMed Central

    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.

    2016-01-01

    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

  13. 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.

  14. Three year continuous abstinence in a smoking cessation study using the nicotine transdermal patch.

    PubMed

    Richmond, R L; Kehoe, L; de Almeida Neto, A C

    1997-12-01

    A total of 305 subjects from Sydney were randomly allocated to receive either an active (24 hour transdermal nicotine patch over a 10 week course) or placebo nicotine patch. All subjects participated in a multicomponent cognitive-behavioural smoking cessation programme over five weeks in two-hour group sessions. The continuous abstinence rates at three years (validated by expired carbon monoxide) were 13.8% for the active group and 5.2% for placebo group (p = 0.011). The active nicotine patch with behavioural therapy achieved more than double the abstinence rates early in treatment compared with placebo and this difference was maintained throughout the three year follow up.

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

    PubMed

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

    2014-12-01

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

  16. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier integrity through a mechanism involving P2X7 receptors.

    PubMed

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

    2014-08-01

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

  17. 3,4-methylenedioxymethamphetamine (MDMA) interacts with therapeutic drugs on CYP3A by inhibition of pregnane X receptor (PXR) activation and catalytic enzyme inhibition.

    PubMed

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

    2011-05-30

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

  18. 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…

  19. 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,…

  20. 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

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

    PubMed

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

    2015-01-01

    3,4-Methylenedioxymethamphetamine (MDMA), also known as "Ecstasy", is a common recreational drug of abuse. Several previous studies have attributed the central serotonergic neurotoxicity of MDMA to distal axotomy, since only fine serotonergic axons ascending from the raphe nucleus are lost without apparent damage to their cell bodies. However, this axotomy has never been visualized directly in vivo. The present study examined the axonal integrity of the efferent projections from the midbrain raphe nucleus after MDMA exposure using in vivo manganese-enhanced magnetic resonance imaging (MEMRI). Rats were injected subcutaneously six times with MDMA (5 mg/kg) or saline once daily. Eight days after the last injection, manganese ions (Mn2+) were injected stereotactically into the raphe nucleus, and a series of MEMRI images was acquired over a period of 38 h to monitor the evolution of Mn2+-induced signal enhancement across the ventral tegmental area, the medial forebrain bundle (MFB), and the striatum. The MDMA-induced loss of serotonin transporters was clearly evidenced by immunohistological staining consistent with the Mn2+-induced signal enhancement observed across the MFB and striatum. MEMRI successfully revealed the disruption of the serotonergic raphe-striatal projections and the variable effect of MDMA on the kinetics of Mn2+ accumulation in the MFB and striatum. PMID:26378923

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Parrott, Andrew C

    2014-03-01

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

  4. 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.

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

    PubMed

    Parrott, Andrew C

    2014-03-01

    Human Psychopharmacology recently published my review into the increase in empirical knowledge about the human psychobiology of MDMA over the past 25 years (Parrott, 2013a). Deficits have been demonstrated in retrospective memory, prospective memory, higher cognition, complex visual processing, sleep architecture, sleep apnoea, pain, neurohormonal activity, and psychiatric status. Neuroimaging studies have shown serotonergic deficits, which are associated with lifetime Ecstasy/MDMA usage, and degree of neurocognitive impairment. Basic psychological skills remain intact. Ecstasy/MDMA use by pregnant mothers leads to psychomotor impairments in the children. Hence, the damaging effects of Ecstasy/MDMA were far more widespread than was realized a few years ago. In their critique of my review, Doblin et al. (2014) argued that my review contained misstatements, omitted contrary findings, and recited dated misconceptions. In this reply, I have answered all the points they raised. I have been able to refute each of their criticisms by citing the relevant empirical data, since many of their points were based on inaccurate summaries of the actual research findings. Doblin and colleagues are proponents of the use of MDMA for drug-assisted psychotherapy, and their strongest criticisms were focused on my concerns about this proposal. However, again all the issues I raised were based on sound empirical evidence or theoretical understanding. Indeed I would recommend potentially far safer co-drugs such as D-cycloserine or oxytocin. In summary, MDMA can induce a wide range of neuropsychobiological changes, many of which are damaging to humans. PMID:24590542

  6. Attendance rates in a workplace predict subsequent outcome of employment-based reinforcement of cocaine abstinence in methadone patients.

    PubMed

    Donlin, Wendy D; Knealing, Todd W; Needham, Mick; Wong, Conrad J; Silverman, Kenneth

    2008-01-01

    This study assessed whether attendance rates in a workplace predicted subsequent outcome of employment-based reinforcement of cocaine abstinence. Unemployed adults in Baltimore methadone programs who used cocaine (N=111) could work in a workplace for 4 hr every weekday and earn $10.00 per hour in vouchers for 26 weeks. During an induction period, participants provided urine samples but could work independent of their urinalysis results. After the induction period, participants had to provide urinalysis evidence of cocaine abstinence to work and maintain maximum pay. A multiple regression analysis showed that induction period attendance was independently associated with urinalysis evidence of cocaine abstinence under the employment-based abstinence reinforcement contingency. Induction period attendance may measure the reinforcing value of employment and could be used to guide the improvement of employment-based abstinence reinforcement.

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

    PubMed

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

    2015-02-01

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

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

    PubMed

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

    2008-05-01

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

  9. 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…

  10. The effects of fixed versus escalating reinforcement schedules on smoking abstinence.

    PubMed

    Romanowich, Paul; Lamb, R J

    2015-01-01

    Studies indicate that when abstinence is initiated, escalating reinforcement schedules maintain continuous abstinence longer than fixed reinforcement schedules. However, these studies were conducted for shorter durations than most clinical trials and also resulted in larger reinforcer value for escalating participants during the 1st week of the experiment. We tested whether escalating reinforcement schedules maintained abstinence longer than fixed reinforcement schedules in a 12-week clinical trial. Smokers (146) were randomized to an escalating reinforcement schedule, a fixed reinforcement schedule, or a control condition. Escalating reinforcement participants received $5.00 for their first breath carbon monoxide (CO) sample <3 ppm, with a $0.50 increase for each consecutive sample. Fixed reinforcement participants received $19.75 for each breath CO sample <3 ppm. Control participants received payments only for delivering a breath CO sample. Similar proportions of escalating and fixed reinforcement participants met the breath CO criterion at least once. Escalating reinforcement participants maintained criterion breath CO levels longer than fixed reinforcement and control participants. Similar to previous short-term studies, escalating reinforcement schedules maintained longer durations of abstinence than fixed reinforcement schedules during a clinical trial.

  11. 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…

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

    PubMed Central

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

    2012-01-01

    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 586 (~5%) 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

  13. 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…

  14. 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…

  15. 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…

  16. 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…

  17. Persistent variations in neuronal DNA methylation following cocaine self-administration and protracted abstinence in mice

    PubMed Central

    Zhao, Qiongyi; Li, Xiang; Jupp, Bianca; Chesworth, Rose; Lawrence, Andrew J.; Bredy, Timothy

    2016-01-01

    Continued vulnerability to relapse during abstinence is characteristic of cocaine addiction and suggests that drug-induced neuroadaptations persist during abstinence. However, the precise cellular and molecular attributes of these adaptations remain equivocal. One possibility is that cocaine self-administration leads to enduring changes in DNA methylation. To address this possibility, we isolated neurons from medial prefrontal cortex and performed high throughput DNA sequencing to examine changes in DNA methylation following cocaine self-administration. Twenty-nine genomic regions became persistently differentially methylated during cocaine self-administration, and an additional 28 regions became selectively differentially methylated during abstinence. Altered DNA methylation was associated with isoform-specific changes in the expression of co-localizing genes. These results provide the first neuron-specific, genome-wide profile of changes in DNA methylation induced by cocaine self-administration and protracted abstinence. Moreover, our findings suggest that altered DNA methylation facilitates long-term behavioral adaptation in a manner that extends beyond the perpetuation of altered transcriptional states. PMID:27213137

  18. 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

    ... From the Federal Register Online via the Government Publishing Office OFFICE OF NATIONAL DRUG CONTROL POLICY Leadership Meeting on Maternal, Fetal, and Infant Opioid Exposure and Neonatal Abstinence Syndrome AGENCY: Office of National Drug Control Policy. ACTION: Notice. SUMMARY: An ONDCP...

  19. Cognitive-Behavioral Intervention Increases Abstinence Rates for Depressive-History Smokers.

    ERIC Educational Resources Information Center

    Hall, Sharon M.; And Others

    1994-01-01

    Tested hypothesis that cognitive-behavioral mood management intervention would be effective for smokers with history of major depressive disorder (MDD). Findings from 149 smokers, 31% of whom had history of MDD, revealed that history-positive subjects were more likely to be abstinent when treated with mood management; treatment condition…

  20. 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.…

  1. 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…

  2. 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…

  3. Morphine causes persistent induction of nitrated neurofilaments in cortex and subcortex even during abstinence.

    PubMed

    Pal, A; Das, S

    2015-04-16

    Morphine has a profound role in neurofilament (NF) expression. However, there are very few studies on the fate of NFs during morphine abstinence coinciding with periods of relapse. Mice were treated chronically with morphine to render them tolerant to and dependent on morphine and sacrificed thereafter while another group, treated similarly, was left for 2 months without morphine. A long-lasting alteration in the stoichiometric ratio of the three NFs was observed under both conditions in both the cortex and subcortex. Morphine abstinence caused significant alterations in the phosphorylated and nitrated forms of the three NF subunits. Nitrated neurofilament light polypeptide chain (NFL) was significantly increased during chronic morphine treatment which persisted even after 2 months of morphine withdrawal. Mass spectrometric analysis following two-dimensional gel electrophoresis (2DE)-gel electrophoresis of cytoskeleton fractions of both cortex and subcortex regions identified enzymes associated with energy metabolism, cytoskeleton-associated proteins as well as NFs which showed sustained regulation even after abstinence of morphine for 2 months. It is suggestive that alteration in the levels of some of these proteins may be instrumental in the increased nitration of NFL during morphine exposure. Such gross alteration in NF dynamics is indicative of a concerted biological process of neuroadaptation during morphine abstinence.

  4. 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…

  5. 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

  6. Involvement in a Drug Subculture and Abstinence Following Treatment Among Puerto Rican Narcotic Addicts.

    ERIC Educational Resources Information Center

    Snarr, Richard W.; Ball, John C.

    The study investigated the life career of a sample of native Puerto Rican narcotic addicts who were treated at the Lexington, Kentucky Public Health Service Hospital. Specifically, it deals with the relationship between the addicts' involvement in a drug subculture and their subsequent drug use and abstinence. The hypothesis presented states that…

  7. 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…

  8. 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…

  9. Attributional Processes in Behavior Change and Maintenance: Smoking Cessation and Continued Abstinence.

    ERIC Educational Resources Information Center

    Harackiewicz, Judith M.; And Others

    1987-01-01

    Examined the role of attributions in initial and long-term smoking behavior change. Manipulated the externality of treatment. Subjects receiving nicotine gum were superior to the intrinsic self-help group in initial cessation but were inferior in maintaining abstinence. Subjects in the intrinsic self-help group made fewer external attributions for…

  10. 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…

  11. 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

  12. Psychosocial stress enhances non-drug-related positive memory retrieval in male abstinent heroin addicts.

    PubMed

    Zhao, Li-Yan; Shi, Jie; Zhang, Xiao-Li; Lu, Lin

    2010-11-12

    Stress exposure in addicted individuals is known to provoke drug craving, presumably through a memory-like process, but less is known about the effects of stress on non-drug-related affective memory retrieval per se in such individuals, which is likely to provide important insights into therapy for relapse. In present study, we explored the effect of stress on retrieval of neutral and emotionally valenced (positive and negative) words in abstinent heroin addicts. In present study, 28 male inpatient abstinent heroin addicts and 20 sex-, age-, education- and economic status-matched healthy control participants were assessed for 24h delayed recall of valenced and neutral word lists on two occasions 4 weeks apart-once in a nonstress control condition, once after exposure to the Trier Social Stress Test in a counterbalanced design. In addition, attention, working memory, blood pressure, heart rate and salivary cortisol were assessed. We found acute stress at the time of word list recall enhanced retrieval of positively valenced words, but no effect on negative and neutral word retrieval in abstinent heroin addicts was observed. No changes were detected for attention and working memory. The stressor induced a significant increase in salivary free cortisol, blood pressure and heart rate. Stress can enhance non-drug-related positive memory in abstinent heroin addicts. Our findings will provide richer information in understanding dysregulation of their emotional memory processing under stress and hopefully provide insight into designing improved treatments for drug addiction.

  13. 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.

  14. 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

    2015-06-17

    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.

  15. 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…

  16. 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…

  17. 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…

  18. 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…

  19. 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…

  20. 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

  1. The Effectiveness of Abstinence Education Programs in Reducing Sexual Activity among Youth. The Heritage Foundation Backgrounder.

    ERIC Educational Resources Information Center

    Rector, Robert

    Teenage sexual activity is a major problem confronting the nation and has led to a rising incidence of sexually transmitted diseases, emotional and psychological injuries, and out-of-wedlock childbearing. Abstinence education programs for youth have proven effective in reducing early sexual activity. They can also provide the foundation for…

  2. 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…

  3. THE EFFECTS OF FIXED VERSUS ESCALATING REINFORCEMENT SCHEDULES ON SMOKING ABSTINENCE

    PubMed Central

    Romanowich, Paul; Lamb, R. J.

    2015-01-01

    Studies indicate that when abstinence is initiated, escalating reinforcement schedules maintain continuous abstinence longer than fixed reinforcement schedules. However, these studies were conducted for shorter durations than most clinical trials and also resulted in larger reinforcer value for escalating participants during the 1st week of the experiment. We tested whether escalating reinforcement schedules maintained abstinence longer than fixed reinforcement schedules in a 12-week clinical trial. Smokers (146) were randomized to an escalating reinforcement schedule, a fixed reinforcement schedule, or a control condition. Escalating reinforcement participants received $5.00 for their first breath carbon monoxide (CO) sample <3 ppm, with a $0.50 increase for each consecutive sample. Fixed reinforcement participants received $19.75 for each breath CO sample <3 ppm. Control participants received payments only for delivering a breath CO sample. Similar proportions of escalating and fixed reinforcement participants met the breath CO criterion at least once. Escalating reinforcement participants maintained criterion breath CO levels longer than fixed reinforcement and control participants. Similar to previous short-term studies, escalating reinforcement schedules maintained longer durations of abstinence than fixed reinforcement schedules during a clinical trial. PMID:25640764

  4. A Preliminary Evaluation of an Abstinence-Oriented Empowerment Program for Public School Youth

    ERIC Educational Resources Information Center

    Abel, Eileen Mazur; Greco, Michele

    2008-01-01

    Objective: This article describes the process and outcomes of an abstinence-orientated empowerment program that was delivered to an adolescent multicultural population. Method: The study employed a time-limited pretest-posttest OXO design with an N of 130 drawn from youth in public schools from fifth grade to ninth grade. A paired-samples t test…

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

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

    PubMed

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

    2013-09-01

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

  11. 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 a