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Sample records for sustained cocaine abstinence

  1. Cocaine and Sleep: Early Abstinence

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    Peter T. Morgan

    2007-01-01

    Full Text Available Compulsive cocaine use is associated with a profound dysregulation of sleep. Perhaps the result of chronic use, a significant deterioration in sleep is apparent over the first 3 weeks of abstinence, with no indication of recovery. Interestingly, the diminished sleep is not accompanied by subjective reports of poor or worsening sleep. Rather, subjective reports actually improve over abstinence, while sleep-related cognitive performance declines. A mechanistic understanding of the apparent difference in objective and subjective measures is currently lacking. Here we review the relevant literature on cocaine use and sleep, and discuss the possible relevance of this sleep disturbance in relationship to the underlying disorder and its treatment.

  2. Neuropsychological performance of recently abstinent alcoholics and cocaine abusers.

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    Beatty, W W; Katzung, V M; Moreland, V J; Nixon, S J

    1995-03-01

    To examine possible influences of premorbid and comorbid factors on the neuropsychological test performance of recently abstinent (3-5 weeks) drug abusers, we studied 24 alcoholics, 23 cocaine abusers, and 22 healthy controls of comparable age and education. Both alcoholics and cocaine abusers performed significantly more poorly than controls on most measures of learning and memory, problem solving and abstraction and perceptual-motor speed, but the groups did not differ on the measure of sustained attention. Correlational analyses revealed no significant relationships between measures of childhood and residual hyperactivity and neuropsychological performance; scores on the Beck Depression Inventory were related only to performance on the Wisconsin Card Sorting Test. The findings indicate that abuse of cocaine or alcohol is associated with deficits on neuropsychological tests which cannot be attributed to specific premorbid or comorbid factors such as depression or childhood or residual attention deficit disorder.

  3. Sleep Perception and Misperception in Chronic Cocaine Users During Abstinence.

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    Hodges, Sarah E; Pittman, Brian; Morgan, Peter T

    2017-03-01

    During abstinence, chronic cocaine users experience an objective worsening of sleep that is perceived as qualitatively improving. This phenomenon has been termed "occult insomnia." The objective of this study was to determine whether chronic cocaine users experience positive sleep state misperception during abstinence. Forty-three cocaine-dependent persons were admitted to an inpatient research facility for 12 days and 11 nights to participate in a treatment study of modafinil. Polysomnographic sleep recordings were performed on study nights 3, 4, 10, and 11, when participants were on average 1 and 2 weeks abstinent from cocaine. Participants also completed sleep diary questionnaires every evening before bed and every morning upon awakening. Polysomnographic and sleep diary measurements of total sleep time, sleep latency, time awake after sleep onset, and time in bed after final awakening were compared. Chronic cocaine users accurately reported total sleep time after 1 week of abstinence but overreported total sleep time by an average of 40 min after 2 weeks of abstinence. Underestimating sleep latency and time spent awake after sleep onset were responsible for this difference. Positive sleep state misperception is revealed in chronic cocaine users after 2 weeks of abstinence and is consistent with the previously identified "occult insomnia" in this population.

  4. Schedule of voucher delivery influences initiation of cocaine abstinence.

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    Kirby, K C; Marlowe, D B; Festinger, D S; Lamb, R J; Platt, J J

    1998-10-01

    This study examined whether voucher delivery arrangements affect treatment outcome. First, 90 cocaine-dependent adults were randomly assigned to behavioral counseling or counseling plus vouchers for cocaine-free urine samples. The value of each voucher was low at the beginning but increased as the patient progressed (Voucher Schedule 1). Voucher Schedule 1 produced no improvements relative to counseling only. Next, 23 patients received vouchers on either Voucher Schedule 1 or Voucher Schedule 2. Voucher Schedule 2 began with high voucher values, but requirements for earning vouchers increased as the patient progressed. Average durations of cocaine abstinence were 6.9 weeks on Voucher Schedule 2 versus 2.0 weeks on Voucher Schedule 1 (p = .02). This confirms that vouchers can assist in initiating abstinence and that voucher delivery arrangements are critical.

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

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    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. One month of cocaine abstinence potentiates rapid dopamine signaling in the nucleus accumbens core.

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    Cameron, Courtney M; Wightman, R Mark; Carelli, Regina M

    2016-12-01

    Cocaine addiction is a chronic relapsing disorder that is difficult to treat in part because addicts relapse even after extended periods of abstinence. Given the importance of the mesolimbic dopamine (DA) system in drug addiction, we sought to characterize cocaine abstinence induced changes in rapid DA signaling in the nucleus accumbens (NAc). Here, rats were trained to self-administer cocaine for 14 consecutive days, then divided into two groups. Day 1 rats (D1; n = 7) underwent 24 h of abstinence; Day 30 rats (D30; n = 7) underwent one month of abstinence. After abstinence, all rats underwent a single extinction session. Immediately after, rats were deeply anesthetized and fast scan cyclic voltammetry (FSCV) was used to measure DA release and uptake dynamics in the NAc core before and following a single cocaine injection. We show that one month of cocaine abstinence potentiates the peak concentration of electrically evoked DA in the NAc core following an acute injection of cocaine. This potentiation is not related to alterations in DA uptake parameters, which are unchanged following abstinence, but may reflect alterations in release. These results further support the abundance of literature showing that cocaine abstinence induces neuroplasticity in brain areas implicated in drug reward and relapse. The present findings also demonstrate critical differences between abstinence-induced neuroadaptations in DA signaling and those caused by drug exposure itself. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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    Clow, D.W.; Hammer, R.P. Jr. (Univ. of Hawaii School of Medicine, Honolulu (USA))

    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.

  8. Dissociated grey matter changes with prolonged addiction and extended abstinence in cocaine users.

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    Colm G Connolly

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

  9. The brief abstinence test: voucher-based reinforcement of cocaine abstinence

    National Research Council Canada - National Science Library

    Robles, Elias; Silverman, Kenneth; Preston, Kenzie L; Cone, Edward J; Katz, Elizabeth; Bigelow, George E; Stitzer, Maxine L

    2000-01-01

    .... On Monday of the test week, 72 cocaine-abusing methadone patients were offered a $100 voucher if urine samples collected on Wednesday indicated that they had abstained from cocaine across that 2-day period...

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

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    Danay Baker-Andresen

    2015-10-01

    Full Text Available Continued vulnerability to relapse during abstinence is a 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.

  11. Pilot study of lorazepam and tiagabine effects on sleep, motor learning, and impulsivity in cocaine abstinence.

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    Morgan, Peter T; Malison, Robert T

    2008-01-01

    To test the effects of mechanistically different GABA modulating agents on the disrupted sleep and cognitive function associated with abstinence from cocaine. We examined the effects of lorazepam and tiagabine on polysomnographically measured sleep and cognition in six cocaine dependent persons. Participants were studied during the first and second week of controlled abstinence following intravenous, laboratory cocaine administration. Lorazepam and tiagabine decreased sleep latency, but whereas lorazepam markedly increased light sleep, tiagabine caused a dramatic shift toward slow-wave sleep. Despite increasing total sleep time, lorazepam impaired sleep dependent learning and increased next day impulsivity. These results introduce the possibility of different, sleep-related cognitive effects of mechanistically distinct GABAergic sedative hypnotics.

  12. Sex Differences in Psychiatric Comorbidity and Plasma Biomarkers for Cocaine Addiction in Abstinent Cocaine-Addicted Subjects in Outpatient Settings

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    Pedraz, María; Araos, Pedro; García-Marchena, Nuria; Serrano, Antonia; Romero-Sanchiz, Pablo; Suárez, Juan; Castilla-Ortega, Estela; Mayoral-Cleries, Fermín; Ruiz, Juan Jesús; Pastor, Antoni; Barrios, Vicente; Chowen, Julie A.; Argente, Jesús; Torrens, Marta; de la Torre, Rafael; Rodríguez De Fonseca, Fernando; Pavón, Francisco Javier

    2015-01-01

    There are sex differences in the progression of drug addiction, relapse, and response to therapies. Because biological factors participate in these differences, they should be considered when using biomarkers for addiction. In the current study, we evaluated the sex differences in psychiatric comorbidity and the concentrations of plasma mediators that have been reported to be affected by cocaine. Fifty-five abstinent cocaine-addicted subjects diagnosed with lifetime cocaine use disorders (40 men and 15 women) and 73 healthy controls (48 men and 25 women) were clinically assessed with the diagnostic interview “Psychiatric Research Interview for Substance and Mental Disorders.” Plasma concentrations of chemokines, cytokines, N-acyl-ethanolamines, and 2-acyl-glycerols were analyzed according to history of cocaine addiction and sex, controlling for covariates age and body mass index (BMI). Relationships between these concentrations and variables related to cocaine addiction were also analyzed in addicted subjects. The results showed that the concentrations of chemokine (C-C motif) ligand 2/monocyte chemotactic protein-1 (CCL2/MCP-1) and chemokine (C-X-C motif) ligand 12/stromal cell-derived factor-1 (CXCL12/SDF-1) were only affected by history of cocaine addiction. The plasma concentrations of interleukin 1-beta (IL-1β), IL-6, IL-10, and tumor necrosis factor-alpha (TNFα) were affected by history of cocaine addiction and sex. In fact, whereas cytokine concentrations were higher in control women relative to men, these concentrations were reduced in cocaine-addicted women without changes in addicted men. Regarding fatty acid derivatives, history of cocaine addiction had a main effect on the concentration of each acyl derivative, whereas N-acyl-ethanolamines were increased overall in the cocaine group, 2-acyl-glycerols were decreased. Interestingly, N-palmitoleoyl-ethanolamine (POEA) was only increased in cocaine-addicted women. The covariate BMI had a significant

  13. Gene expression changes in the medial prefrontal cortex and nucleus accumbens following abstinence from cocaine self-administration

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    Morgan Drake

    2010-02-01

    Full Text Available Abstract Background Many studies of cocaine-responsive gene expression have focused on changes occurring during cocaine exposure, but few studies have examined the persistence of these changes with cocaine abstinence. Persistent changes in gene expression, as well as alterations induced during abstinence may underlie long-lasting drug craving and relapse liability. Results Whole-genome expression analysis was conducted on a rat cocaine binge-abstinence model that has previously been demonstrated to engender increased drug seeking and taking with abstinence. Gene expression changes in two mesolimbic terminal fields (mPFC and NAc were identified in a comparison of cocaine-naïve rats with rats after 10 days of cocaine self-administration followed by 1, 10, or 100 days of enforced abstinence (n = 6-11 per group. A total of 1,461 genes in the mPFC and 414 genes in the NAc were altered between at least two time points (ANOVA, p Conclusions Together, these changes help to illuminate processes and networks involved in abstinence-induced behaviors, including synaptic plasticity, MAPK signaling, and TNF signaling.

  14. Attendance Rates in a Workplace Predict Subsequent Outcome of Employment-Based Reinforcement of Cocaine Abstinence in Methadone Patients

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    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…

  15. Changes in brain-derived neurotrophic factor (BDNF) during abstinence could be associated with relapse in cocaine-dependent patients.

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    Corominas-Roso, Margarida; Roncero, Carlos; Daigre, Constanza; Grau-Lopez, Lara; Ros-Cucurull, Elena; Rodríguez-Cintas, Laia; Sanchez-Mora, Cristina; Lopez, Maria Victoria; Ribases, Marta; Casas, Miguel

    2015-02-28

    Brain-derived neurotrophic factor (BDNF) is involved in cocaine craving in humans and drug seeking in rodents. Based on this, the aim of this study was to explore the possible role of serum BDNF in cocaine relapse in abstinent addicts. Forty cocaine dependent subjects (DSM-IV criteria) were included in an inpatient 2 weeks abstinence program. Organic and psychiatric co-morbidities were excluded. Two serum samples were collected for each subject at baseline and at after 14 abstinence days. After discharge, all cocaine addicts underwent a 22 weeks follow-up, after which they were classified into early relapsers (ER) (resumed during the first 14 days after discharge,) or late relapsers (LR) (resumed beyond 14 days after discharge). The only clinical differences between groups were the number of consumption days during the last month before detoxification. Serum BDNF levels increased significantly across the 12 days of abstinence in the LR group (p=0.02), whereas in the ER group BDNF remained unchanged. In the ER group, the change of serum BDNF during abstinence negatively correlated with the improvement in depressive symptoms (p=0.02). These results suggest that BDNF has a role in relapse to cocaine consumption in abstinent addicts, although the underlying neurobiological mechanisms remain to be clarified. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Drp1 Mitochondrial Fission in D1 Neurons Mediates Behavioral and Cellular Plasticity during Early Cocaine Abstinence.

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    Chandra, Ramesh; Engeln, Michel; Schiefer, Christopher; Patton, Mary H; Martin, Jennifer A; Werner, Craig T; Riggs, Lace M; Francis, T Chase; McGlincy, Madeleine; Evans, Brianna; Nam, Hyungwoo; Das, Shweta; Girven, Kasey; Konkalmatt, Prasad; Gancarz, Amy M; Golden, Sam A; Iñiguez, Sergio D; Russo, Scott J; Turecki, Gustavo; Mathur, Brian N; Creed, Meaghan; Dietz, David M; Lobo, Mary Kay

    2017-12-20

    Altered brain energy homeostasis is a key adaptation occurring in the cocaine-addicted brain, but the effect of cocaine on the fundamental source of energy, mitochondria, is unknown. We demonstrate an increase of dynamin-related protein-1 (Drp1), the mitochondrial fission mediator, in nucleus accumbens (NAc) after repeated cocaine exposure and in cocaine-dependent individuals. Mdivi-1, a demonstrated fission inhibitor, blunts cocaine seeking and locomotor sensitization, while blocking c-Fos induction and excitatory input onto dopamine receptor-1 (D1) containing NAc medium spiny neurons (MSNs). Drp1 and fission promoting Drp1 are increased in D1-MSNs, consistent with increased smaller mitochondria in D1-MSN dendrites after repeated cocaine. Knockdown of Drp1 in D1-MSNs blocks drug seeking after cocaine self-administration, while enhancing the fission promoting Drp1 enhances seeking after long-term abstinence from cocaine. We demonstrate a role for altered mitochondrial fission in the NAc, during early cocaine abstinence, suggesting potential therapeutic treatment of disrupting mitochondrial fission in cocaine addiction. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Event-related potentials indicate motivational relevance of cocaine cues in abstinent cocaine addicts

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    van der Laar, M.C.; Licht, R.; Franken, H.A.; Hendriks, V.M.

    2004-01-01

    Rationale: Motivational drive and its underlying affect-related states are the core mechanisms that precede the seeking and taking of drugs in substance dependence. Objective: The present study aimed to investigate the motivational relevance of cocaine cues and whether or not an appetitive emotional

  18. Enhancement of behavioral sensitization, anxiety-like behavior, and hippocampal and frontal cortical CREB levels following cocaine abstinence in mice exposed to cocaine during adolescence.

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    Maria Cristina Valzachi

    Full Text Available Adolescence has been linked to greater risk-taking and novelty-seeking behavior and a higher prevalence of drug abuse and risk of relapse. Decreases in cyclic adenosine monophosphate response element binding protein (CREB and phosphorylated CREB (pCREB have been reported after repeated cocaine administration in animal models. We compared the behavioral effects of cocaine and abstinence in adolescent and adult mice and investigated possible age-related differences in CREB and pCREB levels. Adolescent and adult male Swiss mice received one daily injection of saline or cocaine (10 mg/kg, i.p. for 8 days. On day 9, the mice received a saline injection to evaluate possible environmental conditioning. After 9 days of withdrawal, the mice were tested in the elevated plus maze to evaluate anxiety-like behavior. Twelve days after the last saline/cocaine injection, the mice received a challenge injection of either cocaine or saline, and locomotor activity was assessed. One hour after the last injection, the brains were extracted, and CREB and pCREB levels were evaluated using Western blot in the prefrontal cortex (PFC and hippocampus. The cocaine-pretreated mice during adolescence exhibited a greater magnitude of the expression of behavioral sensitization and greater cocaine withdrawal-induced anxiety-like behavior compared with the control group. Significant increases in CREB levels in the PFC and hippocampus and pCREB in the hippocampus were observed in cocaine-abstinent animals compared with the animals treated with cocaine in adulthood. Interestingly, significant negative correlations were observed between cocaine sensitization and CREB levels in both regions. These results suggest that the behavioral and neurochemical consequences of psychoactive substances in a still-developing nervous system can be more severe than in an already mature nervous system.

  19. Cocaine Self-Administration Experience Induces Pathological Phasic Accumbens Dopamine Signals and Abnormal Incentive Behaviors in Drug-Abstinent Rats.

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    Saddoris, Michael P; Wang, Xuefei; Sugam, Jonathan A; Carelli, Regina M

    2016-01-06

    Chronic exposure to drugs of abuse is linked to long-lasting alterations in the function of limbic system structures, including the nucleus accumbens (NAc). Although cocaine acts via dopaminergic mechanisms within the NAc, less is known about whether phasic dopamine (DA) signaling in the NAc is altered in animals with cocaine self-administration experience or if these animals learn and interact normally with stimuli in their environment. Here, separate groups of rats self-administered either intravenous cocaine or water to a receptacle (controls), followed by 30 d of enforced abstinence. Next, all rats learned an appetitive Pavlovian discrimination and voltammetric recordings of real-time DA release were taken in either the NAc core or shell of cocaine and control subjects. Cocaine experience differentially impaired DA signaling in the core and shell relative to controls. Although phasic DA signals in the shell were essentially abolished for all stimuli, in the core, DA did not distinguish between cues and was abnormally biased toward reward delivery. Further, cocaine rats were unable to learn higher-order associations and even altered simple conditioned approach behaviors, displaying enhanced preoccupation with cue-associated stimuli (sign-tracking; ST) but diminished time at the food cup awaiting reward delivery (goal-tracking). Critically, whereas control DA signaling correlated with ST behaviors, cocaine experience abolished this relationship. These findings show that cocaine has persistent, differential, and pathological effects on both DA signaling and DA-dependent behaviors and suggest that psychostimulant experience may remodel the very circuits that bias organisms toward repeated relapse. Relapsing to drug abuse despite periods of abstinence and sincere attempts to quit is one of the most pernicious facets of addiction. Unfortunately, little is known about how the dopamine (DA) system functions after periods of drug abstinence, particularly its role in

  20. ELEVATIONS OF FOSB IN THE NUCLEUS ACCUMBENS DURING FORCED COCAINE ABSTINENCE CORRELATE WITH DIVERGENT CHANGES IN REWARD FUNCTION

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    Harris, Glenda C.; Hummel, Michele; Wimmer, Mathieu; Mague, Stephen D.; Aston-Jones, Gary

    2007-01-01

    Dysregulation of hedonic processing, in which seeking of drug reward becomes more desirable than seeking natural rewards, like food, sex, and novelty, is a consequence of chronic drug exposure and potentially leads to escalating drug usage and addiction. Here, we investigated the effects of chronic cocaine treatment (10 days of escalating doses of cocaine, 10-30 mg/kg) and multiple forced abstinence periods (2, 3 or 5 weeks) on the acute rewarding properties of either cocaine (10 mg/kg) or novel-objects using the conditioned place preference procedure. Following all cocaine withdrawal periods, cocaine preference was significantly elevated while novel object preference was abolished compared to saline-treated rats. At the earliest withdrawal period, these behavioral changes were accompanied by elevations in FosB-like immunoreactive staining in the basolateral amygdala (BLA) and nucleus accumbens shell (NAc-Sh) and core (NAc-C). FosB staining in all three brain areas correlated positively with cocaine preference, but negatively with novelty preference. After 5 weeks of withdrawal, FosB staining was only elevated in the NAc-Sh and again correlated positively with elevated cocaine preference but negatively with decreased novelty preference. These data indicate that alterations in the expression of FosB-like transcription factors in the NAc can predict the dysregulation of hedonic processing that occurs during protracted withdrawal from cocaine. PMID:17560044

  1. Chronic escalating cocaine exposure, abstinence/withdrawal, and chronic re-exposure: Effects on striatal dopamine and opioid systems in C57BL/6J mice

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    Zhang, Yong; Schlussman, Stefan D.; Rabkin, Jacqui; Butelman, Eduardo R.; Ho, Ann; Kreek, Mary Jeanne

    2013-01-01

    Cocaine addiction is a chronic relapsing disease with periods of chronic escalating self-exposure, separated by periods of abstinence/withdrawal of varying duration. Few studies compare such cycles in preclinical models. This study models an “addiction-like cycle” in mice to determine neurochemical/molecular alterations that underlie the chronic, relapsing nature of this disease. Groups of male C57BL/6J mice received acute cocaine exposure (14-day saline/14-day withdrawal /13-day saline + 1-day cocaine), chronic cocaine exposure (14 day cocaine) or chronic re-exposure (14-day cocaine/14-day withdrawal /14-day cocaine). Escalating-dose binge cocaine (15-30 mg/kg/injection x 3/day, i.p. at hourly intervals) or saline (14-day saline) was administered, modeling initial exposure. In “re-exposure” groups, after a 14-day injection-free period (modeling abstinence/withdrawal), mice that had received cocaine were re-injected with 14-day escalating-dose binge cocaine, whereas controls received saline. Microdialysis was conducted on the 14th day of exposure or re-exposure to determine striatal dopamine content. Messenger RNA levels of preprodynorphin (Pdyn), dopamine D1 (Drd1) and D2 (Drd2) in the caudate putamen were determined by real-time PCR. Basal striatal dopamine levels were lower in mice after 14-day escalating exposure or re-exposure than in those in the acute cocaine group and controls. Pdyn mRNA levels were higher in the cocaine groups than in controls. Long-term adaptation was observed across the stages of this addiction-like cycle, in that the effects of cocaine on dopamine levels were increased after re-exposure compared to exposure. Changes in striatal dopaminergic responses across chronic escalating cocaine exposure and re-exposure are a central feature of the neurobiology of relapsing addictive states. PMID:23164614

  2. Synapse density and dendritic complexity are reduced in the prefrontal cortex following seven days of forced abstinence from cocaine self-administration.

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    Khampaseuth Rasakham

    Full Text Available Chronic cocaine exposure in both human addicts and in rodent models of addiction reduces prefrontal cortical activity, which subsequently dysregulates reward processing and higher order executive function. The net effect of this impaired gating of behavior is enhanced vulnerability to relapse. Previously we have shown that cocaine-induced increases in brain-derived neurotrophic factor (BDNF expression in the medial prefrontal cortex (PFC is a neuroadaptive mechanism that blunts the reinforcing efficacy of cocaine. As BDNF is known to affect neuronal survival and synaptic plasticity, we tested the hypothesis that abstinence from cocaine self-administration would lead to alterations in neuronal morphology and synaptic density in the PFC. Using a novel technique, array tomography and Golgi staining, morphological changes in the rat PFC were analyzed following 14 days of cocaine self-administration and 7 days of forced abstinence. Our results indicate that overall dendritic branching and total synaptic density are significantly reduced in the rat PFC. In contrast, the density of thin dendritic spines are significantly increased on layer V pyramidal neurons of the PFC. These findings indicate that dynamic structural changes occur during cocaine abstinence that may contribute to the observed hypo-activity of the PFC in cocaine-addicted individuals.

  3. Context-induced relapse to cocaine seeking after punishment-imposed abstinence is associated with activation of cortical and subcortical brain regions.

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    Pelloux, Yann; Hoots, Jennifer K; Cifani, Carlo; Adhikary, Sweta; Martin, Jennifer; Minier-Toribio, Angelica; Bossert, Jennifer M; Shaham, Yavin

    2017-06-29

    We recently developed a rat model of context-induced relapse to alcohol seeking after punishment-imposed abstinence to mimic relapse after self-imposed abstinence due to adverse consequences of drug use. Here, we determined the model's generality to cocaine and have begun to explore brain mechanisms of context-induced relapse to cocaine seeking after punishment-imposed abstinence, using the activity marker Fos. In exp. 1, we trained rats to self-administer cocaine (0.75 mg/kg/infusion, 6 hours/day, 12 days) in context A. Next, we transferred them to context B where for the paired group, but not unpaired group, 50 percent of cocaine-reinforced lever presses caused aversive footshock. We then tested the rats for cocaine seeking under extinction conditions in contexts A and B. We also retested them for relapse after retraining in context A and repunishment in context B. In exp. 2, we used Fos immunoreactivity to determine relapse-associated neuronal activation in brain regions of rats exposed to context A, context B or neither context. Results showed the selective shock-induced suppression of cocaine self-administration and context-induced relapse after punishment-imposed abstinence in rats exposed to paired, but not unpaired, footshock. Additionally, context-induced relapse was associated with selective activation of dorsal and ventral medial prefrontal cortex, anterior insula, dorsal striatum, basolateral amygdala, paraventricular nucleus of the thalamus, lateral habenula, substantia nigra, ventral subiculum, and dorsal raphe, but not nucleus accumbens, central amygdala, lateral hypothalamus, ventral tegmental area and other brain regions. Together, context-induced relapse after punishment-imposed abstinence generalizes to rats with a history of cocaine self-administration and is associated with selective activation of cortical and subcortical regions. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  4. Abstinence from cocaine and sucrose self-administration reveals altered mesocorticolimbic circuit connectivity by resting state MRI.

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    Lu, Hanbing; Zou, Qihong; Chefer, Svetlana; Ross, Thomas J; Vaupel, D Bruce; Guillem, Karine; Rea, William P; Yang, Yihong; Peoples, Laura L; Stein, Elliot A

    2014-09-01

    Previous preclinical studies have emphasized that drugs of abuse, through actions within and between mesocorticolimbic (MCL) regions, usurp learning and memory processes normally involved in the pursuit of natural rewards. To distinguish MCL circuit pathobiological neuroadaptations that accompany addiction from general learning processes associated with natural reward, we trained two groups of rats to self-administer either cocaine (IV) or sucrose (orally) followed by an identically enforced 30 day abstinence period. These procedures are known to induce behavioral changes and neuroadaptations. A third group of sedentary animals served as a negative control group for general handling effects. We examined low-frequency spontaneous fluctuations in the functional magnetic resonance imaging (fMRI) signal, known as resting-state functional connectivity (rsFC), as a measure of intrinsic neurobiological interactions between brain regions. Decreased rsFC was seen in the cocaine-SA compared with both sucrose-SA and housing control groups between prelimbic (PrL) cortex and entopeduncular nucleus and between nucleus accumbens core (AcbC) and dorsomedial prefrontal cortex (dmPFC). Moreover, individual differences in cocaine SA escalation predicted connectivity strength only in the Acb-dmPFC circuit. These data provide evidence of fronto-striatal plasticity across the addiction trajectory, which are consistent with Acb-PFC hypoactivity seen in abstinent human drug addicts, indicating potential circuit level biomarkers that may inform therapeutic interventions. They further suggest that available data from cross-sectional human studies may reflect the consequence of rather a predispositional predecessor to their dependence.

  5. Recovery of neurocognitive functions following sustained abstinence after substance dependence and implications for treatment

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    Schulte, M.H.J.; Cousijn, J.; den Uyl, T.E.; Goudriaan, A.E.; van den Brink, W.; Veltman, D.J.; Schilt, T.; Wiers, R.W.

    2014-01-01

    Background: Substance Use Disorders (SUDs) have been associated with impaired neurocognitive functioning, which may (partly) improve with sustained abstinence. New treatments are emerging, aimed at improving cognitive functions, and being tested. However, no integrated review is available regarding

  6. Recovery of neurocognitive functions following sustained abstinence after substance dependence and implications for treatment

    NARCIS (Netherlands)

    Schulte, Mieke H. J.; Cousijn, Janna; den Uyl, Tess E.; Goudriaan, Anna E.; van den Brink, Wim; Veltman, Dick J.; Schilt, Thelma; Wiers, Reinout W.

    2014-01-01

    Substance Use Disorders (SUDs) have been associated with impaired neurocognitive functioning, which may (partly) improve with sustained abstinence. New treatments are emerging, aimed at improving cognitive functions, and being tested. However, no integrated review is available regarding

  7. Recovery of neurocognitive functions following sustained abstinence after substance dependence and implications for treatment

    NARCIS (Netherlands)

    Schulte, Mieke H J; Cousijn, Janna; den Uyl, Tess E; Goudriaan, Anna E; van den Brink, Wim; Veltman, Dick J; Schilt, Thelma; Wiers, Reinout W

    2014-01-01

    BACKGROUND: Substance Use Disorders (SUDs) have been associated with impaired neurocognitive functioning, which may (partly) improve with sustained abstinence. New treatments are emerging, aimed at improving cognitive functions, and being tested. However, no integrated review is available regarding

  8. Forced abstinence from cocaine self-administration is associated with DNA methylation changes in myelin genes in the corpus callosum: a preliminary study

    Directory of Open Access Journals (Sweden)

    David Andrew Nielsen

    2012-06-01

    Full Text Available Background: Human cocaine abuse is associated with alterations in white matter integrity revealed upon brain imaging, an observation that is recapitulated in an animal model of continuous cocaine exposure. The mechanism through which cocaine may affect white matter is unknown and the present study tested the hypothesis that cocaine self-administration results in changes in DNA methylation that could result in altered expression of several myelin genes that could contribute to the effects of cocaine on white matter integrity.Methods: In the present study, we examined the impact of forced abstinence from cocaine self-administration on chromatin-associated changes in white matter. To this end, rats were trained to self-administer cocaine (0.75 mg/kg/0.1 ml infusion for 14 days followed by forced abstinence for 1 day (N = 6 or 30 days (N = 6 before sacrifice. Drug-free, sham surgery controls (n = 7 were paired with the experimental groups. Global DNA methylation and DNA methylation at specific CpG sites in the promoter regions of myelin basic protein (Mbp, proteolipid protein-1 (Plp1, and SRY-related HMG-box-10 (Sox10 genes were analyzed in DNA extracted from corpus callosum.Results: Significant differences in the overall methylation patterns of the Sox10 promoter region were observed in the corpus callosum of rats at 30 days of forced abstinence from cocaine self-administration relative to sham controls; the -189, -142, -93 and -62 CpG sites were significantly hypomethylated point-wise at this time point. After correction for multiple comparisons, no differences in global methylation or the methylation patterns of Mbp or Plp1 were found.Conclusions: Forced abstinence from cocaine self-administration was associated with differences in DNA methylation at specific CpG sites in the promoter region of the Sox10 gene in corpus callosum. These changes may be related to reductions in normal age related changes in DNA methylation and could be a factor in

  9. Cocaine.

    Science.gov (United States)

    Piazza, Nick J.; Yeager, Rebecca D.

    Cocaine was first used by Europeans in the nineteenth century when extract from the coca leaf was combined with various beverages. Cocaine comes as a white crystalline powder. However, a product called crack cocaine may come as an opaque crystal similar in size and shape to rock salt. A third form of cocaine is known as coca paste, which is an…

  10. Cocaine

    Science.gov (United States)

    ... made from the dried leaves of the coca plant. Cocaine is usually a white powder that is ... their nostrils. They may have lots of nosebleeds , hoarseness, or trouble swallowing. Injecting cocaine and sharing needles ...

  11. Cocaine

    Science.gov (United States)

    ... leading to risky sexual behavior strange, unpredictable behavior, panic attacks, or paranoid psychosis (losing touch with reality) Can you get addicted to cocaine? Yes, repeated cocaine use can lead to addiction. Addiction is a devastating brain disease in which ...

  12. Cocaine

    Science.gov (United States)

    Cocaine is a white powder. It can be snorted up the nose or mixed with water and injected with a needle. Cocaine can also be made into small white rocks, ... Crack is smoked in a small glass pipe. Cocaine speeds up your whole body. You may feel ...

  13. Cocaine

    Science.gov (United States)

    ... Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the ... of Cocaine Statistics and Trends Swipe left or right to scroll. Monitoring the Future Study: Trends in ...

  14. Evaluation of plasma cytokines in patients with cocaine use disorders in abstinence identifies transforming growth factor alpha (TGFα as a potential biomarker of consumption and dual diagnosis

    Directory of Open Access Journals (Sweden)

    Rosa Maza-Quiroga

    2017-10-01

    Full Text Available Background Cocaine use disorder (CUD is a complex health condition, especially when it is accompanied by comorbid psychiatric disorders (dual diagnosis. Dual diagnosis is associated with difficulties in the stratification and treatment of patients. One of the major challenges in clinical practice of addiction psychiatry is the lack of objective biological markers that indicate the degree of consumption, severity of addiction, level of toxicity and response to treatment in patients with CUD. These potential biomarkers would be fundamental players in the diagnosis, stratification, prognosis and therapeutic orientation in addiction. Due to growing evidence of the involvement of the immune system in addiction and psychiatric disorders, we tested the hypothesis that patients with CUD in abstinence might have altered circulating levels of signaling proteins related to systemic inflammation. Methods The study was designed as a cross-sectional study of CUD treatment-seeking patients. These patients were recruited from outpatient programs in the province of Malaga (Spain. The study was performed with a total of 160 white Caucasian subjects, who were divided into the following groups: patients diagnosed with CUD in abstinence (N = 79, cocaine group and matched control subjects (N = 81, control group. Participants were clinically evaluated with the diagnostic interview PRISM according to the DSM-IV-TR, and blood samples were collected for the determination of chemokine C-C motif ligand 11 (CCL11, eotaxin-1, interferon gamma (IFNγ, interleukin-4 (IL-4, interleukin-8 (IL-8, interleukin-17α (IL-17α, macrophage inflammatory protein 1α (MIP-1α and transforming growth factor α (TGFα levels in the plasma. Clinical and biochemical data were analyzed in order to find relationships between variables. Results While 57% of patients with CUD were diagnosed with dual diagnosis, approximately 73% of patients had other substance use disorders. Cocaine patients

  15. Extended findings of Brain Metabolite Normalization in MA-Dependent Subjects Across Sustained Abstinence: A Proton MRS Study

    Science.gov (United States)

    Salo, Ruth; Buonocore, Michael H.; Leamon, Martin; Natsuaki, Yutaka; Waters, Christy; Moore, Charles D.; Galloway, Gantt P.; Nordahl, Thomas E.

    2010-01-01

    Objective The goal of the present study was to extend our previous findings on long-term methamphetamine (MA) use and drug abstinence on brain metabolite levels in an expanded group of MA-dependent individuals. Methods Seventeen MA abusers with sustained drug abstinence (1 year to 5 years), 30 MA abusers with short-term drug abstinence (1 month to 6 months) and 24 non-substance using controls were studied using MR spectroscopy (MRS). MRS measures of NAA/Cr, Cho/Cr and Cho/NAA were obtained in the anterior cingulate cortex (ACC) and in the primary visual cortex (PVC). Results ACC-Cho/NAA values were abnormally high in the short-term abstinent group compared to controls [F(1,52)=18.76, p<0.0001]. No differences were observed between controls and the long-term abstinent group [F(1,39)=0.97, p=0.97]. New evidence of lower ACC-NAA/Cr levels were observed in the short-term abstinent MA abusers compared to controls [F(1,52)=23.05, p<0.0001] and long-term abstinent MA abusers [F(1,45)=7.06, p=0.01]. No differences were observed between long-term abstinent MA abusers and controls [F(1,39)=0.48, p=0.49]. Conclusions The new findings of relative NAA/Cr normalization across periods of abstinence suggest that adaptive changes following cessation of MA abuse may be broader than initially thought. These changes may contribute to some degree of normalization of neuronal function in the ACC. PMID:20739127

  16. Bidirectional plasticity in the primate inferior olive induced by chronic ethanol intoxication and sustained abstinence.

    Science.gov (United States)

    Welsh, John P; Han, Victor Z; Rossi, David J; Mohr, Claudia; Odagiri, Misa; Daunais, James B; Grant, Kathleen A

    2011-06-21

    The brain adapts to chronic ethanol intoxication by altering synaptic and ion-channel function to increase excitability, a homeostatic counterbalance to inhibition by alcohol. Delirium tremens occurs when those adaptations are unmasked during withdrawal, but little is known about whether the primate brain returns to normal with repeated bouts of ethanol abuse and abstinence. Here, we show a form of bidirectional plasticity of pacemaking currents induced by chronic heavy drinking within the inferior olive of cynomolgus monkeys. Intracellular recordings of inferior olive neurons demonstrated that ethanol inhibited the tail current triggered by release from hyperpolarization (I(tail)). Both the slow deactivation of hyperpolarization-activated cyclic nucleotide-gated channels conducting the hyperpolarization-activated inward current and the activation of Ca(v)3.1 channels conducting the T-type calcium current (I(T)) contributed to I(tail), but ethanol inhibited only the I(T) component of I(tail). Recordings of inferior olive neurons obtained from chronically intoxicated monkeys revealed a significant up-regulation in I(tail) that was induced by 1 y of daily ethanol self-administration. The up-regulation was caused by a specific increase in I(T) which (i) greatly increased neurons' susceptibility for rebound excitation following hyperpolarization and (ii) may have accounted for intention tremors observed during ethanol withdrawal. In another set of monkeys, sustained abstinence produced the opposite effects: (i) a reduction in rebound excitability and (ii) a down-regulation of I(tail) caused by the down-regulation of both the hyperpolarization-activated inward current and I(T). Bidirectional plasticity of two hyperpolarization-sensitive currents following chronic ethanol abuse and abstinence may underlie persistent brain dysfunction in primates and be a target for therapy.

  17. Modulation of risky choices in recently abstinent dependent cocaine users: a transcranial direct-current stimulation (tDCS study

    Directory of Open Access Journals (Sweden)

    Alessandra eGorini

    2014-08-01

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

  18. The beta-lactam antibiotic ceftriaxone inhibits physical dependence and abstinence-induced withdrawal from cocaine, amphetamine, methamphetamine, and clorazepate in planarians.

    Science.gov (United States)

    Rawls, Scott M; Cavallo, Federica; Capasso, Anna; Ding, Zhe; Raffa, Robert B

    2008-04-28

    Ceftriaxone (a beta-lactam antibiotic) has recently been identified as having the rare ability to increase the expression and functional activity of the glutamate transporter subtype 1 (GLT-1) in rat spinal cord cultures. GLT-1 has been implicated in diverse neurological disorders and in opioid dependence and withdrawal. It has been speculated that it might also be involved in the physical dependence and withdrawal of other abused drugs, but demonstration of this property can be difficult in mammalian models. Here, we demonstrate for the first time using a planarian model that ceftriaxone attenuates both the development of physical dependence and abstinence-induced withdrawal from cocaine, amphetamine, methamphetamine, and a benzodiazepine (clorazepate) in a concentration-related manner. These results suggest that physical dependence and withdrawal from several drugs involve a common - beta-lactam-sensitive - mechanism in planarians. If these findings can be shown to extend to mammals, beta-lactam antibiotics might represent a novel pharmacotherapy or adjunct approach for treating drug abuse or serve as a template for drug discovery efforts aimed at treating drug abuse, recovery from drug abuse, or ameliorating the withdrawal from chronic use of therapeutic medications.

  19. Neuroplasticity in the mesolimbic dopamine system and cocaine addiction.

    Science.gov (United States)

    Thomas, M J; Kalivas, P W; Shaham, Y

    2008-05-01

    The main characteristics of cocaine addiction are compulsive drug use despite adverse consequences and high rates of relapse during periods of abstinence. A current popular hypothesis is that compulsive cocaine use and cocaine relapse is due to drug-induced neuroadaptations in reward-related learning and memory processes, which cause hypersensitivity to cocaine-associated cues, impulsive decision making and abnormal habit-like learned behaviours that are insensitive to adverse consequences. Here, we review results from studies on the effect of cocaine exposure on selected signalling cascades, growth factors and physiological processes previously implicated in neuroplasticity underlying normal learning and memory. These include the extracellular signal-regulated kinase (ERK) signalling pathway, brain-derived neurotrophic factor (BDNF), glutamate transmission, and synaptic plasticity (primarily in the form of long-term potentiation and depression, LTP and LTD). We also discuss the degree to which these cocaine-induced neuroplasticity changes in the mesolimbic dopamine system mediate cocaine psychomotor sensitization and cocaine-seeking behaviours, as assessed in animal models of drug addiction. Finally, we speculate on how these factors may interact to initiate and sustain cocaine psychomotor sensitization and cocaine seeking.

  20. Synthetic cathinones and stereochemistry: S enantiomer of mephedrone reduces anxiety- and depressant-like effects in cocaine- or MDPV-abstinent rats.

    Science.gov (United States)

    Philogene-Khalid, Helene L; Hicks, Callum; Reitz, Allen B; Liu-Chen, Lee-Yuan; Rawls, Scott M

    2017-09-01

    The neuropharmacological profile of the synthetic cathinone mephedrone (MEPH) is influenced by stereochemistry. Both MEPH enantiomers are monoamine transporter substrates, but R-MEPH is primarily responsible for rewarding effects of MEPH as it produces greater locomotor activation and intracranial self-stimulation than S-MEPH. S-MEPH is a 50-fold more potent 5-HT releaser than R-MEPH and does not place preference in rats. MEPH is also structurally similar to the cathinone derivative bupropion, an antidepressant and smoking cessation medication, suggesting MEPH has therapeutic and addictive properties. We tested the hypothesis that S-MEPH reduces anxiety- and depression-like behaviors in rats withdrawn from chronic cocaine or methylenedioxypyrovalerone (MDPV) using the elevated plus maze (EPM) and forced swim test (FST), respectively. Rats were tested 48-h after a binge-like paradigm (3×/day for 10days in 1-h intervals) of cocaine (10mg/kg), MDPV (1mg/kg) or saline. In vitro studies assessed the receptor binding and activity of S-MEPH. Rats withdrawn from chronic cocaine or MDPV displayed an increase in anxiety- and depression-like behaviors that was antagonized by treatment with S-MEPH (10, 30mg/kg). S-MEPH displayed affinity, but not agonist activity, for 5-HT 2 receptors (2A-2C) and showed negligible affinity for dopaminergic, adrenergic and nicotinic receptors. S-MEPH attenuated withdrawal behaviors following chronic cocaine or MDPV, perhaps through 5-HT release and/or 5-HT 2 receptor interactions. The present data suggest S-MEPH may be a possible structural and pharmacological template to develop maintenance therapy for acute anxiety and depression during early withdrawal from psychostimulant abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Synaptic mechanisms underlying persistent cocaine craving

    Science.gov (United States)

    Wolf, Marina E.

    2017-01-01

    Although it is challenging for individuals with cocaine addiction to achieve abstinence, the greatest difficulty is avoiding relapse to drug taking, which is often triggered by cues associated with prior cocaine use. This vulnerability to relapse persists for long periods (months to years) after abstinence is achieved. Here I discuss rodent studies of cue-induced cocaine craving during abstinence, with a focus on neuronal plasticity in the reward circuitry that maintains high levels of craving. Such work has the potential to identify new therapeutic targets and further our understanding of experience-dependent plasticity in the adult brain under normal circumstances and in the context of addiction. PMID:27150400

  2. Social stress, economic hardship, and psychological distress as predictors of sustained abstinence from substance use after treatment.

    Science.gov (United States)

    Wahler, Elizabeth A; Otis, Melanie D

    2014-11-01

    Social characteristics associated with disadvantage, such as racial/ethnic minority status, female gender, and low socioeconomic status (SES), are often associated with increased psychological distress and substance use disorders. This project tests a conceptual model derived from Pearlin's social stress theory for predicting abstinence from substance use between baseline and 1-year follow-up in secondary data from a large statewide sample of Kentucky substance abuse treatment participants (N = 1,123). Racial minority status, employment, and higher education level were predictive of substance use at follow-up, while female gender was predictive of abstinence. Limitations, implications for practice, and suggestions for future research are discussed.

  3. Drug-related decrease in neuropsychological functions of abstinent drug users.

    Science.gov (United States)

    van Holst, Ruth Janke; Schilt, Thelma

    2011-03-01

    This article reviews neuropsychological performance in frequent users of cocaine, (meth)amphetamines, ecstasy, opiates, alcohol, and cannabis. We searched the scientific literature published in the last five years, focusing on studies that required at least 2 weeks of abstinence from drug use, and included a control group. All substances of abuse, except cannabis, were associated with sustained deficits in executive functioning, especially inhibition. In addition, verbal memory decrements were consistently found in cocaine, (meth)amphetamines and ecstasy users, but not in heroin or cannabis users. More specific executive functioning deficits were reported depending on the substance of abuse. Cocaine was associated with diminished cognitive flexibility, whereas (meth)amphetamines were associated with worse cognitive planning functions compared to controls. Opiate studies showed lower scores on verbal fluency in opiate dependent subjects compared to controls. Working memory and visuospatial abilities were compromised in alcohol abusers. In ecstasy users, inconsistent findings have been reported across neuropsychological domains, with the exception of inhibition and verbal memory. There was little evidence for sustained cognitive impairments in adult abstinent cannabis users. Recognition of neuropsychological problems related to different substances can help to select subjects that will benefit most from treatment. Furthermore, a better understanding of the neuropsychological impairments in drug abusing individuals could help to explain the remitting course of substance abuse disorders and to improve psychological interventions.

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

    Science.gov (United States)

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

    2016-04-26

    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.

  5. Personality traits of cocaine-dependent patients associated with cocaine-positive baseline urine at hospitalization.

    Science.gov (United States)

    de Los Cobos, José Pérez; Siñol, Núria; Bañulus, Enrique; Batlle, Francisca; Tejero, Antoni; Trujols, Joan

    2010-01-01

    Cocaine abstinence at treatment entry is considered a predictor of good response in cocaine dependence treatment. Therefore, identification of factors facilitating pretreatment cocaine abstinence could be useful for developing new therapeutic strategies. This retrospective chart review study examines the association between personality traits and cocaine-positive baseline urinalysis (CPB) in cocaine-dependent inpatients. All 107 participants met DSM-IV criteria for cocaine dependence, and were admitted consecutively to a closed addiction unit for detoxification treatment. Personality was assessed with the Temperament and Character Inventory and the Millon Clinical Multiaxial Inventory (MCMI-II). CPB was detected in 80 patients (74.8%). The logistic regression model solely based on personality dimensions showed that only the MCMI-II avoidant traits were significantly associated with a decreased probability of cocaine-dependent patients presenting CPB. The logistic regression model based on both personality dimensions and substance use-related variables alike retained the number of days of cocaine use during the last 30 days as a risk factor, and alcohol dependence and the MCMI-II schizoid dimension as protective factors in predicting CPB results. Avoidant and schizoid traits are personality dimensions of cocaine-dependent patients that are associated with cocaine abstinence prior to inpatient admission. These findings suggest an inverse relationship between social isolation and CPB. Notwithstanding, more research is needed, not only to assess the generalizability of these findings, but also to enrich the personality and substance use model with variables related to readiness to change.

  6. PPARγ agonism attenuates cocaine cue reactivity.

    Science.gov (United States)

    Miller, William R; Fox, Robert G; Stutz, Sonja J; Lane, Scott D; Denner, Larry; Cunningham, Kathryn A; Dineley, Kelly T

    2016-11-11

    Cocaine use disorder is a chronic relapsing condition characterized by compulsive drug seeking and taking even after prolonged abstinence periods. Subsequent exposure to drug-associated cues can promote intense craving and lead to relapse in abstinent humans and rodent models. The responsiveness to these cocaine-related cues, or 'cue reactivity', can trigger relapse and cocaine-seeking behaviors; cue reactivity is measurable in cocaine-dependent humans as well as rodent models. Cue reactivity is thought to be predictive of cocaine craving and relapse. Here we report that PPARγ agonism during abstinence from cocaine self-administration reduced previously active lever pressing in Sprague Dawley rats during cue-reactivity tests, while administration of the PPARγ antagonist, GW9662, reversed this effect. PPARγ agonism also normalized nuclear ERK activity in the medial prefrontal cortex and hippocampus which was reversed with GW9662. Our results support the utility of PPARγ agonism as a relapse prevention strategy to maintain abstinence in the presence of cocaine-associated cues. © 2016 Society for the Study of Addiction.

  7. 5-HT6 antagonism attenuates cue-induced relapse to cocaine seeking without affecting cocaine reinforcement

    NARCIS (Netherlands)

    Gaalen, M.M.; Schetters, D.; Schoffelmeer, A.N.M.; de Vries, T.J.

    2010-01-01

    Re-exposure to drug-related cues elicits drug-seeking behaviour and relapse in humans even after months of abstinence. Similarly, in laboratory rats, drug-associated stimuli reinstate cocaine seeking after prolonged withdrawal periods, thus providing a model to study mechanisms underlying cocaine

  8. Topiramate in the treatment of cocaine use disorder.

    Science.gov (United States)

    Prince, Valerie; Bowling, Kellie C

    2018-01-01

    The literature on topiramate use in cocaine-dependent patients was reviewed. Six randomized, double-blind, controlled clinical trials evaluating the use of topiramate in patients who were cocaine dependent were analyzed. The results from the studies indicated that topiramate, when used in combination with cognitive behavioral therapy, may be effective in reducing short-term cocaine use and should be considered as a possible treatment option. Other trials suggested that topiramate was not effective in patients with a dual diagnosis of opioid and cocaine dependence. Two trials suggested that short-term abstinence assisted by pharmacotherapy is a predictor of longer-term (6 months and 1 year, respectively) abstinence. Cocaine use is dependent on multiple factors; therefore, a reduction in use or craving is not definitively associated with abstinence. However, decreased use reduces potential patient harm and the amount of money spent on illicit cocaine. The findings of this literature review should be used to encourage the completion of more trials that are appropriately designed. Topiramate was shown to be effective for increasing cocaine abstinence, the proportion of cocaine nonuse days, and the proportion of patients to attain 3 consecutive weeks of cocaine abstinence and decreasing the abuse liability of cocaine. Conflicting results in clinical trials do not provide a definitive answer regarding topiramate's efficacy in managing cocaine dependence. Available research neither validates nor invalidates the hypothesis that topiramate is efficacious in attaining abstinence in cocaine-dependent patients. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  9. Maternal cocaine use during breastfeeding

    Science.gov (United States)

    Cressman, Alex M.; Koren, Gideon; Pupco, Anna; Kim, Eunji; Ito, Shinya; Bozzo, Pina

    2012-01-01

    Abstract Question In my practice several patients have struggled with cocaine abuse during their pregnancies. One woman, now postpartum, wants to breastfeed her infant. Despite being abstinent for the final few months of her pregnancy, I am concerned about the potential adverse effects on her child if she happens to relapse. What is the current evidence about the risks of cocaine exposure during breastfeeding? Answer Given the substantial benefits of breastfeeding for infant health and development, there is no reason for mothers who previously abused cocaine to avoid breastfeeding. It is important for the health care team to counsel patients both on the serious potential risks of cocaine exposure for babies and on the benefits of breastfeeding, to allow for an informed choice. Additionally, attempts should be made to estimate maternal commitment to breastfeeding and discontinuation of cocaine use, and to offer addiction counseling to mitigate the potential risks of infant cocaine exposure. It is paramount to minimize the risk to the infant, which would certainly include mothers ceasing use of cocaine while breastfeeding. For mothers who elect to breastfeed and use cocaine intermittently, breastfeeding should be delayed sufficiently after cocaine use to allow for drug elimination (approximately 24 hours). PMID:23152457

  10. Maternal cocaine use during breastfeeding.

    Science.gov (United States)

    Cressman, Alex M; Koren, Gideon; Pupco, Anna; Kim, Eunji; Ito, Shinya; Bozzo, Pina

    2012-11-01

    In my practice several patients have struggled with cocaine abuse during their pregnancies. One woman, now postpartum, wants to breastfeed her infant. Despite being abstinent for the final few months of her pregnancy, I am concerned about the potential adverse effects on her child if she happens to relapse. What is the current evidence about the risks of cocaine exposure during breastfeeding? Given the substantial benefits of breastfeeding for infant health and development, there is no reason for mothers who previously abused cocaine to avoid breastfeeding. It is important for the health care team to counsel patients both on the serious potential risks of cocaine exposure for babies and on the benefits of breastfeeding, to allow for an informed choice. Additionally, attempts should be made to estimate maternal commitment to breastfeeding and discontinuation of cocaine use, and to offer addiction counseling to mitigate the potential risks of infant cocaine exposure. It is paramount to minimize the risk to the infant, which would certainly include mothers ceasing use of cocaine while breastfeeding. For mothers who elect to breastfeed and use cocaine intermittently, breastfeeding should be delayed sufficiently after cocaine use to allow for drug elimination (approximately 24 hours).

  11. The Effects of Excitatory and Inhibitory Social Cues on Cocaine-Seeking Behavior

    Directory of Open Access Journals (Sweden)

    Mark Andrew Smith

    2016-11-01

    Full Text Available Social partners influence the likelihood of using drugs, developing a substance use disorder, and relapse to drug use after a period of abstinence. Preclinical studies report that social cues influence the acquisition of cocaine use, the escalation of cocaine use over time, and the compulsive patterns of cocaine use that emerge during an extended binge. The purpose of this study was to examine the effects of social cues on the reinstatement of cocaine-seeking behavior after a period of abstinence. Male rats were obtained at weaning, assigned to triads (3 rats/cage, reared to adulthood, and implanted with intravenous catheters. Rats from each triad were then assigned to one of three conditions: (1 test rats were trained to self-administer cocaine and were tested for reinstatement, (2 cocaine partners were trained to self-administer cocaine and were predictive of response-contingent cocaine delivery, and (3 abstinent partners were not given access to cocaine and were predictive of extinction. Test rats alternated social partners every 5 days for 20 days such that responding was reinforced with cocaine in the presence of the cocaine partner (S+ for 10 days and not reinforced with cocaine in the presence of the abstinent partner (S- for 10 days. Responding of the test rats was then extinguished over 7 days under isolated conditions. Tests of reinstatement were then conducted in the presence of the cocaine partner and abstinent partner under extinction conditions. Neither social partner reinstated responding relative to that observed on the final day of extinction; however, responding was greater in the presence of the cocaine partner (S+ than the abstinent partner (S- during the reinstatement test. These data fail to demonstrate that a social partner reinstates cocaine-seeking behavior after a period of abstinence, but they do indicate that social partners can serve as either excitatory or inhibitory discriminative stimuli to influence drug

  12. Predictors of treatment outcome in outpatient cocaine and alcohol dependence treatment.

    Science.gov (United States)

    Ahmadi, Jamshid; Kampman, Kyle M; Oslin, David M; Pettinati, Helen M; Dackis, Charles; Sparkman, Thorne

    2009-01-01

    We examined the ability of several baseline variables to predict treatment outcome in a pharmacotherapy trial that included 164 participants who were both cocaine- and alcohol-dependent and were selected for a randomized, double-blind, placebo-controlled study. Predictor variables included results from the baseline Addiction Severity Index (ASI), initial Urine Drug Screen results, cocaine and alcohol craving and cocaine and alcohol withdrawal symptoms at the start of treatment. Successful treatment was defined as four continuous weeks of self-reported cocaine abstinence verified by urine drug screens. In respect to demographic characteristics, there were no significant differences between patients who achieved four weeks of abstinence from cocaine and those who did not. Baseline variables that most consistently predicted cocaine abstinence included initial urine drug screen (UDS) results, the initial Cocaine Selective Severity Assessment (CSSA) scores, and initial self-reported cocaine use in past 30 days, whereas cocaine craving, cocaine composite scores, alcohol craving, alcohol withdrawal symptoms, and alcohol composite scores did not. The results of this study suggest that cocaine dependence severity in general, and initial UDS results, the CSSA scores and frequency of recent cocaine use in particular, have a significant impact on treatment outcome in the treatment of cocaine-dependent patients with comorbid alcoholism. Initial UDS results and CSSA scores are very useful predictors of treatment outcome and could be used as stratifying variables in outpatient cocaine and alcohol medication trials.

  13. [Cocaine and alcohol: a risky association].

    Science.gov (United States)

    Lacoste, Jérôme; Pedrera-Melgire, Manuela; Charles-Nicolas, Aimé; Ballon, Nicolas

    2010-03-01

    Key points. Cocaine, the second most frequently consumed illicit substance after cannabis in both United States and Europe, remains the psychostimulant of choice for many, often mixed with other psychoactive substances. It is most frequently associated with alcohol, and a diagnosis of alcohol dependence may be made in 50%-90% of cocaine-dependent subjects. When treating cocaine addicts, it is important to characterize not only the modalities of cocaine use but also the modes of consumption of other substances, notably alcohol. Alcohol is often consumed to reduce the anxiety and discomfort resulting from cocaine withdrawal. Alcohol may also trigger an irresistible craving for cocaine, which can result in frequent relapses even after several months of cocaine abstinence. Brief intervention and motivational interview techniques can help to reduce alcohol use and prevent cocaine relapses in this context. In the absence of severe cocaine withdrawal symptoms, the guidelines for treating alcohol withdrawal syndrome may be applied for cocaine and alcohol codependence. Lower doses of benzodiazepine are needed for treating this alcohol-cocaine withdrawal syndrome. Cognitive behavioral therapies, alone or in combination with psychotropic medication, are accepted therapeutic approaches for alcohol-cocaine dependence. It is also accepted that over the long term the combination of psychotherapeutic treatments is usually more effective than any single approach. In the absence of a therapeutic consensus, four drugs (disulfiram, baclofen, topiramate and naltrexone) are most often recommended to promote and maintain abstinence; nevertheless, their efficacy has not been proven and their use remains experimental and off-label: they have not been approved by health authorities as treatment for addictions. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

  14. Attributions for Abstinence from Illicit Drugs by University Students

    Science.gov (United States)

    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…

  15. The use of hair analysis to document a cocaine overdose following a sustained survival period before death.

    Science.gov (United States)

    Martz, R; Donnelly, B; Fetterolf, D; Lasswell, L; Hime, G W; Hearn, W L

    1991-01-01

    Hair analysis for cocaine was used in the investigation of a case of accidental cocaine poisoning. A 25-year-old man consumed an entire bottle of Pony Malta, an imported Colombian soft drink. Unbeknownst to him, the 6.2-oz bottle contained a large quantity of cocaine. It was subsequently discovered that this bottle was one of 45 recovered that contained cocaine as part of a smuggling scheme. The subject was hospitalized for acute cocaine intoxication but died 24 days later. The admission blood contained 2.3 mg/L of cocaine and 4.5 mg/L of benzoylecgonine. Subsequent segmental analysis by MS/MS of hair samples taken at the autopsy revealed a peak cocaine concentration in the segment corresponding to the time he ingested the tainted beverage. The use of hair analysis as an adjunct to traditional analytical techniques may help document drug use history and is especially useful in situations have blood and urine specimens have not been collected in a timely fashion.

  16. Neonatal abstinence syndrome

    Science.gov (United States)

    ... management of neonatal abstinence syndrome secondary to intrauterine opioid exposure. J Pediatr. 2014;165:440-446. www.jpeds.com/article/S0022-3476(14)00429-6/abstract . Review Date 11/3/2015 Updated by: Kimberly G ...

  17. Intra-prelimbic cortical inhibition of striatal-enriched tyrosine phosphatase suppresses cocaine seeking in rats.

    Science.gov (United States)

    Siemsen, Ben M; Lombroso, Paul J; McGinty, Jacqueline F

    2018-01-01

    Cocaine self-administration in rats results in dysfunctional neuroadaptations in the prelimbic (PrL) cortex during early abstinence. Central to these adaptations is decreased phospho-extracellular signal-regulated kinase (p-ERK), which plays a key role in cocaine seeking. Normalizing ERK phosphorylation in the PrL cortex immediately after cocaine self-administration decreases subsequent cocaine seeking. The disturbance in ERK phosphorylation is accompanied by decreased phosphorylation of striatal-enriched protein tyrosine phosphatase (STEP), indicating increased STEP activity. STEP is a well-recognized ERK phosphatase but whether STEP activation during early abstinence mediates the decrease in p-ERK and is involved in relapse is unknown. Here, we show that a single intra-PrL cortical microinfusion of the selective STEP inhibitor, TC-2153, immediately after self-administration suppressed post-abstinence context-induced relapse under extinction conditions and cue-induced reinstatement, but not cocaine prime-induced drug seeking or sucrose seeking. Moreover, an intra-PrL cortical TC-2153 microinfusion immediately after self-administration prevented the cocaine-induced decrease in p-ERK within the PrL cortex during early abstinence. Interestingly, a systemic TC-2153 injection at the same timepoint failed to suppress post-abstinence context-induced relapse or cue-induced reinstatement, but did suppress cocaine prime-induced reinstatement. These data indicate that the STEP-induced ERK dephosphorylation in the PrL cortex during early abstinence is a critical neuroadaptation that promotes relapse to cocaine seeking and that systemic versus intra-PrL cortical inhibition of STEP during early abstinence differentially suppresses cocaine seeking. © 2017 Society for the Study of Addiction.

  18. Levamisole-contaminated cocaine: a hairy affair.

    Science.gov (United States)

    van der Veer, Tjeerd; Pennings, Ed; Tervaert, J W Cohen; Korswagen, Lindy-Anne

    2015-08-26

    Levamisole-contaminated cocaine can induce severe systemic vasculitis. The diagnosis can be challenging, especially when substance abuse is uncertain. We present the case of a 42-year-old woman suffering from vasculitis due to levamisole-contaminated cocaine, who persistently denied substance abuse. Symptoms included ulcerating skin lesions, arthralgia and myalgia, and the occurrence of an ileal intussusception. The definitive diagnosis was made using hair testing for toxins. She recovered through cocaine abstinence, but re-exposure resulted in a severe relapse with glomerulonephritis. Importantly, at time of the relapse, the patient became positive for both myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA) and proteinase 3-ANCA. Cocaine-levamisole-induced vasculitis poses a great clinical challenge. The proper diagnostic strategy and therapy is still controversial. We highlight our diagnostic and therapeutic considerations, including hair testing for definitive proof of exposure. 2015 BMJ Publishing Group Ltd.

  19. Effects of chronic cocaine self-administration on cognition and cerebral glucose utilization in Rhesus monkeys.

    Science.gov (United States)

    Gould, Robert W; Gage, H Donald; Nader, Michael A

    2012-11-15

    Chronic cocaine use is associated with neurobiological and cognitive deficits that persist into abstinence, hindering success of behavioral treatment strategies and perhaps increasing likelihood of relapse. The effects of current cocaine use and abstinence on neurobiology and cognition are not well characterized. Adult male rhesus monkeys with an extensive cocaine self-administration history (∼ 5 years) and age-matched control animals (n = 4/group) performed cognitive tasks in morning sessions and self-administered cocaine or food in afternoon sessions. Positron emission tomography and [(18)F]-fluorodeoxyglucose were employed to assess cerebral metabolic rates of glucose utilization during cognitive testing. Cocaine-experienced monkeys required significantly more trials and committed more errors on reversal learning and multidimensional discriminations, compared with control animals. Cocaine-naive, but not cocaine-experienced, monkeys showed greater metabolic rates of glucose utilization during a multidimensional discrimination task in the caudate nucleus, hippocampus, anterior and posterior cingulate, and regions associated with attention, error detection, memory, and reward. Using a delayed match-to-sample task, there were no differences in baseline working memory performance between groups. High-dose cocaine self-administration disrupted delayed match-to-sample performance but tolerance developed. Acute abstinence from cocaine did not affect performance, but by day 30 of abstinence, accuracy increased significantly, while performance of cocaine-naive monkeys was unchanged. These data document direct effects of cocaine self-administration on cognition and neurobiological sequelae underlying cognitive deficits. Improvements in working memory can occur in abstinence, albeit across an extended period critical for treatment seekers, suggesting pharmacotherapies designed to enhance cognition may improve success of current behavioral modification strategies

  20. Cocaine (Coke, Crack) Facts

    Science.gov (United States)

    ... That People Abuse » Cocaine (Coke, Crack) Facts Cocaine (Coke, Crack) Facts Listen Cocaine is a white ... Version Download "My life was built around getting cocaine and getting high." ©istock.com/ Marjot Stacey is ...

  1. The Effects of Smoking Abstinence on Incentivized Spatial Working Memory.

    Science.gov (United States)

    Geier, Charles; Roberts, Nicole; Lydon-Staley, David

    2018-01-02

    Reward processing and working memory (WM) underlie value-based decision-making; consequently, joint examination of these systems may further our understanding of why smokers choose to smoke again following a quit attempt (relapse). While previous studies have demonstrated altered reward and WM function associated with nicotine exposure, little is known about the effects of abstinence on the joint function of these systems. The current study aims to address this gap. Eighteen daily smokers were tested on a monetarily incentivized memory guided saccade (MGS) task on two separate, counterbalanced occasions, an abstinent and a non-abstinent session. The MGS task is a widely used metric of spatial working memory and enables precise quantification of the effects of rewards and nicotine exposure on behavior. During the non-abstinent session, participants showed increased accuracy of the initial saccade towards the remembered target location on reward vs. neutral trials. Participants also showed increased accuracy of the final saccade towards the target, across incentive types, only during the non-abstinent condition. Our observation that rewards improve the accuracy of the initial memory guided saccade during the non-abstinent but not abstinent condition extends a growing literature indicating reduced motivation towards monetary rewards during abstinence. Further, differences in the accuracy of the final corrective saccade during the non-abstinent but not the abstinent condition suggests smoking abstinence-related effects on WM precision beyond those related to incentive motivation (e.g., sustained attention). This work extends our fundamental understanding of smoking's effects on core affective and cognitive processes.

  2. Predictors of Smokeless Tobacco Abstinence

    Science.gov (United States)

    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…

  3. Hormones, Nicotine and Cocaine: Clinical Studies

    Science.gov (United States)

    Mello, Nancy K.

    2009-01-01

    Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels, and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (two min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine’s sustained positive effects (hormones on nicotine dependence and cocaine abuse, and implications for treatment of these addictive disorders is discussed. PMID:19835877

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

    Science.gov (United States)

    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…

  5. Drug-related decrease in neuropsychological functions of abstinent drug users

    NARCIS (Netherlands)

    van Holst, Ruth Janke; Schilt, Thelma

    2011-01-01

    This article reviews neuropsychological performance in frequent users of cocaine, (meth)amphetamines, ecstasy, opiates, alcohol, and cannabis. We searched the scientific literature published in the last five years, focusing on studies that required at least 2 weeks of abstinence from drug use, and

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

    Science.gov (United States)

    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…

  7. Cocaine Addiction Treatments to improve Control and reduce Harm (CATCH: New Pharmacological Treatment Options for Crack-Cocaine Dependence in the Netherlands

    Directory of Open Access Journals (Sweden)

    van den Brink Wim

    2011-08-01

    Full Text Available Abstract Background Cocaine, particularly in its base form ('crack', has become one of the drugs of most concern in the Netherlands, being associated with a wide range of medical, psychiatric and social problems for the individual, and with significant public order consequences for society. Available treatment options for cocaine dependent users are limited, and a substantial part of the cocaine dependent population is not reached by the addiction treatment system. Psychosocial interventions for cocaine dependence generally show modest results, and there are no registered pharmacological treatments to date, despite the wide range of medications tested for this type of dependence. The present study (Cocaine Addiction Treatments to improve Control and reduce Harm; CATCH investigates the possibilities and problems associated with new pharmacological treatments for crack dependent patients. Methods/Design The CATCH-study consists of three separate randomised controlled, open-label, parallel-group feasibility trials, conducted at three separate addiction treatment institutes in the Netherlands. Patients are either new referrals or patients already in treatment. A total of 216 eligible outpatients are randomised using pre-randomisation double-consent design and receive either 12 weeks treatment with oral topiramate (n = 36; Brijder Addiction Treatment, The Hague, oral modafinil (n = 36; Arkin, Amsterdam, or oral dexamphetamine sustained-release (n = 36; Bouman GGZ, Rotterdam as an add-on to cognitive behavioural therapy (CBT, or receive a 12-week CBT only (controls: n = 3 × 36. Primary outcome in these feasibility trials is retention in the underlying psychosocial treatment (CBT. Secondary outcomes are acceptance and compliance with the study medication, safety, changes in cocaine (and other drug use, physical and mental health, social functioning, and patient satisfaction. Discussion To date, the CATCH-study is the first study in the Netherlands

  8. Modafinil and sleep architecture in an inpatient-outpatient treatment study of cocaine dependence.

    Science.gov (United States)

    Morgan, Peter T; Angarita, Gustavo A; Canavan, Sofija; Pittman, Brian; Oberleitner, Lindsay; Malison, Robert T; Mohsenin, Vahid; Hodges, Sarah; Easton, Caroline; McKee, Sherry; Bessette, Andrew; Forselius, Erica

    2016-03-01

    To determine whether the increase in slow-wave sleep associated with modafinil treatment in chronic cocaine users mediates improved clinical outcomes. 57 cocaine dependent participants were randomized to receive modafinil 400mg or placebo daily during a period of inpatient treatment followed by six weeks of outpatient treatment. Participants underwent polysomnographic sleep recording during inpatient treatment prior to and after starting modafinil. Outpatient treatment consisted of weekly cognitive behavioral therapy. Contingency management was used to promote participation in treatment and research demands, including thrice weekly visits during the outpatient phase for urine toxicology screens and other assessments. The primary clinical outcome was the percent of urine toxicology screens that were negative for cocaine. Modafinil treatment was associated with a higher mean percentage (52% vs. 26%) of cocaine-free urine screens (p=0.02) and an increase in N3 sleep time (p=0.002). The change in N3 sleep time mediated the higher rate of cocaine-free urine screens. Modafinil treatment was also associated with more consecutive days abstinent during outpatient treatment, greater survival of abstinence, higher daily rates of abstinence, and less sleep degradation typically associated with abstinence from chronic cocaine use. Morning-dosed modafinil improves slow-wave sleep in abstinent cocaine users in the inpatient setting, and this effect is a statistical mediator of improved clinical outcomes associated with continued modafinil treatment. The high rates of abstinence achieved in this trial suggest that promoting healthy sleep physiology in an inpatient setting may be important in the effective treatment of cocaine dependence. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. A Double-Blind, Placebo-Controlled Trial of Modafinil for Cocaine Dependence

    Science.gov (United States)

    Dackis, Charles A.; Kampman, Kyle M.; Lynch, Kevin G.; Plebani, Jennifer G.; Pettinati, Helen M.; Sparkman, Thorne; O’Brien, Charles P.

    2012-01-01

    This is a randomized, double blind, placebo-controlled study of modafinil treatment for cocaine dependence. Patients (n=210), who were actively using cocaine at baseline, were randomized to 8-weeks of modafinil (0 mg/day, 200 mg/day or 400 mg/day) combined with once-weekly cognitive behavioral therapy (CBT). Our primary efficacy measure was cocaine abstinence, based on urine benzoylecgonine (BE) levels, with secondary measures of craving, cocaine withdrawal, retention and tolerability. We found no significant differences between modafinil and placebo patients on any of these measures. However, there was a significant gender difference in that male patients treated with 400 mg/day tended to be more abstinent than their placebo-treated counterparts (p=0.06). Our negative findings might be explained by gender differences and/or inadequate psychosocial treatment intensity in patients with severe cocaine dependence. PMID:22377391

  10. Mind Over Matter: Cocaine

    Science.gov (United States)

    ... Term(s): Teachers / NIDA Teaching Guide / Mind Over Matter Teaching Guide and Series / Cocaine Mind Over Matter: Cocaine Print Order Free Publication in: English Spanish Download PDF 806.08 KB Cocaine is ...

  11. Substance use -- cocaine

    Science.gov (United States)

    ... active. Cocaine also causes the brain to release dopamine. Dopamine is a chemical that is involved with mood ... can be Addictive Using cocaine can lead to addiction. This means your mind is dependent on cocaine. ...

  12. The neurobiology of successful abstinence.

    Science.gov (United States)

    Garavan, H; Brennan, K L; Hester, R; Whelan, R

    2013-08-01

    This review focuses on the neurobiological processes involved in achieving successful abstinence from drugs of abuse. While there is clinical and public health value in knowing if the deficits associated with drug use correct with abstinence, studying the neurobiology that underlies successful abstinence can also illuminate the processes that enable drug-dependent individuals to successfully quit. Here, we review studies on human addicts that assess the neurobiological changes that arise with abstinence and the neurobiological predictors of successfully avoiding relapse. The literature, while modest in size, suggests that abstinence is associated with improvement in prefrontal structure and function, which may underscore the importance of prefrontally mediated cognitive control processes in avoiding relapse. Given the implication that the prefrontal cortex may be an important target for therapeutic interventions, we also review evidence indicating the efficacy of cognitive control training for abstinence. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Re-appraisal of negative emotions in cocaine dependence: dysfunctional corticolimbic activation and connectivity.

    Science.gov (United States)

    Albein-Urios, Natalia; Verdejo-Román, Juan; Asensio, Samuel; Soriano-Mas, Carles; Martínez-González, José M; Verdejo-García, Antonio

    2014-05-01

    Cocaine dependence is associated with pronounced elevations of negative affect and deficient regulation of negative emotions. We aimed to investigate the neural substrates of negative emotion regulation in cocaine-dependent individuals (CDI), as compared to non-drug-using controls, using functional magnetic resonance imaging (fMRI) during a re-appraisal task. Seventeen CDI abstinent for at least 15 days and without other psychiatric co-morbidities and 18 intelligence quotient-matched non-drug-using controls participated in the study. Participants performed the re-appraisal task during fMRI scanning: they were exposed to 24 blocks of negative affective or neutral pictures that they should Observe (neutral pictures), Maintain (sustain the emotion elicited by negative pictures) or Suppress (regulate the emotion elicited by negative pictures through previously trained re-appraisal techniques). Task-related activations during two conditions of interest (Maintain>Observe and Suppress>Maintain) were analyzed using the general linear model in SPM8 software. We also performed psychophysiological interaction (PPI) seed-based analyses based on one region from each condition: the dorsolateral prefrontal cortex (dlPFC-Maintain>Observe) and the inferior frontal gyrus (IFG-Suppress>Maintain). Results showed that cocaine users had increased right dlPFC and bilateral temporoparietal junction activations during Maintain>Observe, whereas they showed decreased right IFG, posterior cingulate cortex, insula and fusiform gyrus activations during Suppress>Maintain. PPI analyses showed that cocaine users had increased functional coupling between the dlPFC and emotion-related regions during Maintain>Observe, whereas they showed decreased functional coupling between the right IFG and the amygdala during Suppress>Maintain. These findings indicate that CDI have dysfunctional corticolimbic activation and connectivity during negative emotion experience and re-appraisal. © 2012 The Authors

  14. Regulation of glutamate transporter 1 (GLT-1) gene expression by cocaine self-administration and withdrawal.

    Science.gov (United States)

    Kim, Ronald; Sepulveda-Orengo, Marian T; Healey, Kati L; Williams, Emily A; Reissner, Kathryn J

    2017-09-14

    Downregulation of the astroglial glutamate transporter GLT-1 is observed in the nucleus accumbens (NAc) following administration of multiple drugs of abuse. The decrease in GLT-1 protein expression following cocaine self-administration is dependent on both the amount of cocaine self-administered and the length of withdrawal, with longer access to cocaine and longer withdrawal periods leading to greater decreases in GLT-1 protein. However, the mechanism(s) by which cocaine downregulates GLT-1 protein remains unknown. We used qRT-PCR to examine gene expression of GLT-1 splice isoforms (GLT-1A, GLT-1B) in the NAc, prelimbic cortex (PL) and basolateral amygdala (BLA) of rats, following two widely used models of cocaine self-administration: short-access (ShA) self-administration, and the long-access (LgA) self-administration/incubation model. While downregulation of GLT-1 protein is observed following ShA cocaine self-administration and extinction, this model did not lead to a change in GLT-1A or GLT-1B gene expression in any brain region examined. Forced abstinence following ShA cocaine self-administration also was without effect. In contrast, LgA cocaine self-administration and prolonged abstinence significantly decreased GLT-1A gene expression in the NAc and BLA, and significantly decreased GLT-1B gene expression in the PL. No change was observed in NAc GLT-1A gene expression one day after LgA cocaine self-administration, indicating withdrawal-induced decreases in GLT-1A mRNA. In addition, LgA cocaine self-administration and withdrawal induced hypermethylation of the GLT-1 gene in the NAc. These results indicate that a decrease in NAc GLT-1 mRNA is only observed after extended access to cocaine combined with protracted abstinence, and that epigenetic mechanisms likely contribute to this effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Extinction of conditioned cues attenuates incubation of cocaine craving in adolescent and adult rats.

    Science.gov (United States)

    Madsen, Heather B; Zbukvic, Isabel C; Luikinga, Sophia J; Lawrence, Andrew J; Kim, Jee Hyun

    2017-09-01

    Relapse to drug use is often precipitated by exposure to drug associated cues that evoke craving. Cue-induced drug craving has been observed in both animals and humans to increase over the first few weeks of abstinence and remain high over extended periods, a phenomenon known as 'incubation of craving'. As adolescence represents a period of vulnerability to developing drug addiction, potentially due to persistent reactivity to drug associated cues, we first compared incubation of cocaine craving in adolescent and adult rats. Adolescent (P35) and adult (P70) rats were trained to lever press to obtain intravenous cocaine, with each drug delivery accompanied by a light cue that served as the conditioned stimulus (CS). Following acquisition of stable responding, rats were tested for cue-induced cocaine-seeking after either 1 or 30days of abstinence. Additional groups of rats were also tested after 30days of abstinence, however these rats were subjected to a cue extinction session 1week into the abstinence period. Rats were injected with aripiprazole, a dopamine 2 receptor (D2R)-like partial agonist, or vehicle, 30min prior to cue extinction. We found that adolescent and adult rats acquired and maintained a similar level of cocaine self-administration, and rats of both ages exhibited a higher level of cue-induced cocaine-seeking if they were tested after 30days of abstinence compared to 1day. Incubation of cocaine craving was significantly reduced to 1day levels in both adults and adolescents that received cue extinction training. Administration of aripiprazole prior to cue extinction did not further reduce cue-induced drug-seeking. These results indicate that cue extinction training during abstinence may effectively reduce cue-induced relapse at a time when cue-induced drug craving is usually high. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Adolescent Exposure to the Synthetic Cannabinoid WIN 55212-2 Modifies Cocaine Withdrawal Symptoms in Adult Mice.

    Science.gov (United States)

    Aguilar, María A; Ledesma, Juan Carlos; Rodríguez-Arias, Marta; Penalva, Carles; Manzanedo, Carmen; Miñarro, José; Arenas, M Carmen

    2017-06-21

    Chronic cannabinoid consumption is an increasingly common behavior among teenagers and has been shown to cause long-lasting neurobehavioral alterations. Besides, it has been demonstrated that cocaine addiction in adulthood is highly correlated with cannabis abuse during adolescence. Cocaine consumption and subsequent abstinence from it can cause psychiatric symptoms, such as psychosis, cognitive impairment, anxiety, and depression. The aim of the present research was to study the consequences of adolescent exposure to cannabis on the psychiatric-like effects promoted by cocaine withdrawal in adult mice. We pre-treated juvenile mice with the cannabinoid CB1 receptor agonist WIN 55212-2 (WIN) and then subjected them to a chronic cocaine treatment during adulthood. Following these treatments, animals were tested under cocaine withdrawal in the following paradigms: pre-pulse inhibition, object recognition, elevated plus maze, and tail suspension. The long-term psychotic-like actions induced by WIN were not modified after cocaine cessation. Moreover, the memory impairments induced by cocaine withdrawal were not altered by previous adolescent WIN intake. However, WIN pre-treatment prevented the anxiogenic effects observed after cocaine abstinence, and led to greater depressive-like symptoms following cocaine removal in adulthood. This study is the first to show the long-lasting behavioral consequences of juvenile exposure to WIN on cocaine withdrawal in adult mice.

  17. Modafinil in the treatment of crack-cocaine dependence in the Netherlands: Results of an open-label randomised controlled feasibility trial

    NARCIS (Netherlands)

    Nuijten, Mascha; Blanken, Peter; van den Brink, Wim; Hendriks, Vincent

    2015-01-01

    Crack-cocaine dependence is a serious disorder with no approved pharmacological treatment. Modafinil is a promising medication with increased cocaine abstinence and reduced craving in some previous studies. In the present study, we examined the acceptance, safety and potential benefits of modafinil

  18. Reactivity to laboratory stress provocation predicts relapse to cocaine.

    Science.gov (United States)

    Back, Sudie E; Hartwell, Karen; DeSantis, Stacia M; Saladin, Michael; McRae-Clark, Aimee L; Price, Kimber L; Moran-Santa Maria, Megan M; Baker, Nathaniel L; Spratt, Eve; Kreek, Mary Jeanne; Brady, Kathleen T

    2010-01-01

    Cocaine dependence is a chronic relapsing disorder characterized by periods of abstinence and high rates of return to drug using behavior. Elevated levels of stress have been associated with relapse to cocaine; however, the nature of this association is not well understood. The relationship between reactivity to three human laboratory provocations and relapse to cocaine was investigated. Participants were 53 cocaine-dependent individuals who were admitted for a 2-day inpatient stay during which a psychosocial provocation (i.e., the Trier Social Stress Task), a pharmacological provocation (i.e., administration of 1 microg/kg corticotrophin releasing hormone; CRH), and a drug cue exposure paradigm were completed. Adrenocortico-trophic hormone (ACTH), cortisol, heart rate, and subjective cocaine craving and stress were assessed at baseline and at multiple time points post-task. Participants' cocaine use was monitored for approximately 1 month following testing. The majority (72.3%) of participants relapsed to cocaine during the follow-up period. In response to the CRH and drug cue exposure, elevated subjective craving and stress were significant predictors of cocaine use during follow-up. In response to the Trier, attenuated neuroendocrine responses were significant predictors of cocaine use. The findings provide further evidence of the ability of laboratory paradigms to predict relapse. The observed associations between stress reactivity and subsequent cocaine use highlight the clinical importance of the findings. Predictors of relapse may vary based on the type of provocation utilized. Interventions aimed at normalizing stress response, as measured using laboratory paradigms, may prove useful in relapse prevention. Published by Elsevier Ireland Ltd.

  19. The limited impact that cocaine use patterns have on neurocognitive functioning in individuals with cocaine use disorder.

    Science.gov (United States)

    Mahoney, James J; Kalechstein, Ari D; Newton, Thomas F; De La Garza, Richard

    2017-08-01

    It is well-documented in the literature that cocaine use is associated with neurocognitive impairment. The manner in which patterns of cocaine use, such as years of use, recent use over the past month, and daily amount of cocaine use, moderate neurocognition has been studied in a relatively piecemeal manner. Hence, the purpose of the study was to evaluate whether cocaine use patterns modulate neurocognition in individuals with cocaine use disorder. Cocaine users who were cocaine-negative ( n=125) were divided into tertiles based on cocaine use patterns and the performances of the highest and lowest groups were compared on the following cognitive measures: Continuous Performance Task-II, n-back, and Hopkins Verbal Learning Task-Revised. Participants with cocaine use disorder who used for more years (25.2±0.6 versus 10.1±0.6 years; mean±standard error of the mean) and who had more recent cocaine use over the past month (26.3±0.5 versus 6.0±0.6 days) did not differ significantly on any of the neurocognitive variables when compared to those with use patterns of shorter duration and less frequency (all p's >0.05). Lastly, participants reporting the greatest amount daily cocaine use (1.8±0.0 g) demonstrated better performance on an auditory working memory task when compared to those with the lowest daily use (0.7±0.0 g; p=0.04). While one might expect that individuals who used greater amounts of cocaine over longer periods of time would demonstrate relatively poorer performance on measures of neurocognition, particularly in the initial phase of abstinence, our findings did not confirm this. While speculative, a potential explanation for these findings is that after an individual uses cocaine for a certain number of years, or uses a specific amount over time, then the deleterious effects of cocaine on neurocognition stabilizes, and increased duration of cocaine use does not further exacerbate those impairments.

  20. Self-Reports of Interoceptive Responses During Stress and Drug Cue-Related Experiences in Cocaine- and Alcohol-Dependent Individuals

    OpenAIRE

    Bergquist, Keri L.; Fox, Helen C; Sinha, Rajita

    2010-01-01

    Cocaine dependence is associated with neuroadaptations in stress and reward pathways that could alter stress and drug-related experiences and associated interoceptive sensations and result in enhanced craving states. Subjective interoceptive emotional and physiological responses experienced in stressful and drug cue situations were examined in abstinent cocaine-dependent individuals. Fifty-six treatment engaged cocaine-dependent patients with comorbid alcohol abuse or dependence were intervie...

  1. Cocaine is low on the value ladder of rats: possible evidence for resilience to addiction.

    Science.gov (United States)

    Cantin, Lauriane; Lenoir, Magalie; Augier, Eric; Vanhille, Nathalie; Dubreucq, Sarah; Serre, Fuschia; Vouillac, Caroline; Ahmed, Serge H

    2010-07-28

    Assessing the relative value of cocaine and how it changes with chronic drug use represents a long-standing goal in addiction research. Surprisingly, recent experiments in rats--by far the most frequently used animal model in this field--suggest that the value of cocaine is lower than previously thought. Here we report a series of choice experiments that better define the relative position of cocaine on the value ladder of rats (i.e., preference rank-ordering of different rewards). Rats were allowed to choose either taking cocaine or drinking water sweetened with saccharin--a nondrug alternative that is not biologically essential. By systematically varying the cost and concentration of sweet water, we found that cocaine is low on the value ladder of the large majority of rats, near the lowest concentrations of sweet water. In addition, a retrospective analysis of all experiments over the past 5 years revealed that no matter how heavy was past cocaine use most rats readily give up cocaine use in favor of the nondrug alternative. Only a minority, fewer than 15% at the heaviest level of past cocaine use, continued to take cocaine, even when hungry and offered a natural sugar that could relieve their need of calories. This pattern of results (cocaine abstinence in most rats; cocaine preference in few rats) maps well onto the epidemiology of human cocaine addiction and suggests that only a minority of rats would be vulnerable to cocaine addiction while the large majority would be resilient despite extensive drug use. Resilience to drug addiction has long been suspected in humans but could not be firmly established, mostly because it is difficult to control retrospectively for differences in drug self-exposure and/or availability in human drug users. This conclusion has important implications for preclinical research on the neurobiology of cocaine addiction and for future medication development.

  2. Cocaine is low on the value ladder of rats: possible evidence for resilience to addiction.

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    Lauriane Cantin

    Full Text Available BACKGROUND: Assessing the relative value of cocaine and how it changes with chronic drug use represents a long-standing goal in addiction research. Surprisingly, recent experiments in rats--by far the most frequently used animal model in this field--suggest that the value of cocaine is lower than previously thought. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a series of choice experiments that better define the relative position of cocaine on the value ladder of rats (i.e., preference rank-ordering of different rewards. Rats were allowed to choose either taking cocaine or drinking water sweetened with saccharin--a nondrug alternative that is not biologically essential. By systematically varying the cost and concentration of sweet water, we found that cocaine is low on the value ladder of the large majority of rats, near the lowest concentrations of sweet water. In addition, a retrospective analysis of all experiments over the past 5 years revealed that no matter how heavy was past cocaine use most rats readily give up cocaine use in favor of the nondrug alternative. Only a minority, fewer than 15% at the heaviest level of past cocaine use, continued to take cocaine, even when hungry and offered a natural sugar that could relieve their need of calories. CONCLUSIONS/SIGNIFICANCE: This pattern of results (cocaine abstinence in most rats; cocaine preference in few rats maps well onto the epidemiology of human cocaine addiction and suggests that only a minority of rats would be vulnerable to cocaine addiction while the large majority would be resilient despite extensive drug use. Resilience to drug addiction has long been suspected in humans but could not be firmly established, mostly because it is difficult to control retrospectively for differences in drug self-exposure and/or availability in human drug users. This conclusion has important implications for preclinical research on the neurobiology of cocaine addiction and for future medication

  3. Cocaine Is Low on the Value Ladder of Rats: Possible Evidence for Resilience to Addiction

    Science.gov (United States)

    Dubreucq, Sarah; Serre, Fuschia; Vouillac, Caroline; Ahmed, Serge H.

    2010-01-01

    Background Assessing the relative value of cocaine and how it changes with chronic drug use represents a long-standing goal in addiction research. Surprisingly, recent experiments in rats – by far the most frequently used animal model in this field – suggest that the value of cocaine is lower than previously thought. Methodology/Principal Findings Here we report a series of choice experiments that better define the relative position of cocaine on the value ladder of rats (i.e., preference rank-ordering of different rewards). Rats were allowed to choose either taking cocaine or drinking water sweetened with saccharin – a nondrug alternative that is not biologically essential. By systematically varying the cost and concentration of sweet water, we found that cocaine is low on the value ladder of the large majority of rats, near the lowest concentrations of sweet water. In addition, a retrospective analysis of all experiments over the past 5 years revealed that no matter how heavy was past cocaine use most rats readily give up cocaine use in favor of the nondrug alternative. Only a minority, fewer than 15% at the heaviest level of past cocaine use, continued to take cocaine, even when hungry and offered a natural sugar that could relieve their need of calories. Conclusions/Significance This pattern of results (cocaine abstinence in most rats; cocaine preference in few rats) maps well onto the epidemiology of human cocaine addiction and suggests that only a minority of rats would be vulnerable to cocaine addiction while the large majority would be resilient despite extensive drug use. Resilience to drug addiction has long been suspected in humans but could not be firmly established, mostly because it is difficult to control retrospectively for differences in drug self-exposure and/or availability in human drug users. This conclusion has important implications for preclinical research on the neurobiology of cocaine addiction and for future medication development

  4. Effects of sleep deprivation on brain bioenergetics, sleep, and cognitive performance in cocaine-dependent individuals.

    Science.gov (United States)

    Trksak, George H; Bracken, Bethany K; Jensen, J Eric; Plante, David T; Penetar, David M; Tartarini, Wendy L; Maywalt, Melissa A; Dorsey, Cynthia M; Renshaw, Perry F; Lukas, Scott E

    2013-01-01

    In cocaine-dependent individuals, sleep is disturbed during cocaine use and abstinence, highlighting the importance of examining the behavioral and homeostatic response to acute sleep loss in these individuals. The current study was designed to identify a differential effect of sleep deprivation on brain bioenergetics, cognitive performance, and sleep between cocaine-dependent and healthy control participants. 14 healthy control and 8 cocaine-dependent participants experienced consecutive nights of baseline, total sleep deprivation, and recovery sleep in the research laboratory. Participants underwent ³¹P magnetic resonance spectroscopy (MRS) brain imaging, polysomnography, Continuous Performance Task, and Digit Symbol Substitution Task. Following recovery sleep, ³¹P MRS scans revealed that cocaine-dependent participants exhibited elevated global brain β-NTP (direct measure of adenosine triphosphate), α-NTP, and total NTP levels compared to those of healthy controls. Cocaine-dependent participants performed worse on the Continuous Performance Task and Digit Symbol Substitution Task at baseline compared to healthy control participants, but sleep deprivation did not worsen cognitive performance in either group. Enhancements of brain ATP levels in cocaine dependent participants following recovery sleep may reflect a greater impact of sleep deprivation on sleep homeostasis, which may highlight the importance of monitoring sleep during abstinence and the potential influence of sleep loss in drug relapse.

  5. Effects of Sleep Deprivation on Brain Bioenergetics, Sleep, and Cognitive Performance in Cocaine-Dependent Individuals

    Directory of Open Access Journals (Sweden)

    George H. Trksak

    2013-01-01

    Full Text Available In cocaine-dependent individuals, sleep is disturbed during cocaine use and abstinence, highlighting the importance of examining the behavioral and homeostatic response to acute sleep loss in these individuals. The current study was designed to identify a differential effect of sleep deprivation on brain bioenergetics, cognitive performance, and sleep between cocaine-dependent and healthy control participants. 14 healthy control and 8 cocaine-dependent participants experienced consecutive nights of baseline, total sleep deprivation, and recovery sleep in the research laboratory. Participants underwent [31]P magnetic resonance spectroscopy (MRS brain imaging, polysomnography, Continuous Performance Task, and Digit Symbol Substitution Task. Following recovery sleep, [31]P MRS scans revealed that cocaine-dependent participants exhibited elevated global brain β-NTP (direct measure of adenosine triphosphate, α-NTP, and total NTP levels compared to those of healthy controls. Cocaine-dependent participants performed worse on the Continuous Performance Task and Digit Symbol Substitution Task at baseline compared to healthy control participants, but sleep deprivation did not worsen cognitive performance in either group. Enhancements of brain ATP levels in cocaine dependent participants following recovery sleep may reflect a greater impact of sleep deprivation on sleep homeostasis, which may highlight the importance of monitoring sleep during abstinence and the potential influence of sleep loss in drug relapse.

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

    Science.gov (United States)

    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

  7. Neural Changes Developed during the Extinction of Cocaine Self-Administration Behavior

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    Nuria del Olmo

    2011-10-01

    Full Text Available The high rate of recidivism in cocaine addiction after prolonged periods of abstinence poses a significant problem for the effective treatment of this condition. Moreover, the neurobiological basis of this relapse phenomenon remains poorly understood. In this review, we will discuss the evidence currently available regarding the neurobiological changes during the extinction of cocaine self-administration. Specifically, we will focus on alterations in the dopaminergic, opioidergic, glutamatergic, cholinergic, serotoninergic and CRF systems described in self-administration experiments and extinction studies after chronic cocaine administration. We will also discuss the differences related to contingent versus non-contingent cocaine administration, which highlights the importance of environmental cues on drug effects and extinction. The findings discussed in this review may aid the development of more effective therapeutic approaches to treat cocaine relapse.

  8. Treadmill exercise improves fitness and reduces craving and use of cocaine in individuals with concurrent cocaine and tobacco-use disorder.

    Science.gov (United States)

    De La Garza, Richard; Yoon, Jin H; Thompson-Lake, Daisy G Y; Haile, Colin N; Eisenhofer, Joel D; Newton, Thomas F; Mahoney, James J

    2016-11-30

    Exercise may be a useful treatment for substance use disorders. Participants (N=24) included treatment-seeking individuals with concurrent cocaine and tobacco-use disorder (cigarette smokers). Participants were randomized to either running or walking (30min per session, 3 times per week) or sitting (control condition) for 4 consecutive weeks. Several metrics indicated significant differences among runners, walkers, and sitters during sessions, including mean distance covered and calories burned. In addition, remote physiological monitoring showed that the groups differed significantly according to mean maximum heart rate (HR), respiration, and locomotor activity. Across the 4-week study, exercise improved fitness measures including significantly decreasing resting HR. Though not statistically significant, exercise improved abstinence from cocaine and increased self-reports of no cocaine use in last 24h. In general, reductions in tobacco use and craving were not as robust. To our knowledge, this is the first study to evaluate the effects of a multi-week exercise program in individuals with concurrent cocaine and tobacco-use disorder. The data clearly show significant improvements in basic fitness measures and several indices reveal that exercise improved both self-report and biochemically verified reports of cocaine abstinence. Taken together, the data from this study provide preliminary evidence for the efficacy of exercise for improving fitness and reducing cocaine use. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Cocaine craving during protracted withdrawal requires PKCε priming within vmPFC.

    Science.gov (United States)

    Miller, Bailey W; Wroten, Melissa G; Sacramento, Arianne D; Silva, Hannah E; Shin, Christina B; Vieira, Philip A; Ben-Shahar, Osnat; Kippin, Tod E; Szumlinski, Karen K

    2017-05-01

    In individuals with a history of drug taking, the capacity of drug-associated cues to elicit indices of drug craving intensifies or incubates with the passage of time during drug abstinence. This incubation of cocaine craving, as well as difficulties with learning to suppress drug-seeking behavior during protracted withdrawal, are associated with a time-dependent deregulation of ventromedial prefrontal cortex (vmPFC) function. As the molecular bases for cocaine-related vmPFC deregulation remain elusive, the present study assayed the consequences of extended access to intravenous cocaine (6 hours/day; 0.25 mg/infusion for 10 day) on the activational state of protein kinase C epsilon (PKCε), an enzyme highly implicated in drug-induced neuroplasticity. The opportunity to engage in cocaine seeking during cocaine abstinence time-dependently altered PKCε phosphorylation within vmPFC, with reduced and increased p-PKCε expression observed in early (3 days) and protracted (30 days) withdrawal, respectively. This effect was more robust within the ventromedial versus dorsomedial PFC, was not observed in comparable cocaine-experienced rats not tested for drug-seeking behavior and was distinct from the rise in phosphorylated extracellular signal-regulated kinase observed in cocaine-seeking rats. Further, the impact of inhibiting PKCε translocation within the vmPFC using TAT infusion proteins upon cue-elicited responding was determined and inhibition coinciding with the period of testing attenuated cocaine-seeking behavior, with an effect also apparent the next day. In contrast, inhibitor pretreatment prior to testing during early withdrawal was without effect. Thus, a history of excessive cocaine taking influences the cue reactivity of important intracellular signaling molecules within the vmPFC, with PKCε playing a critical role in the manifestation of cue-elicited cocaine seeking during protracted drug withdrawal. © 2016 Society for the Study of Addiction.

  10. Adolescent but not adult ethanol binge drinking modulates cocaine withdrawal symptoms in mice.

    Science.gov (United States)

    Ledesma, Juan Carlos; Aguilar, Maria A; Giménez-Gómez, Pablo; Miñarro, José; Rodríguez-Arias, Marta

    2017-01-01

    Ethanol (EtOH) binge drinking is an increasingly common behavior among teenagers that induces long-lasting neurobehavioral alterations in adulthood. An early history of EtOH abuse during adolescence is highly correlated with cocaine addiction in adulthood. Abstinence of cocaine abuse can cause psychiatric symptoms, such as anxiety, psychosis, depression, and cognitive impairments. This study assessed the consequences of adolescent exposure to EtOH on the behavioral alterations promoted by cocaine withdrawal in adulthood. We pretreated juvenile (34-47 days old) or adult (68-81 days old) mice with EtOH (1.25 g/kg) following a binge-drinking pattern. Then, after a three-week period without drug delivery, they were subjected to a chronic cocaine treatment in adulthood and tested under cocaine withdrawal by the ensuing paradigms: open field, elevated plus maze, prepulse inhibition, tail suspension test, and object recognition. Another set of mice were treated with the same EtOH binge-drinking procedure during adolescence and were tested immediately afterwards under the same behavioral paradigms. Adolescent EtOH pretreatment undermined the anxiogenic effects observed after cocaine abstinence, reduced prepulse inhibition, and increased immobility scores in the tail suspension test following cocaine withdrawal. Moreover, the memory deficits evoked by these substances when given separately were enhanced in cocaine-withdrawn mice exposed to EtOH during adolescence. EtOH binge drinking during adolescence also induced anxiety, depressive symptoms, and memory impairments when measured immediately afterwards. In contrast, neither EtOH nor cocaine alone or in combination altered any of these behaviors when given in adulthood. EtOH binge drinking induces short- and long-term behavioral alterations and modulates cocaine withdrawal symptoms when given in adolescent mice.

  11. Adolescent but not adult ethanol binge drinking modulates cocaine withdrawal symptoms in mice

    Science.gov (United States)

    Aguilar, Maria A.; Giménez-Gómez, Pablo; Miñarro, José; Rodríguez-Arias, Marta

    2017-01-01

    Background Ethanol (EtOH) binge drinking is an increasingly common behavior among teenagers that induces long-lasting neurobehavioral alterations in adulthood. An early history of EtOH abuse during adolescence is highly correlated with cocaine addiction in adulthood. Abstinence of cocaine abuse can cause psychiatric symptoms, such as anxiety, psychosis, depression, and cognitive impairments. This study assessed the consequences of adolescent exposure to EtOH on the behavioral alterations promoted by cocaine withdrawal in adulthood. Methods We pretreated juvenile (34–47 days old) or adult (68–81 days old) mice with EtOH (1.25 g/kg) following a binge-drinking pattern. Then, after a three-week period without drug delivery, they were subjected to a chronic cocaine treatment in adulthood and tested under cocaine withdrawal by the ensuing paradigms: open field, elevated plus maze, prepulse inhibition, tail suspension test, and object recognition. Another set of mice were treated with the same EtOH binge-drinking procedure during adolescence and were tested immediately afterwards under the same behavioral paradigms. Results Adolescent EtOH pretreatment undermined the anxiogenic effects observed after cocaine abstinence, reduced prepulse inhibition, and increased immobility scores in the tail suspension test following cocaine withdrawal. Moreover, the memory deficits evoked by these substances when given separately were enhanced in cocaine-withdrawn mice exposed to EtOH during adolescence. EtOH binge drinking during adolescence also induced anxiety, depressive symptoms, and memory impairments when measured immediately afterwards. In contrast, neither EtOH nor cocaine alone or in combination altered any of these behaviors when given in adulthood. Conclusions EtOH binge drinking induces short- and long-term behavioral alterations and modulates cocaine withdrawal symptoms when given in adolescent mice. PMID:28291777

  12. Adolescent but not adult ethanol binge drinking modulates cocaine withdrawal symptoms in mice.

    Directory of Open Access Journals (Sweden)

    Juan Carlos Ledesma

    Full Text Available Ethanol (EtOH binge drinking is an increasingly common behavior among teenagers that induces long-lasting neurobehavioral alterations in adulthood. An early history of EtOH abuse during adolescence is highly correlated with cocaine addiction in adulthood. Abstinence of cocaine abuse can cause psychiatric symptoms, such as anxiety, psychosis, depression, and cognitive impairments. This study assessed the consequences of adolescent exposure to EtOH on the behavioral alterations promoted by cocaine withdrawal in adulthood.We pretreated juvenile (34-47 days old or adult (68-81 days old mice with EtOH (1.25 g/kg following a binge-drinking pattern. Then, after a three-week period without drug delivery, they were subjected to a chronic cocaine treatment in adulthood and tested under cocaine withdrawal by the ensuing paradigms: open field, elevated plus maze, prepulse inhibition, tail suspension test, and object recognition. Another set of mice were treated with the same EtOH binge-drinking procedure during adolescence and were tested immediately afterwards under the same behavioral paradigms.Adolescent EtOH pretreatment undermined the anxiogenic effects observed after cocaine abstinence, reduced prepulse inhibition, and increased immobility scores in the tail suspension test following cocaine withdrawal. Moreover, the memory deficits evoked by these substances when given separately were enhanced in cocaine-withdrawn mice exposed to EtOH during adolescence. EtOH binge drinking during adolescence also induced anxiety, depressive symptoms, and memory impairments when measured immediately afterwards. In contrast, neither EtOH nor cocaine alone or in combination altered any of these behaviors when given in adulthood.EtOH binge drinking induces short- and long-term behavioral alterations and modulates cocaine withdrawal symptoms when given in adolescent mice.

  13. Maintenance Sessions Prolong Cigarette Abstinence.

    Science.gov (United States)

    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…

  14. Adolescence and abstinence. Fact sheet.

    Science.gov (United States)

    1997-01-01

    This fact sheet presents statistics on adolescent sexual activity in the US and a brief description of comprehensive sex education and abstinence-only programs. The statistical profile indicates that over 50% of teenagers are virgins until at least 17 years of age. 20% of boys and 24% of girls are virgins by the age of 20 years. Only 6.9% of men 18-59 years old and 21% of women 18-59 years old were still virgins on their wedding night. However, among a sample of high school students, over 33% of male and female virgins had engaged in some form of heterosexual genital sexual activity in the preceding year. 29% of virgins had masturbated a partner of the opposite gender. 31% had been masturbated by a partner of the opposite gender. 9% had engaged in fellatio with ejaculation with a partner of the opposite gender. 10% had engaged in cunnilingus with a partner of the opposite gender. 1% had engaged in anal intercourse with a partner of the opposite gender. Comprehensive sex education aims to help adolescents postpone sexual intercourse until they are ready for mature relationships by helping them develop interpersonal skills to resist premature sexual involvement. Messages include information about sexual abstinence, contraception, and safer sex. A 1993 study found that sexual abstinence messages were one of the most frequently covered topics in state curricula and guidelines. Other key topics were families, decision making, and sexually transmitted diseases including AIDS. The least covered topics were sexual identity, shared sexual behavior, sexual response, masturbation, and abortion. There were only six studies of abstinence-only programs, of which at least two showed no impact on sexual or contraceptive behavior. The National Institute of Health says that abstinence-only programs ignore the success of other programs and conflict with science.

  15. A protein synthesis-dependent mechanism sustains calcium-permeable AMPA receptor transmission in nucleus accumbens synapses during withdrawal from cocaine self-administration.

    Science.gov (United States)

    Scheyer, Andrew F; Wolf, Marina E; Tseng, Kuei Y

    2014-02-19

    Extended-access cocaine self-administration results in withdrawal-dependent incubation of cocaine craving. Rats evaluated after ∼1 month of withdrawal from such regimens ("incubated rats") exhibit changes in medium spiny neurons (MSNs) of the nucleus accumbens (NAc) that include accumulation of Ca(2+)-permeable AMPA receptors (CP-AMPARs) and a switch in group I metabotropic glutamate receptor (mGluR)-mediated suppression of synaptic transmission from mGluR5-dependent to mGluR1-dependent. To determine the role of protein synthesis in mediating these adaptations, we conducted whole-cell patch-clamp recordings in NAc core MSNs of "incubated rats" in the presence of translational inhibitors (anisomycin, cycloheximide, rapamycin) or the transcriptional inhibitor actinomycin-D. The contribution of CP-AMPARs to synaptic transmission was determined by the rectification index and the sensitivity to the CP-AMPAR antagonist 1-naphthyl acetyl spermine. We found that CP-AMPAR-mediated transmission in the NAc of "incubated rats" was reduced to levels comparable to those found in saline control rats when brain slices were treated with translational inhibitors, whereas actinomycin-D had no effect. We also investigated the effect of protein translation inhibitors on the switch of mGluR function in MSNs of "incubated rats" using the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine in combination with either an mGluR1 (LY367385) or an mGluR5 (3-[(2-methyl-4-thiazolyl)ethynyl]pyridine) antagonist. Data revealed that inhibition of protein translation eliminated the mGluR1-mediated inhibition and restored the mGluR5 responsiveness to a state functionally similar to that of saline control rats. Together, these results suggest that aberrant regulation of local protein synthesis contributes to the maintenance of adaptations accrued at NAc MSN synapses during incubation of cocaine craving.

  16. Clinical presentation and management of neonatal abstinence syndrome: an update

    Directory of Open Access Journals (Sweden)

    Ordean A

    2014-04-01

    Full Text Available Alice Ordean,1 Brian C Chisamore21Department of Family Medicine, 2Department of Pediatrics, St Joseph's Health Centre, and University of Toronto, Toronto, ON, CanadaAbstract: Exposure to prescription medications and illicit drug use during pregnancy has been associated with neonatal abstinence syndrome. The clinical presentation consists of neurological respiratory, gastrointestinal, and vasomotor disturbances. All infants require observation and supportive care to ensure appropriate adaptation and growth in the newborn period. A smaller percentage may also require additional pharmacotherapy, depending on the specific gestational substance exposure. Women should be counseled antenatally about the possible neonatal effects, and mother–baby dyad care should be implemented for this particular patient population.Keywords: neonatal withdrawal, opioids, marijuana, cocaine, benzodiazepines, selective serotonin reuptake inhibitors

  17. Cocaine addiction as a neurological disorder: implications for treatment.

    Science.gov (United States)

    Majewska, M D

    1996-01-01

    biological psychiatry. While a majority of drug addicts are polydrug users, there seems to be a preference for a particular type of drug among different populations of addicts. Addicts who experience distress, anxious dysphoria, and turbulent anger prefer the calming actions of opiates, whereas addicts with preceding attention deficit disorder, depression, or bipolar disorder often prefer stimulants (Khantzian 1985). Figure 1 presents conceptual relationships between brain damage and cocaine/stimulant abuse. More clinical studies are needed to establish unequivocally the epidemiological relationships between preexisting neurological deficits-resulting either from genetic, developmental, traumatic, or neurotoxic factors- and vulnerability to drug addictions. Nonetheless, deducing from the results of preclinical studies, it is conceivable that individuals with neurological deficits associated with attention deficit disorder, developmental neuroanatomical abnormalities, lead poisoning, alcoholism, posttraumatic brain lesions, and PTSD may be more vulnerable to stimulant addiction. This notion has significant empirical support as preclinical studies have shown that animals with lesioned prefrontal cortex became supersensitive to cocaine (Schenk et al. 1991) and animals with lesions at the amygdala, VTA, or raphe nuclei manifest more rapid acquisition of amphetamine self-administration than control rats (Deminiere et al. 1989). The above arguments, postulating neuropathology as an intrinsic component of stimulant addiction, should be taken into consideration with the caveat that the clinical manifestations of the disease are heterogenous and addicts may express varying stages and degrees of the disease as determined by environmental and genetic factors. Therefore, it is likely that stimulant addicts who have less advanced neuropathology may recover spontaneously after detoxification with proper nutritional and psychotherapeutic support if they can sustain abstinence. (ABSTR

  18. Modafinil Treatment of Cocaine Dependence: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Sangroula, Dinesh; Motiwala, Fatima; Wagle, Bivek; Shah, Vivek C; Hagi, Katsuhiko; Lippmann, Steven

    2017-08-24

    Currently, there is none FDA-approved medication to treat cocaine dependency. Studies conducted with various medications, including antipsychotics, antidepressants, anticonvulsants, and others, revealed inconsistent results. To meta-analytically investigate the efficacy and safety of modafinil in the treatment of cocaine-dependent patients. Randomized controlled trials with ≥20 subjects comparing the numerical therapeutic outcomes of modafinil with placebo were identified in databases, such as PUBMED, psycINFO, EMBASE, and Clinicaltrials.gov. Relevant data on efficacy and safety were extracted. Relative risk (RR) and standardized mean difference were applied for reporting dichotomous and continuous outcomes respectively. Random effects, subgroup, and meta-regression analyses were conducted to further explore the results and evaluate for any moderators. In total, 11 studies (participants = 896, duration = 6.7 ± 1.9 weeks) comparing modafinil with placebo were systematically analyzed, which indicated that modafinil was not superior to placebo in improving the treatment retention rate (studies = 11, participants = 891, RR = 1.030, 95% CI = 0.918-1.156, p = .613). Similarly, data from 7/11 studies did not evidence superiority of modafinil in achieving cocaine abstinence (participants = 696, RR = 1.259, 95% CI = 0.813-1.949, p = .302). However, subgroup analysis of six studies conducted in the United States demonstrated superiority of modafinil in cocaine abstinence rate (studies = 6, participants = 669, 95% CI = 1.027-2.020, p = 0.035). In addition, no evidence suggested modafinil-related discontinuation or specific adverse events than placebo. Overall, there is no evidence to conclude superiority of modafinil in increasing cocaine abstinence and treatment retention rate. However, promising result in subgroup analysis of cocaine abstinence, secondary outcomes, and good safety profile urged the need of larger studies to derive more conclusive results.

  19. Cocaine-Induced Vasculitis

    Directory of Open Access Journals (Sweden)

    Mark Berman

    2016-10-01

    Full Text Available The use of cocaine continues to grow worldwide. One of the possible side-effects of cocaine is vasculitis. Two distinct vasculitic syndromes have been described due to cocaine. One is cocaine-induced midline destructive lesion, secondary to a direct vasoconstrictor effect of cocaine, inducing ischemic necrosis of the septal cartilage and perforation of the nasal septum, mimicking findings of granulomatosis with polyangiitis in the upper airways. The other is ANCA-associated vasculitis, attributed to the levamisole component that contaminates about 70% of the cocaine. This type of vasculitis may be myeloperoxidase (MPO and proteinase 3 (PR3 positive, and its main manifestations are typical cutaneous findings, arthralgia, otolaryngologic involvement, and agranulocytosis. A high degree of suspicion and awareness is needed in order properly to diagnose and treat these patients.

  20. Gene x abstinence effects on drug cue reactivity in addiction: multimodal evidence.

    Science.gov (United States)

    Moeller, Scott J; Parvaz, Muhammad A; Shumay, Elena; Beebe-Wang, Nicasia; Konova, Anna B; Alia-Klein, Nelly; Volkow, Nora D; Goldstein, Rita Z

    2013-06-12

    Functional polymorphisms in the dopamine transporter gene (DAT1 or SLC6A3) modulate responsiveness to salient stimuli, such that carriers of one 9R-allele of DAT1 (compared with homozygote carriers of the 10R-allele) show heightened reactivity to drug-related reinforcement in addiction. Here, using multimodal neuroimaging and behavioral dependent variables in 73 human cocaine-addicted individuals and 47 healthy controls, we hypothesized and found that cocaine-addicted carriers of a 9R-allele exhibited higher responses to drug cues, but only among individuals who had used cocaine within 72 h of the study as verified by positive cocaine urine screens (a state characterized by intense craving). Importantly, this responsiveness to drug cues was reliably preserved across multimodal imaging and behavioral probes: psychophysiological event-related potentials, self-report, simulated cocaine choice, and fMRI. Because drug cues contribute to relapse, our results identify the DAT1R 9R-allele as a vulnerability allele for relapse especially during early abstinence (e.g., detoxification).

  1. Pharmacokinetics of disappearance of cocaine from hair after discontinuation of drug use.

    Science.gov (United States)

    Garcia-Bournissen, F; Moller, M; Nesterenko, M; Karaskov, T; Koren, G

    2009-08-10

    Methods that employ detection of drugs of abuse in hair are important for monitoring compliance with drug abstinence. Understanding the mechanisms and timeline of drug disappearance from hair is critical for clinical and forensic application of hair testing. We aimed to evaluate the kinetics of disappearance of cocaine and its metabolite, benzoylecgonine (BE), from hair after discontinuation of drug use. The Motherisk laboratory at the Hospital for Sick Children in Toronto routinely receives hair samples for toxicology analysis. Cocaine and BE hair results were obtained from the Motherisk Database for calculation of half-life of these compounds in hair. Subjects were included in the study if they had gradually decreasing concentrations of cocaine and/or BE in sequential hair samples, with higher levels in the 1-3 cm distal segments (i.e. earlier in time) and low or non-measurable levels in the segment closest to the scalp (i.e. closer to the date of sampling). Elimination half-life of cocaine and BE in hair was calculated using standard kinetics calculations. The study was anonymous, and received ethics approval by the Ethics Review Board of our institution. 137 subjects met the inclusion criteria for the study. The median half-life of cocaine in hair was 1.5 months (95% CI 1.2-1.8) in females and 1.5 months (95% CI 1.1-1.8) in males. The median half-life of BE was 1.5 months (95% CI 1.1-2) in females and 1.5 months (95% CI 0.8-1.8) in males. Half lives of cocaine or BE were not statistically different between males and females (Mann-Whitney U-test; P=0.93 for cocaine, P=0.99 for BE). Half lives of cocaine and BE were strongly correlated (Spearman rank rho=0.73; P<0.001). Cocaine and BE could be detected in hair of former drug users for several months after abstinence. The calculated half-life of over 1 month for cocaine implies that, assuming first order elimination, approximately 3-4 months have to pass for hair testing to become negative in the segment proximal

  2. Serotonin at the Nexus of Impulsivity and Cue Reactivity in Cocaine Addiction

    Science.gov (United States)

    Cunningham, Kathryn A.; Anastasio, Noelle C.

    2014-01-01

    Cocaine abuse and addiction remain great challenges on the public health agendas in the U.S. and the world. Increasingly sophisticated perspectives on addiction to cocaine and other drugs of abuse have evolved with concerted research efforts over the last 30 years. Relapse remains a particularly powerful clinical problem as, even upon termination of drug use and initiation of abstinence, the recidivism rates can be very high. The cycling course of cocaine intake, abstinence and relapse is tied to a multitude of behavioral and cognitive processes including impulsivity (a predisposition toward rapid unplanned reactions to stimuli without regard to the negative consequences), and cocaine cue reactivity (responsivity to cocaine-associated stimuli) cited as two key phenotypes that contribute to relapse vulnerability even years into recovery. Preclinical studies suggest that serotonin (5-hydroxytryptamine; 5-HT) neurotransmission in key neural circuits may contribute to these interlocked phenotypes well as the altered neurobiological states evoked by cocaine that precipitate relapse events. As such, 5-HT is an important target in the quest to to understand the neurobiology of relapse-predictive phenotypes, to successfully treat this complex disorder and improve diagnostic and prognostic capabilities. This review emphasizes the role of 5-HT and its receptor proteins in key addiction phenotypes and the implications of current findings to the future of therapeutics in addiction. PMID:23850573

  3. Anxiety, depression and tobacco abstinence.

    Science.gov (United States)

    Almadana Pacheco, Virginia; Gómez-Bastero Fernández, Ana Paulina; Valido Morales, Agustín; Luque Crespo, Estefanía; Monserrat, Soledad; Montemayor Rubio, Teodoro

    2017-09-29

    There is evidence of the relationship between mental illness and smoking and increased risk of depressive episodes after quitting smoking, even with specific treatments for abstinence. To assess the influence of a cessation program on the emotional state of patients by measuring levels of anxiety / depression and differences depending on the presence of psychiatric history. A prospective observational study of patients taking part in a combined program (pharmacological and cognitive-behavioral) for giving up smoking. Anxiety (A) and depression (D) were measured using the HADS questionnaire at baseline, first and third month of abstinence. Anxiety and depression showed significant and progressive improvement during treatment (A: baseline 9.2 ± 4.5, 5.9 ± 3.6 1 month, 3 months 4.5 ± 3.1, p.

  4. A double blind, placebo controlled trial of modafinil for the treatment of cocaine dependence without co-morbid alcohol dependence.

    Science.gov (United States)

    Kampman, Kyle M; Lynch, Kevin G; Pettinati, Helen M; Spratt, Kelly; Wierzbicki, Michael R; Dackis, Charles; O'Brien, Charles P

    2015-10-01

    Modafinil is a medication approved for narcolepsy and shift work sleep disorder. It has both dopaminergic and glutamatergic activity that could be useful for the treatment of cocaine dependence. Modafinil has reduced cocaine subjective effects and cocaine self-administration in human laboratory trials and has reduced cocaine use in cocaine dependent patients in some clinical trials. This was an 8-week, double blind, placebo controlled clinical trial involving 94 cocaine dependent subjects. Subjects received 300mg of modafinil or identical placebo daily along with weekly individual therapy. The primary outcome measure was cocaine use measured by self-report, and confirmed by twice weekly urine benzoylecgonine tests (UBT). Additional outcome measures included cocaine craving measured by the Brief Substance Craving Scale and global improvement measured by the Clinical Global Impression Scale (CGI). The odds ratio (OR) in favor of abstinence for modafinil vs. placebo was 2.54 (p=. 03) and modafinil-treated subjects were significantly more likely than placebo-treated subjects to be abstinent from cocaine during the last 3 weeks of the trial, 23% vs. 9%, χ(2)=3.9, pModafinil treated subjects were more likely to report very low levels of cocaine craving intensity and duration on the Brief Substance Craving Scale (OR=2.04, p=.03 and OR 1.06, p=.03 respectively). Modafinil-treated subjects were also more likely than placebo-treated subjects to rate themselves as "very much improved" on the CGI (OR=2.69, p=.03). Modafinil may be an efficacious treatment for cocaine dependence. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Deletion of Type 2 Metabotropic Glutamate Receptor Decreases Sensitivity to Cocaine Reward in Rats

    Directory of Open Access Journals (Sweden)

    Hong-Ju Yang

    2017-07-01

    Full Text Available Cocaine users show reduced expression of the metabotropic glutamate receptor (mGluR2, but it is not clear whether this is a predisposing trait for addiction or a consequence of drug exposure. In this study, we found that a nonsense mutation at the mGluR2 gene decreased mGluR2 expression and altered the seeking and taking of cocaine. mGluR2 mutant rats show reduced sensitivity to cocaine reward, requiring more cocaine to reach satiation when it was freely available and ceasing their drug-seeking behavior sooner than controls when the response requirement was increased. mGluR2 mutant rats also show a lower propensity to relapse after a period of cocaine abstinence, an effect associated with reduced cocaine-induced dopamine and glutamate overflow in the nucleus accumbens. These findings suggest that mGluR2 polymorphisms or reduced availability of mGluR2 might be risk factors for the initial development of cocaine use but could actually protect against addiction by reducing sensitivity to cocaine reward.

  6. Hair testing is superior to urine to disclose cocaine consumption in driver's licence regranting.

    Science.gov (United States)

    Polla, M; Stramesi, C; Pichini, S; Palmi, I; Vignali, C; Dall'Olio, G

    2009-08-10

    In driver licence regranting, subjects with a history of cocaine use are requested to undergo laboratory testing to verify both current and past abstinence from the drug. Identification of cocaine use based only on urinalysis may miss some cases because of the short elimination half-life of the drug. Moreover, many abusers know how to time their cocaine consumption in such a way that they can "beat" the urinalysis, having a series of negative urine tests. We report on the use of hair testing to disclose sporadic cocaine consumption in seven subjects attending the Local Medical Commission to reobtain driver licence, with constant negative urinalysis. Even with one or two weekly negative urine screens along several months, all the subjects were positive using hair testing for cocaine and benzoylecgonine, above the internationally recommended limit of quantification: 0.5 ng/mg and 0.05 ng/mg for cocaine and benzoylecgonine, respectively (concentration range for cocaine: 0.51-2.23 ng/mg hair; concentration range for benzoylecgonine: 0.08-1.70 ng/mg hair). The obtained results support strongly the use of hair testing for cocaine in drug addicts and occasional abusers applying for regranting of driver licence in order to minimize social risk behaviours.

  7. Subtypes of cocaine abusers.

    Science.gov (United States)

    Weiss, R D; Mirin, S M

    1986-09-01

    We have characterized five subtypes of cocaine abusers on the basis of clinical presentation, family history data, and response to specific treatment interventions. These include depressed patients who value the euphorigenic effects of the drug, patients with bipolar or cyclothymic disorder who use cocaine to augment manic or hypomanic symptoms or to alleviate depression, adults with ADD, residual type, who find that cocaine has a paradoxical effect of increasing attention span and decreasing motor restlessness, patients with narcissistic and borderline personality disorders who use cocaine for its social prestige and because it bolsters self-esteem, and patients with antisocial personality disorder who use cocaine as part of an overall pattern of antisocial behavior. Although not all cocaine abusers fit neatly into these categories, careful psychiatric evaluation and subtyping is essential in designing a specific treatment program for these patients. As the prevalence rate of cocaine abuse increases, studies that examine the efficacy of various treatment approaches for specific subtypes of cocaine abusers will be essential. It is hoped that our work will be a step in that direction.

  8. Opposing roles for the ventral prefrontal cortex and the basolateral amygdala on the spontaneous recovery of cocaine-seeking in rats.

    Science.gov (United States)

    Peters, Jamie; Vallone, Joseph; Laurendi, Kelly; Kalivas, Peter W

    2008-04-01

    The neural circuitry subserving cocaine-seeking after extinction vs abstinence alone requires different constituent brain structures. Spontaneous recovery of cocaine-seeking, a model, which incorporates both extinction and abstinence, depends on an unknown neural circuit. The present study examined the hypothesis that the spontaneous recovery of cocaine-seeking would require overlapping but distinct neural circuits compared to models that incorporate either extinction or abstinence alone. Rats were trained to self-administer cocaine (0.2 mg/inf), then responding on the cocaine-paired lever was extinguished, followed by an additional period of abstinence in the home cage. Finally, rats were returned to the self-administration context for a test of spontaneous recovery (SR TEST). Just before the SR TEST, discrete brain regions were inactivated with a GABA agonist cocktail (1 mM baclofen + 0.1mM muscimol) to determine the relative importance of these brain regions in the spontaneous recovery of cocaine-seeking. The inactivation of the ventromedial prefrontal cortex (vPFC) enhanced cocaine-seeking, whereas the inactivation of the basolateral amygdala (BLA) attenuated spontaneous recovery. Inactivation of the nucleus accumbens core (Core) resembled the effects of BLA inactivation, but these results were confounded by an inhibitory effect of the vehicle treatment. Finally, the spontaneous recovery of cocaine-seeking was unaltered by manipulations of the dorsomedial prefrontal cortex (dPFC) and the nucleus accumbens shell (Shell). The neural circuitry subserving cocaine-seeking behavior in a spontaneous recovery model requires the BLA and possibly the Core, like extinction models. In addition, this behavior is subject to regulation by vPFC, in a manner functionally opposite to that of the BLA.

  9. [Complications of cocaine addiction].

    Science.gov (United States)

    Karila, Laurent; Lowenstein, William; Coscas, Sarah; Benyamina, Amine; Reynaud, Michel

    2009-06-20

    Addiction is a chronic relapsing disorder characterized by repetitive and compulsive drug-seeking behavior and drug abuse despite negative health or social consequences. Cocaine addiction is a significant worldwide public health problem, which has somatic, psychological, psychiatric, socio-economic and judicial complications. Some of the most frequent complications are cardiovascular effects (acute coronary syndrome, cardiac arrhythmias, increased blood pressure); respiratory effects (fibrosis, interstitial pneumonitis, pulmonary hypertension, alveolar haemorrhage, asthma exacerbation; emphysema), neurological effects (strokes, aneurysms, seizures, headaches); risk for contracting HIV/AIDS, hepatitis B and C, sexual transmitted disease and otolaryngologic effects. Other complications are not discussed here. The vast majority of studies indicate that there are cognitive deficits induced by cocaine addiction. Attention, visual and working memories, executive functioning are affected in cocaine users. Psychiatric complications found in clinical practice are major depressive disorders, cocaine-induced paranoia, cocaine-induced compulsive foraging and panic attacks.

  10. Cocaine Use Reduction with Buprenorphine (CURB): Rationale, design, and methodology☆

    Science.gov (United States)

    Mooney, Larissa J.; Nielsen, Suzanne; Saxon, Andrew; Hillhouse, Maureen; Thomas, Christie; Hasson, Albert; Stablein, Don; McCormack, Jennifer; Lindblad, Robert; Ling, Walter

    2013-01-01

    Background Effective medications to treat cocaine dependence have not been identified. Recent pharmacotherapy trials demonstrate the potential efficacy of buprenorphine (BUP) (alone or with naltrexone) for reducing cocaine use. The National Institute on Drug Abuse Clinical Trials Network (CTN) launched the Cocaine Use Reduction with Buprenorphine (CURB) investigation to examine the safety and efficacy of sublingual BUP (as Suboxone®) in the presence of extended-release injectable naltrexone (XR-NTX, as Vivitrol®) for the treatment of cocaine dependence. This paper describes the design and rationale for this study. Methods This multi-site, double-blind, placebo-controlled study will randomize 300 participants across 11 sites. Participants must meet the DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. Participants are inducted onto XR-NTX after self-reporting at least 7 days of abstinence from opioids and tolerating a naloxone challenge followed by oral naltrexone and are then randomly assigned to one of three medication conditions (4 mg BUP, 16 mg BUP, or placebo) for 8 weeks. Participants receive a second injection of XR-NTX 4 weeks after the initial injection, and follow-up visits are scheduled at 1 and 3 months post-treatment. Participants receive weekly cognitive behavioral therapy (CBT). Recruitment commenced in September, 2011. Enrollment, active medication, and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates. Conclusions This research using 2 medications will demonstrate whether BUP, administered in the presence of XR-NTX, reduces cocaine use in adults with cocaine dependence and opioid use disorders and will demonstrate if XR-NTX prevents development of physiologic dependence on BUP. PMID:23159524

  11. Cocaine use reduction with buprenorphine (CURB): rationale, design, and methodology.

    Science.gov (United States)

    Mooney, Larissa J; Nielsen, Suzanne; Saxon, Andrew; Hillhouse, Maureen; Thomas, Christie; Hasson, Albert; Stablein, Don; McCormack, Jennifer; Lindblad, Robert; Ling, Walter

    2013-03-01

    Effective medications to treat cocaine dependence have not been identified. Recent pharmacotherapy trials demonstrate the potential efficacy of buprenorphine (BUP) (alone or with naltrexone) for reducing cocaine use. The National Institute on Drug Abuse Clinical Trials Network (CTN) launched the Cocaine Use Reduction with Buprenorphine (CURB) investigation to examine the safety and efficacy of sublingual BUP (as Suboxone®) in the presence of extended-release injectable naltrexone (XR-NTX, as Vivitrol®) for the treatment of cocaine dependence. This paper describes the design and rationale for this study. This multi-site, double-blind, placebo-controlled study will randomize 300 participants across 11 sites. Participants must meet the DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. Participants are inducted onto XR-NTX after self-reporting at least 7 days of abstinence from opioids and tolerating a naloxone challenge followed by oral naltrexone and are then randomly assigned to one of three medication conditions (4 mg BUP, 16 mg BUP, or placebo) for 8 weeks. Participants receive a second injection of XR-NTX 4 weeks after the initial injection, and follow-up visits are scheduled at 1 and 3 months post-treatment. Participants receive weekly cognitive behavioral therapy (CBT). Recruitment commenced in September, 2011. Enrollment, active medication, and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates. This research using 2 medications will demonstrate whether BUP, administered in the presence of XR-NTX, reduces cocaine use in adults with cocaine dependence and opioid use disorders and will demonstrate if XR-NTX prevents development of physiologic dependence on BUP. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. The Obsessive Compulsive Cocaine Use Scale: development and initial validation of a self-rated instrument for the quantification of thoughts about cocaine use.

    Science.gov (United States)

    Hormes, Julia M; Coffey, Scott F; Drobes, David J; Saladin, Michael E

    2012-01-01

    Craving is a hallmark of addiction and characterized by obsessive thoughts about, and compulsive urges to use, a substance. While craving is frequently thought of as primarily being a feature of acute withdrawal, there is evidence to suggest that it increases in strength over extended periods of abstinence. While several measures are available to assess acute craving states, there remains a lack of clinical measures appropriate for capturing the enduring cognitive aspects of urges to use drugs. The present study was designed to develop and validate a measure of obsessive-compulsive thoughts in cocaine-dependent individuals. The proposed 14-item Obsessive Compulsive Cocaine Use Scale (OCCUS) was administered to 107 individuals: 55 participants meeting diagnostic criteria for cocaine dependence and 52 recreational users of cocaine. In addition to the OCCUS, participants also completed the Drug Abuse Screening Test, Cocaine Craving Questionnaire-Now, and Social Desirability Scale of the California Personality Inventory. Results of confirmatory factor analysis indicated that the OCCUS fit the two-factor structure of the Obsessive Compulsive Drinking Scale on which it was based, independently assessing the "obsessive" and "compulsive" aspects of cocaine dependence. The OCCUS demonstrated good internal consistency reliability and convergent, discriminant, and criterion validity. The proposed measure is a promising step towards the successful capture of the long-term cognitive features of craving for cocaine via self-report, and should represent a useful tool for clinical and research use. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. [Cocaine - Characteristics and addiction].

    Science.gov (United States)

    Girczys-Połedniok, Katarzyna; Pudlo, Robert; Jarząb, Magdalena; Szymlak, Agnieszka

    Cocaine use leads to health, social and legal problems. The aim of this paper is to discuss cocaine action, addicts characteristics, use patterns and consequences, as well as addiction treatment methods. A literature review was based on the Medline, PubMed, Polish Medical Bibliography databases and the Silesian Library resources. The Police and Central Statistical Office statistics, as well as the World Health Organization, the European Monitoring Centre for Drugs and Drug Addiction and the National Office for Combating Drug Addiction reports were used. Cocaine leads to mood improvement, appetite decrease, physical and intellectual activity enhancement, euphoria, inflated self-esteem, social networking ease and increased sexual desire. Cocaine hydrochloride is mainly used intranasaly, but also as intravenous and subcutaneous injections. Cocaine use and first addiction treatment fall in later age compared to other psychoactive substances. There is a high men to women ratio among addicts. There is a relationship between cocaine addiction, the presence of other disorders and genetic predisposition to addiction development. Polish reports indicate higher popularity of cocaine among people with a high economic and social status. Although Poland is a country with the low percentage of cocaine use, its popularity is growing. The consequences of cocaine use concern somatic and mental health problems, socioeconomic and legal conditions. The drug plays a role in crimes and traffic accidents. Because of the risks associated with cocaine use, it has been listed in a register of drugs attached to the Act on Counteracting Drug Addiction. Addiction treatment includes psychological, pharmacological and harm reduction strategies. Med Pr 2016;67(4):537-544. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  14. The ability for cocaine and cocaine-associated cues to compete for attention.

    Science.gov (United States)

    Pitchers, Kyle K; Wood, Taylor R; Skrzynski, Cari J; Robinson, Terry E; Sarter, Martin

    2017-03-01

    In humans, reward cues, including drug cues in individuals experiencing addiction, are especially effective in biasing attention towards them, so much so they can disrupt ongoing task performance. It is not known, however, whether this happens in rats. To address this question, we developed a behavioral paradigm to assess the capacity of an auditory drug (cocaine) cue to evoke cocaine-seeking behavior, thus distracting thirsty rats from performing a well-learned sustained attention task (SAT) to obtain a water reward. First, it was determined that an auditory cocaine cue (tone-CS) reinstated drug-seeking equally in sign-trackers (STs) and goal-trackers (GTs), which otherwise vary in the propensity to attribute incentive salience to a localizable drug cue. Next, we tested the ability of an auditory cocaine cue to disrupt performance on the SAT in STs and GTs. Rats were trained to self-administer cocaine intravenously using an Intermittent Access self-administration procedure known to produce a progressive increase in motivation for cocaine, escalation of intake, and strong discriminative stimulus control over drug-seeking behavior. When presented alone, the auditory discriminative stimulus elicited cocaine-seeking behavior while rats were performing the SAT, but it was not sufficiently disruptive to impair SAT performance. In contrast, if cocaine was available in the presence of the cue, or when administered non-contingently, SAT performance was severely disrupted. We suggest that performance on a relatively automatic, stimulus-driven task, such as the basic version of the SAT used here, may be difficult to disrupt with a drug cue alone. A task that requires more top-down cognitive control may be needed. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Gene expression in human hippocampus from cocaine abusers identifies genes which regulate extracellular matrix remodeling.

    Directory of Open Access Journals (Sweden)

    Deborah C Mash

    2007-11-01

    Full Text Available The chronic effects of cocaine abuse on brain structure and function are blamed for the inability of most addicts to remain abstinent. Part of the difficulty in preventing relapse is the persisting memory of the intense euphoria or cocaine "rush". Most abused drugs and alcohol induce neuroplastic changes in brain pathways subserving emotion and cognition. Such changes may account for the consolidation and structural reconfiguration of synaptic connections with exposure to cocaine. Adaptive hippocampal plasticity could be related to specific patterns of gene expression with chronic cocaine abuse. Here, we compare gene expression profiles in the human hippocampus from cocaine addicts and age-matched drug-free control subjects. Cocaine abusers had 151 gene transcripts upregulated, while 91 gene transcripts were downregulated. Topping the list of cocaine-regulated transcripts was RECK in the human hippocampus (FC = 2.0; p<0.05. RECK is a membrane-anchored MMP inhibitor that is implicated in the coordinated regulation of extracellular matrix integrity and angiogenesis. In keeping with elevated RECK expression, active MMP9 protein levels were decreased in the hippocampus from cocaine abusers. Pathway analysis identified other genes regulated by cocaine that code for proteins involved in the remodeling of the cytomatrix and synaptic connections and the inhibition of blood vessel proliferation (PCDH8, LAMB1, ITGB6, CTGF and EphB4. The observed microarray phenotype in the human hippocampus identified RECK and other region-specific genes that may promote long-lasting structural changes with repeated cocaine abuse. Extracellular matrix remodeling in the hippocampus may be a persisting effect of chronic abuse that contributes to the compulsive and relapsing nature of cocaine addiction.

  16. Abstinence

    Science.gov (United States)

    ... right for you. The truth is that most teens are not having sex. A couple can still have a relationship without ... you've made a decision not to have sex, it's an important personal choice and the people who care about you should ... Kids For Parents MORE ON THIS TOPIC ...

  17. A method to achieve extended cannabis abstinence in cannabis dependent patients with schizophrenia and non-psychiatric controls.

    Science.gov (United States)

    Rabin, Rachel A; Kozak, Karolina; Zakzanis, Konstantine K; Remington, Gary; Stefan, Cristiana; Budney, Alan J; George, Tony P

    2017-05-12

    Cannabis use disorders (CUD) are common in schizophrenia (~25%) compared to the general population (~3%). Tetrahydrocannabinol (THC), the principal psychoactive component in cannabis is fat-soluble, resulting in an extended period for cannabinoid elimination. While detection of cannabinoids in urine is indicative of prior cannabis exposure, time of last use is difficult to verify sustained abstinence for extended periods (e.g., 28-days) in chronic cannabis users. Therefore, we evaluated the utility of a sustained cannabis abstinence paradigm in patients with schizophrenia and non-psychiatric controls. Cannabis dependent patients (n=19) and controls (n=20) underwent 28-days of monitored cannabis abstinence facilitated with contingency management. Urine samples were taken twice weekly. Abstinence was evaluated using 1) Self-report; 2) Qualitative biochemical confirmation using MEDTOX; and 3) in a subset of participants (schizophrenia, n=13; controls, n=13) gas chromatography-mass spectrometry (GC-MS) was performed to obtain quantitative creatinine-normalized carboxy-THC (THC-COOH) metabolite levels cannabis abstinence and further supported time-dependent abstinence trajectories. Abstinence rates of 42.1% (8/19) in patients and 55% (11/19) in controls (p=0.53) were observed. Increased cannabis withdrawal symptoms in both patients and controls supported abstinence. Our results suggest a feasible method for identification of short-term cannabis abstinence in individuals with schizophrenia at rates comparable to controls. Monitoring sustained abstinence may have implications for potential interventions for CUDs in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The role of adenylyl cyclase in the medial prefrontal cortex in cocaine-induced behavioral sensitization in rats.

    Science.gov (United States)

    Liu, Kun; Steketee, Jeffery D

    2016-12-01

    Repeated exposure to cocaine progressively increases drug-induced locomotor activity, which is termed behavioral sensitization. Previous research has demonstrated that in the medial prefrontal cortex (mPFC) modulation of cocaine-induced motor activity by agonists of Gi-coupled receptors, such as dopamine D2, GABAB and Group II metabotropic glutamate receptors, is reduced in sensitized animals, suggesting a loss in receptor function. Stimulation of each of these receptors acts in part to inhibit adenylyl cyclase activity, and thus, the formation of cAMP. The present studies tested the hypothesis that intra-mPFC inhibition of adenylyl cyclase by infusion of an inhibitor, SQ22536, could bypass the loss of inhibitory receptor function seen in this region, and thereby inhibit the expression of cocaine sensitization. Additional studies determined whether activation of mPFC adenylyl cyclase with NKH 477 could enhance the motor-stimulant response to cocaine. Initial studies demonstrated that cocaine-induced (15 mg/kg, i.p.) motor activity was dose-dependently reduced by injection of SQ22536 (5-75 nmol/side) into the mPFC, whereas NKH 477 (1.25-40 nmol/side) produced no significant effects. Additional studies showed that intra-mPFC injection of SQ22536 (50 nmol/side) attenuated the initiation of cocaine-induced behavioral sensitization and blocked the expression of sensitization following 1, 7 or 30 days of abstinence from cocaine. Also, intra-mPFC injection of NKH 477 enhanced cocaine-induced behavioral sensitization following 21 days of abstinence from cocaine. The results of the present study suggest modulation of adenylyl cyclase in the medial prefrontal cortex plays a key role in the expression of cocaine sensitization. Copyright © 2016. Published by Elsevier Ltd.

  19. Effects of continuous nicotine treatment and subsequent termination on cocaine versus food choice in male rhesus monkeys.

    Science.gov (United States)

    Schwienteck, Kathryn L; Negus, S Stevens; Poklis, Justin L; Banks, Matthew L

    2015-10-01

    One complicating factor in cocaine addiction may be concurrent exposure and potential dependence on nicotine. The aim of the present study was to determine the effects of continuous nicotine treatment and subsequent termination on cocaine versus food choice in rhesus monkeys (Macaca mulatta). For comparison, we also determined effects of the nicotinic receptor antagonist mecamylamine on cocaine versus food choice during continuous saline and nicotine treatment. Rhesus monkeys (N = 3) responded under a concurrent schedule of food pellet (1 g) and intravenous cocaine (0-0.1 mg/kg/injection) availability. Saline and ascending nicotine doses (0.1-1.0 mg/kg/hr, intravenous) were continuously infused for 7-day treatment periods and separated by 24-hr saline treatment periods. Acute effects of mecamylamine (0.32-1.8 mg/kg, intramuscular, 15 min pretreatment) were determined during continuous saline and 0.32-mg/kg/hr nicotine treatments. During saline treatment, cocaine maintained a dose-dependent increase in cocaine choice. Nicotine treatment did not alter cocaine versus food choice. In contrast, preference of 0.032 mg/kg/injection cocaine was attenuated 24 hr following termination of 0.32-mg/kg/hr nicotine treatment, despite no somatic abstinence signs being observed. Acute mecamylamine enhanced cocaine choice during saline treatment and mainly suppressed rates of behavior during nicotine treatment. Overall, continuous nicotine exposure, up to 1 mg/kg/hr, does not enhance cocaine choice and does not produce nicotine dependence, as demonstrated by the lack of abstinence signs. (c) 2015 APA, all rights reserved).

  20. The role of ventral and dorsal striatum mGluR5 in relapse to cocaine-seeking and extinction learning.

    Science.gov (United States)

    Knackstedt, Lori A; Trantham-Davidson, Heather L; Schwendt, Marek

    2014-01-01

    Cocaine addiction is a chronic, relapsing disease characterized by an inability to regulate drug-seeking behavior. Here we investigated the role of mGluR5 in the ventral and dorsal striatum in regulating cocaine-seeking following both abstinence and extinction. Animals underwent 2 weeks of cocaine self-administration followed by 3 weeks of home-cage abstinence. Animals were then reintroduced to the operant chamber for a context-induced relapse test, followed by 7-10 days of extinction training. Once responding was extinguished, cue-primed reinstatement test was conducted. Both drug-seeking tests were conducted in the presence of either mGluR5 negative allosteric modulator, MTEP or vehicle infused into either the nucleus accumbens (NA) core or dorsolateral striatum (dSTR). We found that MTEP infused in the NA core attenuated both context-induced relapse following abstinence and cue-primed reinstatement following extinction training. Blocking dSTR mGluR5 had no effect on context- or cue-induced cocaine-seeking. However, the intra-dSTR MTEP infusion on the context-induced relapse test day attenuated extinction learning for 4 days after the infusion. Furthermore, mGluR5 surface expression was reduced and LTD was absent in dSTR slices of animals undergoing 3 weeks of abstinence from cocaine but not sucrose self-administration. LTD was restored by bath application of VU-29, a positive allosteric modulator of mGluR5. Bath application of MTEP prevented the induction of LTD in dSTR slices from sucrose animals. Taken together, this data indicates that dSTR mGluR5 plays an essential role in extinction learning but not cocaine relapse, while NA core mGluR5 modulates drug-seeking following both extinction and abstinence from cocaine self-administration. © 2013 Society for the Study of Addiction.

  1. Modafinil in the treatment of crack-cocaine dependence in the Netherlands: Results of an open-label randomised controlled feasibility trial.

    Science.gov (United States)

    Nuijten, Mascha; Blanken, Peter; van den Brink, Wim; Hendriks, Vincent

    2015-06-01

    Crack-cocaine dependence is a serious disorder with no approved pharmacological treatment. Modafinil is a promising medication with increased cocaine abstinence and reduced craving in some previous studies. In the present study, we examined the acceptance, safety and potential benefits of modafinil as an add-on treatment to cognitive behavioural therapy (CBT) in crack-cocaine dependent patients. Sixty-five crack-cocaine dependent outpatients participated in an open-label, randomised feasibility trial. Patients were randomised to receive either 12-week individual CBT plus 400 mg/day modafinil or 12-week individual CBT only. The primary outcome measure was CBT treatment retention. Secondary outcomes included modafinil adherence, tolerability and safety, use of cocaine and other substances, cocaine craving, health, social functioning and patient satisfaction. Modafinil adherence was low, with only 10% treatment completers. Intent-to-treat analyses showed that modafinil did not improve CBT treatment retention or any of the secondary cocaine-related outcomes. Both groups showed similar, large reductions in cocaine use during the study treatment. Post hoc exploratory analyses within the CBT plus modafinil group showed significantly larger baseline to week 12 reductions in cocaine use days in high (⩾ 8 weeks) modafinil adherent patients. Acceptance and benefits of modafinil were not demonstrated in the present study. Since reduction in cocaine use was observed in high modafinil adherent patients, further research in the treatment of cocaine dependence, in which modafinil adherence is optimised, is warranted. © The Author(s) 2015.

  2. Conditioned Contribution of Peripheral Cocaine Actions to Cocaine Reward and Cocaine-Seeking

    OpenAIRE

    Wang, Bin; You, Zhi-Bing; Oleson, Erik B.; Cheer, Joseph F.; Myal, Stephanie; Wise, Roy A.

    2013-01-01

    Cocaine has actions in the peripheral nervous system that reliably precede—and thus predict—its soon-to-follow central rewarding effects. In cocaine-experienced animals, the peripheral cocaine signal is relayed to the central nervous system, triggering excitatory input to the ventral tegmental origin of the mesocorticolimbic dopamine system, the system that mediates the rewarding effects of the drug. We used cocaine methiodide, a cocaine analog that does not cross the blood–brain barrier, to ...

  3. White Matter Changes in HIV+ Women with a History of Cocaine Dependence

    Directory of Open Access Journals (Sweden)

    Kathryn-Mary Wakim

    2017-10-01

    Full Text Available Cocaine use is associated with the transmission of human immunodeficiency (HIV virus through risky sexual behavior. In HIV+ individuals, cocaine use is linked with poor health outcomes, including HIV-medication non-adherence and faster disease progression. Both HIV and cocaine dependence are associated with reduced integrity of cerebral white matter (WM, but the effects of HIV during cocaine abstinence have not yet been explored. We used diffusion tensor imaging (DTI to understand the effect of combined HIV+ serostatus and former cocaine dependence on cerebral WM integrity. DTI data obtained from 15 HIV+ women with a history of cocaine dependence (COC+/HIV+ and 21 healthy females were included in the analysis. Diffusion-based measures [fractional anisotropy (FA, radial diffusivity (RD, mean diffusivity, and axial diffusivity] were examined using tract-based spatial statistics and region-of-interest analyses. In a whole-brain analysis, COC+/HIV+ women showed significantly reduced FA and increased RD in all major WM tracts, except the left corticospinal tract for RD. The tract with greatest percentage of voxels showing significant between-group differences was the forceps minor (FA: 75.6%, RD: 59.7%. These widespread changes in diffusion measures indicate an extensive neuropathological effect of HIV and former cocaine dependence on WM.

  4. The α-1 adrenoceptor (ADRA1A) genotype moderates the magnitude of acute cocaine-induced subjective effects in cocaine-dependent individuals.

    Science.gov (United States)

    Shorter, Daryl; Nielsen, David A; Hamon, Sara C; Nielsen, Ellen M; Kosten, Thomas R; Newton, Thomas F; De La Garza, Richard

    2016-09-01

    We examined whether a functional variant of the ADRA1A gene moderated cocaine-induced subjective effects in a group of cocaine-dependent individuals. This study was a within-participant, double-blind, placebo-controlled inpatient human laboratory evaluation of 65 nontreatment-seeking, cocaine-dependent [Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV)] individuals aged 18-55 years. Participants received both placebo (saline, IV) and cocaine (40 mg, IV), and subjective responses were assessed 15 min before receiving an infusion and at 5 min intervals for the subsequent 20 min. The rs1048101 variant of the α1A-adrenoceptor (ADRA1A) gene was genotyped and it was evaluated whether the Cys to Arg substitution at codon 347 in exon 2 (Cys347Arg) moderated the magnitude of the subjective effects produced by cocaine. Thirty (46%) participants were found to have the major allele CC genotype and 35 (44%) carried at least one minor T-allele of rs1048101 (TT or TC genotype). Individuals with the CC genotype showed greater responses for 'desire' (P<0.0001), 'high' (P<0.0001), 'any drug effect' (P<0.0001), 'like cocaine' (P<0.0001), and 'likely to use cocaine if given access' (P<0.05) with experiment-wise significance. This study indicates that the ADRA1A genotype could be used to identify individuals for whom acute cocaine exposure may be more rewarding and by inference may result in greater difficulty in establishing and/or maintaining abstinence from cocaine.

  5. [Pneumomediastinum and cocaine use].

    Science.gov (United States)

    Underner, Michel; Perriot, Jean; Peiffer, Gérard

    2017-03-01

    In France, cocaine is the second most commonly used illicit drug after cannabis. It can be responsible for many respiratory disorders among which pneumomediastinum. Systematic literature review of data on pneumediastinum in cocaine users. Documentary sources. Medline, on the period 1980-2016 with the keywords "pneumomediastinum" and "cocaine" or "free-base" or "freebasing" or "crack"; limits "title/abstract"; the selected languages were English or French. Among 72 articles, 48 abstracts have given use to a dual reading to select 37 studies. Thirty-five selected articles related 44 subjects (sex-ratio: 5.2) whose age ranged from 15 to 36 years. Fourteen subjects used cocaine nasally and 30 others smoked it (12 as free-base and 18 in the form of crack). Thirty-two subjects had an isolated pneumomediastinum and 12 others had a pneumomediastinum combined with other gaseous effusions (pneumothorax, pneumopericardium, pneumoperitoneum or pneumorachis). Chest pain of sudden onset in the most common symptom which is often associated with tightness or swelling of the neck; more rarely there are dyspnea and/or a dry cough. The time between taking cocaine and the onset of the symptoms varies from a few minutes to 3 days. The course is usually good with healing in 1 to 4 days. Cocaine use may be responsible for spontaneous pneumomediastinum. Practitioners must seek cocaine use in case of pneumomediastinum in a young person and consider the diagnosis in the case of sudden chest pain in cocaine users; they must help them to stop their consumption. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. NEONATAL ABSTINENCE SYNDROME - CASE REPORT

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    Aleksandra Matic

    2008-01-01

    Full Text Available Neonatal abstinence syndrome (NAS refers to the constellation of signs and symptoms exhibited by a newborn of drug-abusing mother. NAS is multisystemic disorder, most frequently involving central nervous and gastrointestinal systems with irritability, high-pitched cry, hyperactive reflexes, increased muscle tone, tremors, generalized convulsions, feeding and sleeping disorders, tachycardia, tachypnea, apnea, termolability and sweating, frequent hiccups, yawning and sneezing, vomiting, diarrhea and dehydration.Intrauterine narcotic disposition can give some other adverse effects beside NAS: fetal distress, premature birth, intrauterine growth retardation, microcephaly, increased incidence of congenital anomalies (cardiac and genitourinary anomalies, cleft palate, biliar atresia. Significantly increased risks of sudden infant’s death syndrome (SIDS, abnormalities in neurocognitive and behavioral development and deficiency in motor functions have also been noticed after the long-term surveys of these children.This paper is a case report of a newborn with developed clinical signs of NAS, but it also discusses diagnostics and management of such cases

  7. Plasma profile of pro-inflammatory cytokines and chemokines in cocaine users under outpatient treatment: influence of cocaine symptom severity and psychiatric co-morbidity.

    Science.gov (United States)

    Araos, Pedro; Pedraz, María; Serrano, Antonia; Lucena, Miguel; Barrios, Vicente; García-Marchena, Nuria; Campos-Cloute, Rafael; Ruiz, Juan J; Romero, Pablo; Suárez, Juan; Baixeras, Elena; de la Torre, Rafael; Montesinos, Jorge; Guerri, Consuelo; Rodríguez-Arias, Marta; Miñarro, José; Martínez-Riera, Roser; Torrens, Marta; Chowen, Julie A; Argente, Jesús; Mason, Barbara J; Pavón, Francisco J; Rodríguez de Fonseca, Fernando

    2015-07-01

    The treatment for cocaine use constitutes a clinical challenge because of the lack of appropriate therapies and the high rate of relapse. Recent evidence indicates that the immune system might be involved in the pathogenesis of cocaine addiction and its co-morbid psychiatric disorders. This work examined the plasma pro-inflammatory cytokine and chemokine profile in abstinent cocaine users (n = 82) who sought outpatient cocaine treatment and age/sex/body mass-matched controls (n = 65). Participants were assessed with the diagnostic interview Psychiatric Research Interview for Substance and Mental Diseases according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Tumor necrosis factor-alpha, chemokine (C-C motif) ligand 2/monocyte chemotactic protein-1 and chemokine (C-X-C motif) ligand 12 (CXCL12)/stromal cell-derived factor-1 (SDF-1) were decreased in cocaine users, although all cytokines were identified as predictors of a lifetime pathological use of cocaine. Interleukin-1 beta (IL-1β), chemokine (C-X3-C motif) ligand 1 (CX3CL1)/fractalkine and CXCL12/SDF-1 positively correlated with the cocaine symptom severity when using the DSM-IV-TR criteria for cocaine abuse/dependence. These cytokines allowed the categorization of the outpatients into subgroups according to severity, identifying a subgroup of severe cocaine users (9-11 criteria) with increased prevalence of co-morbid psychiatric disorders [mood (54%), anxiety (32%), psychotic (30%) and personality (60%) disorders]. IL-1β was observed to be increased in users with such psychiatric disorders relative to those users with no diagnosis. In addition to these clinical data, studies in mice demonstrated that plasma IL-1β, CX3CL1 and CXCL12 were also affected after acute and chronic cocaine administration, providing a preclinical model for further research. In conclusion, cocaine exposure modifies the circulating levels of pro-inflammatory mediators. Plasma

  8. Effects of prolonged abstinence from METH on the hippocampal BDNF levels, neuronal numbers and apoptosis in methamphetamine-sensitized rats.

    Science.gov (United States)

    Hajheidari, Samira; Sameni, Hamid Reza; Bandegi, Ahmad Reza; Miladi-Gorji, Hossein

    2017-04-03

    Methamphetamine (METH) use is associated with neuronal damage in various regions of brain, while effects of prolonged abstinence on METH-induced damage are not quite clear. This study evaluated serum and hippocampal BDNF levels, neuronal numbers and apoptosis in METH-sensitized and abstinent rats. Rats were sensitized to METH (2mg/kg, daily/18 days, s.c.). All rats were evaluated for neuron counting, the TUNEL test and serum and hippocampal BDNF levels after 30 days of forced abstinence from METH. The results showed that increased BDNF levels in the hippocampus and serum of METH-sensitized rats returned to control level after 30 days of abstinence. The number of neurons in the DG and CA1 of hippocampus and also, the total hippocampal perimeter and area in METH-sensitized rats were significantly lower than the saline rats. While, the number of neurons was not significantly increased in the hippocampus after prolonged abstinence from METH. Also, METH-sensitized rats showed a significant increase in TUNEL-positive cells, whereas METH-abstinent rats showed a slight but significant decrease in TUNEL-positive cells in the DG and CA3 of hippocampus. These results suggest that despite the reduction in BDNF levels, reducing the number of neurons, perimeter and area of the hippocampus were stable after abstinence. Thus, the degenerative effects of METH have been sustained even after prolonged abstinence in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Prenatal and postnatal cocaine exposure predict teen cocaine use

    OpenAIRE

    Delaney-Black, Virginia; Chiodo, Lisa M.; Hannigan, John H.; Greenwald, Mark K.; Janisse, James; Patterson, Grace; Huestis, Marilyn A.; Partridge, Robert T.; Ager, Joel; Sokol, Robert J.

    2010-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adul...

  10. Intracellular mechanisms of cocaine-memory reconsolidation in the basolateral amygdala and dorsal hippocampus

    Science.gov (United States)

    Wells, Audrey Marie

    The ability of cocaine-associated environmental contexts to promote relapse in abstinent humans and reinstatement of cocaine-seeking behavior in laboratory animals depends on the formation and maintenance of maladaptive context-response-cocaine associative memories, the latter of which can be disrupted by manipulations that interfere with memory reconsolidation. Memory reconsolidation refers to a protein synthesis-dependent phenomenon whereby memory traces are reincorporated back into long-term memory storage following their retrieval and subsequent destabilization. To elucidate the distinctive roles of the basolateral amygdala (BLA) and dorsal hippocampus (DH) in the reconsolidation of context-response-cocaine memories, Experiments 1-3 evaluated novel molecular mechanisms within each structure that control this phenomenon. Experiment 1 tested the hypothesis that activation of the extracellular signal-regulated kinase (ERK) in the BLA and nucleus accumbens core (NACc - a substrate for Pavlovian cocaine-memory reconsolidation) would critically control instrumental cocaine-memory reconsolidation. To determine this, rats were re-exposed to a context that had previously been used for cocaine self-administration (i.e., cocaine memory-reactivation) and immediately thereafter received bilateral intra-BLA or intra-NACc microinfusions of the ERK inhibitor U0126 or vehicle (VEH) and were subsequently tested for drug context-induced cocaine-seeking behavior (non-reinforced lever responding) ~72 h later. Re-exposure to the cocaine-paired context at test fully reinstated cocaine-seeking behavior, relative to responding in an alternate, extinction context, and post-reactivation U0126 treatment in the BLA, but not the NACc, impaired cocaine-seeking behavior, relative to VEH. This effect was associated with a temporary increase in ERK2, but not ERK1, phosphorylation in the BLA and required explicit reactivation of the target memory trace (i.e., did not similarly manifest when U

  11. Antipsychotics for cocaine or psychostimulant dependence: systematic review and meta-analysis of randomized, placebo-controlled trials.

    Science.gov (United States)

    Kishi, Taro; Matsuda, Yuki; Iwata, Nakao; Correll, Christoph U

    2013-12-01

    Since cocaine and psychostimulant dependence are related to increased dopamine release, antipsychotics have been tried to reduce their reinforcing properties. A meta-analysis was undertaken to assess the efficacy and tolerability of antipsychotics in cocaine- or stimulant-dependent patients. We searched PubMed, Cochrane Library databases, and PsycINFO from database inception until June 24, 2013, using the following keywords: (randomized OR random OR randomly) AND (placebo) AND (methylphenidate OR cocaine OR methamphetamine OR amphetamine OR 3,4-methylenedioxymethamphetamine) AND (dependence OR abuse) AND (antipsychotic OR neuroleptic OR 34 specific antipsychotic names). Included were randomized, placebo-controlled trials of antipsychotics lasting at least 2 weeks in patients with primary cocaine or psychostimulant dependence. Of 363 hits, we removed 316 duplicates, 20 references based on abstract/title, and 13 ineligible full-text articles, retaining 14 trials for this meta-analysis. Two authors independently extracted the data. Coprimary outcomes included degree of substance use and lack of abstinence. Risk ratio (RR), 95% CI, and standardized mean difference were calculated. Ten studies in patients with primary cocaine dependence (risperidone = 5, olanzapine = 3, reserpine = 2; n = 562) and 4 in those with amphetamine/methamphetamine dependence (aripiprazole = 4; n = 179) were meta-analyzed (14 studies, total n = 741). When study results were pooled together, antipsychotics did not differ from placebo in regard to cocaine use days and lack of cocaine or amphetamine/methamphetamine abstinence, severity of addiction, cocaine or amphetamine/methamphetamine craving, Clinical Global Impressions-Severity of Illness (CGI-S) scores, depression, anxiety, compliance, all-cause discontinuation, and several side effects. However, antipsychotics caused more intolerability-related discontinuation than placebo (P = .0009). Individually, aripiprazole was superior to placebo in

  12. Cortico-amygdala coupling as a marker of early relapse risk in cocaine-addicted individuals

    Directory of Open Access Journals (Sweden)

    Meredith J Mchugh

    2014-02-01

    Full Text Available Addiction to cocaine is a chronic condition characterized by high rates of early relapse. This study builds on efforts to identify neural markers of relapse risk by studying resting state functional connectivity (rsFC in neural circuits arising from the amygdala; a brain region implicated in relapse-related processes including craving and reactivity to stress following acute and protracted withdrawal from cocaine. Whole-brain resting-state fMRI connectivity (6 min was assessed in 45 cocaine-addicted individuals and 22 healthy controls. Cocaine-addicted individuals completed scans in the final week of a residential treatment episode. To approximate preclinical models of relapse-related circuitry separate seeds were derived for the left and right basolateral (BLA and corticomedial (CMA amygdala. Participants also completed the Iowa Gambling Task, Wisconsin Card Sorting Test, Cocaine Craving Questionnaire, Obsessive Compulsive Cocaine Use scale, Temperament and Character Inventory and the NEO-PI-R. Relapse within the first 30 days post-treatment (n = 24 was associated with reduced rsFC between the left CMA and ventromedial prefrontal cortex/rostral anterior cingulate cortex (vmPFC/rACC relative to cocaine-addicted individuals who remained abstinent (non-relapse, n = 21. Non-relapse participants evidenced reduced rsFC between the bilateral BLA and visual processing regions (lingual gyrus/cuneus compared to controls and relapsed participants. Early relapse was associated with fewer years of education but unrelated to trait reactivity to stress, neurocognitive and clinical characteristics or cocaine use history. Findings suggest that rsFC within neural circuits implicated in preclinical models of relapse may provide a promising marker of relapse risk in cocaine-addicted individuals. Future efforts to replicate the current findings and alter connectivity within these circuits may yield novel interventions and improve treatment outcomes.

  13. Optimal neurocognitive, personality and behavioral measures for assessing impulsivity in cocaine dependence.

    Science.gov (United States)

    LoBue, Christian; Cullum, C Munro; Braud, Jacqueline; Walker, Robrina; Winhusen, Theresa; Suderajan, Prabha; Adinoff, Bryon

    2014-11-01

    Impulsivity may underlie the poor treatment retention and high relapse rates observed in cocaine-dependent persons. However, observed differences in measures of impulsivity between cocaine-dependent and healthy control participants often do not reach clinical significance, suggesting that the clinical relevance of these differences may be limited. To examine which measures of impulsivity (i.e. self-report impulsivity, self-report personality, neurocognitive testing) best distinguish cocaine-dependent and healthy control participants (i.e. showing differences at least 1.5 standard deviations [SD] from controls). Optimal measures were considered to demonstrate sufficient classification accuracy. Sixty-five recently abstinent cocaine-dependent and 25 healthy control participants were assessed using select neurocognitive tests and self-report questionnaires including the NEO Personality Inventory-Revised (NEO-PI-R), Temperament and Character Inventory (TCI), Barratt Impulsiveness Scale (BIS-11a), and the Frontal Systems Behavior Scale (FrSBe). When corrected for years of education and gender, neurocognitive measures did not demonstrate clinically significant differences between cocaine-dependent and control participants. The personality measures TCI Purposefulness and Congruent Second Nature and NEO-PI-R Impulsiveness, and the self-rating measures FrSBe Disinhibition and BIS-11 Motor Impulsivity and Total successfully identified clinically meaningful elevations in impulsivity within cocaine-dependent participants (>1.5 SDs from controls). Furthermore, these measures achieved 84-93% accuracy in discriminating cocaine-dependent from control participants. Clinically significant neurocognitive impairment in cocaine-dependent participants was not observed in this sample. As the BIS-11 or FrSBe are brief to administer, accurate, and have been shown to predict treatment retention and relapse, these measures appear to be optimal, relative to the personality measures, for

  14. Optimal neurocognitive, personality and behavioral measures for assessing impulsivity in cocaine dependence

    Science.gov (United States)

    LoBue, Christian; Cullum, C. Munro; Braud, Jacqueline; Walker, Robrina; Winhusen, Theresa; Suderajan, Prabha; Adinoff, Bryon

    2015-01-01

    Background Impulsivity may underlie the poor treatment retention and high relapse rates observed in cocaine-dependent persons. However, observed differences in measures of impulsivity between cocaine-dependent and healthy control participants often do not reach clinical significance, suggesting that the clinical relevance of these differences may be limited. Objectives To examine which measures of impulsivity (i.e. self-report impulsivity, self-report personality, neurocognitive testing) best distinguish cocaine-dependent and healthy control participants (i.e. showing differences at least 1.5 standard deviations [SD] from controls). Optimal measures were considered to demonstrate sufficient classification accuracy. Methods Sixty-five recently abstinent cocaine-dependent and 25 healthy control participants were assessed using select neurocognitive tests and self-report questionnaires including the NEO Personality Inventory-Revised (NEO-PI-R), Temperament and Character Inventory (TCI), Barratt Impulsiveness Scale (BIS-11a), and the Frontal Systems Behavior Scale (FrSBe). Results When corrected for years of education and gender, neurocognitive measures did not demonstrate clinically significant differences between cocaine-dependent and control participants. The personality measures TCI Purposefulness and Congruent Second Nature and NEO-PI-R Impulsiveness, and the self-rating measures FrSBe Disinhibition and BIS-11 Motor Impulsivity and Total successfully identified clinically meaningful elevations in impulsivity within cocaine-dependent participants (>1.5 SDs from controls). Furthermore, these measures achieved 84–93% accuracy in discriminating cocaine-dependent from control participants. Conclusion Clinically significant neurocognitive impairment in cocaine-dependent participants was not observed in this sample. As the BIS-11 or FrSBe are brief to administer, accurate, and have been shown to predict treatment retention and relapse, these measures appear to be

  15. Effective Connectivity Within the Mesocorticolimbic System During Resting-State in Cocaine Users

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    Suchismita Ray

    2016-11-01

    Full Text Available Objective: Although effective connectivity between brain regions has been examined in cocaine users during tasks, no effective connectivity study has been conducted on cocaine users during resting-state. In the present fMRI study, we examined effective connectivity in resting-brain, between the brain regions within the mesocorticolimbic dopamine system, implicated in reward and motivated behavior, while the chronic cocaine users and controls took part in a resting-state scan by using a spectral Dynamic causal modeling (spDCM approach. Method: As part of a study testing cocaine cue reactivity in cocaine users (Ray et al., 2015b, 20 non-treatment seeking cocaine-smoking (abstinent for at least 3 days and 17 control participants completed a resting state scan and an anatomical scan. A mean voxel-based time series data extracted from four key brain areas (ventral tegmental area, VTA; nucleus accumbens, NAc; hippocampus, medial frontal cortex within the mesocorticolimbic dopamine system during resting-state from the cocaine and control participants were used as input to the spDCM program to generate spDCM analysis outputs. Results: Compared to the control group, the cocaine group had higher effective connectivity from the VTA to NAc, hippocampus and medial frontal cortex. In contrast, the control group showed a higher effective connectivity from the medial frontal cortex to VTA, from the NAc to medial frontal cortex, and on the hippocampus self-loop. Conclusions: The present study is the first to show that during resting-state in abstaining cocaine users compared to controls, the VTA initiates an enhanced effective connectivity to NAc, hippocampus and medial frontal cortex areas within the mesocorticolimbic dopamine system, the brain’s reward system. Future studies of effective connectivity analysis during resting-state may eventually be used to monitor treatment outcome.

  16. Abstinence and neutrality: development and diverse views.

    Science.gov (United States)

    Schachter, J

    1994-08-01

    Usually, Freud adopted a technical device for personal or practical reasons and only later formulated its theoretical basis. His conception of abstinence initially seemed designed to curb his own troublesome erotic countertransference. These speculations, while having no bearing on the clinical value of abstinence and related neutrality, do emphasise the necessity to assess their utility objectively, on the basis of clinical data. Diverse views of abstinence and neutrality persist in part because early inconsistencies in Freud's conceptions remain unresolved, and in part because these views are derived from the analyst's personality and character, are not based upon clinical data, but are buttressed by iteration. An approach to empirical assessment is suggested using multiple analyst-observers: (1) to develop reliable criteria for four analyst behaviours: abstinence, neutrality, gratification and suggestion; and (2) to evaluate enhancement or impairment of analytic work. Utilisation of this approach in the supervision of candidates would enhance analytic pedagogy and to some degree facilitate a research orientation in candidates.

  17. Potencies of cocaine methiodide on major cocaine targets in mice.

    Directory of Open Access Journals (Sweden)

    Erik R Hill

    2009-10-01

    Full Text Available Cocaine methiodide (CM, a charged cocaine analog, cannot pass the blood brain barrier. It has been assumed the effects of systemic CM represent cocaine actions in peripheral tissues. However, the IC(50 values of CM have not been clearly determined for the major cocaine targets: dopamine, norepinephrine, and serotonin transporters, and sodium channels. Using cells transfected with individual transporters from mice and synaptosomes from mouse striatum tissues, we observed that the inhibition IC(50 values for monoamine uptake by CM were 31-fold to 184-fold higher compared to cocaine at each of the transporters. In dorsal root ganglion neurons, cocaine inhibited sodium channels with an apparent IC(50 of 75 microM, while CM showed no observable effect at concentrations up to 3 mM. These results indicate that an equal dose of CM will not produce an equivalent peripheral effect of cocaine.

  18. Cocaine cardiomyopathy: A case report

    Directory of Open Access Journals (Sweden)

    Georgiev Antonio

    2014-12-01

    Full Text Available Cocaine is the second most common illicit drug used and the most frequent cause of drug related deaths. The use of cocaine is associated with both, acute and chronic complications, that may involve any system, but the most common system affected is cardiovascular one. Cocaine cardiomyopathy may result from the use of cocaine. This article presents a first case in Republic of Macedonia of 24-year-old male with reversible cocaine-related cardiomyopathy. Clinical presentation, laboratory, X-ray, ultrasound findings and treatment are reviewed.

  19. The tango of cocaine

    Directory of Open Access Journals (Sweden)

    Xavier CARBONELL

    2017-12-01

    Full Text Available After a brief historical context, the authors discussed the relevance of cocaine consumption in Barcelona in the second decade of the 20th century and how this influence was reflected in popular music, especially in tango, which was heard in theaters. Below are some examples in famous or relevant lyrics. Finally, the low impact that this popular culture had on preventing the second epidemic of cocaine use that began at the end of the 20th century and the mediatization of the media was discussed.

  20. Selective cocaine-related difficulties in emotional intelligence: relationship to stress and impulse control.

    Science.gov (United States)

    Fox, Helen C; Bergquist, Keri L; Casey, James; Hong, K Adam; Sinha, Rajita

    2011-01-01

    Emotional Intelligence (EI) comprises the ability to perceive, use, understand, and regulate emotions and may potentially contribute to variability in risk-related factors such as stress perception and impulse control in cocaine dependent individuals. The main objective of the current study is to better define EI in cocaine dependent individuals compared with healthy controls, using the Mayer, Salovey, and Caruso Emotional Intelligence Test (MSCEIT). Secondary analysis investigates the association between EI, IQ factors, perceived stress, and impulse control in both populations. Seventy-two abstinent treatment-seeking cocaine patients and 52 healthy controls were administered the MSCEIT as well as measures of IQ, perceived stress, and impulse control. Findings showed that cocaine dependent participants demonstrated highly selective EI difficulties compared with healthy controls, specifically with regard to higher-level emotional reasoning including the understanding, management, and regulation of emotion. These EI problems were associated with increased perceived stress and impulse control difficulties. IQ was significantly associated with all MSCEIT measures in the cocaine dependent participants, but not controls. Findings indicate that specific aspects of EI may be of clinical importance to cocaine dependent populations, impacting relapse-related factors such as stress dysregulation and impulse control.  © American Academy of Addiction Psychiatry.

  1. Selective Cocaine-Related Difficulties in Emotional Intelligence: Relationship to Stress and Impulse Control

    Science.gov (United States)

    Fox, Helen C.; Bergquist, Keri L.; Casey, James; Hong, K. Adam; Sinha, Rajita

    2010-01-01

    Emotional Intelligence (EI) comprises the ability to perceive, use, understand and regulate emotions and may potentially contribute to variability in risk-related factors such as stress perception and impulse control in cocaine dependent individuals. The main objective of the current study is to better define EI in cocaine dependent individuals compared with healthy controls, using the Mayer, Salovey, and Caruso Emotional Intelligence Test (MSCEIT1). Secondary analysis investigates the association between EI, IQ factors, perceived stress and impulse control in both populations. Seventy-two abstinent treatment-seeking cocaine patients and 52 healthy controls were administered the MSCEIT as well as measures of IQ, perceived stress and impulse control. Findings showed that cocaine dependent participants demonstrated highly selective EI difficulties compared with healthy controls, specifically with regard to higher level emotional reasoning including the understanding, management and regulation of emotion. These EI problems were associated with increased perceived stress and impulse control difficulties. IQ was significantly associated with all MSCEIT measures in the cocaine dependent participants, but not controls. Findings indicate that specific aspects of EI may be of clinical importance to cocaine dependent populations, impacting relapse related factors such as stress dysregulation and impulse control. PMID:21314758

  2. ADAR2-dependent GluA2 editing regulates cocaine seeking.

    Science.gov (United States)

    Schmidt, H D; McFarland, K N; Darnell, S B; Huizenga, M N; Sangrey, G R; Cha, J-H J; Pierce, R C; Sadri-Vakili, G

    2015-11-01

    Activation of AMPA receptors (AMPARs) in the nucleus accumbens is necessary for the reinstatement of cocaine-seeking behavior, an animal model of drug craving and relapse. AMPARs are tetrameric protein complexes that consist of GluA1-4 subunits, of which GluA2 imparts calcium permeability. Adenosine deaminase acting on RNA 2 (ADAR2) is a nuclear enzyme that is essential for editing GluA2 pre-mRNA at Q/R site 607. Unedited GluA2(Q) subunits form calcium-permeable AMPARs (CP-AMPARs), whereas edited GluA2(R) subunits form calcium-impermeable channels (CI-AMPARs). Emerging evidence suggests that the reinstatement of cocaine seeking is associated with increased synaptic expression of CP-AMPARs in the nucleus accumbens. However, the role of GluA2 Q/R site editing and ADAR2 in cocaine seeking is unclear. In the present study, we investigated the effects of forced cocaine abstinence on GluA2 Q/R site editing and ADAR2 expression in the nucleus accumbens. Our results demonstrate that 7 days of cocaine abstinence is associated with decreased GluA2 Q/R site editing and reduced ADAR2 expression in the accumbens shell, but not core, of cocaine-experienced rats compared with yoked saline controls. To examine the functional significance of ADAR2 and GluA2 Q/R site editing in cocaine seeking, we used viral-mediated gene delivery to overexpress ADAR2b in the accumbens shell. Increased ADAR2b expression in the shell attenuated cocaine priming-induced reinstatement of drug seeking and was associated with increased GluA2 Q/R site editing and surface expression of GluA2-containing AMPARs. Taken together, these findings support the novel hypothesis that an increased contribution of accumbens shell CP-AMPARs containing unedited GluA2(Q) promotes cocaine seeking. Therefore, CP-AMPARs containing unedited GluA2(Q) represent a novel target for cocaine addiction pharmacotherapies.

  3. A faith-based intervention for cocaine-dependent Black women.

    Science.gov (United States)

    Stahler, Gerald J; Kirby, Kimberly C; Kerwin, MaryLouise E

    2007-06-01

    The purpose of the present study was to obtain preliminary data on the effectiveness of a faith-based treatment adjunct for cocaine-using homeless mothers in residential treatment. The Bridges intervention utilizes various Black church communities to provide culturally-relevant group activities and individual mentoring from volunteers. Eighteen women who were recent treatment admissions were randomly assigned to receive Standard Treatment plus Bridges or Standard Treatment with an Attention Control. Participants were assessed at intake and three and six months after intake. Bridges treatment resulted in significantly better treatment retention (75% vs. 20% at six months) than standard residential treatment alone. In addition, Bridges produced superior outcomes at the six month follow-up assessment on a secondary measure of cocaine abstinence. Creating a community of social support through Black churches appears feasible and promising, and may be a cost-effective means of providing longer-term post-treatment support for cocaine-addicted women.

  4. Demand curves for hypothetical cocaine in cocaine-dependent individuals.

    Science.gov (United States)

    Bruner, Natalie R; Johnson, Matthew W

    2014-03-01

    Drug purchasing tasks have been successfully used to examine demand for hypothetical consumption of abused drugs including heroin, nicotine, and alcohol. In these tasks, drug users make hypothetical choices whether to buy drugs, and if so, at what quantity, at various potential prices. These tasks allow for behavioral economic assessment of that drug's intensity of demand (preferred level of consumption at extremely low prices) and demand elasticity (sensitivity of consumption to price), among other metrics. However, a purchasing task for cocaine in cocaine-dependent individuals has not been investigated. This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. Participants completed a questionnaire assessing hypothetical purchases of cocaine units at prices ranging from $0.01 to $1,000. Demand curves were generated from responses on the Cocaine Purchasing Task. Correlations compared metrics from the demand curve to measures of real-world cocaine use. Group and individual data were well modeled by a demand curve function. The validity of the Cocaine Purchasing Task was supported by a significant correlation between the demand curve metrics of demand intensity and O max (determined from Cocaine Purchasing Task data) and self-reported measures of cocaine use. Partial correlations revealed that after controlling for demand intensity, demand elasticity and the related measure, P max, were significantly correlated with real-world cocaine use. Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use.

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

    Science.gov (United States)

    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…

  6. Cocaine/levamisole-induced systemic vasculitis with retiform purpura and pauci-immune glomerulonephritis.

    Science.gov (United States)

    Veronese, F V; Dode, R S O; Friderichs, M; Thomé, G G; da Silva, D R; Schaefer, P G; Sebben, V C; Nicolella, A R; Barros, E J G

    2016-01-01

    Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes.

  7. Effects of extended cannabis abstinence on clinical symptoms in cannabis dependent schizophrenia patients versus non-psychiatric controls.

    Science.gov (United States)

    Rabin, Rachel A; Kozak, Karolina; Zakzanis, Konstantine K; Remington, Gary; George, Tony P

    2017-03-08

    Rates of cannabis use among patients with schizophrenia are high, however little is understood about clinical effects of continued cannabis use and cessation after illness onset. Therefore, we investigated the effects of 28-days of cannabis abstinence on psychotic and depressive symptomatology in cannabis dependent patients with schizophrenia. Males with cannabis dependence and co-morbid schizophrenia (n=19) and non-psychiatric controls (n=20) underwent 28-days of monitored cannabis abstinence. Clinical symptoms were assessed at baseline and then weekly. Abstinence was encouraged using weekly therapy sessions and contingency reinforcement, confirmed by twice-weekly urine assays. Forty-two percent (8/19) of patients and 55% (11/20) of controls achieved 28-days of sustained cannabis abstinence. In patients, PANSS subscores did not change over time irrespective of abstinence status. In contrast, patient abstainers demonstrated a more pronounced reduction in depression scores compared to non-abstainers, however, the Abstinence Status x Time interaction was non-significant. Short-term (28-days) cannabis abstinence is not associated with improvement in psychotic symptoms, but may be associated with improvement in depressive symptomatology in patients with schizophrenia. Future studies employing larger samples as well as a continuous cannabis-using group may help to better characterize the causal effects of cannabis on symptom outcomes in this disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Costs and Effectiveness of Treating Homeless Persons with Cocaine Addiction with Alternative Contingency Management Strategies.

    Science.gov (United States)

    Mennemeyer, Stephen T; Schumacher, Joseph E; Milby, Jesse B; Wallace, Dennis

    2017-03-01

    Between 1990 and 2006 in Birmingham, Alabama USA, 4 separate randomized controlled studies, called "Homeless 1" through "Homeless 4", treated cocaine substance abuse among chronically homeless adults, largely black men, many with non-psychotic mental health problems. The 4 studies had 9 treatment arms that used various counseling methods plus, in some arms, the provision of housing and work therapy usually with a contingent requirement of urine-test verified abstinence from substances. Participants in the abstinent-contingent arms who lapsed on abstinence were removed from housing and sent to an evening public shelter from which they were daily transported to day treatment until they returned to abstinence. This paper compares the cost effectiveness of the treatment arms. Societal cost per participant (in 2014 dollars) for each arm is defined as direct treatment cost plus cost of jail or hospital plus societal expense of public shelter use by lapsed participants. An untreated Base Case is defined as 5 percent abstinence with 95 percent usage of a public shelter. Incremental Cost Effectiveness Ratios (ICERs) for paired arms are defined as the change in cost per participant divided by the change in abstinence. Bootstrapping estimates confidence intervals. Average cost per participant at the end of 6 months of active treatment in 7 arms with comparable data ranged from USD 10,447 to USD 36,194 with corresponding average weeks abstinent ranging from 6.1 to 15.3 out of a possible 26 weeks. In contrast, the Base Case would cost USD 6,123 for 1.3 weeks of abstinence. Compared to the Base Case, the least expensive "DT2" treatment has an ICER of USD 901 (95% CI = USD 571 to USD 1,681) per additional week of abstinence and the most expensive "CMP4" has an ICER of USD 2,147 (95% CI = USD 1,701 to USD 2,848). Additionally, the Homeless 3 study found that the abstinent contingent housing (ACH3) treatment compared to the Non Abstinent Contingent Housing (NAC3), analogous to

  9. Enhanced Choice for Viewing Cocaine Pictures in Cocaine Addiction

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, S.J.; Goldstein, R.; Moeller, S.J.; Maloney, T. Parvaz, M.A.; Dunning, J.P.; Alia-Klein, N.; Woicik, P.A.; Hajcak, G.; Telang, F.; Wang, G.-J.; Volkow, N.D.; Goldstein, R.Z.

    2009-02-01

    Individuals with cocaine use disorder (CUD) chose cocaine over nondrug rewards. In two newly designed laboratory tasks with pictures, we document this modified choice outside of a cocaine administration paradigm. Choice for viewing cocaine, pleasant, unpleasant, or neutral pictures-under explicit contingencies (choice made between two fully visible side-by-side images) and under more implicit contingencies (selections made between pictures hidden under flipped-over cards)-was examined in 20 CUD and 20 matched healthy control subjects. Subjects also provided self-reported ratings of each picture's pleasantness and arousal. Under both contingencies, CUD subjects chose to view more cocaine pictures than control subjects, group differences that were not fully explained by the self-reported picture ratings. Furthermore, whereas CUD subjects choice for viewing cocaine pictures exceeded choice for viewing unpleasant pictures (but did not exceed choice for viewing pleasant pictures, in contrast to their self-reported ratings), healthy control subjects avoided viewing cocaine pictures as frequently as, or even more than, unpleasant pictures. Finally, CUD subjects with the most cocaine viewing selections, even when directly compared with selections of the pleasant pictures, also reported the most frequent recent cocaine use. Enhanced drug-related choice in cocaine addiction can be demonstrated even for nonpharmacologic (pictorial) stimuli. This choice, which is modulated by alternative stimuli, partly transcends self-reports (possibly indicative of a disconnect in cocaine addiction between self-reports and objective behavior) to provide an objective marker of addiction severity. Neuroimaging studies are needed to establish the neural underpinnings of such enhanced cocaine-related choice.

  10. Enhanced choice for viewing cocaine pictures in cocaine addiction.

    Science.gov (United States)

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

    2009-07-15

    Individuals with cocaine use disorder (CUD) chose cocaine over nondrug rewards. In two newly designed laboratory tasks with pictures, we document this modified choice outside of a cocaine administration paradigm. Choice for viewing cocaine, pleasant, unpleasant, or neutral pictures--under explicit contingencies (choice made between two fully visible side-by-side images) and under more implicit contingencies (selections made between pictures hidden under flipped-over cards)--was examined in 20 CUD and 20 matched healthy control subjects. Subjects also provided self-reported ratings of each picture's pleasantness and arousal. Under both contingencies, CUD subjects chose to view more cocaine pictures than control subjects, group differences that were not fully explained by the self-reported picture ratings. Furthermore, whereas CUD subjects' choice for viewing cocaine pictures exceeded choice for viewing unpleasant pictures (but did not exceed choice for viewing pleasant pictures, in contrast to their self-reported ratings), healthy control subjects avoided viewing cocaine pictures as frequently as, or even more than, unpleasant pictures. Finally, CUD subjects with the most cocaine viewing selections, even when directly compared with selections of the pleasant pictures, also reported the most frequent recent cocaine use. Enhanced drug-related choice in cocaine addiction can be demonstrated even for nonpharmacologic (pictorial) stimuli. This choice, which is modulated by alternative stimuli, partly transcends self-reports (possibly indicative of a disconnect in cocaine addiction between self-reports and objective behavior) to provide an objective marker of addiction severity. Neuroimaging studies are needed to establish the neural underpinnings of such enhanced cocaine-related choice.

  11. Reduced attentional scope in cocaine polydrug users

    NARCIS (Netherlands)

    Colzato, L.S.; van den Wildenberg, W.P.M.; Hommel, B.

    2009-01-01

    Cocaine is Europe's second preferred recreational drug after cannabis but very little is known about possible cognitive impairments in the upcoming type of recreational cocaine user (monthly consumption). We asked whether recreational use of cocaine impacts early attentional selection processes.

  12. Prenatal and postnatal cocaine exposure predict teen cocaine use.

    Science.gov (United States)

    Delaney-Black, Virginia; Chiodo, Lisa M; Hannigan, John H; Greenwald, Mark K; Janisse, James; Patterson, Grace; Huestis, Marilyn A; Partridge, Robert T; Ager, Joel; Sokol, Robert J

    2011-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n=316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Prevalence of traumatic brain injury in cocaine-dependent research volunteers.

    Science.gov (United States)

    Ramesh, Divya; Keyser-Marcus, Lori A; Ma, Liangsuo; Schmitz, Joy M; Lane, Scott D; Marwitz, Jennifer H; Kreutzer, Jeffrey S; Moeller, Frederick Gerard

    2015-06-01

    There is a high prevalence of traumatic brain injury (TBI) among those with substance dependence. However, TBI often remains undiagnosed in these individuals, due to lack of routine screening in substance use treatment settings or due to overlap in some of the cognitive sequelae (eg impulsivity, disinhibition) of TBI and cocaine dependence. The prevalence of self-reported mild to moderate TBI in a group of cocaine-dependent (n = 95) and a group of healthy volunteers (n = 75) enrolled at the same facility was assessed. Additionally, the relationship between TBI and clinically relevant correlates, including impulsivity, cocaine use history, and treatment outcome in the cocaine-dependent group was also examined. A higher proportion of individuals with cocaine dependence (29.5%) reported having suffered a TBI in their lifetime compared to controls (8%) on a Closed Head Injury scale. Among cocaine users, the average age of sustaining TBI was significantly lower than the age of initiating cocaine use. Presence of TBI was not associated with higher impulsivity on the Barratt Impulsiveness Scale-11 or self-reported years of cocaine use. No differences were noted on treatment outcome for cocaine dependence as measured by treatment effectiveness scores (TES) between cocaine users with TBI and their non-TBI counterparts. These results are the first to highlight the high prevalence of TBI among individuals with cocaine dependence. This study underscores the possible role of TBI history as a risk factor for onset of cocaine use, however, more research is needed to determine the impact of co-morbid TBI as a complicating factor in the substance abuse treatment setting. © American Academy of Addiction Psychiatry.

  14. Comorbidades psiquiátricas em dependentes químicos em abstinência em ambiente protegido Psychiatric comorbidities in abstinent drug addict in a protected environment

    Directory of Open Access Journals (Sweden)

    Adriana Raquel Binsfeld Hess

    2012-04-01

    Full Text Available O objetivo desta pesquisa foi verificar a frequência de comorbidades psiquiátricas, utilizando Mini International Neuropsychiatric Interview, em diferentes grupos de dependentes químicos em abstinência, em ambiente protegido, classificados de acordo com o tipo de droga utilizada: (1 grupo controle (n = 37; (2 dependentes em abstinência de álcool (n = 8; (3 dependentes em abstinência de álcool, maconha e crack/cocaína (n = 24; e (4 dependentes em abstinência de múltiplas substâncias psicoativas (n=25, ou seja, indivíduos que faziam uso de vários tipos de drogas sem apresentar uma droga de escolha. Participaram 94 homens, com idade média de 30,41 anos (DP = 9,88. O período de abstinência variou entre 30 e 240 dias. A maioria dos participantes tinha baixa escolaridade e era solteira. Os resultados apontaram maior ocorrência de psicopatologias e risco de suicídio nos grupos formados por pacientes com histórico de consumo múltiplo de substâncias, sugerindo a importância da avaliação de outros transtornos associados à dependência química.The objective of this research was to determine the frequency of psychiatric comorbidity, using Mini International Neuropsychiatric Interview, in different groups of former drug addicts, classified according to the type of drug used: (1 control group (n = 37, (2 ex-users of alcohol only (n = 8, (3 former users of alcohol, marijuana and crack /cocaine (n = 24, and (4 ex-poly drug users (n = 25, in other words, individuals who use various types of drugs without a clear drug of choice. Participants comprised 94 men, mean age 30.41 years (SD = 9.88. The withdrawal period varied between 30 and 240 days. Most participants had little schooling and were single. The results showed a higher incidence of psychopathology and suicide risk in the groups formed by patients with a history of multiple substance use, suggesting the importance of evaluation of other disorders associated with addiction.

  15. Cocaine Self-Administration Produces Long-Lasting Alterations in Dopamine Transporter Responses to Cocaine

    OpenAIRE

    Siciliano, Cody A.; Fordahl, Steve C.; Jones, Sara R.

    2016-01-01

    Cocaine addiction is a debilitating neuropsychiatric disorder characterized by uncontrolled cocaine intake, which is thought to be driven, at least in part, by cocaine-induced deficits in dopamine system function. A decreased ability of cocaine to elevate dopamine levels has been repeatedly observed as a consequence of cocaine use in humans, and preclinical work has highlighted tolerance to cocaine's effects as a primary determinant in the development of aberrant cocaine taking behaviors. Her...

  16. Sample Differentiation: Cocaine Example.

    Science.gov (United States)

    Baugh, L D; Liu, R H

    1991-12-01

    Since the analyses of drug samples in crime laboratories are often associated with investigations, potential differentiations of test samples are frequently requested and explored. Cocaine sample differentiation requires the determination of synthetic or natural origin. Synthetic samples are characterized by the presence of optical isomers, certain diastereoisomers and other by-products, and chemical residues used in synthesis. Samples derived from a natural origin (coca leaves) are characterized by the presence of certain natural products or their derivatives that are carried through the overall process and by residual chemicals reflecting the treatment procedures. Various approaches and analytical data available in the literature concerning the differentiation of cocaine samples are reviewed. Each sample must carry its own "signature"; however, true sample "individualization" cannot be accomplished using the technologies commonly available and used in crime laboratories, and is not usually needed. Alternatively, "classifying" cocaine samples in certain categories or groups can be accomplished routinely and often provides adequate information for investigatory purposes. Copyright © 1991 Central Police University.

  17. Is serum brain-derived neurotrophic factor related to craving for or use of alcohol, cocaine, or methamphetamine?

    Directory of Open Access Journals (Sweden)

    Gangwani P

    2011-06-01

    Full Text Available Craig Hilburn, Vicki A Nejtek, Wendy A Underwood, Meharvan Singh, Gauravkumar Patel, Pooja Gangwani, Michael J ForsterUniversity of North Texas Health Science Center at Fort Worth, TX, USABackground: Data suggests that brain-derived neurotropic factor (BDNF plays a neuroadaptive role in addiction. Whether serum BDNF levels are different in alcohol or psychostimulants as a function of craving is unknown. Here, we examined craving and serum BDNF levels in persons with alcohol versus psychostimulant dependence. Our goals were to explore BDNF as an objective biomarker for 1 craving 2 abstinence, and 3 years of chronic substance use.Methods: An exploratory, cross-sectional study was designed. Men and women between 20–65 years old with alcohol, cocaine, or methamphetamine dependence were eligible. A craving questionnaire was used to measure alcohol, cocaine and methamphetamine cravings. Serum levels of BDNF were measured using enzyme linked immunoassay. Analysis of variance, chi-square, and correlations were performed using a 95% confidence interval and a significance level of P < 0.05.Results: We found a significant difference in the mean craving score among alcohol, cocaine and methamphetamine dependent subjects. There were no significant influences of race, gender, psychiatric disorder or psychotropic medication on serum BDNF levels. We found that among psychostimulant users BDNF levels were significantly higher in men than in women when the number of abstinent days was statistically controlled. Further, a significant correlation between serum BDNF levels and the number of abstinent days since last psychostimulant use was found.Conclusion: These data suggest that BDNF may be a biomarker of abstinence in psychostimulant dependent subjects and inform clinicians about treatment initiatives. The results are interpreted with caution due to small sample size and lack of a control group.Keywords: BDNF, alcohol, cocaine, methamphetamine, craving

  18. Music-induced context preference following cocaine conditioning in rats.

    Science.gov (United States)

    Polston, J E; Glick, S D

    2011-08-01

    Traditional models of drug-seeking behavior have shown that exposure to associated environmental cues can trigger relapse. These learned associations take place during repeated drug administration, resulting in conditioned reinforcement. Although considerable investigation has occurred regarding simple conditioned stimuli, less is known about complex environmental cues, particularly those that may be salient in human addiction. Recent studies indicate that music can serve as a contextual conditioned stimulus in rats and influence drug-seeking behavior during abstinence. The purpose of the present study was to further assess the effectiveness of music as a conditioned stimulus in rats, to determine rats' preferences for two contrasting pieces of music, and to determine rats' preferences for music versus silence. To this end, we created an apparatus that gave instrumental control of musical choice (Miles Davis vs. Beethoven) to the rats themselves. After determining baseline musical preference, animals were conditioned with cocaine (10 mg/kg) to the music they initially preferred least, with alternating conditioning sessions pairing saline with the music preferred most. The animals were subsequently tested in a drug-free state to determine what effect this conditioning had on musical preference. The results indicate that music serves as an effective contextual conditioned stimulus, significantly increasing both musical preference and locomotor activity after repeated cocaine conditioning. Furthermore, we found that rats initially favor silence over music, but that this preference can be altered as a result of cocaine-paired conditioning. These findings demonstrate that, after repeated association with reward (cocaine), music can engender a conditioned context preference in rats; these findings are consistent with other evidence showing that musical contextual cues can reinstate drug-seeking behavior in rats. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

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

    Science.gov (United States)

    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…

  20. Maintenance pharmacotherapy normalizes the relapse curve in recently abstinent tobacco smokers with schizophrenia and bipolar disorder.

    Science.gov (United States)

    Evins, A Eden; Hoeppner, Susanne S; Schoenfeld, David A; Hoeppner, Bettina B; Cather, Corinne; Pachas, Gladys N; Cieslak, Kristina M; Maravic, Melissa Culhane

    2017-05-01

    To compare the effect of maintenance pharmacotherapy on sustained abstinence rates between recently abstinent smokers with schizophrenia and bipolar disorder (SBD) and general population smokers without psychiatric illness. We performed a person-level, pooled analysis of two randomized controlled trials of maintenance varenicline, conducted in adult smokers with SBD and general population smokers, controlling for severity of dependence. Smokers abstinent after 12-weeks of open varenicline treatment were randomly assigned to ≥12-weeks maintenance varenicline or identical placebo. In those assigned to maintenance placebo, the abstinence rate at week-24 was lower in those with SBD than for those without psychiatric illness (29.4±1.1% vs. 61.8±0.4%, OR:0.26, 95% CI: 0.13, 0.52, pmaintenance pharmacotherapy, however, there was no effect of diagnosis on abstinence rates at week-24 (87.2±0.8% vs. 81.9±0.2%, OR: 1.68, 95% CI: 0.53, 5.32, p=0.38). Time to first lapse was shortest in those with SBD assigned to maintenance placebo (Q1=12days, 95%CI: 4, 16), longer in those without psychiatric illness assigned to maintenance placebo (Q1=17days, 95%CI: 17, 29), still longer in general-population smokers assigned to maintenance varenicline (Q1=88, 95% CI:58,91, and longest in those with SBD who received maintenance varenicline (Q1>95days, 95%CI:non-est), (Χ23df=96.99, pmaintenance varenicline treatment. Maintenance pharmacotherapy could improve longer-term tobacco abstinence rates and reduce known smoking-related health disparities in those with SMI. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Dopaminergic mechanisms of cocaine use

    NARCIS (Netherlands)

    Veeneman - Rijkens, M.M.J.

    2011-01-01

    Cocaine addiction is an enormous medical problem for which there is currently no effective pharmacotherapy. In order to develop treatments for this disorder, it is essential to understand the neurobiological underpinnings of cocaine addiction. One of the behavioral characteristics of addiction is an

  2. Dose-dependent effectiveness of wheel running to attenuate cocaine-seeking: impact of sex and estrous cycle in rats.

    Science.gov (United States)

    Peterson, Alexis B; Hivick, Daniel P; Lynch, Wendy J

    2014-07-01

    Exercise has shown promise as an intervention for drug addiction; however, little is known regarding the exercise conditions that most effectively reduce relapse vulnerability and whether these conditions differ by sex. Here, we examined sex differences in the dose-dependent effects of wheel running, an animal model of exercise, during abstinence on subsequent cocaine-seeking. Male and female rats self-administered cocaine (1.5 mg/kg/infusion) under extended access conditions (24 h/day, 4 discrete trials/h) for 10 days. Rats were then given voluntary access to either an unlocked or locked running wheel for 1, 2, 6, or 24 h/day during the 14-day abstinence period. Separate groups of rats were housed in polycarbonate cages during abstinence to control for physical activity that the wheel may provide. Subsequent cocaine-seeking was assessed under a within-session extinction/cue-induced reinstatement procedure. Estrous cycle was monitored in females to determine whether the effectiveness of wheel running varied by estrous cycle phase. Although females ran more than males, males were more sensitive to the effects of running and showed a dose-dependent decrease in cocaine-seeking with longer access resulting in greater suppression. The dose-effect relationship was less straightforward in females and access to both a locked and unlocked wheel decreased cocaine-seeking with effects dependent on estrous cycle phase. Notably, extended (6 and 24 h/day), but not limited (1 and 2 h/day) access to a wheel surmounted the heightened vulnerability observed in females during estrus. Taken together, our findings suggest that the effectiveness of wheel running is dose-, sex-, and estrous cycle-dependent.

  3. A variant in ANKK1 modulates acute subjective effects of cocaine: a preliminary study

    Science.gov (United States)

    Spellicy, Catherine J.; Harding, Mark J.; Hamon, Sara C.; Mahoney, James J.; Reyes, Jennifer A.; Kosten, Thomas R.; Newton, Thomas F.; De La Garza, Richard; Nielsen, David A.

    2014-01-01

    This study aimed to evaluate whether functional variants in the ankyrin repeat and kinase domain-containing 1 gene (ANKK1) and/or the dopamine receptor D2 gene (DRD2) modulate the subjective effects (reward or non-reward response to a stimulus) produced by cocaine administration. Cocaine-dependent participants (N = 47) were administered 40 mg of cocaine or placebo at time 0, and a subjective effects questionnaire (visual analog scale) was administered 15 minutes prior to cocaine administration, and at 5, 10,15, and 20 minutes following administration. The influence of polymorphisms in the ANKK1 and DRD2 genes on subjective experience of cocaine in the laboratory was tested. Participants with a T allele of ANKK1 rs1800497 experienced greater subjective ‘high’ (p = 0.00006), ‘any drug effect’ (p = 0.0003), and ‘like’ (p = 0.0004) relative to the CC genotype group. Although the variant in the DRD2 gene was shown to be associated with subjective effects, LD analysis revealed this association was driven by the ANKK1 rs1800497 variant. A participant’s ANKK1 genotype may identify individuals who are likely to experience greater positive subjective effects following cocaine exposure, including greater ‘high’ and ‘like’, and these individuals may have increased vulnerability to continue using cocaine or they may be at greater risk to relapse during periods of abstinence. However, these results are preliminary and replication is necessary to confirm these findings. PMID:24528631

  4. Cocaine – Characteristics and addiction

    Directory of Open Access Journals (Sweden)

    Katarzyna Girczys-Połedniok

    2016-08-01

    Full Text Available Cocaine use leads to health, social and legal problems. The aim of this paper is to discuss cocaine action, addicts characteristics, use patterns and consequences, as well as addiction treatment methods. A literature review was based on the Medline, PubMed, Polish Medical Bibliography databases and the Silesian Library resources. The Police and Central Statistical Office statistics, as well as the World Health Organization, the European Monitoring Centre for Drugs and Drug Addiction and the National Office for Combating Drug Addiction reports were used. Cocaine leads to mood improvement, appetite decrease, physical and intellectual activity enhancement, euphoria, inflated self-esteem, social networking ease and increased sexual desire. Cocaine hydrochloride is mainly used intranasaly, but also as intravenous and subcutaneous injections. Cocaine use and first addiction treatment fall in later age compared to other psychoactive substances. There is a high men to women ratio among addicts. There is a relationship between cocaine addiction, the presence of other disorders and genetic predisposition to addiction development. Polish reports indicate higher popularity of cocaine among people with a high economic and social status. Although Poland is a country with the low percentage of cocaine use, its popularity is growing. The consequences of cocaine use concern somatic and mental health problems, socioeconomic and legal conditions. The drug plays a role in crimes and traffic accidents. Because of the risks associated with cocaine use, it has been listed in a register of drugs attached to the Act on Counteracting Drug Addiction. Addiction treatment includes psychological, pharmacological and harm reduction strategies. Med Pr 2016;67(4:537–544

  5. mGlu5 Receptors and Relapse to Cocaine-Seeking: The Role of Receptor Trafficking in Postrelapse Extinction Learning Deficits.

    Science.gov (United States)

    Knackstedt, Lori A; Schwendt, Marek

    2016-01-01

    We have previously demonstrated that MTEP, an allosteric antagonist of mGlu5, infused into the nucleus accumbens attenuates relapse after abstinence from cocaine self-administration. MTEP infused into the dorsolateral striatum (dlSTR) does not alter relapse but has long-lasting effects on subsequent extinction learning. Here we tested whether systemic MTEP would prevent relapse after abstinence or alter extinction learning. We also investigated the mechanism of action by which intra-dlSTR MTEP on test day alters extinction on subsequent days. Animals self-administered cocaine for 12 days followed by abstinence for 20-21 days. MTEP (0.5-5 mg/kg IP) was administered prior to placement into the operant chamber for a context-primed relapse test. A separate group of animals received intra-dlSTR MTEP prior to the relapse test and were sacrificed day later. Systemic administration of MTEP attenuated abstinent-relapse without significantly affecting extinction learning. Surface biotinylation analysis of protein expression in the dlSTR revealed that, in cocaine animals, intra-dlSTR MTEP administration decreased mGlu5 surface expression and prevented changes in Arc and GluA1/GluA2 observed in their vehicle counterparts. Thus, blockade of mGlu5 receptors may be utilized in future treatment strategies for relapse prevention in humans, although the effects of chronic blockade on extinction learning should be further evaluated.

  6. Acute and chronic effects of the M1/M4-preferring muscarinic agonist xanomeline on cocaine vs. food choice in rats.

    Science.gov (United States)

    Thomsen, Morgane; Fulton, Brian S; Caine, S Barak

    2014-02-01

    We previously showed that the M1/M4-preferring muscarinic agonist xanomeline can acutely attenuate or eliminate cocaine self-administration in mice. Medications used to treat addictions will arguably be administered in (sub)chronic or repeated regimens. Tests of acute effects often fail to predict chronic effects, highlighting the need for chronic testing of candidate medications. Rats were trained to lever press under a concurrent FR5 FR5 schedule of intravenous cocaine and food reinforcement. Once baseline behavior stabilized, the effects of 7 days once-daily injections of xanomeline were evaluated. Xanomeline pretreatment dose-dependently (1.8-10 mg/kg/day) shifted the dose-effect curve for cocaine rightward (up to 5.6-fold increase in A 50), with reallocation of behavior to the food-reinforced lever. There was no indication of tolerance, rather effects grew over days. The suppression of cocaine choice appeared surmountable at high cocaine doses, and xanomeline treatment did not significantly decrease total-session cocaine or food intake. In terms of xanomeline's potential for promoting abstinence from cocaine in humans, the findings were mixed. Xanomeline did produce reallocation of behavior from cocaine to food with a robust increase in food reinforcers earned at some cocaine/xanomeline dose combinations. However, effects appeared surmountable, and food-maintained behavior was also decreased at some xanomeline/cocaine dose combinations, suggesting clinical usefulness may be limited. These data nevertheless support the notion that chronic muscarinic receptor stimulation can reduce cocaine self-administration. Future studies should show whether ligands with higher selectivity for M1 or M1/M4 subtypes would be less limited by undesired effects and can achieve higher efficacy.

  7. Is serum brain-derived neurotrophic factor related to craving for or use of alcohol, cocaine, or methamphetamine?

    Science.gov (United States)

    Hilburn, Craig; Nejtek, Vicki A; Underwood, Wendy A; Singh, Meharvan; Patel, Gauravkumar; Gangwani, Pooja; Forster, Michael J

    2011-01-01

    Background Data suggests that brain-derived neurotropic factor (BDNF) plays a neuroadaptive role in addiction. Whether serum BDNF levels are different in alcohol or psychostimulants as a function of craving is unknown. Here, we examined craving and serum BDNF levels in persons with alcohol versus psychostimulant dependence. Our goals were to explore BDNF as an objective biomarker for 1) craving 2) abstinence, and 3) years of chronic substance use. Methods An exploratory, cross-sectional study was designed. Men and women between 20–65 years old with alcohol, cocaine, or methamphetamine dependence were eligible. A craving questionnaire was used to measure alcohol, cocaine and methamphetamine cravings. Serum levels of BDNF were measured using enzyme linked immunoassay. Analysis of variance, chi-square, and correlations were performed using a 95% confidence interval and a significance level of P methamphetamine dependent subjects. There were no significant influences of race, gender, psychiatric disorder or psychotropic medication on serum BDNF levels. We found that among psychostimulant users BDNF levels were significantly higher in men than in women when the number of abstinent days was statistically controlled. Further, a significant correlation between serum BDNF levels and the number of abstinent days since last psychostimulant use was found. Conclusion These data suggest that BDNF may be a biomarker of abstinence in psychostimulant dependent subjects and inform clinicians about treatment initiatives. The results are interpreted with caution due to small sample size and lack of a control group. PMID:21792305

  8. Effects of muscarinic M1 and M4 acetylcholine receptor stimulation on extinction and reinstatement of cocaine seeking in male mice, independent of extinction learning

    DEFF Research Database (Denmark)

    Stoll, Kevin; Hart, Rachel; Lindsley, Craig W

    2017-01-01

    RATIONALE: Stimulating muscarinic M1/M4 receptors can blunt reinforcing and other effects of cocaine. A hallmark of addiction is continued drug seeking/craving after abstinence and relapse. OBJECTIVES: We tested whether stimulating M1 and/or M4 receptors could facilitate extinction of cocaine...... extinction from 17.2 sessions to 8.3 using xanomeline or 7.8 using VU0357017 + VU0152100. VU0357017 alone and VU0152100 alone did not significantly modify rates of extinction (12.6 and 14.6 sessions). The effect of xanomeline was fully preserved when administered delayed after or unpaired from extinction...... sessions (7.5 and 6.4 sessions). Xanomeline-treated mice showed no cocaine-induced reinstatement. CONCLUSIONS: These findings show that M1/M4 receptor stimulation can decrease cocaine seeking in mice. The effect lasted beyond treatment duration and was not dependent upon extinction learning. This suggests...

  9. Pancreatitis Induced by Cocaine

    Directory of Open Access Journals (Sweden)

    Sebastián Pablo Chapela

    2017-04-01

    Full Text Available Pancreatitis is one of the commonest diseases of the gastrointestinal tract, characterized by epigastric pain of moderate to severe intensity, which radiates to the back, elevation of pancreatic lipase and amylase enzymes, and changes in pancreatic parenchyma in imaging methods. The most common etiologies vary, generally the most frequent being biliary lithiasis and alcohol, followed by hypertriglyceridemia. Among the less frequent causes is drug-induced pancreatitis. We report a case of acute pancreatitis caused by cocaine, rarely described in literature.

  10. Cocaine Use Reverses Striatal Plasticity Produced During Cocaine Seeking.

    Science.gov (United States)

    Spencer, Sade; Garcia-Keller, Constanza; Roberts-Wolfe, Douglas; Heinsbroek, Jasper A; Mulvaney, Mallory; Sorrell, Anne; Kalivas, Peter W

    2017-04-01

    Relapse is a two-component process consisting of a highly motivated drug-seeking phase that, if successful, is followed by a drug-using phase resulting in temporary satiation. In rodents, cue-induced drug seeking requires transient synaptic potentiation (t-SP) of cortical glutamatergic synapses on nucleus accumbens core medium spiny neurons, but it is unknown how achieving drug use affects this plasticity. We modeled the two phases of relapse after extinction from cocaine self-administration to assess how cocaine use affects t-SP associated with cue-induced drug seeking. Rats were trained to self-administer cocaine (n = 96) or were used as yoked-saline control animals (n = 21). After extinction, reinstatement was initiated by 10 minutes of cue-induced drug seeking, followed by 45 minutes with contingent cocaine access, after which cocaine was discontinued and unreinforced lever pressing ensued. Three measures of t-SP were assayed during reinstatement: dendritic spine morphology, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) to N-methyl-D-aspartate (NMDA) ratios, and matrix metalloproteinase activity. We found that cocaine use for 10 minutes collapsed all three measures of cue-potentiated t-SP back to baseline. Moreover, when cocaine use was discontinued 45 minutes later, dendritic spine morphology and AMPA to NMDA ratios were restored as animals became motivated to engage unrewarded lever pressing. Nonreinforced drug seeking was positively correlated with changes in spine morphology, and cocaine access reversed this relationship. Using a novel modification of the reinstatement paradigm, we show that achieving cocaine use reversed the synaptic plasticity underpinning the motivation to seek the drug. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Treatment of chronic cocaine abuse and attention deficit disorder, residual type, with magnesium pemoline.

    Science.gov (United States)

    Weiss, R D; Pope, H G; Mirin, S M

    1985-05-01

    Research suggests that attention deficit disorder (ADD) may persist into adulthood, perhaps predisposing certain individuals to stimulant abuse. The authors describe two adults with chronic cocaine abuse and apparent residual ADD. After failing to respond to conventional treatment modalities, these patients were administered magnesium pemoline. Both displayed a sustained reduction in their cocaine use, without abusing pemoline. This finding suggests that the diagnostic assessment of cocaine abusers should include a search for a history of ADD. A carefully selected subgroup of this population may benefit from treatment with other stimulant medications.

  12. Postpartum Sexual Abstinence and Breastfeeding Pattern in ...

    African Journals Online (AJOL)

    elearning

    Postpartum Sexual Abstinence and. Breastfeeding Pattern in Sagamu,. Nigeria. A.O. Sule-Odu, T. A Fakoya, F.A. Oluwole1, O.A. Ogundahunsi2, A.O. Olowu3. D.M. Olanrewaju3, F.A. Akesode3, O.A. Dada4, E.A. Sofekun4. ABSTRACT. This was a prospective study involving 371 mothers. The mean age of the mothers was ...

  13. Cocaine self-administration abolishes associative neural encoding in the nucleus accumbens necessary for higher-order learning.

    Science.gov (United States)

    Saddoris, Michael P; Carelli, Regina M

    2014-01-15

    Cocaine use is often associated with diminished cognitive function, persisting even after abstinence from the drug. Likely targets for these changes are the core and shell of the nucleus accumbens (NAc), which are critical for mediating the rewarding aspects of drugs of abuse as well as supporting associative learning. To understand this deficit, we recorded neural activity in the NAc of rats with a history of cocaine self-administration or control subjects while they learned Pavlovian first- and second-order associations. Rats were trained for 2 weeks to self-administer intravenous cocaine or water. Later, rats learned a first-order Pavlovian discrimination where a conditioned stimulus (CS)+ predicted food, and a control (CS-) did not. Rats then learned a second-order association where, absent any food reinforcement, a novel cued (SOC+) predicted the CS+ and another (SOC-) predicted the CS-. Electrophysiological recordings were taken during performance of these tasks in the NAc core and shell. Both control subjects and cocaine-experienced rats learned the first-order association, but only control subjects learned the second-order association. Neural recordings indicated that core and shell neurons encoded task-relevant information that correlated with behavioral performance, whereas this type of encoding was abolished in cocaine-experienced rats. The NAc core and shell perform complementary roles in supporting normal associative learning, functions that are impaired after cocaine experience. This impoverished encoding of motivational behavior, even after abstinence from the drug, might provide a key mechanism to understand why addiction remains a chronically relapsing disorder despite repeated attempts at sobriety. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Effects of Lorcaserin on Cocaine and Methamphetamine Self-Administration and Reinstatement of Responding Previously Maintained by Cocaine in Rhesus Monkeys.

    Science.gov (United States)

    Gerak, Lisa R; Collins, Gregory T; France, Charles P

    2016-12-01

    Stimulant abuse is a serious public health issue for which there is no effective pharmacotherapy. The serotonin 2C [5-hydroxytryptamine 2C (5-HT 2C )] receptor agonist lorcaserin decreases some abuse-related effects of cocaine in monkeys and might be useful for treating stimulant abuse. The current study investigated the effectiveness of lorcaserin to reduce self-administration of either cocaine or methamphetamine and cocaine-induced reinstatement of extinguished responding. Four rhesus monkeys responded under a progressive-ratio (PR) schedule in which the response requirement increased after each cocaine infusion (32-320 μg/kg/infusion). A separate group of four monkeys responded under a fixed-ratio (FR) schedule for cocaine (32 μg/kg/infusion) and reinstatement of extinguished responding was examined following administration of noncontingent infusions of cocaine (0.1-1 mg/kg) that were combined with response-contingent presentations of the drug-associated stimuli. Finally, three monkeys responded under a FR schedule for methamphetamine (0.32-100 μg/kg/infusion). Lorcaserin (3.2 mg/kg) significantly decreased the final ratio completed (i.e., decreased break point) in monkeys responding under the PR schedule and reduced the reinstatement of responding for drug-associated stimuli following a noncontingent infusion of cocaine; these effects did not appear to change when lorcaserin was administered daily. The same dose of lorcaserin decreased responding for methamphetamine in two of the three monkeys, and the effect was maintained during daily lorcaserin administration; larger doses given acutely (10-17.8 mg/kg) significantly decreased responding for methamphetamine, although that effect was not sustained during daily lorcaserin administration. Together, these results indicate that lorcaserin might be effective in reducing cocaine and methamphetamine abuse and cocaine relapse at least in some individuals. Copyright © 2016 by The American Society for Pharmacology

  15. rsfMRI effects of KB220Z™ on Neural Pathways in Reward Circuitry of Abstinent Genotyped Heroin Addicts

    Science.gov (United States)

    Blum, Kenneth; Liu, Yijun; Wang, Wei; Wang, Yarong; Zhang, Yi; Oscar-Berman, Marlene; Smolen, Andrew; Febo, Marcelo; Han, David; Simpatico, Thomas; Cronjé, Frans J; Demetrovics, Zsolt; Gold, Mark S.

    2016-01-01

    Recently Willuhn et al. reported that cocaine use and even non-substance related addictive behavior, increases, as dopaminergic function is reduced. Chronic cocaine exposure has been associated with decreases in D2/D3 receptors, also associated with lower activation to cues in occipital cortex and cerebellum in a recent PET study from Volkow’s group. Therefore, treatment strategies, like dopamine agonist therapy, that might conserve dopamine function may be an interesting approach to relapse prevention in psychoactive drug and behavioral addictions. To this aim, we evaluated the effect of KB220Z™ on reward circuitry of ten heroin addicts undergoing protracted abstinence, an average 16.9 months. In a randomized placebo-controlled crossover study of KB220Z™ five subjects completed a triple blinded–experiment in which the subject, the person administering the treatment and the person evaluating the response to treatment were blinded as to which treatment any particular subject was receiving. In addition, nine subjects total were genotyped utilizing the GARSRX™ test. We preliminarily report that KB220Z ™ induced an increase in BOLD activation in caudate-accumbens-dopaminergic pathways compared to placebo following one-hour acute administration. Furthermore, KB220Z™ also reduced resting state activity in the putamen of abstinent heroin addicts. In the second phase of this pilot study of all ten abstinent heroin-dependent subjects, three brain regions of interest (ROIs) we observed to be significantly activated from resting state by KB220Z compared to placebo (P addiction by direct or indirect dopaminergic interaction. Due to small sample size, we caution definitive interpretation of these preliminary results and confirmation with additional research and ongoing rodent and human studies of KB220Z, is required. PMID:25526228

  16. Cocaine enhances HIV-1 gp120-induced lymphatic endothelial dysfunction in the lung.

    Science.gov (United States)

    Zhang, Xuefeng; Jiang, Susan; Yu, Jinlong; Kuzontkoski, Paula M; Groopman, Jerome E

    2015-08-01

    Pulmonary complications are common in both AIDS patients and cocaine users. We addressed the cellular and molecular mechanisms by which HIV and cocaine may partner to induce their deleterious effects. Using primary lung lymphatic endothelial cells (L-LECs), we examined how cocaine and HIV-1 gp120, alone and together, modulate signaling and functional properties of L-LECs. We found that brief cocaine exposure activated paxillin and induced cytoskeletal rearrangement, while sustained exposure increased fibronectin (FN) expression, decreased Robo4 expression, and enhanced the permeability of L-LEC monolayers. Moreover, incubating L-LECs with both cocaine and HIV-1 gp120 exacerbated hyperpermeability, significantly enhanced apoptosis, and further impaired in vitro wound healing as compared with cocaine alone. Our studies also suggested that the sigma-1 receptor (Sigma-1R) and the dopamine-4 receptor (D4R) are involved in cocaine-induced pathology in L-LECs. Seeking clinical correlation, we found that FN levels in sera and lung tissue of HIV(+) donors were significantly elevated as compared to HIV(-) donors. Our in vitro data demonstrate that cocaine and HIV-1 gp120 induce dysfunction and damage of lung lymphatics, and suggest that cocaine use may exacerbate pulmonary edema and fibrosis associated with HIV infection. Continued exploration of the interplay between cocaine and HIV should assist the design of therapeutics to ameliorate HIV-induced pulmonary disorders within the drug using population. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  17. The Smoking Abstinence Questionnaire: measurement of smokers' abstinence-related expectancies.

    Science.gov (United States)

    Hendricks, Peter S; Wood, Sabrina B; Baker, Majel R; Delucchi, Kevin L; Hall, Sharon M

    2011-04-01

    To develop and validate a measure of smokers' expectancies for the abstinence process upon quitting smoking: the Smoking Abstinence Questionnaire (SAQ). Principal component analysis and other psychometric analyses of self-report data. San Francisco, California. A total of 507 adult smokers of at least 10 cigarettes per day diverse in gender, sexual orientation and ethnoracial status. The primary measure was a draft version of the SAQ. Additional measures assessed a variety of other smoking-related constructs. Analyses yielded 10 scales of the SAQ: Withdrawal, Social Improvement/Non-smoker Identity, Adverse Outcomes, Treatment Effectiveness, Common Reasons, Barriers to Treatment, Social Support, Optimistic Outcomes, Coffee Use and Weight Gain. The SAQ scales demonstrated internal consistencies ranging from 0.62 to 0.85 and were associated with tobacco dependence, motivation to quit, abstinence self-efficacy, withdrawal symptoms, dietary restraint, shape and weight concern and tobacco use expectancies. The SAQ predicted smoking-related constructs above and beyond tobacco use expectancies, suggesting that abstinence-related expectancies and tobacco use expectancies are distinct from one another. A newly developed questionnaire, the Smoking Abstinence Questionnaire, appears to capture reliably smokers' expectancies for abstinence (Withdrawal, Social Improvement/Non-smoker Identity, Adverse Outcomes, Common Reasons, Optimistic Outcomes, Coffee Use, and Weight Gain) and expectancies related to the success of a quit attempt (Treatment Effectiveness, Barriers to Treatment and Social Support). It remains to be seen how far any of these expectancies predict attempts to quit, withdrawal, treatment utilization and response and quitting success above and beyond existing measures. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

  18. The effect of chronic amphetamine treatment on cocaine-induced facilitation of intracranial self-stimulation in rats

    Science.gov (United States)

    Bauer, Clayton T.; Banks, Matthew L.; Negus, S. Stevens

    2014-01-01

    Rationale: Chronic amphetamine treatment reduces cocaine self-administration in pre-clinical and clinical settings, and amphetamine has been proposed as a candidate medication for treatment of cocaine abuse. Objectives: Investigate whether chronic amphetamine treatment can decrease the abuse-related cocaine effects in an assay of intracranial self-stimulation (ICSS). Methods: Thirteen adult male Sprague-Dawley rats were equipped with intracranial electrodes targeting the medial forebrain bundle and trained to lever press for pulses of brain stimulation in a “frequency-rate” ICSS procedure. Cocaine (10 mg/kg) was administered before (Day 0), during (Days 7 and 14) and after (post-treatment days 1 and 3) two weeks of continuous treatment with either amphetamine (0.32mg/kg/hr, n=7) or saline (n=6) via osmotic pump. Results: Prior to treatment, cocaine facilitated ICSS in all rats. Saline treatment had no effect on baseline ICSS or cocaine-induced facilitation of ICSS at any time. Conversely, amphetamine produced a sustained though sub-maximal facilitation of baseline ICSS, and cocaine produced little additional facilitation of ICSS during amphetamine treatment. Termination of amphetamine treatment produced a depression of baseline ICSS and recovery of cocaine-induced facilitation of ICSS. Conclusions: These data suggest that chronic amphetamine treatment blunts expression of abuse-related cocaine effects on ICSS in rats. PMID:24408209

  19. Day treatment for cocaine dependence: incremental utility over outpatient counseling and voucher incentives.

    Science.gov (United States)

    Marlowe, Douglas B; Kirby, Kimberly C; Festinger, David S; Merikle, Elizabeth P; Tran, Giao Q; Platt, Jerome J

    2003-03-01

    Urban, poor, crack cocaine-dependent clients were randomly assigned to outpatient addiction counseling (n=39) or day treatment (n=40). Participants in both conditions received equivalent individual cognitive-behavioral counseling and earned equivalent payment vouchers for providing cocaine-negative urine samples. However, day treatment participants attended significantly more psychoeducational and recreational groups and received two meals per day. Prior to random assignment, more participants expressed a preference for day treatment and participants were more likely to return for an initial appointment following assignment to day treatment. However, no significant between-groups differences in tenure or abstinence were detected during the 3-month course of treatment. These null findings were attributable to an absence of a dose-response effect for the group interventions in the day treatment condition. In addition, there may have been a ceiling effect from the vouchers, which masked the influence of the additional day treatment components.

  20. Effects of social reorganization on dopamine D2/D3 receptor availability and cocaine self-administration in male cynomolgus monkeys.

    Science.gov (United States)

    Czoty, P W; Gould, R W; Gage, H D; Nader, M A

    2017-09-01

    Studies have demonstrated that brain dopamine D2/D3 receptors (D2/D3R) and the reinforcing effects of cocaine can be influenced by a monkey's position in the social dominance hierarchy. In this study, we manipulated the social ranks of monkeys by reorganizing social groups and assessed effects on D2/D3R availability and cocaine self-administration. Male cynomolgus monkeys (N = 12) had been trained to self-administer cocaine under a concurrent cocaine-food reinforcement schedule. Previously, PET measures of D2/D3R availability in the caudate nucleus and putamen had been obtained with [ 18 F]fluoroclebopride during cocaine abstinence, while monkeys lived in stable social groups of four monkeys/pen. For this study, monkeys were reorganized into groups that consisted of (1) four previously dominant, (2) four previously subordinate, and (3) a mix of previously dominant and subordinate monkeys. After 3 months, D2/D3R availability was redetermined and cocaine self-administration was reexamined. D2/D3R availability significantly increased after reorganization in monkeys who were formerly subordinate, with the greatest increases observed in those that became dominant. No consistent changes in D2/D3R availability were observed in formerly dominant monkeys. Cocaine self-administration did not vary according to rank after reorganization of social groups. However, when compared to their previous cocaine self-administration data, the potency of cocaine as a reinforcer decreased in 9 of 11 monkeys. These results indicate that changing the social conditions can alter D2/D3R availability in subordinate monkeys in a manner suggestive of environmental enrichment. In most monkeys, social reorganization shifted the cocaine dose-response curve to the right, also consistent with environmental enrichment.

  1. Cocaine-induced neuroadaptations in glutamate transmission

    Science.gov (United States)

    Schmidt, Heath D.; Pierce, R. Christopher

    2017-01-01

    A growing body of evidence indicates that repeated exposure to cocaine leads to profound changes in glutamate transmission in limbic nuclei, particularly the nucleus accumbens. This review focuses on preclinical studies of cocaine-induced behavioral plasticity, including behavioral sensitization, self-administration, and the reinstatement of cocaine seeking. Behavioral, pharmacological, neurochemical, electrophysiological, biochemical, and molecular biological changes associated with cocaine-induced plasticity in glutamate systems are reviewed. The ultimate goal of these lines of research is to identify novel targets for the development of therapies for cocaine craving and addiction. Therefore, we also outline the progress and prospects of glutamate modulators for the treatment of cocaine addiction. PMID:20201846

  2. Relationships of Behavioral Measures of Frontal Lobe Dysfunction with Underlying Electrophysiology in Cocaine-Dependent Patients

    Science.gov (United States)

    Gjini, Klevest; Qazi, Aisha; Greenwald, Mark K.; Sandhu, Ravinder; Gooding, Diane C.; Boutros, Nash N.

    2013-01-01

    Background and Objectives Despite evidence that frontal lobe functioning is impaired in cocaine-dependent individuals, relationships between behavioral measures of frontal dysfunction and electrophysiological measures of inhibition in cocaine use have not been explored. Methods Using the Frontal System Behavior Scale (FrSBe), frontal dysfunction was assessed in a group of abstinent cocaine-dependent subjects (N=49) and healthy controls (N=32). Using transcranial magnetic stimulation (TMS) and evoked potential (EP)-based electrophysiological measures of inhibition, we assessed associations between these measures and FrSBe estimates of frontal dysfunction. Results Patients had significantly higher FrSBe scores for executive dysfunction, disinhibition and apathy than controls. Lower TMS-based resting motor thresholds (i.e., hyperexcitability) were significantly associated with higher Executive Dysfunction scores in the patients. Conclusions and Scientific Significance Relationships between FrSBe scores and TMS-based measures highlight neurophysiological aberrations underlying frontal lobe dysfunction in cocaine abusers. TMS and EP measures may be useful probes of the intermediary steps between frontal lobe dysfunction and addictive behavior. PMID:24724884

  3. Role of Corticotropin Releasing Factor 1 Signaling in Cocaine Seeking during Early Extinction in Female and Male Rats.

    Science.gov (United States)

    Cason, Angie M; Kohtz, Amy; Aston-Jones, Gary

    2016-01-01

    Locus coeruleus norepinephrine (LC-NE) and corticotropin releasing factor (CRF) neurons are involved in stress responses, including stress's ability to drive drug relapse. Previous animal studies indicate that female rats exhibit greater drug seeking than male rats during initial drug abstinence. Moreover, females are more sensitive to the effect of stress to drive drug seeking than males. Finally, LC-NE neurons are more sensitive to CRF in females compared to males. We hypothesized that increased drug seeking in females on extinction day one (ED1) is due to increased response to the stress of early withdrawal and is dependent upon the increased response of LC in females to CRF. We predicted that LC-NE neurons would exhibit Fos activation on ED1, and that blocking CRF1 signaling would decrease drug seeking on ED1 measured by responding on an active lever previously associated with cocaine self- administration. After chronic cocaine self-administration, female and male rats underwent a test for initial extinction responding by measuring lever pressing in the absence of cocaine. Prior to this Extinction Day 1 (ED1) session, rats were injected with vehicle or the selective CRF1 antagonist (CP) to measure effects of CRF antagonism on drug seeking during early abstinence. ED1 increased corticosterone in female rats, in proportion to lever responding in male and female, indicating that ED1 was stressful. Pretreatment with CP decreased cocaine seeking on ED1 more effectively in female compared to male rats. This increase in responding was associated with an increase in activation of LC NE neurons. Together, these findings indicate that stress, and signaling at CRF receptors in LC, may be involved in the increased drug seeking during initial abstinence.

  4. Role of Corticotropin Releasing Factor 1 Signaling in Cocaine Seeking during Early Extinction in Female and Male Rats.

    Directory of Open Access Journals (Sweden)

    Angie M Cason

    Full Text Available Locus coeruleus norepinephrine (LC-NE and corticotropin releasing factor (CRF neurons are involved in stress responses, including stress's ability to drive drug relapse. Previous animal studies indicate that female rats exhibit greater drug seeking than male rats during initial drug abstinence. Moreover, females are more sensitive to the effect of stress to drive drug seeking than males. Finally, LC-NE neurons are more sensitive to CRF in females compared to males. We hypothesized that increased drug seeking in females on extinction day one (ED1 is due to increased response to the stress of early withdrawal and is dependent upon the increased response of LC in females to CRF. We predicted that LC-NE neurons would exhibit Fos activation on ED1, and that blocking CRF1 signaling would decrease drug seeking on ED1 measured by responding on an active lever previously associated with cocaine self- administration. After chronic cocaine self-administration, female and male rats underwent a test for initial extinction responding by measuring lever pressing in the absence of cocaine. Prior to this Extinction Day 1 (ED1 session, rats were injected with vehicle or the selective CRF1 antagonist (CP to measure effects of CRF antagonism on drug seeking during early abstinence. ED1 increased corticosterone in female rats, in proportion to lever responding in male and female, indicating that ED1 was stressful. Pretreatment with CP decreased cocaine seeking on ED1 more effectively in female compared to male rats. This increase in responding was associated with an increase in activation of LC NE neurons. Together, these findings indicate that stress, and signaling at CRF receptors in LC, may be involved in the increased drug seeking during initial abstinence.

  5. Does abstinence resolve poor sleep quality in former methamphetamine dependents?

    Directory of Open Access Journals (Sweden)

    Amir Rezaei Ardani

    2016-07-01

    Conclusions: This study showed that the patients' quality of sleep improved significantly four weeks after abstinence and its variation was independent from variations in anxiety and depressive symptoms.

  6. Compassion Fatigue, Burnout, and Neonatal Abstinence Syndrome.

    Science.gov (United States)

    Sweigart, Erin

    2017-01-01

    NICU nurses have seen a dramatic increase in cases of neonatal abstinence syndrome (NAS). The care needs of infants with NAS are highly demanding and can lead to feelings of frustration and emotional exhaustion among NICU nurses. Although studies have examined the experiences of nurses caring for NAS patients, none have specifically addressed the risk for compassion fatigue and burnout. Nurses need practical strategies to reduce their risk for compassion fatigue and burnout when caring for these patients. Improved education and implementation of self-care measures can help nurses more effectively manage stress and positively impact care of these infants and their families.

  7. Profiling of cocaine by micellar electrokinetic chromatography

    NARCIS (Netherlands)

    Hilhorst, MJ; van Hout, MWJ; Somsen, GW; Franke, JP; de Jong, GJ

    1998-01-01

    The potential of micellar electrokinetic chromatography (MEKC) for the profiling of cocaine samples is described. An MEKC system containing sodium dodecyl sulfate (SDS) and methanol was optimized using a test mixture of cocaine, its common impurities (benzoylecgonine, norcocaine, tropacocaine, and

  8. Cocaine Conditioned Behavior: A Cocaine Memory Trace or an Anti-Habituation Effect

    OpenAIRE

    Robert J. Carey; Damianopoulos, Ernest N.; Shanahan, Arielle B.

    2008-01-01

    Whether cocaine locomotor conditioning represents a cocaine positive effect; i.e., a Pavlovian cocaine conditioned response; or, a cocaine negative effect; i.e., interference with habituation to the test environment, is a subject of some controversy. Three separate experiments were conducted to compare the behavior (locomotion and grooming) of separate groups of rats given 1, 9 or 14 cocaine (10 mg/kg) treatments paired/unpaired with placement into an open-field arena. The behavior of the coc...

  9. Prenatal Cocaine Exposure and Infant Cortisol Reactivity

    Science.gov (United States)

    Eiden, Rina D.; Veira, Yvette; Granger, Douglas A.

    2009-01-01

    This study examined the effects of prenatal cocaine exposure on infant hypothalamic-pituitary-adrenal axis activity and reactivity at 7 months of infant age. Participants were 168 caregiver-infant dyads (87 cocaine exposed, 81 not cocaine exposed; 47% boys). Maternal behavior, caregiving instability, and infant growth and behavior were assessed,…

  10. Cocaine use in pregnancy in Amsterdam

    NARCIS (Netherlands)

    Smit, B. J.; Boer, K.; van Huis, A. M.; Lie-A-Ling, I. S.; Schmidt, S. C.

    1994-01-01

    To study the effects of cocaine use in pregnancy in Amsterdam, clinical data on cocaine-using pregnant women (n = 21) and their offspring (n = 23) were obtained retrospectively (1987-1994) at the Academic Medical Center, Amsterdam. Infants exposed to cocaine had a median gestational age of 39 weeks

  11. Sexual abstinence: What is the understanding and views of ...

    African Journals Online (AJOL)

    2016-06-17

    Jun 17, 2016 ... West Province, South Africa?, SAHARA-J: Journal of Social Aspects of HIV/AIDS, 13:1, 81-87, DOI: 10.1080/17290376.2016. ..... understanding of sexual abstinence, abstinence as protection. Fig. 1. Grades of the ... sex, use of alcohol and drugs and influence of the media and television. Peer pressure.

  12. Sexual abstinence: What is the understanding and views of ...

    African Journals Online (AJOL)

    Among strategies to prevent HIV, other sexually transmitted infections (STIs) and unwanted pregnancies, are programs that promote sexual abstinence among adolescents. However, literature suggests that there may be differences in the understanding of abstinence across adolescents, and this study sought to explore the ...

  13. Young South Africans' views on, and perceptions of, abstinence and ...

    African Journals Online (AJOL)

    The goals of the Abstinence and Be Faithful Among Youth (ABY) project were to enhance local responses among the youth in South Africa to prevent HIV infection through encouraging abstinence, faithfulness and avoidance of unhealthy sexual behaviour among youths over a five-year period. A quantitative baseline ...

  14. Abstinence And Faithfulness Programmes For Prevention Of Hiv ...

    African Journals Online (AJOL)

    Questions have been raised on whether abstinence and faithfulness programs work, particularly for young people. Research is needed for evidence-based documentation of the effectiveness or otherwise of abstinence and faithfulness programmes in young people. This review was conducted in three stages: identification ...

  15. Evaluation of buspirone for relapse-prevention in adults with cocaine dependence: an efficacy trial conducted in the real world.

    Science.gov (United States)

    Winhusen, Theresa; Brady, Kathleen T; Stitzer, Maxine; Woody, George; Lindblad, Robert; Kropp, Frankie; Brigham, Gregory; Liu, David; Sparenborg, Steven; Sharma, Gaurav; Vanveldhuisen, Paul; Adinoff, Bryon; Somoza, Eugene

    2012-09-01

    Cocaine dependence is a significant public health problem for which there are currently no FDA-approved medications. Hence, identifying candidate compounds and employing an efficient evaluation process is crucial. This paper describes key design decisions made for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) study that uses a novel two-stage process to evaluate buspirone (60 mg/day) for cocaine-relapse prevention. The study includes pilot (N=60) and full-scale (estimated N=264) trials. Both trials will be randomized, double-blind, and placebo-controlled and both will enroll treatment-seeking cocaine-dependent participants engaged in inpatient/residential treatment and scheduled for outpatient treatment post-discharge. All participants will receive contingency management in which incentives are given for medication adherence as evaluated by the Medication Events Monitoring System (MEMS). The primary outcome measure is maximum days of continuous cocaine abstinence, as assessed by twice-weekly urine drug screens (UDS) and self-report, during the 15-week outpatient treatment phase. Drug-abuse outcomes include cocaine use as assessed by UDS and self-report of cocaine use, other substance use as assessed by UDS and self-report of substance use (i.e., alcohol and/or illicit drugs), cocaine bingeing, HIV risk behavior, quality of life, functioning, and substance abuse treatment attendance. Unique aspects of the study include conducting an efficacy trial in community treatment programs, a two-stage process to efficiently evaluate buspirone, and an evaluation of mediators by which buspirone might exert a beneficial effect on relapse prevention. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Motivational interviewing combined with chess accelerates improvement in executive functions in cocaine dependent patients: a one-month prospective study.

    Science.gov (United States)

    Gonçalves, Priscila Dib; Ometto, Mariella; Bechara, Antoine; Malbergier, André; Amaral, Ricardo; Nicastri, Sergio; Martins, Paula A; Beraldo, Livia; dos Santos, Bernardo; Fuentes, Daniel; Andrade, Arthur G; Busatto, Geraldo F; Cunha, Paulo Jannuzzi

    2014-08-01

    In cocaine-dependent individuals, executive function (EF) deficits are associated with poor treatment outcomes. Psychological interventions and pharmacological approaches have produced only modest effect sizes. To date, studies of this topic have been few and limited. The aim of this study was to examine the effects of a new model of intervention, which integrates chess and Motivational Interviewing, Motivational Chess (MC) METHODS: We evaluated 46 cocaine-dependent inpatients (aged 18-45), in two groups-MC (n=26); and active comparison-AC (n=20). Using neuropsychological tests and an impulsivity scale, we assessed the subjects before and after the study period (one month of abstinence monitored by urine toxicology screening). The MC and AC groups did not differ at baseline. In the post-intervention assessment (after one month), both groups showed significant improvements in attention, mental flexibility, inhibitory control, abstraction abilities, and decision-making (pattentional and executive domains in cocaine-dependent subjects. The MC intervention was associated with greater improvements in EFs, especially working memory, suggesting that tailored interventions focusing on complex EFs accelerate the process of cognitive recovery during the initial period of abstinence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Drug smuggling using clothing impregnated with cocaine.

    Science.gov (United States)

    McDermott, Seán D; Power, John D

    2005-11-01

    A case study is presented where a woman travelling from South America to the Republic of Ireland was detained at Dublin Airport and articles of clothing she had in her luggage were found to be impregnated with cocaine. The study shows that the amount of powder recovered from the garments was approximately 14% of the total weight of the garments. The cocaine was in the form of cocaine hydrochloride and the purity was approximately 80%. An examination of the garments under filtered light highlighted the areas exposed to cocaine and indicated that the method of impregnation was by pouring liquid containing cocaine onto the clothing.

  18. COCAINE CARDIOMYOPATHY—A CASE REPORT

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    Georgiev Antonio

    2014-12-01

    Full Text Available Abstract: Cocaine is the second most common illicit drug used and the most frequent cause of drug related deaths. The use of cocaine is associated with both, acute and chronic complications, that may involve any system, but the most common system affected is cardiovascular one. Cocaine cardiomyopathy may result from the use of cocaine. This article presents a first case in Republic of Macedonia of 24-year-old male with reversible cocaine- related cardiomyopathy. Clinical presentation, laboratory, X-ray, ultrasound findings and treatment are reviewed.

  19. Rat ultrasonic vocalizations demonstrate that the motivation to contextually reinstate cocaine-seeking behavior does not necessarily involve a hedonic response.

    Science.gov (United States)

    Barker, David J; Bercovicz, Danielle; Servilio, Lisa C; Simmons, Steven J; Ma, Sisi; Root, David H; Pawlak, Anthony P; West, Mark O

    2014-09-01

    Human self-reports often indicate that changes in mood are a major contributor to drug relapse. Still, arguments have been made that instances of drug-seeking following abstinence in animal models (i.e. relapse/reinstatement) may be outside of hedonic control. Therefore, the present study utilized ultrasonic vocalizations in the rat in order to evaluate affect during cocaine self-administration and contextual reinstatement of cocaine-seeking in a pre-clinical model of drug relapse (abstinence-reinstatement model). Results show that while subjects effectively reinstated drug-seeking (lever pressing) following 30 days of abstinence, and spontaneously recovered/reinstated drug-seeking following 60 days of abstinence, ultrasonic vocalizations did not increase over baseline levels during either reinstatement session. These results are consistent with previous results from our laboratory and current theories of addiction suggesting that cues that are weakly associated with drug consumption can motivate drug-seeking behavior that is outside of hedonic processing. © 2013 The Authors, Addiction Biology © 2013 Society for the Study of Addiction.

  20. Minocycline affects cocaine sensitization in mice

    Science.gov (United States)

    Chen, Hu; Uz, Tolga; Manev, Hari

    2009-01-01

    Growing evidence has pointed to an interaction between the tetracycline antibiotic minocycline and drugs with abuse liability such as opioids and amphetamines. In this work, we tested the hypothesis that similar to its effects on methamphetamine-induced locomotor sensitization, minocycline may influence the behavioral effects of cocaine. Experiments were performed in male C57BL/6J mice using an automated system to measure locomotor activity. We found that 80 mg/kg minocycline significantly reduced locomotor activity when administered either alone or injected 30 min prior to cocaine, which increased locomotor activity. To investigate whether minocycline selectively affects the development of locomotor sensitization induced by four daily injections of 10 mg/kg cocaine, we sought a schedule of minocycline administration that does not per se affect locomotor activity. Thus, we selected 40 mg/kg minocycline administered 3 hours prior to cocaine; minocycline did not affect cocaine-stimulated locomotor activity on the first day of administration but prevented the development of cocaine sensitization. We also tested whether minocycline would affect an already established cocaine sensitization. After establishing the sensitization effect by four daily injections, cocaine treatment was discontinued and mice were treated with minocycline daily (days 5–11) or on day 11 only. There was no effect of minocycline treatment on the response of cocaine-sensitized mice to the challenge dose of cocaine on day 11. The mechanisms by which minocycline interferes with the development of cocaine sensitization needs to be characterized. PMID:19348734

  1. Neonatal abstinence syndrome: a never ending story!

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    Johannes N. van den Anker

    2013-06-01

    Full Text Available Neonatal Abstinence syndrome (NAS is the result of fetal exposure to illicit or prescription drugs (for example opioids, benzodiazepines, and selective serotonin reuptake inhibitors taken by the mother prenatally. NAS is a complex of symptoms, caused by acute withdrawal of the illicit drug(s used by their mothers during pregnancy, seen in neonates hours or days after being born. In the United States of America around 16% of teenagers and 7% of women between the ages of 18 and 25 use illicit drugs during their pregnancies. In this paper the treatment of opioid dependence during pregnancy and treatment of NAS are presented. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  2. Cocaine Hoppers : The Nigerian Involvement in the Global Cocaine Trade

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    Oboh, Jude Roys

    2016-01-01

    In recent decades, Nigerian criminal drug ‘barons’ and ‘gangs’ have come to dominate international cocaine trafficking via West Africa to destination countries globally, a trend that presents a serious security threat to Africa and the world. This work provides empirical evidence to define and

  3. The relationship between premorbid IQ and neurocognitive functioning in individuals with cocaine use disorders.

    Science.gov (United States)

    Mahoney, James J; Kalechstein, Ari D; De Marco, Anthony P; Newton, Thomas F; De La Garza, Richard

    2017-03-01

    To determine whether premorbid IQ mediates performance on neurocognitive tests in individuals diagnosed with cocaine use disorder (CUD). Recently abstinent cocaine users (N = 113) completed measures sensitive to the effects of cocaine on cognition: Conners' Continuous Performance Task-II (CPT-II), n-back working memory test, and Hopkins Verbal Learning Task-Revised (HVLT-R). Premorbid IQ was calculated using the Oklahoma Premorbid Intelligence Estimate, which integrates scores from the Wechsler Adult Intelligence Scale-III and demographic variables. Participants were grouped according to their premorbid IQ using commonly accepted classifications of ability level (above average [>110], average [90-109], and below average [<90]) and comparisons in neurocognitive performance were performed using one-way analysis of variance. Significant differences were detected between groups on the HVLT-R including Trial 1 (p = .002), total word recall across the 3 list-learning trials (p < .001), and recall following a delay (p < .001). Significant differences were also detected on the N-back, including auditory and visual accuracy (p = .022 and p < .001, respectively) and mean and maximum block length (p < .001). Although significant differences were observed between the above average and average groups (mean effect size = .418 [Cohen's d]), the magnitude of group differences was greatest between the average and below average groups (mean effect size = .716). These results raise questions as to whether the neurocognitive impairment observed in individuals diagnosed with CUD predated the onset of cocaine use or whether the impairments were caused by cocaine use. Because these impairments are potential risk factors for poor treatment outcomes, it is important to consider the need to modify treatment programs to account for lower premorbid IQ. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  4. Adolescent Toluene Inhalation in Rats Affects White Matter Maturation with the Potential for Recovery Following Abstinence

    Science.gov (United States)

    Egan, Gary; Kolbe, Scott; Gavrilescu, Maria; Wright, David; Lubman, Dan Ian; Lawrence, Andrew John

    2012-01-01

    Inhalant misuse is common during adolescence, with ongoing chronic misuse associated with neurobiological and cognitive abnormalities. While human imaging studies consistently report white matter abnormalities among long-term inhalant users, longitudinal studies have been lacking with limited data available regarding the progressive nature of such abnormalities, including the potential for recovery following periods of sustained abstinence. We exposed adolescent male Wistar rats (postnatal day 27) to chronic intermittent inhaled toluene (3,000 ppm) for 1 hour/day, 3 times/week for 8 weeks to model abuse patterns observed in adolescent and young adult human users. This dosing regimen resulted in a significant retardation in weight gain during the exposure period (ptoluene exposure during adolescence and early adulthood resulted in white matter abnormalities, including a decrease in axial (pToluene-induced effects on both body weight and white matter parameters recovered following abstinence. Behaviourally, we observed a progressive decrease in rearing activity following toluene exposure but no difference in motor function, suggesting cognitive function may be more sensitive to the effects of toluene. Furthermore, deficits in rearing were present by 4 weeks suggesting that toluene may affect behaviour prior to detectable white matter abnormalities. Consequently, exposure to inhalants that contain toluene during adolescence and early adulthood appear to differentially affect white matter maturation and behavioural outcomes, although recovery can occur following abstinence. PMID:23028622

  5. Effects of a cocaine hydrolase engineered from human butyrylcholinesterase on metabolic profile of cocaine in rats.

    Science.gov (United States)

    Chen, Xiabin; Zheng, Xirong; Zhou, Ziyuan; Zhan, Chang-Guo; Zheng, Fang

    2016-11-25

    Accelerating cocaine metabolism through enzymatic hydrolysis at cocaine benzoyl ester is recognized as a promising therapeutic approach for cocaine abuse treatment. Our more recently designed A199S/F227A/S287G/A328W/Y332G mutant of human BChE, denoted as cocaine hydrolase-3 (CocH3), has a considerably improved catalytic efficiency against cocaine and has been proven active in blocking cocaine-induced toxicity and physiological effects. In the present study, we have further characterized the effects of CocH3 on the detailed metabolic profile of cocaine in rats administrated intravenously (IV) with 5 mg/kg cocaine, demonstrating that IV administration of 0.15 mg/kg CocH3 dramatically changed the metabolic profile of cocaine. Without CocH3 administration, the dominant cocaine-metabolizing pathway in rats was cocaine methyl ester hydrolysis to benzoylecgonine (BZE). With the CocH3 administration, the dominant cocaine-metabolizing pathway in rats became cocaine benzoyl ester hydrolysis to ecgonine methyl ester (EME), and the other two metabolic pathways (i.e. cocaine methyl ester hydrolysis to BZE and cocaine oxidation to norcocaine) became insignificant. The CocH3-catalyzed cocaine benzoyl ester hydrolysis to EME was so efficient such that the measured maximum blood cocaine concentration (∼38 ng/ml) was significantly lower than the threshold blood cocaine concentration (∼72 ng/ml) required to produce any measurable physiological effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Clinically relevant characteristics associated with early treatment drug use versus abstinence.

    Science.gov (United States)

    Cochran, Gerald; Stitzer, Maxine; Nunes, Edward V; Hu, Mei-Chen; Campbell, Aimee

    2014-04-04

    This study describes early treatment drug use status and associated clinical characteristics in a diverse sample of patients entering outpatient substance abuse psychosocial counseling treatment. The goal is to more fully characterize those entering treatment with and without active use of their primary drug in order to better understand associated treatment needs and resilience factors. We examined baseline data from a NIDA Clinical Trials Network (CTN) study (Web-delivery of Treatment for Substance Use) with an all-comers sample of patients (N = 494) entering 10 outpatient treatment centers. Patients were categorized according to self-identified primary drug of abuse (alcohol, cocaine/stimulants, opioids, marijuana) and by baseline drug use status (positive/negative) based on urine testing or self-reports of recent use (alcohol). Characteristics were examined by primary drug and early use status. Classified as drug-negative were 84%, 76%, 62%, and 33% of primary opioid, stimulant, alcohol, and marijuana users; respectively. Drug-positive versus -negative patients did not differ on demographics or rates of substance abuse/dependence diagnoses. However, those negative for active use had better physical and mental health profiles, were less likely to be using a secondary drug, and were more likely to be attending 12-step self-help meetings. Early treatment drug abstinence is common among substance users entering outpatient psychosocial counseling programs, regardless of primary abused drug. Abstinence (by negative UA) is associated with better health and mental health profiles, less secondary drug use, and more days of 12-step attendance. These data highlight differential treatment needs and resiliencies associated with early treatment drug use status. NCT01104805.

  7. University students' definitions of sexual abstinence and having sex.

    Science.gov (United States)

    Byers, E Sandra; Henderson, Joel; Hobson, Kristina M

    2009-10-01

    We asked 298 heterosexual Canadian university students about their definitions of the terms abstinence and having sex. For both terms, students were provided with a list of 17 sexual behaviors and indicated whether they would include each in their definition. The majority of both male and female students included activities that did not involve genital stimulation in their definition of sexual abstinence and did not include these activities in their definition of having sex. Conversely, most students did not include bidirectional sexual stimulation (penile-vaginal intercourse or penile-anal intercourse) in their definitions of sexual abstinence but did include them in their definitions of having sex. Students were quite mixed in whether activities involving unidirectional genital stimulation (e.g., oral sex, genital fondling) constituted abstinence, having sex, or neither abstinence nor having sex. However, they were more likely to see these behaviors as abstinent than as having sex. Students were more likely to rate a behavior as abstinence if orgasm did not occur. A canonical correlation analysis was used to examine the patterns of association between a number of predictors and inclusions of behaviors involving no genital stimulation, unidirectional stimulation, and bidirectional genital stimulation in abstinence definitions. The results indicated that male participants who were more involved with their religion and sexually conservative, less sexually experienced, and who had not received sexual health education at home were more likely to define bidirectional genital stimulation and less likely to define no genital stimulation and unidirectional sexual stimulation as sexual abstinence. The research and health promotion implications of these results are discussed.

  8. The relationship between impulsivity and craving in cocaine- and methamphetamine-dependent volunteers.

    Science.gov (United States)

    Tziortzis, Desey; Mahoney, James J; Kalechstein, Ari D; Newton, Thomas F; De La Garza, Richard

    2011-04-01

    Impulsivity and craving have been independently hypothesized to contribute to sustained drug use and relapse in addiction. The primary focus of this project was to determine the relationship between impulsivity and craving in 85 cocaine-dependent and 73 methamphetamine-dependent, non-treatment-seeking volunteers. Drug use was assessed with a 14-item, self-report drug and alcohol use questionnaire. Self report instruments utilized included the Barratt Impulsivity Scale (BIS) and the Visual Analog Scale (VAS), which probed "just before your last use of cocaine (for cocaine-dependent participants) or methamphetamine (for methamphetamine-dependent participants), how much craving did you experience?" The groups were similar with respect to recent use of cocaine or methamphetamine, alcohol, nicotine, and marijuana. Analysis of variance (ANOVA) did not reveal significant differences between cocaine and methamphetamine groups for total impulsivity or total craving. Simple linear regression revealed correlations between total impulsivity and total craving in cocaine (r(2)=0.05, p≤0.03) and methamphetamine users (r(2)=0.09, p≤0.008). Participants were separated into high impulsivity (HIBIS) or low impulsivity (LOBIS) subgroups using a median split. ANOVA revealed significantly higher craving in the HIBIS group versus the LOBIS group in methamphetamine users (p≤0.02), but not in cocaine users. For both cocaine and methamphetamine groups, level of impulsivity and craving were found to be related to some drug use variables including years of alcohol use, severity of withdrawal, and craving level following drug use. Taken together, this study shows a marginal relationship between impulsivity and craving, which may further the understanding of motivational factors contributing to ongoing drug use and addiction in psychostimulant users. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Effects of pregnanolone in rats discriminating cocaine.

    Science.gov (United States)

    Quinton, M S; Gerak, L R; Moerschbaecher, J M; Winsauer, P J

    2006-10-01

    The discriminative stimulus effects of cocaine are typically attributed to its ability to increase dopaminergic transmission, although drugs that have different mechanisms of action can substitute for cocaine and modulation of the GABA(A) receptor system has been reported to alter its discriminative effects. Therefore, a discrimination procedure was used to extend the characterization of cocaine's discriminative effects and to examine the interaction between cocaine and pregnanolone, a drug that can modulate the GABA(A) receptor complex. Rats (n=15) were trained to discriminate saline from 5.6 or 10 mg/kg of cocaine under a fixed-ratio (FR) 20 schedule of food presentation. The dopamine releaser d-amphetamine and two monoamine uptake inhibitors bupropion and desipramine substituted for cocaine. In contrast, the positive GABA(A) modulators pregnanolone and lorazepam and the opioid agonist morphine did not substitute for cocaine. When administered prior to cocaine, the D(2) receptor antagonist haloperidol and pregnanolone, but not lorazepam, produced a small rightward shift of the cocaine dose-effect curve. The results of the present studies suggest that the discriminative stimulus effects of cocaine are not solely mediated by increases in dopaminergic transmission and that positive modulation of GABA(A) receptors by pregnanolone can alter these effects, albeit at doses that also decrease overall response rate.

  10. Treatment of cocaine dependence and depression.

    Science.gov (United States)

    Rounsaville, Bruce J

    2004-11-15

    In common with all other classes of substance use disorders, cocaine dependence has been shown to be strongly associated with depression by community and clinical surveys. Diagnosing depression in cocaine abusers can be challenging because it is difficult to distinguish transient symptoms caused by cocaine from enduring depression syndromes. Nonetheless, both "substance-induced" and "independent" depression syndromes require clinical attention, especially when symptoms have been persistent and severe before entering treatment. Use of antidepressant medications for combined cocaine dependence and depression is supported by a preponderance of evidence from 4 randomized clinical trials (RCTs) that prospectively targeted both depression and cocaine dependence and 7 RCTs in which a post hoc analyses demonstrated efficacy in the subgroup of cocaine abusers with comorbid depression. Notably, most negative studies have evaluated SSRIs while positive studies have used agents such as desipramine or buproprion. A substantial clinical trials literature supports the efficacy of behavioral treatments for general populations of cocaine abusers and of patients with depression but few studies have addressed patients with both disorders. Treatment development and research are needed on models of care that truly integrate strategies for addressing both cocaine use and depression. Recent advances have paved the way for a new generation of research. These include validation of efficacious cocaine treatments, improved diagnostic methods, organization of the Clinical Trials Network and development of guidelines for managing methodological challenges posed by high rates of current medication use and polysubstance abuse in treatment entering cocaine abusers.

  11. Medical complications of illicit cocaine use.

    Science.gov (United States)

    VanDette, J M; Cornish, L A

    1989-06-01

    The chemistry, pharmacology, and pharmacokinetics of cocaine are described, and the medical complications of illicit cocaine use are reviewed. Cocaine is readily absorbed from mucous membranes, the gastrointestinal tract, and the vascular beds of the lungs. Thus there are a number of routes for illicit cocaine administration, with the most popular one being intranasal. The most prevalent problems associated with the use of cocaine appear to be route and dose independent and are cardiovascular in nature; they include myocardial infarction and ischemia, sudden death, cardiac arrhythmias, and hypertension. Seizures, cerebrovascular accidents, hepatotoxicity, rhabdomyolysis, pulmonary complications, and obstetrical complications have also been reported. Gastrointestinal complications and acute toxicity may occur in cocaine smugglers who ingest cocaine-filled packets. Route-dependent complications of cocaine use are also of concern. The mechanism underlying the medical complications has not been fully elucidated but appears to be an extension of the drug's pharmacological properties. The treatment of cocaine-related toxicities is supportive and is based on the organ system affected. Drugs such as propranolol, labetalol, and nitrendipine have been advocated for treating the cardiovascular complications, and measures such as maintaining arterial blood pH, monitoring core body temperature, and diazepam therapy have been used to manage seizures. As the number of case reports of cocaine toxicity increases and the underlying mechanism is conclusively defined, management of the medical complications will improve.

  12. Comparing rewarding and reinforcing properties between 'bath salt' 3,4-methylenedioxypyrovalerone (MDPV) and cocaine using ultrasonic vocalizations in rats.

    Science.gov (United States)

    Simmons, Steven J; Gregg, Ryan A; Tran, Fionya H; Mo, Lili; von Weltin, Eva; Barker, David J; Gentile, Taylor A; Watterson, Lucas R; Rawls, Scott M; Muschamp, John W

    2018-01-01

    Abuse of synthetic psychostimulants like synthetic cathinones has risen in recent years. 3,4-Methylenedioxypyrovalerone (MDPV) is one such synthetic cathinone that demonstrates a mechanism of action similar to cocaine. Compared to cocaine, MDPV is more potent at blocking dopamine and norepinephrine reuptake and is readily self-administered by rodents. The present study compared the rewarding and reinforcing properties of MDPV and cocaine using systemic injection dose-response and self-administration models. Fifty kilohertz ultrasonic vocalizations (USVs) were recorded as an index of positive affect throughout experiments. In Experiment 1, MDPV and cocaine dose-dependently elicited 50-kHz USVs upon systemic injection, but MDPV increased USVs at greater rates and with greater persistence relative to cocaine. In Experiment 2, latency to begin MDPV self-administration was shorter than latency to begin cocaine self-administration, and self-administered MDPV elicited greater and more persistent rates of 50-kHz USVs versus cocaine. MDPV-elicited 50-kHz USVs were sustained over the course of drug load-up whereas cocaine-elicited USVs waned following initial infusions. Notably, we observed a robust presence of context-elicited 50-kHz USVs from both MDPV and cocaine self-administering rats. Collectively, these data suggest that MDPV has powerfully rewarding and reinforcing effects relative to cocaine at one-tenth doses. Consistent with prior work, we additionally interpret these data in supporting that MDPV has significant abuse risk based on its potency and subjectively positive effects. Future studies will be needed to better refine therapeutic strategies targeted at reducing the rewarding effects of cathinone analogs in efforts to ultimately reduce abuse liability. © 2016 Society for the Study of Addiction.

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

    Science.gov (United States)

    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…

  14. Enhanced anxiety observed in cocaine withdrawn rats is associated with altered reactivity of the dorsomedial prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Cynthia El Hage

    Full Text Available Discontinuation of drug intake in cocaine abusers commonly produces a variety of adverse withdrawal symptoms among which anxiety and depression-related behavior are prevailing during the initial period of abstinence. The aim of this study was to provide further insight into the neurobiological dysregulations that might contribute to these pathological states. Rats were treated with cocaine or saline for 14 days (20 mg/kg; i.p and anxiety-related behavior was assessed in different paradigms (elevated plus-maze (EPM, confinement to an open arm of the EPM and shock-probe burying tests for up to 4 weeks after withdrawal. Depression-like behavior was assessed by the forced swim test and sucrose preference test. Altogether our results demonstrated that cocaine withdrawal induced persistent heightened levels of anxiety that last for at least 28 days but did not affect depression-like behavior. We then used Fos immunohistochemistry to map neuronal activation patterns in withdrawn rats confined to one open arm of an EPM, and a double labeling procedure using Fos immunohistochemistry and in situ hybridization of glutamic acid decarboxylase or vesicular glutamate transporter mRNAs to identify the phenotype of the activated neurons. Our data showed that the exacerbated anxiety observed in cocaine withdrawn rats exposed to an elevated open arm was accompanied by an altered reactivity of the dorsal part of the medial prefrontal cortex (anterior cingulate and dorsal prelimbic cortices, the paraventricular thalamic nucleus and the lateral and anterior areas of the hypothalamus. In the medial prefrontal cortex, we evidenced a negative correlation between Fos expression in its dorsal part and open arm-induced freezing in NaCl-treated rats but not in cocaine withdrawn rats. We also found that more than 65% of activated neurons were glutamatergic projection neurons. The present study provides new insights into the neuroanatomical regions and neuronal cell types

  15. Enhanced midbrain response at 6-month follow-up in cocaine addiction, association with reduced drug-related choice.

    Science.gov (United States)

    Moeller, Scott J; Tomasi, Dardo; Woicik, Patricia A; Maloney, Thomas; Alia-Klein, Nelly; Honorio, Jean; Telang, Frank; Wang, Gene-Jack; Wang, Ruiliang; Sinha, Rajita; Carise, Deni; Astone-Twerell, Janetta; Bolger, Joy; Volkow, Nora D; Goldstein, Rita Z

    2012-11-01

    Drug addiction is characterized by dysregulated dopamine neurotransmission. Although dopamine functioning appears to partially recover with abstinence, the specific regions that recover and potential impact on drug seeking remain to be determined. Here we used functional magnetic resonance imaging (fMRI) to study an ecologically valid sample of 15 treatment-seeking cocaine addicted individuals at baseline and 6-month follow-up. At both study sessions, we collected fMRI scans during performance of a drug Stroop task, clinical self-report measures of addiction severity and behavioral measures of cocaine seeking (simulated cocaine choice); actual drug use in between the two study sessions was also monitored. At 6-month follow-up (compared with baseline), we predicted functional enhancement of dopaminergically innervated brain regions, relevant to the behavioral responsiveness toward salient stimuli. Consistent with predictions, whole-brain analyses revealed responses in the midbrain (encompassing the ventral tegmental area/substantia nigra complex) and thalamus (encompassing the mediodorsal nucleus) that were higher (and more positively correlated) at follow-up than baseline. Increased midbrain activity from baseline to follow-up correlated with reduced simulated cocaine choice, indicating that heightened midbrain activations in this context may be marking lower approach motivation for cocaine. Normalization of midbrain function at follow-up was also suggested by exploratory comparisons with active cocaine users and healthy controls (who were assessed only at baseline). Enhanced self-control at follow-up was suggested by a trend for the commonly hypoactive dorsal anterior cingulate cortex to increase response during a drug-related context. Together, these results suggest that fMRI could be useful in sensitively tracking follow-up outcomes in drug addiction. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

  16. Reduced attentional scope in cocaine polydrug users.

    Directory of Open Access Journals (Sweden)

    Lorenza S Colzato

    Full Text Available Cocaine is Europe's second preferred recreational drug after cannabis but very little is known about possible cognitive impairments in the upcoming type of recreational cocaine user (monthly consumption. We asked whether recreational use of cocaine impacts early attentional selection processes. Cocaine-free polydrug controls (n = 18 and cocaine polydrug users (n = 18 were matched on sex, age, alcohol consumption, and IQ (using the Raven's progressive matrices, and were tested by using the Global-Local task to measure the scope of attention. Cocaine polydrug users attended significantly more to local aspects of attended events, which fits with the idea that a reduced scope of attention may be associated with the perpetuation of the use of the drug.

  17. The Genomics of Neonatal Abstinence Syndrome

    Directory of Open Access Journals (Sweden)

    F. Sessions Cole

    2017-08-01

    Full Text Available Significant variability has been observed in the development and severity of neonatal abstinence syndrome (NAS among neonates exposed to prenatal opioids. Since maternal opioid dose does not appear to correlate directly with neonatal outcome, maternal, placental, and fetal genomic variants may play important roles in NAS. Previous studies in small cohorts have demonstrated associations of variants in maternal and infant genes that encode the μ-opioid receptor (OPRM1, catechol-O-methyltransferase (COMT, and prepronociceptin (PNOC with a shorter length of hospital stay and less need for treatment in neonates exposed to opioids in utero. Consistently falling genomic sequencing costs and computational approaches to predict variant function will permit unbiased discovery of genomic variants and gene pathways associated with differences in maternal and fetal opioid pharmacokinetics and pharmacodynamics and with placental opioid transport and metabolism. Discovery of pathogenic variants should permit better delineation of the risk of developing more severe forms of NAS. This review provides a summary of the current role of genomic factors in the development of NAS and suggests strategies for further genomic discovery.

  18. Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats

    Science.gov (United States)

    Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M.; See, Ronald E.; Reichel, Carmela M.

    2015-01-01

    Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin’s impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxytocin (1.0 mg/kg) attenuated cue-induced cocaine seeking following extinction. Cocaine increased baseline locomotor activity to a greater degree in females relative to males. Oxytocin (0.1, 0.3, 1.0, and 3.0 mg/kg) reduced cocaine-induced locomotor activity in females, but not significantly in males. These data illustrate sex similarities in oxytocin’s attenuation of cocaine seeking, but sex differences in cocaine-induced locomotor effects. While reductions in cocaine seeking cannot be attributed to a reduction in locomotor activity in males, attenuation of locomotor function cannot be entirely ruled out as an explanation for a decrease in cocaine seeking in females suggesting that oxytocin’s effect on cocaine seeking may be mediated by different mechanisms in male and females. PMID:26523890

  19. Impaired insight in cocaine addiction: laboratory evidence and effects on cocaine-seeking behaviour

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    Moeller, S.J.; Moeller, S.J.; Maloney, T.; Parvaz, M.A.; Alia-Klein, N.; Woicik, P.A.; Telang, F.; Wang, G.-J.; Volkow, N.D.; Goldstein, R.Z.

    2010-04-15

    Neuropsychiatric disorders are often characterized by impaired insight into behaviour. Such an insight deficit has been suggested, but never directly tested, in drug addiction. Here we tested for the first time this impaired insight hypothesis in drug addiction, and examined its potential association with drug-seeking behaviour. We also tested potential modulation of these effects by cocaine urine status, an individual difference known to impact underlying cognitive functions and prognosis. Sixteen cocaine addicted individuals testing positive for cocaine in urine, 26 cocaine addicted individuals testing negative for cocaine in urine, and 23 healthy controls completed a probabilistic choice task that assessed objective preference for viewing four types of pictures (pleasant, unpleasant, neutral and cocaine). This choice task concluded by asking subjects to report their most selected picture type; correspondence between subjects self-reports with their objective choice behaviour provided our index of behavioural insight. Results showed that the urine positive cocaine subjects exhibited impaired insight into their own choice behaviour compared with healthy controls; this same study group also selected the most cocaine pictures (and fewest pleasant pictures) for viewing. Importantly, however, it was the urine negative cocaine subjects whose behaviour was most influenced by insight, such that impaired insight in this subgroup only was associated with higher cocaine-related choice on the task and more severe actual cocaine use. These findings suggest that interventions to enhance insight may decrease drug-seeking behaviour, especially in urine negative cocaine subjects, potentially to improve their longer-term clinical outcomes.

  20. Impaired insight in cocaine addiction: laboratory evidence and effects on cocaine-seeking behaviour.

    Science.gov (United States)

    Moeller, Scott J; Maloney, Thomas; Parvaz, Muhammad A; Alia-Klein, Nelly; Woicik, Patricia A; Telang, Frank; Wang, Gene-Jack; Volkow, Nora D; Goldstein, Rita Z

    2010-05-01

    Neuropsychiatric disorders are often characterized by impaired insight into behaviour. Such an insight deficit has been suggested, but never directly tested, in drug addiction. Here we tested for the first time this impaired insight hypothesis in drug addiction, and examined its potential association with drug-seeking behaviour. We also tested potential modulation of these effects by cocaine urine status, an individual difference known to impact underlying cognitive functions and prognosis. Sixteen cocaine addicted individuals testing positive for cocaine in urine, 26 cocaine addicted individuals testing negative for cocaine in urine, and 23 healthy controls completed a probabilistic choice task that assessed objective preference for viewing four types of pictures (pleasant, unpleasant, neutral and cocaine). This choice task concluded by asking subjects to report their most selected picture type; correspondence between subjects' self-reports with their objective choice behaviour provided our index of behavioural insight. Results showed that the urine positive cocaine subjects exhibited impaired insight into their own choice behaviour compared with healthy controls; this same study group also selected the most cocaine pictures (and fewest pleasant pictures) for viewing. Importantly, however, it was the urine negative cocaine subjects whose behaviour was most influenced by insight, such that impaired insight in this subgroup only was associated with higher cocaine-related choice on the task and more severe actual cocaine use. These findings suggest that interventions to enhance insight may decrease drug-seeking behaviour, especially in urine negative cocaine subjects, potentially to improve their longer-term clinical outcomes.

  1. Cognitive Performance in Long-Term Abstinent Elderly Alcoholics

    Science.gov (United States)

    Fein, George; McGillivray, Shannon

    2010-01-01

    Background To date, there is a wealth of literature describing the deleterious effects of active alcoholism on cognitive function. There has also been, more recently, a growing body of literature investigating the extent of cognitive recovery that can or may occur with abstinence. However, there is still a dearth of published findings on cognitive functioning in very long-term abstinence alcoholics, especially in the elderly population. Methods The current study examines 91 elderly abstinent alcoholics (EAA) (49 men and 42 women) with an average age of 67.3 years, abstinent for an average of 14.8 years (range 0.5 to 45 years), and age and gender comparable light/non-drinking controls. The EAA group was broken down into three sub-groups, individuals who attained abstinence before the age of 50, between the ages 50 and 60, and after the age of 60. Attention, verbal fluency, abstraction/cognitive flexibility, psychomotor, immediate memory, delayed memory, reaction time, spatial processing, and auditory working memory were assessed. Results Overall, the three EAA groups performed comparably to controls on all of the assessments of cognitive function. In fact, only the abstinent before age 50 group performed worse than controls, and this was only in the domain of auditory working memory. Conclusions Our data clearly show that it’s possible for elderly alcoholics with long-term abstinence to attain essentially normal cognitive functioning, even for those individuals who drank relatively late into life. These results don’t imply, however, that all individuals with long-term abstinence will attain normal cognition. It’s possible that selective survivorship may play a part in these findings (e.g. cognitively healthier alcoholics may be more likely to live into their sixties, seventies, or eighties). PMID:17877784

  2. Social relations and smoking abstinence among ever-smokers

    DEFF Research Database (Denmark)

    Ross, Lone; Thomsen, Birthe Lykke Riegels; Boesen, Sidsel Helle

    2013-01-01

    Relational strain may be a risk factor for relapse after smoking cessation whereas social support may be protective. This study aimed to assess which aspects of social relations were associated with smoking abstinence among ever-smokers.......Relational strain may be a risk factor for relapse after smoking cessation whereas social support may be protective. This study aimed to assess which aspects of social relations were associated with smoking abstinence among ever-smokers....

  3. Characterizing Smoking and Drinking Abstinence from Social Media.

    Science.gov (United States)

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

    2015-09-01

    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.

  4. Characterizing Smoking and Drinking Abstinence from Social Media

    Science.gov (United States)

    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

  5. Sleep Regulates Incubation of Cocaine Craving.

    Science.gov (United States)

    Chen, Bo; Wang, Yao; Liu, Xiaodong; Liu, Zheng; Dong, Yan; Huang, Yanhua H

    2015-09-30

    After withdrawal from cocaine, chronic cocaine users often experience persistent reduction in total sleep time, which is accompanied by increased sleep fragmentation resembling chronic insomnia. This and other sleep abnormalities have long been speculated to foster relapse and further drug addiction, but direct evidence is lacking. Here, we report that after prolonged withdrawal from cocaine self-administration, rats exhibited persistent reduction in nonrapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep, as well as increased sleep fragmentation. In an attempt to improve sleep after cocaine withdrawal, we applied chronic sleep restriction to the rats during their active (dark) phase of the day, which selectively decreased the fragmentation of REM sleep during their inactive (light) phase without changing NREM or the total amount of daily sleep. Animals with improved REM sleep exhibited decreased incubation of cocaine craving, a phenomenon depicting the progressive intensification of cocaine seeking after withdrawal. In contrast, experimentally increasing sleep fragmentation after cocaine self-administration expedited the development of incubation of cocaine craving. Incubation of cocaine craving is partially mediated by progressive accumulation of calcium-permeable AMPA receptors (CP-AMPARs) in the nucleus accumbens (NAc). After withdrawal from cocaine, animals with improved REM sleep exhibited reduced accumulation of CP-AMPARs in the NAc, whereas increasing sleep fragmentation accelerated NAc CP-AMPAR accumulation. These results reveal a potential molecular substrate that can be engaged by sleep to regulate cocaine craving and relapse, and demonstrate sleep-based therapeutic opportunities for cocaine addiction. Significance statement: Sleep abnormalities are common symptoms in chronic drug users long after drug withdrawal. These withdrawal-associated sleep symptoms, particularly reduction in total sleep time and deteriorating sleep quality, have been

  6. Molecular approaches to treatments for cocaine abuse

    Science.gov (United States)

    Flippen-Anderson, Judith L.; George, Clifford; Deschamps, Jeffrey R.

    2003-02-01

    Cocaine is a potent stimulant of the central nervous system with severe addiction potential. Its abuse is a major problem worldwide. The exact mechanism of action of cocaine is still uncertain but it is known that its reinforcing and stimulant effects are related to its ability to inhibit the membrane bound dopamine transporter (DAT). This paper discusses efforts that are underway to identify ligands for possible use in the treatment of cocaine abuse. Much of this effort has been focussed on understanding cocaine interactions at DAT receptor sites.

  7. Initial Preference for Drinking Goal in the Treatment of Alcohol Problems: I. Baseline Differences Between Abstinence and Non-Abstinence Groups

    National Research Council Canada - National Science Library

    Heather, Nick; Adamson, Simon J; Raistrick, Duncan; Slegg, Gary P

    2010-01-01

    Aims: To compare baseline characteristics of clients initially preferring abstinence with those preferring non-abstinence at the screening stage of a randomized controlled trial of treatment for alcohol problems (UKATT...

  8. Diazepam alters cocaine self-administration, but not cocaine-stimulated locomotion or nucleus accumbens dopamine

    OpenAIRE

    Maier, Esther Y.; Ledesma, Ramon T.; Seiwell, Andrew P.; Duvauchelle, Christine L.

    2008-01-01

    Cocaine is known to enhance nucleus accumbens dopamine (NAcc DA), serve as a positive reinforcer and produce negative effects, such as anxiety. The influence of diazepam on cocaine intake, cocaine-stimulated behavioral activity and NAcc DA was investigated using self-administration and experimenter-administered intravenous (i.v.) cocaine. In Experiment 1, rats were pretreated with diazepam (0.25 mg/kg) or saline (0.1 ml) 30 minutes prior to 20 daily 1-hr cocaine (0.75 mg/kg/inj) self-administ...

  9. Food addiction: detox and abstinence reinterpreted?

    Science.gov (United States)

    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. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Sinus Bradycardia in Habitual Cocaine Users.

    Science.gov (United States)

    Franklin, Sona M; Thihalolipavan, Sudarone; Fontaine, John M

    2017-05-15

    Common physiological manifestations of cocaine are related to its adrenergic effects, due to inhibition of dopamine and norepinephrine uptake at the postsynaptic terminal. Few studies have documented bradycardia secondary to cocaine use, representing the antithesis of its adrenergic effects. We assessed the prevalence of sinus bradycardia (SB) in habitual cocaine users and postulated a mechanism for this effect. One hundred sixty-two patients with a history of cocaine use were analyzed and compared with age- and gender-matched controls. SB was defined as a rate of cocaine use as 2 or more documented uses >30 days apart. Propensity score-matching analysis was applied to balance covariates between cocaine users and nonusers and reduce selection bias. Patients with a history of bradycardia, hypothyroidism, or concomitant beta-blocker use were excluded. Mean age of study patients was 44 ± 8 years. SB was observed in 43 of 162 (27%) cocaine users and in 9 of 149 (6%) nonusers (p = 0.0001). Propensity score-matching analysis matched 218 patients from both groups. Among matched patients SB was observed in 25 of 109 (23%) cocaine users and in 5 of 109 (5%) nonusers (p = 0.0001). Habitual cocaine use was an independent predictor of SB and associated with a sevenfold increase in the risk of SB (95% CI 2.52 to 19.74, p = 0.0002). In conclusion, habitual cocaine use is a strong predictor of SB and was unrelated to recency of use. A potential mechanism for SB may be related to cocaine-induced desensitization of the beta-adrenergic receptor secondary to continuous exposure. Symptomatic SB was not observed; thus, pacemaker therapy was not indicated. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Plasma Selenium Levels in Chronic Cocaine Abuse.

    Science.gov (United States)

    Petrova, Julia; Manolov, Victor; Kiryakova, Theodora; Vasilev, Vasil; Tzatchev, Kamen; Borislav, Marinov; Radoslava, Emilova

    2016-01-01

    Cocaine abuse is a significant health problem worldwide. We aim to evaluate the role of selenium in oxidative stress in patients with cocaine related cardio- and cerebrovascular diseases. Selenium is of fundamental importance to human health. It is an essential component of several major metabolic pathways. We included 26 patients with chronic cocaine abuse separated into two groups according to duration of intake--from six months up to one year and more than a year, with and without only vascular incidents (TIA, stroke, myocardial infarction), or presence of hypertension. All included groups were analyzed for laboratory parameters: CBC, CRP, AST, ALT, γ-GT, serum creatinine, urea, K, Na, and Ca. Main risk factors were evaluated: total cholesterol, LDL and HDL-cholesterol, triglycerides, glucose, and selenium. Our result shows that in the first group only 20% have cardiovascular problems. In the group with cocaine abuse more than a year, number of vascular incidents has increased (58.3%). Patients from the group cocaine abuse up to 1 year showed no changes in lipid profile, but cocaine abuse more than a year showed interesting changes in the lipid profile. We found a high positive correlation between the two cocaine groups for plasma selenium concentrations. This means that after the first six months oxidative stress has occured. It increases with duration of cocaine abuse. CRP correlated positively between these two groups, showing an endothelial function disorder. Development of oxidative stress increased with cocaine abuse, which leads to lower plasma selenium levels in patients with different duration of intake--less and more than a year. It is possible to supplement selenium during the early period of cocaine dependence to prevent hard vascular accidents, which are common after more than one year of cocaine abuse.

  12. Accelerating cocaine metabolism as an approach to the treatment of cocaine abuse and toxicity

    Science.gov (United States)

    Schindler, Charles W; Goldberg, Steven R

    2012-01-01

    One pharmacokinetic approach to the treatment of cocaine abuse and toxicity involves the development of compounds that can be safely administered to humans and that accelerate the metabolism of cocaine to inactive components. Catalytic antibodies have been developed and shown to accelerate cocaine metabolism, but their catalytic efficiency for cocaine is relatively low. Mutations of human butyrylcholinesterase and a bacterial cocaine esterase found in the soil of coca plants have also been developed. These compounds accelerate cocaine metabolism and antagonize the behavioral and toxic effects of cocaine in animal models. Of these two approaches, the human butyrylcholinesterase mutants show the most immediate promise as they would not be expected to evoke an immune response in humans. PMID:22300096

  13. Cocaine self-administration, extinction training and drug-induced relapse change metabotropic glutamate mGlu5 receptors expression: Evidence from radioligand binding and immunohistochemistry assays.

    Science.gov (United States)

    Pomierny-Chamiolo, Lucyna; Miszkiel, Joanna; Frankowska, Malgorzata; Bystrowska, Beata; Filip, Malgorzata

    2017-01-15

    Several behavioral findings highlight the importance of glutamatergic transmission and its metabotropic receptor type 5 (mGlu5) in the controlling of cocaine reward and seeking behaviors. The molecular or neurochemical nature of such interactions is not well recognized, so in the present paper we determine if cocaine self-administration and extinction/reinstatement models with the yoked triad control procedure alter mGlu5 receptor density in rats. [³H]MPEP was used to evaluate mGlu5 receptors density and affinity in selected brain structures, while immunofluorescence analysis was used to detect changes in mGlu5 receptors' brain location. Cocaine self-administration and yoked cocaine delivery evoked a significant elevation in mGlu5 receptors' density in the dorsal striatum, while receptor protein expression was importantly elevated in the substantia nigra and reduced in the nucleus accumbens shell. Cocaine administration followed by 10 extinction training sessions resulted in biphasic mGlu5 receptor density changes in the prefrontal cortex-nucleus accumbens pathway. mGlu5 receptors' up-regulation was noted for cocaine self-administration and extinction training in the hippocampus and in yoked cocaine controls following drug abstinence in the dorsal striatum. A cocaine priming dose (but not a saline priming) resulted in a significant decrease of mGlu5 receptors' density in the nucleus accumbens of rats previously treated with the drug and in the hippocampus of rats previously self-administered cocaine. The latter decrease in mGlu5 receptors' density and protein expression in the hippocampus was parallel to an increase in [³H]MPEP affinity and opposite to a rise observed after single cocaine administration (ip) to drug-naïve yoked saline controls. Additionally, we also observed a significant elevation in the protein expression of the tested receptors in the limbic cortex in both cocaine groups. The present results shown modality dependent and brain-region specific

  14. Sex differences in time perception during smoking abstinence.

    Science.gov (United States)

    Ashare, Rebecca L; Kable, Joseph W

    2015-04-01

    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. 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. 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. 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. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    Science.gov (United States)

    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. (c) 2015 APA, all rights reserved).

  16. Contingency management for cocaine treatment: cash vs. vouchers.

    Science.gov (United States)

    Festinger, David S; Dugosh, Karen L; Kirby, Kimberly C; Seymour, Brittany L

    2014-08-01

    The efficacy of contingency management (CM) for treating drug abuse is well supported. The most widely used form of CM is voucher-based reinforcement therapy (VBRT), where clients receive an escalating schedule of vouchers that can be redeemed for goods and services for meeting treatment goals. Though generally rejected due to concerns about potential harms to drug using participants, research suggests that cash may be a more effective reinforcer. This three-group randomized trial compared the efficacy of cash-based reinforcement therapy (CBRT) to VBRT and a non-CM condition on cocaine abstinence and treatment attendance; and examined whether CBRT resulted in greater levels of harm than VBRT. Findings indicated that the CBRT was as effective as VBRT when compared to the non-CM condition and that it did not increase rates of drug use, cravings, or high-risk behaviors. Future research should examine potential cost savings associated with a cash-based CM approach as this could have important implications for the wider adoption of the CM model. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Anhydroecgonine methyl ester, a cocaine pyrolysis product, may contribute to cocaine behavioral sensitization.

    Science.gov (United States)

    Garcia, Raphael Caio Tamborelli; Torres, Larissa Helena; Balestrin, Natália Trigo; Andrioli, Tatiana Costa; Flório, Jorge Camilo; de Oliveira, Carolina Dizioli Rodrigues; da Costa, José Luiz; Yonamine, Mauricio; Sandoval, Maria Regina Lopes; Camarini, Rosana; Marcourakis, Tania

    2017-02-01

    Crack cocaine has a high potential to induce cocaine addiction and its smoke contains cocaine's pyrolysis product anhydroecgonine methyl ester (AEME), a partial agonist at M1- and M3-muscarinic acetylcholine receptor and an antagonist at the remaining subtypes. No reports have assessed AEME's role in addiction. Adult male Wistar rats were intraperitoneally administered with saline, 3mg/kg AEME, 15mg/kg cocaine, or a cocaine-AEME combination on every other day during a period of 9 days. After a 7-days withdrawal period, a challenge injection of the respective drugs was performed on the 17th day. The locomotor activity was evaluated on days 1, 3, 5, 7, 9 and 17, as well as dopamine levels (9th day) and dopaminergic receptors proteins (D1R and D2R on the 17th day) in the caudate-putamen (CPu) and nucleus accumbens (NAc). AEME was not able to induce the expression of behavioral sensitization, but it substantially potentiates cocaine-effects, with cocaine-AEME combination presenting higher expression than cocaine alone. An increase in the dopamine levels in the CPu in all non-saline groups was observed, with the highest levels in the cocaine-AEME group. There was a decrease in D1R protein level in this brain region only for cocaine and cocaine-AEME groups. In the NAc, an increase in the dopamine levels was only observed for cocaine and cocaine-AEME groups, with no changes in both D1R and D2R protein levels. These behavioral and neurochemical data indicate that AEME alone does not elicit behavioral sensitization but it significantly potentiates cocaine effects when co-administered, resulting in dopamine increase in CPu and NAc, brain regions where dopamine release is mediated by cholinergic activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Osteonecrosis following alcohol, cocaine, and steroid use.

    Science.gov (United States)

    Ziraldo, Laura; O'Connor, Mortimer B; Blake, Simon P; Phelan, Mark J

    2011-07-01

    Alcohol, steroids and cocaine have all been shown to be independent risk factors for osteonecrosis when taken in excess. Here we present a case of a young girl who developed debilitating osteonecrosis secondary to low doses of alcohol, steroids and cocaine. We feel it is important to highlight to those caring for such patients of the potential devastating complication of these three agents.

  19. [Sucrose reward promotes rats' motivation for cocaine].

    Science.gov (United States)

    Li, Yan-Qing; LE, Qiu-Min; Yu, Xiang-Chen; Ma, Lan; Wang, Fei-Fei

    2016-06-25

    Caloric diet, such as fat and sugar intake, has rewarding effects, and has been indicated to affect the responses to addictive substances in animal experiments. However, the possible association between sucrose reward and the motivation for addictive drugs remains to be elucidated. Thus, we carried out behavioral tests after sucrose self-administration training to determine the effects of sucrose experience on rats' motivation for cocaine, locomotor sensitivity to cocaine, basal locomotor activity, anxiety level, and associative learning ability. The sucrose-experienced (sucrose) group exhibited higher lever press, cocaine infusion and break point, as well as upshift of cocaine dose-response curve in cocaine self-administration test, as compared with the control (chow) group. Additionally, despite similar locomotor activity in open field test and comparable score in cocaine-induced conditioned place preference, the sucrose group showed higher cocaine-induced locomotor sensitivity as compared with the chow group. The anxiety level and the performance in vocal-cue induced fear memory were similar between these two groups in elevated plus maze and fear conditioning tests, respectively. Taken together, our work indicates that sucrose experience promotes the rats' motivation for cocaine.

  20. Cilioretinal artery occlusion following intranasal cocaine insufflations

    Directory of Open Access Journals (Sweden)

    Balaji Kannan

    2011-01-01

    Full Text Available Cocaine is used to produce a euphoric effect by abusers, who may be unaware of the devastating systemic and ocular side effects of this drug. We describe the first known case of cilioretinal artery occlusion after intranasal cocaine abuse.

  1. Tips for Teens: The Truth about Cocaine

    Science.gov (United States)

    ... visit the Office of National Drug Control Policy Web site at www. whitehousedrugpolicy. gov. Q.Is cocaine really still a problem? A.Yes.In 2006,more than 1.0 million people tried cocaine. 2 Q.Isn’t ...

  2. Cilioretinal artery occlusion following intranasal cocaine insufflations

    Science.gov (United States)

    Kannan, Balaji; Balaji, Vijayalakshmi; Kummararaj, Sherin; Govindarajan, Kummararaj

    2011-01-01

    Cocaine is used to produce a euphoric effect by abusers, who may be unaware of the devastating systemic and ocular side effects of this drug. We describe the first known case of cilioretinal artery occlusion after intranasal cocaine abuse. PMID:21836348

  3. Osteonecrosis following alcohol, cocaine, and steroid use.

    LENUS (Irish Health Repository)

    Ziraldo, Laura

    2012-02-01

    Alcohol, steroids and cocaine have all been shown to be independent risk factors for osteonecrosis when taken in excess. Here we present a case of a young girl who developed debilitating osteonecrosis secondary to low doses of alcohol, steroids and cocaine. We feel it is important to highlight to those caring for such patients of the potential devastating complication of these three agents.

  4. Alterações neuropsicológicas em dependentes de cocaína/crack internados: dados preliminares Neuropsychological impairments in crack cocaine-dependent inpatients: preliminary findings

    Directory of Open Access Journals (Sweden)

    Paulo J Cunha

    2004-06-01

    Full Text Available OBJETIVO: Embora o uso de cocaína seja um problema significativo de saúde pública, há uma relativa escassez de dados científicos sobre as conseqüências neurocognitivas decorrentes da exposição à substância. MÉTODOS: Esse estudo avaliou a associação entre dependência de cocaína e crack e desempenho cognitivo. Uma ampla bateria de testes neuropsicológicos foi aplicada a 15 dependentes de cocaína, em abstinência por duas semanas, em tratamento em regime de internação, e em 15 sujeitos controles, não usuários de drogas, pareados por idade, sexo, escolaridade, nível sócio-econômico, lateralidade e QI. RESULTADOS: Os resultados preliminares mostraram significação estatística (pOBJECTIVE: Although cocaine use is a significant public health problem, there is relative paucity of scientific data on long-term neurocognitive consequences of the exposure to the substance. METHODS: This study examined the association between crack cocaine dependence and neuropsychological performance. An extended battery of neuropsychological tests was administered to 15 abstinent cocaine abusers, inpatients in abstinence for two weeks, and 15 non-drug-using control subjects matched for age, gender, education, socio-economic status, handedness and IQ. RESULTS: The preliminary findings showed statistical significance (p<0,05 on differences of performance in attention, verbal fluency, verbal memory, visual memory, learning ability and executive functions. CONCLUSIONS: These results represent evidences that cocaine abuse is associated with decrements in cognitive functioning, similar to cognitive disorders associated to prefrontal and temporal brain impairments. Knowledge of specific cognitive deficits in cocaine abusers may be useful for designing more effective substance abuse prevention and treatment programs.

  5. Remote physiological monitoring of acute cocaine exposure.

    Science.gov (United States)

    Yoon, Jin H; Shah, Ravi S; Arnoudse, Nicholas M; De La Garza, Richard

    2014-07-01

    Cocaine exposure results in predictable cardiovascular changes. The current study evaluated the utility of BioHarness for assessing cardiovascular and respiratory changes following cocaine exposure (0 and 40 mg, IV) under controlled laboratory conditions. Participants (n = 28) included non-treatment-seeking, cocaine-dependent volunteers. Results showed that BioHarness was able to detect a significant increase in heart rate following cocaine exposure, in comparison to placebo, (p < 0.0001). Additionally, heart rate values obtained using BioHarness were significantly correlated with those obtained from standard hospital equipment (p < 0.001). Significantly greater peak effects in breathing rate were also observed (p = 0.04). BioHarness is a promising remote physiological monitoring device that can accurately assess exposure to cocaine in the laboratory and may provide additional advantages when compared to standard hospital equipment.

  6. Role of Wnt/β-catenin pathway in the nucleus accumbens in long-term cocaine-induced neuroplasticity: a possible novel target for addiction treatment.

    Science.gov (United States)

    Cuesta, Santiago; Batuecas, Jorgelina; Severin, Maria J; Funes, Alejandrina; Rosso, Silvana B; Pacchioni, Alejandra M

    2017-01-01

    Cocaine addiction is a chronic relapsing disorder characterized by the loss of control over drug-seeking and taking, and continued drug use regardless of adverse consequences. Despite years of research, effective treatments for psycho-stimulant addiction have not been identified. Persistent vulnerability to relapse arises from a number of long-lasting adaptations in the reward circuitry that mediate the enduring response to the drug. Recently, we reported that the activity of the canonical or Wnt/β-catenin pathway in the prefrontal cortex (PFC) is very important in the early stages of cocaine-induced neuroadaptations. In the present work, our main goal was to elucidate the relevance of this pathway in cocaine-induced long-term neuroadaptations that may underlie relapse. We found that a cocaine challenge, after a period of abstinence, induced an increase in the activity of the pathway which is revealed as an increase in the total and nuclear levels of β-catenin (final effector of the pathway) in the nucleus accumbens (NAcc), together with a decrease in the activity of glycogen synthase kinase 3β (GSK3β). Moreover, we found that the pharmacological modulation of the activity of the pathway has long-term effects on the cocaine-induced neuroplasticity at behavioral and molecular levels. All the results imply that changes in the Wnt/β-catenin pathway effectors are long-term neuroadaptations necessary for the behavioral response to cocaine. Even though more research is needed, the present results introduce the Wnt canonical pathway as a possible target to manage cocaine long-term neuroadaptations. © 2016 International Society for Neurochemistry.

  7. Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo.

    Science.gov (United States)

    Tallarida, Christopher S; Egan, Erin; Alejo, Gissel D; Raffa, Robert; Tallarida, Ronald J; Rawls, Scott M

    2014-04-01

    Levamisole is estimated by the Drug Enforcement Agency (DEA) to be present in about 80% of cocaine seized in the United States and linked to debilitating, and sometimes fatal, immunologic effects in cocaine abusers. One explanation for the addition of levamisole to cocaine is that it increases the amount of product and enhances profits. An alternative possibility, and one investigated here, is that levamisole alters cocaine's action in vivo. We specifically investigated effects of levamisole on cocaine's stereotypical and place-conditioning effects in an established invertebrate (planarian) assay. Acute exposure to levamisole or cocaine produced concentration-dependent increases in stereotyped movements. For combined administration of the two agents, isobolographic analysis revealed that the observed stereotypical response was enhanced relative to the predicted effect, indicating synergism for the interaction. In conditioned place preference (CPP) experiments, cocaine produced a significant preference shift; in contrast, levamisole was ineffective at all concentrations tested. For combination experiments, a submaximal concentration of cocaine produced CPP that was enhanced by inactive concentrations of levamisole, indicating synergism. The present results provide the first experimental evidence that levamisole enhances cocaine's action in vivo. Most important is the identification of synergism for the levamisole/cocaine interaction, which now requires further study in mammals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Development of a smoking abstinence self-efficacy questionnaire

    DEFF Research Database (Denmark)

    Spek, Viola; Lemmens, Fieke; Chatrou, Marlène

    2013-01-01

    is to investigate the psychometric properties of a six-item questionnaire to assess smoking cessation self-efficacy. METHODS: We used longitudinal data from a smoking cessation study. A total of 513 smokers completed the Smoking Abstinence Self-efficacy Questionnaire (SASEQ) and questionnaires assessing depressive...... that self-efficacy is measured independently of these concepts. Furthermore, high baseline SASEQ scores significantly predicted smoking abstinence at 52 weeks after the quit date (OR = 1.85; 95% CI = 1.20~2.84). CONCLUSIONS: The SASEQ appeared to be a short, reliable, and valid questionnaire to assess self......-efficacy beliefs regarding smoking abstinence. In the present study, this instrument also had good predictive validity. The short SASEQ can easily be used in busy clinical practice to guide smoking cessation interventions....

  9. Reversible brain shrinkage in abstinent alcoholics, measured by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Schroth, G.; Naegele, T.; Klose, U.; Petersen, D.; Mann, K.

    1988-11-01

    Magnetic resonance imaging of the intracranial CSF volume was compared before and after 5 weeks of confirmed abstinence in 9 alcohol-dependent patients. All patients showed a highly significant reduction in CSF volume in accordance with reexpansion of the brain after alcohol abstinence. T2 values for white matter, estimated by linear regression from 16 echoes of a CPGM sequence, however, showed no significant increase such as occurs in rehydration. This indicates, that alcohol-induced reversible brain atrophy cannot be attributed to fluctuation of free water in the brain only.

  10. Gratitude, abstinence, and alcohol use disorders: Report of a preliminary finding.

    Science.gov (United States)

    Krentzman, Amy R

    2017-07-01

    Gratitude is a central component of addiction recovery for many, yet it has received scant attention in addiction research. In a sample of 67 individuals entering abstinence-based alcohol-use-disorder treatment, this study employed gratitude and abstinence variables from sequential assessments (baseline, 6months, 12months) to model theorized causal relationships: gratitude would increase pre-post treatment and gratitude after treatment would predict greater percent days abstinent 6months later. Neither hypothesis was supported. This unexpected result led to the theory that gratitude for sobriety was the construct of interest; therefore, the association between gratitude and future abstinence would be positive among those already abstinent. Thus, post-treatment abstinence was tested as a moderator of the effect of gratitude on future abstinence: this effect was statistically significant. For those who were abstinent after treatment, the relationship between gratitude and future abstinence was positive; for those drinking most frequently after treatment, the relationship between gratitude and future abstinence was negative. In this preliminary study, dispositional tendency to affirm that there is much to be thankful for appeared to perpetuate the status quo-frequent drinkers with high gratitude were drinking frequently 6months later; abstinent individuals with high gratitude were abstinent 6months later. Gratitude exercises might be contraindicated for clients who are drinking frequently and have abstinence as their treatment goal. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Fatal cocaine intoxication in a body packer

    Directory of Open Access Journals (Sweden)

    Brajković Gordana

    2016-01-01

    Full Text Available Introduction. ‘Body packer’ syndrome with severe intoxication or sudden death may happen in persons who smuggle drugs in their body cavities. In case of lethal outcome when carrying cocaine, it is important, but sometimes difficult to determine whether death was due to intoxication or due to other causes. Therefore, it is necessary not only to quantify cocaine and its metabolites in biological material, but also based on their distribution in body fluids and tissues to conclude whether it is acute intoxication. We described a well-documented case of fatal poisoning in a body packer and post mortem distribution of the drug in biological samples. Case report. A 26-year-old man was brought to hospital with no vital signs. Resuscitation measures started at once, but with no success. Autopsy revealed 66 packets of cocaine in his digestive tract, one of which was ruptured. Hyperemia of the most of all internal organs and pulmonary and brain edema were found. High concentrations of cocaine, its metabolites benzoylecgonine and ecgonine methyl ester, as well as cocaine adulteration levamisole were proven in the post mortem blood and tissues by liquid chromatography-mass spectrometry (LC-MC method with selective-ion monitoring. Conclusion. The ratio of cocaine and its metabolites concentrations in the brain and blood obtained by LC-MS method can be used for forensic confirmation of acute intoxication with cocaine.

  12. Regulation of cocaine craving by cognitive strategies in an online sample of cocaine users.

    Science.gov (United States)

    Strickland, Justin C; Reynolds, Anna R; Stoops, William W

    2016-08-01

    Emphasis on the negative consequences of drug use is a critical component of cognitive-behavioral therapy (CBT) skills to regulate craving. Despite the relative success of CBT for treating substance use disorders, effective human laboratory models of CBT are lacking. Recent reports have indicated that the regulation of craving (ROC) task provides a valid model of craving regulation for nicotine, alcohol, and methamphetamine use. The present study examined ROC in an online sample of regular cocaine users (n = 44) recruited from Amazon.com's Mechanical Turk. In the ROC task, cognitive regulation strategies were manipulated by instructing participants to think about either the positive or negative consequences of consuming cocaine. Participants were then presented with cocaine images while engaging in each cognitive regulation strategy and asked to report current craving that was then compared to neutral look conditions. Food images served as a control. A cocaine purchase task was also completed to assess economic demand for cocaine and its relationship with cocaine craving. The use of negative appraisal strategies that model those used in CBT significantly attenuated craving for cocaine. Cocaine craving was also stimulus-specific, with greater smoked cocaine craving reported by individuals with a history of smoked cocaine use. This online extension of the ROC task provides converging evidence for its use as a model of CBT cocaine-craving regulation. Futures studies can use this model to examine the mechanisms underlying the effectiveness of CBT for cocaine use and the relationship between craving regulation and drug-use behavior. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  13. Choice to view cocaine images predicts concurrent and prospective drug use in cocaine addiction.

    Science.gov (United States)

    Moeller, Scott J; Beebe-Wang, Nicasia; Woicik, Patricia A; Konova, Anna B; Maloney, Thomas; Goldstein, Rita Z

    2013-06-01

    Identifying variables that predict drug use in treatment-seeking drug addicted individuals is a crucial research and therapeutic goal. This study tested the hypothesis that choice to view cocaine images is associated with concurrent and prospective drug use in cocaine addiction. To establish choice-concurrent drug use associations, 71 cocaine addicted subjects (43 current users and 28 treatment seekers) provided data on (A) choice to view cocaine images and affectively pleasant, unpleasant, and neutral images [collected under explicit contingencies (when choice was made between two fully visible side-by-side images) and under more probabilistic contingencies (when choice was made between pictures hidden under flipped-over cards)]; and (B) past-month cocaine and other drug use. To establish choice-prospective drug use associations, 20 of these treatment-seeking subjects were followed over the next 6 months. Baseline cocaine-related picture choice as measured by both tasks positively correlated with subjects' concurrent cocaine and other drug use as driven by the actively-using subjects. In a subsequent multiple regression analysis, choice to view cocaine images as compared with affectively pleasant images (under probabilistic contingencies) was the only predictor that continued to be significantly associated with drug use. Importantly, this same baseline cocaine>pleasant probabilistic choice also predicted the number of days drugs were used (cocaine, alcohol, and marijuana) over the next 6 months. Simulated cocaine choice - especially when probabilistic and when compared with other positive reinforcers - may provide a valid laboratory marker of current and future drug use in cocaine addiction. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Cocaine-associated lower limb ischemia.

    LENUS (Irish Health Repository)

    Collins, Chris G

    2011-07-25

    Cocaine-associated thrombosis has been reported in the literature with reports of vascular injuries to cardiac, pulmonary, intestinal, placental, and musculoskeletal vessels; however, injury of the pedal vessels is rare. We report on a 31-year-old man who presented 2 months following a cocaine binge with limb-threatening ischemia without an otherwise identifiable embolic source. Angiography confirmed extensive occlusive disease of the tibioperoneal vessels. The patient improved following therapy with heparin and a prostacyclin analogue. Cocaine-induced thrombosis should be considered in patients presenting with acute arterial insufficiency in the lower limb without any other identifiable cause.

  15. Methadone, Cocaine, Opiates and Metabolite Disposition in Umbilical Cord and Correlations to Maternal Methadone Dose and Neonatal Outcomes

    Science.gov (United States)

    de Castro, Ana; Jones, Hendreé E.; Johnson, Rolley E.; Gray, Teresa R; Shakleya, Diaa M; Huestis, Marilyn A

    2011-01-01

    Objectives To explore methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) umbilical cord disposition, correlate with maternal methadone dose and neonatal outcomes, and evaluate the window of drug detection in umbilical cord of in utero illicit drug exposure. Methods Subjects, 19 opioid-dependent pregnant women from two clinical studies, one comparing methadone and buprenorphine pharmacotherapy for opioid-dependence treatment, and the second examining monetary reinforcement schedules to maintain drug abstinence. Correlations were calculated for methadone and EDDP umbilical cord concentrations and maternal methadone dose, and neonatal outcomes. Cocaine- and opiate-positive umbilical cord concentrations were compared to those in placenta and meconium, and urine specimens collected throughout gestation. Results Significant positive correlations were found for umbilical cord methadone concentrations and methadone mean daily dose, mean dose during the 3rd trimester and methadone cumulative daily dose. Umbilical cord EDDP concentrations and EDDP/methadone concentration ratios were positively correlated to newborn length, peak neonatal abstinence syndrome (NAS) score and time-to-peak NAS score. Methadone concentrations and EDDP/methadone ratios in umbilical cord and placenta were positively correlated. Meconium identified many more cocaine and opiate positive specimens than umbilical cord. Conclusion Umbilical cord methadone concentrations were correlated to methadone doses. Also, our results indicate that methadone and EDDP concentrations might help to predict NAS severity. Meconium proved to be more suitable than umbilical cord to detect in utero exposure to cocaine and opiates; however, umbilical cord could be useful when meconium is unavailable due to in utero or delayed expulsion. PMID:21743375

  16. Smoking topography and abstinence in adult female smokers.

    Science.gov (United States)

    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. © 2013 Elsevier Ltd. All rights reserved.

  17. Role Of Parents In Supporting Youth Who Participate In Abstinence ...

    African Journals Online (AJOL)

    However, some parents, conservatives and religious critics of these programs are concerned that promoting condom use encourages promiscuity. This has apparently led to an increase in programs designed to promote abstinence from sex before marriage and faithfulness in relationships as safer and more moral ways to ...

  18. Development and Validation of the Sexual Abstinence Scale (SAS ...

    African Journals Online (AJOL)

    The Sexual Abstinence Scale (SAS) is designed to assess healthy sexual behaviour among adolescents as a way to reduce the incidence of HIV and other sexually transmitted diseases. This cross sectional study took place in two phases. The first phase comprised of 1030 adolescents randomly selected from senior ...

  19. Factors Associated with Sexual Abstinence among Adolescents in ...

    African Journals Online (AJOL)

    The percentage of primary abstinent adolescents ranged from 42% (Malawian males) to 85% (Ghanaian males). In general, a greater proportion of females than males were primary abstainers. Primary abstainers were younger than sexually experienced adolescents. Current involvement in a romantic relationship was a ...

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

    Science.gov (United States)

    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…

  1. Smoking abstinence and reinstatement effects in adolescent cigarette smokers.

    Science.gov (United States)

    Colby, Suzanne M; Leventhal, Adam M; Brazil, Linda; Lewis-Esquerre, Johanna; Stein, L A R; Rohsenow, Damaris J; Monti, Peter M; Niaura, Raymond S

    2010-01-01

    The study objectives were to examine smoking abstinence and reinstatement effects on subjective experience and cognitive performance among adolescent smokers. Adolescents (aged 14-17 years, 60 daily smokers and 32 nonsmokers) participated. Participants completed baseline assessments (Session 1) and returned to the laboratory 1-3 days later to repeat assessments (Session 2); half of the smokers were randomly assigned to 15-17 hr tobacco abstinence preceding Session 2. During Session 2, abstaining smokers reported significantly greater increases in withdrawal symptoms, smoking urges, and negative affect compared with smokers who did not abstain and compared with nonsmokers. Smoking reinstatement reversed abstinence effects, returning to baseline levels for smoking urges and negative affect. Abstaining smokers showed significantly enhanced cognitive performance on two of six tasks (two-letter search compared with nonabstaining smokers; serial reaction time compared with nonsmokers); smoking reinstatement resulted in significant decrements on these two tasks relative to nonabstaining smokers. Effects of smoking abstinence and reinstatement on self-report measures are consistent with earlier research with adolescent as well as adult smokers and may help to elucidate the motivational underpinnings of smoking maintenance among adolescent smokers. Effects found on cognitive performance were contrary to hypotheses; further research is needed to understand better the role of cognitive performance effects in smoking maintenance among adolescents.

  2. 2. UNZA students as leaders for abstinence programmes

    African Journals Online (AJOL)

    Esem

    HIV/AIDS.The monitoring and evaluation tool was firstly administered randomly with larger groups then after sensitisation, within smaller groups. Results: The pupils exhibited high knowledge about HIV and AIDS ... sexual debut or abstinence has been widely promoted. .... esteem and we have clearer picture of where we.

  3. Childhood Symptoms of ADHD and Impulsivity in Abstinent Heroin Users

    Science.gov (United States)

    Segalà, Laura; Vasilev, Georgi; Raynov, Ivaylo; Gonzalez, Raul; Vassileva, Jasmin

    2015-01-01

    Objectives Heroin dependence is associated with deficits in impulsivity, which is also a core feature of ADHD. This study aimed to explore the association between childhood ADHD symptoms and cognitive/choice and motor/action impulsivity among abstinent individuals with a history of heroin dependence. Methods Thirty-two abstinent Bulgarian males with a history of heroin dependence participated in the study. Self-rated childhood ADHD symptoms were obtained using the Wender-Utah Rating Scale. Cognitive/choice impulsivity was measured using the Iowa Gambling Task (IGT), an index of impulsive decision-making and the Delayed Reward Discounting Task (DRDT), a measure of inter-temporal choice. Motor/action impulsivity was indexed with the Stop Signal Task (SST), a measure of response inhibition. Results Participants, whose average age was 27.66 years (SD = 2.7), had an average ADHD symptom score of 36.6 (SD = 18.6), roughly 7 years (SD = 2.9) of heroin use, and been abstinent for just over a year (M = 402.5 days, SD = 223.8). Linear regression analyses revealed that self-reported ADHD symptoms predicted impulsive decision-making (IGT), but not delay discounting (DRDT) or response inhibition (SST). Conclusions Self-reported childhood ADHD symptoms do not uniformly predict impulsivity among abstinent individuals with heroin dependence. Results suggest the IGT may be more sensitive to externalizing psychopathology among individuals with heroin dependence than other measures of impulsivity. PMID:26457770

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

    Science.gov (United States)

    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,…

  5. Implementation of Cognitive-Behavioral Substance Abuse Treatment in Sub-Saharan Africa: Treatment Engagement and Abstinence at Treatment Exit.

    Science.gov (United States)

    Gouse, Hetta; Magidson, Jessica F; Burnhams, Warren; Remmert, Jocelyn E; Myers, Bronwyn; Joska, John A; Carrico, Adam W

    2016-01-01

    This study documented the treatment cascade for engagement in care and abstinence at treatment exit as well as examined correlates of these outcomes for the first certified Matrix Model® substance abuse treatment site in Sub-Saharan Africa. This retrospective chart review conducted at a resource-limited community clinic in Cape Town, South Africa, assessed treatment readiness and substance use severity at treatment entry as correlates of the number of sessions attended and biologically confirmed abstinence at treatment exit among 986 clients who initiated treatment from 2009-2014. Sociodemographic and clinical correlates of treatment outcomes were examined using logistic regression, modeling treatment completion and abstinence at treatment exit separately. Of the 2,233 clients who completed screening, approximately 44% (n = 986) initiated treatment. Among those who initiated treatment, 45% completed at least four group sessions, 30% completed early recovery skills training (i.e., at least eight group sessions), and 13% completed the full 16-week program. Approximately half (54%) of clients who provided a urine sample had negative urine toxicology results for any substance at treatment exit. Higher motivation at treatment entry was independently associated with greater odds of treatment completion and negative urine toxicology results at treatment exit. Findings provide initial support for the successful implementation the Matrix Model in a resource-limited setting. Motivational enhancement interventions could support treatment initiation, promote sustained engagement in treatment, and achieve better treatment outcomes.

  6. Cost-effectiveness of peer-delivered interventions for cocaine and alcohol abuse among women: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Jennifer Prah Ruger

    Full Text Available To determine whether the additional interventions to standard care are cost-effective in addressing cocaine and alcohol abuse at 4 months (4 M and 12 months (12 M from baseline.We conducted a cost-effectiveness analysis of a randomized controlled trial with three arms: (1 NIDA's Standard intervention (SI; (2 SI plus a Well Woman Exam (WWE; and, (3 SI, WWE, plus four Educational Sessions (4ES.To obtain an additional cocaine abstainer, WWE compared to SI cost $7,223 at 4 M and $3,611 at 12 M. Per additional alcohol abstainer, WWE compared to SI cost $3,611 and $7,223 at 4 M and 12 M, respectively. At 12 M, 4ES was dominated (more costly and less effective by WWE for abstinence outcomes.To our knowledge, this is the first cost-effectiveness analysis simultaneously examining cocaine and alcohol abuse in women. Depending on primary outcomes sought and priorities of policy makers, peer-delivered interventions can be a cost-effective way to address the needs of this growing, underserved population.ClinicalTrials.gov NCT01235091.

  7. Prenatal Cocaine Exposure and Infantile Psychomotor Outcome

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-05-01

    Full Text Available The effects of prenatal cocaine exposure on child development outcomes were studied prospectively in an obstetric unit of a large US urban teaching hospital at Case Western Reserve University, Cleveland, OH.

  8. Signs of Cocaine Abuse and Addiction

    Science.gov (United States)

    ... com/ Marjot Stacey is recovering from her cocaine addiction. She's thankful that her life is different now than it was before. Read Stacey's story Treatment & Recovery Information Treatment and Recovery Does Drug Treatment Work? ...

  9. Impaired inhibitory control in recreational cocaine users.

    Directory of Open Access Journals (Sweden)

    Lorenza S Colzato

    Full Text Available Chronic use of cocaine is associated with impairment in response inhibition but it is an open question whether and to which degree findings from chronic users generalize to the upcoming type of recreational users. This study compared the ability to inhibit and execute behavioral responses in adult recreational users and in a cocaine-free-matched sample controlled for age, race, gender distribution, level of intelligence, and alcohol consumption. Response inhibition and response execution were measured by a stop-signal paradigm. Results show that users and non users are comparable in terms of response execution but users need significantly more time to inhibit responses to stop-signals than non users. Interestingly, the magnitude of the inhibitory deficit was positively correlated with the individuals lifetime cocaine exposure suggesting that the magnitude of the impairment is proportional to the degree of cocaine consumed.

  10. Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers.

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Tomasi, D.; Telang, F.; Fowler, J.S.; Pradhan, K.; Jayne, M.; Logan, J.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

    2010-07-01

    Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and {sup 18}FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue

  11. Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    2010-07-01

    Full Text Available Dopamine (phasic release is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function was measured with PET and (18FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg. The Cocaine-cues video increased craving to the same extent with placebo (68% and with methylphenidate (64%. In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005 in left limbic regions (insula, orbitofrontal, accumbens and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005, amygdala, striatum and middle insula (p<0.05. This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes, which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic

  12. A Simple Economic Model of Cocaine Production

    Science.gov (United States)

    1994-01-01

    the production dhain that are vulnerable to itr o as well as providing a clearer picture of the path that cocaine takes before reading retail markts in...Washington, D.C., 1990. 7. Committee on Governmental Affairs, US. Senate, Cocaine Production, Eradiation, and Environment: Policy, impact, and Options...the Permanent Subcommittee on Investigations of the Committee on Governmental Affairs, U.S. Senate, September 27,28 and 29,1989. Hearing 101-311. 62

  13. Immunopharmacotherapeutic manifolds and modulation of cocaine overdose.

    Science.gov (United States)

    Treweek, Jennifer B; Roberts, Amanda J; Janda, Kim D

    2011-05-01

    Cocaine achieves its psychostimulant, reinforcing properties through selectively blocking dopamine transporters, and this neurobiological mechanism impedes the use of classical receptor-antagonist pharmacotherapies to outcompete cocaine at CNS sites. Passive immunization with monoclonal antibodies (mAb) specific for cocaine circumvents this problem as drug is sequestered in the periphery prior to entry into the brain. To optimize an immunopharmacotherapeutic strategy for reversing severe cocaine toxicity, the therapeutic properties of mAb GNC92H2 IgG were compared to those of its engineered formats in a mouse overdose model. Whereas the extended half-life of an IgG justifies its application to the prophylactic treatment of addiction, the rapid, thorough biodistribution of mAb-based fragments, including F(ab')₂, Fab and scFv, may correlate to accelerated scavenging of cocaine and reversal of toxicity. To test this hypothesis, mice were administered the anti-cocaine IgG (180 mg/kg, i.v.) or GNC92H2-based agent after receiving an LD₅₀ cocaine dose (93 mg/kg, i.p.), and the timeline of overdose symptoms was recorded. All formats lowered the rate of lethality despite the >100-fold molar excess of drug to antibody binding capacity. However, only F(ab')₂-92H2 and Fab-92 H2 significantly attenuated the progression of premorbid behaviors, and Fab-92H2 prevented seizure generation in a percentage of mice. The calculation of serum half-life of each format demonstrated that the pharmacokinetic profile of Fab-92H2 (elimination half-life, t½~100 min) best approximated that of cocaine. These results not only confirm the importance of highly specific and tight drug binding by the mAb, but also highlight the benefit of aligning the pharmacokinetic and pharmacodynamic properties of the immunopharmacotherapeutic with the targeted drug. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-06-01

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

  15. Opioid and cocaine combined effect on cocaine-induced changes in HPA and HPG axes hormones in men.

    Science.gov (United States)

    Goletiani, Nathalie V; Mendelson, Jack H; Sholar, Michelle B; Siegel, Arthur J; Mello, Nancy K

    2009-02-01

    Nalbuphine, a mixed micro-/kappa-opioid analgesic, may have potential as a new medication for the treatment of cocaine abuse. Kappa-opioid agonists functionally antagonize some abuse-related and locomotor effects of cocaine, and both kappa-selective and mixed micro-/kappa-opioids reduce cocaine self-administration by rhesus monkeys. Because cocaine's interactions with the hypothalamic-pituitary-adrenal and (HPA) hypothalamic-pituitary-gonadal (HPG) axes may contribute to its reinforcing properties, we examined the effects of cocaine alone and in combination with nalbuphine. Neuroendocrine effects of a single dose of cocaine alone (0.2 mg/kg, IV), with nalbuphine (5 mg/70 kg, IV)+cocaine (0.2 mg/kg, IV) in combination were compared in seven adult men (ages 18-35) who met DSM-IV criteria for current cocaine abuse. Cocaine alone, and in combination with nalbuphine was administered on separate test days under placebo-controlled, double blind conditions. Cocaine stimulated ACTH, cortisol, and LH, whereas cocaine+nalbuphine in combination produced a smaller increase in ACTH, and decreased cortisol and LH. Thus it appears that nalbuphine attenuated cocaine's effects on ACTH, cortisol, and LH. These data are consistent with our earlier report that nalbuphine modestly attenuated cocaine's positive subjective effects, and that the subjective and cardiovascular effects of cocaine+nalbuphine in combination were not additive.

  16. Enhanced midbrain response at 6-month follow-up in cocaine addiction, association with reduced drug-related choice: Midbrain in drug choice

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, Scott J.; Tomasi, Dardo; Woicik, Patricia A.; Maloney, Thomas; Alia-Klein, Nelly; Honorio, Jean; Telang, Frank; Wang, Gene-Jack; Wang, Ruiliang; Sinha, Rajita; Carise, Deni; Astone-Twerell, Janetta; Bolger, Joy; Volkow, Nora D.; Goldstein, Rita Z.

    2012-03-28

    Drug addiction is characterized by dysregulated dopamine neurotransmission. Although dopamine functioning appears to partially recover with abstinence, the specific regions that recover and potential impact on drug seeking remain to be determined. Here we used functional magnetic resonance imaging (fMRI) to study an ecologically valid sample of 15 treatment-seeking cocaine addicted individuals at baseline and 6-month follow-up. At both study sessions, we collected fMRI scans during performance of a drug Stroop task, clinical self-report measures of addiction severity and behavioral measures of cocaine seeking (simulated cocaine choice); actual drug use in between the two study sessions was also monitored. At 6-month follow-up (compared with baseline), we predicted functional enhancement of dopaminergically innervated brain regions, relevant to the behavioral responsiveness toward salient stimuli. Consistent with predictions, whole-brain analyses revealed responses in the midbrain (encompassing the ventral tegmental area/substantia nigra complex) and thalamus (encompassing the mediodorsal nucleus) that were higher (and more positively correlated) at follow-up than baseline. Increased midbrain activity from baseline to follow-up correlated with reduced simulated cocaine choice, indicating that heightened midbrain activations in this context may be marking lower approach motivation for cocaine. Normalization of midbrain function at follow-up was also suggested by exploratory comparisons with active cocaine users and healthy controls (who were assessed only at baseline). Enhanced self-control at follow-up was suggested by a trend for the commonly hypoactive dorsal anterior cingulate cortex to increase response during a drug-related context. Together, these results suggest that fMRI could be useful in sensitively tracking follow-up outcomes in drug addiction.

  17. Cocaine smuggling in the gastrointestinal tract resulting in mechanical pylorostenosis.

    Science.gov (United States)

    Sein Anand, Jacek; Chodorowski, Zygmunt; Masal, Andrzej; Nowak-Banasik, Livia

    2005-01-01

    A 45-year-old male, body packer, who confessed to have swallowed 44 packages of cocaine in a total dose of approx. 360 g, was admitted to hospital because of clinical signs of acute intoxication with cocaine followed by ileus. The emergency surgical gastrotomy was initiated, and the conglomerate of Scotch tape and packages with cocaine were removed. Small rupture of one package of cocaine in a body packer stomach caused acute poisoning with cocaine, confirmed additionally by the presence of its metabolites in the urine. Mechanical pylorostenosis provoked by cocaine packages required emergency surgical operation.

  18. Financing Cocaine Use in a Homeless Population

    Directory of Open Access Journals (Sweden)

    Carol S. North

    2017-10-01

    Full Text Available Background: Cocaine use is highly prevalent among homeless populations, yet little is known about how it is financed. This study examined associations of income sources with cocaine use and financing of drugs in a longitudinal evaluation of a homeless sample. Methods: A homeless sample was recruited systematically in St. Louis in 1999–2001 and longitudinally assessed annually over two years using the Diagnostic Interview Schedule and the Homeless Supplement, with urine drug testing. Results: More than half (55% of participants with complete follow-up data (N = 255/400 had current year cocaine use. Current users spent nearly $400 (half their income in the last month on drugs at baseline. Benefits, welfare, and disability were negatively associated and employment and income from family/friends, panhandling, and other illegal activities were positively associated with cocaine use and monetary expenditures for cocaine. Conclusions: Findings suggest that illegal and informal income-generating activities are primary sources for immediate gratification with cocaine use and public entitlements do not appear to be primary funding sources used by homeless populations. Policy linking drug testing to benefits is likely to have little utility, and public expenditures on measures to unlink drug use and income might be more effectively used to fund employment and treatment programs.

  19. Cocaine

    Science.gov (United States)

    ... JUSTICE CONTACT US A-Z INDEX Search for HOME ABOUT Mission History Office Locations Domestic Office Locations Foreign Office Locations Leadership Museum Wall of Honor CAREERS Occupations How to Apply ...

  20. Cocaine

    Science.gov (United States)

    ... Trends Nationwide Trends Prevention and Treatment Lessons from Prevention Research Substance Abuse in the Military Treatment Approaches for Drug Addiction Get this Publication Español PDF (701KB) Cite this ...

  1. Self-reports of interoceptive responses during stress and drug cue-related experiences in cocaine- and alcohol-dependent individuals.

    Science.gov (United States)

    Bergquist, Keri L; Fox, Helen C; Sinha, Rajita

    2010-06-01

    Cocaine dependence is associated with neuroadaptations in stress and reward pathways that could alter stress and drug-related experiences and associated interoceptive sensations and result in enhanced craving states. Subjective interoceptive emotional and physiological responses experienced in stressful and drug cue situations were examined in abstinent cocaine-dependent individuals. Fifty-six treatment engaged cocaine-dependent patients with comorbid alcohol abuse or dependence were interviewed to identify personal stressful, drug cue, and neutral situations using a scene construction questionnaire (SCQ) that includes an emotional and physiological response checklist. Using this checklist, subjects identified emotional and bodily sensations that they recently experienced in the stress- and drug-related scenarios. Kappa coefficients indicated fair to moderate but significant degree of concordance in heart (p stomach (p stomach (p butterflies in stomach, increased heartbeat and tension, jittery, restless, and warm excitement (53%-73%) were the most frequently endorsed sensations in the drug cue-related experiences. These self-reported sensations comprise both general arousal and specific interoceptive responses pertaining to stress or drug cue-related experiences in cocaine dependence, with potential value in guiding treatments targeting craving reduction.

  2. Resting state brain connectivity patterns before eventual relapse into cocaine abuse.

    Science.gov (United States)

    Berlingeri, M; Losasso, D; Girolo, A; Cozzolino, E; Masullo, T; Scotto, M; Sberna, M; Bottini, G; Paulesu, E

    2017-06-01

    According to recent theories, drug addicted patients suffer of an impaired response inhibition and salience attribution (I-RISA) together with a perturbed connectivity between the nuclei accumbens (NAcs) and the orbito-prefrontal (oPFC) and dorsal prefrontal (dPFC) cortices, brain regions associated with motivation and cognitive control. To empirically test these assumptions, we evaluated the (neuro)psychological trait and the functional organization of the resting state brain networks associated with the NAcs in 18 former cocaine abusers (FCAs), while being in drug abstinence since 5 months. The psychological data were grouped into three empirical variables related with emotion regulation, emotion awareness and strategic and controlled behaviour. Comparison of the resting state patterns between the entire sample of FCAs and 19 controls revealed a reduction of functional connectivity between the NAcs and the dPFC and enhanced connectivity between the NAcs and the dorsal-striatum. In the 8 FCAs who relapsed into cocaine use after 3 months, the level of functional connectivity between the NAcs and dPFC was lower than the functional connectivity estimated in the group of patients that did not relapsed. Finally, in the entire sample of FCAs, the higher the connectivity between the NAc and the oPFC the lower was the level of strategic and controlled behaviour. Taken together, these results are compatible with models of the interactions between the NAcs, the dorsal striatum and frontal cortices in the I-RISA syndrome, showing that such interactions are particularly perturbed in patients at greater risk of relapse into cocaine abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. 21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cocaine and cocaine metabolite test system. 862.3250 Section 862.3250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology...

  4. Levamisole-adulterated cocaine: Two fatal case reports and evaluation of possible cocaine toxicity potentiation.

    Science.gov (United States)

    Indorato, Francesca; Romano, Guido; Barbera, Nunziata

    2016-08-01

    Levamisole has been identified as a cocaine adulterant in the United States since 2002. Although there is a variation in the percentage of levamisole in cocaine samples between European countries, measurement of levamisole in human samples of cocaine users has become increasingly important. To our best knowledge, only five deaths are reported (one twice) as a result of complications secondary to levamisole-tainted cocaine and none of these cases reports the post-mortem levamisole concentration. In this article, we present the post-mortem levamisole concentrations in fluids and tissues in two young cocaine users, dead after levamisole-adulterated cocaine intake. With the dearth of levamisole reported concentrations in literature, this particular report is of interest to the forensic toxicological and pathological communities. This article aims to be a supplementary alert to aware the risk that may occur using levamisole-adulterated cocaine and an incentive to publication of toxicity reports and new researches involving the combination of levamisole and cocaine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Episodic Social Stress-Escalated Cocaine Self-Administration: Role of Phasic and Tonic Corticotropin Releasing Factor in the Anterior and Posterior Ventral Tegmental Area

    Science.gov (United States)

    Boyson, Christopher O.; Montagud-Romero, Sandra; Stein, Dirson J.; Gobrogge, Kyle L.; DeBold, Joseph F.; Miczek, Klaus A.

    2016-01-01

    Intermittent social defeat stress escalates later cocaine self-administration. Reward and stress both activate ventral tegmental area (VTA) dopamine neurons, increasing downstream extracellular dopamine concentration in the medial prefrontal cortex and nucleus accumbens. The stress neuropeptide corticotropin releasing factor (CRF) and its receptors (CRF-R1, CRF-R2) are located in the VTA and influence dopaminergic activity. These experiments explore how CRF release and the activation of its receptors within the VTA both during and after stress influence later cocaine self-administration in rats. In vivo microdialysis of CRF in the VTA demonstrated that CRF is phasically released in the posterior VTA (pVTA) during acute defeat, but, with repeated defeat, CRF is recruited into the anterior VTA (aVTA) and CRF tone is increased in both subregions. Intra-VTA antagonism of CRF-R1 in the pVTA and CRF-R2 in the aVTA during each social defeat prevented escalated cocaine self-administration in a 24 h “binge.” VTA CRF continues to influence cocaine seeking in stressed animals long after social defeat exposure. Unlike nonstressed controls, previously stressed rats show significant cocaine seeking after 15 d of forced abstinence. Previously stressed rats continue to express elevated CRF tone within the VTA and antagonism of pVTA CRF-R1 or aVTA CRF-R2 reverses cocaine seeking. In conclusion, these experiments demonstrate neuroadaptive changes in tonic and phasic CRF with repeated stress, that CRF release during stress may contribute to later escalated cocaine taking, and that persistently elevated CRF tone in the VTA may drive later cocaine seeking through increased activation of pVTA CRF-R1 and aVTA CRF-R2. SIGNIFICANCE STATEMENT Corticotropin releasing factor (CRF) within the ventral tegmental area (VTA) has emerged as a likely candidate molecule underlying the fundamental link between stress history and escalated drug self-administration. However, the nature of CRF

  6. Associations between behavioral disinhibition and cocaine use history in individuals with cocaine dependence.

    Science.gov (United States)

    Prisciandaro, James J; Korte, Jeffrey E; McRae-Clark, Aimee L; Brady, Kathleen T

    2012-10-01

    Behavioral disinhibition has been suggested as both a cause and consequence of substance use disorders. Many studies examining associations between behavioral disinhibition and substance use history have focused on individuals with alcohol dependence or non-dependent college students. In the present study, the relationship between behavioral disinhibition and cocaine use history in individuals with cocaine dependence is examined. Forty-six non-treatment-seeking cocaine-dependent men and women completed impulsivity (Barratt impulsiveness scale; BIS) and novelty seeking (temperament and character inventory; TCI) questionnaires at the baseline visit of an ongoing study. Unadjusted, and adjusted for gender and age, Pearson correlations were calculated between BIS, TCI, and cocaine use variables from the structured clinical interview for DSM-IV and timeline follow-back (age of onset, quantity/frequency of past 30 day cocaine use). As expected, elevated motor impulsivity and novelty seeking were each associated with younger age of dependence onset. Also, individuals with lower levels of persistence on the TCI reported more days of cocaine use over the previous month. Unexpectedly, increased novelty seeking and attentional impulsivity were associated with fewer days of cocaine use and less money spent on cocaine, respectively. Controlling for age and gender did not substantially change the pattern of observed associations. The present study provides preliminary evidence for associations between behavioral disinhibition and cocaine use history in cocaine-dependent individuals. Given our relatively small sample size and the correlational nature of our findings, further research is needed to replicate and extend our results. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Acute Myocardial Infarction Secondary to Catecholamine Release Owing to Cocaine Abuse and Pheochromocytoma Crisis

    Science.gov (United States)

    Martinez-Quintana, Efren; Jaimes-Vivas, Ricardo; Cuba-Herrera, Javiel; Saiz-Udaeta, Beatriz; Rodríguez-Gonzalez, Fayna; Martinez-Martin, Maria Soledad

    2012-01-01

    Abstract Most pheochromocytomas are not suspected clinically while a high percentage of them are curable with surgery. We present the case of an adult cocaine-addicted male patient with an underlying pheochromocytoma and repeated myocardial infarctions. Computed tomography showed a left round adrenal mass, also high 24-hour urine levels of catecholamines and metanephrines were detected from urinalysis. The patient was given alpha and beta blockers, moreover a laparoscopic left adrenalectomy was performed. Cocaine can block the reuptake of noradrenaline, leading to increasing its concentration and consequently its effects as well, and induce local or diffuse coronary vasoconstriction in normal coronary artery segments per se, cocaine can also trigger pheochromocytoma crisis, and therefore, cardiac complications such as myocardial infarction due to these additive effects are intended to occur. For this reason, in the presence of typical clinical manifestations of pheochromocytoma, such as sustained or paroxysmal hypertension, headache, sweating, tachycardia and abdominal pain, probable association of this tumor in patients with cocaine abuse and associated cardiac complications must be ruled out. PMID:23853620

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

    Science.gov (United States)

    Rinker, Dipali Venkataraman; Neighbors, Clayton

    2013-07-01

    Few studies have examined the association between reasons for not drinking and social norms among abstinent college students. Research suggests that drinking motives are associated with perceived injunctive norms and drinking. Therefore, it seems likely that reasons for not drinking may also be associated with perceived injunctive norms and abstinence. The aim of this study was to examine the relationship between reasons for not drinking and perceived injunctive norms on alcohol abstinence. Participants were 423 light-drinking and abstinent college students from a public northwestern university who completed online surveys at baseline, 3-, and 6-month follow-up. We examined abstinence as a function of all subscales of the Reasons for Not Drinking scale using logistic regression, as well as conducted two mediational analyses indicating: (1) perceived injunctive norms as a mediator of the relationship between reasons for not drinking and abstinence, and (2) reasons for not drinking as a mediator of the relationship between perceived injunctive norms and abstinence. The Disapproval/Lack of Interest subscale was the only subscale of the Reasons for Not Drinking scale that was significantly associated with 6-month abstinence. Further, Disapproval/Lack of Interest both directly predicted abstinence and indirectly predicted abstinence via perceived injunctive norms. Perceived injunctive norms indirectly predicted abstinence via Disapproval/Lack of Interest, but did not directly predict abstinence. Results suggest that self-defining personal values are an important component of keeping abstaining college students abstinent. These results are discussed with regard to implications for interventions designed specifically for maintaining abstinence throughout college. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Modafinil decreases cocaine choice in human cocaine smokers only when the response requirement and the alternative reinforcer magnitude are large.

    Science.gov (United States)

    Foltin, Richard W; Haney, Margaret; Bedi, Gillinder; Evans, Suzette M

    This study examined how response effort (pressing a keyboard button) for cocaine and the value of an alternative reinforcer (opportunity to play a game of chance for money) combined with 'free' cocaine (with no response effort) affected cocaine choice when participants were maintained on modafinil or placebo. Nontreatment-seeking current cocaine smokers were enrolled in a placebo-controlled, double-blind, within-subject study comprising both inpatient and outpatient phases. Participants were maintained on placebo capsules (0mg/day) during one inpatient phase and modafinil (300mg/day) capsules during another inpatient phase in counter-balanced order. A minimum of 8 medication-free days separated the two 15-day inpatient phases to allow for medication clearance. Under each medication condition participants had the opportunity to self-administer smoked cocaine (25mg) when the response effort for cocaine was low (500responses/dose) and had a low value alternative (2 game plays for money) or when the response effort for cocaine was large (2500responses/dose) and had a more valuable alternative (4 game plays for money). Under both conditions, participants received one free dose of cocaine (0, 12, 25 or 50mg) prior to making their first choice of the session. Fifteen individuals began the study and 7 completed it. Participants chose fewer cocaine doses when the response effort for cocaine and the alternative value was high (4.4±0.19) compared to when the response effort for cocaine and the alternative value was low (5.3±0.14). Providing individuals a free "priming" dose of cocaine prior to making their cocaine choice did not alter cocaine taking. Modafinil decreased cocaine choice only when the response effort for cocaine and the alternative value was high. These results suggest that modafinil may be most effective when combined with therapy emphasizing the large personal costs of using cocaine. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Examining supply changes in Australia's cocaine market.

    Science.gov (United States)

    Hughes, Caitlin E; Chalmers, Jenny; Bright, David A; Matthew-Simmons, Francis; Sindicich, Natasha

    2012-05-01

    Media attention to cocaine use and supply has increased following some of the largest cocaine seizures in Australia's history. Whether there has been an expansion in supply remains unclear. This paper examines the evidence behind assertions of increased supply in Australia and the scale and nature of any apparent increase, using proxy indicators of cocaine importation, distribution and use. Eight proxies of cocaine importation, distribution and use were adopted, including amount of importation, mode of importation and supply flows to Australia. Each proxy indicator was sourced using publicly available and Australia-wide data, including information on the total weight of border seizures, mode of detection and country of embarkation of individual seizures. Data permitting, trends were examined for up to a 12 year period (1997-1998 to 2009-2010). Since 2006-2007 there was evidence of increased cocaine importation, albeit less than between 1998-1999 and 2001-2002. There were further signs that the 2006-2007 expansion coincided with a diversification of trafficking routes to and through Australia (beyond the traditional site of entry-Sydney) and shifts in the geographic distribution of use. The congruity between indicators suggests that there has been a recent expansion in cocaine supply to and distribution within Australia, but that the more notable shift has concerned the nature of supply, with an apparent growth in importation and distribution beyond New South Wales. The diversification of cocaine supply routes may increase risks of market entrenchment and organised crime throughout Australia. © 2011 Australasian Professional Society on Alcohol and other Drugs.

  11. Lisuride reduces intravenous cocaine self-administration in rats.

    Science.gov (United States)

    Pulvirenti, L; Koob, G F

    1994-04-01

    The maintenance of intravenous (i.v.) cocaine self-administration appears to depend upon activation of dopamine terminals within mesocorticolimbic areas. Since the nonaddictive ergot derivative lisuride is a direct dopamine receptor agonist, the present study was designed to investigate whether administration of lisuride to rats trained to lever-press for IV self-administration of cocaine could affect the intake of cocaine. IP administration of several doses of lisuride reduced, in a dose-dependent manner, cocaine self-administration. In a control experiment, lisuride did not increase the psychomotor-activating properties of cocaine as measured by locomotor activity, suggesting that lisuride did not simply potentiate the activating effects of cocaine. The present results show that lisuride reduced IV cocaine self-administration in rats; the possibility of a new therapeutic approach to the treatment of cocaine abuse in humans using lisuride may therefore deserve clinical attention.

  12. D-cycloserine and cocaine cue reactivity: preliminary findings.

    Science.gov (United States)

    Price, Kimber L; McRae-Clark, Aimee L; Saladin, Michael E; Maria, Megan M Moran-Santa; DeSantis, Stacia M; Back, Sudie E; Brady, Kathleen T

    2009-01-01

    D-cycloserine (DCS), a partial glutamate N-methyl-D-aspartic acid (NMDA) receptor agonist, enhances extinction of conditioned fear responding in rodents and facilitates exposure-based learning in humans with anxiety disorders. This preliminary study investigates DCS pretreatment on response to cocaine cues in cocaine-dependent subjects. Ten cocaine-dependent subjects were randomly assigned to receive either 50 mg DCS or matching placebo two hours before each of two 1-hour cocaine cue exposure sessions one day apart. HR and craving ratings were obtained before and during cue exposure sessions. There was a trend towards increased craving to cocaine cues in cocaine-dependent individuals after administration of DCS. The administration of DCS prior to cue exposure sessions may facilitate response activation. While facilitation of extinction-based learning by DCS may have therapeutic potential for cocaine dependence, this drug may exhibit a different profile in cocaine-dependent individuals as compared to those with anxiety disorders.

  13. The fast and furious : Cocaine, amphetamines and harm reduction

    NARCIS (Netherlands)

    J-P.C. Grund (Jean-Paul); P. Coffin (Philip); M. Jauffret-Roustide (Marie); M. Dijkstra (Minke); D. de Bruin (Dick); P. Blanken (Peter)

    2010-01-01

    textabstractCocaine and amphetamines (‘stimulants’) are distinct central nervous system stimulants with similar effects (Pleuvry, 2009; Holman, 1994). Cocaine is a crystalline tropane alkaloid extracted from coca leaves. Amphetamines are a subclass of phenylethylamines with primarily stimulant

  14. Measurement of neonatal abstinence syndrome: Evaluation of short forms.

    Science.gov (United States)

    Jones, Hendrée E; Seashore, Carl; Johnson, Elisabeth; Horton, Evette; O'Grady, Kevin E; Andringa, Kim

    2016-01-01

    1) How well do the short forms previously developed from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) neonatal abstinence syndrome (NAS) scale (MNS) discriminate between neonates untreated and treated for NAS? (2) Can a short form be developed that is superior to other short forms in discriminating between the two groups? This secondary analysis study used data from 131 delivered neonates in the MOTHER study, a randomized controlled trial comparing neonatal and maternal outcomes in opioid-dependent pregnant women administered buprenorphine or methadone. Comprehensive care was provided at seven university hospitals. A 19-item instrument measuring neonatal abstinence signs. A five-item index proved superior to the previous indices (ps < 0.01) and discriminated between the treated and untreated NAS groups as well as did the MNS total score (p=0.09). A short form developed from the MNS shows promise as a possible screening measure.

  15. Disrupted Control Network Connectivity in Abstinent Patients with Alcohol Dependence

    OpenAIRE

    Kim, Siekyeong; Im, Sungjin; Lee, Jeonghwan; Lee, Sang-Gu

    2017-01-01

    Objective Alcohol causes damage to the brain and is associated with various functional impairments. However, much of the brain damage can be reversed by abstaining for enough time. This study aims to investigate the patterns and degrees of brain function in abstinent patients with alcohol dependence by using resting-state functional connectivity. Methods 26 male patients with alcohol dependence (alcohol group) and 28 age-matched male healthy volunteers (control group) were recruited from a me...

  16. Review of the assessment and management of neonatal abstinence syndrome

    OpenAIRE

    Bagley, Sarah Mary; Wachman, Elisha M.; Holland, Erica; Brogly, Susan B

    2014-01-01

    Neonatal abstinence syndrome (NAS) secondary to in-utero opioid exposure is an increasing problem. Variability in assessment and treatment of NAS has been attributed to the lack of high-quality evidence to guide management of exposed neonates. This systematic review examines available evidence for NAS assessment tools, nonpharmacologic interventions, and pharmacologic management of opioid-exposed infants. There is limited data on the inter-observer reliability of NAS assessment tools due to l...

  17. Abstinence and alcohol consumption among secondary school students

    OpenAIRE

    Bonito, Jorge; Boné, Maria

    2014-01-01

    A young person tend to drink alcohol due to the curiosity, imitation belonging to a peer group and in some cases the motivation of the family. Alcohol is therefore socially tolerated moderate alcohol consumption can lead risk forms of consumption. The study shows that attempts to understand the consumption and abstinence from alcohol consumption among young people in secondary education who attend a school in the district of Evora in co use of learning spaces and leisure. The research was qua...

  18. Analytic neutrality, anonymity, abstinence, and elective self-disclosure.

    Science.gov (United States)

    Shill, Merton A

    2004-01-01

    Recent contributions to the psychoanalytic literature propose new ways of understanding analytic neutrality, anonymity, abstinence, and self-disclosure. They advocate elective self-disclosure by the analyst as an antidote to the allegedly game-playing quality of transference and resistance analysis. The analytic relationship, they assert, becomes unreal when attempts are made to observe the principles of neutrality and abstinence. Both are seen as ill-conceived because of the irreducible subjectivity and unwarranted authority of the analyst. These relational and interactional views are criticized because (1) they ignore the fact that transference and resistance analysis have from Freud onward been accepted as minimal criteria qualifying a clinical process as psychoanalytic; (2) elective self-disclosure carries metapsychological implications dismissing not only Freud's theory of motivation but motivation as a basic feature of human personality; (3) they do not recognize interpersonal relations as mental events and so do not consider the ego's ability to create intrapsychic representations of object relations; (4) elective self-disclosures within the empathic parameters of the analytic situation are themselves unreal compared to the reality of the patient's experience with other objects. Abstinence and neutrality as ideals facilitate maintenance of an internal holding environment or container for the analyst's countertransference.

  19. Factors associated with Indigenous youths' abstinence from drinking.

    Science.gov (United States)

    Sittner, Kelley J

    2017-08-01

    The proportion of youth who abstain from alcohol use decreases during adolescence but little attention has focused on factors associated with abstinence. No research has examined this question for Indigenous youth, many of whom live in communities experiencing high rates of alcohol-related health problems. Using data from a longitudinal study of Indigenous youth (n = 649, ages 10-17 years) in the U.S. and Canada, the current study investigates factors associated promoting or decreasing abstaining from alcohol use. Results from generalized linear growth models demonstrate that abstinence declines significantly during adolescence. In concurrent models, caretaker monitoring and school adjustment increased the odds of abstaining, and frequency of smoking cigarettes and number of best friends who drink decreased the odds. In lagged analysis, only school adjustment, smoking, and peer drinking remained significant. Time-stable characteristics moderated several time-varying associations. This study has important implications for programs aimed at encouraging alcohol abstinence. Copyright © 2017 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  20. Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome.

    Science.gov (United States)

    Kraft, Walter K; Adeniyi-Jones, Susan C; Chervoneva, Inna; Greenspan, Jay S; Abatemarco, Diane; Kaltenbach, Karol; Ehrlich, Michelle E

    2017-06-15

    Current pharmacologic treatment of the neonatal abstinence syndrome with morphine is associated with a lengthy duration of therapy and hospitalization. Buprenorphine may be more effective than morphine for this indication. In this single-site, double-blind, double-dummy clinical trial, we randomly assigned 63 term infants (≥37 weeks of gestation) who had been exposed to opioids in utero and who had signs of the neonatal abstinence syndrome to receive either sublingual buprenorphine or oral morphine. Infants with symptoms that were not controlled with the maximum dose of opioid were treated with adjunctive phenobarbital. The primary end point was the duration of treatment for symptoms of neonatal opioid withdrawal. Secondary clinical end points were the length of hospital stay, the percentage of infants who required supplemental treatment with phenobarbital, and safety. The median duration of treatment was significantly shorter with buprenorphine than with morphine (15 days vs. 28 days), as was the median length of hospital stay (21 days vs. 33 days) (Pbuprenorphine group and in 7 of 30 infants (23%) in the morphine group (P=0.36). Rates of adverse events were similar in the two groups. Among infants with the neonatal abstinence syndrome, treatment with sublingual buprenorphine resulted in a shorter duration of treatment and shorter length of hospital stay than treatment with oral morphine, with similar rates of adverse events. (Funded by the National Institute on Drug Abuse; BBORN ClinicalTrials.gov number, NCT01452789 .).

  1. Effects of repeated social defeat on adolescent mice on cocaine-induced CPP and self-administration in adulthood: integrity of the blood-brain barrier.

    Science.gov (United States)

    Rodríguez-Arias, Marta; Montagud-Romero, Sandra; Rubio-Araiz, Ana; Aguilar, María A; Martín-García, Elena; Cabrera, Roberto; Maldonado, Rafael; Porcu, Francesca; Colado, María Isabel; Miñarro, José

    2017-01-01

    Social stress in adulthood enhances cocaine self-administration, an effect that has been related with an increase in extracellular signal-regulated kinase and p38α mitogen-activated protein kinase phosphorylation. A detrimental effect of cocaine on blood-brain barrier (BBB) integrity has also been reported. This study evaluates the effects of repeated social defeat (RSD) during adolescence on the reinforcing and motivational effects of cocaine in adult mice and the changes induced by RSD on BBB permeability. Cocaine self-administration, conditioned place preference and quantitative analysis of claudin-5, laminin, collagen-IV and IgG immunoreactivity took place 3 weeks after RSD. Mice socially defeated during adolescence developed conditioned place preference and exhibited reinstated preference with a non-effective dose of cocaine (1 mg/kg). RSD mice needed significantly more sessions than control animals for the preference induced by 25 mg/kg of cocaine to be extinguished. However, acquisition of cocaine self-administration (0.5 mg/kg per injection) was delayed in the RSD group. Mice exposed to RSD displayed significant changes in BBB structure in adulthood, with a marked reduction in expression of the tight junction protein claudin-5 and an increase in basal laminin degradation (reflected by a decrease in laminin and collagen-IV expression) in the nucleus accumbens and hippocampus. The detrimental effect induced by cocaine (25 mg/kg) on collagen-IV expression in the hippocampus was more pronounced in RSD mice. In summary, our findings suggest that stress and cocaine can increase the long-term vulnerability of the brain to subsequent environmental insults as a consequence of a sustained disruption of the BBB. © 2015 Society for the Study of Addiction.

  2. Cocaine challenge enhances release of neuroprotective amino acid taurine in the striatum of chronic cocaine treated rats: a microdialysis study.

    Science.gov (United States)

    Yablonsky-Alter, Elena; Agovic, Mervan S; Gashi, Eleonora; Lidsky, Theodore I; Friedman, Eitan; Banerjee, Shailesh P

    2009-05-29

    Drug addiction is a serious public health problem. There is increasing evidence on the involvement of augmented glutamatergic transmission in cocaine-induced addiction and neurotoxicity. We investigated effects of acute or chronic cocaine administration and cocaine challenge following chronic cocaine exposure on the release of excitotoxic glutamate and neuroprotective taurine in the rat striatum by microdialysis. Cocaine challenge, following withdrawal after repeated cocaine exposure markedly increased the release of glutamate, which may cause neurotoxicity. Simultaneously, cocaine challenge after withdrawal also significantly increased the release of taurine, which counteracts glutamate-mediated excitotoxicity and possibly cell death. Thus, the mammalian brain has an endogenous self-protective mechanism against cocaine-mediated neurotoxicity and potentially addiction.

  3. Cocaine use severity and cerebellar gray matter are associated with reversal learning deficits in cocaine-dependent individuals

    NARCIS (Netherlands)

    Moreno-López, L.; Perales, J.C.; van Son, D.; Albein-Urios, N.; Soriano-Mas, C.; Martinez-Gonzalez, J.M.; Wiers, R.W.; Verdejo-García, A.

    2015-01-01

    Cocaine addiction involves persistent deficits to unlearn previously rewarded response options, potentially due to neuroadaptations in learning-sensitive regions. Cocaine-targeted prefrontal systems have been consistently associated with reinforcement learning and reversal deficits, but more recent

  4. Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum

    Directory of Open Access Journals (Sweden)

    Ana ePalomino

    2014-03-01

    Full Text Available Growing awareness of cerebellar involvement in addiction is based on the cerebellum’s intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression (CB1 receptors and enzymes that produce (DAGLα/β and NAPE-PLD and degrade (MAGL and FAAH eCB were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system (glutamate synthesizing enzymes LGA and KGA, mGluR3/5 metabotropic receptors, and NR1/2A/2B/2C-NMDA and GluR1/2/3/4-AMPA ionotropic receptor subunits and the gene expression of tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-AG production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and glutamate systems. Repeated cocaine results in normalization of glutamate receptor expression, although sustained changes in eCB is observed. We suggest that cocaine-induced alterations to cerebellar eCB should be considered when analyzing the adaptations imposed by psychostimulants that

  5. Mice lacking neuropeptide Y show increased sensitivity to cocaine

    DEFF Research Database (Denmark)

    Sørensen, Gunnar; Woldbye, David Paul Drucker

    2012-01-01

    There is increasing data implicating neuropeptide Y (NPY) in the neurobiology of addiction. This study explored the possible role of NPY in cocaine-induced behavior using NPY knockout mice. The transgenic mice showed a hypersensitive response to cocaine in three animal models of cocaine addiction...

  6. Cocaine contamination of banknotes: a review.

    Science.gov (United States)

    Troiano, Gianmarco; Mercurio, Isabella; Golfera, Marco; Nante, Nicola; Melai, Paola; Lancia, Massimo; Bacci, Mauro

    2017-07-16

    The analysis of drug traces on banknotes with different validated techniques can provide important information about the types of substances that are used in a geographical region. The aim of our review was to investigate banknotes' contamination by cocaine, by its metabolite, but also by other drugs. A systematic literature search (English written literature) was conducted in MEDLINE, and Scopus, collecting studies from 1974 till 2017. The Key search terms included: 'banknote AND drug'; 'banknote AND cocaine'. The literature search yielded 88 publications; 9 were included in our review. In six studies that showed banknotes' positivity to cocaine, the percentage ranged from 2.5% to 100%. The concentration of cocaine ranged from 0.09 ng/note to 889 µg/note. Benzoylecgonine was indentified only in three studies with a range from 0.71 to 130 ng/note. Other indentified drugs were: amphetamine derivatives, opiates, benzodiazepines. Circulating banknotes could be used to indicate substances used in a population, and those recently introduced in a geographical macro-area. The identification of very high amounts of cocaine can provide important information for the identification of banknotes used in illegal trafficking.

  7. Gambling Problems Among Community Cocaine Users.

    Science.gov (United States)

    Dufour, Magali; Nguyen, Noël; Bertrand, Karine; Perreault, Michel; Jutras-Aswad, Didier; Morvannou, Adèle; Bruneau, Julie; Berbiche, Djamal; Roy, Élise

    2016-09-01

    Cocaine use is highly prevalent and a major public health problem. While some studies have reported frequent comorbidity problems among cocaine users, few studies have included evaluation of gambling problems. This study aimed to estimate the prevalence of gambling problems and compare those who were at-risk gamblers with non-problem gamblers in terms of mental health problems, substance use problems, and some risk factors (i.e. family antecedents, erroneous perceptions and coping strategies) among individuals who smoke or inject cocaine. A total of 424 smoked or injected cocaine users recruited through community-based programs in Montreal (Quebec) completed the questionnaire, including the Canadian Pathological Gambling Index, the Composite International Diagnostic Interview, the CAGE, and the Severity Dependence Scale. Of the sample, 18.4 % were considered at-risk gamblers, of whom 7.8 % had problems gambling and 10.6 % were moderate-risk gamblers. The at-risk group was more likely to have experienced a recent phobic disorder and alcohol problems than the non-problem group. A multivariate analysis showed that, compared to those who were non-problem gamblers, the at-risk ones were more likely to have lost a large sum of money when they first started gambling, believed that their luck would turn, and gambled in reaction to painful life events. These results indicate the need to include routines for screening to identify gambling problem among cocaine users.

  8. Cocaine benzoyl thioester: synthesis, kinetics of base hydrolysis, and application to the assay of cocaine esterases.

    Science.gov (United States)

    Cashman, J R; Berkman, C E; Underiner, G; Kolly, C A; Hunter, A D

    1998-08-01

    The synthesis and characterization of diastereomers of cocaine benzoyl thioester is described. Allococaine benzoyl thioester and allopseudococaine benzoyl thioester were synthesized by the conjugate addition of p-methoxytolyl thiol to ecgonine methyl ester followed by debenzylation and benzoylation. The absolute structure of the hydrochloride salt of the major ecgonine p-methoxytolyl sulfide formed was determined by single-crystal diffraction analysis and used to establish the addition geometry. When placed in aqueous solution, the cocaine benzoyl thioester diastereomers hydrolyzed to give thioecgonine methyl ester. The rate of cocaine benzoyl thioester hydrolysis was carefully investigated spectrophotometrically by using the Ellman reagent. At neutral pH, the hydrolysis of the diastereomers was found to proceed at detectable rates. Upon increasing pH, the rate of hydrolysis of cocaine benzoyl thioester diastereomers was increased and the reaction was catalyzed by basic buffer species. In addition to defining the kinetics of hydrolysis in aqueous solution, cocaine benzoyl thioester was utilized as a highly efficient method to monitor the activity of cholinesterases and pig liver esterase. Use of cocaine benzoyl thioester represents a rapid and sensitive way to screen for cocaine esterase activity.

  9. Reduced metabolism in brain "control networks" following cocaine-cues exposure in female cocaine abusers.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    2011-02-01

    Full Text Available Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved.To test this we compared brain metabolism (using PET and ¹⁸FDG between female (n = 10 and male (n = 16 active cocaine abusers when they watched a neutral video (nature scenes versus a cocaine-cues video.Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05; females significantly decreased metabolism (-8.6%±10 whereas males tended to increase it (+5.5%±18. SPM analysis (Cocaine-cues vs Neutral in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001 whereas males showed increases in right inferior frontal gyrus (BA 44/45 (only at p<0.005. The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001 in frontal (BA 8, 9, 10, anterior cingulate (BA 24, 32, posterior cingulate (BA 23, 31, inferior parietal (BA 40 and thalamus (dorsomedial nucleus.Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from "control networks" (prefrontal, cingulate, inferior parietal, thalamus in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition. This highlights the importance of gender tailored interventions for cocaine addiction.

  10. NEUROPEPTIDE Y (NPY) SUPPRESSES ETHANOL DRINKING IN ETHANOL-ABSTINENT, BUT NOT NON-ETHANOL-ABSTINENT, WISTAR RATS

    OpenAIRE

    Gilpin, N.W.; Stewart, R.B.; Badia-Elder, N.E.

    2008-01-01

    In outbred rats, increases in brain neuropeptide Y (NPY) activity suppress ethanol consumption in a variety of access conditions, but only following a history of ethanol dependence. NPY reliably suppresses ethanol drinking in alcohol-preferring (P) rats and this effect is augmented following a period of ethanol abstinence. The purpose of this experiment was to examine the effects of NPY on 2-bottle choice ethanol drinking and feeding in Wistar rats that had undergone chronic ethanol vapor exp...

  11. Effects of buspirone and the dopamine D3 receptor compound PG619 on cocaine and methamphetamine self-administration in rhesus monkeys using a food-drug choice paradigm.

    Science.gov (United States)

    John, William S; Banala, Ashwini K; Newman, Amy H; Nader, Michael A

    2015-04-01

    The dopamine (DA) D2 and D3 receptors have been associated with cocaine abuse. A recent study with the D3 receptor (D3R) partial agonist PG619 found that it attenuated cocaine-induced reinstatement and the D2-like receptor antagonist buspirone has shown positive outcomes in two studies of cocaine abuse in monkeys. However, a recent clinical trial indicated that buspirone did not improve abstinence in treatment-seeking cocaine abusers. The objective of the study was to examine PG619 and buspirone under a food-drug choice paradigm in order to better model the clinical findings. In addition, we extended the characterization of both compounds to include methamphetamine (MA) self-administration (SA). Six adult male rhesus monkeys were trained to respond under a concurrent food (1.0-g pellets) and drug (0.01-0.3 mg/kg/injection cocaine or MA) choice paradigm in which complete SA dose-response curves were determined each session (N = 3/group). Monkeys received 5 days of treatment with either PG619 (0.1-3.0 mg/kg, i.v.) or buspirone (0.01-1.0 mg/kg, i.m.). In a follow-up study, the SA doses were reduced (0.003-0.1 mg/kg/injection) to increase reinforcement frequency and buspirone was retested. PG619 did not affect cocaine or MA choice, while buspirone increased low-dose cocaine choice. Changing the SA doses increased the number of reinforcers received each session, but buspirone did not decrease drug choice. Consistent with clinical findings, these results do not support the use of buspirone for psychostimulant abuse and suggest that food-drug choice paradigms may have greater predictive validity than the use of other schedules of reinforcement.

  12. Differential Antagonism of Cocaine Self-Administration and Cocaine-Induced Disruptions of Learning by Haloperidol in Rhesus Monkeys

    Science.gov (United States)

    Winsauer, Peter J.; Moerschbaecher, Joseph M.; Roussell, Alison M.

    2008-01-01

    Six rhesus monkeys responding under a three-component multiple schedule were administered haloperidol to determine its effects on cocaine self-administration and on cocaine's disruptive effects on the repeated acquisition and performance of response chains. In the absence of haloperidol, 0.0032 - 0.032 mg/kg/infusion of cocaine increased response…

  13. Cocaine-induced reflex sympathetic dystrophy.

    Science.gov (United States)

    Gay, D; Singh, A

    2000-11-01

    Reflex sympathetic dystrophy (RSD) usually follows traumatic injuries or neurologic disorders. The authors report a rare case of RSD that followed intraarterial administration of cocaine in a patient with a history of intravenous drug abuse. The cocaine was self-administered inadvertently into the femoral artery rather than the femoral vein. Despite the intense pain, swelling, and dermatologic changes that followed, the diagnosis of RSD was not considered until scintigraphic studies suggested it. A combination of normal radiographs, a normal leukocyte study, and an abnormal bone scan in the region of tenderness and swelling excluded other possibilities and suggested RSD. In our patient, RSD was likely caused by an ischemic autonomic injury from the vasoconstrictor action of cocaine. Clinical follow-up and relief using phentolamine, an alpha-adrenergic blocker and vasodilator, made the diagnosis of RSD most likely.

  14. MDMA reinstates cocaine-seeking behaviour in mice.

    Science.gov (United States)

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

    2009-06-01

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

  15. Polysomnographic Sleep Dysregulation in Cocaine Dependence

    Directory of Open Access Journals (Sweden)

    Edwin M. Valladares

    2007-01-01

    Full Text Available Insomnia and sleep disturbance are associated with declines in health functioning, alongwith increases in mortality risk. Given the prominence of reported sleep disturbance incocaine-dependent subjects and persistence into recovery, understanding the natureand severity of these disturbances in this population may help to identify relevantpathways that contribute to the increased mortality in cocaine dependence. Polysomnography provides a means of objectively characterizing sleep and, in turn, sleep disturbances. Few studies have used polysomnography to evaluate sleep incocaine-dependent persons, yet these studies have the potential to advance treatmentsthat will ultimately reduce morbidity in cocaine-dependent subjects.

  16. Novel Cocaine Vaccine Linked to a Disrupted Adenovirus Gene Transfer Vector Blocks Cocaine Psychostimulant and Reinforcing Effects

    Science.gov (United States)

    Wee, Sunmee; Hicks, Martin J; De, Bishnu P; Rosenberg, Jonathan B; Moreno, Amira Y; Kaminsky, Stephen M; Janda, Kim D; Crystal, Ronald G; Koob, George F

    2012-01-01

    Immunotherapy is a promising treatment for drug addiction. However, insufficient immune responses to vaccines in most subjects pose a challenge. In this study, we tested the efficacy of a new cocaine vaccine (dAd5GNE) in antagonizing cocaine addiction-related behaviors in rats. This vaccine used a disrupted serotype 5 adenovirus (Ad) gene transfer vector coupled to a third-generation cocaine hapten, termed GNE (6-(2R,3S)-3-(benzoyloxy)-8-methyl-8-azabicyclo [3.2.1] octane-2-carboxamido-hexanoic acid). Three groups of rats were immunized with dAd5GNE. One group was injected with 3H-cocaine, and radioactivity in the blood and brain was determined. A second group was tested for cocaine-induced locomotor sensitization. A third group was examined for cocaine self-administration, extinction, and reinstatement of responding for cocaine. Antibody titers were determined at various time-points. In each experiment, we added a control group that was immunized with dAd5 without a hapten. The vaccination with dAd5GNE produced long-lasting high titers (>105) of anti-cocaine antibodies in all of the rats. The vaccination inhibited cocaine-induced hyperlocomotor activity and sensitization. Vaccinated rats acquired cocaine self-administration, but they showed less motivation to self-administer cocaine under a progressive-ratio schedule than control rats. When cocaine was not available in a session, control rats exhibited ‘extinction burst' responding, whereas vaccinated rats did not. Moreover, when primed with cocaine, vaccinated rats did not reinstate responding, suggesting a blockade of cocaine-seeking behavior. These data strongly suggest that our dAd5GNE vector-based vaccine may be effective in treating cocaine abuse and addiction. PMID:21918504

  17. Maternal cocaine use and mother-toddler aggression.

    Science.gov (United States)

    Eiden, Rina D; Schuetze, Pamela; Colder, Craig R; Veira, Yvette

    2011-01-01

    This study examined the direct and indirect associations between maternal cocaine use during pregnancy and mother-toddler aggression in an interactive context at 2 years of child age. We hypothesized that in addition to direct effects of cocaine exposure on maternal and child aggression, the association between maternal cocaine use and mother-toddler aggression may be indirect via higher maternal psychiatric symptoms, negative affect, or poor infant autonomic regulation at 13 months. Participants consisted of 220 (119 cocaine exposed, 101 non-cocaine exposed) mother-toddler dyads participating in an ongoing longitudinal study of prenatal cocaine exposure. Results indicated that mothers who used cocaine during pregnancy displayed higher levels of aggression toward their toddlers compared to mothers in the control group. Results from model testing indicated significant indirect associations between maternal cocaine use and maternal aggression via higher maternal negative affect as well as lower infant autonomic regulation at 13 months. Although there were no direct associations between cocaine exposure and toddler aggression, there was a significant indirect effect via lower infant autonomic regulation at 13 months. Results highlight the importance of including maternal aggression in predictive models of prenatal cocaine exposure examining child aggression. Results also emphasize the important role of infant regulation as a mechanism partially explaining associations between cocaine exposure and mother-toddler aggression. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Cocaine is pharmacologically active in the nonhuman primate fetal brain

    DEFF Research Database (Denmark)

    Benveniste, Helene; Fowler, Joanna S; Rooney, William D

    2010-01-01

    -trimester pregnant nonhuman primates, cocaine at doses typically used by drug abusers significantly increased brain glucose metabolism to the same extent in the mother as in the fetus (approximately 100%). Inasmuch as brain glucose metabolism is a sensitive marker of brain function, the current findings provide...... evidence that cocaine use by a pregnant mother will also affect the function of the fetal brain. We are also unique in showing that cocaine's effects in brain glucose metabolism differed in pregnant (increased) and nonpregnant (decreased) animals, which suggests that the psychoactive effects of cocaine...... are influenced by the state of pregnancy. Our findings have clinical implications because they imply that the adverse effects of prenatal cocaine exposure to the newborn child include not only cocaine's deleterious effects to the placental circulation, but also cocaine's direct pharmacological effect...

  19. Effects of D-cycloserine on cue-induced craving and cigarette smoking among concurrent cocaine- and nicotine-dependent volunteers.

    Science.gov (United States)

    Yoon, Jin H; Newton, Thomas F; Haile, Colin N; Bordnick, Patrick S; Fintzy, Rachel E; Culbertson, Chris; Mahoney, James J; Hawkins, Rollin Y; Labounty, Kathleen R; Ross, Elizabeth L; Aziziyeh, Adel I; De La Garza, Richard

    2013-02-01

    Rates of cigarette smoking are 3- to 4-fold greater among those with cocaine-dependence, and compared to non-users, cocaine users are at greater risk of incurring smoking-related negative health effects and death. The current study examined D-cycloserine's (0 or 50mg once weekly) effects on 1) extinction of cue-induced craving for cigarettes, 2) cigarette smoking in conjunction with cognitive-behavioral therapy, and 3) safety and tolerability in cocaine-dependent smokers. This was a double-blind, placebo-controlled, between groups, outpatient study. Participants (N=29) were concurrent cocaine- and nicotine-dependent volunteers seeking treatment for their cigarette smoking. Study visits were 3 times per week for 4 consecutive weeks. At each visit, participants received cognitive-behavioral therapy for smoking, were exposed to smoking cues. A subset of participants (N=22) returned for 6-month follow-up visits. While craving decreased, no significant effects of D-cycloserine treatment were observed. Likewise, significant decreases in smoking were observed at study days 6 (p<0.002) and 12 (p<0.0001) relative to baseline, although no participants achieved complete abstinence. However, there was no effect of D-cycloserine on cigarette smoking during treatment or at 6-mos follow-up. The treatment was safe and tolerable, with nearly 90% of treatment sessions attended based on an intent-to-treat analysis. While no effects of D-cycloserine on craving or smoking were observed in the current study, the results do suggest that smoking treatment is well accepted and may be effective for cocaine-dependent individuals. Published by Elsevier Ltd.

  20. The influence of smoking cigarettes on the high and desire for cocaine among active cocaine users.

    Science.gov (United States)

    Brewer, Alex J; Mahoney, James J; Nerumalla, Chandra S; Newton, Thomas F; De La Garza, Richard

    2013-05-01

    The primary aim was to evaluate whether nicotine use alters the high or desire for cocaine among active cocaine users who concurrently smoke cigarettes. Participants answered the Fagerstrom Test for Nicotine Dependence (FTND), Nicotine-Stimulant Interaction Questionnaire (NSIQ), and Multiple Drug Use Questionnaire (MDUQ). These questionnaires employ subject recall of participants' drug use habits. The participants that smoked (N=163/188) were primarily African American males who were 45.0±0.5 (mean±S.E.M.) years of age, and used cocaine for 17.9±0.6 years and 19.8±0.6 days out of the last 30. These individuals smoked 14.0±0.8 cigarettes/day (CPD), scored 4.6±0.2 (on a scale of 0-10) on the FTND, and smoked cigarettes for 23.5±0.7 years. Two questions from the MDUQ, which evaluates the interaction between cocaine and nicotine, (-5: reduces effect, 0: no change, +5: increases effect) included "Does nicotine affect the high that you experience from cocaine?" and "Does nicotine affect your desire for cocaine?", and the scores were 1.3±0.2 and 0.8±0.2, respectively. The NSIQ also evaluated interactive effects of nicotine and cocaine, on a scale of 0 to 100 (0: not at all, 100: most ever). Smokers responded most strongly that using cocaine increased both the urge to smoke and cigarette craving. Additional analyses were performed by separating participants into HighCPD vs. LowCPD groups via median split. The HighCPD group smoked 22.7±1.1 CPD while the LowCPD group smoked 6.4±0.3 CPD [F(1,161)=228.4, p<0.0001], and the HighCPD group had a mean FTND score twice that of the LowCPD group. Significant differences emerged between the two groups on multiple items of the NSIQ, but not the MDUQ. The subjective ratings of high and desire for cocaine, and several subjective effects produced by cocaine, were modestly altered by cigarette smoking. Taken together, these data suggest that cigarette smoking may augment the craving and high produced by cocaine. Copyright

  1. Osteoprotegerin Levels Decrease in Abstinent Alcohol-Dependent Patients.

    Science.gov (United States)

    Malik, Peter; von Gleissenthall, Gabriele; Gasser, Rudolf W; Moncayo, Roy; Giesinger, Johannes M; Mechtcheriakov, Sergei

    2016-06-01

    Osteoprotegerin (OPG) is a parameter of increasing interest in the search for pathophysiological mechanisms of reduced bone mineral density (BMD). It has been shown to be increased in alcohol-dependent subjects. In our study, we wanted to examine whether changes in OPG and receptor activator of the nuclear factor-κB ligand (RANKL) levels during an 8-week abstinence period in alcohol-dependent patients treated in an alcohol rehabilitation clinic would occur and whether alcohol-related variables, smoking, status, or physical activity prior to the study served as an influence on BMD and on OPG/RANKL levels. Forty-three patients, who were abstinent not longer than a week, were included in the study. OPG and RANKL as well as other markers of bone metabolism were measured at baseline, and after 8 weeks of treatment, BMD was measured once. OPG levels decreased significantly, while osteocalcin, a marker of bone formation, increased significantly. RANKL as well as RANKL/OPG ratio, Serum CrossLaps, and all examined hormones showed no significant changes over time. Inflammatory parameters showed a significant reduction after 8 weeks. We detected no influence of potentially confounding variables of alcohol dependency on the course of OPG or other laboratory values. Our results could point to the well-known risk for reduced BMD in these patients being reversible with abstinence through an excess of bone formation. We also confirmed earlier findings that inflammatory processes play a role in the pathogenesis of alcohol-induced disturbances in bone metabolism. Copyright © 2016 by the Research Society on Alcoholism.

  2. The opposite of sex? Adolescents' thoughts about abstinence and sex, and their sexual behavior.

    Science.gov (United States)

    Masters, N Tatiana; Beadnell, Blair A; Morrison, Diane M; Hoppe, Marilyn J; Gillmore, Mary Rogers

    2008-06-01

    Little research has explored how teenagers think about abstinence and how it functions in their lives. These questions are particularly salient in light of widespread funding of abstinence-only programs in the United States. Data on attitudes and intentions related to abstinence and sex were collected from 365 adolescents aged 12-15 who participated in an HIV risk reduction program in Seattle in 2001-2003. Logistic regression analyses assessed associations between these cognitions, as measured six months after the program, and teenagers' likelihood of having vaginal or anal sex in the subsequent six months. Adolescents who had positive attitudes and intentions about abstinence had a reduced likelihood of subsequently engaging in sex (odds ratio, 0.6 for each), whereas those with positive attitudes and intentions about having sex had an elevated likelihood of engaging in sex (2.2 and 3.5, respectively). A regression model including only sex cognitions accounted for substantially more variation in sexual activity than did one including only abstinence cognitions (15-26% vs. 6-8%). Significant interaction effects were also seen: Among teenagers with low levels of sex intention, greater abstinence intention had little relationship to the predicted probability of having sex, but among teenagers with high levels of sex intention, greater abstinence intention was associated with increases in the predicted probability of having sex. Youth do not consider abstinence and sexual activity opposing constructs, and solely instilling positive abstinence attitudes and intentions in youth may not have robust effects in preventing sexual activity.

  3. COMT Val158Met modulates subjective responses to intravenous nicotine and cognitive performance in abstinent smokers

    National Research Council Canada - National Science Library

    Herman, A I; Jatlow, P I; Gelernter, J; Listman, J B; Sofuoglu, M

    2013-01-01

    ...)/Val genotype, compared with methionine (Met) carriers, had greater negative subjective effects from IV nicotine and had more severe withdrawal severity following overnight abstinence from smoking...

  4. Withdrawal-Related Changes in Delay Discounting Predict Short-Term Smoking Abstinence.

    Science.gov (United States)

    Miglin, Rickie; Kable, Joseph W; Bowers, Maureen E; Ashare, Rebecca L

    2017-06-01

    Impulsive decision making is associated with smoking behavior and reflects preferences for smaller, immediate rewards and intolerance of temporal delays. Nicotine withdrawal may alter impulsive decision making and time perception. However, little is known about whether withdrawal-related changes in decision making and time perception predict smoking relapse. Forty-five smokers (14 female) completed two laboratory sessions, one following 24-hour abstinence and one smoking-as-usual (order counterbalanced; biochemically verified abstinence). During each visit, participants completed measures of time perception, decision making (ie, discount rates), craving, and withdrawal. Following the second laboratory session, subjects underwent a well-validated model of short-term abstinence (quit week) with small monetary incentives for each day of biochemically confirmed abstinence. Smokers significantly overestimated time during abstinence, compared to smoking-as-usual (p = .021), but there were no abstinence effects on discount rates (p = .6). During the quit week, subjects were abstinent for 3.5 days (SD = 2.15) and smoked a total of 12.9 cigarettes (SD = 15.8). Importantly, higher discount rates (ie, preferences for immediate rewards) during abstinence (abstinence minus smoking difference score) predicted greater number of days abstinent (p = .01) and fewer cigarettes smoked during the quit week (p = .02). Withdrawal-related change in time reproduction did not predict relapse (p = .2). These data suggest that individuals who have a greater preference for immediate rewards during abstinence (vs. smoking-as-usual) may be more successful at maintaining short-term abstinence when provided with frequent (eg, daily) versus less frequent incentive schedules (eg, 1 month). Abstinence-induced changes in decision making may be important for identifying smokers who may benefit from interventions that incentivize abstinence such as contingency management (CM). The present results

  5. Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations.

    Science.gov (United States)

    Zhang, Yuxin; Huang, Xiaoqin; Han, Keli; Zheng, Fang; Zhan, Chang-Guo

    2016-11-25

    The combined molecular dynamics (MD) and potential of mean force (PMF) simulations have been performed to determine the free energy profile of the CocE)-(+)-cocaine binding process in comparison with that of the corresponding CocE-(-)-cocaine binding process. According to the MD simulations, the equilibrium CocE-(+)-cocaine binding mode is similar to the CocE-(-)-cocaine binding mode. However, based on the simulated free energy profiles, a significant free energy barrier (∼5 kcal/mol) exists in the CocE-(+)-cocaine binding process whereas no obvious free energy barrier exists in the CocE-(-)-cocaine binding process, although the free energy barrier of ∼5 kcal/mol is not high enough to really slow down the CocE-(+)-cocaine binding process. In addition, the obtained free energy profiles also demonstrate that (+)-cocaine and (-)-cocaine have very close binding free energies with CocE, with a negligible difference (∼0.2 kcal/mol), which is qualitatively consistent with the nearly same experimental KM values of the CocE enzyme for (+)-cocaine and (-)-cocaine. The consistency between the computational results and available experimental data suggests that the mechanistic insights obtained from this study are reasonable. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. The impact of cocaine on adult hippocampal neurogenesis: Potential neurobiological mechanisms and contributions to maladaptive cognition in cocaine addiction disorder.

    Science.gov (United States)

    Castilla-Ortega, Estela; Ladrón de Guevara-Miranda, David; Serrano, Antonia; Pavón, Francisco J; Suárez, Juan; Rodríguez de Fonseca, Fernando; Santín, Luis J

    2017-10-01

    After discovering that addictive drugs alter adult neurogenesis, the potential role of adult-born hippocampal neurons in drug addiction has become a promising research field, in which cocaine is the most frequently investigated drug. Although a substantial amount of pre-clinical evidence has accumulated, additional studies are required to reveal the mechanisms by which cocaine modulates adult hippocampal neurogenesis (AHN) and determine whether these adult-born neurons have a role in cocaine-related behaviors, such as cocaine-mediated cognitive symptoms. First, this review will summarize the cocaine-induced alterations in a number of neurobiological factors (neurotransmitters, neurotrophins, glucocorticoids, inflammatory mediators) that likely regulate both hippocampal-dependent learning and adult hippocampal neurogenesis after cocaine exposure. A separate section will provide a detailed review of the available literature that challenges the common view that cocaine reduces adult hippocampal neurogenesis. In fact, cocaine has a short-term anti-proliferative role, but the young adult-born neurons are apparently spared, or even enhanced, following certain cocaine protocols. Thus, we will try to reconcile this evidence with the hippocampal-dependent cognitive symptoms that are typically observed in cocaine addicts, and we will propose new directions for future studies to test the relevant hypothesis. Based on the evidence presented here, the regulation of adult hippocampal neurogenesis might be one of the many mechanisms by which cocaine sculpts hippocampus-dependent learning. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Daily stressor sensitivity, abuse effects, and cocaine use in cocaine dependence.

    Science.gov (United States)

    Waldrop, Angela E; Back, Sudie E; Brady, Kathleen T; Upadhyaya, Himanshu P; McRae, Aimee L; Saladin, Michael E

    2007-12-01

    This study highlights respondent sensitivity to daily hassles as it relates to situational cocaine use and perceived long-term effects of adverse events in childhood. Data were drawn from a larger study on stress reactivity in cocaine dependent individuals. Participants (n=104) were cocaine dependent men and women without comorbid posttraumatic stress disorder (PTSD). They completed the Early Trauma Inventory (ETI), the Daily Hassles Scale (DHS), the Inventory of Drug-Taking Situations (IDTS), and the Time-Line Follow-Back (TLFB; for 90 days prior to interview). There were no gender differences in the amount or frequency of cocaine use, although the patterns of use differed between male and female users. Overall, there were some associations in the patterns of cocaine use and sensitivity to daily hassles, particularly the use in response to conflict with others. Early negative life events were positively related to response to daily hassles, but current triggers were more relevant. Reactivity to cocaine cues was related to daily hassle sensitivity among women only. Limitations and implications of the findings are discussed.

  8. Alexithymia level and response to computer-based training in cognitive behavioral therapy among cocaine-dependent methadone maintained individuals.

    Science.gov (United States)

    Morie, Kristen P; Nich, Charla; Hunkele, Karen; Potenza, Marc N; Carroll, Kathleen M

    2015-07-01

    Alexithymia, a characteristic marked by poor ability to identify, define and communicate emotions, has been associated with poorer treatment outcome, including traditional clinician delivered CBT. Computerized cognitive behavioral therapy (CBT4CBT), an effective adjunct to treatment, may provide a means of conveying skills without requiring interaction with a clinician. Seventy-three methadone maintained, cocaine dependent individuals participating in an 8-week randomized clinical trial comparing standard methadone maintenance to methadone maintenance plus CBT4CBT completed the Toronto Alexithymia Scale (TAS-20) at pretreatment, post-treatment, and follow-ups conducted one, two, and 6 months after treatment. There were no statistically significant differences on baseline TAS-20 scores by multiple demographic and substance use variables including gender and substance use severity. Higher TAS-20 scores were associated with somewhat higher levels of distress as measured by the Beck Depression Inventory and multiple Brief Severity Index scales. TAS-20 scores remained relatively stable throughout the duration of treatment and follow-up. Indicators of treatment process, including treatment retention, adherence and therapeutic alliance, were not significantly correlated with TAS-20 scores. There was a significant interaction of alexithymia and treatment condition, such that individuals with higher baseline scores on the TAS-20 submitted significantly higher percentages of cocaine-negative urine toxicology specimens and reported a higher percentage of abstinence days, and longer periods of consecutive abstinence within treatment when assigned to CBT4CBT compared with treatment as usual. These findings suggest that individuals with increased alexithymia may benefit from computerized CBT; possibly via reduced demands on interpersonal skills and interactions associated with computerized therapies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. A review of the effects of prenatal cocaine exposure among school-aged children.

    Science.gov (United States)

    Ackerman, John P; Riggins, Tracy; Black, Maureen M

    2010-03-01

    Studies through 6 years have shown no long-term direct effects of prenatal cocaine exposure (PCE) on children's physical growth, developmental test scores, or language outcomes. Little is known about the effects of PCE among school-aged children aged 6 years and older. We reviewed articles from studies that examined the effects of PCE on growth, cognitive ability, academic functioning, and brain structure and function among school-aged children. Articles were obtained by searching PubMed, Medline, TOXNET, and PsycInfo databases from January 1980 to December 2008 with the terms "prenatal cocaine exposure," "cocaine," "drug exposure," "substance exposure," "maternal drug use," "polysubstance," "children," "adolescent," "in utero," "pregnancy," "development," and "behavior." Criteria for inclusion were (1) empirical research on children aged 6 years and older prenatally exposed to cocaine, (2) peer-reviewed English-language journal, (3) comparison group, (4) longitudinal follow-up or historical prospective design, (5) masked assessment, (6) exclusion of subjects with serious medical disabilities, and (7) studies that reported nonredundant findings for samples used in multiple investigations. Thirty-two unique studies met the criteria. Each article was independently abstracted by 2 authors to obtain sample composition, methods of PCE assessment, study design, comparison groups, dependent variables, covariates, and results. Associations between PCE and growth, cognitive ability, academic achievement, and language functioning were small and attenuated by environmental variables. PCE had significant negative associations with sustained attention and behavioral self-regulation, even with covariate control. Although emerging evidence suggests PCE-related alterations in brain structure and function, interpretation is limited by methodologic inconsistencies. Consistent with findings among preschool-aged children, environmental variables play a key role in moderating and

  10. Cocaine withdrawal causes delayed dysregulation of stress genes in the hippocampus.

    Directory of Open Access Journals (Sweden)

    M Julia García-Fuster

    Full Text Available Relapse, even following an extended period of withdrawal, is a major challenge in substance abuse management. Delayed neurobiological effects of the drug during prolonged withdrawal likely contribute to sustained vulnerability to relapse. Stress is a major trigger of relapse, and the hippocampus regulates the magnitude and duration of stress responses. Recent work has implicated hippocampal plasticity in various aspects of substance abuse. We asked whether changes in stress regulatory mechanisms in the hippocampus may participate in the neuroadaptations that occur during prolonged withdrawal. We therefore examined changes in the rat stress system during the course of withdrawal from extended daily access (5-hours of cocaine self-administration, an animal model of addiction. Tissue was collected at 1, 14 and 28 days of withdrawal. Plasma corticosterone levels were determined and corticosteroid receptors (GR, MR, MR/GR mRNA ratios and expression of other stress-related molecules (HSP90AA1 and HSP90AB1 mRNA were measured in hippocampal subfields using in situ hybridization. Results showed a delayed emergence of dysregulation of stress genes in the posterior hippocampus following 28 days of cocaine withdrawal. This included increased GR mRNA in DG and CA3, increased MR and HSP90AA1 mRNA in DG, and decreased MR/GR mRNA ratio in DG and CA1. Corticosterone levels progressively decreased during the course of withdrawal, were normalized following 28 days of withdrawal, and were correlated negatively with GR and positively with MR/GR mRNA ratio in DG. These results suggest a role for the posterior hippocampus in the neuroadaptations that occur during prolonged withdrawal, and point to a signaling partner of GR, HSP90AA1, as a novel dysregulated target during cocaine withdrawal. These delayed neurobiological effects of extended cocaine exposure likely contribute to sustained vulnerability to relapse.

  11. A Simple Economic Model of Cocaine Production

    Science.gov (United States)

    1994-01-01

    River, one of Peru’s largest, have all but died from chemical dumping . 16 Table A.4 Labor Requirements per Unit of Coca Leaf Labor-Years Required to...various years. 17. Samuel Doria Medina, La Economia Informal en Bolivia, undated. 18. Edmundo Morales, Cocaine: White Gold Rush in Peru, University of

  12. Controlling Cocaine. Supply Versus Demand Programs

    Science.gov (United States)

    1994-01-01

    Santa Monica, CA: RAND. Haaga, John G., and Elizabeth A. McGlynn (1993), The DrugAbuse Treatment System: Prospects for Reform, MR-226-DRPC, Santa...Prevalence, Los Angeles, CA: UCLA DrugAbuse Research Group. Homer, Jack B. (1993a), "A System Dynamics Model for Cocaine Prevalence Estimation and Trend

  13. Case Study: The Chemistry of Cocaine

    Science.gov (United States)

    Dewprashad, Brahmadeo

    2011-01-01

    This column provides original articles on innovations in case study teaching, assessment of the method, as well as case studies with teaching notes. This month's case study focuses on the chemistry of cocaine to teach a number of core concepts in organic chemistry. It also requires that students read and analyze an original research paper on…

  14. Cocaine-induced pulmonary changes: HRCT findings

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Renata Rocha de; Zanetti, Glaucia; Marchiori, Edson, E-mail: edmarchiori@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Programa de Pos-Graduacao em Radiologia; Souza Junior, Arthur Soares [Faculdade de Medicina de Petropolis, Petropolis, RJ (Brazil); Souza, Luciana Soares de [Ultra-X, Sao Jose do Rio Preto, SP (Brazil); Silva, Jorge Luiz Pereira e [Universidade Federal da Bahia (UFBA), Salvador (Brazil). Dep. de Medicina e Apoio Diagnostico; Escuissato, Dante Luiz [Universidade Federal do Parana (UFPR), Curitiba (Brazil). Dept. de Clinica Medica; Irion, Klaus Loureiro [Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool (United Kingdom); Mancano, Alexandre Dias [Hospital Anchieta, Taguatinga, DF (Brazil); Nobre, Luiz Felipe [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil); Hochhegger, Bruno [Universidade Federal de Ciencias da Saude de Porto Alegre, Porto Alegre, RS (Brazil); Marchiori, Edson [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil)

    2015-07-15

    Objective: To evaluate HRCT scans of the chest in 22 patients with cocaine-induced pulmonary disease. Methods: We included patients between 19 and 52 years of age. The HRCT scans were evaluated by two radiologists independently, discordant results being resolved by consensus. The inclusion criterion was an HRCT scan showing abnormalities that were temporally related to cocaine use, with no other apparent causal factors. Results: In 8 patients (36.4%), the clinical and tomographic findings were consistent with 'crack lung', those cases being studied separately. The major HRCT findings in that subgroup of patients included ground-glass opacities, in 100% of the cases; consolidations, in 50%; and the halo sign, in 25%. In 12.5% of the cases, smooth septal thickening, paraseptal emphysema, centrilobular nodules, and the tree-in-bud pattern were identified. Among the remaining 14 patients (63.6%), barotrauma was identified in 3 cases, presenting as pneumomediastinum, pneumothorax, and hemopneumothorax, respectively. Talcosis, characterized as perihilar conglomerate masses, architectural distortion, and emphysema, was diagnosed in 3 patients. Other patterns were found less frequently: organizing pneumonia and bullous emphysema, in 2 patients each; and pulmonary infarction, septic embolism, eosinophilic pneumonia, and cardiogenic pulmonary edema, in 1 patient each. Conclusions: Pulmonary changes induced by cocaine use are varied and nonspecific. The diagnostic suspicion of cocaine-induced pulmonary disease depends, in most of the cases, on a careful drawing of correlations between clinical and radiological findings. (author)

  15. Outpatient Cocaine Abuse Treatment: Predictors of Success.

    Science.gov (United States)

    Westhuis, David J.; Gwaltney, Lisa; Hayashi, Reiko

    2001-01-01

    Uses data from the U.S. Army's Alcohol and Drug Abuse Prevention and Control Program to analyze which treatment and demographic variables have an effect on cocaine treatment outcomes. Results suggest the following treatment variables had an effect on outcomes: type of treatment; length of time in treatment; and the length of time since the patient…

  16. Cocaine-induced pulmonary changes: HRCT findings *

    Science.gov (United States)

    de Almeida, Renata Rocha; Zanetti, Gláucia; Souza, Arthur Soares; de Souza, Luciana Soares; Silva, Jorge Luiz Pereira e; Escuissato, Dante Luiz; Irion, Klaus Loureiro; Mançano, Alexandre Dias; Nobre, Luiz Felipe; Hochhegger, Bruno; Marchiori, Edson

    2015-01-01

    Abstract Objective: To evaluate HRCT scans of the chest in 22 patients with cocaine-induced pulmonary disease. Methods: We included patients between 19 and 52 years of age. The HRCT scans were evaluated by two radiologists independently, discordant results being resolved by consensus. The inclusion criterion was an HRCT scan showing abnormalities that were temporally related to cocaine use, with no other apparent causal factors. Results: In 8 patients (36.4%), the clinical and tomographic findings were consistent with "crack lung", those cases being studied separately. The major HRCT findings in that subgroup of patients included ground-glass opacities, in 100% of the cases; consolidations, in 50%; and the halo sign, in 25%. In 12.5% of the cases, smooth septal thickening, paraseptal emphysema, centrilobular nodules, and the tree-in-bud pattern were identified. Among the remaining 14 patients (63.6%), barotrauma was identified in 3 cases, presenting as pneumomediastinum, pneumothorax, and hemopneumothorax, respectively. Talcosis, characterized as perihilar conglomerate masses, architectural distortion, and emphysema, was diagnosed in 3 patients. Other patterns were found less frequently: organizing pneumonia and bullous emphysema, in 2 patients each; and pulmonary infarction, septic embolism, eosinophilic pneumonia, and cardiogenic pulmonary edema, in 1 patient each. Conclusions: Pulmonary changes induced by cocaine use are varied and nonspecific. The diagnostic suspicion of cocaine-induced pulmonary disease depends, in most of the cases, on a careful drawing of correlations between clinical and radiological findings. PMID:26398752

  17. Pharmacological treatments for heroin and cocaine addiction

    NARCIS (Netherlands)

    van den Brink, Wim; van Ree, Jan M.

    2003-01-01

    Aims: To provide an overview of the pharmacological options for the treatment of heroin- and cocaine-dependent patients based on known biochemical pathways to addiction and the chronic disease model as a starting point for treatment planning. Results: Recent pre-clinical and clinical studies

  18. Caffeine, a common active adulterant of cocaine, enhances the reinforcing effect of cocaine and its motivational value.

    Science.gov (United States)

    Prieto, José Pedro; Scorza, Cecilia; Serra, Gian Pietro; Perra, Valentina; Galvalisi, Martín; Abin-Carriquiry, Juan Andrés; Piras, Giovanna; Valentini, Valentina

    2016-08-01

    Caffeine is one of the psychoactive substances most widely used as an adulterant in illicit drugs, such as cocaine. Animal studies have demonstrated that caffeine is able to potentiate several cocaine actions, although the enhancement of the cocaine reinforcing property by caffeine is less reported, and the results depend on the paradigms and experimental protocols used. We examined the ability of caffeine to enhance the motivational and rewarding properties of cocaine using an intravenous self-administration paradigm in rats. Additionally, the role of caffeine as a primer cue during extinction was evaluated. In naïve rats, we assessed (1) the ability of the cocaine (0.250-0.125 mg/kg/infusion) and caffeine (0.125-0.0625 mg/kg/infusion) combination to maintain self-administration in fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement compared with cocaine or caffeine alone and (2) the effect of caffeine (0.0625 mg/kg/infusion) in the maintenance of responding in the animals exposed to the combination of the drugs during cocaine extinction. Cocaine combined with caffeine and cocaine alone was self-administered on FR and PR schedules of reinforcement. Interestingly, the breaking point determined for the cocaine + caffeine group was significantly higher than the cocaine group. Moreover, caffeine, that by itself did not maintain self-administration behavior in naïve rats, maintained drug-seeking behavior of rats previously exposed to combinations of cocaine + caffeine. Caffeine enhances the reinforcing effects of cocaine and its motivational value. Our results highlight the role of active adulterants commonly used in cocaine-based illicit street drugs.

  19. Neural correlates of the severity of cocaine, heroin, alcohol, MDMA and cannabis use in polysubstance abusers: a resting-PET brain metabolism study.

    Directory of Open Access Journals (Sweden)

    Laura Moreno-López

    Full Text Available 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.

  20. Polysomnographic measures of sleep in cocaine dependence and alcohol dependence: Implications for age‐related loss of slow wave, stage 3 sleep

    Science.gov (United States)

    Bjurstrom, Martin F.; Olmstead, Richard

    2016-01-01

    Abstract Background and aims Sleep disturbance is a prominent complaint in cocaine and alcohol dependence. This controlled study evaluated differences of polysomnographic (PSG) sleep in cocaine‐ and alcohol‐dependent subjects, and examined whether substance dependence interacts with age to alter slow wave sleep and rapid eye movement (REM) sleep. Design Cross‐sectional comparison. Setting Los Angeles and San Diego, CA, USA. Participants Abstinent cocaine‐dependent subjects (n = 32), abstinent alcohol‐dependent subjects (n = 73) and controls (n = 108); mean age 40.3 years recruited 2005–12. Measurements PSG measures of sleep continuity and sleep architecture primary outcomes of Stage 3 sleep and REM sleep. Covariates included age, ethnicity, education, smoking, body mass index and depressive symptoms. Findings Compared with controls, both groups of substance dependent subjects showed loss of Stage 3 sleep (P < 0.001). A substance dependence × age interaction was found in which both cocaine‐ and alcohol‐dependent groups showed loss of Stage 3 sleep at an earlier age than controls (P < 0.05 for all), and cocaine‐dependent subjects showed loss of Stage 3 sleep at an earlier age than alcoholics (P < 0.05). Compared with controls, REM sleep was increased in both substance‐dependent groups (P < 0.001), and cocaine and alcohol dependence were associated with earlier age‐related increase in REM sleep (P < 0.05 for all). Conclusions Cocaine and alcohol dependence appear to be associated with marked disturbances of sleep architecture, including increased rapid eye movement sleep and accelerated age‐related loss of slow wave, Stage 3 sleep. PMID:26749502

  1. Cocaine-Associated Seizures and Incidence of Status Epilepticus

    Directory of Open Access Journals (Sweden)

    Majlesi, Nima DO

    2010-05-01

    Full Text Available Objectives: Acute complications from cocaine abuse are commonly treated in the emergency department (ED; one of the most consequential is status epilepticus. The incidence of this complication is not clearly defined in the prior literature on cocaine-associated sequelae. We evaluated the incidence of status epilepticus in patients with seizures secondary to suspected cocaine use.Methods: We performed a retrospective multi-center study of patients with seizures resulting from cocaine use. We identified study subjects at 15 hospitals by record review and conducted a computer-assisted records search to identify patients with seizures for each institution over a four-year period. We selected subjects from this group on the basis of cocaine use and determined the occurrence of status epilepticus among them. Data were collected on each subject using a standardized data collection form.Results: We evaluated 43 patients in the ED for cocaine-associated seizures. Their age range was 17 to 54, with a mean age was 31 years; 53% were male. Of 43 patients, 42 experienced a single tonic-clonic seizure and one developed status epilepticus. All patients had either a history of cocaine use or positive urine drug screen for cocaine.Conclusion: Despite reported cases of status epilepticus with cocaine-induced seizures, the incidence of this complication was unclear based on prior literature. This study shows that most cocaine-associated seizures are self-limited. [West J Emerg Med. 2010; 11(2:157-160.

  2. Environmental enrichment induces early heroin abstinence in an animal conflict model.

    Science.gov (United States)

    Peck, Joshua A; Galaj, Ewa; Eshak, Stephanie; Newman, Kristena L; Ranaldi, Robert

    2015-11-01

    Heroin addiction is a significant health and societal problem for which there is no highly effective long-term behavioral or pharmacological treatment. Therefore, strategies that support heroin abstinence should be a primary focus of heroin treatment research. To this end, the current study used an animal conflict model that captures the aversive consequences of drug seeking (as are typical in humans, e.g., incarceration and job loss) to induce abstinence. Using this abstinence model, we examined the capacity of environmental enrichment (EE) to facilitate abstinence in heroin seeking rats. The procedure consisted of two phases: drug self-administration (phase 1) and electric barrier application (phase 2) that resulted in abstinence. For phase 1, male rats were trained to self-administer intravenous heroin under a fixed-ratio schedule of reinforcement. After self-administration was acquired, animals were housed either in EE or standard cages (non-EE control). During abstinence in phase 2, the electric barrier was introduced in the operant conditioning chambers by electrifying the floor area near the levers. We found that EE rats achieved abstinence (zero active lever presses for 3 consecutive sessions) in significantly fewer sessions than NEE rats. Further, EE rats abstained at significantly lower electric currents than NEE rats. EE facilitated abstinence in the conflict model. The current use of the abstinence-conflict model to investigate EE as a behavioral strategy to facilitate abstinence will help in the development of effective treatments for human addicts by bringing together the positive consequences of abstinent behavior in an enriched environment with the aversive consequences of drug seeking. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Variation in chemical profiles within large seizures of cocaine bricks.

    Science.gov (United States)

    Stride Nielsen, Louise; Villesen, Palle; Lindholst, Christian

    2017-11-01

    Cocaine is usually trafficked from South America throughout the world in packages of approximately one kilogram shaped as bricks and imprinted with a logo. Seizures consisting of multiple cocaine bricks gives the opportunity to examine the variation in the chemical profile within cocaine bricks assumed to originate from the same manufacturer and maybe even the same production batch. This knowledge may be important to the forensic investigator when chemical profiles from cocaine samples of unknown origin are compared. In the present study, the alkaloid and residual solvent profiles from three large cocaine seizures each containing identical cocaine bricks was examined. The three cases consisted of 36, 84 and 100 cocaine bricks, respectively. Each cocaine brick was profiled according to its cocaine alkaloid and residual solvent content using gas chromatography-mass spectrometry (GC-MS) and headspace GC-MS. The study showed that each of the three identical looking seizures consisted of up to four groups of cocaine bricks displaying the same cocaine alkaloid and residual solvent profile. The size of the groups varied from 2.4 to 63.3kg cocaine. The study also showed that the residual solvent profile within each of the three large seizures exhibited very little variation whereas the alkaloid profile varied considerably more. This finding suggest that the same organic solvent is used for the production of several batches of cocaine HCl. Therefore, the residual solvent profile may be a tool to link different production batches from the same manufacturer even though the alkaloid profile are different. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. College students’ use of cocaine: Results from a longitudinal study

    Science.gov (United States)

    Kasperski, Sarah J.; Vincent, Kathryn B.; Caldeira, Kimberly M.; Garnier-Dykstra, Laura M.; O’Grady, Kevin E.; Arria, Amelia M.

    2010-01-01

    College students have high rates of heavy drinking and other risky behaviors, but little is known about trends in their use of cocaine. In this longitudinal study of 1,253 college students at one large, public university in the mid-Atlantic region, annual interviews assessed opportunity to use cocaine, cocaine use, and DSM-IV criteria for cocaine abuse and dependence. Follow-up rates exceeded 87% annually. Data from the first four years of college were analyzed to detect changes over time and possible gender differences. By their fourth year of college, 36%wt of students had been offered cocaine at least once in their lifetime, and 13%wt had used cocaine. Annual prevalence of cocaine use increased significantly over time (4%wt in Year 1 to 10%wt in Year 4) and remained similar across genders. Opportunities to use cocaine were significantly more prevalent for males than females during Years 2 through 4. Cocaine use given opportunity increased significantly over time for both males and females. Among 243 cocaine users, females (n=113) had more serious use patterns than males, with higher average frequency of use (18.39 vs. 8.83 days during the peak year of use, p<.05) and greater likelihood of meeting criteria for cocaine dependence (9.3% vs. 2.5%, p<.05). Gender differences in typical cocaine dosage were not apparent. College administrators and health providers should be aware of the prevalence of cocaine use among student populations and design strategies to address the problem. PMID:21196083

  5. The effect of methadone dose regimen on neonatal abstinence syndrome.

    Science.gov (United States)

    McCarthy, John J; Leamon, Martin H; Willits, Neil H; Salo, Ruth

    2015-01-01

    To evaluate the effects of a multiple daily dose methadone regimen in pregnancy on neonatal outcomes. Although methadone maintenance has been the standard for the treatment of opioid dependence in pregnancy, there is no consensus on proper dosing. Single daily dosing is the most common strategy. Because of accelerated metabolism of methadone in pregnancy, this regimen may expose mother and fetus to daily episodes of withdrawal and possibly contribute to more severe Neonatal Abstinence Syndrome (NAS). This study reports on a protocol that increased both methadone dose and dose frequency in response to maternal reports of withdrawal. Treatment of NAS was needed in 29% of neonates, compared to a published rate of 60% to 80%. The mean methadone dose was 152 mg at delivery, divided into 2 to 6 doses per day. Ninety-two percent of mothers were free of illicit drug use at delivery. There was no relationship between methadone dose and treatment of NAS. Female babies had a treatment rate of 16% versus 38% for male babies. Beyond abstinence symptoms, cohort outcomes in terms of gestational age, birth weight, prematurity, Caesarian sections, and breastfeeding equaled or approximated US population norms. The protocol was associated with low rates of treatment of NAS and high rates of maternal recovery. High rates of treatment for NAS reported in methadone-exposed neonates might relate in part to iatrogenic factors and be reduced through the use of divided daily doses and protocols that minimize maternal withdrawal.

  6. Born Into Addiction: Neonatal Abstinence Syndrome and Pediatric Dentistry.

    Science.gov (United States)

    Cully, Jennifer L

    2017-09-15

    Drug overdose and opioid-involved deaths continue to increase across the United States. An end-condition related to opioid abuse is neonatal abstinence syndrome (NAS). The implications for pregnant or post-partum women using an opioid, whether prescribed or illicit, can have significant effects on their infant. First described in the 1970s, NAS is defined as a postnatal drug withdrawal syndrome that primarily occurs in opioid-exposed infants. There are no nationally accepted, evidence-based treatment protocols for these infants. Pediatric dentists should be cognizant of potential dental development issues and developmental delays in children with NAS. Basic behavior guidance techniques, such as tell-show-do, may not be as effective. In addition, adherence to prescription drug monitoring programs can help identify patients who may have received multiple opioids, alerting the provider to possible misuse or abuse. The purpose of this paper was to provide background information on the incidences and potential dental implications for children with neonatal abstinence syndrome.

  7. Placebo caffeine reduces withdrawal in abstinent coffee drinkers.

    Science.gov (United States)

    Mills, Llewellyn; Boakes, Robert A; Colagiuri, Ben

    2016-04-01

    Expectancies have been shown to play a role in the withdrawal syndrome of many drugs of addiction; however, no studies have examined the effects of expectancies across a broad range of caffeine withdrawal symptoms, including craving. The purpose of the current study was to use caffeine as a model to test the effect of expectancy on withdrawal symptoms, specifically whether the belief that one has ingested caffeine is sufficient to reduce caffeine withdrawal symptoms and cravings in abstinent coffee drinkers. We had 24-h abstinent regular coffee drinkers complete the Caffeine Withdrawal Symptom Questionnaire (CWSQ) before and after receiving decaffeinated coffee. One-half of the participants were led to believe the coffee was regular caffeinated coffee (the 'Told Caffeine' condition) and one-half were told that it was decaffeinated (the 'Told Decaf' condition). Participants in the Told Caffeine condition reported a significantly greater reduction in the factors of cravings, fatigue, lack of alertness and flu-like feelings of the CWSQ, than those in the Told Decaf condition. Our results indicated that the belief that one has consumed caffeine can affect caffeine withdrawal symptoms, especially cravings, even when no caffeine was consumed. © The Author(s) 2016.

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

    Science.gov (United States)

    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. Neonatal abstinence syndrome: Historical perspective, current focus, future directions.

    Science.gov (United States)

    Jones, Hendrée E; Fielder, Andrea

    2015-11-01

    Neonatal abstinence syndrome (NAS) occurs following prenatal opioid exposure. It is characterized by signs and symptoms indicating central nervous system hyperirritability and autonomic nervous system, gastrointestinal tract, and respiratory system dysfunction. This article: (1) briefly reviews NAS history, including initial identification, assessment, and treatment efforts; (2) summarizes the current status of and current issues surrounding recent NAS assessment and treatment, and (3) details future directions in NAS conceptualization, measurement, and treatment. Mortality rate estimates in neonates treated for NAS exceeded 33%, and surpassed 90% for un-treated infants during the late-1800s until the mid-1900s. The focus of both assessment and treatment over the past 50years is predominantly due to two forces. First, methadone pharmacotherapy for "heroin addiction" led to women in methadone maintenance programs who were, or became pregnant. The second was defining NAS and developing a measure of neonatal withdrawal, the Neonatal Abstinence Scoring System (NASS). Various NAS treatment protocols were based on the NASS as well as other NAS measures. Future research must focus on psychometrically sound screening and assessment measures of neonatal opioid withdrawal for premature, term and older infants, measuring and treating possible withdrawal from non-opioids, particularly benzodiazepines, integrated non-pharmacological treatment of NAS, weight-based versus symptom-based treatment of NAS, and second-line treatment for NAS. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. A guided abstinence experience to illustrate addiction recovery principles.

    Science.gov (United States)

    Baldwin, Jeffrey N

    2008-08-15

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

  11. Stable immediate early gene expression patterns in medial prefrontal cortex and striatum after long-term cocaine self-administration.

    Science.gov (United States)

    Gao, Ping; Limpens, Jules H W; Spijker, Sabine; Vanderschuren, Louk J M J; Voorn, Pieter

    2017-03-01

    The transition from casual to compulsive drug use is thought to occur as a consequence of repeated drug taking leading to neuroadaptive changes in brain circuitry involved in emotion and cognition. At the basis of such neuroadaptations lie changes in the expression of immediate early genes (IEGs) implicated in transcriptional regulation, synaptic plasticity and intracellular signalling. However, little is known about how IEG expression patterns change during long-term drug self-administration. The present study, therefore, compares the effects of 10 and 60-day self-administration of cocaine and sucrose on the expression of 17 IEGs in brain regions implicated in addictive behaviour, i.e. dorsal striatum, ventral striatum and medial prefrontal cortex (mPFC). Increased expression after cocaine self-administration was found for 6 IEGs in dorsal and ventral striatum (c-fos, Mkp1, Fosb/ΔFosb, Egr2, Egr4, and Arc) and 10 IEGs in mPFC (same 6 IEGs as in striatum, plus Bdnf, Homer1, Sgk1 and Rgs2). Five of these 10 IEGs (Egr2, Fosb/ΔFosb, Bdnf, Homer1 and Jun) and Trkb in mPFC were responsive to long-term sucrose self-administration. Importantly, no major differences were found between IEG expression patterns after 10 or 60 days of cocaine self-administration, except Fosb/ΔFosb in dorsal striatum and Egr2 in mPFC, whereas the amount of cocaine obtained per session was comparable for short-term and long-term self-administration. These steady changes in IEG expression are, therefore, associated with stable self-administration behaviour rather than the total amount of cocaine consumed. Thus, sustained impulses to IEG regulation during prolonged cocaine self-administration may evoke neuroplastic changes underlying compulsive drug use. © 2015 Society for the Study of Addiction.

  12. The role of D-serine as co-agonist of NMDA receptors in the nucleus accumbens: relevance to cocaine addiction

    Directory of Open Access Journals (Sweden)

    Marcello eD'Ascenzo

    2014-07-01

    Full Text Available Cocaine addiction is characterized by compulsive drug use despite adverse consequences and high rate of relapse during periods of abstinence. Increasing consensus suggests that addiction to drugs of abuse usurps learning and memory mechanisms normally related to natural rewards, ultimately producing long-lasting neuroadaptations in the mesocorticolimbic system. This system, formed in part by the ventral tegmental area and nucleus accumbens (NAc, has a central role in the development and expression of addictive behaviors. In addition to a broad spectrum of changes that affect morphology and function of NAc excitatory circuits in cocaine–treated animals, impaired N-methyl-D-aspartate receptor (NMDAR-dependent synaptic plasticity is a typical feature. D-serine, a D-amino acid that has been found at high levels in mammalian brain, binds with high affinity the co-agonist site of NMDAR and mediates, along with glutamate, several important processes including synaptic plasticity. Here we review recent literature focusing on cocaine-induced impairment in synaptic plasticity mechanisms in the NAc and on the fundamental role of D-serine as co-agonist of NMDAR in functional and dysfunctional synaptic plasticity within this nucleus. The emerging picture is that reduced D-serine levels play a crucial role in synaptic plasticity relevant to cocaine addiction. This finding opens new perspectives for therapeutic approaches to treat this addictive state.

  13. Subchronic administration of atomoxetine causes an enduring reduction in context-induced relapse to cocaine seeking without affecting impulsive decision making.

    Science.gov (United States)

    Broos, Nienke; Loonstra, Rhianne; van Mourik, Yvar; Schetters, Dustin; Schoffelmeer, Anton N M; Pattij, Tommy; De Vries, Taco J

    2015-07-01

    Previous work has established a robust relationship between impulsivity and addiction, and revealed that impulsive decision making predisposes the vulnerability to cocaine-seeking behavior in rats. An important next step is to assess whether elevated relapse vulnerability can be treated via the reduction of impulsive decision making. Therefore, this study explored whether subchronic atomoxetine treatment can reduce relapse vulnerability by reducing impulsive decision making. Rats were trained in the delayed reward task and were subjected to 3 weeks of cocaine self-administration. Following drug self-administration, animals were divided to different experimental groups and received the noradrenaline transporter inhibitor and attention-deficit/hyperactivity disorder drug atomoxetine or vehicle subchronically for 20 days. On days 1 and 10 after treatment cessation, a context-induced reinstatement test was performed. Throughout the entire experiment, changes in impulsive decision making were continuously monitored. Subchronic treatment with atomoxetine reduced context-induced reinstatement both 1 and 10 days after treatment cessation, only in animals receiving no extinction training. Interestingly, neither subchronic nor acute atomoxetine treatments affected impulsive decision making. Our data indicate that the enduring reduction in relapse sensitivity by atomoxetine occurred independent of a reduction in impulsive decision making. Nonetheless, repeated atomoxetine administration seems a promising pharmacotherapeutical strategy to prevent relapse to cocaine seeking in abstinent drug-dependent subjects. © 2014 Society for the Study of Addiction.

  14. Myocardial uptake of cocaine and effects of cocaine on myocardial substrate utilization and perfusion in hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Som, P.; Wang, G.J. (Brookhaven National Lab., Upton, NY (United States)); Oster, Z.H. (State Univ. of New York, Stony Brook, NY (United States)); Knapp, F.F. Jr. (Oak Ridge National Lab., TN (United States)); Yonekura, Y. (Kyoto Univ. (Japan). Faculty of Medicine); Fujibayashi, Y. (Kyoto Univ. (Japan). Hospital); Yamamoto, K. (Fukui Univ. (Japan). Medical School); Kubota, K. (Tohoku Univ., Sendai

    1992-01-01

    Cocaine abuse is a problem causing world-wide concern and the number of deaths following cocaine use is increasing. Cardiovascular complications following cocaine include severe tachyarrythmias, pulmonary edema, myocardial infarction, and acute renal failure, which are major problems confronting emergency facilities. While the studies of cocaine effects on the brain have been given the most attention, it is clear that the effects of cocaine on the cardiovascular system are of great importance, given the increasing number of reports on sudden death and myocardial infarctions in young adults related to cocaine use. The precise mechanisms of cardiotoxic actions of cocaine are unclear. We investigated the whole-body distribution of C-14-labeled cocaine to determine the cocaine-binding sites, including blocking experiments to determine the nature of regional binding sites, and differential response of the normal vs. diseased heart (hypertensive cardiomyopathy) in an animal model to mimic a potentially high risk population. We investigated the acute effects of cocaine on myocardial metabolism using two myocardial energy substrate analogs, fatty acid and glucose with comparison with regional perfusion.

  15. Myocardial uptake of cocaine and effects of cocaine on myocardial substrate utilization and perfusion in hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Som, P.; Wang, G.J. [Brookhaven National Lab., Upton, NY (United States); Oster, Z.H. [State Univ. of New York, Stony Brook, NY (United States); Knapp, F.F. Jr. [Oak Ridge National Lab., TN (United States); Yonekura, Y. [Kyoto Univ. (Japan). Faculty of Medicine; Fujibayashi, Y. [Kyoto Univ. (Japan). Hospital; Yamamoto, K. [Fukui Univ. (Japan). Medical School; Kubota, K. [Tohoku Univ., Sendai (Japan)

    1992-12-31

    Cocaine abuse is a problem causing world-wide concern and the number of deaths following cocaine use is increasing. Cardiovascular complications following cocaine include severe tachyarrythmias, pulmonary edema, myocardial infarction, and acute renal failure, which are major problems confronting emergency facilities. While the studies of cocaine effects on the brain have been given the most attention, it is clear that the effects of cocaine on the cardiovascular system are of great importance, given the increasing number of reports on sudden death and myocardial infarctions in young adults related to cocaine use. The precise mechanisms of cardiotoxic actions of cocaine are unclear. We investigated the whole-body distribution of C-14-labeled cocaine to determine the cocaine-binding sites, including blocking experiments to determine the nature of regional binding sites, and differential response of the normal vs. diseased heart (hypertensive cardiomyopathy) in an animal model to mimic a potentially high risk population. We investigated the acute effects of cocaine on myocardial metabolism using two myocardial energy substrate analogs, fatty acid and glucose with comparison with regional perfusion.

  16. Synaptic depression via mGluR1 positive allosteric modulation suppresses cue-induced cocaine craving

    Science.gov (United States)

    Loweth, Jessica A.; Scheyer, Andrew F.; Milovanovic, Mike; LaCrosse, Amber L.; Flores-Barrera, Eden; Werner, Craig T.; Li, Xuan; Ford, Kerstin A.; Le, Tuan; Olive, M. Foster; Szumlinski, Karen K.; Tseng, Kuei Y.; Wolf, Marina E.

    2014-01-01

    Cue-induced cocaine craving is a major cause of relapse in abstinent addicts. In rats, cue-induced craving progressively intensifies (incubates) during withdrawal from extended-access cocaine self-administration. After ~1 month of withdrawal, incubated craving is mediated by Ca2+-permeable AMPARs (CP-AMPARs) that accumulate in the nucleus accumbens (NAc). We found that decreased mGluR1 surface expression in the NAc precedes and enables CP-AMPAR accumulation. Thus, restoring mGluR1 tone by administering repeated injections of an mGluR1 positive allosteric modulator (PAM) prevented CP-AMPAR accumulation and incubation, whereas blocking mGluR1 transmission at even earlier withdrawal times accelerated CP-AMPAR accumulation. In studies conducted after prolonged withdrawal, when CP-AMPAR levels and cue-induced craving are high, we found that systemic administration of an mGluR1 PAM attenuated the expression of incubated craving by reducing CP-AMPAR transmission in the NAc to control levels. These results demonstrate a strategy whereby recovering addicts could use a systemically active compound to protect against cue-induced relapse. PMID:24270186

  17. Neural correlates of reward-based spatial learning in persons with cocaine dependence.

    Science.gov (United States)

    Tau, Gregory Z; Marsh, Rachel; Wang, Zhishun; Torres-Sanchez, Tania; Graniello, Barbara; Hao, Xuejun; Xu, Dongrong; Packard, Mark G; Duan, Yunsuo; Kangarlu, Alayar; Martinez, Diana; Peterson, Bradley S

    2014-02-01

    Dysfunctional learning systems are thought to be central to the pathogenesis of and impair recovery from addictions. The functioning of the brain circuits for episodic memory or learning that support goal-directed behavior has not been studied previously in persons with cocaine dependence (CD). Thirteen abstinent CD and 13 healthy participants underwent MRI scanning while performing a task that requires the use of spatial cues to navigate a virtual-reality environment and find monetary rewards, allowing the functional assessment of the brain systems for spatial learning, a form of episodic memory. Whereas both groups performed similarly on the reward-based spatial learning task, we identified disturbances in brain regions involved in learning and reward in CD participants. In particular, CD was associated with impaired functioning of medial temporal lobe (MTL), a brain region that is crucial for spatial learning (and episodic memory) with concomitant recruitment of striatum (which normally participates in stimulus-response, or habit, learning), and prefrontal cortex. CD was also associated with enhanced sensitivity of the ventral striatum to unexpected rewards but not to expected rewards earned during spatial learning. We provide evidence that spatial learning in CD is characterized by disturbances in functioning of an MTL-based system for episodic memory and a striatum-based system for stimulus-response learning and reward. We have found additional abnormalities in distributed cortical regions. Consistent with findings from animal studies, we provide the first evidence in humans describing the disruptive effects of cocaine on the coordinated functioning of multiple neural systems for learning and memory.

  18. The motivation to stay abstinent in ex-smokers : Comparing the present with the past

    NARCIS (Netherlands)

    Dijkstra, Arie; Borland, Ron; Buunk, Bram P.

    2007-01-01

    Little is known about the motivation of ex-smokers to stay abstinent. In the present study we argue that ex-smokers compare their present to their past when they still smoked to conclude whether they make good progress towards a satisfactory state of continued abstinence. These temporal comparisons

  19. Physiological and endocrine reactions to psychosocial stress in alcohol use disorders: duration of abstinence matters

    NARCIS (Netherlands)

    Starcke, Katrin; van Holst, Ruth J.; van den Brink, Wim; Veltman, Dick J.; Goudriaan, Anna E.

    2013-01-01

    Recent research findings suggest that heavy alcohol use is associated with alterations of the hypothalamic-pituitary-adrenal axis and autonomic nervous system function and that early abstinence is associated with blunted stress responsiveness. This study investigated abstinent alcohol-dependent

  20. Feasibility of abstinence as a preventive strategy for HIV/AIDS ...

    African Journals Online (AJOL)

    HIV is spreading and the youth bear the brunt of its onslaught. Though abstinence until marriage is thought to be the most effective method of HIV prevention for the youth, others think it is ineffective. This study assessed the feasibility of abstinence in preventing HIV/AIDS spread among tertiary students of the KNUST.

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

    Science.gov (United States)

    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)

  2. Quasi-morphine abstinence behaviour GABA-ergic mechanisms and their localization

    NARCIS (Netherlands)

    J.W. van der Laan

    1981-01-01

    textabstractDi-n-propylacetate (DPA), generally known to be an anti-epileptic drug, induces a behavioural syndrome in rats resembling morphine abstinence behaviour, which is called, therefore, quasi-morphine abstinence beh~viour. An increase in GABA-ergic activity is probably responsible for this

  3. Cocaine is pharmacologically active in the nonhuman primate fetal brain

    DEFF Research Database (Denmark)

    Benveniste, Helene; Fowler, Joanna S; Rooney, William D

    2010-01-01

    -trimester pregnant nonhuman primates, cocaine at doses typically used by drug abusers significantly increased brain glucose metabolism to the same extent in the mother as in the fetus (approximately 100%). Inasmuch as brain glucose metabolism is a sensitive marker of brain function, the current findings provide......Cocaine use during pregnancy is deleterious to the newborn child, in part via its disruption of placental blood flow. However, the extent to which cocaine can affect the function of the fetal primate brain is still an unresolved question. Here we used PET and MRI and show that in third...... evidence that cocaine use by a pregnant mother will also affect the function of the fetal brain. We are also unique in showing that cocaine's effects in brain glucose metabolism differed in pregnant (increased) and nonpregnant (decreased) animals, which suggests that the psychoactive effects of cocaine...

  4. Dancing on coke: smuggling cocaine dispersed in polyvinyl alcohol.

    Science.gov (United States)

    van Nuijs, Alexander L N; Maudens, Kristof E; Lambert, Willy E; Van Calenbergh, Serge; Risseeuw, Martijn D P; Van hee, Paul; Covaci, Adrian; Neels, Hugo

    2012-01-01

    Recent trends suggest that cocaine smugglers have become more and more inventive to avoid seizures of large amounts of cocaine transported between countries. We report a case of a mail parcel containing a dance pad which was seized at the Customs Department of Brussels Airport, Belgium. After investigation, the inside of the dance pad was found to contain a thick polymer, which tested positive for cocaine. Analysis was performed using a routine colorimetric swipe test, gas chromatography coupled with mass spectrometry and nuclear magnetic resonance spectroscopy. The polymer was identified as polyvinyl alcohol (PVA) and contained 18% cocaine, corresponding to a street value of € 20,000. Laboratory experiments showed that cocaine could be easily extracted from the PVA matrix. This case report reveals a new smuggling technique for the transportation of large amounts of cocaine from one country to another. © 2011 American Academy of Forensic Sciences.

  5. Modafinil for the treatment of cocaine dependence

    National Research Council Canada - National Science Library

    Anderson, Ann L; Reid, Malcolm S; Li, Shou-Hua; Holmes, Tyson; Shemanski, Lynn; Slee, April; Smith, Edwina V; Kahn, Roberta; Chiang, Nora; Vocci, Frank; Ciraulo, Domenic; Dackis, Charles; Roache, John D; Salloum, Ihsan M; Somoza, Eugene; Urschel, Harold C; Elkashef, Ahmed M

    2009-01-01

    ... years of abstinence ( Hser et al., 2006 ). Modafinil is a novel, non-amphetamine psychostimulant, approved by the US Food and Drug Administration (FDA, www.fda.gov/cder/foi/label/2007/020717s020s013s018lbl.pdf [accessed date May 8, 2009]) in 1998 for the treatment of narcolepsy. It is as effective as traditional dopamine-acting stimulants for that i...

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

    Science.gov (United States)

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

    2010-01-01

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

  7. Endocrine response to masturbation-induced orgasm in healthy men following a 3-week sexual abstinence.

    Science.gov (United States)

    Exton, M S; Krüger, T H; Bursch, N; Haake, P; Knapp, W; Schedlowski, M; Hartmann, U

    2001-11-01

    This current study examined the effect of a 3-week period of sexual abstinence on the neuroendocrine response to masturbation-induced orgasm. Hormonal and cardiovascular parameters were examined in ten healthy adult men during sexual arousal and masturbation-induced orgasm. Blood was drawn continuously and cardiovascular parameters were constantly monitored. This procedure was conducted for each participant twice, both before and after a 3-week period of sexual abstinence. Plasma was subsequently analysed for concentrations of adrenaline, noradrenaline, cortisol, prolactin, luteinizing hormone and testosterone concentrations. Orgasm increased blood pressure, heart rate, plasma catecholamines and prolactin. These effects were observed both before and after sexual abstinence. In contrast, although plasma testosterone was unaltered by orgasm, higher testosterone concentrations were observed following the period of abstinence. These data demonstrate that acute abstinence does not change the neuroendocrine response to orgasm but does produce elevated levels of testosterone in males.

  8. Cocaine-related stimuli impair inhibitory control in cocaine users following short stimulus onset asynchronies.

    Science.gov (United States)

    Pike, Erika; Marks, Katherine R; Stoops, William W; Rush, Craig R

    2015-08-01

    Cocaine users display a significant increase in inhibitory failures following cocaine-related images compared with neutral images in a modified cued Go/No-Go task, the Attentional Bias-Behavioral Activation (ABBA) task. The aim of this study was to demonstrate that stimulus onset asynchrony (SOA) impacts inhibitory failures on the ABBA task. A between-subjects experiment. An out-patient research unit in the United States. Ninety-one cocaine users recruited from the community. Participants were assigned to groups in which they saw either cocaine (n=46) or neutral (n=45) images as the go condition. Cues were presented for one of five SOAs (i.e. 100, 200, 300, 400 or 500 ms) before a go or no-go target was displayed. Participants in the cocaine go condition had a significantly higher proportion of inhibitory failures to no-go targets (F4,356=2.50, P=0.04) with significantly more inhibitory failures following all SOAs (PSOAs than after the 300, 400 or 500 ms SOAs (PSOAs: the amount of time between the start of one stimulus and the start of another stimulus), but not at longer (300, 400 and 500 ms) SOAs. © 2015 Society for the Study of Addiction.

  9. Liking and wanting of drug and nondrug rewards in active cocaine users: the STRAP-R questionnaire

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, R.Z.; Goldstein, R.Z.; Woicik, P.A..; Moeller, S.J.; Telang, F.; Jayne, M.; Wong, C.; Wang, G-J.; Fowler, J.S.; Volkow, N.D.

    2008-10-01

    Few studies have examined the subjective value attributed to drug rewards specifically as it compares with the value attributed to primary non-drug rewards in addicted individuals. The objective of this study is to assess liking and wanting of expected drug rewards as compared to food and sex while respondents report about three different situations (current, and hypothetical in general, and under drug influence). In all, 20 cocaine-addicted individuals (mean abstinence = 2 days) and 20 healthy control subjects were administered the STRAP-R (Sensitivity To Reinforcement of Addictive and other Primary Rewards) questionnaire after receiving an oral dose of the dopamine agonist methylphenidate (20 mg) or placebo. The reinforcers relative value changed within the addicted sample when reporting about the under drug influence situation (drug > food; otherwise, drug < food). This change was highest in the addicted individuals with the youngest age of cocaine use onset. Moreover, drug wanting exceeded drug liking in the addicted subjects when reporting about this situation during methylphenidate. Thus, cocaine-addicted individuals assign the highest subjective valence to drug rewards but only when recalling cue-related situations. When recalling this situation, they also report higher drug wanting than hedonic liking, a motivational shift that was only significant during methylphenidate. Together, these valence shifts may underlie compulsive stimulant abuse upon pharmacological or behavioural cue exposure in addicted individuals. Additional studies are required to assess the reliability of the STRAP-R in larger samples and to examine its validity in measuring the subjective value attributed to experienced reinforcers or in predicting behaviour.

  10. Attentional bias to negative affect moderates negative affect's relationship with smoking abstinence.

    Science.gov (United States)

    Etcheverry, Paul E; Waters, Andrew J; Lam, Cho; Correa-Fernandez, Virmarie; Vidrine, Jennifer Irvin; Cinciripini, Paul M; Wetter, David W

    2016-08-01

    To examine whether initial orienting (IO) and inability to disengage (ITD) attention from negative affective stimuli moderate the association of negative affect with smoking abstinence during a quit attempt. Data were from a longitudinal cohort study of smoking cessation (N = 424). A negative affect modified Stroop task was administered 1 week before and on quit day to measure IO and ITD. Ecological Momentary Assessments were used to create negative affect intercepts and linear slopes for the week before quitting and on quit day. Quit day and long-term abstinence measures were collected. Continuation ratio logit model analyses found significant interactions for prequit negative affect slope with prequit ITD, odds ratio (OR) = 0.738 (0.57, 0.96), p = .02, and for quit day negative affect intercept with quit day ITD, OR = 0.62 (0.41, 950), p = .03, predicting abstinence. The Prequit Negative Affect Intercept × Prequit IO interaction predicting quit day abstinence was significant, OR = 1.42 (1.06, 1.90), p = .02, as was the Quit Day Negative Affect Slope × Quit Day IO interaction predicting long-term abstinence, OR = 1.45 (1.02, 2.08), p = .04. The hypothesis that the association of negative affect with smoking abstinence would be moderated by ITD was generally supported. Among individuals with high ITD, negative affect was inversely related to abstinence, but unrelated to abstinence among individuals with lower levels of ITD. Unexpectedly, among individuals with low IO, negative affect was inversely related to abstinence, but unrelated to abstinence among individuals with higher levels of ITD. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  11. Headache in chronic cocaine users: A cross-sectional study.

    Science.gov (United States)

    Fofi, Luisa; Orlandi, Valerio; Vanacore, Nicola; Mizzoni, Maria C; Rosa, Alba; Aurilia, Cinzia; Egeo, Gabriella; Casella, Pietro; Barbanti, Piero

    2014-08-01

    Headache is one of the most common symptoms after cocaine use. We investigated headache frequency and characteristics and the correlation between headache and acute cocaine intake in a cross-sectional study in a consecutive series of chronic cocaine users. Participation rate was 94.1%. Of the 80 subjects enrolled, 72 (90%) reported current headaches, in most cases migraine or probable migraine without aura. Of these 72, 29 (40.3%) had a headache history, whereas 43 (59.7%) reported de novo headache after beginning to use cocaine. After acute cocaine use, a large percentage of users reported headache attacks: 86.2% of previous headache sufferers (migraine or probable migraine without aura in all cases) and 93% of de novo headache sufferers (migraine/probable migraine without aura = 35; episodic tension-type headache = three patients; cocaine-induced headache= two patients). Most subjects reported that when they used cocaine headaches worsened. Chronic cocaine use frequently seems to worsen or induce headache with migraine or migraine-like characteristics, probably owing to a serotoninergic and dopaminergic system impairment. In headache sufferers, especially those with migraine headaches, clinicians should enquire into possible cocaine use. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  12. Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

    Science.gov (United States)

    Vilela, Luciano Rezende; Gomides, Lindisley Ferreira; David, Bruna Araújo; Antunes, Maísa Mota; Diniz, Ariane Barros; Moreira, Fabrício de Araújo; Menezes, Gustavo Batista

    2015-01-01

    Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD), protects against cocaine toxicity. URB597 (1.0 mg/kg) abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg) reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen) increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse. PMID:25999668

  13. Optogenetic Central Amygdala Stimulation Intensifies and Narrows Motivation for Cocaine.

    Science.gov (United States)

    Warlow, Shelley M; Robinson, Mike J F; Berridge, Kent C

    2017-08-30

    Addiction is often characterized by intense motivation for a drug, which may be narrowly focused at the expense of other rewards. Here, we examined the role of amygdala-related circuitry in the amplification and narrowing of motivation focus for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2) stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala (BLA) of female rats with one particular nose-poke porthole option for earning cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned identical cocaine but without ChR2 stimulation. Consequently, CeA rats quickly came to pursue their CeA ChR2-paired cocaine option intensely and exclusively, elevating cocaine intake while ignoring their alternative cocaine alone option. By comparison, BLA ChR2 pairing failed to enhance cocaine motivation. CeA rats also emitted consummatory bites toward their laser-paired porthole, suggesting that higher incentive salience made that cue more attractive. A separate progressive ratio test of incentive motivation confirmed that CeA ChR2 amplified rats' motivation, raising their breakpoint effort price for cocaine by 10-fold. However, CeA ChR2 laser on its own lacked any reinforcement value: laser by itself was never self-stimulated, not even by the same rats in which it amplified motivation for cocaine. Conversely, CeA inhibition by muscimol/baclofen microinjections prevented acquisition of cocaine self-administration and laser preference, whereas CeA inhibition by optogenetic halorhodopsin suppressed cocaine intake, indicating that CeA circuitry is needed for ordinary cocaine motivation. We conclude that CeA ChR2 excitation paired with a cocaine option specifically focuses and amplifies motivation to produce intense pursuit and consumption focused on that single target. SIGNIFICANCE STATEMENT In addiction, intense incentive motivation often becomes narrowly focused on a particular drug of abuse. Here we show that pairing central

  14. Cocaine-induced changes in NMDA receptor signaling

    Science.gov (United States)

    Ortinski, Pavel I.

    2014-01-01

    Addictive states are often thought to rely on lasting modification of signaling at relevant synapses. A long-standing theory posits that activity at N-methyl-D-aspartate receptors (NMDARs) is a critical component of long-term synaptic plasticity in many brain areas. Indeed, NMDAR signaling has been found to play a role in the etiology of addictive states, in particular following cocaine exposure. However, no consensus is apparent with respect to the specific effects of cocaine exposure on NMDARs. Part of the difficulty lies in the fact that NMDARs interact extensively with multiple membrane proteins and intracellular signaling cascades. This allows for highly heterogeneous patterns of NMDAR regulation by cocaine in distinct brain regions and at distinct synapses. The picture is further complicated by findings that cocaine effects on NMDARs are sensitive to the behavioral history of cocaine exposure, such as the mode of cocaine administration. This review provides a summary of evidence for cocaine-induced changes in NMDAR expression, cocaine-induced alterations in NMDAR function and cocaine effects on NMDAR control of intracellular signaling cascades. PMID:24445951

  15. Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

    Directory of Open Access Journals (Sweden)

    Luciano Rezende Vilela

    2015-01-01

    Full Text Available Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD, protects against cocaine toxicity. URB597 (1.0 mg/kg abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse.

  16. Neurotensin Agonist Attenuates Nicotine Potentiation to Cocaine Sensitization

    Directory of Open Access Journals (Sweden)

    Paul Fredrickson

    2014-01-01

    Full Text Available Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a “gateway drug”. Neurotensin (NT is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13 analog, blocks behavioral sensitization (an animal model for psychostimulant addiction to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine.

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

    Science.gov (United States)

    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.

  18. Post-Retrieval Extinction Attenuates Cocaine Memories

    OpenAIRE

    Sartor, Gregory C.; Aston-Jones, Gary

    2013-01-01

    Recent studies have shown that post-retrieval extinction training attenuates fear and reward-related memories in both humans and rodents. This noninvasive, behavioral approach has the potential to be used in clinical settings to treat maladaptive memories that underlie several psychiatric disorders, including drug addiction. However, few studies to date have used a post-retrieval extinction approach to attenuate addiction-related memories. In the current study, we attempted to disrupt cocaine...

  19. A Recombinant Humanized Anti-Cocaine Monoclonal Antibody Inhibits the Distribution of Cocaine to the Brain in Rats

    Science.gov (United States)

    Gooden, Felicia C. T.; Tabet, Michael R.; Ball, William J.

    2014-01-01

    The monoclonal antibody (mAb), h2E2, is a humanized version of the chimeric human/murine anti-cocaine mAb 2E2. The recombinant h2E2 protein was produced in vitro from a transfected mammalian cell line and retained high affinity (4 nM Kd) and specificity for cocaine over its inactive metabolites benzoylecgonine (BE) and ecgonine methyl ester. In rats, pharmacokinetic studies of h2E2 (120 mg/kg i.v.) showed a long terminal elimination half-life of 9.0 days and a low volume of distribution at steady state (Vdss) of 0.3 l/kg. Pretreatment with h2E2 produced a dramatic 8.8-fold increase in the area under the plasma cocaine concentration-time curve (AUC) and in brain a concomitant decrease of 68% of cocaine’s AUC following an i.v. injection of an equimolar cocaine dose. Sequestration of cocaine in plasma by h2E2, shown via reduction of cocaine’s Vdss, indicates potential clinical efficacy. Although the binding of cocaine to h2E2 in plasma should inhibit distribution and metabolism, the elimination of cocaine remained multicompartmental and was still rapidly eliminated from plasma despite the presence of h2E2. BE was the major cocaine metabolite, and brain BE concentrations were sixfold higher than in plasma, indicating that cocaine is normally metabolized in the brain. In the presence of h2E2, brain BE concentrations were decreased and plasma BE was increased, consistent with the observed h2E2-induced changes in cocaine disposition. The inhibition of cocaine distribution to the brain confirms the humanized mAb, h2E2, as a lead candidate for development as an immunotherapy for cocaine abuse. PMID:24733787

  20. Effects of phendimetrazine treatment on cocaine vs food choice and extended-access cocaine consumption in rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L; Blough, Bruce E; Fennell, Timothy R; Snyder, Rodney W; Negus, S Stevens

    2013-12-01

    There is currently no Food and Drug Administration-approved pharmacotherapy for cocaine addiction. Monoamine releasers such as d-amphetamine constitute one class of candidate medications, but clinical use and acceptance are hindered by their own high-abuse liability. Phendimetrazine (PDM) is a schedule III anorectic agent that functions as both a low-potency monoamine-uptake inhibitor and as a prodrug for the monoamine-releaser phenmetrazine (PM), and it may serve as a clinically available, effective, and safer alternative to d-amphetamine. This study determined efficacy of chronic PDM to reduce cocaine self-administration by rhesus monkeys (N=4) using a novel procedure that featured both daily assessments of cocaine vs food choice (to assess medication efficacy to reallocate behavior away from cocaine choice and toward choice of an alternative reinforcer) and 20 h/day cocaine access (to allow high-cocaine intake). Continuous 21-day treatment with ramping PDM doses (days 1-7: 0.32 mg/kg/h; days 8-21: 1.0 mg/kg/h) reduced cocaine choices, increased food choices, and nearly eliminated extended-access cocaine self-administration without affecting body weight. There was a trend for plasma PDM and PM levels to correlate with efficacy to decrease cocaine choice such that the monkey with the highest plasma PDM and PM levels also demonstrated the greatest reductions in cocaine choice. These results support further consideration of PDM as a candidate anti-cocaine addiction pharmacotherapy. Moreover, PDM may represent a novel pharmacotherapeutic approach for cocaine addiction because it may simultaneously function as both a monoamine-uptake inhibitor (via the parent drug PDM) and as a monoamine releaser (via the active metabolite PM).

  1. Pro-abstinence Discourses and the Definition of the Conservative Christian Identity in the Contemporary United States

    OpenAIRE

    Greslé-Favier, Claire

    2006-01-01

    This article argues that pro-abstinence discourses play a key role in the definition of the conservative Christian identity in contemporary United States. Using conservative Christian authors coming from various perspectives in the pro-abstinence movements I explain how they, in my view, use abstinence to reinforce and reassert concepts which play a crucial role in the definition of their community's identity.

  2. Cocaine induced pleural and pericardial effusion syndrome.

    Science.gov (United States)

    Alqalyoobi, Shehabaldin; Vaidya, Omkar; Abu Ghanimah, Al-Ma'Mon; Elkhanany, Ahmed; Gohar, Ashraf

    2015-01-01

    A 42-year-old African American female with chronic cocaine use for 20 years, presented with two-day history of exertional shortness of breath and pleuritic chest pain. She was admitted three years back with acute kidney injury and skin rashes. At that time, skin biopsy was consistent with leukocytoclastic vasculitis and renal biopsy revealed proliferative glomerulonephritis. She responded to oral prednisone and mycophenolate with complete recovery of her kidney functions. Skin rash was waxing and waning over the last two years. On the second admission, patient was found to have large pleural effusion on computerized tomography scan and pericardial effusion on echocardiogram as shown in the figures. Pleural fluid analysis was exudative. Her serology was negative for ANA (antineutrophilic antibody) and anti-dsDNA (double stranded DNA). Complements levels were normal. She had positive low titers of ANCA levels. The patient was started on a course of prednisone for 6 months. Her pleural and pericardial effusion resolved completely on follow-up imaging with computerized tomography scan and echocardiogram. This case is unique since the pericardial and pleural effusions developed without any other etiology in the setting of cocaine; hence, we describe this clinical syndrome as cocaine induced pleural and pericardial effusions syndrome (CIPP).

  3. Cocaine Induced Pleural and Pericardial Effusion Syndrome

    Directory of Open Access Journals (Sweden)

    Shehabaldin Alqalyoobi

    2015-01-01

    Full Text Available A 42-year-old African American female with chronic cocaine use for 20 years, presented with two-day history of exertional shortness of breath and pleuritic chest pain. She was admitted three years back with acute kidney injury and skin rashes. At that time, skin biopsy was consistent with leukocytoclastic vasculitis and renal biopsy revealed proliferative glomerulonephritis. She responded to oral prednisone and mycophenolate with complete recovery of her kidney functions. Skin rash was waxing and waning over the last two years. On the second admission, patient was found to have large pleural effusion on computerized tomography scan and pericardial effusion on echocardiogram as shown in the figures. Pleural fluid analysis was exudative. Her serology was negative for ANA (antineutrophilic antibody and anti-dsDNA (double stranded DNA. Complements levels were normal. She had positive low titers of ANCA levels. The patient was started on a course of prednisone for 6 months. Her pleural and pericardial effusion resolved completely on follow-up imaging with computerized tomography scan and echocardiogram. This case is unique since the pericardial and pleural effusions developed without any other etiology in the setting of cocaine; hence, we describe this clinical syndrome as cocaine induced pleural and pericardial effusions syndrome (CIPP.

  4. [Consequences of cocaine use among prostitutes].

    Science.gov (United States)

    Falcón, Carmen Meneses

    2007-01-01

    To describe the circumstances and consequences of cocaine use in the setting of prostitution. We performed a qualitative study with fieldwork in 6 Spanish cities. Semi-structured interviews were carried out to 60 persons aged between 18 and 50 years old involved in prostitution in different settings: street, flat and brothel. The main substances used in prostitution were alcohol and cocaine. Consumption was occasional and instrumental and helped to reduce psychological barriers or inhibition and increase tolerance to long hours of sex work with different clients, thus increasing earnings. Cocaine use was also associated with providing clients with company without having to perform sexual services. Among the consequences of drug use in prostitutes were unprotected sex and a higher risk of violence by clients. Prostitutes developed harm reduction strategies for drug use: dose reduction, simulated drug use, and selection of clients who were users. This study shows that there is connection between drug use and the provision of sexual services. Drug use can pose a health risk as consumption is associated with unprotected sex.

  5. Cocaine: from addiction to functional imaging; La cocaine: de la toxicomanie a l`imagerie fonctionnelle ombres et lumieres

    Energy Technology Data Exchange (ETDEWEB)

    Tamgac, F.; Baillet, G.; Moretti, J.L. [Hopital Avicenne, 93 - Bobigny (France); Tikofski, R. [Columbia Univ., New York, NY (United States)

    1997-12-31

    Cocaine is wrongly held as a benign recreative drug whereas it is a highly addictive substance with possible dreadful cardiac a neurologic complications. Cocaine abuse results in patchy cerebral hypoperfusion and hypo-metabolism, clearly demonstrated by PET and SPECT imaging. Improvement after drug withdrawal is still unclear. Cocaine binds with a very high affinity to the dopamine reuptake transporter. Labelled cocaine congeners can be used to assess dopaminergic pathways, especially nigrostriatal neurons that play a key role in movement control. {sup 123}I labelled beta-CIT can reproducibly be used to measure dopamine transporter density in the striatum, in one day. This approach seems very promising. (authors).

  6. Predictors of early versus late smoking abstinence within a 24-month disease management program.

    Science.gov (United States)

    Cox, Lisa Sanderson; Wick, Jo A; Nazir, Niaman; Cupertino, A Paula; Mussulman, Laura M; Ahluwalia, Jasjit S; Ellerbeck, Edward F

    2011-03-01

    Standard smoking cessation treatment studies have been limited to 6- to 12-month follow-up, and examination of predictors of abstinence has been restricted to this timeframe. The KanQuit study enrolled 750 rural smokers across all stages of readiness to stop smoking and provided pharmacotherapy management and/or disease management, including motivational interviewing (MI) counseling every 6 months over 2 years. This paper examines differences in predictors of abstinence following initial (6-month) and extended (24-month) intervention. Baseline variables were analyzed as potential predictors of self-reported smoking abstinence at Month 6 and at Month 24. Chi-square tests, 2-sample t tests, and multiple logistic regression analyses were used to identify predictors of abstinence among 592 participants who completed assessment at baseline and Months 6 and 24. Controlling for treatment group, the final regression models showed that male gender and lower baseline cigarettes per day predicted abstinence at both 6 and 24 months. While remaining significant, the relative advantage of being male decreased over time. Global motivation to stop smoking, controlled motivation, and self-efficacy predicted abstinence at 6 months but did not predict abstinence at Month 24. In contrast, stage of change was strongly predictive of 24-month smoking status. While the importance of some predictors of successful smoking cessation appeared to diminish over time, initial lack of interest in cessation and number of cigarettes per day strongly predicted continued smoking following a 2-year program.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Evidence on unusual way of cocaine smuggling: cocaine-polymethyl methacrylate (PMMA) solid solution--study of clandestine laboratory samples.

    Science.gov (United States)

    Gostic, T; Klemenc, S

    2007-07-04

    An abandoned clandestine laboratory was seized in Slovenia. All confiscated exhibits were analysed in a forensic laboratory, where the following analytical methods were applied: capillary gas chromatography coupled with mass spectrometry (GC-MS) combined also by solid-phase micro extraction (SPME) and pyrolysis (Py) technique, Fourier transform infrared spectrometry (FTIR) and scanning electron microscopy with energy dispersive X-ray detector (SEM-EDX). The most interesting analytical findings can be summarised as follows: at the crime scene some plastic pieces, which contained cocaine dissolved (as solid solution) in polymethyl methacrylate-plexiglass (PMMA), were found. The highest cocaine concentration measured in the plastic sample was about 15% by weight. Two larger lumps of material (12 and 3 kg) were composed mainly of PMMA and CaCO3 and contained only 0.4 and 0.5% of cocaine, respectively. As for the low cocaine concentration, we assume that those two lumps of material represent discarded waste product--residue after the isolation of cocaine from plastic. Higher quantities of pure solvents (41 l) and solvent mixtures (87 l) were seized. We identified three types of pure solvents (acetone, gasoline and benzine) and two different types of solvent mixtures (benzine/acetone and gasoline/acetone). The total seized volume (87 l) of solvent mixtures holds approximately 395 g of solid residue formed mainly of PMMA and cocaine. Obviously solvent mixtures were used for isolation of cocaine from the plastic. Small quantities of relatively pure cocaine base were identified on different objects. There were two cotton sheets, most probably used for filtration. One sheet had traces of cocaine base (76% purity) on the surface, while cocaine in hydrochloride form (96%) was identified on the other sheet. GC-MS analyses of micro traces isolated from analytical balances showed the presence of cocaine and some common adulterants: phenacetine, lidocaine and procaine. A cocaine

  9. A mathematical model of a recombinant humanized anti-cocaine monoclonal antibody's effects on cocaine pharmacokinetics in mice.

    Science.gov (United States)

    Wetzel, Hanna N; Zhang, Tongli; Norman, Andrew B

    2017-09-01

    A recombinant humanized anti-cocaine monoclonal antibody (mAb), h2E2, is at an advanced stage of pre-clinical development as an immunotherapy for cocaine abuse. It is hypothesized that h2E2 binds to and sequesters cocaine in the blood. A three-compartment model of the effects of h2E2 on cocaine's distribution was constructed. The model assumes that h2E2 binds to cocaine and that the h2E2-cocaine complex does not enter the brain but distributes between the central and peripheral compartments. Free cocaine is eliminated from both the central and peripheral compartments, and h2E2 and the h2E2-cocaine complex are eliminated from the central compartment only. This model was tested against a new dataset measuring cocaine concentrations in the brain and plasma over 1h in the presence and absence of h2E2. The mAb significantly increased plasma cocaine concentrations with a concomitant significant decrease in brain concentration. Plasma concentrations declined over the 1-hour sampling period in both groups. With a set of parameters within reasonable physiological ranges, the three-compartment model was able to qualitatively and quantitatively simulate the increased plasma concentration in the presence of the antibody and the decreased peak brain concentration in the presence of antibody. Importantly, the model explained the decline in plasma concentrations over time as distribution of the cocaine-h2E2 complex into a peripheral compartment. This model will facilitate the targeting of ideal mAb PK/PD properties thus accelerating the identification of lead candidate anti-drug mAbs. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Cocaine and Pavlovian fear conditioning: dose-effect analysis.

    Science.gov (United States)

    Wood, Suzanne C; Fay, Jonathan; Sage, Jennifer R; Anagnostaras, Stephan G

    2007-01-25

    Emerging evidence suggests that cocaine and other drugs of abuse can interfere with many aspects of cognitive functioning. The authors examined the effects of 0.1-15mg/kg of cocaine on Pavlovian contextual and cued fear conditioning in mice. As expected, pre-training cocaine dose-dependently produced hyperactivity and disrupted freezing. Surprisingly, when the mice were tested off-drug later, the group pre-treated with a moderate dose of cocaine (15mg/kg) displayed significantly less contextual and cued memory, compared to saline control animals. Conversely, mice pre-treated with a very low dose of cocaine (0.1mg/kg) showed significantly enhanced fear memory for both context and tone, compared to controls. These results were not due to cocaine's anesthetic effects, as shock reactivity was unaffected by cocaine. The data suggest that despite cocaine's reputation as a performance-enhancing and anxiogenic drug, this effect is seen only at very low doses, whereas a moderate dose disrupts hippocampus and amygdala-dependent fear conditioning.

  11. CRF1 receptor-deficiency increases cocaine reward.

    Science.gov (United States)

    Contarino, Angelo; Kitchener, Pierre; Vallée, Monique; Papaleo, Francesco; Piazza, Pier-Vincenzo

    2017-05-01

    Stimulant drugs produce reward but also activate stress-responsive systems. The corticotropin-releasing factor (CRF) and the related hypothalamus-pituitary-adrenal (HPA) axis stress-responsive systems are activated by stimulant drugs. However, their role in stimulant drug-induced reward remains poorly understood. Herein, we report that CRF1 receptor-deficient (CRF1-/-), but not wild-type, mice show conditioned place preference (CPP) responses to a relatively low cocaine dose (5 mg/kg, i.p.). Conversely, wild-type, but not CRF1-/-, mice display CPP responses to a relatively high cocaine dose (20 mg/kg, i.p.), indicating that CRF1 receptor-deficiency alters the rewarding effects of cocaine. Acute pharmacological antagonism of the CRF1 receptor by antalarmin also eliminates cocaine reward. Nevertheless, CRF1-/- mice display higher stereotypy responses to cocaine than wild-type mice. Despite the very low plasma corticosterone concentration, CRF1-/- mice show higher nuclear glucocorticoid receptor (GR) levels in the brain region of the hippocampus than wild-type mice. Full rescue of wild-type-like corticosterone and GR circadian rhythm and level in CRF1-/- mice by exogenous corticosterone does not affect CRF1 receptor-dependent cocaine reward but induces stereotypy responses to cocaine. These results indicate a critical role for the CRF1 receptor in cocaine reward, independently of the closely related HPA axis activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Levamisole-adulterated cocaine: what about in European countries?

    Science.gov (United States)

    Eiden, Céline; Diot, Caroline; Mathieu, Olivier; Mallaret, Michel; Peyrière, Hélène

    2014-01-01

    A wide variety of somatic complications is reported or expected among cocaine users because of the adulterant levamisole. Most of the reports come from North America. To update the data on levamisole-adulterated cocaine in European countries, we present here a synthesis of data on samples seized by the police with the detection of levamisole, the amount of levamisole in cocaine samples, European drug information reports, and clinical cases. Although there is a variation in the percentage of levamisole in cocaine samples between European countries, the trend is an increase of these percentages. As in North America, levamisole is becoming the most common cocaine adulterant. First European cases of complications secondary to the use of adulterated cocaine with levamisole were skin necrosis, vasculitis, and agranulocytosis. Levamisole postmortem data concerned two cases of complications leading to death, possibly related to levamisole or its metabolite (acute coronary syndrome, pulmonary hypertension). Even if it is difficult to have a global European view with comparable data, levamisole is present in European cocaine specimens and can lead to severe adverse health effects. However data on the prevalence of toxicity related to levamisole-adulterated cocaine abuse are missing.

  13. Adolescent cocaine exposure simplifies orbitofrontal cortical dendritic arbors

    Directory of Open Access Journals (Sweden)

    Lauren M DePoy

    2014-10-01

    Full Text Available Cocaine and amphetamine remodel dendritic spines within discrete cortico-limbic brain structures including the orbitofrontal cortex (oPFC. Whether dendrite structure is similarly affected, and whether pre-existing cellular characteristics influence behavioral vulnerabilities to drugs of abuse, remain unclear. Animal models provide an ideal venue to address these issues because neurobehavioral phenotypes can be defined both before, and following, drug exposure. We exposed mice to cocaine from postnatal days 31-35, corresponding to early adolescence, using a dosing protocol that causes impairments in an instrumental reversal task in adulthood. We then imaged and reconstructed excitatory neurons in deep-layer oPFC. Prior cocaine exposure shortened and simplified arbors, particularly in the basal region. Next, we imaged and reconstructed orbital neurons in a developmental-genetic model of cocaine vulnerability – the p190rhogap+/- mouse. p190RhoGAP is an actin cytoskeleton regulatory protein that stabilizes dendrites and dendritic spines, and p190rhogap+/- mice develop rapid and robust locomotor activation in response to cocaine. Despite this, oPFC dendritic arbors were intact in drug-naïve p190rhogap+/- mice. Together, these findings provide evidence that adolescent cocaine exposure has long-term effects on dendrite structure in the oPFC, and they suggest that cocaine-induced modifications in dendrite structure may contribute to the behavioral effects of cocaine more so than pre-existing structural abnormalities in this cell population.

  14. A role for BDNF in cocaine reward and relapse

    Science.gov (United States)

    Schoenbaum, Geoffrey; Stalnaker, Thomas A; Shaham, Yavin

    2009-01-01

    Brain-derived neurotrophic factor (BDNF) is important in regulating synaptic plasticity in the brain areas that process reward information. A new study reports that BDNF in the nucleus accumbens, a brain area critical for the rewarding effects of cocaine, promotes persistent cocaine-seeking behaviors and heightens relapse vulnerability. PMID:17657232

  15. The interplay between brain 5-hydroxytryptamine levels and cocaine addiction.

    NARCIS (Netherlands)

    Nonkes, L.J.P.; Bussel, I.P. van; Verheij, M.M.M.; Homberg, J.R.

    2011-01-01

    Cocaine addiction is a major health problem that affects millions of people. Cocaine acts by inhibiting dopamine, noradrenaline and serotonin [5-hydroxytryptamine(5-HT)] reuptake. The dopaminergic system is generally assumed to be involved in the reinforcing aspects of the drug, but the role of 5-HT

  16. Recurrent myocardial infarction in a young cocaine abuser | Stiha ...

    African Journals Online (AJOL)

    Cocaine increases the risk of cardiovascular diseases, including myocardial infarction. We herein describe a case of a 22-year-old man with a long history of cocaine abuse. He presented at our institution because of acute coronary syndrome with ST segment elevation. Emergency coronary angiography revealed ostial ...

  17. Sonographic and Endoscopic Findings in Cocaine-Induced Ischemic Colitis

    DEFF Research Database (Denmark)

    Leth, Thomas; Wilkens, Rune; Bonderup, Ole Kristian

    2015-01-01

    Cocaine-induced ischemic colitis is a recognized entity. The diagnosis is based on clinical and endoscopic findings. However, diagnostic imaging is helpful in the evaluation of abdominal symptoms and prior studies have suggested specific sonographic findings in ischemic colitis. We report...... sonographic and endoscopic images along with abdominal computed tomography in a case of cocaine-induced ischemic colitis....

  18. Marijuana and Cocaine Effect Expectancies and Drug Use Patterns.

    Science.gov (United States)

    Schafer, John; Brown, Sandra A.

    1991-01-01

    Content analyzed self-reports from 704 college students and used results to develop Marijuana Effect Expectancy Questionnaire and Cocaine Effect Expectancy Questionnaire. Identified six marijuana expectancies and five cocaine expectancies. Drug effect expectancies distinguished between patterns of nonuse and varying degrees of use of these two…

  19. [Rhabdomyolysis in acute cocaine poisoning. Presentation of 2 cases].

    LENUS (Irish Health Repository)

    Bernad, M

    1990-12-01

    Because the important increase of cocaine abuse and the frequent pathology associated, we present two cases of males who had a multiorganic failure cause by severe rabdomyolysis, renal failure with myoglobinuria and disseminated intravascular coagulation, after the cocaine consumption. In one case a pancreatitis associated was observed, this not being described before. Both cases are recovered.

  20. The use of labetalol in the management of cocaine crisis.

    Science.gov (United States)

    Gay, G R; Loper, K A

    1988-03-01

    We report a case of successful resuscitation and clinical management in a 31-year-old man who allegedly ingested 20 g of cocaine hydrochloride. The physiologic and pharmacologic mechanisms of cocaine toxicity are reviewed. The use of labetalol in resolving the cardiovascular crisis is specifically detailed.

  1. Preclinical Assessment of Lisdexamfetamine as an Agonist Medication Candidate for Cocaine Addiction: Effects in Rhesus Monkeys Trained to Discriminate Cocaine or to Self-Administer Cocaine in a Cocaine Versus Food Choice Procedure.

    Science.gov (United States)

    Banks, Matthew L; Hutsell, Blake A; Blough, Bruce E; Poklis, Justin L; Negus, S Stevens

    2015-01-24

    Chronic amphetamine treatment decreases cocaine consumption in preclinical and human laboratory studies and in clinical trials. Lisdexamfetamine is an amphetamine prodrug in which L-lysine is conjugated to the terminal nitrogen of d-amphetamine. Prodrugs may be advantageous relative to their active metabolites due to slower onsets and longer durations of action; however, lisdexamfetamine treatment's efficacy in decreasing cocaine consumption is unknown. This study compared lisdexamfetamine and d-amphetamine effects in rhesus monkeys using two behavioral procedures: (1) a cocaine discrimination procedure (training dose = 0.32mg/kg cocaine, i.m.); and (2) a cocaine-versus-food choice self-administration procedure. In the cocaine-discrimination procedure, lisdexamfetamine (0.32-3.2mg/kg, i.m.) substituted for cocaine with lower potency, slower onset, and longer duration of action than d-amphetamine (0.032-0.32mg/kg, i.m.). Consistent with the function of lisdexamfetamine as an inactive prodrug for amphetamine, the time course of lisdexamfetamine effects was related to d-amphetamine plasma levels by a counter-clockwise hysteresis loop. In the choice procedure, cocaine (0-0.1mg/kg/injection, i.v.) and food (1g banana-flavored pellets) were concurrently available, and cocaine maintained a dose-dependent increase in cocaine choice under baseline conditions. Treatment for 7 consecutive days with lisdexamfetamine (0.32-3.2mg/kg/day, i.m.) or d-amphetamine (0.032-0.1mg/kg/h, i.v.) produced similar dose-dependent rightward shifts in cocaine dose-effect curves and decreases in preference for 0.032mg/kg/injection cocaine. Lisdexamfetamine has a slower onset and longer duration of action than amphetamine but retains amphetamine's efficacy to reduce the choice of cocaine in rhesus monkeys. These results support further consideration of lisdexamfetamine as an agonist-based medication candidate for cocaine addiction. © The Author 2015. Published by Oxford University Press on

  2. Effects of 21-day d-amphetamine and risperidone treatment on cocaine vs food choice and extended-access cocaine intake in male rhesus monkeys.

    Science.gov (United States)

    Hutsell, Blake A; Negus, S Stevens; Banks, Matthew L

    2016-11-01

    Clinical trial data suggest amphetamine treatment is most efficacious in moderate to high frequency cocaine users. However, preclinical studies have examined amphetamine treatment effects under relatively limited cocaine access conditions with low to moderate cocaine intakes. This study determined d-amphetamine treatment effects on cocaine self-administration in rhesus monkeys under cocaine access conditions allowing for high daily cocaine intake. For comparison and as a negative control, treatment effects with the antipsychotic risperidone were also examined. Continuous 21-day treatments with ramping doses of d-amphetamine (days 1-7: 0.032mg/kg/h; days 8-21: 0.1mg/kg/h, i.v.) or risperidone (days 1-7: 0.001mg/kg/h; days 8-14: 0.0032mg/kg/h; days 15-21: 0.0056mg/kg/h, i.v.) were administered to rhesus monkeys (n=4) with daily access to two types of cocaine self-administration sessions: (1) a 2-h 'choice' session with concurrent availability of 1-g food pellets and intravenous cocaine injections (0-0.1mg/kg per injection) and (2) a 20-h 'extended-access' session with 0.1mg/kg per injection cocaine availability. Total daily cocaine intake increased >6-fold during extended cocaine access. d-Amphetamine significantly decreased total cocaine intake, but not cocaine vs food choice. In contrast, risperidone did not significantly alter either total cocaine intake or cocaine vs. food choice. These results confirm and extend previous results supporting treatment effectiveness for monoamine releasers, but not dopamine antagonists, to reduce cocaine self-administration. Moreover, these results suggest amphetamine treatment efficacy to decrease preclinical cocaine vs. food choice may depend upon cocaine access conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Clozapine protection against gestational cocaine-induced neurochemical abnormalities.

    Science.gov (United States)

    Yablonsky-Alter, Elena; Gashi, Eleonora; Lidsky, Theodore I; Wang, Hoau-Yan; Banerjee, Shailesh P

    2005-01-01

    Clozapine was found to be effective in attenuating cocaine-induced neurochemical effects. We investigate whether clozapine influences in utero cocaine exposure-induced changes in striatal dopamine levels and cortical N-methyl-D-aspartate (NMDA) receptor density in mouse and rat brains. Pregnant mice or rats were injected with cocaine (5 or 10 mg/kg intraperitoneally) or saline every 24 h throughout gestation and continued for 6 weeks following the delivery. Striatal dopamine levels measured by high-pressure liquid chromatography were found to decrease 24 to 33% in gestational cocaine exposed between the ages of 3 to 15 days, but not in 42-day-old pups. The cortical NMDA receptor densities assessed either in the presence of 100 microM glutamate or 30 microM glycine were significantly increased in 15-day-old gestational cocaine-exposed rats. Simultaneous daily administration of 3 mg/kg clozapine with 5 mg/kg cocaine to pregnant mice protected against the decrease in striatal dopamine levels or an increase in the concentration of NMDA receptor measured in the presence of 100 microM glutamate in 15-day-old pups. Clozapine did not affect striatal dopamine levels by itself or when coadministered with cocaine in 42-day-old pups. The results show gestational cocaine may induce neurochemical abnormalities in brain exhibited as an increased glutamate NMDA receptor density together with a decreased striatal dopamine level. These effects of gestational cocaine exposure may be prevented by simultaneous administration of clozapine. Thus clozapine, which is a partial agonist at the NMDA receptor, may be of value in protecting against gestational cocaine-induced adverse effects in the brain.

  4. Enhanced regional brain metabolic responses to benzodiazepines in cocaine abusers

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.J.; Fowler, J.S. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1997-05-01

    While dopamine (DA) appears to be crucial for cocaine reinforcement, its involvement in cocaine addiction is much less clear. Using PET we have shown persistent reductions in striatal DA D2 receptors (which arc predominantly located on GABA cells) in cocaine abusers. This finding coupled to GABA`s role as an effector for DA led us to investigate if there were GABAergic abnormalities in cocaine abusers. In this study we measured regional brain metabolic responses to lorazepam, to indirectly assess GABA function (benzodiazepines facilitate GABAergic neurotransmission). Methods: The experimental subjects consisted of 12 active cocaine abusers and 32 age matched controls. Each subject underwent two PET FDG scans obtained within 1 week of each other. The first FDG scan was obtained after administration of placebo (3 cc of saline solution) given 40-50 minutes prior to FDG; and the second after administration of lorazepam (30 {mu}g/kg) given 40-50 minutes prior to FDG. The subjects were blind to the drugs received. Results: Lorazepam-induced sleepiness was significantly greater in abusers than in controls (p<0.001). Lorazepam-induced decreases in brain glucose metabolism were significantly larger in cocaine abusers than in controls. Whereas in controls whole brain metabolism decreased 13{+-}7 %, in cocaine abusers it decreased 21{+-}13 % (p < 0.05). Lorazepam-induced decrements in regional metabolism were significantly larger in striatum (p < 0.0 1), thalamus (p < 0.01) and cerebellum (p < 0.005) of cocaine abusers than of controls (ANOVA diagnosis by condition (placebo versus lorazepam) interaction effect). The only brain region for which the absolute metabolic changes-induced by lorazepam in cocaine abusers were equivalent to those in controls was the orbitofrontal cortex. These results document an accentuated sensitivity to benzodiazepines in cocaine abusers which is compatible with disrupted GABAergic function in these patients.

  5. The romanticization of abstinence: Fan response to sexual restraint in the Twilight series

    OpenAIRE

    Jennifer Stevens Aubrey, Elizabeth Behm-Morawitz, and Melissa A. Click

    2010-01-01

    Meyer's Twilight series has been criticized for its regressive gender representations. To understand its continuing appeal, we problematize the messages of abstinence and romance in the series, and contextualize fans' response with a discussion of postfeminist culture.

  6. The romanticization of abstinence: Fan response to sexual restraint in the Twilight series

    Directory of Open Access Journals (Sweden)

    Jennifer Stevens Aubrey, Elizabeth Behm-Morawitz, and Melissa A. Click

    2010-09-01

    Full Text Available Meyer's Twilight series has been criticized for its regressive gender representations. To understand its continuing appeal, we problematize the messages of abstinence and romance in the series, and contextualize fans' response with a discussion of postfeminist culture.

  7. Effect of abstinence challenge on brain function and cognition in smokers differs by COMT genotype

    National Research Council Canada - National Science Library

    Loughead, J; Wileyto, E P; Valdez, J N; Sanborn, P; Tang, K; Strasser, A A; Ruparel, K; Ray, R; Gur, R C; Lerman, C

    .... We tested the hypothesis that the val allele is a risk factor for altered brain function and cognition during nicotine abstinence as compared with the normal smoking state. Chronic smokers (n=33...

  8. Compulsory abstinence: integrated treatment measure of schizophrenia combined with comorbid substance abuse

    National Research Council Canada - National Science Library

    Burger, T J; Goudriaan, A E; de Haan, L; de Koning, M B

    2016-01-01

    .... For the patient long-term compulsory abstinence can be seen as an extremely serious measure. Nevertheless, the measure can be justified both ethically and juridically as part of integrated treatment for psychosis and substance use disorder...

  9. The State of Sex Education in North Carolina: Is Abstinence-Only Education Working?

    Directory of Open Access Journals (Sweden)

    Rebecca Bach

    2006-04-01

    Full Text Available Teenage pregnancy rates are falling in North Carolina. They are falling faster in counties where comprehensive sex education is allowed by law compared to those counties and cities where abstinence-only education is permitted.

  10. Evidence that episodic memory impairment during tobacco abstinence is independent of attentional mechanisms.

    Science.gov (United States)

    Merritt, Paul S; Cobb, Adam R; Moissinac, Luke; Hirshman, Elliot

    2010-01-01

    Previous studies have demonstrated reductions in episodic memory during nicotine withdrawal. However, these studies have been unable to dissociate memory reductions from losses in attention associated with tobacco abstinence. In the present study, the authors sought to determine whether episodic memory reduction is a primary effect of nicotine withdrawal during tobacco abstinence. Heavy smokers were tested when smoking normally and following 24 hrs of abstinence. Participants were tested with a recognition memory task in which items were studied under full and divided attention conditions. Forward digit span and backward digit span were also included as control measures. Withdrawal was associated with a reduction in memory performance that was independent of attention at encoding. The authors conclude that impairment of episodic memory is a primary effect of nicotine withdrawal during tobacco abstinence. Further research is required to determine if this is associated with continued use of tobacco and cessation failures.

  11. Feeding Modalities and the Onset of the Neonatal Abstinence Syndrome

    Directory of Open Access Journals (Sweden)

    Anthony eLiu

    2015-02-01

    Full Text Available AbstractBreast milk has been reported to ameliorate the severity and outcome of neonatal abstinence syndrome (NAS. The mechanism of this beneficial effect of breast milk on NAS remains unclear, as the negligible amount of methadone transmitted via breast milk is unlikely to have an impact on NAS. The aim of this study was to compare the impact of different feeding modalities on the onset of NAS.A retrospective medical record review was conducted on one hundred and ninety-four methadone maintained mother/infant dyads. Infants were categorized on the first 2 days of life as predominantly breastfed, fed expressed human breast milk or formula fed. The feeding categories were then analyzed using the onset of NAS as the outcome measure. After adjusting for confounders, there was no significant effect of the modality of feeding on the rates of NAS requiring treatment (p=0.11. Breastfeeding significantly delayed the onset of NAS (p=0.04The act of breastfeeding in the first two days of life had no effect on whether an infant required treatment for NAS when compared to those fed EBM or formula. This only suggests that the advantages of breastfeeding on NAS cannot be substantiated in a small cohort and should not discourage breastfeeding.

  12. Breastfeeding rates among mothers of infants with neonatal abstinence syndrome.

    Science.gov (United States)

    Wachman, Elisha M; Byun, John; Philipp, Barbara L

    2010-08-01

    Woman who struggle with drug addiction during pregnancy are perhaps the most vulnerable of new mothers. The opioid substitution medications methadone and buprenorphine are both compatible with breastfeeding. The objective of this study is to determine breastfeeding rates among opioid-dependent women giving birth in a Baby-Friendly Hospital. We performed a retrospective chart review of all infants born at Boston Medical Center (Boston, MA) between July 2003 and January 2009 with a diagnosis of neonatal abstinence syndrome. Feeding information was obtained, as well as baseline medical information about the mother-infant pairs. Breastfeeding eligibility was determined by a negative urine toxicology screen on admission, no illicit drug use in the third trimester, and a negative human immunodeficiency virus status. Two hundred seventy-six mother-infant pairs were identified. Forty percent of the mothers carried one or more psychiatric diagnoses; 24% were taking two or more psychiatric medications. Sixty-eight percent of the mothers were eligible to breastfeed; of those, 24% breastfed to some extent during their infant's hospitalization. Sixty-percent of those who initiated stopped breastfeeding after an average of 5.88 days (SD 6.51). Breastfeeding rates among opioid-dependent women were low, with three-quarters of those eligible electing not to breastfeed. Of the minority of women who did choose to breastfeed, more than half stopped within 1 week.

  13. Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum

    Science.gov (United States)

    Palomino, Ana; Pavón, Francisco-Javier; Blanco-Calvo, Eduardo; Serrano, Antonia; Arrabal, Sergio; Rivera, Patricia; Alén, Francisco; Vargas, Antonio; Bilbao, Ainhoa; Rubio, Leticia; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2014-01-01

    glutamate systems. Repeated cocaine results in normalization of glutamate receptor expression, although sustained changes in eCB is observed. We suggest that cocaine-induced alterations to cerebellar eCB should be considered when analyzing the adaptations imposed by psychostimulants that lead to addiction. PMID:24634647

  14. Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum.

    Science.gov (United States)

    Palomino, Ana; Pavón, Francisco-Javier; Blanco-Calvo, Eduardo; Serrano, Antonia; Arrabal, Sergio; Rivera, Patricia; Alén, Francisco; Vargas, Antonio; Bilbao, Ainhoa; Rubio, Leticia; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2014-01-01

    glutamate systems. Repeated cocaine results in normalization of glutamate receptor expression, although sustained changes in eCB is observed. We suggest that cocaine-induced alterations to cerebellar eCB should be considered when analyzing the adaptations imposed by psychostimulants that lead to addiction.

  15. Effect of preoperative abstinence on poor postoperative outcome in alcohol misusers: randomised controlled trial

    DEFF Research Database (Denmark)

    Tonnesen, H; Rosenberg, J; Nielsen, Hans Jørgen

    1999-01-01

    OBJECTIVE: To evaluate the influence of preoperative abstinence on postoperative outcome in alcohol misusers with no symptoms who were drinking the equivalent of at least 60 g ethanol/day. DESIGN: Randomised controlled trial. Setting: Copenhagen, Denmark. SUBJECTS: 42 alcoholic patients without...... often in the intervention group. Surgical stress responses were lower in the intervention group (P LT / =0.05). CONCLUSIONS: One month of preoperative abstinence reduces postoperative morbidity in alcohol abusers. The mechanism is probably reduced preclinical organ dysfunction and reduction...

  16. A Thermally Stable Form of Bacterial Cocaine Esterase: A Potential Therapeutic Agent for Treatment of Cocaine Abuse

    Energy Technology Data Exchange (ETDEWEB)

    Brim, Remy L.; Nance, Mark R.; Youngstrom, Daniel W.; Narasimhan, Diwahar; Zhan, Chang-Guo; Tesmer, John J.G.; Sunahara, Roger K.; Woods, James H. (Michigan); (Michigan-Med); (Kentucky)

    2010-09-03

    Rhodococcal cocaine esterase (CocE) is an attractive potential treatment for both cocaine overdose and cocaine addiction. CocE directly degrades cocaine into inactive products, whereas traditional small-molecule approaches require blockade of the inhibitory action of cocaine on a diverse array of monoamine transporters and ion channels. The usefulness of wild-type (wt) cocaine esterase is hampered by its inactivation at 37 C. Herein, we characterize the most thermostable form of this enzyme to date, CocE-L169K/G173Q. In vitro kinetic analyses reveal that CocE-L169K/G173Q displays a half-life of 2.9 days at 37 C, which represents a 340-fold improvement over wt and is 15-fold greater than previously reported mutants. Crystallographic analyses of CocE-L169K/G173Q, determined at 1.6-{angstrom} resolution, suggest that stabilization involves enhanced domain-domain interactions involving van der Waals interactions and hydrogen bonding. In vivo rodent studies reveal that intravenous pretreatment with CocE-L169K/G173Q in mice provides protection from cocaine-induced lethality for longer time periods before cocaine administration than wt CocE. Furthermore, intravenous administration (pretreatment) of CocE-L169K/G173Q prevents self-administration of cocaine in a time-dependent manner. Termination of the in vivo effects of CoCE seems to be dependent on, but not proportional to, its clearance from plasma as its half-life is approximately 2.3 h and similar to that of wt CocE (2.2 h). Taken together these data suggest that CocE-L169K/G173Q possesses many of the properties of a biological therapeutic for treating cocaine abuse but requires additional development to improve its serum half-life.

  17. Modafinil Reinstates a Cocaine Conditioned Place Preference Following Extinction in Rats

    OpenAIRE

    Bernardi, Rick E.; Lewis, Jason R.; Lattal, K. Matthew; Berger, S. Paul

    2009-01-01

    The current study examined whether modafinil would reinstate an extinguished cocaine conditioned place preference (CPP). Following extinction of a cocaine CPP, rats were administered modafinil (128mg/kg), cocaine (5mg/kg) or vehicle and given a 60-min reinstatement test. While the effect of cocaine was transient, modafinil robustly reinstated a cocaine CPP following extinction, suggesting that modafinil may induce relapse or increase the vulnerability of addicts to the reinforcing effects of ...

  18. SOCIO-PSYCHOLOGICAL CHARACTERISTICS OF WOMEN ABSTINENTS AND VOTERS IN BOSNIA AND HERZEGOVINA

    Directory of Open Access Journals (Sweden)

    Srdjan Puhalo

    2009-09-01

    Full Text Available Our research aims to find out if there is a difference between women voters and abstinents in Bosnia and Herzegovina, considering certain socio-psychological characteristics. For the purpose of this research we used Likert scales to measure: tolerance to other ideas, nationalism, ethical superiority, attitude towards leader, conformism, liberalism/conservativism and locus of control. This research was con-ducted in May 2007 on the sample of 547 women voters and 214 women abstinents. Results show that socio-demographic characteristics differ potential women voters from women abstinents. Women who are more active (educated, employed or mem-bers of some political party in their everyday life are more likely to go to the electi-ons and vote. Discriminative analysis showed that women voters and abstinents significantly differed at four of total seven variables. The difference between women voters and abstinents is in ethical superiority, acceptance of nationalism, tolerance to other ideas and attitude towards leader. Therefore it seems that women abstinents have greater democratic potential than women voters.

  19. Effects of receiving additional off-site services on abstinence from illicit drug use among men on methadone: a longitudinal study.

    Science.gov (United States)

    Wu, Elwin; El-Bassel, Nabila; Gilbert, Louisa; Chang, Mingway; Sanders, Glorice

    2010-11-01

    Health and psychosocial service needs that may be co-morbid with opioid addiction may impede the success of drug treatment among patients attending methadone maintenance treatment programs (MMTPs). This longitudinal panel study investigates whether receipt of services from one or more helping professionals outside of the MMTP confers a benefit for drug treatment outcomes among a random sample of male MMTP patients (N=356). Each participant was interviewed 3 times, with 6 months between each interview. Since this observational study did not employ random assignment, propensity score matching was employed to strengthen causal validity of effect estimates. Results support hypotheses that receiving additional off-site services has significant beneficial effects in increasing the likelihood of abstaining from cocaine, heroin, and any illicit drug use over both the ensuing 6- and 12-month time periods. These findings indicate that receipt of additional medical and/or psychosocial services enhances the efficacy of methadone treatment in increasing abstinence from illicit drug use. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  20. Procedural and declarative memory task performance, and the memory consolidation function of sleep, in recent and abstinent ecstasy/MDMA users.

    Science.gov (United States)

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

    2011-04-01

    Ecstasy/MDMA use has been associated with various memory deficits. This study assessed declarative and procedural memory in ecstasy/MDMA users. Participants were tested in two sessions, 24 h apart, so that the memory consolidation function of sleep on both types of memory could also be assessed. Groups were: drug-naive controls (n = 24); recent ecstasy/MDMA users, who had taken ecstasy/MDMA 2-3 days before the first testing session (n = 25), and abstinent users, who had not taken ecstasy/MDMA for at least 8 days before testing (n = 17). Procedural memory did not differ between groups, but greater lifetime consumption of ecstasy was associated with poorer procedural memory. Recent ecstasy/MDMA users who had taken other drugs (mainly cannabis) 48-24 h before testing exhibited poorer declarative memory than controls, but recent users who had not taken other drugs in this 48-24-h period did not differ from controls. Greater lifetime consumption of ecstasy, and of cocaine, were associated with greater deficits in declarative memory. These results suggest that procedural, as well as declarative, memory deficits are associated with the extent of past ecstasy use. However, ecstasy/MDMA did not affect the memory consolidation function of sleep for either the declarative or the procedural memory task.

  1. Cocaine use in pregnancy: perinatal morbidity and mortality.

    Science.gov (United States)

    Chasnoff, I J; Burns, K A; Burns, W J

    1987-01-01

    With the increasing use of cocaine in the United States, there has been growing concern regarding its effects on the fetuses and neonates of pregnant cocaine abusers. Fifty-two cocaine-using women enrolled in a comprehensive perinatal addiction program were evaluated and compared with 73 women who had used narcotics in the past and were maintained on methadone during pregnancy. The groups were similar in maternal age, socioeconomic status, number of pregnancies and cigarette, marijuana and alcohol use. The cocaine-using women had a significantly higher rate of premature labor, precipitous labor, abruptio placentae, fetal monitor abnormality and fetal meconium staining than the women in the methadone group. Neonatal gestational age, birth weight, length and head circumference were not affected by cocaine use compared to methadone use. However, the Brazelton Neonatal Behavioral Assessment Scale revealed that infants exposed to cocaine had significant depression of organizational response to environmental stimuli (state organization) when compared to methadone-exposed infants. In another aspect of the study, an increased rate of SIDS (15%) was found for 66 cocaine-exposed infants as compared to a 4% rate of SIDS in 50 methadone-exposed infants.

  2. Structural analysis of thermostabilizing mutations of cocaine esterase

    Energy Technology Data Exchange (ETDEWEB)

    Narasimhan, Diwahar; Nance, Mark R.; Gao, Daquan; Ko, Mei-Chuan; Macdonald, Joanne; Tamburi, Patricia; Yoon, Dan; Landry, Donald M.; Woods, James H.; Zhan, Chang-Guo; Tesmer, John J.G.; Sunahara, Roger K. (Michigan); (Columbia); (Kentucky)

    2010-09-03

    Cocaine is considered to be the most addictive of all substances of abuse and mediates its effects by inhibiting monoamine transporters, primarily the dopamine transporters. There are currently no small molecules that can be used to combat its toxic and addictive properties, in part because of the difficulty of developing compounds that inhibit cocaine binding without having intrinsic effects on dopamine transport. Most of the effective cocaine inhibitors also display addictive properties. We have recently reported the use of cocaine esterase (CocE) to accelerate the removal of systemic cocaine and to prevent cocaine-induced lethality. However, wild-type CocE is relatively unstable at physiological temperatures ({tau}{sub 1/2} {approx} 13 min at 37 C), presenting challenges for its development as a viable therapeutic agent. We applied computational approaches to predict mutations to stabilize CocE and showed that several of these have increased stability both in vitro and in vivo, with the most efficacious mutant (T172R/G173Q) extending half-life up to 370 min. Here we present novel X-ray crystallographic data on these mutants that provide a plausible model for the observed enhanced stability. We also more extensively characterize the previously reported variants and report on a new stabilizing mutant, L169K. The improved stability of these engineered CocE enzymes will have a profound influence on the use of this protein to combat cocaine-induced toxicity and addiction in humans.

  3. Electroacupuncture Reduces Cocaine-Induced Seizures and Mortality in Mice

    Directory of Open Access Journals (Sweden)

    Yi-Hung Chen

    2013-01-01

    Full Text Available The aims of this study were to characterize the protective profile of electroacupuncture (EA on cocaine-induced seizures and mortality in mice. Mice were treated with EA (2 Hz, 50 Hz, and 100 Hz, or they underwent needle insertion without anesthesia at the Dazhui (GV14 and Baihui (GV20 acupoints before cocaine administration. EA at 50 Hz applied to GV14 and GV20 significantly reduced the seizure severity induced by a single dose of cocaine (75 mg/kg; i.p.. Furthermore, needle insertion into GV14 and GV20 and EA at 2 Hz and 50 Hz at both acupoints significantly reduced the mortality rate induced by a single lethal dose of cocaine (125 mg/kg; i.p.. In the sham control group, EA at 50 Hz applied to bilateral Tianzong (SI11 acupoints had no protective effects against cocaine. In addition, EA at 50 Hz applied to GV14 and GV20 failed to reduce the incidence of seizures and mortality induced by the local anesthetic procaine. In an immunohistochemistry study, EA (50 Hz pretreatment at GV14 and GV20 decreased cocaine (75 mg/kg; i.p.-induced c-Fos expression in the paraventricular thalamus. While the dopamine D3 receptor antagonist, SB-277011-A (30 mg/kg; s.c, did not by itself affect cocaine-induced seizure severity, it prevented the effects of EA on cocaine-induced seizures. These results suggest that EA alleviates cocaine-induced seizures and mortality and that the dopamine D3 receptor is involved, at least in part, in the anticonvulsant effects of EA in mice.

  4. Cocaine and the AP-1 transcription factor complex.

    Science.gov (United States)

    Hope, B T

    1998-05-30

    Cocaine addition in humans develops gradually with repeated administrations and persists long after cocaine has cleared the body. The mechanisms underlying this persistent form of neuroplasticity are not understood and can involve both structural and biochemical mechanisms. The long time course for cocaine addiction in humans and for development of cocaine self-administration in animal models suggest the involvement of alterations in gene expression leading to altered signaling in the brain. In the striatum (Str) and nucleus accumbens (NAc) of rats. Pretreatment with repeated cocaine administrations downregulates the induction of various immediate early genes (IEGs) by a subsequent acute challenge with cocaine. Some of these downregulated IEGs encode Fos-related components of the activator protein-1 (AP-1) complex, which is likely re regulate a number of genes important for neuronal function. Interestingly, repeated cocaine administration induces novel delta FosB-related proteins (called chronic Fos-related antigens (Fras)) in the NAc and Str that replace the downregulated isoforms of Fos. Unlike the acutely induced, short-lasting isoforms of Fos and FosB, the chronic Fras persist long after the last cocaine administration. The known form of delta FosB per se lacks the domain required to activate transcription. If the chronic Fras are similar in structure to delta FosB, then the induction of chronic Fras likely leads to a blockade of AP-1-dependent transcription resulting in altered gene expression. We presently purifying the chronic Fras to obtain amino acid sequence in order to directly examine our hypothesis about the effects of repeated cocaine administration on AP-1 dependent transcription and gene expression in the brain

  5. Acute coronary syndrome after levamisole-adultered cocaine abuse.

    Science.gov (United States)

    Michaud, Katarzyna; Grabherr, Silke; Shiferaw, Kebede; Doenz, Franceso; Augsburger, Marc; Mangin, Patrice

    2014-01-01

    Cocaine is a well known trigger of acute coronary syndromes. Over the last 10 years levamisole, a veterinary anthelminthic drug has been increasingly used as an adulterant of cocaine. Levamisole was used to treat pediatric nephritic syndrome and rheumatoid arthritis before being withdrawn from the market due to its significant toxicity, i.e. hematological complications and vasculitis. The major complications of levamisole-adultered cocaine reported up to now are hematological and dermatological. The case reported here is of a 25 year old man with a history of cocaine abuse who died at home after complaining of retrosternal pain. Postmortem CT-angiography, autopsy, and chemical and toxicological analyses were performed. An eroded coronary artery plaque was found at the proximal segment of the left anterior descending coronary artery. Two myocardial infarct scars were present in the left ventricle. Microscopic examination of the coronary artery revealed infiltration of eosinophils into the adventitia and intima. Toxicological examination confirmed the presence of cocaine and its metabolites in the peripheral blood, and of levamisole in the urine and pericardial fluid. Eosinophilic inflammatory coronary artery pathologies have been clinically linked to coronary dissection, hypersensitivity coronary syndrome and vasospastic allergic angina. The coronary pathology in the presented case could be a complication of levamisole-adultered cocaine use, in which an allergic or immune-mediated mechanism might play a role. The rise in cocaine addiction worldwide and the increase of levamisole adulterated cocaine highlights the importance of updating our knowledge of the effects of adultered cocaine abuse. Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  6. [Volumes of services supplied by Italian Stop-Smoking Services and their characteristics predictive of abstinence].

    Science.gov (United States)

    Gorini, Giuseppe; Ameglio, Matteo; Martini, Andrea; Bosi, Sandra; Laezza, Maurizio

    2013-01-01

    to evaluate differences in terms of smokers' attendance to National Health System (NHS) Stop-Smoking Services with a prevalent individual approach (SSSi), and to those with a prevalent group approach (SSSg). To identify predictive characteristics of success, in terms of quit rates at the end of treatment (QR0) and after 6 months (QR1), according to SSS type (SSSi/SSSg), treatment (individual/ group counseling with/without pharmacologic treatments), 5 SSS scores: type of structure (S), number and hours per week of SSS health professionals (P), SSS involvement in local tobacco control networks (N), and type of smokers' assessment (A); and 3 principal components of SSS characteristics. survey to 19 SSSs, and survey to smokers attending these SSSs, with a six month follow-up. 1,276 smokers attending 19 SSSs (664 at 7 SSSi; 612 at 12 SSSg) in 9 months in the period 2008-2010. smokers' attendance to scheduled sessions; QR0; QR1. even though SSSi treated more smokers per month (12 vs. 8 in SSSg), SSSi scheduled fewer treatment sessions (7 vs. 9 sessions) in a wider treatment period (3 months vs. 2 in SSSg). SSSg recorded lower P and higher A scores. Four out of 5 smokers attending SSSg and 2/5 of smokers attending SSSi completed treatment protocols. Considering all smokers, QR1 in both types of SSS were around 36%. Smokers treated with pharmacotherapy, those more motivated and with high self-efficacy, and those non-living together with smokers were more likely to recorded higher QR1. the most relevant interventions in order to increase the number of smokers treated at SSS and to improve cessation rates among them were: for SSSi, increasing completion to treatment protocol; for SSSg, improving the P scores to increase the number of treated smokers; for all SSS, increasing the use of pharmacotherapy in combination with individual/group counseling to sustain abstinence.

  7. Abstinence-plus programs for HIV infection prevention in high-income countries.

    Science.gov (United States)

    Underhill, K; Montgomery, P; Operario, D

    2008-01-23

    Abstinence-plus interventions promote sexual abstinence as the best means of preventing acquisition of HIV, but also encourage safer-sex strategies (eg condom use) for sexually active participants. To assess the effects of abstinence-plus programs for HIV prevention in high-income countries. We searched 30 electronic databases (eg CENTRAL, PubMed, EMBASE, AIDSLINE, PsycINFO) ending February 2007. Cross-referencing, hand-searching, and contacting experts yielded additional citations. We included randomized and quasi-randomized controlled trials evaluating abstinence-plus interventions in high-income countries (as defined by the World Bank). Interventions were any efforts that encouraged sexual abstinence as the best means of HIV prevention, but also promoted safer sex. Results were self-reported biological outcomes, behavioral outcomes, and HIV knowledge. Three reviewers independently appraised 20070 citations and 325 full-text papers for inclusion and methodological quality; 39 evaluations were included. Due to heterogeneity and data unavailability, we presented the results of individual studies instead of a meta-analysis. Studies enrolled 37724 North American youth; participants were ethnically diverse. Programs took place in schools (10), community facilities (24), both schools and community facilities (2), healthcare facilities (2), and family homes (1). Median final follow-up occurred 12 months after baseline. Results showed no evidence that abstinence-plus programs can affect self-reported sexually transmitted infection (STI) incidence, and limited evidence that programs can reduce self-reported pregnancy incidence. Results for behavioral outcomes were promising; 23 of 39 evaluations found a significantly protective intervention effect for at least one behavioral outcome. Consistently favorable program effects were found for HIV knowledge.No adverse effects were observed. Several evaluations found that one version of an abstinence-plus program was more

  8. On the hydration and conformation of cocaine in solution

    Science.gov (United States)

    Gillams, Richard J.; Lorenz, Christian D.; McLain, Sylvia E.

    2017-05-01

    In order to develop theories relating to the mechanism through which cocaine can diffuse across the blood-brain barrier, it is important to understand the interplay between the hydration of the molecule and the adopted conformation. Here key differences in the hydration of cocaine hydrochloride (CHC) and freebase cocaine (CFB) are highlighted on the atomic scale in solution, through the use of molecular dynamics simulations. By adopting different conformations, CHC and CFB experience differing hydration environments. The interplay between these two factors may account for the vast difference in solubility of these two molecules.

  9. A fibre optic chemical sensor for the detection of cocaine

    Science.gov (United States)

    Nguyen, T. Hien; Sun, Tong; Grattan, Kenneth T. V.; Hardwick, S. A.

    2010-09-01

    A fibre-optic chemical sensor for the detection of cocaine has been developed, based on a molecularly imprinted polymer (MIP) containing a fluorescein moiety as the signalling group. The fluorescent MIP was formed and covalently attached to the distal end of an optical fibre. The sensor exhibited an increase in fluorescence intensity in response to cocaine in the concentration range of 0 - 500 μM in aqueous acetonitrile mixtures with good reproducibility over 24 h. Selectivity for cocaine over others drugs has also been demonstrated.

  10. [Agranulocytosis induced by levamisole in association to cocaine].

    Science.gov (United States)

    Pellegrini, Débora; Young, Pablo; Grosso, Verónica; Massa, María; Bruetman, Julio E

    2013-01-01

    Agranulocytosis in cocaine users is a worldwide recently recognized condition. It is due to the utilization as cutting agent of levamisole, an ancient antiparasitic and immunomodulator drug. We describe the case of a patient with agranulocytosis induced by levamisole in association to cocaine and we review clinical and biochemical characteristics of the clinical picture, as well as the management of these patients. We also analyze the reasons related to a more and more frequent practice, the addition of levamisole to cocaine. This is the first case described in our country, although it is probable that there are many not recognized or not described cases related to this pathology.

  11. Atypical Gastric Ulcer in an Elderly Cocaine User

    Directory of Open Access Journals (Sweden)

    Vinaya Gaduputi

    2013-01-01

    Full Text Available Cocaine or Benzoylmethylecgonine is an alkaloid extracted from the leaves of the Erythroxylon plant, which can cause gastrointestinal ischemia from severe arterial vasoconstriction via stimulation of alpha-adrenergic receptors in the gastric and mesenteric arteries. We report this case of a 65-year-old man who presented with a single massive ulcer at the incisura of the stomach as a result of cocaine use. The size and location of this ulcer were atypical and illustrate the potential for serious gastrointestinal manifestations from cocaine use.

  12. Use of NMR in profiling of cocaine seizures

    DEFF Research Database (Denmark)

    Pagano, Bruno; Lauri, Ilaria; De Tito, Stefano

    2013-01-01

    Cocaine is the most widely used illicit drug, and its origin is always the focus of intense investigation aimed at identifying the trafficking routes. Since NMR represents a unique methodology for performing chemical identification and quantification, here it is proposed a strategy based on (1)H...... NMR spectral analysis in conjunction with multivariate analysis to identify the chemical "fingerprint" of cocaine samples, and to link cocaine samples based on this information. The most relevant spectral regions containing the fingerprint have been identified: δH 0.86-0.96, 1.50-1.56, 5.90-5.93, 6...

  13. A Review of the Effects of Prenatal Cocaine Exposure Among School-Aged Children abstract

    Science.gov (United States)

    Ackerman, John P.; Riggins, Tracy; Black, Maureen M.

    2011-01-01

    CONTEXT Studies through 6 years have shown no long-term direct effects of prenatal cocaine exposure (PCE) on children’s physical growth, developmental test scores, or language outcomes. Little is known about the effects of PCE among school-aged children aged 6 years and older. OBJECTIVE We reviewed articles from studies that examined the effects of PCE on growth, cognitive ability, academic functioning, and brain structure and function among school-aged children. METHODS Articles were obtained by searching PubMed, Medline, TOXNET, and PsycInfo databases from January 1980 to December 2008 with the terms “prenatal cocaine exposure,” “cocaine,” “drug exposure,” “substance exposure,” “maternal drug use,” “polysubstance,” “children,” “adolescent,” “in utero,” “pregnancy,” “development,” and “behavior.” Criteria for inclusion were (1) empirical research on children aged 6 years and older prenatally exposed to cocaine, (2) peer-reviewed English-language journal, (3) comparison group, (4) longitudinal follow-up or historical prospective design, (5) masked assessment, (6) exclusion of subjects with serious medical disabilities, and (7) studies that reported nonredundant findings for samples used in multiple investigations. Thirty-two unique studies met the criteria. Each article was independently abstracted by 2 authors to obtain sample composition, methods of PCE assessment, study design, comparison groups, dependent variables, covariates, and results. RESULTS Associations between PCE and growth, cognitive ability, academic achievement, and language functioning were small and attenuated by environmental variables. PCE had significant negative associations with sustained attention and behavioral self-regulation, even with covariate control. Although emerging evidence suggests PCE-related alterations in brain structure and function, interpretation is limited by methodologic inconsistencies. CONCLUSIONS Consistent with

  14. Neonatal Abstinence Syndrome: Update on Diagnostic and Therapeutic Strategies.

    Science.gov (United States)

    Raffaeli, Genny; Cavallaro, Giacomo; Allegaert, Karel; Wildschut, Enno Diederik; Fumagalli, Monica; Agosti, Massimo; Tibboel, Dick; Mosca, Fabio

    2017-07-01

    Substance use among pregnant women is a major public health issue. Both prescription opioid use and illicit opioid abuse have increased dramatically in recent years. Prolonged in utero drug exposure may result in neonatal abstinence syndrome (NAS), an acute multisystemic clinical entity that occurs in the first days of life. This syndrome is caused by abrupt discontinuation of fetal exposure to licit or illicit drugs chronically consumed by the mother during pregnancy and transmitted to the fetus through the placenta. It usually requires prolonged hospitalization and may have long-term effects. The interplay of many factors contributes to its clinical heterogeneity, and its pathophysiology has not been fully unveiled. The first step in NAS management consists of nonpharmacologic interventions and includes promoting breastfeeding when not contraindicated. If withdrawal signs become severe, pharmacotherapy is needed. The Finnegan scoring system supports care providers across the pharmacotherapy process from initiation through the monitoring phase, until weaning and discontinuation. However, a standardized approach to pharmacotherapy is still lacking. Morphine is usually the first-line agent to treat NAS. Methadone is a valid option, but its safety profile is not completely known. Phenobarbital, despite its lack of effect on gastrointestinal symptoms and unfavorable pharmacologic features, has been identified as a second-line agent to be used in infants unresponsive to opiates. Although buprenorphine and clonidine seem promising, their use requires further validation. Long-term developmental effects of NAS therapy call for more-comprehensive, longitudinal assessments. In this article, key points for use of recommended therapies are outlined, and directions for future research are suggested. © 2017 Pharmacotherapy Publications, Inc.

  15. Neonatal abstinence syndrome: Diagnostic dilemmas in the maternity ward

    Directory of Open Access Journals (Sweden)

    Lazić-Mitrović Tanja

    2015-01-01

    Full Text Available Introduction. Neonatal abstinence syndrome (NAS refers to a newborn neurological, gastrointestinal and/or respiratory disorder if a newborn was exposed to psychoactive substances in the intrauterine period. NAS is difficult to diagnose due to unreliability of the data on addictive substances use during pregnancy, limited possibilities of the prenatal exposure diagnosis and postnatal substance detection, which all lead to diagnostic dilemmas. Objective. The aim of this study was to indicate the problems in patients with early NAS diagnosis in the maternity ward and the importance of clinical presentation used as a guide toward the diagnosis. Methods. This retrospective study included five term eutrophic newborns with high Apgar score, good adaptation in the first day and with clinical presentation of NAS during the second day of life. The clinical presentation was dominated by irritability, increased wakefulness, increased muscle tone, shrilly crying, tremors, problems with accepting food, tachypnea, subfebrility and hyperhidrosis. Finnegan scale was introduced in order to diagnose NAS and apply the therapy. Single-medication therapy of phenobarbitone was applied in four cases and a combination of phenobarbitone and morphine in one case. For toxicological analysis newborns’ urine samples were used. Results. Conditions such as perinatal asphyxia, infection, hunger, polycythemia, hypoglycemia or hypocalcemia were excluded. Finnegan score implied that pharmacological treatment had to be administered. The discrepancy between the NAS anamnesis and toxicological analysis existed. Response to the treatment was positive in all cases. Conclusion. NAS is a multisystemic disorder and should be suspected when it is noticed that children exhibit characteristic signs. However, other pathological conditions have to be excluded. Quantification according to the adopted scales for NAS leads toward appropriate treatment and recovery of the newborns.

  16. Withdrawal in adolescent light smokers following 24-hour abstinence

    Science.gov (United States)

    Benowitz, Neal L.; Auerback, Glenna M.; Moscicki, Anna-Barbara

    2009-01-01

    Introduction: Withdrawal is one of the most important symptoms of nicotine addiction. We examined the extent to which adolescent light smokers experienced withdrawal symptoms when deprived of nicotine for a 24-hr period. Methods: A total of 20 adolescents aged 13–17 years who smoked 1–5 cigarettes/day (CPD) refrained from smoking for a 24-hr period. Withdrawal scales were administered, and heart rate was measured at baseline, 12, and 24 hr. Neuropsychological testing was performed at baseline and 24 hr. Participants were divided into two groups: very light smokers (1–3 CPD) and light smokers (4–5 CPD). Results: At 12 hr, very light smokers experienced a decrease in withdrawal symptoms versus light smokers, who reported an increase in symptoms (−2.9 vs. 2.8, p = .02). Similarly, at 24 hr, very light smokers experienced a mean decrease in withdrawal score compared with a mean increase for the light smoker group (–2.2 vs. 5.8, p = .04). We did not find a significant change in heart rate or any differences in participants’ scores on the memory or concentration tasks. Discussion: Based on our findings in this controlled laboratory experiment, adolescent very light smokers did not appear to have significant withdrawal symptoms following abstinence from nicotine. Adolescent light smokers who smoke 4–5 CPD experienced subjective withdrawal symptoms but did not have objective signs of nicotine withdrawal. The stage of smoking in which adolescents are smoking 5 CPD or fewer appears to be a crucial time for studying development of nicotine addiction in teens as they may be transitioning from social smoking to early addiction. PMID:19246428

  17. Outpatient Management of Neonatal Abstinence Syndrome: A Quality Improvement Project.

    Science.gov (United States)

    Chau, Kim T; Nguyen, Jacqueline; Miladinovic, Branko; Lilly, Carol M; Ashmeade, Terri L; Balakrishnan, Maya

    2016-11-01

    An increasing number of infants are diagnosed with neonatal abstinence syndrome (NAS). The study's primary objectives were to describe an academic medical center's level IV neonatal ICU's (NICU's) comprehensive outpatient NAS management effort, measure guideline compliance, and assess its safety. Secondary objectives were to describe the duration and cumulative methadone exposure, and to improve parent and provider knowledge of NAS. The study included 22 infants having a gestational age of 35-41 weeks, diagnosed with NAS, and discharged for outpatient methadone management. Discharges spanned 10 months and included 3 improvement periods. The outpatient program includes comprehensive discharge planning, a focused electronic health record (EHR) template, management guidelines, and parent and provider education. Providers complied with using the outpatient management guideline and EHR template, and assessed weight, NAS symptoms, and methadone dose during appointments. Two infants required NAS-related hospital readmission in the study period. From improvement period 1 to period 3 there was no difference in total outpatient days on methadone (58, 53, 74 days, respectively) or cumulative methadone dose (2.7, 2.6, 3.1mg/kg, respectively). A downward trend pattern in cumulative methadone exposure was noted in improvement period 2. Pre- and postimplementation surveys revealed that after implementation, parents had better understanding of NAS before delivery (71% vs. 100%, p = 0.009), while providers had increased comfort with outpatient management (24% vs. 67%, p management can be safe when a comprehensive management program is implemented and can result in provider compliance with the program. Copyright 2016 The Joint Commission.

  18. Lower reinforcing strength of the phenyltropane cocaine analogs RTI-336 and RTI-177 compared to cocaine in nonhuman primates.

    Science.gov (United States)

    Czoty, Paul W; Martelle, Jennifer L; Carroll, F Ivy; Nader, Michael A

    2010-09-01

    Drugs that inhibit brain dopamine transporters (DAT) have been developed as potential agonist medications for cocaine abuse and dependence. Because the mechanism of action of such drugs is similar to cocaine, one concern regarding their use is the abuse potential of the medications themselves. The present study compared the reinforcing strength of cocaine (0.003-0.3mg/kg) and two 3-phenyltropane analogs of cocaine, RTI-336 (3beta-(4-chlorophenyl)-2beta-[3-(4'-methylphenyl)isoxazol-5-yl]tropane hydrochloride; 0.003-0.1mg/kg) and RTI-177 (3beta-(4-chlorophenyl)-2beta-[3-phenylisoxazol-5-yl]tropane hydrochloride; 0.003-0.1mg/kg), using a progressive-ratio (PR) schedule in rhesus monkeys (n=4). PR schedules of reinforcement are frequently used to measure reinforcing strength of drugs. Earlier research using limited-access conditions reported that cocaine was a stronger reinforcer than either RTI-336 or RTI-177. Because the 3-phenyltropanes have longer durations of action, one purpose of the present study was to examine reinforcing strength using longer experimental sessions. Under these conditions, cocaine functioned as a reinforcer in all monkeys, and RTI-336 and RTI-177 functioned as a reinforcer in three of four subjects. Consistent with their documented slower onset of neurochemical and pharmacological effects, RTI-336 and RTI-177 were weaker reinforcers, resulting in fewer injections than cocaine. On average, the potencies of the two RTI compounds were not different than that of cocaine. These results support the view that slow-onset DA-selective uptake inhibitors have lower abuse liability than cocaine. In addition, the present findings suggest that changes in PR session length can influence potency comparisons between drugs, but not measures of reinforcing strength. Copyright 2010 Elsevier Inc. All rights reserved.

  19. ProSAAS-derived peptides are regulated by cocaine and are required for sensitization to the locomotor effects of cocaine.

    Science.gov (United States)

    Berezniuk, Iryna; Rodriguiz, Ramona M; Zee, Michael L; Marcus, David J; Pintar, John; Morgan, Daniel J; Wetsel, William C; Fricker, Lloyd D

    2017-11-01

    To identify neuropeptides that are regulated by cocaine, we used a quantitative peptidomic technique to examine the relative levels of neuropeptides in several regions of mouse brain following daily intraperitoneal administration of 10 mg/kg cocaine or saline for 7 days. A total of 102 distinct peptides were identified in one or more of the following brain regions: nucleus accumbens, caudate putamen, frontal cortex, and ventral tegmental area. None of the peptides detected in the caudate putamen or frontal cortex were altered by cocaine administration. Three peptides in the nucleus accumbens and seven peptides in the ventral tegmental area were significantly decreased in cocaine-treated mice. Five of these ten peptides are derived from proSAAS, a secretory pathway protein and neuropeptide precursor. To investigate whether proSAAS peptides contribute to the physiological effects of psychostimulants, we examined acute responses to cocaine and amphetamine in the open field with wild-type (WT) and proSAAS knockout (KO) mice. Locomotion was stimulated more robustly in the WT compared to mutant mice for both psychostimulants. Behavioral sensitization to amphetamine was not maintained in proSAAS KO mice and these mutants failed to sensitize to cocaine. To determine whether the rewarding effects of cocaine were altered, mice were tested in conditioned place preference (CPP). Both WT and proSAAS KO mice showed dose-dependent CPP to cocaine that was not distinguished by genotype. Taken together, these results suggest that proSAAS-derived peptides contribute differentially to the behavioral sensitization to psychostimulants, while the rewarding effects of cocaine appear intact in mice lacking proSAAS. © 2017 International Society for Neurochemistry.

  20. Reduced Metabolsim in Brain 'Control Networks' Following Cocaine-Cues Exposure in Female Cocaine Abusers

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Telang, F.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

    2011-03-01

    Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved. To test this we compared brain metabolism (using PET and {sup 18}FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral video (nature scenes) versus a cocaine-cues video. Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05); females significantly decreased metabolism (-8.6% {+-} 10) whereas males tended to increase it (+5.5% {+-} 18). SPM analysis (Cocaine-cues vs Neutral) in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001) whereas males showed increases in right inferior frontal gyrus (BA 44/45) (only at p<0.005). The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001) in frontal (BA 8, 9, 10), anterior cingulate (BA 24, 32), posterior cingulate (BA 23, 31), inferior parietal (BA 40) and thalamus (dorsomedial nucleus). Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from 'control networks' (prefrontal, cingulate, inferior parietal, thalamus) in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition). This highlights the importance of gender tailored interventions for cocaine addiction.

  1. Outcomes of adult heroin users v. abstinent users four years after presenting for heroin detoxification treatment

    Directory of Open Access Journals (Sweden)

    Zureida Khan

    2014-08-01

    Full Text Available Background. There are no studies in South Africa (SA on the outcomes following detoxification and psychosocial rehabilitation of heroin-dependent patients. Objective. To compare the demographic, clinical, forensic and treatment data of active heroin users v. users who were abstinent at the time of interview 4 years after attending the Opioid Detoxification Unit at Stikland Hospital in the Western Cape Province, SA.  Method. Participants included patients above the age of 16 years who had been admitted to the Opioid Detoxification Unit at Stikland Hospital for heroin detoxification between July 2006 and June 2007. Participants were individually interviewed (either in person or tele­phonically using a structured self-report questionnaire to collect demographic, clinical, forensic and treatment data 4 years following heroin detoxification treatment at this unit.  Results. Of the participants, 60% were abstinent and a large portion (34% attributed this to social support. Furthermore, there was a significant (p=0.04 difference in the longest period of abstinence between the past user group and active users, with more participants in the past user group being abstinent for 18 months or longer (n=24, 57% than in the active users group (n=8, 29%. Active users (n=18, 64% had significantly (p=0.03 more legal problems than abstinent users (n=14, 33%. Most participants (n=38, 54% relapsed within 3 months after index detoxification and rehabilitation.  Conclusion. Active users had more legal problems than abstinent users, with social support structures playing a pivotal role in abstinence. Future research should assess the impact of interventions such as post-discharge social support programmes on criminality and heroin use in those that relapse following treatment.

  2. Placebo-group responders in methamphetamine pharmacotherapy trials: the role of immediate establishment of abstinence.

    Science.gov (United States)

    Brensilver, Matthew; Heinzerling, Keith G; Swanson, Aimee-Noelle; Shoptaw, Steven J

    2012-10-01

    Treatment responses of placebo groups in addiction medicine trials have important implications for research methodology and clinical practice, however studies examining placebo group responses in addiction medicine are scarce. Extant data suggest the importance of early treatment responsiveness for long-term outcomes. Among methamphetamine-(MA) dependent individuals randomized to placebo pill plus behavioral support conditions in pharmacotherapy development trials, we hypothesized that immediate abstinence would be a necessary but insufficient predictor for end-of-trial (EOT) abstinence. The study is a secondary analysis of participants (n = 184; 36% female) in the placebo condition of three randomized, placebo-controlled methamphetamine dependence pharmacotherapy trials. Receiver operating characteristic (ROC) curve analyses assessed the predictive power of initial abstinence, assessed by thrice weekly urine samples, for EOT abstinence. Sixty percent of individuals with complete abstinence in the first two weeks of treatment were abstinent at EOT, while 18% of people who failed to meet this standard were abstinent at EOT. Early response was related to retention at EOT and 12-month follow-up. Findings suggest that the inability to achieve at least three MA negative screenings in the first two weeks is associated with greater than 90% likelihood of treatment failure. A third week of screening added minimally to the prediction of EOT outcomes. The prediction of treatment failure was more precise than the prediction of treatment success. The absence of a clinical response in the first two weeks of treatment among participants in the placebo group signals high risk of treatment failure. The majority of information regarding response in the placebo group from a 12-week trial is obtained early in the trial.

  3. Cocaine-induced cardiovascular effects: lack of evidence for a central nervous system site of action based on hemodynamic studies with cocaine methiodide.

    Science.gov (United States)

    Dickerson, L W; Rodak, D J; Kuhn, F E; Wahlstrom, S K; Tessel, R E; Visner, M S; Schaer, G L; Gillis, R A

    1999-01-01

    It has been suggested that cocaine acts directly in the brain to enhance central sympathetic outflow. However, some studies suggested that the cardiovascular effects of cocaine are related to a peripheral action. To characterize further the site of cocaine's cardiovascular effect, we compared the hemodynamic effects of cocaine (2 mg/kg, i.v. bolus) with those observed after administration of an equimolar dose (2.62 mg/kg, i.v. bolus) of cocaine methiodide, a quaternary derivative of cocaine that does not penetrate the blood-brain barrier, by using sufentanil-sedated dogs. Cocaine produced significant (p < 0.05) increases in heart rate (+37+/-11 beats/min), mean arterial pressure (+55+/-11 mm Hg), left ventricular end-diastolic pressure (+5.3+/-1.0 mm Hg), and cardiac output (+2.4+/-0.9 L/min). Cocaine methiodide produced increases in heart rate (+57+/-11 beats/min), mean arterial pressure (+45+/-11 mm Hg), left ventricular end-diastolic pressure (+3.4+/-1.0 mm Hg), and cardiac output (1.1+/-0.9 L/min), which were not significantly different from those observed with cocaine. Because opiate sedation potentially might have attenuated central sympathetic outflow, we further confirmed the qualitative similarity of the actions of cocaine and cocaine methiodide on heart rate and blood pressure in unsedated, conscious dogs. Our data suggest that the cardiovascular effects of cocaine result primarily from a peripheral site of action.

  4. Probing the Behavioral and Neurophysiological Effects of Acute Smoking Abstinence on Drug and Nondrug Reinforcement During a Cognitive Task.

    Science.gov (United States)

    Schlienz, Nicolas J; Hawk, Larry W

    2017-06-01

    Smoking abstinence is theorized to increase smoking reinforcement and decrease nondrug reinforcement. A separate literature demonstrates the detrimental effects of abstinence on cognition. The present study integrates these two areas by examining the separate and combined effects of reinforcement and smoking abstinence on behavior and a neurophysiological index of response monitoring (ie, error-related negativity [ERN]) during a cognitive task. After a screening visit, adult smokers attended two laboratory visits, once while smoking and once while abstinent. Participants completed a flanker task under cigarette-, money-, and no-reinforcement conditions. The initial 15 participants had an easier reaction time (RT) requirement; to ensure sufficient error rates for ERN computation, a harder RT deadline was employed for the remaining 21 participants. Smoking abstinence reduced speeded accuracy and ERN amplitude only among participants tested with the harder RT deadline. Cigarette and money reinforcement each increased speeded accuracy and ERN amplitude compared to no reinforcement. The effect of cigarette reinforcement tended to be greater during abstinence for speeded accuracy but not the ERN. The effect of money reinforcement was unaffected by abstinence. The impact of smoking abstinence on reinforcement may depend on task demands. However, the effects of cigarette and money reinforcement generalize well from operant paradigms to cognitive tasks, fostering integration between the two literatures. Results provided modest evidence of abstinence-induced increases in smoking reinforcement; the absence of abstinence-induced reductions in nondrug reinforcement is consistent with recent work in suggesting that such effects are limited to a subset of sensory reinforcers. This study draws attention to the need for greater integration of reinforcement and cognition to better understand the mechanisms that contribute to smoking relapse. Results emphasize thoughtful

  5. Effect of computerized cognitive behavioral therapy on acquisition of coping skills among cocaine-dependent individuals enrolled in methadone maintenance.

    Science.gov (United States)

    Kiluk, Brian D; DeVito, Elise E; Buck, Matthew B; Hunkele, Karen; Nich, Charla; Carroll, Kathleen M

    2017-11-01

    The acquisition of coping skills has long been considered one of the putative mechanisms of cognitive behavioral therapy (CBT) for substance use disorders, yet consistent statistical support is lacking. This study sought to replicate and extend prior findings regarding the quality of coping skills as a mediator of abstinence outcomes from a computerized CBT program for substance users. Participants were methadone-maintained, cocaine dependent individuals enrolled in a clinical trial evaluating the efficacy of computer-based training for CBT ('CBT4CBT') as an add-on to treatment as usual (TAU+CBT4CBT) compared to TAU only. A subsample (N=71) completed a role play assessment to measure coping skills, the Drug Risk Response Test (DRRT), which was administered before, during (week 4), and after the 8-week treatment period. Participants' verbal responses to various high-risk situations for cocaine use were recorded and independent evaluators rated the quality of the coping responses. Results of repeated measures analyses revealed a main effect of time for the quality of overall responses [F(1, 141.26)=4.29, pcoping skills across groups, yet no differential effect of treatment. Despite the significant association between coping responses and abstinence outcomes, analyses did not support the quality of coping skills as a mediator of treatment effects. However, among the high-risk situations wherein individuals provided lower quality responses at baseline, those assigned to TAU+CBT4CBT showed greater improvement compared to those assigned to TAU only [F(1, 697.65)=6.47, p=0.01]. This study failed to replicate the quality of coping skills as a mediator of CBT4CBT's effect on reducing drug use previously shown in a mixed outpatient substance use sample. However, in this methadone maintained sample, those with poorer quality skills in response to certain high-risk situations at baseline appeared to improve their coping strategies following CBT4CBT compared to standard

  6. Perinatal cocaine exposure inhibits the development of the male SDN.

    Science.gov (United States)

    Maecker, H L

    1993-12-17

    The sexually dimorphic nucleus of the hypothalamus (SDN) is involved in sexual differentiation of the rat brain. Perinatal cocaine exposure was found to significantly reduce the volume of the male rat SDN (P SDN. Pregnant dams and their pups were exposed to either saline, 7.5, 15, or 30 mg/kg of cocaine from gestational day 15 through postnatal day 10. Litter size, pup weight, male-female sex ratio, and gross birth defects were unaffected, but maternal weight gain was significantly reduced in cocaine-treated dams. These findings imply that males perinatally exposed to cocaine during their critical period of SDN differentiation may exhibit compromised coital capabilities as well as impaired gonadotropin regulation.

  7. Carrots and sticks fail to change behavior in cocaine addiction

    NARCIS (Netherlands)

    Ersche, K.D.; Gillan, C.M.; Jones, P.S.; Williams, G.B.; Ward, L.H.E.; Luijten, M.; de Wit, S.; Sahakian, B.J.; Bullmore, E.T.; Robbins, T.W.

    2016-01-01

    Cocaine addiction is a major public health problem that is particularly difficult to treat. Without medically proven pharmacological treatments, interventions to change the maladaptive behavior of addicted individuals mainly rely on psychosocial approaches. Here we report on impairments in

  8. Costs and benefits of treatment for cocaine addiction in DATOS

    National Research Council Canada - National Science Library

    Flynn, Patrick M; Kristiansen, Patricia L; Porto, James V; Hubbard, Robert L

    1999-01-01

    ...), calculate the tangible cost of crime to society, and determine treatment benefits. Subjects were 502 cocaine-dependent patients selected from a national and naturalistic nonexperimental evaluation of community-based treatment...

  9. Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning.

    Science.gov (United States)

    Mills, Fergil; Globa, Andrea K; Liu, Shuai; Cowan, Catherine M; Mobasser, Mahsan; Phillips, Anthony G; Borgland, Stephanie L; Bamji, Shernaz X

    2017-04-01

    Drugs of abuse alter synaptic connections in the reward circuitry of the brain, which leads to long-lasting behavioral changes that underlie addiction. Here we show that cadherin adhesion molecules play a critical role in mediating synaptic plasticity and behavioral changes driven by cocaine. We demonstrate that cadherin is essential for long-term potentiation in the ventral tegmental area and is recruited to the synaptic membranes of excitatory synapses onto dopaminergic neurons following cocaine-mediated behavioral conditioning. Furthermore, we show that stabilization of cadherin at the membrane of these synapses blocks cocaine-induced synaptic plasticity, leading to a reduction in conditioned place preference induced by cocaine. Our findings identify cadherins and associated molecules as targets of interest for understanding pathological plasticity associated with addiction.

  10. Levamisole-Adulterated Cocaine Nephrotoxicity:  Ultrastructural Features.

    Science.gov (United States)

    Liu, Yi-Wei Justin; Mutnuri, Sangeeta; Siddiqui, Sarah Batool; Weikle, Geoff Richard; Oladipo, Olajumoke; Ganti, Niharika; Beach, Robert E; Afrouzian, Marjan

    2016-05-01

    The issue of levamisole-adulterated cocaine is emerging as a rapidly growing public health concern due to an increasing number of reports describing its role in cutaneous vasculitis and agranulocytosis. Of note, levamisole is recognized as a contaminant in 69% of the cocaine used within the United States. We describe a patient who was a chronic cocaine user and developed systemic vasculitis characterized by polyarthralgia, bullous skin lesions, agranulocytosis, and antineutrophil cytoplasmic antibody-positive rapidly progressive glomerulonephritis. The skin biopsy specimen demonstrated leukocytoclastic vasculitis. The renal biopsy specimen revealed pauci-immune necrotizing and crescentic glomerulonephritis and unusual deposits with medium electron density composed of granules, microspherules, and rare single fibrils on electron microscopy. The electron microscopic features of levamisole-adulterated cocaine toxicity are novel findings that are presented for the first time, to our knowledge, in this report. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Chronic Inhibition of Dopamine β-Hydroxylase Facilitates Behavioral Responses to Cocaine in Mice

    Science.gov (United States)

    Gaval-Cruz, Meriem; Liles, Larry Cameron; Iuvone, Paul Michael; Weinshenker, David

    2012-01-01

    The anti-alcoholism medication, disulfiram (Antabuse), decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH), the enzyme that converts dopamine (DA) to norepinephrine (NE) in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh −/−) mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/−) and Dbh −/− mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh −/− mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/− mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/− mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh −/− mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor) enhance qualitatively different cocaine-induced behaviors. PMID:23209785

  12. Chronic inhibition of dopamine β-hydroxylase facilitates behavioral responses to cocaine in mice.

    Directory of Open Access Journals (Sweden)

    Meriem Gaval-Cruz

    Full Text Available The anti-alcoholism medication, disulfiram (Antabuse, decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH, the enzyme that converts dopamine (DA to norepinephrine (NE in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh -/- mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/- and Dbh -/- mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh -/- mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/- mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/- mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh -/- mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor enhance qualitatively different cocaine-induced behaviors.

  13. The Bermuda Triangle of Cocaine-Induced Neuroadaptations

    OpenAIRE

    Wolf, Marina E.

    2010-01-01

    Activation of medium spiny neurons (MSN) of the nucleus accumbens is critical for goal-directed behaviors including cocaine seeking. Studies in cocaine-experienced rodents have revealed three major categories of neuroadaptations that influence the ability of glutamate inputs to activate MSN: changes in synaptic AMPA receptor levels, changes in extracellular non-synaptic glutamate levels, and changes in MSN intrinsic membrane excitability. Most studies have focused on one of these adaptations....

  14. Cocaine-Associated Myocardial Infarction: Should They All Be Stented?

    Directory of Open Access Journals (Sweden)

    Sazzli Kasim

    2011-01-01

    Full Text Available Cocaine use is a known cause of chest pain and acute myocardial infarction and frequently leads to cardiac catheterization procedure. The treatment of cocaine-related acute coronary syndromes presents unique challenges because a variety of mechanisms including atherosclerotic plaque rupture, platelet activation, and coronary vasospasm may contribute to the pathogenesis. Our case highlights important considerations taken in dealing with this acute scenario

  15. Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity

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    Vilela, Luciano R. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Gobira, Pedro H.; Viana, Thercia G. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Medeiros, Daniel C.; Ferreira-Vieira, Talita H. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Doria, Juliana G. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Rodrigues, Flávia [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Aguiar, Daniele C. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Pereira, Grace S.; Massessini, André R. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ribeiro, Fabíola M. [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Oliveira, Antonio Carlos P. de [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moraes, Marcio F.D., E-mail: mfdm@icb.ufmg.br [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moreira, Fabricio A., E-mail: fabriciomoreira@icb.ufmg.br [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2015-08-01

    Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB{sub 1} receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB{sub 1} receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity. - Highlights: • Cocaine toxicity is characterized by seizures and hippocampal cell death. • The endocannabinoid anandamide acts as a brain protective mechanism. • Inhibition of anandamide hydrolysis

  16. Fingertip and nasal tip thermal burn in crack cocaine user*

    Science.gov (United States)

    Bernardes, Fred; da Silva, Ystannyslau Bernardes; Martins, Luiz Gustavo; Sasso, Letícia Soares; de Abreu, Marilda Aparecida Milanez Morgado

    2013-01-01

    Crack cocaine addiction is a public health problem in Brazil. It is an endemic disease that affects rural and urban areas. The Ministry of Health has launched emergency programs for the treatment of dependents and to combat drug trafficking. Recognition of dermatological signs of this disease is important because through them the diagnosis can be suspected and early treatment of patients with crack cocaine addiction be provided. PMID:24173204

  17. A shorter duration of pre-transplant abstinence predicts problem drinking after liver transplantation.

    Science.gov (United States)

    Tandon, Puneeta; Goodman, Karen J; Ma, Mang M; Wong, Winnie W; Mason, Andrew L; Meeberg, Glenda; Bergsten, Donna; Carbonneau, Michelle; Bain, Vincent G

    2009-07-01

    Liver transplantation for alcoholic liver disease (ALD) can be complicated by abusive or "problem" drinking (PD) after transplant. There are limited data for evaluating the effect of pre-transplant abstinence on post-transplant PD. Few existing studies have included a substantial number of patients with co-existing causes of hepatic dysfunction, and the effect of PD on survival in recent European studies has been controversial. We hypothesized that a longer duration of pre-transplant abstinence would lead to less PD after transplantation. Accordingly, the objectives of this study are to analyze a North American cohort of patients with ALD with or without a secondary diagnosis of liver disease to estimate (i) the incidence of PD and its predictors, as well as (ii) the effect of PD on patient survival. We conducted a retrospective review of all patients transplanted for ALD surviving for more than 3 months after transplant. PD was defined as either any drinking (AD) to the point of intoxication or drinking above the toxic threshold (>20 g/day in women and >40 g/day in men) on at least two separate occasions. We used Cox's proportional hazards regression to estimate risk ratios and Kaplan-Meier curves with log-rank analysis to compare survival. Of 213 eligible transplant patients, 42 were excluded. Of the 171 remaining patients, 78% were male; mean age was 52 years. Overall 53% of patients had co-existing causes of liver dysfunction. The mean follow-up was 64.8 months. The median pre-transplant abstinence was 19 months. In all patients, the risk of AD was 24% and PD 13%. Pre-transplant abstinence duration was the only independent predictor of PD after transplant. For every 1-month increment in pre-transplant abstinence, there was a 5% decrease in the adjusted relapse rate. There was no survival difference noted between problem drinkers and non-drinkers. The risk of PD decreased with increasing pre-transplant abstinence. Our data support pre-transplant abstinence as an

  18. Role of Dorsomedial Striatum Neuronal Ensembles in Incubation of Methamphetamine Craving after Voluntary Abstinence.

    Science.gov (United States)

    Caprioli, Daniele; Venniro, Marco; Zhang, Michelle; Bossert, Jennifer M; Warren, Brandon L; Hope, Bruce T; Shaham, Yavin

    2017-01-25

    We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we studied the role of dorsolateral striatum (DLS) and dorsomedial striatum (DMS) in this incubation. We trained rats to self-administer palatable food pellets (6 d, 6 h/d) and methamphetamine (12 d, 6 h/d). We then assessed relapse to methamphetamine seeking under extinction conditions after 1 and 21 abstinence days. Between tests, the rats underwent voluntary abstinence (using a discrete choice procedure between methamphetamine and food; 20 trials/d) for 19 d. We used in situ hybridization to measure the colabeling of the activity marker Fos with Drd1 and Drd2 in DMS and DLS after the tests. Based on the in situ hybridization colabeling results, we tested the causal role of DMS D1 and D2 family receptors, and DMS neuronal ensembles in "incubated" methamphetamine seeking, using selective dopamine receptor antagonists (SCH39166 or raclopride) and the Daun02 chemogenetic inactivation procedure, respectively. Methamphetamine seeking was higher after 21 d of voluntary abstinence than after 1 d (incubation of methamphetamine craving). The incubated response was associated with increased Fos expression in DMS but not in DLS; Fos was colabeled with both Drd1 and Drd2 DMS injections of SCH39166 or raclopride selectively decreased methamphetamine seeking after 21 abstinence days. In Fos-lacZ transgenic rats, selective inactivation of relapse test-activated Fos neurons in DMS on abstinence day 18 decreased incubated methamphetamine seeking on day 21. Results demonstrate a role of DMS dopamine D1 and D2 receptors in the incubation of methamphetamine craving after voluntary abstinence and that DMS neuronal ensembles mediate this incubation. In human addicts, abstinence is often self-imposed and relapse can be triggered by exposure to drug-associated cues that induce drug craving. We recently developed a rat model of incubation of methamphetamine craving

  19. Breast feeding is associated with postpartum smoking abstinence among women who quit smoking due to pregnancy

    Science.gov (United States)

    Businelle, Michael S.; Costello, Tracy J.; Castro, Yessenia; Reitzel, Lorraine R.; Vidrine, Jennifer I.; Mullen, Patricia Dolan; Velasquez, Mary M.; Cinciripini, Paul M.; Cofta-Woerpel, Ludmila M.; Wetter, David W.

    2010-01-01

    Introduction: The purpose of this study was to characterize the relationship between breast feeding and postpartum smoking abstinence among women who quit smoking due to pregnancy and who were participating in a randomized clinical trial of an intervention designed to prevent postpartum relapse. Methods: A total of 251 women were enrolled in the intervention between 30 and 33 weeks postpartum and were followed through 26 weeks postpartum. Participant characteristics were assessed at the prepartum baseline visit, any breast feeding was assessed at 8 weeks postpartum, and smoking abstinence was assessed at 8 and 26 weeks postpartum. Results: Although 79.1% of participants intended to breast feed, only 40.2% reported breast feeding at 8 weeks postpartum. Characteristics associated with breast feeding at 8 weeks postpartum included Caucasian race/ethnicity, greater education, higher household income, and being married/living with a significant other. Logistic regression analysis indicated that breast feeding at 8 weeks postpartum was significantly associated with smoking abstinence at 8 weeks postpartum, odds ratio (OR) = 7.27 (95% CI = 3.27, 16.13), p Breast feeding at 8 weeks postpartum was also associated with abstinence at 26 weeks postpartum after controlling for smoking status at 8 weeks postpartum, OR = 2.64 (95% CI = 1.14, 6.10), p = .02. Discussion: Encouraging breast feeding among women who quit smoking due to pregnancy may facilitate postpartum smoking abstinence while increasing adherence to current infant feeding guidelines. PMID:20713441

  20. Effectiveness of Brief Abstinence for Modifying Problematic Internet Gaming Cognitions and Behaviors.

    Science.gov (United States)

    King, Daniel L; Kaptsis, Dean; Delfabbro, Paul H; Gradisar, Michael

    2017-12-01

    This pilot study tested the efficacy of a voluntary 84-hour abstinence protocol for modifying problematic Internet gaming cognitions and behaviors METHOD: Twenty-four adults from online gaming communities, including 9 individuals who screened positively for Internet gaming disorder (IGD), abstained from Internet games for 84 hours. Surveys were collected at baseline, at daily intervals during abstinence, and at 7-day and 28-day follow-up RESULTS: Brief voluntary abstinence was successful in reducing hours of gaming, maladaptive gaming cognitions, and IGD symptoms. Abstinence was highly acceptable to participants with total compliance and no study attrition. Clinically significant improvement in IGD symptoms occurred in 75% of the IGD group at 28-day follow-up. Reliable improvement in maladaptive gaming cognitions occurred in 63% of the IGD group, whose cognition score reduced by 50% and was comparable to the non-IGD group at 28-day follow-up CONCLUSIONS: Despite limitations of sample size, this study provides promising support for brief abstinence as a simple, practical, and cost-effective treatment technique for modifying unhelpful gaming cognitions and reducing Internet gaming problems. © 2017 Wiley Periodicals, Inc.

  1. Improvement of Smoking Abstinence Rates With Increased Varenicline Dosage: A Propensity Score-Matched Analysis.

    Science.gov (United States)

    Karam-Hage, Maher; Kypriotakis, George; Robinson, Jason D; Green, Charles E; Mann, Gurtej; Rabius, Vance; Wippold, Rosario; Blalock, Janice A; Mouhayar, Elie; Tayar, Jean; Chaftari, Patrick; Cinciripini, Paul M

    2018-02-01

    It is unclear whether increasing the dose of varenicline beyond the standard dose of 2 mg/d would improve smoking abstinence. We examined the effect of 3 mg/d of varenicline on smoking abstinence among smokers who had reduced their smoking by 50% or more in response to 2 mg/d for at least 6 weeks but had not quit smoking. Of 2833 patients treated with varenicline, dosage of a subset of 73 smokers was increased to 3 mg/d after 6 weeks. We used a propensity score analysis involving multiple baseline covariates to create a comparative sample of 356 smokers who remained on 2 mg/d. All smokers received concurrent and similar smoking-cessation counseling. At 3 months, we found higher 7-day point prevalence smoking-abstinence rate in the 3-mg group (26%) than in the 2-mg group (11.5%, χ = 10.60, P < 0.001; risk ratio [RR], 2.3; 95% confidence interval [CI], 1.4-3.6). The difference in abstinence rates remained significant at the 6-month (P < 0.001; RR, 2.6; 95% CI, 1.6-3.9) and 9-month follow-up (P < 0.001; RR, 2.2; 95% CI, 1.4-3.3). A relatively small increase in the daily dose of varenicline seems to offer a benefit for those who are not able to achieve total abstinence after approximately 6 weeks of 2 mg/d.

  2. Engagement and abstinence among users of a smoking cessation text message program for veterans

    Science.gov (United States)

    Christofferson, Dana E.; Hertzberg, Jeffrey S.; Beckham, Jean C.; Dennis, Paul A.; Hamlett-Berry, Kim

    2016-01-01

    BACKGROUND SmokefreeVET is a text messaging smoking cessation program available to veterans enrolled in the Veterans Health Administration. SmokefreeVET was developed in collaboration with the National Cancer Institute as part of the SmokefreeTXT initiative. PURPOSE To evaluate the real world use of and effectiveness of the SmokefreeVET program for SmokefreeVET users who enrolled between 2013 and 2014. METHODS Demographics and smoking behavior of 1,470 SmokefreeVET users who enrolled between 2013 and 2014 were analyzed. Latent growth mixture modeling was used to identify discrete classes of SmokefreeVET users based on engagement patterns. Multi-level modeling determined class differences in abstinence. RESULTS The average age of the SmokefreeVET user was 48, 75% of users were male, and 84% were daily smokers. After five weeks, 13% of all users reported abstinence from smoking. Five statistically distinct engagement classes of SmokefreeVET users were identified. Highly engaged classes were significantly less likely to opt-out and more likely to report abstinence. Over 60% of users who were classified as high engagers throughout the program reported abstinence 5 weeks after their quit date. Users were more likely to report abstinence after two weeks if they used smoking cessation medication than those that did not use medication (OR=9.01, ptext messaging smoking cessation intervention. PMID:27318948

  3. Psychosocial findings in alcohol-dependent patients before and after three months of total alcohol abstinence

    Directory of Open Access Journals (Sweden)

    Anna Ferrulli

    2010-07-01

    Full Text Available Alcohol use disorders (AUDs may be associated with several psychological and affective disorders. It is controversial, however, if these symptoms are a cause or rather a consequence of alcohol dependence. There are few data testing simultaneously psychosocial and affective disorders before and after a period of alcohol abstinence. The aim of this study was to perform multiple psychometric evaluations in alcohol-dependent patients before and after 12 weeks of abstinence. Twenty-five alcohol-dependent patients were included in the study. The following psychometric tests were administered at baseline (T0 and after 12 weeks (T1: Addiction Severity Index (ASI, Brief Psychiatric Rating Scale (BPRS, Social Behaviour Scale (SBS, Sheehan Disability Scale (DISS, Aggression Questionnaire (AQ. At T1, 16 (64% patients were abstinent, 5 (20% patients dropped out and 4 (16% patients relapsed. Compared to T0, patients totally abstinent at T1 showed a significant reduction of the scores related to BPRS, BPRS-E and its subscales (except BPRS 5, ASI 1, ASI 2, ASI 3, ASI 6, ASI 7, BSM, AQ, DISS 1, DISS 2, DISS 3 (p<0.05. No significant changes in ASI 4, ASI 5, DISS 4 and DISS 5, BPRS 5 scores were found at T1 compared to T0. The present study indicates that total alcohol abstinence improves psychometric features, such as alcohol addiction severity, psychiatric rating, social behaviour, aggressiveness, and disability. Larger controlled studies are needed to confirm these findings.

  4. Longitudinal study of cognition among adolescent marijuana users over three weeks of abstinence.

    Science.gov (United States)

    Hanson, Karen L; Winward, Jennifer L; Schweinsburg, Alecia D; Medina, Krista Lisdahl; Brown, Sandra A; Tapert, Susan F

    2010-11-01

    Cognitive deficits that persist up to a month have been detected among adult marijuana users, but decrements and their pattern of recovery are less known in adolescent users. Previously, we reported cognitive deficits among adolescent marijuana users after one month of abstinence (Medina, Hanson, Schweinsburg, Cohen-Zion, Nagel, & Tapert, 2007). In this longitudinal study, we characterized neurocognitive changes among marijuana-using adolescents across the first three weeks of abstinence. Participants were adolescent marijuana users with limited alcohol and other drug use (n=19) and demographically similar non-using controls (n=21) ages 15-19. Participants completed a brief neuropsychological battery on three occasions, after 3days, 2weeks, and 3weeks of stopping substance use. Abstinence was ascertained by decreasing tetrahydrocannabinol metabolite values on serial urine drug screens. Verbal learning, verbal working memory, attention and vigilance, and time estimation were evaluated. Marijuana users demonstrated poorer verbal learning (pworking memory (pworking memory after 3weeks. While attention processing speed was similar between groups, attention accuracy remained deficient in users throughout the 3-week abstinence period. This preliminary study detected poorer verbal learning and verbal working memory among adolescent marijuana users that improved during three weeks of abstinence, while attention deficits persisted. These results implicate possible hippocampal, subcortical, and prefrontal cortex abnormalities. Copyright 2010 Elsevier Ltd. All rights reserved.

  5. Clonidine Increases the Likelihood That Abstinence Can Withstand Unstructured Time in Buprenorphine-maintained Outpatients.

    Science.gov (United States)

    Kowalczyk, William J; Bertz, Jeremiah W; Moran, Landhing M; Phillips, Karran A; Ghitza, Udi E; Epstein, David H; Preston, Kenzie L

    In a clinical trial examining daily clonidine as an adjunct to buprenorphine treatment for opioid dependence, we found that clonidine increased opioid abstinence and decoupled stress from craving. From a personalized-medicine perspective, the next step is to identify people for whom clonidine would be beneficial. To that end, using data from the same clinical trial, we examined the associations of daily-life activities with treatment success. Outpatients (N = 118) received clonidine (0.3 mg/d) or placebo during 18 weeks of buprenorphine treatment. Participants carried a smartphone that randomly prompted them 4 times per day to report their moods and activities. Using generalized linear mixed models, we assessed the likelihoods of different types of daily activity as a function of clonidine versus placebo, days of longest continuous opioid abstinence, and their interaction. Participants in the buprenorphine-only (buprenorphine plus placebo) control group who engaged in more responsibilities (work and child/elder care) had longer streaks of abstinence, whereas those who engaged in more unstructured-time activities had shorter streaks of abstinence. Conversely, for participants in the buprenorphine-plus-clonidine group, longer streaks of abstinence were associated with higher frequencies of activities associated with "unstructured" time. The study replicates findings that engaging in responsibilities is related to positive treatment outcomes in standard opioid agonist therapy. The pattern of results also suggests that clonidine helped participants engage in unstructured-time activities with less risk of craving or use than they might otherwise have had.

  6. Cocaine and coronary artery diseases: a systematic review of the literature.

    Science.gov (United States)

    Talarico, Giovanni P; Crosta, Maria L; Giannico, Maria B; Summaria, Francesco; Calò, Leonardo; Patrizi, Roberto

    2017-05-01

    Cocaine is associated with important cardiac complications such as sudden death, acute myocarditis, dilated cardiomyopathy, life-threatening arrhythmias, and myocardial ischemia as well as infarction. It is well known that cocaine may induce vasospasm through adrenergic stimulation of the coronary arteries. Moreover, cocaine may promote intracoronary thrombosis, triggered by alterations in the plasma constituents, and platelet aggregation, leading to subsequent myocardial infarction. The long-term use of cocaine may stimulate atherosclerosis, probably through endothelial cell dysfunction. Significant and severe coronary atherosclerosis is common in young chronic cocaine users and there is probably a relationship between the duration and frequency of cocaine use and the extent of coronary disease.

  7. Optogenetically evoked gamma oscillations are disturbed by cocaine administration

    Directory of Open Access Journals (Sweden)

    Jonathan E Dilgen

    2013-11-01

    Full Text Available Drugs of abuse have enormous societal impact by degrading the cognitive abilities, emotional state and social behavior of addicted individuals. Among other events involved in the addiction cycle, the study of a single exposure to cocaine, and the contribution of the effects of that event to the continuous and further use of drugs of abuse are fundamental. Gamma oscillations are thought to be important neural correlates of cognitive processing in the prefrontal cortex (PFC which include decision making, set shifting and working memory. It follows that cocaine exposure might modulate gamma oscillations, which could result in reduced cognitive ability. Parvalbumin-positive fast-spiking interneurons play an orchestrating role in gamma oscillation induction and it has been shown recently that gamma oscillations can be induced in an anesthetized animal using optogenetic techniques. We use a knock-in mouse model together with optogenetics and in vivo electrophysiology to study the effects of acute cocaine on PFC gamma oscillation as a step toward understanding the cortical changes that may underlie continuous use of stimulants. Our results show that acute cocaine administration increases entrainment of the gamma oscillation to the optogentically induced driving frequency. Our results also suggest that this modulation of gamma oscillations is driven trough activation of DAD1 receptors. The acute cocaine-mediated changes in mPFC may underlie the enhancement of attention and awareness commonly reported by cocaine users and may contribute to the further use and abuse of psychostimulants.

  8. Excessive state switching underlies reversal learning deficits in cocaine users.

    Science.gov (United States)

    Patzelt, Edward H; Kurth-Nelson, Zeb; Lim, Kelvin O; MacDonald, Angus W

    2014-01-01

    Markers of chronic cocaine exposure on neural mechanisms in animals and humans is of great interest. The probabilistic reversal-learning task may be an effective way to examine dysfunction associated with cocaine addiction. However the exact nature of the performance deficits observed in cocaine users has yet to be disambiguated. Data from a probabilistic reversal-learning task performed by 45 cocaine users and 41 controls was compared and fit to a Bayesian hidden Markov model (HMM). Cocaine users demonstrated the predicted performance deficit in achieving the reversal criterion relative to controls. The deficit appeared to be due to excessive switching behavior as evidenced by responsivity to false feedback and spontaneous switching. This decision-making behavior could be captured by a single parameter in an HMM and did not require an additional parameter to represent perseverative errors. Cocaine users are characterized by excessive switching behavior on the reversal-learning task. While there may be a compulsive component to behavior on this task, impulsive decision-making may be more relevant to observed impairment. This is important in building diagnostic tools to quantify the degree to which each type of dysfunction is present in individuals, and may play a role in developing treatments for those dysfunctions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Differences between Alcoholics and Cocaine Addicts Seeking Treatment.

    Science.gov (United States)

    López-Goñi, José J; Fernández-Montalvo, Javier; Arteaga, Alfonso

    2015-03-03

    This study explored the characteristics of a representative sample of patients who were addicted to either alcohol or cocaine, comparing the profiles of both types of drug users. A sample of 234 addicted patients (109 alcoholics and 125 cocaine addicts) who sought outpatient treatment in a Spanish clinical centre was assessed. Data on socio-demographic, consumption, psychopathological and maladjustment characteristics were collected using the European Addiction Severity Index (EuropASI), the Symptom Checklist-90-Revised (SCL-90-R) and the Millon Clinical Multiaxial Inventory (MCMI-II). Demographically, differences were observed with regard to age (alcoholics were older than cocaine addicts; t = 12.2, p = .001), employment (the alcoholic group had more labor problems; χ 2 = 6.2, p = .045) and family consequences (worse in alcoholics; t = 2.3, p = .025). The EuropASI results showed statistically significant differences in addiction severity, with alcoholics showing a greater severity than cocaine addicts. In terms of psychopathology, alcoholics presented more associated symptomatology than cocaine addicts. According to these results, patients with alcohol dependence have a different profile from patients with cocaine dependence, resulting in different repercussions for important areas of their lives. These differences should be taken into account when standard treatments for addiction are implemented.

  10. Recreational cocaine use is associated with attenuated latent inhibition.

    Science.gov (United States)

    Soar, Kirstie; Dawkins, Lynne; Page, Frederick; Wooldridge, Joseph

    2015-11-01

    Evidence has linked chronic cocaine use with various cognitive deficits; however few studies have investigated the effects of recreational (non-dependent) use. The present study aimed to assess whether recreational users show deficits in latent inhibition (LI: a measure of delayed learning of an association between 2 stimuli, one of which has been previously exposed (PE) without consequence and thus deemed irrelevant). Using a quasi-experimental between groups design, recreational cocaine users (n = 21), poly-drug users (n = 17) and drug-naive controls (n = 18) were compared on a LI task. Questionnaires assessing psychological health and drug use were also completed. There was a statistically significant interaction between condition (PE vs non PE) and group (cocaine, polydrug and control); cocaine users scored lower in the PE condition compared to polydrug users and controls, indicating quicker learning. Recreational cocaine users show attenuated LI reflecting reduced ability to filter out irrelevant stimuli enabling faste