Withdrawal symptoms in internet gaming disorder: A systematic review.

Science.gov (United States)

Kaptsis, Dean; King, Daniel L; Delfabbro, Paul H; Gradisar, Michael

2016-02-01

Internet gaming disorder (IGD) is currently positioned in the appendix of the DSM-5 as a condition requiring further study. The aim of this review was to examine the state of current knowledge of gaming withdrawal symptomatology, given the importance of withdrawal in positioning the disorder as a behavioral addiction. A total of 34 studies, including 10 qualitative studies, 17 research reports on psychometric instruments, and 7 treatment studies, were evaluated. The results indicated that the available evidence on Internet gaming withdrawal is very underdeveloped. Internet gaming withdrawal is most consistently referred to as 'irritability' and 'restlessness' following cessation of the activity. There exists a concerning paucity of qualitative studies that provide detailed clinical descriptions of symptoms arising from cessation of internet gaming. This has arguably compromised efforts to quantify withdrawal symptoms in empirical studies of gaming populations. Treatment studies have not reported on the natural course of withdrawal and/or withdrawal symptom trajectory following intervention. It is concluded that many more qualitative clinical studies are needed, and should be prioritised, to develop our understanding of gaming withdrawal. This should improve clinical descriptions of problematic internet gaming and in turn improve the quantification of IGD withdrawal and thus treatments for harmful internet gaming. Copyright © 2015 Elsevier Ltd. All rights reserved.

Time-course of the DSM-5 cannabis withdrawal symptoms in poly-substance abusers

DEFF Research Database (Denmark)

Hesse, Morten; Thylstrup, Birgitte

2013-01-01

Background Evidence is accumulating that a cannabis withdrawal syndrome is common, of clinical significance, and has a clear time course. Up till now, very limited data exist on the cannabis withdrawal symptoms in patients with co-morbid substance use disorders, other than cannabis use and tobacco...... the DSM-5 Withdrawal Symptom Check List with withdrawal symptoms from all classes of substances, with no indication that the described symptoms should be attributed to withdrawal. Self-reported time since last use of cannabis was used as a predictor of cannabis withdrawal severity. Results...... With the exception of loss of appetite, time since last use of cannabis was associated with all types of withdrawal symptoms listed in the DSM-5. Only four of 19 symptoms intended to measure withdrawal from other substances were related to time since last use of cannabis, including vivid, unpleasant dreams...

Cocaine Administration and Its Withdrawal Enhance the Expression of Genes Encoding Histone-Modifying Enzymes and Histone Acetylation in the Rat Prefrontal Cortex.

Science.gov (United States)

Sadakierska-Chudy, Anna; Frankowska, Małgorzata; Jastrzębska, Joanna; Wydra, Karolina; Miszkiel, Joanna; Sanak, Marek; Filip, Małgorzata

2017-07-01

Chronic exposure to cocaine, craving, and relapse are attributed to long-lasting changes in gene expression arising through epigenetic and transcriptional mechanisms. Although several brain regions are involved in these processes, the prefrontal cortex seems to play a crucial role not only in motivation and decision-making but also in extinction and seeking behavior. In this study, we applied cocaine self-administration and extinction training procedures in rats with a yoked triad to determine differentially expressed genes in prefrontal cortex. Microarray analysis showed significant upregulation of several genes encoding histone modification enzymes during early extinction training. Subsequent real-time PCR testing of these genes following cocaine self-administration or early (third day) and late (tenth day) extinction revealed elevated levels of their transcripts. Interestingly, we found the enrichment of Brd1 messenger RNA in rats self-administering cocaine that lasted until extinction training during cocaine withdrawal with concomitant increased acetylation of H3K9 and H4K8. However, despite elevated levels of methyl- and demethyltransferase-encoded transcripts, no changes in global di- and tri-methylation of histone H3 at lysine 4, 9, 27, and 79 were observed. Surprisingly, at the end of extinction training (10 days of cocaine withdrawal), most of the analyzed genes in the rats actively and passively administering cocaine returned to the control level. Together, the alterations identified in the rat prefrontal cortex may suggest enhanced chromatin remodeling and transcriptional activity induced by early cocaine abstinence; however, to know whether they are beneficial or not for the extinction of drug-seeking behavior, further in vivo evaluation is required.

Crack cocaine inhalation induces schizophrenia-like symptoms and molecular alterations in mice prefrontal cortex.

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Areal, Lorena Bianchine; Herlinger, Alice Laschuk; Pelição, Fabrício Souza; Martins-Silva, Cristina; Pires, Rita Gomes Wanderley

2017-08-01

Crack cocaine (crack) addiction represents a major social and health burden, especially seeing as users are more prone to engage in criminal and violent acts. Crack users show a higher prevalence of psychiatric comorbidities - particularly antisocial personality disorders - when compared to powder cocaine users. They also develop cognitive deficits related mainly to executive functions, including working memory. It is noteworthy that stimulant drugs can induce psychotic states, which appear to mimic some symptoms of schizophrenia among users. Social withdraw and executive function deficits are, respectively, negative and cognitive symptoms of schizophrenia mediated by reduced dopamine (DA) tone in the prefrontal cortex (PFC) of patients. That could be explained by an increased expression of D2R short isoform (D2S) in the PFC of such patients and/or by hypofunctioning NMDA receptors in this region. Reduced DA tone has already been described in the PFC of mice exposed to crack smoke. Therefore, it is possible that behavioral alterations presented by crack users result from molecular and biochemical neuronal alterations akin to schizophrenia. Accordingly, we found that upon crack inhalation mice have shown decreased social interaction and working memory deficits analogous to schizophrenia's symptoms, along with increased D2S/D2L expression ratio and decreased expression of NR1, NR2A and NR2B NMDA receptor subunits in the PFC. Herein we propose two possible mechanisms to explain the reduced DA tone in the PFC elicited by crack consumption in mice, bringing also the first direct evidence that crack use may result in schizophrenia-like neurochemical, molecular and behavioral alterations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Self-reported cue-induced physical symptoms of craving as an indicator of cocaine dependence

NARCIS (Netherlands)

Vorspan, Florence; Fortias, Maeva; Zerdazi, El-Hadi; Karsinti, Emily; Bloch, Vanessa; Lépine, Jean-Pierre; Bellivier, Frank; Brousse, Georges; van den Brink, Wim; Derks, Eske M.

2015-01-01

The presence of cocaine dependence is under-recognized by cocaine users and requires a careful standardized interview to be ascertained by clinicians. To test if past experiences of cue-induced physical symptoms of craving (nausea, vomiting, sweating, shaking, nervousness) before cocaine use could

Psychotic Symptoms Associated with the use of Dopaminergic Drugs, in Patients with Cocaine Dependence or Abuse.

Science.gov (United States)

Roncero, Carlos; Abad, Alfonso C; Padilla-Mata, Antonio; Ros-Cucurull, Elena; Barral, Carmen; Casas, Miquel; Grau-López, Lara

2017-01-01

In the field of dual diagnosis, physicians are frequently presented with pharmacological questions. Questions about the risk of developing psychotic symptoms in cocaine users who need treatment with dopaminergic drugs could lead to an undertreatment. Review the presence of psychotic symptoms in patients with cocaine abuse/dependence, in treatment with dopaminergic drugs. Systematic PubMed searches were conducted including December 2014, using the keywords: "cocaine", dopaminergic drug ("disulfuram-methylphenidate-bupropion-bromocriptine-sibutramineapomorphine- caffeine") and ("psychosis-psychotic symptoms-delusional-paranoia"). Articles in English, Spanish, Portuguese, French, and Italian were included. Articles in which there was no history of cocaine abuse/dependence, absence of psychotic symptoms, systematic reviews, and animal studies, were excluded. 313 papers were reviewed. 7 articles fulfilled the inclusion-exclusion criteria. There is a clinical trial including 8 cocaine-dependent patients using disulfiram in which 3 of them presented psychotic symptoms and 6 case-reports: disulfuram (1), methylphenidate (1), disulfiram with methylphenidate (2), and bupropion (2), reporting psychotic symptoms, especially delusions of reference and persecutory ideation. Few cases have been described, which suggests that the appearance of these symptoms is infrequent. The synergy of dopaminergic effects or the dopaminergic sensitization in chronic consumption are the explanatory theories proposed by the authors. In these cases, a relationship was found between taking these drugs and the appearance of psychotic symptoms. Given the low number of studies found, further research is required. The risk of psychotic symptoms seems to be acceptable if we compare it with the benefits for the patients but a closer monitoring seems to be advisable.

Opioid withdrawal signs and symptoms in children: frequency and determinants.

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Fisher, Deborah; Grap, Mary Jo; Younger, Janet B; Ameringer, Suzanne; Elswick, R K

2013-01-01

The purpose of this study was to, in a pediatric population, describe the frequency of opioid withdrawal signs and symptoms and to identify factors associated with these opioid withdrawal signs and symptoms. Opioids are used routinely in the pediatric intensive care population for analgesia, sedation, blunting of physiologic responses to stress, and safety. In children, physical dependence may occur in as little as 2-3 days of continuous opioid therapy. Once the child no longer needs the opioid, the medications are reduced over time. A prospective, descriptive study was conducted. The sample of 26 was drawn from all patients, ages 2 weeks to 21 years admitted to the Children's Hospital of Richmond pediatric intensive care unit (PICU) and who have received continuous infusion or scheduled opioids for at least 5 days. Data collected included: opioid withdrawal score (WAT-1), opioid taper rate (total dose of opioid per day in morphine equivalents per kilogram [MEK]), pretaper peak MEK, pretaper cumulative MEK, number of days of opioid exposure prior to taper, and age. Out of 26 enrolled participants, only 9 (45%) had opioid withdrawal on any given day. In addition, there was limited variability in WAT-1 scores. The most common symptoms notes were diarrhea, vomit, sweat, and fever. For optimal opioid withdrawal assessments, clinicians should use a validated instrument such as the WAT-1 to measure for signs and symptoms of opioid withdrawal. Further research is indicated to examine risk factors for opioid withdrawal in children. Copyright © 2013 Elsevier Inc. All rights reserved.

Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes

Directory of Open Access Journals (Sweden)

Deborah C. Mash

2018-06-01

Full Text Available Ibogaine may be effective for transitioning opioid and cocaine dependent individuals to sobriety. American and European self-help groups provided public testimonials that ibogaine alleviated drug craving and opioid withdrawal symptoms after only a single dose administration. Preclinical studies in animal models of addiction have provided proof-of-concept evidence in support of these claims. However, the purported therapeutic benefits of ibogaine are based on anecdotal reports from a small series of case reports that used retrospective recruitment procedures. We reviewed clinical results from an open label case series (N = 191 of human volunteers seeking to detoxify from opioids or cocaine with medical monitoring during inpatient treatment. Whole blood was assayed to obtain pharmacokinetic measures to determine the metabolism and clearance of ibogaine. Clinical safety data and adverse events (AEs were studied in male and female subjects. There were no significant adverse events following administration of ibogaine in a dose range that was shown to be effective for blocking opioid withdrawal symptoms in this study. We used multi-dimensional craving questionnaires during inpatient detoxification to test if ibogaine was effective in diminishing heroin and cocaine cravings. Participants also completed standardized questionnaires about their health and mood before and after ibogaine treatment, and at program discharge. One-month follow-up data were reviewed where available to determine if ibogaine’s effects on drug craving would persist outside of an inpatient setting. We report here that ibogaine therapy administered in a safe dose range diminishes opioid withdrawal symptoms and reduces drug cravings. Pharmacological treatments for opioid dependence include detoxification, narcotic antagonists and long-term opioid maintenance therapy. Our results support product development of single oral dose administration of ibogaine for the treatment of opioid

Tobacco withdrawal symptoms mediate motivation to reinstate smoking during abstinence.

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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).

Timing of nicotine lozenge administration to minimize trigger induced craving and withdrawal symptoms.

Science.gov (United States)

Kotlyar, Michael; Lindgren, Bruce R; Vuchetich, John P; Le, Chap; Mills, Anne M; Amiot, Elizabeth; Hatsukami, Dorothy K

2017-08-01

Smokers are often advised to use nicotine lozenge when craving or withdrawal symptoms occur. This may be too late to prevent lapses. This study assessed if nicotine lozenge use prior to a common smoking trigger can minimize trigger induced increases in craving and withdrawal symptoms. Eighty-four smokers completed two laboratory sessions in random order. At one session, nicotine lozenge was given immediately after a stressor (to approximate current recommended use - i.e., after craving and withdrawal symptoms occur); at the other session subjects were randomized to receive nicotine lozenge at time points ranging from immediately to 30min prior to the stressor. Withdrawal symptoms and urge to smoke were measured using the Minnesota Nicotine Withdrawal Scale and the Questionnaire of Smoking Urges (QSU). Relative to receiving lozenge after the stressor, a smaller increase in pre-stressor to post-stressor withdrawal symptom scores occurred when lozenge was used immediately (p=0.03) and 10min prior (p=0.044) to the stressor. Results were similar for factors 1 and 2 of the QSU when lozenge was used immediately prior to the stressor (pnicotine lozenge prior to a smoking trigger can decrease trigger induced craving and withdrawal symptoms. Future studies are needed to determine if such use would increase cessation rates. Clinicaltrials.gov # NCT01522963. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased sensorimotor gating in recreational and dependent cocaine users is modulated by craving and attention-deficit/hyperactivity disorder symptoms.

Science.gov (United States)

Preller, Katrin H; Ingold, Nina; Hulka, Lea M; Vonmoos, Matthias; Jenni, Daniela; Baumgartner, Markus R; Vollenweider, Franz X; Quednow, Boris B

2013-02-01

Cocaine dependence has been associated with blunted dopamine and norepinephrine signaling, but it is unknown if recreational cocaine use is also associated with alterations of catecholamine systems. Prepulse inhibition (PPI) of the acoustic startle response-a measure of sensorimotor gating-is highly sensitive for manipulations of the catecholamine system. Therefore, we investigated whether relatively pure recreational users (RCU) and dependent cocaine users (DCU) display alterations of PPI, startle reactivity, and habituation. Moreover, the influences of methylenedioxymethamphetamine and cannabis co-use, craving, and attention-deficit/hyperactivity disorder (ADHD) symptoms on startle measures were examined. In 64 RCU, 29 DCU, and 66 stimulant-naïve control subjects, PPI of acoustic startle response, startle reactivity, habituation, ADHD symptoms, and cocaine craving were assessed. Drug use of all participants was controlled by hair and urine toxicologies. Both RCU and DCU showed increased PPI in comparison with control participants (Cohen's d=.38 and d=.67, respectively), while RCU and DCU did not differ in PPI measures (d=.12). No significant group differences were found in startle reactivity or habituation measures. In cocaine users, PPI was positively correlated with cumulative cocaine dose used, craving for cocaine, and ADHD symptoms. Users with a diagnosis of ADHD and strong craving symptoms displayed the highest PPI levels compared with control subjects (d=.78). The augmented PPI in RCU and DCU suggests that recreational use of cocaine is associated with altered catecholamine signaling, in particular if ADHD or craving symptoms are present. Finally, ADHD might be a critical risk factor for cocaine-induced changes of the catecholamine system. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice.

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Metten, Pamela; Schlumbohm, Jason P; Huang, Lawrence C; Greenberg, Gian D; Hack, Wyatt R; Spence, Stephanie E; Crabbe, John C

2018-05-01

Despite acceptance that risk for alcohol-use disorder (AUD) has a large genetic component, the identification of genes underlying various components of risk for AUD has been hampered in humans, in part by the heterogeneity of expression of the phenotype. One aspect of AUD is physical dependence. Alcohol withdrawal is a serious consequence of alcohol dependence with multiple symptoms, many of which are seen in multiple species, and can be experienced over a wide-ranging time course. In the present three studies, we developed a battery of withdrawal tests in mice, examining behavioral symptoms from multiple domains that could be measured over time. To permit eventual use of the battery in different strains of mice, we used male and female mice of a genetically heterogeneous stock developed from intercrossing eight inbred strains. Withdrawal symptoms were assessed using commonly used tests after administration of ethanol in vapor for 72 continuous hours. We found significant effects of ethanol withdrawal versus air-breathing controls on nearly all symptoms, spanning 4 days following ethanol vapor inhalation. Withdrawal produced hypothermia, greater neurohyperexcitability (seizures and tremor), anxiety-like behaviors using an apparatus (such as reduced transitions between light and dark compartments), anhedonia (reduced sucrose preference), Straub tail, backward walking, and reductions in activity; however, there were no changes in thermal pain sensitivity, hyper-reactivity to handling, or anxiety-like emergence behaviors in other apparatus. Using these data, we constructed a refined battery of withdrawal tests. Individual differences in severity of withdrawal among different tests were weakly correlated at best. This battery should be useful for identifying genetic influences on particular withdrawal behaviors, which should reflect the influences of different constellations of genes. Published by Elsevier Inc.

Personality Disorders Classification and Symptoms in Cocaine and Opioid Addicts.

Science.gov (United States)

Malow, Robert M.; And Others

1989-01-01

Examined extent to which personality disorders and associated symptom criteria were found among 117 cocaine- and opioid-dependent men in drug dependence treatment unit. Drug groups were distinguished by higher rates of antisocial and borderline symptomatology rather than by features associated with other personality disorders. Different…

A 'symptom-triggered' approach to alcohol withdrawal management.

Science.gov (United States)

Murdoch, Jay; Marsden, Janet

In acute hospital settings, alcohol withdrawal often causes significant management problems and complicates a wide variety of concurrent conditions, placing a huge burden on the NHS. A significant number of critical incidents around patients who were undergoing detoxification in a general hospital setting led to the need for a project to implement and evaluate an evidence-based approach to the management of alcohol detoxification-a project that included a pre-intervention case note audit, the implementation of an evidence-based symptom-triggered detoxification protocol, and a post-intervention case note audit. This change in practice resulted in an average reduction of almost 60% in length of hospital stay and a 66% reduction in the amount of chlordiazepoxide used in detoxification, as well as highlighting that 10% of the sample group did not display any signs of withdrawal and did not require any medication. Even with these reductions, no patient post-intervention developed any severe signs of withdrawal phenomena, such as seizures or delirium tremens. The savings to the trust (The Pennine Acute Hospital Trust) are obvious,but the development of a consistent, quality service will lead to fewer long-term negative effects for patients that can be caused by detoxification. This work is a project evaluation of a locally implemented strategy, which, it was hypothesised,would improve care by providing an individualised treatment plan for the management of alcohol withdrawal symptoms.

Short-course diphenoxylate hydrochloride for treatment of methadone withdrawal symptoms.

Science.gov (United States)

Ives, T J; Stults, C C

1983-11-01

The authors conducted a preliminary trial of a 5-day course of diphenoxylate in the treatment of out-patients with methadone withdrawal symptoms. Diphenoxylate provided substantial relief from detoxification symptoms with no drug-associated adverse effects.

Trajectories of abstinence-induced Internet gaming withdrawal symptoms: A prospective pilot study

Directory of Open Access Journals (Sweden)

Dean Kaptsis

2016-12-01

Full Text Available Internet Gaming Disorder (IGD is positioned in the appendix of the DSM-5 as a condition requiring further study. The IGD criteria refer to withdrawal symptoms, including irritability, anxiety, or sadness, that follow cessation of Internet gaming (APA, 2013. The aim of this study was to prospectively examine the nature of Internet gaming withdrawal symptoms, if they occur, under gaming abstinence conditions. This study employed a repeated-measures protocol to examine the cognitive-affective reactions of participants undertaking an 84-h Internet gaming abstinence period. The sample included individuals who met the IGD criteria as well as those who regularly played Internet games but did not meet the IGD criteria. Outcome variables included affect (positive and negative, psychological distress (depression, anxiety, stress, and Internet gaming withdrawal symptoms (craving/urge, thoughts about gaming, inability to resist gaming. A total of 24 participants (Mage = 24.6 years, SD = 5.8 were recruited from online gaming communities, and completed a series of online surveys before, during, and after abstaining from Massively Multiplayer Online (MMO games. Both the IGD group and the non-IGD group experienced an abstinence-induced decline in withdrawal symptomatology, negative affect, and psychological distress. The IGD group experienced its largest decline in withdrawal symptomatology within the first 24 h of abstinence. These preliminary data suggest that gaming withdrawal symptoms may follow, at least initially, negative linear and quadratic trends. Further prospective work in larger samples involving longer periods of abstinence is required to verify and expand upon these observations.

Trajectories of abstinence-induced Internet gaming withdrawal symptoms: A prospective pilot study.

Science.gov (United States)

Kaptsis, Dean; King, Daniel L; Delfabbro, Paul H; Gradisar, Michael

2016-12-01

Internet Gaming Disorder (IGD) is positioned in the appendix of the DSM-5 as a condition requiring further study. The IGD criteria refer to withdrawal symptoms, including irritability, anxiety, or sadness, that follow cessation of Internet gaming (APA, 2013). The aim of this study was to prospectively examine the nature of Internet gaming withdrawal symptoms, if they occur, under gaming abstinence conditions. This study employed a repeated-measures protocol to examine the cognitive-affective reactions of participants undertaking an 84-h Internet gaming abstinence period. The sample included individuals who met the IGD criteria as well as those who regularly played Internet games but did not meet the IGD criteria. Outcome variables included affect (positive and negative), psychological distress (depression, anxiety, stress), and Internet gaming withdrawal symptoms (craving/urge, thoughts about gaming, inability to resist gaming). A total of 24 participants ( M age  = 24.6 years, SD  = 5.8) were recruited from online gaming communities, and completed a series of online surveys before, during, and after abstaining from Massively Multiplayer Online (MMO) games. Both the IGD group and the non-IGD group experienced an abstinence-induced decline in withdrawal symptomatology, negative affect, and psychological distress. The IGD group experienced its largest decline in withdrawal symptomatology within the first 24 h of abstinence. These preliminary data suggest that gaming withdrawal symptoms may follow, at least initially, negative linear and quadratic trends. Further prospective work in larger samples involving longer periods of abstinence is required to verify and expand upon these observations.

Opioid interruptions, pain, and withdrawal symptoms in nursing home residents.

Science.gov (United States)

Redding, Sarah E; Liu, Sophia; Hung, William W; Boockvar, Kenneth S

2014-11-01

Interruptions in opioid use have the potential to cause pain relapse and withdrawal symptoms. The objectives of this study were to observe patterns of opioid interruption during acute illness in nursing home residents and examine associations between interruptions and pain and withdrawal symptoms. Patients from 3 nursing homes in a metropolitan area who were prescribed opioids were assessed for symptoms of pain and withdrawal by researchers blinded to opioid dosage received, using the Brief Pain Inventory Scale and the Clinical Opioid Withdrawal Scale, respectively, during prespecified time periods. The prespecified time periods were 2 weeks after onset of acute illness (eg, urinary tract infection), and 2 weeks after hospital admission and nursing home readmission, if they occurred. Opioid dosing was recorded and a significant interruption was defined as a complete discontinuation or a reduction in dose of >50% for ≥1 day. The covariates age, sex, race, comorbid conditions, initial opioid dose, and initial pain level were recorded. Symptoms pre- and post-opioid interruptions were compared and contrasted with those in a group without opioid interruptions. Sixty-six patients receiving opioids were followed for a mean of 10.9 months and experienced a total of 104 acute illnesses. During 64 (62%) illnesses, patients experienced any reduction in opioid dosing, with a mean (SD) dose reduction of 63.9% (29.9%). During 39 (38%) illnesses, patients experienced a significant opioid interruption. In a multivariable model, residence at 1 of the 3 nursing homes was associated with a lower risk of interruption (odds ratio = 0.073; 95% CI, 0.009 to 0.597; P pain score (difference -0.50 [2.66]; 95% CI, -3.16 to 2.16) and withdrawal score (difference -0.91 [3.12]; 95% CI, -4.03 to 2.21) after the interruption as compared with before interruption. However, when compared with patients without interruptions, patients with interruptions experienced larger increases in pain scores

Cocaine Dysregulates Opioid Gating of GABA Neurotransmission in the Ventral Pallidum

Science.gov (United States)

Scofield, Michael D.; Rice, Kenner C.; Cheng, Kejun; Roques, Bernard P.

2014-01-01

The ventral pallidum (VP) is a target of dense nucleus accumbens projections. Many of these projections coexpress GABA and the neuropeptide enkephalin, a δ and μ opioid receptor (MOR) ligand. Of these two, the MOR in the VP is known to be involved in reward-related behaviors, such as hedonic responses to palatable food, alcohol intake, and reinstatement of cocaine seeking. Stimulating MORs in the VP decreases extracellular GABA, indicating that the effects of MORs in the VP on cocaine seeking are via modulating GABA neurotransmission. Here, we use whole-cell patch-clamp on a rat model of withdrawal from cocaine self-administration to test the hypothesis that MORs presynaptically regulate GABA transmission in the VP and that cocaine withdrawal changes the interaction between MORs and GABA. We found that in cocaine-extinguished rats pharmacological activation of MORs no longer presynaptically inhibited GABA release, whereas blocking the MORs disinhibited GABA release. Moreover, MOR-dependent long-term depression of GABA neurotransmission in the VP was lost in cocaine-extinguished rats. Last, GABA neurotransmission was found to be tonically suppressed in cocaine-extinguished rats. These substantial synaptic changes indicated that cocaine was increasing tone on MOR receptors. Accordingly, increasing endogenous tone by blocking the enzymatic degradation of enkephalin inhibited GABA neurotransmission in yoked saline rats but not in cocaine-extinguished rats. In conclusion, our results indicate that following withdrawal from cocaine self-administration enkephalin levels in the VP are elevated and the opioid modulation of GABA neurotransmission is impaired. This may contribute to the difficulties withdrawn addicts experience when trying to resist relapse. PMID:24431463

Trajectories of abstinence-induced Internet gaming withdrawal symptoms: A prospective pilot study

OpenAIRE

Dean Kaptsis; Daniel L. King; Paul H. Delfabbro; Michael Gradisar

2016-01-01

Internet Gaming Disorder (IGD) is positioned in the appendix of the DSM-5 as a condition requiring further study. The IGD criteria refer to withdrawal symptoms, including irritability, anxiety, or sadness, that follow cessation of Internet gaming (APA, 2013). The aim of this study was to prospectively examine the nature of Internet gaming withdrawal symptoms, if they occur, under gaming abstinence conditions. This study employed a repeated-measures protocol to examine the cognitive-affective ...

Drug withdrawal symptoms in children after continuous infusions of fentanyl.

Science.gov (United States)

French, J P; Nocera, M

1994-04-01

The purpose of this research was to determine the extent to which critically ill infants exhibited signs and symptoms of narcotic withdrawal after receiving continuous infusions of fentanyl. The convenience sample consisted of 12 pediatric intensive care unit (PICU) patients under 25 months of age who received fentanyl infusions for at least 24 hours. Drug withdrawal symptoms were monitored using the Neonatal Abstinence Score Tool (NAST), which assigns a score to each behavior indicative of withdrawal. A score of 8 or greater indicates Neonatal Abstinence Syndrome (NAS). Scoring began 4 hours after discontinuation of fentanyl and was conducted once per hour for 8 hours. Six subjects had a NAST score exceeding 8; these infants frequently exhibited tremors with or without stimulation, increased muscle tone, insomnia, and increased respiratory rate and effort. There were significant correlations between fentanyl dosage and NAST score (r = .76, p observation protocol and a possible weaning regimen after fentanyl is discontinued.

Cocaine: from addiction to functional imaging

International Nuclear Information System (INIS)

Tamgac, F.; Baillet, G.; Moretti, J.L.; Tikofski, R.

1997-01-01

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. 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)

Brain imaging studies of the cocaine addict: Implications for reinforcement and addiction

Energy Technology Data Exchange (ETDEWEB)

Volkow, N.D.; Fowler, J.S. [Brookhaven National Lab., Upton, NY (United States)]|[SUNY, Stony Brook, Stony Brook, NY (United States). Dept. of Psychiatry

1995-07-01

These studies document dopaminergic abnormalities in cocaine abusers. They also suggest a regulatory role of Dopamine (DA) in frontal metabolism. The correlation of striatal D{sub 2} receptor availability with metabolism was strongest for orbital frontal cortex (OFC) cingulate and prefrontal cortices. In cocaine abusers tested during early withdrawal (<1 week) the OFC was found to be hypermetabolic and metabolism in OFC and prefrontal cortices were found to be significantly associated with cocaine craving . Thus, we postulate that repeated and intermittent DA stimulation, as seen during a cocaine binge, activates the prefrontal and OFC cortices increasing the drive to compulsively self-administer cocaine. During cocaine discontinuation and protracted withdrawal and with decreased DA stimulation, these frontal cortical regions become hyponietabolic. Dopaminergic stimulation by a DA-enhancing drug and/or environmental conditioning will reactivate these frontal regions resetting the compulsion to self-administer cocaine and the inability to terminate this behavior. The pharmacokionetic studies with [11C]cocaine are consistent with behavioral and pharmacological studies in animals as well as in vitro studies which have revealed that while the mechanisms for cocaine`s reinforcing properties are complex, they partly involve the brain`s dopamine system and also highlight the importance of cocaine`s pharmacokinetic on its unique reinforcing properties.

Chronic restraint stress during withdrawal increases vulnerability to drug priming-induced cocaine seeking via a dopamine D1-like receptor-mediated mechanism.

Science.gov (United States)

Ball, Kevin T; Stone, Eric; Best, Olivia; Collins, Tyler; Edson, Hunter; Hagan, Erin; Nardini, Salvatore; Neuciler, Phelan; Smolinsky, Michael; Tosh, Lindsay; Woodlen, Kristin

2018-06-01

A major obstacle in the treatment of individuals with cocaine addiction is their high propensity for relapse. Although the clinical scenario of acute stress-induced relapse has been well studied in animal models, few pre-clinical studies have investigated the role of chronic stress in relapse or the interaction between chronic stress and other relapse triggers. We tested the effect of chronic restraint stress on cocaine seeking in rats using both extinction- and abstinence-based animal relapse models. Rats were trained to press a lever for I.V. cocaine infusions (0.50 mg/kg/infusion) paired with a discrete tone + light cue in daily 3-h sessions. Following self-administration, rats were exposed to a chronic restraint stress procedure (3 h/day) or control procedure (unstressed) during the first seven days of a 13-day extinction period during which lever presses had no programmed consequences. This was followed by cue- and cocaine priming-induced drug seeking tests. In a separate group of rats, cocaine seeking was assessed during forced abstinence both before and after the same chronic stress procedure. A history of chronic restraint stress was associated with increased cocaine priming-induced drug seeking, an effect attenuated by co-administration of SCH-23390 (10.0 μg/kg; i.p.), a dopamine D 1 -like receptor antagonist, with daily restraint. Repeated SCH-23390 administration but not stress during extinction increased cue-induced reinstatement. Exposure to chronic stress during early withdrawal may confer lasting vulnerability to some types of relapse, and dopamine D 1 -like receptors appear to mediate both chronic stress effects on cocaine seeking and extinction of cocaine seeking. Copyright © 2018 Elsevier B.V. All rights reserved.

Caffeine withdrawal symptoms and self-administration following caffeine deprivation.

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Mitchell, S H; de Wit, H; Zacny, J P

1995-08-01

This study examined the effects of complete or partial caffeine deprivation on withdrawal symptomatology and self-administration of coffee in caffeine-dependent coffee drinkers. Nine habitual coffee drinkers abstained from dietary sources of caffeine for 33.5 h. Caffeine deprivation was manipulated by administering capsules containing 0%, 50%, or 100% of each subject's daily caffeine intake (complete, partial, and no deprivation conditions). Caffeine withdrawal symptomatology was measured using self-report questionnaires. Caffeine self-administration was measured using: i) the amount of coffee subjects earned on a series of concurrent random-ratio schedules that yielded coffee and money reinforcers; ii) the amount of earned coffee they consumed. Saliva samples revealed that subjects complied with the caffeine abstinence instructions. Caffeine withdrawal symptoms occurred reliably following complete caffeine deprivation, though not in the partial deprivation condition. Caffeine self-administration was not related to deprivation condition. We conclude that caffeine withdrawal symptomatology is not necessarily associated with increased caffeine consumption.

Mothers' early depressive symptoms and children's first-grade adjustment: a transactional analysis of child withdrawal as a mediator.

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Yan, Ni; Dix, Theodore

2014-05-01

The depression-inhibition hypothesis suggests that mothers' depressive symptoms undermine development because they lead children to withdraw from social contact. To test this, this study examined whether poor first-grade adjustment among children of mothers with depressive symptoms is mediated by the emergence of child withdrawal in early development. Based on 1,364 dyads, four waves of data spanning from 24 months to first grade (7 years) were used to examine paths by which children's withdrawal mediates relations between mothers' early depressive symptoms and three first-grade outcomes: social competence, academic performance, and externalizing behavior problems. Structural equation modeling revealed three principal paths. First, direct relations were observed: Mothers' depressive symptoms predicted early child withdrawal and increases in child withdrawal over time, which predicted poor first-grade adjustment. Second, reciprocal relations were observed: Mothers' depressive symptoms predicted child withdrawal, which predicted increases in depressive symptoms. Third, relations via mother-child mutual responsiveness were observed: Depression-related increases in child withdrawal predicted declines in mutual responsiveness, which predicted poor first-grade adjustment. The findings suggest that, due to its interdependence with maternal depression and low mother-child mutual responsiveness over time, child withdrawal may play an important role in the poor first-grade adjustment of children whose mothers are high in depressive symptoms. © 2013 The Authors. Journal of Child Psychology and Psychiatry. © 2013 Association for Child and Adolescent Mental Health.

Response of the Ubiquitin-Proteasome System to Memory Retrieval After Extended-Access Cocaine or Saline Self-Administration.

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Werner, Craig T; Milovanovic, Mike; Christian, Daniel T; Loweth, Jessica A; Wolf, Marina E

2015-12-01

The ubiquitin-proteasome system (UPS) has been implicated in the retrieval-induced destabilization of cocaine- and fear-related memories in Pavlovian paradigms. However, nothing is known about its role in memory retrieval after self-administration of cocaine, an operant paradigm, or how the length of withdrawal from cocaine may influence retrieval mechanisms. Here, we examined UPS activity after an extended-access cocaine self-administration regimen that leads to withdrawal-dependent incubation of cue-induced cocaine craving. Controls self-administered saline. In initial experiments, memory retrieval was elicited via a cue-induced seeking/retrieval test on withdrawal day (WD) 50-60, when craving has incubated. We found that retrieval of cocaine- and saline-associated memories produced similar increases in polyubiquitinated proteins in the nucleus accumbens (NAc), compared with rats that did not undergo a seeking/retrieval test. Measures of proteasome catalytic activity confirmed similar activation of the UPS after retrieval of saline and cocaine memories. However, in a subsequent experiment in which testing was conducted on WD1, proteasome activity in the NAc was greater after retrieval of cocaine memory than saline memory. Analysis of other brain regions confirmed that effects of cocaine memory retrieval on proteasome activity, relative to saline memory retrieval, depend on withdrawal time. These results, combined with prior studies, suggest that the relationship between UPS activity and memory retrieval depends on training paradigm, brain region, and time elapsed between training and retrieval. The observation that mechanisms underlying cocaine memory retrieval change depending on the age of the memory has implications for development of memory destabilization therapies for cue-induced relapse in cocaine addicts.

Acute exercise effects on smoking withdrawal symptoms and desire to smoke are not related to expectation.

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Daniel, James Z; Cropley, Mark; Fife-Schaw, Chris

2007-11-01

Recent research has shown that 10 min of moderate intensity exercise reduce smoking withdrawal symptoms and desire to smoke in acutely abstinent smokers. The aim of the current study was to determine whether the reductions are related to participant expectation of these effects. Forty-five sedentary participants who had smoked ten or more cigarettes per day for at least 3 years reported their expectation of the effects of exercise on smoking withdrawal symptoms. Approximately 1 month later, participants were randomly assigned to one of three groups after 11-15 h of overnight smoking abstinence. Each group read either a positive, negative or neutral statement concerning exercise effects on smoking withdrawal symptoms. They rated their expectation again and then completed 10 min of moderate intensity exercise on a stationary bicycle ergometer. Using standardised scales, participants rated smoking withdrawal symptoms and desire to smoke at 10, 5 and 0 min before exercise, then at 5 and 10 min during exercise and 15 and 20 min post-exercise. Expectation of exercise effects on withdrawal were manipulated in the predicted directions. No significant group main effects were found for any symptom. Significant reductions in symptoms and desire to smoke occurred during and after exercise regardless of participant expectation. Ten minutes of moderate intensity exercise can lead to reductions in desire to smoke and smoking withdrawal symptoms, which are not due to the participant's expectation of exercise effects. These findings support the use of short periods of exercise as an aid to smoking cessation.

Brain imaging studies of the cocaine addict: Implications for reinforcement and addiction

International Nuclear Information System (INIS)

Volkow, N.D.; Fowler, J.S.; SUNY, Stony Brook, Stony Brook, NY

1995-01-01

These studies document dopaminergic abnormalities in cocaine abusers. They also suggest a regulatory role of Dopamine (DA) in frontal metabolism. The correlation of striatal D 2 receptor availability with metabolism was strongest for orbital frontal cortex (OFC) cingulate and prefrontal cortices. In cocaine abusers tested during early withdrawal (<1 week) the OFC was found to be hypermetabolic and metabolism in OFC and prefrontal cortices were found to be significantly associated with cocaine craving . Thus, we postulate that repeated and intermittent DA stimulation, as seen during a cocaine binge, activates the prefrontal and OFC cortices increasing the drive to compulsively self-administer cocaine. During cocaine discontinuation and protracted withdrawal and with decreased DA stimulation, these frontal cortical regions become hyponietabolic. Dopaminergic stimulation by a DA-enhancing drug and/or environmental conditioning will reactivate these frontal regions resetting the compulsion to self-administer cocaine and the inability to terminate this behavior. The pharmacokionetic studies with [11C]cocaine are consistent with behavioral and pharmacological studies in animals as well as in vitro studies which have revealed that while the mechanisms for cocaine's reinforcing properties are complex, they partly involve the brain's dopamine system and also highlight the importance of cocaine's pharmacokinetic on its unique reinforcing properties

Acute effects of glucose tablets on craving, withdrawal symptoms, and sustained attention in 12-h abstinent tobacco smokers.

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Harakas, P; Foulds, J

2002-05-01

Glucose administration may decrease desire to smoke in abstinent smokers. Moreover, glucose administration has been associated with improved performance on measures of attention in healthy humans but evidence remains modest. The present study aimed to determine whether reported craving and nicotine withdrawal symptoms can be relieved, and sustained attention on the Rapid Visual Information Processing (RVIP) task improved, with the administration of 12 g oral glucose in nicotine-deprived smokers. Forty-one smokers, abstinent for 12 h, participated in a double-blind, placebo-controlled, randomized study to examine the effect of glucose on desire to smoke, withdrawal symptoms, and attention. Participants completed the RVIP task once and then rated craving and nicotine withdrawal symptoms before chewing four 3 g glucose tablets (experimental group) or four matched placebo tablets (control group). Following tablet consumption participants rated craving and withdrawal symptoms at 5-min intervals for 20 min. Subsequently a second RVIP task was performed, followed by a final rating of craving and withdrawal symptoms. Any effect of glucose across time was not statistically significant on craving, withdrawal symptoms, or performance on the RVIP task. There were no differences between the groups in measures of 'satisfaction' or 'sickness'. The present study failed to find a significant effect of 12 g oral glucose on tobacco craving, withdrawal symptoms, or sustained attention in relatively young tobacco smokers after 12 h of tobacco abstinence.

The comparative efficacy of first- versus second-generation electronic cigarettes in reducing symptoms of nicotine withdrawal.

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Lechner, William V; Meier, Ellen; Wiener, Josh L; Grant, DeMond M; Gilmore, Jenna; Judah, Matt R; Mills, Adam C; Wagener, Theodore L

2015-05-01

Currently, electronic cigarettes (e-cigarettes) are studied as though they are a homogeneous category. However, there are several noteworthy differences in the products that fall under this name, including potential differences in the efficacy of these products as smoking cessation aids. The current study examined the comparative efficacy of first- and second-generation e-cigarettes in reducing nicotine withdrawal symptoms in a sample of current smokers with little or no experience of using e-cigarettes. Twenty-two mildly to moderately nicotine-dependent individuals were randomized to a cross-over design in which they used first- and second-generation e-cigarettes on separate days with assessment of withdrawal symptoms directly prior to and after product use. A community-based sample recruited in the Midwest region of the United States reported a mean age of 28.6 [standard deviation (SD) = 12.9]. The majority were male (56.5%), Caucasian (91.3%), reported smoking an average of 15.2 (SD = 9.6) tobacco cigarettes per day, and a mean baseline carbon monoxide (CO) level of 18.7 parts per million (p.p.m.). Symptoms of withdrawal from nicotine were measured via the Mood and Physical Symptoms Scale. Analysis of changes in withdrawal symptoms revealed a significant time × product interaction F(1, 21)  = 5.057, P = 0.036, n(2) P  = 0.202. Participants experienced a larger reduction in symptoms of nicotine withdrawal after using second-generation compared with first-generation e-cigarettes. Second-generation e-cigarettes seem to be more effective in reducing symptoms of nicotine withdrawal than do first-generation e-cigarettes. © 2015 Society for the Study of Addiction.

Chronic inhibition of dopamine β-hydroxylase facilitates behavioral responses to cocaine in mice.

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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.

Chronic Inhibition of Dopamine β-Hydroxylase Facilitates Behavioral Responses to Cocaine in Mice

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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

Do withdrawal-like symptoms mediate increased marijuana smoking in individuals treated with venlafaxine-XR?

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Kelly, Meredith A; Pavlicova, Martina; Glass, Andrew; Mariani, John J; Bisaga, Adam; Sullivan, Maria A; Nunes, Edward V; Levin, Frances R

2014-11-01

Cannabis-dependent participants with depressive disorder are less likely to achieve abstinence with venlafaxine-XR (VEN-XR) treatment. Individuals on VEN-XR reported more severe withdrawal, despite not reducing their smoking behavior. We hypothesized that withdrawal-like symptoms, likely medication side effects, led to continued marijuana smoking in this group. We conducted a secondary analysis using Marijuana Withdrawal Checklist (MWC) scores and urine THC to test whether severity of withdrawal-like symptoms mediates the relationship between VEN-XR treatment and continued marijuana smoking. We included 103 participants (VEN-XR=51, Placebo=52). Marijuana use was dichotomized into smoking (THC>100 ng/ml) and non-smoking (THC ≤ 100 ng/ml) weeks. MWC scores were obtained weekly. We used three models in a regression based mediation analysis. The estimated risk of smoking marijuana was greater for individuals on VEN-XR in weeks 7-9, even when controlling for MWC scores (week 7 Risk Difference (RD)=0.11, p=0.034; week 8 RD=0.20, p=0.014), and higher scores mediated this effect. In weeks 10 and 11, the estimated effect was stronger (week 10 RD=0.03, p=0.380; week 11 RD=0.07, p=0.504), and worse withdrawal-like symptoms more fully accounted for continued marijuana smoking in the VEN-XR group, according to the models. Individuals treated with VEN-XR had more severe withdrawal-like symptoms, which mediated their continued marijuana smoking. Noradrenergic agents, such as VEN-XR, may negatively impact treatment outcomes in cannabis-dependent patients attempting to reduce or stop their use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effect of Short-term Forced Exercise on Naloxone Induced Withdrawal Symptoms in Morphine Addicted Male Rats

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KH Saadipour

2008-01-01

Full Text Available ABSTRACT: Introduction & Objective: Opioid dependence has been causing limitation in usage of morphine and other opioid drugs in pain control. The aim of this study was to assess the effect of short-term forced exercise on withdrawal syndrome in morphine addicted male rats. Materials & Methods: This experimental study was done in the physiology research center of Ahwas Jondishapour University of Medical Sciences. Twenty four young male Wistar rats, weighing 200-300gr, were randomly divided into four groups: no addiction and no exercise, no addiction and exercise, addiction and no exercise and addiction and exercise. The exercise groups underwent treadmill forced exercise for ten days. The first five days morphine was administrated (ip twice daily with increasing dose (5، 10، 20، 40, 50 mg/kg to addicted groups. Also single dose (50mg/kg of morphine was administrated to them on the 10th day of exercise. After administration of naloxone hydrochloride the withdrawal symptoms were evaluated for 5 minutes. The findings of this study were analyzed by SPSS software and One- way ANOVA (Tukey test. Results: The findings of this study showed that the withdrawal symptoms was elevated in exercise and addicted groups in comparison with control group (p<0.05 , p<0.01. However, most of withdrawal symptoms decreased in addicted and exercise group in comparison with addicted and no exercise group (p<0.01, p<0.001. Conclusion: The exercise could increase endogenous opioid and withdrawal symptoms in animals but reduce withdrawal symptoms in addicted and exercise groups compared to addicted and no exercise group. Its mechanism might be related to down regulation and low sensitivity of opioid receptors

The relation between Bulimic symptoms and the social withdrawal syndrome during early adolescence.

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Rotenberg, Ken J; Sangha, Rajvir

2015-12-01

The short-term longitudinal study tested the hypothesis that there was a prospective relation between the social withdrawal syndrome and Bulimic symptoms during early adolescence. Ninety-six adolescents (47 males, mean age=13 years - 10 months) completed standardized scales assessing Bulimic symptoms, trust beliefs in others and loneliness at Time 1/T1 and again 5 months later at Time 2/T2. Analyses showed that: (1) Bulimic symptoms were negatively correlated with trust beliefs, (2) Bulimic symptoms were positively correlated with loneliness, and (3) trust beliefs were negatively correlated with loneliness. The SEM and mediation analyses showed that trust beliefs at T1 were negatively and concurrently associated with Bulimic symptoms at T1 and longitudinally (and negatively) predicted changes in Bulimic symptoms. It was found that loneliness at T1 statistically mediated those concurrent and longitudinal relations. The findings yielded support for the conclusion that the social withdrawal syndrome, as assessed by low trust beliefs and resulting experiences of loneliness, contributes to Bulimia nervosa during early adolescence. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Preventive withdrawal from work, psychosocial work demands and major depressive symptoms].

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Fall, A; Goulet, L; Vézina, M

2015-12-01

Our study objectives were as follows: assess exposure to psychosocial work demands among working pregnant women and women on preventive withdrawal from work; and measure the association between psychosocial work demands and major depressive symptoms, according to time of withdrawal from work. Karasek's abbreviated scale was used to measure psychosocial work demands (Job strain and "Iso-strain") and CES-D scale (Center for Epidemiological Studies Depression Scale) was used to measure major depressive symptoms (CES-D score≥23), at 24-26 weeks of pregnancy, among 3043 pregnant women in Montreal (Quebec) who worked at paid jobs at least 15 h/week and at least four consecutive weeks since the beginning of their pregnancy. Multivariate logistic regression models were built. At 24-26 weeks of pregnancy, 31.4% (956/3043) of pregnant women were on preventive withdrawal from work. They were more in "high-strain" (31.1% vs. 21.1%) and "Iso-strain" groups (21.0% vs. 14.2%) than those who continued to work (Pdemands are an important risk factor for the mental health of pregnant workers and require that preventive actions be put forward. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope.

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Tsai, Shang-Yi A; Chuang, Jian-Ying; Tsai, Meng-Shan; Wang, Xiao-Fei; Xi, Zheng-Xiong; Hung, Jan-Jong; Chang, Wen-Chang; Bonci, Antonello; Su, Tsung-Ping

2015-11-24

The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at the ER-mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild-type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of the MAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest the MAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal.

The electronic-cigarette: effects on desire to smoke, withdrawal symptoms and cognition.

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Dawkins, Lynne; Turner, John; Hasna, Surrayyah; Soar, Kirstie

2012-08-01

Electronic cigarettes (e-cigarettes) are battery operated devices that deliver nicotine via inhaled vapour. Few studies have evaluated acute effects on craving and mood, and none have explored effects on cognition. This study aimed to explore the effects of the White Super e-cigarette on desire to smoke, nicotine withdrawal symptoms, attention and working memory. Eighty-six smokers were randomly allocated to either: 18 mg nicotine e-cigarette (nicotine), 0mg e-cigarette (placebo), or just hold the e-cigarette (just hold) conditions. Participants rated their desire to smoke and withdrawal symptoms at baseline (T1), and five (T2) and twenty (T3) minutes after using the e-cigarette ad libitum for 5 min. A subset of participants completed the Letter Cancellation and Brown-Peterson Working Memory Tasks. After 20 min, compared with the just hold group, desire to smoke and some aspects of nicotine withdrawal were significantly reduced in the nicotine and placebo group; the nicotine e-cigarette was superior to placebo in males but not in females. The nicotine e-cigarette also improved working memory performance compared with placebo at the longer interference intervals. There was no effect of nicotine on Letter Cancellation performance. To conclude, the White Super e-cigarette alleviated desire to smoke and withdrawal symptoms 20 min after use although the nicotine content was more important for males. This study also demonstrated for the first time that the nicotine e-cigarette can enhance working memory performance. Further evaluation of the cognitive effects of the e-cigarette and its efficacy as a cessation tool is merited. Copyright © 2012 Elsevier Ltd. All rights reserved.

Are smartphone dependence symptoms related to FoMO, craving and withdrawal symptoms during smartphone abstinence? : Findings from a natural experiment

NARCIS (Netherlands)

van den Eijnden, R.J.J.M.; Doornwaard, S.M.; ter Bogt, T.F.M.

Background and aims: Adding to the ongoing discussion about the concept of behavioral addictions (Rosenburg & Feder, 2014), the present study tested whether or not individuals high on symptoms of smartphone addiction experience more craving and more withdrawal symptoms during a period of smartphone

Severe chronic hepatitis secondary to prolonged use of ecstasy and cocaine.

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Payancé, Audrey; Scotto, Béatrice; Perarnau, Jean-Marc; de Muret, Anne; Bacq, Yannick

2013-11-01

Severe acute hepatotoxicity is a well known complication following the ingestion of ecstasy (3,4-methylenedioxymethamphetamine [MDMA] ecstasy). Hepatic dysfunction has also been reported after acute cocaine intoxication. However, chronic hepatitis after prolonged use of ecstasy and/or cocaine has rarely been reported. We report the case of a 27-year-old woman hospitalized with edema, ascites and severe liver failure (prothrombin rate 33%), following the use of ecstasy and cocaine over the previous 9 months. Clinical, biological, radiological and pathology findings were recorded at admission and over 8 years' follow-up. Liver biopsy showed architectural distortion caused by bridging fibrosis, proliferation of cholangioles, and lesions of active interface hepatitis. Other causes of acute and chronic liver disease were excluded. Magnetic resonance imaging showed marked liver fibrosis. After withdrawal of both substances clinical examination and liver function tests progressively normalized. Long-term monitoring with magnetic resonance imaging showed progressive regression of fibrosis. Use of ecstasy and cocaine may cause chronic hepatitis leading to marked liver fibrosis, which may regress after withdrawal of both substances. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Bulimic symptoms and the social withdrawal syndrome.

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Rotenberg, Ken J; Bharathi, Carla; Davies, Helen; Finch, Tom

2013-08-01

One hundred and thirty-seven undergraduates (81 females; mean age = 21 years-10 months) completed the Bulimic SEDS subscale and standardized measures of trust beliefs in close others (mother, father, and friend), disclosure to them, and loneliness. Structural Equation Modelling yielded: (1) a negative path between Bulimic Symptoms and trust beliefs, (2) a positive path between trust beliefs and disclosure, (3) a negative path between trust beliefs and loneliness, and (4) a negative path between disclosure and loneliness. As expected, trust beliefs statistically mediated the relations between Bulimic Symptoms and both disclosure and loneliness and disclosure statistically mediated the relation between trust beliefs and loneliness. The findings supported the conclusion that individuals with bulimia nervosa are prone to the social withdrawal syndrome comprising a coherent and integrated pattern of low trust beliefs in close others, low disclosure to close others, and high loneliness. Copyright © 2013 Elsevier Ltd. All rights reserved.

Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence.

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Kendler, Kenneth S; Myers, John; Prescott, Carol A

2007-11-01

Although genetic risk factors have been found to contribute to dependence on both licit and illicit psychoactive substances, we know little of how these risk factors interrelate. To clarify the structure of genetic and environmental risk factors for symptoms of dependence on cannabis, cocaine, alcohol, caffeine, and nicotine in males and females. Lifetime history by structured clinical interview. General community. Four thousand eight hundred sixty-five members of male-male and female-female pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Main Outcome Measure Lifetime symptoms of abuse of and dependence on cannabis, cocaine, alcohol, caffeine, and nicotine. Controlling for greater symptom prevalence in males, genetic and environmental parameters could be equated across sexes. Two models explained the data well. The best-fit exploratory model contained 2 genetic factors and 1 individual environmental factor contributing to all substances. The first genetic factor loaded strongly on cocaine and cannabis dependence; the second, on alcohol and nicotine dependence. Nicotine and caffeine had high substance-specific genetic effects. A confirmatory model, which also fit well, contained 1 illicit drug genetic factor--loading only on cannabis and cocaine--and 1 licit drug genetic factor loading on alcohol, caffeine, and nicotine. However, these factors were highly intercorrelated (r = + 0.82). Large substance-specific genetic effects remained for nicotine and caffeine. The pattern of genetic and environmental risk factors for psychoactive substance dependence was similar in males and females. Genetic risk factors for dependence on common psychoactive substances cannot be explained by a single factor. Rather, 2 genetic factors-one predisposing largely to illicit drug dependence, the other primarily to licit drug dependence-are needed. Furthermore, a large proportion of the genetic influences on nicotine and particularly caffeine dependence

A Methanol Extract of Brugmansia arborea Affects the Reinforcing and Motor Effects of Morphine and Cocaine in Mice

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Antonio Bracci

2013-01-01

Full Text Available Previous reports have shown that several of the effects of morphine, including the development of tolerance and physical withdrawal symptoms, are reduced by extracts of Brugmansia arborea (L. Lagerheim (Solanaceae (B. arborea. In the present study we evaluate the action of the methanol extract of B. arborea (7.5–60 mg/kg on the motor and reinforcing effects of morphine (20 and 40 mg/kg and cocaine (25 mg/kg using the conditioned place preference (CPP procedure. At the doses employed, B. arborea did not affect motor activity or induce any effect on CPP. The extract partially counteracted morphine-induced motor activity and completely blocked the CPP induced by 20 mg/kg morphine. On the other hand, B. arborea blocked cocaine-induced hyperactivity but did not block cocaine-induced CPP. Reinstatement of extinguished preference with a priming dose of morphine or cocaine was also inhibited by B. arborea. The complex mechanism of action of B. arborea, which affects the dopaminergic and the cholinergic systems, seems to provide a neurobiological substrate for the effects observed. Considered as a whole, these results point to B. arborea as a useful tool for the treatment of morphine or cocaine abuse.

Bupropion Reduces Some of the Symptoms of Marihuana Withdrawal in Chronic Marihuana Users: A Pilot Study

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David M. Penetar

2012-01-01

Full Text Available Bupropion's (Zyban ® SR effectiveness to treat symptoms experienced in marihuana withdrawal was tested in a double-blind, placebo-controlled study with chronic, heavy marihuana users. Participants maintained their usual marihuana intake until Quit Day after which they were required to cease intake of THC products for 14 days. A Withdrawal Discomfort Score revealed that for 7 days immediately following cessation, placebo-treated subjects reported more symptoms than bupropion-treated subjects. Self-reported craving for marihuana increased for the placebo-treated group but not for those treated with bupropion. Measures of sleep and cognitive performance were not different between the two groups. Participants in the bupropion treatment arm were more likely to complete the study than those randomized to the placebo arm (50% completion for bupropion vs. 33% completion for placebo. These results suggest that bupropion may be useful for alleviating marihuana withdrawal symptoms and be useful in subject retention during long-term cessation programs.

[Comparison of Two Symptom-Triggered Treatments for Alcohol Withdrawal: HAES vs. SAB-P].

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Holzbach, R; Ihlow, C; Takla, T; Kemper, U; Naber, D

2016-02-01

For alcohol withdrawal during hospitalization, often a medication as means for withdrawal needs to be chosen. Modern, score-controlled processes that can be used by the nursing staff after instruction by physicians are frequently not used and even unknown in hospitals. One reason for this is that some of the scores require checking several criteria and are therefore more time-consuming and complicated than use of a fixed-dosage strategy. The SAB-P and HAES are short with only 6 items that can be checked by the nursing staff. Safety of the Hamburg Alcohol Withdrawal Scale (Hamburger Alkoholentzugs-Skala (HAES)) was analyzed retrospectively and prospectively with regard to score-controlled alcohol-withdrawal treatment after rating by the nurse staff (Scoregesteuerte Alkoholentzugsbehandlung nach Rating durch das Pflegepersonal (SAB-P)). Incidence of complications in patients treated with SAB-P and HAES was nearly similar with 1% start of delirium and 3% seizures (SAB-P) and 0.5 to 1.5% start of delirium and 0 to 0.5% seizures in the HAES group. With both scales it was possible to start medical treatment while still under falling alcohol levels (0.93 and 0.91%, respectively). Medication dosage was initially higher using the HAES, so that the time needed to monitor withdrawal symptoms could be reduced (3.8 vs. 3.1 days). Using a score-controlled strategy for alcohol withdrawal leads to a lower complication rate than found in literature. The structured procedure was helpful for the nursing staff as well as for the physicians. SAB-P as well as HAES made withdrawal for the patients more comfortable and led to fewer complaints. Because of rapid reaction and faster symptom reduction of HAES, there was less time necessary for monitoring. Simple handling, clomethiazol, oxazepam or diazepam as applicable medication and clear documentation are the advantages of HAES. © Georg Thieme Verlag KG Stuttgart · New York.

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.

Anxiety symptoms in crack cocaine and inhalant users admitted to a psychiatric hospital in southern Brazil.

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Zubaran, Carlos; Foresti, Katia; Thorell, Mariana Rossi; Franceschini, Paulo Roberto

2013-01-01

The occurrence of psychiatric comorbidity among individuals with crack or inhalant dependence is frequently observed. The objective of this study was to investigate anxiety symptoms among crack cocaine and inhalant users in southern Brazil. The study investigated two groups of volunteers of equal size (n=50): one group consisted of crack cocaine users, and the other group consisted of inhalant users. Research volunteers completed the Portuguese versions of the State-Trait Anxiety Inventory (STAI), Hamilton Anxiety Rating Scale (HAM-A), and Self-Report Questionnaire (SRQ). Both crack and inhalant users experience significant symptoms of anxiety. Inhalant users presented significantly more anxiety symptoms than crack users according to the HAM-A questionnaire only. In contrast to the results of the HAM-A, the STAI failed to demonstrate a significant difference between the two groups of substance users. SRQ scores revealed that crack and inhalants users had significant degrees of morbidity. A significant difference regarding anxiety symptomatology, especially state anxiety, was observed among inhalant and crack users. Anxiety and overall mental psychopathology were significantly correlated in this sample. The results indicate that screening initiatives to detect anxiety and additional psychiatric comorbidities among crack and inhalant users are feasible and relevant. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

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.

The Neuropsychology of Cocaine Addiction: Recent Cocaine Use Masks Impairment

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Woicik, Patricia A; Moeller, Scott J; Alia-Klein, Nelly; Maloney, Thomas; Lukasik, Tanya M; Yeliosof, Olga; Wang, Gene-Jack; Volkow, Nora D; Goldstein, Rita Z

2009-01-01

Individuals with current cocaine use disorders (CUD) form a heterogeneous group, making sensitive neuropsychological (NP) comparisons with healthy individuals difficult. The current study examined the effects on NP functioning of four factors that commonly vary among CUD: urine status for cocaine (positive vs negative on study day), cigarette smoking, alcohol consumption, and dysphoria. Sixty-four cocaine abusers were matched to healthy comparison subjects on gender and race; the groups also did not differ in measures of general intellectual functioning. All subjects were administered an extensive NP battery measuring attention, executive function, memory, facial and emotion recognition, and motor function. Compared with healthy control subjects, CUD exhibited performance deficits on tasks of attention, executive function, and verbal memory (within one standard deviation of controls). Although CUD with positive urine status, who had higher frequency and more recent cocaine use, reported greater symptoms of dysphoria, these cognitive deficits were most pronounced in the CUD with negative urine status. Cigarette smoking, frequency of alcohol consumption, and dysphoria did not alter these results. The current findings replicate a previously reported statistically significant, but relatively mild NP impairment in CUD as compared with matched healthy control individuals and further suggest that frequent/recent cocaine may mask underlying cognitive (but not mood) disturbances. These results call for development of pharmacological agents targeted to enhance cognition, without negatively impacting mood in individuals addicted to cocaine. PMID:18496524

Opiate and opioid withdrawal

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... opiate withdrawal; Oxycontin - opiate withdrawal; Hydrocodone - opiate withdrawal; Detox - opiates; Detoxification - opiates ... facilities set up to help people with detoxification (detox). In a regular hospital, if symptoms are severe. ...

Longitudinal Modeling of Depressive Trajectories Among HIV-Infected Men Using Cocaine.

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Mukerji, Shibani; Haghighat, Roxanna; Misra, Vikas; Lorenz, David R; Holman, Alex; Dutta, Anupriya; Gabuzda, Dana

2017-07-01

Cocaine use is prevalent among HIV-infected individuals. While cross-sectional studies suggest that cocaine users may be at increased risk for depression, long-term effects of cocaine on depressive symptoms remain unclear. This is a longitudinal study of 341 HIV-infected and uninfected men (135 cocaine users and 206 controls) ages 30-60 enrolled in the Multicenter AIDS Cohort Study during 1996-2009. The median baseline age was 41; 73% were African-American. In mixed-effects models over a median of 4.8 years of observation, cocaine use was associated with higher depressive symptoms independent of age, education level, and smoking (n = 288; p = 0.02); HIV infection modified this association (p = 0.03). Latent class mixed models were used to empirically identify distinct depressive trajectories (n = 160). In adjusted models, cocaine use was associated with threefold increased odds of membership in the class with persistent high depressive symptoms (95% confidence interval (CI) 1.38-6.69) and eightfold increased odds (95% CI (2.73-25.83) when tested among HIV-infected subjects only. Cocaine use is a risk factor for chronic depressive symptoms, particularly among HIV-infected men, highlighting the importance of integrating mental health and substance use treatments to address barriers to well-being and successful HIV-care.

Social interaction and social withdrawal in rodents as readouts for investigating the negative symptoms of schizophrenia

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Wilson, Christina A.; Koenig, James I.

2015-01-01

Negative symptoms (e.g., asociality and anhedonia) are a distinct symptomatic domain that has been found to significantly affect the quality of life in patients diagnosed with schizophrenia. Additionally, the primary negative symptom of asociality (i.e., withdrawal from social contact that derives from indifference or lack of desire to have social contact) is a major contributor to poor psychosocial functioning and has been found to play an important role in the course of the disorder. Nonetheless, the pathophysiology underlying these symptoms is unknown and currently available treatment options (e.g., antipsychotics and cognitive-behavioral therapy) fail to reliably produce efficacious benefits. Utilizing rodent paradigms that measure social behaviors (e.g., social withdrawal) to elucidate the neurobiological substrates that underlie social dysfunction and to identify novel therapeutic targets may be highly informative and useful to understand more about the negative symptoms of schizophrenia. Accordingly, the purpose of this review is to provide an overview of the behavioral tasks for assessing social functioning that may be translationally relevant for investigating negative symptoms associated with schizophrenia. PMID:24342774

Social interaction and social withdrawal in rodents as readouts for investigating the negative symptoms of schizophrenia.

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Wilson, Christina A; Koenig, James I

2014-05-01

Negative symptoms (e.g., asociality and anhedonia) are a distinct symptomatic domain that has been found to significantly affect the quality of life in patients diagnosed with schizophrenia. Additionally, the primary negative symptom of asociality (i.e., withdrawal from social contact that derives from indifference or lack of desire to have social contact) is a major contributor to poor psychosocial functioning and has been found to play an important role in the course of the disorder. Nonetheless, the pathophysiology underlying these symptoms is unknown and currently available treatment options (e.g., antipsychotics and cognitive-behavioral therapy) fail to reliably produce efficacious benefits. Utilizing rodent paradigms that measure social behaviors (e.g., social withdrawal) to elucidate the neurobiological substrates that underlie social dysfunction and to identify novel therapeutic targets may be highly informative and useful to understand more about the negative symptoms of schizophrenia. Accordingly, the purpose of this review is to provide an overview of the behavioral tasks for assessing social functioning that may be translationally relevant for investigating negative symptoms associated with schizophrenia. © 2013 Published by Elsevier B.V. and ECNP.

Serum concentrations of psychotropic drugs in neonates as a PROgnOstic Factor for admission to the neonatology ward and withdrawal symptoms: PROOF-1.

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Sparla, Shirley C A; Coppens, Hans; Evers, Inge M; Stramrood, Claire A I; Pasker-de Jong, Pieternel C M; van der Westerlaken, Monique M L; Hogeman, Paul H G; Malingré, Mirte M

2017-05-01

The aim is to determine whether serum drug concentrations obtained from the neonate's umbilical cord can be used as a prognostic factor for admission to the neonatology ward and the occurrence of withdrawal symptoms. A retrospective observational monocenter cohort study was carried out among pregnant women using psychotropic drugs and their baby. Binary logistic regression was used for the multivariate analysis. Of the 186 neonates included, 22.6% (n=42) were admitted to the neonatology ward, 6.5% (n=12) because of withdrawal. Among women with therapeutic concentrations of psychotropic medication, 22.0% (n=5) of the neonates had withdrawal symptoms. When comparing neonates with therapeutic versus undetectable drug concentrations, an odds ratio of 3.1 (95% confidence interval: 1.1-8.6) was found for admission to the neonatology ward and an odds ratio of 20.5 (95% confidence interval: 2.2-186.1) for the occurrence of withdrawal symptoms. Therapeutic concentrations of psychotropic drugs in neonates' umbilical cord blood correspond with higher odds for admission to the neonatology ward and the occurrence of withdrawal symptoms compared with neonates with undetectable drug concentrations. The measurement of drug concentrations in the neonate may contribute toward the general clinical assessment of the physician to predict the necessity of admission to the neonatology ward and the risk of withdrawal symptoms.

Calcium-permeable AMPA receptors in the VTA and nucleus accumbens after cocaine exposure: When, how and why?

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Marina E Wolf

2012-06-01

Full Text Available In animal models of drug addiction, cocaine exposure has been shown to increase levels of calcium-permeable AMPA receptors (CP-AMPARs in two brain regions that are critical for motivation and reward - the ventral tegmental area (VTA and the nucleus accumbens (NAc. This review compares CP-AMPAR plasticity in the two brain regions and addresses its functional significance. In VTA dopamine neurons, cocaine exposure results in synaptic insertion of high conductance CP-AMPARs in exchange for lower conductance calcium-impermeable AMPARs (CI-AMPARs. This plasticity is rapid (hours, GluA2-dependent, and can be observed with a single cocaine injection. In addition to strengthening synapses and altering Ca2+ signaling, CP-AMPAR insertion affects subsequent induction of plasticity at VTA synapses. However, CP-AMPAR insertion is unlikely to mediate the increased dopamine cell activity that occurs during early withdrawal from cocaine exposure. Within the VTA, the group I metabotropic glutamate receptor mGluR1 exerts a negative influence on CP-AMPAR accumulation. Acutely, mGluR1 stimulation elicits a form of LTD resulting from CP-AMPAR removal and CI-AMPAR insertion. In medium spiny neurons (MSNs of the NAc, extended access cocaine self-administration is required to increase CP-AMPAR levels. This is first detected after approximately a month of withdrawal and then persists. Once present in NAc synapses, CP-AMPARs mediate the expression of incubation of cue-induced cocaine craving. The mechanism of their accumulation may be GluA1-dependent, which differs from that observed in the VTA. However, similar to VTA, mGluR1 stimulation removes CP-AMPARs from MSN synapses. Loss of mGluR1 tone during cocaine withdrawal may contribute to CP-AMPAR accumulation in the NAc. Thus, results in both brain regions point to the possibility of using positive modulators of mGluR1 as a treatment for cocaine addiction.

Addressing the stimulant treatment gap: A call to investigate the therapeutic benefits potential of cannabinoids for crack-cocaine use.

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Fischer, Benedikt; Kuganesan, Sharan; Gallassi, Andrea; Malcher-Lopes, Renato; van den Brink, Wim; Wood, Evan

2015-12-01

Crack-cocaine use is prevalent in numerous countries, yet concentrated primarily - largely within urban contexts - in the Northern and Southern regions of the Americas. It is associated with a variety of behavioral, physical and mental health and social problems which gravely affect users and their environments. Few evidence-based treatments for crack-cocaine use exist and are available to users in the reality of street drug use. Numerous pharmacological treatments have been investigated but with largely disappointing results. An important therapeutic potential for crack-cocaine use may rest in cannabinoids, which have recently seen a general resurgence for varied possible therapeutic usages for different neurological diseases. Distinct potential therapeutic benefits for crack-cocaine use and common related adverse symptoms may come specifically from cannabidiol (CBD) - one of the numerous cannabinoid components found in cannabis - with its demonstrated anxiolytic, anti-psychotic, anti-convulsant effects and potential benefits for sleep and appetite problems. The possible therapeutic prospects of cannabinoids are corroborated by observational studies from different contexts documenting crack-cocaine users' 'self-medication' efforts towards coping with crack-cocaine-related problems, including withdrawal and craving, impulsivity and paranoia. Cannabinoid therapeutics offer further benefits of being available in multiple formulations, are low in adverse risk potential, and may easily be offered in community-based settings which may add to their feasibility as interventions for - predominantly marginalized - crack-cocaine user populations. Supported by the dearth of current therapeutic options for crack-cocaine use, we are advocating for the implementation of a rigorous research program investigating the potential therapeutic benefits of cannabinoids for crack-cocaine use. Given the high prevalence of this grave substance use problem in the Americas, opportunities for

Withdrawal symptoms in children after long-term administration of sedatives and/or analgesics: A literature review. "Assessment remains troublesome"

NARCIS (Netherlands)

E. Ista (Erwin); M. van Dijk (Monique); C. Gamel (Claudia); D. Tibboel (Dick); M. de Hoog (Matthijs)

2007-01-01

textabstractBackground: Prolonged administration of benzodiazepines and/or opioids to children in a pediatric intensive care unit (PICU) may induce physiological dependence and withdrawal symptoms. Objective: We reviewed the literature for relevant contributions on the nature of these withdrawal

ADHD symptoms impact smoking outcomes and withdrawal in response to Varenicline treatment for smoking cessation.

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Bidwell, L Cinnamon; Karoly, Hollis C; Hutchison, Kent E; Bryan, Angela D

2017-10-01

Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with nicotine dependence and difficulty quitting smoking. Few cessation trials specifically consider the impact of ADHD on treatment outcomes, including those testing established pharmacological therapies, such as varenicline. The current study focused on the impact of pretreatment ADHD inattention (IN) and hyperactivity-impulsivity (HI) symptoms on treatment outcome in a randomized controlled trial of varenicline [N=205, average age=34.13(10.07), average baseline cigarettes per day=14.71(7.06)]. Given that varenicline's putative therapeutic mechanism is attenuation of withdrawal severity during abstinence, we also tested changes in withdrawal as a mediator of treatment effects in high and low ADHD groups. ADHD symptom severity in this sample was in the subclinical range. Cessation was associated with HI, but not IN, such that high HI individuals on varenicline reported the lowest smoking levels at the end of treatment across all groups (3.06cig/day for high HI vs 4.02cig/day for low HI). Individuals with high HI who received placebo had the highest smoking at the end of treatment (7.69cigs/day for high HI vs 5.56cig/day for low HI). Patterns continued at follow-up. Varenicline significantly reduced withdrawal for those with high HI, but not low HI. However, path models did not support an indirect effect of medication on reducing smoking via withdrawal in either group, suggesting that unmeasured variables are involved in varenicline's effect on reducing smoking. These data add to a gap in the smoking cessation literature regarding the impact of ADHD symptoms on the efficacy and mechanisms of frontline pharmacological treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

Is Homepathy Effective for Hot Flashes and other Estrogen-Withdrawal Symptoms in Breast Cancer Survivors? A Preliminary Randomized Controlled Trial

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2000-04-01

AD__________ Award Number: DAMD17-99-1-9438 TITLE: Is Homeopathy Effective for Hot Flashes and Other Estrogen-Withdrawal Symptoms in Breast Cancer...Mar 00) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Is Homeopathy Effective for Hot Flashes and Other Estrogen- DAMD17-99-1-9438 Withdrawal Symptoms in...there is evidence that homeopathy is an effective treatment to improve the quality of life in breast cancer survivors who are experiencing hot flashes

Dopamine transporter down-regulation following repeated cocaine: implications for 3,4-methylenedioxymethamphetamine-induced acute effects and long-term neurotoxicity in mice.

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Peraile, I; Torres, E; Mayado, A; Izco, M; Lopez-Jimenez, A; Lopez-Moreno, J A; Colado, M I; O'Shea, E

2010-01-01

3,4-Methylenedioxymethamphetamine (MDMA) and cocaine are two widely abused psychostimulant drugs targeting the dopamine transporter (DAT). DAT availability regulates dopamine neurotransmission and uptake of MDMA-derived neurotoxic metabolites. We aimed to determine the effect of cocaine pre-exposure on the acute and long-term effects of MDMA in mice. Mice received a course of cocaine (20 mg*kg(-1), x2 for 3 days) followed by MDMA (20 mg*kg(-1), x2, 3 h apart). Locomotor activity, extracellular dopamine levels and dopaminergic neurotoxicity were determined. Furthermore, following the course of cocaine, DAT density in striatal plasma membrane and endosome fractions was measured. Four days after the course of cocaine, challenge with MDMA attenuated the MDMA-induced striatal dopaminergic neurotoxicity. Co-administration of the protein kinase C (PKC) inhibitor NPC 15437 prevented cocaine protection. At the same time, after the course of cocaine, DAT density was reduced in the plasma membrane and increased in the endosome fraction, and this effect was prevented by NPC 15437. The course of cocaine potentiated the MDMA-induced increase in extracellular dopamine and locomotor activity, following challenge 4 days later, compared with those pretreated with saline. Repeated cocaine treatment followed by withdrawal protected against MDMA-induced dopaminergic neurotoxicity by internalizing DAT via a mechanism which may involve PKC. Furthermore, repeated cocaine followed by withdrawal induced behavioural and neurochemical sensitization to MDMA, measures which could be indicative of increased rewarding effects of MDMA.

Phenomenology of gasoline intoxication and withdrawal symptoms among adolescents in India: a case series.

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Shah, R; Vankar, G K; Upadhyaya, H P

1999-01-01

Inhalant withdrawal symptoms have previously been described but not well documented. This case-series describes the sociodemographic and clinical characteristics of nine children and adolescents with gasoline abuse. Gasoline inhalation was the drug of choice in our patients. The mean age was 13.6 years and all the subjects belonged to low socioeconomic status. Most of the subjects used daily and all subjects reported alcohol abuse in the father. All subjects reported a syndrome of intoxication as described in previous reports. All subjects also reported a withdrawal syndrome including irritability, psychomotor retardation, anhedonia, dry mouth, sleep disturbances, craving, and increased lacrimation.

An investigation of interactions between hypocretin/orexin signaling and glutamate receptor surface expression in the rat nucleus accumbens under basal conditions and after cocaine exposure.

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Plaza-Zabala, Ainhoa; Li, Xuan; Milovanovic, Mike; Loweth, Jessica A; Maldonado, Rafael; Berrendero, Fernando; Wolf, Marina E

2013-12-17

Hypocretin peptides are critical for the effects of cocaine on excitatory synaptic strength in the ventral tegmental area (VTA). However, little is known about their role in cocaine-induced synaptic plasticity in the nucleus accumbens (NAc). First, we tested whether hypocretin-1 by itself could acutely modulate glutamate receptor surface expression in the NAc, given that hypocretin-1 in the VTA reproduces cocaine's effects on glutamate transmission. We found no effect of hypocretin-1 infusion on AMPA or NMDA receptor surface expression in the NAc, measured by biotinylation, either 30 min or 3h after the infusion. Second, we were interested in whether changes in hypocretin receptor-2 (Hcrtr-2) expression contribute to cocaine-induced plasticity in the NAc. As a first step towards addressing this question, Hcrtr-2 surface expression was compared in the NAc after withdrawal from extended-access self-administration of saline (control) versus cocaine. We found that surface Hcrtr-2 levels remain unchanged following 14, 25 or 48 days of withdrawal from cocaine, a time period in which high conductance GluA2-lacking AMPA receptors progressively emerge in the NAc. Overall, our results fail to support a role for hypocretins in acute modulation of glutamate receptor levels in the NAc or a role for altered Hcrtr-2 expression in withdrawal-dependent synaptic adaptations in the NAc following cocaine self-administration. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Preliminary Report : The Treatment of Withdrawal Symptoms of Opium Addicts with Vitamin " E " in Ten Cases

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H. Davidian

1957-01-01

Full Text Available The treatment of addiction to opiates, apart from psychological and social problems, has presented up to now a therapeutic prohlem. Various methods are used and each has its disadvantages. Residual symptoms of abstinence from opiates are present in all methods and there is a prolonged period of convalescence which seems to be one of the causes of relapses to addiction. Vitamin E however- has given remarkable results in aiding recovery from the withdrawal symptoms. With vitamin E the period of treatment is shortened, abstinence symptoms are bearable and the convalescent period is eliminated. Patients treated with vitamin E solely are in good health and spirits and appear contented. This treatment also seems to reduce 1he number of relapses. The administration of vitamin E after a complete withdrawal from opium probably compensates Some of the opium's effects on the nervous system, and remedies the hypoxia of the tissues, thus restoring the patient to a normal physiological state.

Sleep, Internalizing Problems, and Social Withdrawal: Unique Associations in Clinic-Referred Youth With Elevated Sluggish Cognitive Tempo Symptoms.

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Rondon, Ana T; Hilton, Dane C; Jarrett, Matthew A; Ollendick, Thomas H

2018-02-01

We compared clinic-referred youth with ADHD + sluggish cognitive tempo (SCT; n = 34), ADHD Only ( n = 108), and SCT Only ( n = 22) on demographics, co-occurring symptomatology, comorbid diagnoses, and social functioning. In total, 164 youth (age = 6-17 years, M = 9.97) and their parent(s) presented to an outpatient clinic for a psychoeducational assessment. Between-group analyses and regressions were used to examine study variables. SCT groups were older and exhibited more parent-reported internalizing problems, externalizing problems, sleep problems, and social withdrawal on the Child Behavior Checklist. No significant differences emerged between groups on the Teacher Report Form. Regression analyses involving multiple covariates revealed that SCT symptoms were uniquely related to social withdrawal but not general social problems. Based on parent report, SCT symptoms have a unique relationship with internalizing problems, sleep problems, and social withdrawal. Future research should explore correlates of SCT in youth using multiple informants.

PI3 kinase is involved in cocaine behavioral sensitization and its reversal with brain area specificity

International Nuclear Information System (INIS)

Zhang Xiuwu; Mi Jing; Wetsel, William C.; Davidson, Colin; Xiong Xieying; Chen Qiang; Ellinwood, Everett H.; Lee, Tong H.

2006-01-01

Phosphatidylinositol 3-kinase (PI3K) is an important signaling molecule involved in cell differentiation, proliferation, survival, and phagocytosis, and may participate in various brain functions. To determine whether it is also involved in cocaine sensitization, we measured the p85α/p110 PI3K activity in the nuclear accumbens (NAc) shell, NAc core, and prefrontal cortex (PFC) following establishment of cocaine sensitization and its subsequent reversal. Naive rats were rank-ordered and split into either daily cocaine or saline pretreatment group based on their locomotor responses to an acute cocaine injection (7.5 mg/kg, i.p.). These two groups were then injected with cocaine (40 mg/kg, s.c.) or saline for 4 consecutive days followed by 9-day withdrawal. Cocaine sensitization was subsequently reversed by 5 daily injections of the D 1 /D 2 agonist pergolide (0.1 mg/kg, s.c.) in combination with the 5-HT 3 antagonist ondansetron (0.2 mg/kg, s.c., 3.5 h after pergolide injection). After another 9-day withdrawal, behavioral cocaine sensitization and its reversal were confirmed with an acute cocaine challenge (7.5 mg/kg, i.p.), and animals were sacrificed the next day for measurement of p85α/p110 PI3K activity. Cocaine-sensitized animals exhibited increased PI3K activity in the NAc shell, and this increase was reversed by combined pergolide/ondansetron treatment, which also reversed behavioral sensitization. In the NAc core and PFC, cocaine sensitization decreased and increased the PI3K activity, respectively. These changes, in contrast to that in the NAc shell, were not normalized following the reversal of cocaine-sensitization. Interestingly, daily injections of pergolide alone in saline-pretreated animals induced PI3K changes that were similar to the cocaine sensitization-associated changes in the NAc core and PFC but not the NAc shell; furthermore, these changes in saline-pretreated animals were prevented by ondansetron given 3.5 h after pergolide. The present

Development of personal narratives as a mediator of the impact of deficits in social cognition and social withdrawal on negative symptoms in schizophrenia.

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Lysaker, Paul H; Erikson, Molly; Macapagal, Kathryn R; Tunze, Chloe; Gilmore, Emily; Ringer, Jamie M

2012-04-01

Although negative symptoms are a barrier to recovery from schizophrenia, little is understood about the psychological processes that reinforce and sustain them. To explore this issue, this study used structural equation modeling to test whether the impact of social withdrawal and emotion recognition deficits upon negative symptoms is mediated by the richness or poverty of personal narratives. The participants were 99 adults with schizophrenia spectrum disorders. Social cognition was assessed using the Bell-Lysaker Emotional Recognition Task; social withdrawal, using the Quality of Life Scale; narrative coherence, using the Scale To Assess Narrative Development; and negative symptoms, using the Positive and Negative Syndrome Scale. The findings reveal that although social cognition deficits and social withdrawal are significantly associated with negative symptom severity, these relationships become nonsignificant when personal narrative integrity is examined as a mediating factor. These results indicate that the development of personal narratives may be directly linked to the severity of negative symptoms; this construct may be a useful target for future interventions.

Obsessive-compulsive symptoms and negative affect during tobacco withdrawal in a non-clinical sample of African American smokers.

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Bello, Mariel S; Pang, Raina D; Chasson, Gregory S; Ray, Lara A; Leventhal, Adam M

2017-05-01

The association between obsessive-compulsive (OC) symptomatology and smoking is poorly understood, particularly in African Americans-a group subject to smoking- and OC-related health disparities. In a non-clinical sample of 253 African American smokers, we tested the negative reinforcement model of OC-smoking comorbidity, purporting that smokers with higher OC symptoms experience greater negative affect (NA) and urge to smoke for NA suppression upon acute tobacco abstinence. Following a baseline visit involving OC assessment, participants completed two counterbalanced experimental visits (non-abstinent vs. 16-h tobacco abstinence) involving affect, smoking urge, and nicotine withdrawal assessment. OC symptom severity predicted larger abstinence-provoked increases in overall NA, anger, anxiety, depression, fatigue, urge to smoke to suppress NA, and composite nicotine withdrawal symptom index. African American smokers with elevated OC symptoms appear to be vulnerable to negative reinforcement-mediated smoking motivation and may benefit from cessation treatments that diminish NA or the urge to quell NA via smoking. Copyright © 2016 Elsevier Ltd. All rights reserved.

Infants' social withdrawal symptoms assessed with a direct infant observation method in primary health care.

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Puura, Kaija; Mäntymaa, Mirjami; Luoma, Ilona; Kaukonen, Pälvi; Guedeney, Antoine; Salmelin, Raili; Tamminen, Tuula

2010-12-01

Distressed infants may withdraw from social interaction, but recognising infants' social withdrawal is difficult. The aims of the study were to see whether an infant observation method can be reliably used by front line workers, and to examine the prevalence of infants' social withdrawal symptoms. A random sample of 363 families with four, eight or 18-month-old infants participated in the study. The infants were examined by general practitioners (GPs) in well-baby clinics with the Alarm Distress BaBy Scale (ADBB), an observation method developed for clinical settings. A score of five or more on the ADBB Scale in two subsequent assessments at a two-week interval was regarded as a sign of clinically significant infant social withdrawal. Kappas were calculated for the GPs' correct rating of withdrawn/not withdrawn against a set of videotapes rated by developer of the method, Professor Guedeney and his research group. The kappas for their ratings ranged from 0.5 to 1. The frequency of infants scoring above the cut off in two subsequent assessments was 3%. The ADBB Scale is a promising method for detecting infant social withdrawal in front line services. Three percents of infants were showing sustained social withdrawal as a sign of distress in this normal population sample. Copyright © 2010 Elsevier Inc. All rights reserved.

Opiate Withdrawal Complicated by Tetany and Cardiac Arrest

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Irfanali R. Kugasia

2014-01-01

Full Text Available Patients with symptoms of opiate withdrawal, after the administration of opiate antagonist by paramedics, are a common presentation in the emergency department of hospitals. Though most of opiate withdrawal symptoms are benign, rarely they can become life threatening. This case highlights how a benign opiate withdrawal symptom of hyperventilation led to severe respiratory alkalosis that degenerated into tetany and cardiac arrest. Though this patient was successfully resuscitated, it is imperative that severe withdrawal symptoms are timely identified and immediate steps are taken to prevent catastrophes. An easier way to reverse the severe opiate withdrawal symptom would be with either low dose methadone or partial opiate agonists like buprenorphine. However, if severe acid-base disorder is identified, it would be safer to electively intubate these patients for better control of their respiratory and acid-base status.

The Impact of Saffron on Symptoms of Withdrawal Syndrome in Patients Undergoing Maintenance Treatment for Opioid Addiction in Sabzevar Parish in 2017

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Mohammad Nemat Shahi

2017-01-01

Full Text Available Background and Objective. Drug dependence is one of the serious problems around the world. Saffron is one of those beneficial medicinal plants which is embedded with a similar mechanism to methadone (e.g., inhibition of serotonin reuptake. Thus, it can be helpful in reducing the withdrawal symptoms. The aim of this study was to reduce the daily dose of methadone usage and reduce its side effects using saffron in the form of medicinal supplements. Methodology. This study was categorized as a clinical trial. Accordingly, 44 clients of addiction treatment centers in Sabzevar parish were randomly selected to participate in this study in 2016–2017. While the experimental group was treated with methadone syrup and self-made saffron capsules, the control group received methadone syrup and placebo capsules. Results. The results showed that the use of saffron and methadone alleviated the symptoms of withdrawal syndrome (p<0.001. Conclusion. Having reviewed the research participants, it was indicated that the introduction of saffron alleviated the symptoms of withdrawal syndrome in patients undergoing maintenance treatment for opioid addiction. Thus, it seems rational to make use of saffron in combination with methadone in order to alleviate the symptoms of withdrawal syndrome.

GluN2B-containing NMDA receptors blockade rescues bidirectional synaptic plasticity in the bed nucleus of the stria terminalis of cocaine self-administering rats.

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deBacker, Julian; Hawken, Emily R; Normandeau, Catherine P; Jones, Andrea A; Di Prospero, Cynthia; Mechefske, Elysia; Gardner Gregory, James; Hayton, Scott J; Dumont, Éric C

2015-01-01

Drugs of abuse have detrimental effects on homeostatic synaptic plasticity in the motivational brain network. Bidirectional plasticity at excitatory synapses helps keep neural circuits within a functional range to allow for behavioral flexibility. Therefore, impaired bidirectional plasticity of excitatory synapses may contribute to the behavioral hallmarks of addiction, yet this relationship remains unclear. Here we tracked excitatory synaptic strength in the oval bed nucleus of the stria terminalis (ovBNST) using whole-cell voltage-clamp recordings in brain slices from rats self-administering sucrose or cocaine. In the cocaine group, we measured both a persistent increase in AMPA to NMDA ratio (A:N) and slow decay time of NMDA currents throughout the self-administration period and after withdrawal from cocaine. In contrast, the sucrose group exhibited an early increase in A:N ratios (acquisition) that returned toward baseline values with continued self-administration (maintenance) and after withdrawal. The sucrose rats also displayed a decrease in NMDA current decay time with continued self-administration (maintenance), which normalized after withdrawal. Cocaine self-administering rats exhibited impairment in NMDA-dependent long-term depression (LTD) that could be rescued by GluN2B-containing NMDA receptor blockade. Sucrose self-administering rats demonstrated no impairment in NMDA-dependent LTD. During the maintenance period of self-administration, in vivo (daily intraperitoneally for 5 days) pharmacologic blockade of GluN2B-containing NMDA receptors did not reduce lever pressing for cocaine. However, in vivo GluN2B blockade did normalize A:N ratios in cocaine self-administrating rats, and dissociated the magnitude of ovBNST A:N ratios from drug-seeking behavior after protracted withdrawal. Altogether, our data demonstrate when and how bidirectional plasticity at ovBNST excitatory synapses becomes dysfunctional with cocaine self-administration and that NMDA

[Cocaine: historical background, neurobiology of the addiction and relapse and therapeutic perspectives].

Science.gov (United States)

Silva, M I; Citó, M C; Vasconcelos, P F; Vasconcelos, S M; Sousa, F C

2010-01-01

Following more than a century of cocaine hydrochloride extraction from Erythroxylon coca, this drug remains representing a serious social and public health problema around the world. This paper intends to provide a review about the cocaine theme, focusing on historical background and on its different neurotransmission systems, as well as addresses therapeutics aspects about drug addiction. Electronic search in databases Medline, Pubmed and Lilacs was accomplished in order to select classics and recent studies relevant to the discussion of issue addressed. Previous studies have shown high vulnerability to relapse to cocaine seeking following prolonged withdrawal periods. Such behavioral consequences have been cre-dited to induced changes in brain neurotransmitters provoked by repeated cocaine use. In recent years, the growing abuse of this drug has mobilized researchers worldwide in seeking for new therapies that reduce the behavioral and neurochemical changes resulting from addiction. Numerous advances regarding the treatment of cocaine abuse and dependence have emerged in recent years. However, researche aiming at a safe and effective users' pharmacological treatment remain necessary and should be continued.

The electronic-cigarette: effects on desire to smoke, withdrawal symptoms and cognition

OpenAIRE

Dawkins, Lynne; Turner, John J.D.; Hasna, Surrayyah; Soar, Kirstie

2012-01-01

Electronic cigarettes (e-cigarettes) are battery operated devices that deliver nicotine via inhaled vapour. Few studies have evaluated acute effects on craving and mood, and none have explored effects on cognition. This study aimed to explore the effects of the White Super e-cigarette on desire to smoke, nicotine withdrawal symptoms, attention and working memory. Eighty-six smokers were randomly allocated to either: 18mg nicotine e-cigarette (nicotine), 0mg e-cigarette (placebo), or just hold...

Withdrawal: Expanding a Key Addiction Construct.

Science.gov (United States)

Piper, Megan E

2015-12-01

Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets. © 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.

Changes in gene expression and sensitivity of cocaine reward produced by a continuous fat diet.

Science.gov (United States)

Blanco-Gandía, M Carmen; Aracil-Fernández, Auxiliadora; Montagud-Romero, Sandra; Aguilar, Maria A; Manzanares, Jorge; Miñarro, José; Rodríguez-Arias, Marta

2017-08-01

Preclinical studies report that free access to a high-fat diet (HFD) alters the response to psychostimulants. The aim of the present study was to examine how HFD exposure during adolescence modifies cocaine effects. Gene expression of CB1 and mu-opioid receptors (MOr) in the nucleus accumbens (N Acc) and prefrontal cortex (PFC) and ghrelin receptor (GHSR) in the ventral tegmental area (VTA) were assessed. Mice were allowed continuous access to fat from PND 29, and the locomotor (10 mg/kg) and reinforcing effects of cocaine (1 and 6 mg/kg) on conditioned place preference (CPP) were evaluated on PND 69. Another group of mice was exposed to a standard diet until the day of post-conditioning, on which free access to the HFD began. HFD induced an increase of MOr gene expression in the N Acc, but decreased CB1 receptor in the N Acc and PFC. After fat withdrawal, the reduction of CB1 receptor in the N Acc was maintained. Gene expression of GHSR in the VTA decreased during the HFD and increased after withdrawal. Following fat discontinuation, mice exhibited increased anxiety, augmented locomotor response to cocaine, and developed CPP for 1 mg/kg cocaine. HFD reduced the number of sessions required to extinguish the preference and decreased sensitivity to drug priming-induced reinstatement. Our results suggest that consumption of a HFD during adolescence induces neurobiochemical changes that increased sensitivity to cocaine when fat is withdrawn, acting as an alternative reward.

The alcohol withdrawal syndrome.

LENUS (Irish Health Repository)

McKeon, A

2008-08-01

The alcohol withdrawal syndrome (AWS) is a common management problem in hospital practice for neurologists, psychiatrists and general physicians alike. Although some patients have mild symptoms and may even be managed in the outpatient setting, others have more severe symptoms or a history of adverse outcomes that requires close inpatient supervision and benzodiazepine therapy. Many patients with AWS have multiple management issues (withdrawal symptoms, delirium tremens, the Wernicke-Korsakoff syndrome, seizures, depression, polysubstance abuse, electrolyte disturbances and liver disease), which requires a coordinated, multidisciplinary approach. Although AWS may be complex, careful evaluation and available treatments should ensure safe detoxification for most patients.

A Prototypical First-Generation Electronic Cigarette Does Not Reduce Reports of Tobacco Urges or Withdrawal Symptoms among Cigarette Smokers

Directory of Open Access Journals (Sweden)

Arit M. Harvanko

2017-01-01

Full Text Available It is unknown whether first-generation electronic cigarettes reduce smoking urges and withdrawal symptoms following a 24 h deprivation period. This study tested whether a first-generation electronic cigarette reduces smoking urges and withdrawal symptoms in cigarette smokers. Following 24 h of tobacco deprivation, using a within-subjects design, eight nontreatment seeking tobacco cigarette smokers (3 females administered 10 puffs from a conventional cigarette or a first-generation electronic cigarette containing liquid with 0, 8 or 16 mg/ml nicotine. Conventional cigarettes ameliorated smoking urges and electronic cigarettes did not, regardless of nicotine concentration. First-generation electronic cigarettes may not effectively substitute for conventional cigarettes in reducing smoking urges, regardless of nicotine concentration.

Quantifying the Clinical Significance of Cannabis Withdrawal

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Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

2012-01-01

Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

Quantifying the clinical significance of cannabis withdrawal.

Directory of Open Access Journals (Sweden)

David J Allsop

Full Text Available Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV. This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt.A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p=0.0001. Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p=0.03. Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p=0.001.Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes.

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 ...

Measurement of nicotine withdrawal symptoms: linguistic validation of the Wisconsin Smoking Withdrawal Scale (WSWS in Malay

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Shafie Asrul A

2010-05-01

Full Text Available Abstract Background The purpose of the linguistic validation of the Wisconsin Smoking Withdrawal Scale (WSWS was to produce a translated version in Malay language which was "conceptually equivalent" to the original U.S. English version for use in clinical practice and research. Methods A seven-member translation committee conducted the translation process using the following methodology: production of two independent forward translations; comparison and reconciliation of the translations; backward translation of the first reconciled version; comparison of the original WSWS and the backward version leading to the production of the second reconciled version; pilot testing and review of the translation, and finalization. Results Linguistic and conceptual issues arose during the process of translating the instrument, particularly pertaining to the title, instructions, and some of the items of the scale. In addition, the researchers had to find culturally acceptable equivalents for some terms and idiomatic phrases. Notable among these include expressions such as "irritability", "feeling upbeat", and "nibbling on snacks", which had to be replaced by culturally acceptable expressions. During cognitive debriefing and clinician's review processes, the Malay translated version of WSWS was found to be easily comprehensible, clear, and appropriate for the smoking withdrawal symptoms intended to be measured. Conclusions We applied a rigorous translation method to ensure conceptual equivalence and acceptability of WSWS in Malay prior to its utilization in research and clinical practice. However, to complete the cultural adaptation process, future psychometric validation is planned to be conducted among Malay speakers.

Ketogenic Diet suppresses Alcohol Withdrawal Syndrome in Rats

DEFF Research Database (Denmark)

Dencker, Ditte; Molander, Anna; Thomsen, Morgane

2018-01-01

, we investigated the potential therapeutic benefit of a ketogenic diet in managing alcohol withdrawal symptoms during detoxification. METHODS: Male Sprague Dawley rats fed either ketogenic or regular diets were administered ethanol or water orally, twice daily for 6 days while the diet conditions were...... maintained. Abstinence symptoms were rated 6, 24, 48, and 72 hours after the last alcohol administration. RESULTS: Maintenance on a ketogenic diet caused a significant decrease in the alcohol withdrawal symptoms 'rigidity' and 'irritability'. CONCLUSION: Our preclinical pilot study suggests that a ketogenic...... diet may be a novel approach for treating alcohol withdrawal symptoms in humans. This article is protected by copyright. All rights reserved....

Smoked cocaine in socially-depressed areas

Directory of Open Access Journals (Sweden)

Díaz Olga

2010-11-01

Full Text Available Abstract Background The main objectives of this study are to describe the smoked cocaine user's profile in socially-depressed areas and their needs from a harm-reduction perspective, to investigate their use of smoking crack and compare the acute effects between injecting and smoking consumption. Methods The study took place in SAPS, Barcelona, Spain. Two focus group sessions were undertaken with a total of 8 drug users. Secondly, the 8 participants answered a structured questionnaire and in the course of the sessions, as a snowball activity, were trained to survey 6 other crack smokers. Results We obtained 56 questionnaires. The majority of participants were from non-European Community countries (62.69%, 70.2% of participants referred to sharing the smoking equipment. The most frequent symptoms reported during smoked cocaine were mydriasis (83.33%, perspiration (72.92% and compulsive object search (70.83% During the group sessions, participants said that smoked cocaine is much more addictive than injected cocaine and causes more anxiety. Participants also reported the difficulty of changing from injected use to smoked use, due to the larger amount of cocaine needed to reach the same effects as when having injected. Conclusions We can conclude that the research, focused on achieving greater knowledge of the smoked cocaine user's profile, their usage of smoking crack, consumption patterns and acute effects, should be incorporated into substance misuse interventions.

Symptom-triggered benzodiazepine therapy for alcohol withdrawal syndrome in the emergency department: a comparison with the standard fixed dose benzodiazepine regimen.

LENUS (Irish Health Repository)

Cassidy, Eugene M

2012-10-01

The aim of the study was to compare symptom-triggered and standard benzodiazepine regimens for the treatment of alcohol withdrawal syndrome in an emergency department clinical decision unit. The authors found that the symptom-triggered approach reduced cumulative benzodiazepine dose and length of stay.

Cocaine Allergy in Drug-Dependent Patients and Allergic People.

Science.gov (United States)

Armentia, Alicia; Martín-Armentia, Blanca; Martín-Armentia, Sara; Ruiz-Muñoz, Pedro; Quesada, Jorge Martínez; Postigo, Idoia; Conde, Rosa; González-Sagrado, Manuel; Pineda, Fernando; Castillo, Miriam; Palacios, Ricardo; Tejedor, Jesús

Adverse reactions to local anesthetics (LAs), especially esters, are not uncommon, but true allergy is rarely diagnosed. To our knowledge, currently there is no reliable method of determining IgE-mediated hypersensitivity to LAs and cocaine. To assess the clinical value of allergy tests (prick, IgE, challenges, and arrays) in people suffering hypersensitivity reactions (asthma and anaphylaxis) during local anesthesia with cocaine derivatives and drug abusers with allergic symptoms after cocaine inhalation. We selected cocaine-dependent patients and allergic patients who suffered severe reactions during local anesthesia from a database of 23,873 patients. The diagnostic yield (sensitivity, specificity, and predictive value) of allergy tests using cocaine and coca leaf extracts in determining cocaine allergy was assessed, taking a positive challenge as the criterion standard. After prick tests, specific IgE, and challenge with cocaine extract, 41 of 211 patients (19.4%) were diagnosed as sensitized to cocaine. Prick tests and IgE to coca leaves (coca tea) had a good sensitivity (95.1% and 92.7%, respectively) and specificity (92.3 and 98.8%, respectively) for the diagnosis of cocaine allergy and LA-derived allergy. Cocaine may be an important allergen. Drug abusers and patients sensitized to local anesthesia and tobacco are at risk. Both prick tests and specific IgE against coca leaf extract detected sensitization to cocaine. The highest levels were related to severe clinical profiles. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A psychometric validation of the Short Alcohol Withdrawal Scale (SAWS)

DEFF Research Database (Denmark)

Elholm, Bjarne; Larsen, Klaus; Hornnes, Nete

2010-01-01

The study aimed to evaluate psychometrically a Danish translation of the Short Alcohol Withdrawal Scale (SAWS) in an outpatient setting in patients with Alcohol Dependence (AD) and Alcohol Withdrawal Symptoms/Syndrome (AWS).......The study aimed to evaluate psychometrically a Danish translation of the Short Alcohol Withdrawal Scale (SAWS) in an outpatient setting in patients with Alcohol Dependence (AD) and Alcohol Withdrawal Symptoms/Syndrome (AWS)....

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... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite...

Reduced frontal brain volume in non-treatment-seeking cocaine-dependent individuals: exploring the role of impulsivity, depression, and smoking.

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Crunelle, Cleo L; Kaag, Anne Marije; van Wingen, Guido; van den Munkhof, Hanna E; Homberg, Judith R; Reneman, Liesbeth; van den Brink, Wim

2014-01-01

In cocaine-dependent patients, gray matter (GM) volume reductions have been observed in the frontal lobes that are associated with the duration of cocaine use. Studies are mostly restricted to treatment-seekers and studies in non-treatment-seeking cocaine abusers are sparse. Here, we assessed GM volume differences between 30 non-treatment-seeking cocaine-dependent individuals and 33 non-drug using controls using voxel-based morphometry. Additionally, within the group of non-treatment-seeking cocaine-dependent individuals, we explored the role of frequently co-occurring features such as trait impulsivity (Barratt Impulsivity Scale, BIS), smoking, and depressive symptoms (Beck Depression Inventory), as well as the role of cocaine use duration, on frontal GM volume. Smaller GM volumes in non-treatment-seeking cocaine-dependent individuals were observed in the left middle frontal gyrus. Moreover, within the group of cocaine users, trait impulsivity was associated with reduced GM volume in the right orbitofrontal cortex, the left precentral gyrus, and the right superior frontal gyrus, whereas no effect of smoking severity, depressive symptoms, or duration of cocaine use was observed on regional GM volumes. Our data show an important association between trait impulsivity and frontal GM volumes in cocaine-dependent individuals. In contrast to previous studies with treatment-seeking cocaine-dependent patients, no significant effects of smoking severity, depressive symptoms, or duration of cocaine use on frontal GM volume were observed. Reduced frontal GM volumes in non-treatment-seeking cocaine-dependent subjects are associated with trait impulsivity and are not associated with co-occurring nicotine dependence or depression.

A phase III, randomized, multi-center, double blind, placebo controlled study of safety and efficacy of lofexidine for relief of symptoms in individuals undergoing inpatient opioid withdrawal.

Science.gov (United States)

Gorodetzky, Charles W; Walsh, Sharon L; Martin, Peter R; Saxon, Andrew J; Gullo, Kristen L; Biswas, Kousick

2017-07-01

Lofexidine is an alpha-2-adrenergic receptor agonist approved in the United Kingdom (UK) for the treatment of opioid withdrawal symptoms. Lofexidine has demonstrated better efficacy than placebo for reducing opioid withdrawal symptoms in patients undergoing opioid withdrawal with less reported hypotension than clonidine. Designed as an FDA registration trial, this 8-day, randomized, double-blind, placebo-controlled, parallel-group study in 264 patients dependent on short-acting opioids evaluated the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid withdrawal. The primary efficacy measures were SOWS-Gossop on Day 3 and time-to-dropout. Secondary endpoints included the proportion of participants who were completers; area under the 5-day SOWS-Gossop - time curve (i.e., AUC 1-5 ), and daily mean SOWS-Gossop, OOWS-Handelsman, MCGI (subject and rater), and VAS-E scores. Participants received lofexidine HCl 3.2mg daily in four divided doses or matching placebo on Days 1-5, followed by 2days of placebo. Lofexidine significantly decreased mean Day 3 SOWS scores compared to placebo, 6.32 versus 8.67, respectively, p=0.0212. Fewer lofexidine patients were early terminators compared to placebo (59 versus 80, respectively); and non-completers in the lofexidine group remained in the study longer than those assigned to placebo (p=0.0034). Secondary endpoints consistently favored lofexidine. Lofexidine was well tolerated in this trial. Lofexidine significantly decreased SOWS scores compared to placebo and demonstrated better retention rates in participants undergoing opioid withdrawal. Lofexidine potentially offers a useful non-opioid alternative to treat opioid withdrawal symptoms. Copyright © 2017. Published by Elsevier B.V.

Asthma associated with the use of cocaine, heroin, and marijuana: A review of the evidence.

Science.gov (United States)

Self, Timothy H; Shah, Samarth P; March, Katherine L; Sands, Christopher W

2017-09-01

A review of the evidence was conducted regarding asthma associated with the use of cocaine, heroin, and marijuana. A search of the English literature was performed via PubMed/Medline and EMBASE using the search terms asthma AND cocaine, heroin, and marijuana. When pertinent articles were found, salient references in those articles were assessed. Due to the relatively small number of studies, we included all studies and cases. For several decades, case reports, retrospective studies, and laboratory investigations have demonstrated that inhalation of cocaine or heroin is associated with increased asthma symptoms and reduced pulmonary function. Smoking crack cocaine, nasal insufflation of cocaine or heroin, and smoking heroin increases the risk of emergency department visits and hospitalizations for asthma. Although frequent smoking of marijuana may cause symptoms of cough, sputum production, and wheezing in the general population, more studies are needed specifically in patients with asthma. Smoking marijuana with concomitant tobacco use is common and further worsens the respiratory symptoms. Use of cocaine and heroin in patients with asthma should be avoided. Pending further studies, it would be prudent for patients with asthma to avoid smoking marijuana. Clinicians need to be vigilant regarding use of these drugs in their patients with hyperreactive airway disease.

Mothers' Early Depressive Symptoms and Children's First-Grade Adjustment: A Transactional Analysis of Child Withdrawal as a Mediator

Science.gov (United States)

Yan, Ni; Dix, Theodore

2014-01-01

Background: The depression-inhibition hypothesis suggests that mothers' depressive symptoms undermine development because they lead children to withdraw from social contact. To test this, this study examined whether poor first-grade adjustment among children of mothers with depressive symptoms is mediated by the emergence of child withdrawal…

Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats.

Science.gov (United States)

Galeano, Pablo; Romero, Juan Ignacio; Luque-Rojas, María Jesús; Suárez, Juan; Holubiec, Mariana Inés; Bisagno, Verónica; Santín, Luis Javier; De Fonseca, Fernando Rodríguez; Capani, Francisco; Blanco, Eduardo

2013-09-01

Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine-related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of this study was to determine whether PA could be associated with altered behavioral sensitization to cocaine. To this end, adult rats born vaginally (CTL), by caesarean section (C+), or by C+ with 15 min (PA15, moderate PA) or 19 min (PA19, severe PA) of global anoxia were repeatedly administered with cocaine (i.p., 15 mg/kg) and then challenged with cocaine (i.p., 15 mg/kg) after a 5-day withdrawal period. In addition, c-Fos, FosB/ΔFosB, DAT, and TH expression were assessed in dorsal (CPu) and ventral (NAcc) striatum. Results indicated that PA15 rats exhibited an increased locomotor sensitization to cocaine, while PA19 rats displayed an abnormal acquisition of locomotor sensitization and did not express a sensitized response to cocaine. c-Fos expression in NAcc, but not in CPu, was associated with these alterations in cocaine sensitization. FosB/ΔFosB expression was increased in all groups and regions after repeated cocaine administration, although it reached lower expression levels in PA19 rats. In CTL, C+, and PA15, but not in PA19 rats, the expression of TH in NAcc was reduced in groups repeatedly treated with cocaine, independently of the challenge test. Furthermore, this reduction was more pronounced in PA15 rats. DAT expression remained unaltered in all groups and regions studied. These results suggest that moderate PA may increase the vulnerability to drug abuse and in particular to cocaine addiction. Copyright © 2013 Wiley Periodicals, Inc.

Possible addiction transference from cocaine insufflation to oral bupropion in bipolar patient.

Science.gov (United States)

Costa, Carolina; Araujo, Alberto; Brasil, Marco; Cruz, Marcelo

2015-01-01

Alert for the risk of oral bupropion addiction in patients with cocaine dependence. Single-case study. After a period of cocaine and alcohol abstinence, a 42-year-old patient started taking oral bupropion to relieve the symptoms of cocaine craving. He increased the bupropion dose up to 2250 mg/d without seizures. This case highlights the possibility of oral bupropion addiction after cocaine dependence. To our knowledge, it is the first case in the literature and emphasizes the risk of bupropion's misuse. Therefore, physicians should carefully examine the patient's profile before prescribing it, as well as follow appropriate measures.

The benzodiazepine withdrawal syndrome and its management.

OpenAIRE

Onyett, S R

1989-01-01

The literature on benzodiazepine dependence and withdrawal is reviewed with an emphasis on social and psychological considerations. The problems of when to prescribe, identifying withdrawal symptoms, effective communication with the patient, the structure of withdrawal programmes, and the use of drugs, psychological approaches and other services are discussed.

A test of the stress-buffering model of social support in smoking cessation: is the relationship between social support and time to relapse mediated by reduced withdrawal symptoms?

Science.gov (United States)

Creswell, Kasey G; Cheng, Yu; Levine, Michele D

2015-05-01

Social support has been linked to quitting smoking, but the mechanisms by which social support affects cessation are poorly understood. The current study tested a stress-buffering model of social support, which posits that social support protects or "buffers" individuals from stress related to quitting smoking. We hypothesized that social support would be negatively associated with risk of relapse, and that this effect would be mediated by reduced withdrawal and depressive symptoms (i.e., cessation-related stress) over time. Further, we predicted that trait neuroticism would moderate this mediational effect, such that individuals high in negative affectivity would show the greatest stress-buffering effects of social support. Participants were weight-concerned women (n = 349) ages 18-65 enrolled in a randomized, double-blind, placebo-controlled smoking cessation trial of bupropion and cognitive behavioral therapy. Social support was assessed at baseline, and biochemically-verified abstinence, withdrawal-related symptoms, and depressive symptoms were assessed at 1-, 3-, 6-, and 12-months follow-up. Social support was negatively related to risk of relapse in survival models and negatively related to withdrawal symptoms and depression in mixed effects models. These relationships held after controlling for the effects of pre-quit day negative affect and depression symptoms, assignment to treatment condition, and number of cigarettes smoked per day. A temporal mediation model showed that the effect of social support on risk of relapse was mediated by reductions in withdrawal symptoms over time but not by depression over time. Contrary to hypotheses, we did not find that neuroticism moderated this mediation effect. Increased social support may buffer women from the harmful effects of cessation-related withdrawal symptoms, which in turn improve cessation outcomes. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and

A rare case of complicated opioid withdrawal in delirium without convulsions

OpenAIRE

B Neeraj Raj; N Manamohan; Divya Hegde; Chandrashekar B Huded; Johnson Pradeep

2017-01-01

Opioids are one of the commonly abused substances in India. Opioid withdrawal symptoms classically include severe muscle cramps, bone aches, autonomic symptoms, anxiety, restlessness, insomnia, and temperature dysregulation. However, reports of cases with delirium during withdrawal are few. A 25-year-old male with severe opioid withdrawal symptoms developed delirium. Investigations were normal. There were no comorbidities, no significant past history and family history. Patient treated for op...

Sedative-hypnotic drug withdrawal syndrome: recognition and treatment [digest].

Science.gov (United States)

Santos, Cynthia; Olmedo, Ruben E; Kim, Jeremy

2017-03-22

Sedative-hypnotic drugs include gamma-Aminobutyric acid (GABA)ergic agents such as benzodiazepines, barbiturates, gamma-Hydroxybutyric acid [GHB], gamma-Butyrolactone [GBL], baclofen, and ethanol. Chronic use of these substances can cause tolerance, and abrupt cessation or a reduction in the quantity of the drug can precipitate a life-threatening withdrawal syndrome. Benzodiazepines, phenobarbital, propofol, and other GABA agonists or analogues can effectively control symptoms of withdrawal from GABAergic agents. Managing withdrawal symptoms requires a patient-specific approach that takes into account the physiologic pathways of the particular drugs used as well as the patient's age and comorbidities. Adjunctive therapies include alpha agonists, beta blockers, anticonvulsants, and antipsychotics. Newer pharmacological therapies offer promise in managing withdrawal symptoms. [Points & Pearls is a digest of Emergency Medicine Practice].

Cocaine adulteration.

Science.gov (United States)

Kudlacek, Oliver; Hofmaier, Tina; Luf, Anton; Mayer, Felix P; Stockner, Thomas; Nagy, Constanze; Holy, Marion; Freissmuth, Michael; Schmid, Rainer; Sitte, Harald H

2017-10-01

Cocaine is a naturally occurring and illicitly used psychostimulant drug. Cocaine acts at monoaminergic neurotransmitter transporters to block uptake of the monoamines, dopamine, serotonin and norepinephrine. The resulting increase of monoamines in the extracellular space underlies the positively reinforcing effects that cocaine users seek. In turn, this increase in monoamines underlies the development of addiction, and can also result in a number of severe side effects. Currently, cocaine is one of the most common illicit drugs available on the European market. However, cocaine is increasingly sold in impure forms. This trend is driven by cocaine dealers seeking to increase their profit margin by mixing ("cutting") cocaine with numerous other compounds ("adulterants"). Importantly, these undeclared compounds put cocaine consumers at risk, because consumers are not aware of the additional potential threats to their health. This review describes adulterants that have been identified in cocaine sold on the street market. Their typical pharmacological profile and possible reasons why these compounds can be used as cutting agents will be discussed. Since a subset of these adulterants has been found to exert effects similar to cocaine itself, we will discuss levamisole, the most frequently used cocaine cutting agent today, and its metabolite aminorex. Copyright © 2017. Published by Elsevier B.V.

Eight weeks of citicoline treatment does not perturb sleep/wake cycles in cocaine-dependent adults.

Science.gov (United States)

Bracken, Bethany K; Penetar, David M; Rodolico, John; Ryan, Elizabeth T; Lukas, Scott E

2011-06-01

Citicoline (cytidine-5'-diphosphate) is a mononucleotide composed of ribose, cytosine, pyrophosphate, and choline, and is involved in the biosynthesis of the structural phosopholipids of cell membranes. Treatment with citicoline, improves memory in patients with dementia, and reduces damage to the brain after traumatic brain injury or stroke. Recent research has been conducted to assess whether citicoline is an effective treatment for cocaine dependence. In cocaine-dependent individuals, withdrawal from cocaine is associated with disturbed sleep, which may contribute to the high rate of relapse to cocaine use. Therefore, it is important to know the impact of citicoline on the sleep/wake cycle in these individuals in order to rate its overall efficacy. In this double-blind, placebo-controlled trial, the effects of citicoline treatment on the sleep/wake cycles of cocaine dependent participants were assessed. The results of the current study are reported as part of a larger study, consisting of an eight-week treatment period to assess the efficacy of longer-term treatment with citicoline at decreasing cocaine consumption in cocaine-dependent polydrug using participants. In this non-abstinent, cocaine-dependent population, citicoline had no effect on any of the sleep parameters measured including sleep efficiency, sleep latency, total sleep time, number of waking episodes, time awake per episode, amount of time in bed spent moving, number of sleep episodes, time asleep per episode, and amount of time in bed spent immobile. These data suggest that eight weeks of citicoline administration does not disturb sleep/wake cycles of cocaine-dependent individuals. Copyright © 2011 Elsevier Inc. All rights reserved.

[Cocaine base paste: experience from the Montevideo Poison Control Center].

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Pascale, Antonio; Negrin, Alba; Laborde, Amalia

2010-01-01

In Uruguay, cocaine base paste (CBP, pasta base) is a widely used form of cocaine. The aim of our study is to determine the main clinical characteristics of CBP abusers. Retrospective, single-center study of consultations at the Montevideo Poison Control Center between January 1, 2004 and December 31, 2005. One hundred and thirteen consultations were included, with an average age of 22 years (+ - 0.5 years) and a female-male sex ratio of 1:4.3. The consultations were related to drug overdose (77%), suicide attempt (16.8%), and wanting to give up CBP use (6.2%). In 48.1% the time elapsed since inhalation of CBP was less than 6 hours. Doses varied between 0.5 gr. and 25 gr. Use of other drugs at the same time, such as alcohol, marijuana or benzodiazepines, was common (51 cases). The symptoms most frequently observed were neuropsychiatric and cardiovascular, followed by respiratory symptoms. In 16.8% of patients, reason for the consultation was intentional acute ingestion of drugs, considered as a suicide attempt, occurring within a few hours of drug consumption. CBP users are mostly young males. Although clinical findings are compatible with those for cocaine abuse, euphoria is a major clinical feature in CBP abusers. The presence of respiratory symptoms reflects the complications associated with the ingestion route. Suicide attempts occurring within a few hours of CBP confirm the high prevalence of suicidal ideation reported by other authors. cocaine base paste, clinical features, suicide attempts.

Precursors of social emotional functioning among full-term and preterm infants at 12 months: Early infant withdrawal behavior and symptoms of maternal depression.

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Moe, Vibeke; Braarud, Hanne Cecilie; Wentzel-Larsen, Tore; Slinning, Kari; Vannebo, Unni Tranaas; Guedeney, Antoine; Heimann, Mikael; Rostad, Anne Margrethe; Smith, Lars

2016-08-01

This study forms part of a longitudinal investigation of early infant social withdrawal, maternal symptoms of depression and later child social emotional functioning. The sample consisted of a group of full-term infants (N=238) and their mothers, and a group of moderately premature infants (N=64) and their mothers. At 3 months, the infants were observed with the Alarm Distress Baby Scale (ADBB) and the mothers completed the Edinburgh Postnatal Depression Scale (EPDS). At 12 months, the mothers filled out questionnaires about the infants' social emotional functioning (Infant Toddler Social Emotional Assessment and the Ages and Stages Questionnaire-Social Emotional). At 3 months, as we have previously shown, the premature infants had exhibited more withdrawal behavior and their mothers reported elevated maternal depressive symptoms as compared with the full-born group. At 12 months the mothers of the premature infants reported more child internalizing behavior. These data suggest that infant withdrawal behavior as well as maternal depressive mood may serve as sensitive indices of early risk status. Further, the results suggest that early maternal depressive symptoms are a salient predictor of later child social emotional functioning. However, neither early infant withdrawal behavior, nor gestational age, did significantly predict social emotional outcome at 12 months. It should be noted that the differences in strength of the relations between ADBB and EPDS, respectively, to the outcome at 12 months was modest. An implication of the study is that clinicians should be aware of the complex interplay between early infant withdrawal and signs of maternal postpartum depression in planning ports of entry for early intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Comorbidity effects on cocaine dependence treatment and examination of reciprocal relationships between abstinence and depression.

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Milby, Jesse B; Conti, Kimberly; Wallace, Dennis; Mennemeyer, Stephen; Mrug, Sylvie; Schumacher, Joseph E

2015-02-01

We examined comorbid disorders' prevalence, their impact on abstinence, and the impact of depressive symptoms on abstinence and of abstinence on depressive symptoms. A randomized controlled trial's data on outcomes from treating cocaine dependence were used. It compared abstinence-contingent housing and work to contingency management plus behavioral day treatment. Regardless of original trial arm assignment, groups of participants with no additional Axis I disorders (n = 87) and 1 or more additional Axis I disorders (n = 113) were compared for abstinence. Changes in depression symptoms, measured by the Beck Depression Inventory, were analyzed as a function of 4 cohorts of increased consecutive weeks abstinent. An autoregressive cross-lagged path model examined reciprocal relationships between depression and abstinence. Most prevalent additional disorders were depressive disorders, followed by anxiety disorders. Additional disorders did not significantly affect abstinence. Cohorts with more abstinence were linearly related to lower depression symptoms. The cross-lagged model showed that longer abstinence predicted decreases in depressive symptoms at 6 months. However, depressive symptoms did not predict changes in abstinence. Our study adds to others that have found an effective treatment targeted at specific problems such as substance abuse, social anxiety disorder, and posttraumatic stress disorder that may have the side benefit of reducing depression. Additionally, we find that depression does not interfere with effective substance abuse treatment for cocaine dependency. This may be the 1st formal analysis comparing the ability of cocaine abstinence to predict future depressive symptoms versus depressive symptoms to predict future cocaine abstinence. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

A bacterial cocaine esterase protects against cocaine-induced epileptogenic activity and lethality.

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Jutkiewicz, Emily M; Baladi, Michelle G; Cooper, Ziva D; Narasimhan, Diwahar; Sunahara, Roger K; Woods, James H

2009-09-01

Cocaine toxicity results in cardiovascular complications, seizures, and death and accounts for approximately 20% of drug-related emergency department visits every year. Presently, there are no treatments to eliminate the toxic effects of cocaine. The present study hypothesizes that a bacterial cocaine esterase with high catalytic efficiency would provide rapid and robust protection from cocaine-induced convulsions, epileptogenic activity, and lethality. Cocaine-induced paroxysmal activity and convulsions were evaluated in rats surgically implanted with radiotelemetry devices (N=6 per treatment group). Cocaine esterase was administered 1 minute after a lethal dose of cocaine or after cocaine-induced convulsions to determine the ability of the enzyme to prevent or reverse, respectively, the effects of cocaine. The cocaine esterase prevented all cocaine-induced electroencephalographic changes and lethality. This effect was specific for cocaine because the esterase did not prevent convulsions and death induced by a cocaine analog, (-)-2beta-carbomethoxy-3beta-phenyltropane. The esterase prevented lethality even after cocaine-induced convulsions occurred. In contrast, the short-acting benzodiazepine, midazolam, prevented cocaine-induced convulsions but not the lethal effects of cocaine. The data showed that cocaine esterase successfully degraded circulating cocaine to prevent lethality and that cocaine-induced convulsions alone are not responsible for the lethal effects of cocaine in this model. Therefore, further investigation into the use of cocaine esterase for treating cocaine overdose and its toxic effects is warranted.

Context-dependent efficacy of a counter-conditioning strategy with atypical neuroleptic drugs in mice previously sensitized to cocaine.

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Oliveira-Lima, A J; Marinho, Eav; Santos-Baldaia, R; Hollais, A W; Baldaia, M A; Talhati, F; Ribeiro, L T; Wuo-Silva, R; Berro, L F; Frussa-Filho, R

2017-02-06

We have previously demonstrated that treatment with ziprasidone and aripiprazole selectively inhibit the development of behavioral sensitization to cocaine in mice. We now investigate their effects on a counter-conditioning strategy in mice and the importance of the treatment environment for this phenomenon. Evaluate the context-specificity of ziprasidone and aripiprazole on conditioned locomotion to cocaine and cocaine-induced hyperlocomotion and behavioral sensitization in a counter-conditioning strategy in mice. Animals were sensitized with saline or cocaine injections in the open-field apparatus in a 15-day intermittent treatment and subsequently treated with vehicle, 5mg/kg ziprasidone or 0.1mg/kg aripiprazole paired to the open-field or the home-cage for 4 alternate days. Mice were then challenged with saline and cocaine in the open-field apparatus on subsequent days. While treatment with ziprasidone decreased spontaneous locomotion and conditioned locomotion alike, treatment with aripiprazole specifically attenuated the expression of conditioned hyperlocomotion to cocaine. Ziprasidone and aripiprazole had no effects on cocaine-induced conditioned hyperlocomotion observed during saline challenge after drug withdrawal. Treatment with either ziprasidone or aripiprazole when previously given in the cocaine-paired environment attenuated the subsequent expression of behavioral sensitization to cocaine. Animals treated with aripiprazole in the open-field, but not in the home-cage, showed a blunted response to cocaine when receiving a cocaine challenge for the first time. Both neuroleptic drugs showed a context-dependent effectiveness in attenuating long-term expression of cocaine-induced behavioral sensitization when administered in the cocaine-associated environment, with aripiprazole also showing effectiveness in blocking the expression of acute cocaine effects. Copyright © 2016. Published by Elsevier Inc.

Cocaine

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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 ...

Enhanced Choice for Viewing Cocaine Pictures in Cocaine Addiction

International Nuclear Information System (INIS)

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.

2009-01-01

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.

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.

Acupuncture for alcohol withdrawal: a randomized controlled trial.

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Trümpler, François; Oez, Suzan; Stähli, Peter; Brenner, Hans Dieter; Jüni, Peter

2003-01-01

Previous trials on acupuncture in alcohol addiction were in outpatients and focused on relapse prevention. Rates of dropout were high and interpretation of results difficult. We compared auricular laser and needle acupuncture with sham laser stimulation in reducing the duration of alcohol withdrawal. Inpatients undergoing alcohol withdrawal were randomly allocated to laser acupuncture (n = 17), needle acupuncture (n = 15) or sham laser stimulation (n = 16). Attempts were made to blind patients, therapists and outcome assessors, but this was not feasible for needle acupuncture. The duration of withdrawal symptoms (as assessed using a nurse-rated scale) was the primary outcome; the duration of sedative prescription was the secondary outcome. Patients randomized to laser and sham laser had identical withdrawal symptom durations (median 4 days). Patients randomized to needle stimulation had a shorter duration of withdrawal symptoms (median 3 days; P = 0.019 versus sham intervention), and tended to have a shorter duration of sedative use, but these differences diminished after adjustment for baseline differences. The data from this pilot trial do not suggest a relevant benefit of auricular laser acupuncture for alcohol withdrawal. A larger trial including adequate sham interventions is needed, however, to reliably determine the effectiveness of any type of auricular acupuncture in this condition.

Drivers under the influence of drugs of abuse: quantification of cocaine and impaired driving.

Science.gov (United States)

Arroyo, Amparo; Sánchez, Marta; Barberia, Eneko; Barbal, Maria; Marrón, M Teresa; Mora, Agustí

2013-01-01

In recent years, the interest in oral fluid as a biological matrix has significantly increased, particularly for detecting driving under the influence of drugs. In this study, the concentration of cocaine and its relationship with clinical symptoms in drivers suspected of driving under the influence of drugs was evaluated. A total of 154 samples of oral fluid, which tested positive for cocaine in previous immunoassay screening, Cozart Drug Detector System, were confirmed using gas chromatography/mass spectrometry method. In Catalonia, during 2007-2010, there were 1791 samples positive for cocaine among a total of 3468 samples taken from drivers who tested positive for any drug of abuse. The evaluation of clinical symptoms was through a questionnaire that was filled in by the police officers who collected the samples. The mean concentration of cocaine was 4.11 mg/l and median concentration was 0.38 mg/l (range 0.01-345.64 mg/l). Clinical impairment symptoms such as motor coordination, walking, speech, mood and state of pupils were not significant. The testing of oral fluids presents fewer ethical problems than blood or urine.

CRFR1 in the ventromedial caudate putamen modulates acute stress-enhanced expression of cocaine locomotor sensitization.

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Liu, Shuli; Wang, Zhiyan; Li, Yijing; Sun, Xiaowei; Ge, Feifei; Yang, Mingda; Wang, Xinjuan; Wang, Na; Wang, Junkai; Cui, Cailian

2017-07-15

Repeated exposure to psychostimulants induces a long-lasting enhancement of locomotor activity called behavioral sensitization, which is often reinforced by stress after drug withdrawal. The mechanisms underlying these phenomena remain elusive. Here we explored the effects of acute stress 3 or 14 days after the cessation of chronic cocaine treatment on the expression of locomotor sensitization induced by a cocaine challenge in rats and the key brain region and molecular mechanism underlying the phenomenon. A single session of forced swimming, as an acute stress (administered 2 days after the cessation of cocaine), significantly enhanced the expression of cocaine locomotor sensitization 14 days after the final cocaine injection (challenge at 12 days after acute stress) but not 3 days after the cessation of cocaine (challenge at 1 day after acute stress). The result indicated that acute stress enhanced the expression of cocaine locomotor sensitization after incubation for 12 days rather than 1 day after the last cocaine injection. Moreover, the enhancement in locomotor sensitization was paralleled by a selective increase in the number of the c-Fos + cells, the level of CRFR1 mRNA in the ventromedial caudate putamen (vmCPu). Furthermore, the enhancement was significantly attenuated by CRFR1 antagonist NBI-27914 into the vmCPu, implying that the up-regulation of CRFR1 in the vmCPu seems to be critical in the acute stress-enhanced expression of cocaine locomotor sensitization. The findings demonstrate that the long-term effect of acute stress on the expression of cocaine locomotor sensitization is partially mediated by CRFR1 in the vmCPu. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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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.

Selegiline prevents long-term changes in dopamine efflux and stress immobility during the second and third weeks of abstinence following opiate withdrawal.

Science.gov (United States)

Grasing, K; Ghosh, S

1998-08-01

Selegiline is an irreversible inhibitor of monoamine oxidase B with trophic and neuroprotective effects. Because of evidence for decreased dopaminergic function during the withdrawal syndromes associated with opiates and other medications with potential for abuse, we investigated effects of treatment with selegiline on in vitro measures of dopamine efflux following opiate withdrawal. Treatment with 2.0 mg/kg/day of selegiline did not modify the severity of opiate withdrawal, as assessed by weight loss over the first 3 days of abstinence. Opiate withdrawal increased immobility in response to a forced warm water swim test performed during the second and third weeks of abstinence following the onset of withdrawal. Brain slices obtained from the nucleus accumbens of opiate-withdrawn animals immediately following swim stress testing displayed diminished efflux of tritiated dopamine after two in vitro exposures to cocaine or amphetamine. Cocaine increases neurotransmitter efflux through blockade of dopamine reuptake, while amphetamine augments efflux by stimulating release of dopamine from intracellular storage vesicles. Although slices from opiate withdrawal subjects showed decreases in efflux after in vitro treatment with these agents, no differences were observed after exposure to 4-aminopyridine, which increases neurotransmitter release by prolonging action potential duration. These findings indicate mechanisms of action that are specific for catecholamine neurotransmitter systems are important for demonstrating long-term changes in dopaminergic function following opiate withdrawal. Selegiline prevented decreases in the efflux of tritiated dopamine in slices obtained from opiate-withdrawn subjects. In addition, selegiline decreased withdrawal-induced immobility during warm water swim testing. In conclusion, treatment with selegiline can prevent long-term changes in stress-induced immobility and deficits in presynaptic dopaminergic function that occur following the

Amantadine as Augmentation in Managing Opioid Withdrawal with Clonidine: a randomized controlled trial.

Directory of Open Access Journals (Sweden)

Shahrokh Amiri

2014-09-01

Full Text Available Withdrawal symptoms are a main reason of continuous use of opioid. This study compares the efficacy of augmentation of amantadine with clonidine in decreasing opioid withdrawal symptoms.This double-blind randomized clinical trial was carried out in the detoxification and rehabilitation inpatient ward at Razi Hospital, Tabriz, Iran during 2012. The patients were randomly assigned to receive clonidine or clonidine plus amantadine; and withdrawal symptoms were evaluated in the admission day and 24, 48, and 72 hours later. Data were analyzed using SPSS by the 2*2 repeated analyses of variances (ANOVA.From the total of 69 participants, 30 patients completed the trial in each group. The severity of symptoms, however, had an increasing trend in both groups. Analysis of variance of the symptom severity score (by The Clinical Opiate Withdrawal Scale revealed a significant group-time interaction, and the patients who were receiving amantadine experienced milder symptoms.Treatment of opioid withdrawal symptoms with amantadine and clonidine would result in a better outcome compared with clonidine alone.

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.

2015-01-01

Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n = 316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. PMID:20609384

Psychosis following Tramadol Withdrawal

OpenAIRE

Rajabizadeh, Ghodratolah; Kheradmand, Ali; Nasirian, Mansoureh

2009-01-01

Background: Tramadol is a centrally acting opioid analgesic used to treat moderate to sever pain. It has more advantage and less opioid adverse effects than conventional opioid analgesia. Case Report: This article reports a patient with tramadol dependency that had psychosis after tramadol withdrawal. Conclusion: By the increase of tramadol usage for relief of chronic pain, tramadol abuse and dependency is increased. Some of tramadol withdrawal symptoms are not related to opioid, for example ...

Cocaine-induced agitated delirium: a case report and review.

Science.gov (United States)

Plush, Theodore; Shakespeare, Walter; Jacobs, Dorian; Ladi, Larry; Sethi, Sheeba; Gasperino, James

2015-01-01

Cocaine use continues to be a major public health problem in the United States. Although many of the initial signs and symptoms of cocaine intoxication result from increased stimulation of the sympathetic nervous system, this condition can present as a spectrum of acuity from hypertension and tachycardia to multiorgan system failure. Classic features of acute intoxication include tachycardia, arterial vasoconstriction, enhanced thrombus formation, mydriasis, psychomotor agitation, and altered level of consciousness. At the extreme end of this toxidrome is a rare condition known as cocaine-induced agitated delirium. This syndrome is characterized by severe cardiopulmonary dysfunction, hyperthermia, and acute neurologic changes frequently leading to death. We report a case of cocaine-induced agitated delirium in a man who presented to our institution in a paradoxical form of circulatory shock. Rapid evaluation, recognition, and proper management enabled our patient not only to survive but also to leave the hospital without neurologic sequelae. © The Author(s) 2013.

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

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Siciliano, Cody A.; Fordahl, Steve C.

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. Here we determined that cocaine self-administration in rats produced tolerance to the dopamine transporter-inhibiting effects of cocaine in the nucleus accumbens core, which was normalized following a 14 or 60 d abstinence period; however, although these rats appeared to be similar to controls, a single self-administered infusion of cocaine at the end of abstinence, even after 60 d, fully reinstated tolerance to cocaine's effects. A single cocaine infusion in a naive rat had no effect on cocaine potency, demonstrating that cocaine self-administration leaves the dopamine transporter in a “primed” state, which allows for cocaine-induced plasticity to be reinstated by a subthreshold cocaine exposure. Further, reinstatement of cocaine tolerance was accompanied by decreased cocaine-induced locomotion and escalated cocaine intake despite extended abstinence from cocaine. These data demonstrate that cocaine leaves a long-lasting imprint on the dopamine system that is activated by re-exposure to cocaine. Further, these results provide a potential mechanism for severe cocaine binge episodes, which occur even after sustained abstinence from cocaine, and suggest that treatments aimed at transporter sites may be efficacious in promoting binge termination following relapse. SIGNIFICANCE STATEMENT Tolerance is a DSM-V criterion for substance abuse disorders. Abusers consistently show reduced subjective effects of cocaine concomitant with reduced effects of cocaine at its main site of action

Is Homeopathy Effective for Hot Flashes and Other Estrogen-Withdrawal Symptoms in Breast Cancer Survivors? A Preliminary Randomized Controlled Trial

Science.gov (United States)

2003-04-01

homeopathy may be effective in improving hot flashes and quality of life in breast cancer survivors with symptoms of estrogen withdrawal. Methods- A...scores improved significantly in both homeopathy groups compared to placebo. Results of this study suggest that a larger study should be done.

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.

Binge-pattern cocaine administration causes long-lasting behavioral hyperarousal but does not enhance vulnerability to single prolonged stress in rats.

Science.gov (United States)

Lisieski, Michael J; Perrine, Shane A

2017-11-01

Cocaine use disorder and post-traumatic stress disorder (PTSD) commonly co-occur. This could be due to vulnerability to post-traumatic symptoms conferred by previous exposure to cocaine. Therefore, we combined chronic binge-pattern cocaine with a model of psychological trauma (single prolonged stress) to determine whether the behavioral effects of psychological trauma are enhanced in cocaine-sensitized individuals. Adult male Sprague Dawley rats received 14 days of cocaine (15mg/kg/injection) or saline in a binge pattern (3 injections per day, 1h apart). Seven days after the last injection animals were exposed to traumatic stress or a control procedure. Seven days after stress, activity and anxiety-like behaviors were measured. Binge-pattern cocaine increased locomotor activity in the open field and elevated plus maze, and both cocaine and SPS exposure increased the rapidity with which rats moved through grooming sequences. Neither binge-pattern cocaine nor SPS increased anxiety-like behaviors, and no interactions were found between binge-pattern cocaine exposure and SPS exposure. A behavioral phenotype categorization approach demonstrated that cocaine-exposed groups expressed a high incidence of hyperactivity-like symptoms. These results suggest that binge-pattern cocaine exposure causes a long-lasting hyper-exploratory phenotype but does not make individuals more vulnerable to a later traumatic stress exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Trajectories of social withdrawal and cognitive decline in the schizophrenia prodrome.

Science.gov (United States)

Cullen, Kathryn; Guimaraes, Angela; Wozniak, Jeffrey; Anjum, Afshan; Schulz, S Charles; White, Tonya

2011-01-01

Schizophrenia is a heterogeneous neurodevelopmental disorder. Patients with high levels of negative symptoms have been identified as a specific subtype, but little is known about how the neurodevelopmental course may differ in this group. This study aimed to characterize developmental trajectories of premorbid social withdrawal and cognitive decline between patients with high versus low levels of negative symptoms in youth with schizophrenia-spectrum disorders. A standardized timeline was used to delineate the emergence of psychosis, social withdrawal, and cognitive decline in 52 subjects aged 8 to 19 with schizophrenia (n=36), schizophreniform (n=6), or schizoaffective disorder (n=10). The sample was divided into subgroups of high- (n=26) versus low- (n=26) negative symptoms, and developmental trajectories of premorbid symptoms were compared between groups. Mean ages for emergence of social withdrawal, cognitive decline, and psychosis were 11.1 years (SD=2.5), 11.9 (SD=4.4) and 13.2 years (SD=1.2), respectively. In the high-negative symptom group, the premorbid developmental trajectory for social withdrawal was more protracted. This group also had more severe cognitive decline at the onset of psychosis, but the premorbid trajectories for cognitive decline did not differ significantly between groups. This work documents a more severe and protracted trajectory of premorbid social withdrawal in patients with high levels of negative symptoms in comparison to those with low-negative symptoms. The findings reported here are supportive of the hypothesis that patients with illness characterized by high levels of negative symptoms may represent a subgroup with distinct neurodevelopmental abnormalities.

Cigarette Cue Attentional Bias in Cocaine-Smoking and Non-Cocaine-Using Cigarette Smokers.

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Marks, Katherine R; Alcorn, Joseph L; Stoops, William W; Rush, Craig R

2016-09-01

Cigarette smoking in cocaine users is nearly four times higher than the national prevalence and cocaine use increases cigarette smoking. The mechanisms underlying cigarette smoking in cocaine-using individuals need to be identified to promote cigarette and cocaine abstinence. Previous studies have examined the salience of cigarette and cocaine cues separately. The present aim was to determine whether cigarette attentional bias (AB) is higher in cigarettes smokers who smoke cocaine relative to individuals who only smoke cigarettes. Twenty cigarette smokers who smoke cocaine and 20 non-cocaine-using cigarette smokers completed a visual probe task with eye-tracking technology. During this task, the magnitude of cigarette and cocaine AB was assessed through orienting bias, fixation time, and response time. Cocaine users displayed an orienting bias towards cigarette cues. Cocaine users also endorsed a more urgent desire to smoke to relieve negative affect associated with cigarette craving than non-cocaine users (g = 0.6). Neither group displayed a cigarette AB, as measured by fixation time. Cocaine users, but not non-cocaine users, displayed a cocaine AB as measured by orienting bias (g = 2.0) and fixation time (g = 1.2). There were no significant effects for response time data. Cocaine-smoking cigarettes smokers display an initial orienting bias toward cigarette cues, but not sustained cigarette AB. The incentive motivation underlying cigarette smoking also differs. Cocaine smokers report more urgent desire to smoke to relieve negative affect. Identifying differences in motivation to smoke cigarettes may provide new treatment targets for cigarette and cocaine use disorders. These results suggest that cocaine-smoking cigarette smokers display an initial orienting bias towards cigarette cues, but not sustained attention towards cigarette cues, relative to non-cocaine-using smokers. Smoked cocaine users also report a more urgent desire to smoke to relieve negative affect

A Case Report of Severe Delirium after Amantadine Withdrawal

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Franz Marxreiter

2017-03-01

Full Text Available Amantadine is frequently used in addition to dopaminergic substances like dopamine agonists or L-Dopa in advanced Parkinson disease (PD. However, adverse effects like hallucinations limit its use. PD patients developing severe psychotic symptoms upon treatment with either dopaminergic substances and/or amantadine need to stop intake of any psychotropic substance. Here, we report the case of a 71-year-old PD patient without previously known cognitive impairment. He presented with drug-induced psychotic symptoms due to changes in his therapeutic regimen (increase in COMT inhibitors, newly introduced MAO B inhibitors. Also, amantadine had been part of his long-term medication for more than 2 years. The severity of his psychotic symptoms required a L-Dopa monotherapy. After changing his medication, the patient developed severe delirium that resolved rapidly after i.v. amantadine infusion, suggesting an amantadine withdrawal syndrome. Amantadine withdrawal syndrome is a rare adverse event that may present even in PD patients without cognitive impairment. This case report highlights the need for a gradual withdrawal of amantadine even if acute and severe psychotic symptoms are present. Moreover, this is the first report of a cognitively unimpaired patient developing an amantadine withdrawal syndrome.

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

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

2016-02-01

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. PsycINFO Database Record (c) 2016 APA, all rights reserved.

Acute pregabalin withdrawal: a case report and review of the literature

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Barrett JA

2015-05-01

Full Text Available Objective: Pregabalin is a commonly prescribed GABA analog most commonly used for the treatment of neuralgia. Recently, case reports on pregabalin have been published describing episodes that may be associated with withdrawal-like symptoms after extended or aggressive therapy. This report describes a case in which long term exposure of high dose pregabalin may have resulted in acute withdrawal, and outlines the subsequent medical management of these symptoms. Case Summary: A 61-year-old male presenting with severe agitation presumed to be withdrawal from long term and high dose exposure to pregabalin. Medical management included the use of haloperidol, diphenhydramine, lorazepam and the addition of clonidine over the course of several days for the pharmacological management of withdrawal symptoms. Discussion: Although case reports are available to guide clinicians in the recognition of acute pregabalin withdrawal, definitive evidence on how best to treat these patients remains severely limited. With an increase in the prescribing practices of pregabalin, insight into the acute management by fellow clinicians is further needed. Conclusion: Caution must be practiced when prescribing and educating patients on the use of pregabalin to prevent associated withdrawal-like symptoms. In addition, documentation by the medical community on methods utilized to treat pregabalin withdrawal syndromes remains crucial for the advancement of patient care. Benzodiazepines and clonidine are the current therapies that have been documented as potentially effective treatment modalities at this time.

Cocaine

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... Viral) HIV/AIDS Mental Health Military Opioid Overdose Reversal with Naloxone (Narcan, Evzio) Pain Prevention Recovery Substance ... cocaine impairs judgment, which can lead to risky sexual behavior with infected partners (see " Cocaine, HIV, and ...

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...

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...

Substance use - cocaine

Science.gov (United States)

Substance abuse - cocaine; Drug abuse - cocaine; Drug use - cocaine ... thinking clearly Mood and emotional problems, such as aggressive or violent behavior Restlessness and tremors Sleep problems ...

Dexmedetomidine infusion to facilitate opioid detoxification and withdrawal in a patient with chronic opioid abuse

Directory of Open Access Journals (Sweden)

Surjya Prasad Upadhyay

2011-01-01

Full Text Available Many patients are admitted to the intensive care unit (ICU for acute intoxication, serious complication of overdose, or withdrawal symptoms of illicit drugs. An acute withdrawal of drugs with addiction potential is associated with a sympathetic overactivity leading to marked psychomimetic disturbances. Acute intoxication or withdrawal of such drugs is often associated with life-threatening complications which require ICU admission and necessitate prolonged sedative analgesic medications, weaning from which is often complicated by withdrawal and other psychomimetic symptoms. Dexmedetomidine, an alpha-2 (α2 agonist, has been used successfully to facilitate withdrawal and detoxification of various drugs and also to control delirium in ICU patients. Herein, we report a case of a chronic opioid abuse (heroin patient admitted with acute overdose complications leading to a prolonged ICU course requiring sedative-analgesic medication; the drug withdrawal-related symptoms further complicated the weaning process. Dexmedetomidine infusion was successfully used as a sedative-analgesic to control the withdrawal-related psychomimetic symptoms and to facilitate smooth detoxification and weaning from opioid and other sedatives.

Nicotine levels, withdrawal symptoms, and smoking reduction success in real world use: A comparison of cigarette smokers and dual users of both cigarettes and E-cigarettes.

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Jorenby, Douglas E; Smith, Stevens S; Fiore, Michael C; Baker, Timothy B

2017-01-01

To evaluate how experienced dual users used cigarettes and e-cigarettes in real-world use and under different levels of cigarette availability. Dual users (cigarettes+e-cigarettes; n=74) and a smoke-only group (just cigarettes; n=74) engaged in a 26-day study with two ad lib use intervals, a week of 75% cigarette reduction and three days of 100% cigarette reduction. After a week of ad lib use of products, all participants were asked to reduce smoking by 75% (dual users were free to use their e-cigarettes as they wished), followed by another week of ad lib use. All participants were then asked to reduce smoking by 100% (cessation) for three days. Primary outcomes were biological samples (carbon monoxide, urinary nicotine and cotinine). Participants also provided real-time reports of product use, craving, and withdrawal symptoms using a smartphone app. Dual users did not smoke fewer cigarettes than smoke-only participants during ad lib periods, but quadrupled their use of e-cigarettes during smoking reduction periods. Dual users were significantly more likely to maintain 100% reduction (97.1% vs. 81.2%). Amongst women, dual use was associated with higher nicotine levels and withdrawal suppression. Among a group of experienced dual users, e-cigarettes helped maintain smoking reduction and reduced some withdrawal symptoms, although both withdrawal symptoms and nicotine levels varied as a function of gender. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Acute detoxification of opioid-addicted patients with naloxone during propofol or methohexital anesthesia: a comparison of withdrawal symptoms, neuroendocrine, metabolic, and cardiovascular patterns

NARCIS (Netherlands)

Kienbaum, P.; Scherbaum, N.; Thürauf, N.; Michel, M. C.; Gastpar, M.; Peters, J.

2000-01-01

OBJECTIVE: Mu-Opioid receptor blockade during general anesthesia is a new treatment for detoxification of opioid addicted patients. We assessed catecholamine plasma concentrations, oxygen consumption, cardiovascular variables, and withdrawal symptoms after naloxone and tested the hypothesis that

Low dopamine transporter occupancy by methylphenidate as a possible reason for reduced treatment effectiveness in ADHD patients with cocaine dependence.

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Crunelle, Cleo L; van den Brink, Wim; Veltman, Dick J; van Emmerik-van Oortmerssen, Katelijne; Dom, Geert; Schoevers, Robert A; Booij, Jan

2013-12-01

Methylphenidate (MPH) occupies brain striatal dopamine transporters (DATs) and is an effective treatment for attention deficit hyperactivity disorder (ADHD). However, patients with ADHD and comorbid cocaine dependence do not benefit significantly from treatment with MPH. To better understand the neurobiology of this phenomenon, we examined DAT availability and the effects of MPH treatment on DAT occupancy in ADHD patients with and without cocaine dependence. ADHD patients without a comorbid substance use disorder (N=16) and ADHD patients with comorbid cocaine dependence (N=8) were imaged at baseline and after two weeks MPH treatment using single photon emission computed tomography (SPECT) with the DAT tracer [(123)I]FP-CIT. Changes in ADHD symptoms were measured with the ADHD symptom rating scale (ASRS). At baseline, we observed lower striatal DAT availability in ADHD patients with cocaine dependence. Following fixed MPH treatment, MPH occupied significantly less striatal DATs in cocaine-dependent than in non-cocaine dependent ADHD patients. There were no significant correlations between baseline DAT availability or DAT occupancy by MPH and ADHD symptom improvement. However, we did find significant correlations between DAT occupancy by MPH and decreases in impulsivity scores and years of cocaine use. These preliminary findings suggest that low DAT occupancy is not the reason why ADHD patients with cocaine dependence do not benefit from MPH treatment. It also suggests that higher dosages of MPH in these patients are probably not the solution and that medications directed at other pharmacological targets should be considered in these comorbid ADHD patients. This trial is registered at the Dutch Trial Register, www.trialregister.nl, under Trial ID number NTR3127. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Monitoring cocaine use and abstinence among cocaine users for contingency management interventions.

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Holtyn, August F; Knealing, Todd W; Jarvis, Brantley P; Subramaniam, Shrinidhi; Silverman, Kenneth

2017-06-01

During contingency management interventions, reinforcement of cocaine abstinence is arranged by delivering an incentive when a urine sample tests cocaine-negative. The use of qualitative versus quantitative urinalysis testing may have important implications for effects on cocaine abstinence. Qualitative testing (i.e., testing that solely identifies whether a particular substance is present or absent) may not detect short-term cocaine abstinence because a single instance of cocaine use can result in cocaine-positive urine over many days. Quantitative testing (i.e., testing that identifies how much of a substance is present) may be more sensitive to short-term cocaine abstinence; however, the selection of a criterion for distinguishing new use versus carryover from previous use is an important consideration. The present study examined benzoylecgonine concentrations, the primary metabolite of cocaine, in urine samples collected three times per week for 30 weeks from 28 cocaine users who were exposed to a cocaine abstinence contingency. Of the positive urine samples (benzoylecgonine concentration >300 ng/ml), 29%, 21%, 14%, and 5% of the samples decreased in benzoylecgonine concentration by more than 20%, 40%, 60%, and 80% per day, respectively. As the size of the decrease increased, the likelihood of that sample occurring during a period leading to a cocaine-negative urine sample (benzoylecgonine concentration ≤300 ng/ml) also increased. The number of days required to produce a cocaine-negative sample following a positive sample ranged from 1 to 10 days and was significantly correlated with the starting benzoylecgonine level ( r = 0.43, p contingency management interventions.

Risky decisions in a lottery task are associated with an increase of cocaine use

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Amrei eWittwer

2016-05-01

Full Text Available Cocaine use disorder is associated with maladaptive decision-making behaviour, which strongly contributes to the harmful consequences of chronic drug use. Prior research has shown that cocaine users exhibit impaired neuropsychological test performances, particularly with regard to attention, learning, and memory but also in executive functions such as decision-making and impulse control. However, to what extent cocaine users show impaired decision-making under risk without feedback has not yet been investigated systematically. Therefore, to examine risk-taking behaviour, 31 chronic cocaine users and 26 stimulant-naïve healthy controls, who were part of the Zurich Cocaine Cognition Study, performed the Randomized Lottery Task (RALT with winning lotteries consisting of an uncertain and a certain prospect. Results revealed that risky decisions were associated with male sex, increased cocaine use in the past year, higher cocaine concentrations in the hair, and younger age. In addition, higher levels of cocaine in the hair and cumulative lifetime consumption were associated with risky decisions, whereas potentially confounding factors including cognition and psychiatric symptoms had no significant effect. Taken together, our results indicate that cocaine users who increased their consumption over a period of one year show deficits in the processing of risky information accompanied with increased risk-taking. Future research should analyse whether risky decisions could potentially serve as a prognostic marker for cocaine use disorder.

Psychosocial withdrawal characteristics of nicotine compared with alcohol and caffeine.

Science.gov (United States)

Miyata, Hisatsugu; Hironaka, Naoyuki; Takada, Kohji; Miyasato, Katsumasa; Nakamura, Koichi; Yanagita, Tomoji

2008-10-01

The purpose of the present study was to observe the psychosocial characteristics of withdrawal from cigarette smoking in comparison with those from caffeine (CAF) and alcoholic (ALC) beverage withdrawal. Twenty-seven healthy volunteers at a medial level of dependence on both cigarettes (nicotine, NCT) and either CAF or ALC, as judged by the DSM-IV-TR criteria for substance dependence, participated in this study. The participants were required to abstain from smoking and either CAF or ALC for 7 days, each one after another, with a 7-day interval. The order of abstinence was counterbalanced among the participants. Psychosocial parameters, including a desire for substances, social activity function, well-being, withdrawal symptoms, and vital signs, were assessed during the withdrawal periods. The study protocol was approved by the Jikei University Review Board. The results indicated that there were no differences in the maximum level of desire for a substance and the influence on social activity function between NCT and other substances during the withdrawal periods. As for withdrawal symptoms, NCT caused a more intensive degree of irritability than CAF or ALC, and a more intensive degree of difficulty concentrating and restlessness than did withdrawal from ALC. However, the subjective well-being questionnaire indicated no differences in these symptoms between NCT and other substances. The present results suggest that there are no significant differences in psychosocial manifestations regarding the difficulty in abstaining from NCT, CAF, and ALC.

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.

The effects of cocaine, alcohol and cocaine/alcohol combinations in conditioned taste aversion learning.

Science.gov (United States)

Busse, Gregory D; Verendeev, Andrey; Jones, Jermaine; Riley, Anthony L

2005-09-01

We have recently reported that alcohol attenuates cocaine place preferences. Although the basis for this effect is unknown, alcohol may attenuate cocaine reward by potentiating its aversive effects. To examine this possibility, these experiments assessed the effects of alcohol on cocaine-induced taste aversions under conditions similar to those that resulted in attenuated place preferences. Specifically, Experiments 1 and 2 assessed the effects of alcohol (0.5 g/kg) on taste aversions induced by 20, 30 and 40 mg/kg cocaine. Experiment 3 examined the role of intertrial interval in the effects of alcohol (0.5 g/kg) on cocaine (30 mg/kg) taste aversions. In Experiments 1 and 2, cocaine was effective at conditioning aversions. Alcohol produced no measurable effect. Combining cocaine and alcohol produced no greater aversion than cocaine alone (and, in fact, weakened aversions at the lowest dose of cocaine). In Experiment 3, varying the intertrial interval from 3 days (as in the case of Experiments 1 and 2) to 1 day (a procedure identical to that in which alcohol attenuated cocaine place preferences) resulted in significant alcohol- and cocaine-induced taste aversions. Nonetheless, alcohol remained ineffective in potentiating cocaine aversions. Thus, under these conditions alcohol does not potentiate cocaine's aversiveness. These results were discussed in terms of their implication for the effects of alcohol on cocaine-induced place preferences. Further, the effects of alcohol on place preferences conditioned by cocaine were discussed in relation to other assessments of the effects of alcohol on the affective properties of cocaine and the implications of these interactions for alcohol and cocaine co-use.

Anticonvulsants for alcohol withdrawal.

Science.gov (United States)

Minozzi, Silvia; Amato, Laura; Vecchi, Simona; Davoli, Marina

2010-03-17

Alcohol abuse and dependence represents a most serious health problem worldwide with major social, interpersonal and legal interpolations. Besides benzodiazepines, anticonvulsants are often used for the treatment of alcohol withdrawal symptoms. Anticonvulsants drugs are indicated for the treatment of alcohol withdrawal syndrome, alone or in combination with benzodiazepine treatments. In spite of the wide use, the exact role of the anticonvulsants for the treatment of alcohol withdrawal has not yet bee adequately assessed. To evaluate the effectiveness and safety of anticonvulsants in the treatment of alcohol withdrawal. We searched Cochrane Drugs and Alcohol Group' Register of Trials (December 2009), PubMed, EMBASE, CINAHL (1966 to December 2009), EconLIT (1969 to December 2009). Parallel searches on web sites of health technology assessment and related agencies, and their databases. Randomized controlled trials (RCTs) examining the effectiveness, safety and overall risk-benefit of anticonvulsants in comparison with a placebo or other pharmacological treatment. All patients were included regardless of age, gender, nationality, and outpatient or inpatient therapy. Two authors independently screened and extracted data from studies. Fifty-six studies, with a total of 4076 participants, met the inclusion criteria. Comparing anticonvulsants with placebo, no statistically significant differences for the six outcomes considered.Comparing anticonvulsant versus other drug, 19 outcomes considered, results favour anticonvulsants only in the comparison carbamazepine versus benzodiazepine (oxazepam and lorazepam) for alcohol withdrawal symptoms (CIWA-Ar score): 3 studies, 262 participants, MD -1.04 (-1.89 to -0.20), none of the other comparisons reached statistical significance.Comparing different anticonvulsants no statistically significant differences in the two outcomes considered.Comparing anticonvulsants plus other drugs versus other drugs (3 outcomes considered), results

Cocaine (Coke, Crack) Facts

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... That People Abuse » Cocaine (Coke, Crack) Facts Cocaine (Coke, Crack) Facts Listen Cocaine is a white ... 69 KB) "My life was built around getting cocaine and getting high." ©istock.com/ Marjot Stacey is ...

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

OpenAIRE

Carey, Robert J.; 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...

The pathogenesis of propranolol-withdrawal syndrome in essential hypertension.

Science.gov (United States)

Kristensen, B O; Steiness, E; Weeke, J

1979-12-01

1. In hypertension, the beta-adrenoreceptor-blocker-withdrawal syndrome comprises tachycardia, sweating, tremor and general malaise, symptoms resembling thyrotoxicosis. 2. The effect of abrupt cessation of propranolol on serum concentrations of thyroxine (T4) and triiodothyronine (T3) was therefore investigated in five patients with uncomplicated essential hypertension, treated with propranolol in doses from 160 to 480 mg/day. 3. Four of the five patients developed one or more of the above-mentioned symptoms within 2-6 days after withdrawal of propranolol. 4. A mean relative increase in serum free T3 of 51% (range 22-74%) was found in these four patients on the day of onset of symptoms. 5. The increase in free T3 in the five patients correlated positively with total serum propranolol on the last day the drug was given (r = 0.91, 2P = 0.03). 6. As an increase in T3 was found only in patients suffering the withdrawal syndrome, and was maximal the day the symptoms appeared, despite a variation in time of onset from 2 to 6 days, it is suggested that the beta-adrenoreceptor-blocker-withdrawal syndrome, at least partially, is caused by rebound increased production of T3, induced by the well-known inhibition of the monodeiodination of T4 to T3 during beta-adrenoreceptor blockade. 7. This assumption may explain the clinical symptoms and the reported transient increased beta-adrenoreceptor sensitivity with unchanged serum concentrations of catecholamines.

Ketogenic Diet Suppresses Alcohol Withdrawal Syndrome in Rats.

Science.gov (United States)

Dencker, Ditte; Molander, Anna; Thomsen, Morgane; Schlumberger, Chantal; Wortwein, Gitta; Weikop, Pia; Benveniste, Helene; Volkow, Nora D; Fink-Jensen, Anders

2018-02-01

Alcohol use disorder is underdiagnosed and undertreated, and up to 50% of alcohol-abstinent patients diagnosed with alcohol dependence relapse within the first year of treatment. Current treatments for the maintenance of alcohol abstinence in patients with alcohol use disorder have limited efficacy, and there is an urgent need for novel treatment strategies. Decreased cerebral glucose metabolism and increased brain uptake of acetate were recently reported in heavy drinkers, relative to controls. Given the switch of metabolic fuel from glucose to acetate in the alcohol-dependent brain, we investigated the potential therapeutic benefit of a ketogenic diet in managing alcohol withdrawal symptoms during detoxification. Male Sprague Dawley rats fed either ketogenic or regular diet were administered ethanol or water orally, twice daily for 6 days while the diet conditions were maintained. Abstinence symptoms were rated 6, 24, 48, and 72 hours after the last alcohol administration. Maintenance on a ketogenic diet caused a significant decrease in the alcohol withdrawal symptoms' "rigidity" and "irritability." Our preclinical pilot study suggests that a ketogenic diet may be a novel approach for treating alcohol withdrawal symptoms in humans. Copyright © 2017 by the Research Society on Alcoholism.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

Science.gov (United States)

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

2010-01-01

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. PMID:20395264

Ethical issues in using a cocaine vaccine to treat and prevent cocaine abuse and dependence.

Science.gov (United States)

Hall, W; Carter, L

2004-08-01

A "cocaine vaccine" is a promising immunotherapeutic approach to treating cocaine dependence which induces the immune system to form antibodies that prevent cocaine from crossing the blood brain barrier to act on receptor sites in the brain. Studies in rats show that cocaine antibodies block cocaine from reaching the brain and prevent the reinstatement of cocaine self administration. A successful phase 1 trial of a human cocaine vaccine has been reported. The most promising application of a cocaine vaccine is to prevent relapse to dependence in abstinent users who voluntarily enter treatment. Any use of a vaccine to treat cocaine addicts under legal coercion raises major ethical issues. If this is done at all, it should be carefully trialled first, and only after considerable clinical experience has been obtained in using the vaccine to treat voluntary patients. There will need to be an informed community debate about what role, if any, a cocaine vaccine may have as a way of preventing cocaine addiction in children and adolescents.

[Treatment of gamma-hydroxybutyrate withdrawal].

Science.gov (United States)

Strand, Niels August Willer; Petersen, Tonny Studsgaard; Nielsen, Lars Martin; Boegevig, Soren

2017-12-11

Gamma-hydroxybutyrate (GHB) is a drug of abuse, for which physical addiction develops quickly. GHB withdrawal can develop into a life-threatening condition and has previously been treated mainly with benzodiazepines. These have not always proven effective, leading to long hospitalizations in intensive care units. Based on successful Dutch treatment results for using GHB to treat GHB withdrawal symptoms, we propose to implement a similar method in Denmark. The method requires an interdisciplinary effort for which The Danish Poison Information Centre should be consulted for expertise.

Hippocampal cell fate regulation by chronic cocaine during periods of adolescent vulnerability: Consequences of cocaine exposure during adolescence on behavioral despair in adulthood.

Science.gov (United States)

García-Cabrerizo, R; Keller, B; García-Fuster, M J

2015-09-24

Given that adolescence represents a critical moment for shaping adult behavior and may predispose to disease vulnerability later in life, the aim of this study was to find a vulnerable period during adolescence in which hippocampal cell fate regulation was altered by cocaine exposure, and to evaluate the long-term consequences of a cocaine experience during adolescence in affecting hippocampal plasticity and behavioral despair in adulthood. Study I: Male rats were treated with cocaine (15mg/kg, i.p.) or saline for 7 consecutive days during adolescence (early post-natal day (PND) 33-39, mid PND 40-46, late PND 47-53). Hippocampal plasticity (i.e., cell fate regulation, cell genesis) was evaluated 24h after the last treatment dose during the course of adolescence (PND 40, PND 47, PND 54). Study II: The consequences of cocaine exposure during adolescence (PND 33-39 or PND 33-46; 7 or 14days) were measured in adulthood at the behavioral (i.e., forced swim test, PND 62-63) and molecular (hippocampal cell markers, PND 64) levels. Chronic cocaine during early adolescence dysregulated FADD forms only in the hippocampus (HC), as compared to other brain regions, and during mid adolescence, impaired cell proliferation (Ki-67) and increased PARP-1 cleavage (a cell death maker) in the HC. Interestingly, chronic cocaine exposure during adolescence did not alter the time adult rats spent immobile in the forced swim test. These results suggest that this paradigm of chronic cocaine administration during adolescence did not contribute to the later manifestation of behavioral despair (i.e., one pro-depressive symptom) as measured by the forced swim test in adulthood. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Demand/withdraw communication in the context of intimate partner violence: Implications for psychological outcomes.

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Pickover, Alison M; Lipinski, Alexandra J; Dodson, Thomas S; Tran, Han N; Woodward, Matthew J; Beck, J Gayle

2017-12-01

Intimate partner violence (IPV) is associated with symptoms of posttraumatic stress disorder (PTSD) and generalized anxiety disorder (GAD). To clarify the influence of a dyadic conflict pattern that has previously been shown to accompany violence in romantic relationships (partner demand/self withdraw) on these mental health outcomes, we examined the associations between three forms of IPV (physical, emotional-verbal, dominance-isolation), partner demand/self withdraw, and PTSD and GAD symptoms, in a sample of 284 IPV-exposed women. Using structural equation modeling, we found significant associations between dominance-isolation IPV, partner demand/self withdraw, and clinician-assessed GAD symptoms. Associations between emotional-verbal IPV and partner demand/self withdraw were also significant. Associations for physical IPV, partner demand/self withdraw, and clinician-assessed PTSD symptoms were not statistically significant. These results underscore the need for research on the mental health outcomes associated with specific forms of IPV and the long-term psychological consequences of the conflict patterns that uniquely characterize violent relationships. Copyright © 2017. Published by Elsevier Ltd.

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

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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

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

International Nuclear Information System (INIS)

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.

2010-01-01

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 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-induced limbic

Neuroticism and Conscientiousness as Moderators of the Relation Between Social Withdrawal and Internalizing Problems in Adolescence.

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Smith, Kelly A; Barstead, Matthew G; Rubin, Kenneth H

2017-04-01

Social withdrawal, or refraining from social interaction in the presence of peers, places adolescents at risk of developing emotional problems like anxiety and depression. The personality traits of neuroticism and conscientiousness also relate to emotional difficulties. For example, high conscientiousness predicts lower incidence of anxiety disorders and depression, while high neuroticism relates to greater likelihood of these problems. Based on these associations, socially withdrawn adolescents high in conscientiousness or low in neuroticism were expected to have lower levels of anxiety and depressive symptoms. Participants included 103 adolescents (59 % female) who reported on their personality traits in 8th grade and their anxiety and depressive symptoms in 9th grade. Peer ratings of social withdrawal were collected within schools in 8th grade. A structural equation model revealed that 8th grade withdrawal positively predicted 9th grade anxiety and depressive symptoms controlling for 8th grade anxiety and depressive symptoms, but neuroticism did not. Conscientiousness moderated the relation of withdrawal with depressive symptoms but not anxiety, such that high levels of conscientiousness attenuated the association between withdrawal and depressive symptoms. This buffering effect may stem from the conceptual relation between conscientiousness and self-regulation. Conscientiousness did not, however, moderate the association between withdrawal and anxiety, which may be partly due to the role anxiety plays in driving withdrawal. Thus, a conscientious, well-regulated personality partially protects withdrawn adolescents from the increased risk of emotional difficulties.

Effects of an alkaloid-rich extract from Mitragyna speciosa leaves and fluoxetine on sleep profiles, EEG spectral frequency and ethanol withdrawal symptoms in rats.

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Cheaha, Dania; Keawpradub, Niwat; Sawangjaroen, Kitja; Phukpattaranont, Pimpimol; Kumarnsit, Ekkasit

2015-10-15

Many antidepressants are effective in alleviating ethanol withdrawal symptoms. However, most of them suppress rapid eye movement (REM) sleep. Thus, development of antidepressants without undesirable side effects would be preferable. Previously, crude alkaloid extract from Mitragyna speciosa (MS) Korth was found to produce antidepressant activities. It was hypothesized that the alkaloid extract from MS may attenuate ethanol withdrawal without REM sleep disturbance. Adult male Wistar rats implanted with electrodes over the frontal and parietal cortices were used for two separated studies. For an acute study, 10 mg/kg fluoxetine or 60 mg/kg alkaloid extract from MS were administered intragastrically. Electroencephalographic (EEG) signals were recorded for 3 h to examine sleep profiles and EEG fingerprints. Another set of animal was used for an ethanol withdrawal study. They were rendered dependent on ethanol via a modified liquid diet (MLD) containing ethanol ad libitum for 28 days. On day 29, fluoxetine (10 mg/kg) or alkaloid extract from MS (60 mg/kg) were administered 15 min before the ethanol-containing MLD was replaced with an isocaloric ethanol-free MLD to induced ethanol withdrawal symptoms. The sleep analysis revealed that alkaloid extract from MS did not change any REM parameters which included average duration of each REM episode, total REM time, number of REM episode and REM latency whereas fluoxetine significantly suppressed all REM parameters and delayed REM latency. However, power spectral analysis revealed similar fingerprints for fluoxetine and alkaloid extract from MS characterized by decreasing powers in the slow frequency range in frontal and parietal cortical EEG. Neither treatment affected spontaneous motor activity. Finally, both alkaloid extract from MS and fluoxetine were found to significantly attenuate ethanol withdrawal-induced hyperexcitability (increases gamma activity) in both cortices and to reduce locomotor activity. The present study

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

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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

Long-lasting memory deficits in mice withdrawn from cocaine are concomitant with neuroadaptations in hippocampal basal activity, GABAergic interneurons and adult neurogenesis

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David Ladrón de Guevara-Miranda

2017-03-01

Full Text Available Cocaine addiction disorder is notably aggravated by concomitant cognitive and emotional pathology that impedes recovery. We studied whether a persistent cognitive/emotional dysregulation in mice withdrawn from cocaine holds a neurobiological correlate within the hippocampus, a limbic region with a key role in anxiety and memory but that has been scarcely investigated in cocaine addiction research. Mice were submitted to a chronic cocaine (20 mg/kg/day for 12 days or vehicle treatment followed by 44 drug-free days. Some mice were then assessed on a battery of emotional (elevated plus-maze, light/dark box, open field, forced swimming and cognitive (object and place recognition memory, cocaine-induced conditioned place preference, continuous spontaneous alternation behavioral tests, while other mice remained in their home cage. Relevant hippocampal features [basal c-Fos activity, GABA+, parvalbumin (PV+ and neuropeptide Y (NPY+ interneurons and adult neurogenesis (cell proliferation and immature neurons] were immunohistochemically assessed 73 days after the chronic cocaine or vehicle protocol. The cocaine-withdrawn mice showed no remarkable exploratory or emotional alterations but were consistently impaired in all the cognitive tasks. All the cocaine-withdrawn groups, independent of whether they were submitted to behavioral assessment or not, showed enhanced basal c-Fos expression and an increased number of GABA+ cells in the dentate gyrus. Moreover, the cocaine-withdrawn mice previously submitted to behavioral training displayed a blunted experience-dependent regulation of PV+ and NPY+ neurons in the dentate gyrus, and neurogenesis in the hippocampus. Results highlight the importance of hippocampal neuroplasticity for the ingrained cognitive deficits present during chronic cocaine withdrawal.

Demand-Withdraw Patterns in Marital Conflict in the Home

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Papp, Lauren M.; Kouros, Chrystyna D.; Cummings, E. Mark

2009-01-01

The present study extended laboratory-based findings of demand-withdraw communication into marital conflict in the home and further explored its linkages with spousal depression. U.S. couples (N = 116) provided diary reports of marital conflict and rated depressive symptoms. Hierarchical linear modeling results indicated that husband demand-wife withdraw and wife demand-husband withdraw occurred in the home at equal frequency, and both were more likely to occur when discussing topics that con...

The Combination Very Low-Dose Naltrexone–Clonidine in the Management of Opioid Withdrawal

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Mannelli, Paolo; Peindl, Kathleen; Wu, Li-Tzy; Patkar, Ashwin A.; Gorelick, David A.

2013-01-01

Background The management of withdrawal absorbs substantial clinical efforts in opioid dependence (OD). The real challenge lies in improving current pharmacotherapies. Although widely used, clonidine causes problematic adverse effects and does not alleviate important symptoms of opioid withdrawal, alone or in combination with the opioid antagonist naltrexone. Very low-dose naltrexone (VLNTX) has been shown to attenuate withdrawal intensity and noradrenaline release following opioid agonist taper, suggesting a combination with clonidine may result in improved safety and efficacy. Objectives We investigated the effects of a VLNTX–clonidine combination in a secondary analysis of data from a double-blind, randomized opioid detoxification trial. Methods Withdrawal symptoms and treatment completion were compared following VLNTX (.125 or .25 mg/day) and clonidine (.1–.2 mg q6h) in 127 individuals with OD undergoing 6-day methadone inpatient taper at a community program. Results VLNTX was more effective than placebo or clonidine in reducing symptoms and signs of withdrawal. The use of VLNTX in combination with clonidine was associated with attenuated subjective withdrawal compared with each medication alone, favoring detoxification completion in comparison with clonidine or naltrexone placebo. VLNTX/clonidine was effective in reducing symptoms that are both undertreated and well controlled with clonidine treatment and was not associated with significant adverse events compared with other treatments. Conclusions and Scientific Significance Preliminary results elucidate neurobiological mechanisms of OD and support the utility of controlled studies on a novel VLNTX + low-dose clonidine combination for the management of opioid withdrawal. PMID:22233189

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

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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.

The effects of N-acetylcysteine on cocaine reward and seeking behaviors in a rat model of depression.

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Frankowska, Małgorzata; Jastrzębska, Joanna; Nowak, Ewa; Białko, Magdalena; Przegaliński, Edmund; Filip, Małgorzata

2014-06-01

Depression and substance-abuse (e.g., cocaine) disorders are common concurrent diagnoses. In the present study, we combined bilateral olfactory bulbectomy (OBX) with a variety of procedures of intravenous cocaine self-administration and extinction/reinstatement in rats. We also investigated the effects of N-acetylcysteine (NAC) on rewarding and seeking behaviors for cocaine in OBX rats and compared the drug's effects in sham-operated control animals (SHAM). The occurrence of depressive symptoms before introduction to cocaine self-administration enhanced subsequent cocaine-seeking behaviors but did not significantly influence cocaine's rewarding properties or extinction training. NAC (25-100mg/kg) given acutely or repeatedly did not alter the co-occurrence of cocaine reward and depression but effectively reduced the cocaine-seeking behavior observed in both phenotypes. Our results indicate that depression behavior is linked to more pronounced drug craving and a higher propensity to relapse in rats. We also show the lack of efficacy of repeated NAC treatment on SHAM or OBX animals in terms of cocaine self-administration, while the drug was an effective blocker of cocaine-seeking behavior in both studied phenotypes, with a more pronounced drug effect observed in OBX animals. The last finding demonstrates the potential clinical utility of NAC to reduce cocaine seeking enhanced by co-existing depression. Copyright © 2014 Elsevier B.V. All rights reserved.

Delirium and High Creatine Kinase and Myoglobin Levels Related to Synthetic Cannabinoid Withdrawal

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Ahmet Bulent Yazici

2017-01-01

Full Text Available Synthetic cannabinoids (SCs are included in a group of drugs called new psychoactive substances. Effects of SCs on the central nervous system are similar to other cannabinoids, but 2–100 times more potent than marijuana. Thus, addiction and withdrawal symptoms are more severe than natural cannabinoids. Withdrawal symptoms of SCs were reported in the literature previously. But there is no report about SC withdrawal delirium and its treatment. Several studies reported that agonists of CB1 receptors play a role in GABA and glutamatergic neurotransmission, which is similar to the effects of alcohol on GABA and glutamatergic receptors. Previous studies on alcohol delirium cases suggested that elevated creatine kinase (CK can be a marker of progress. This study reports delirium and high serum CK levels related to SC withdrawal and offers a treatment with benzodiazepine for them. We described two cases treated in our inpatient clinic about SC withdrawal with increase of serum CK level and other laboratory parameters. One of them demonstrated delirium symptoms and the other did not with early rapid treatment.

Cannabis Withdrawal in Adults With Attention-Deficit/Hyperactivity Disorder.

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Chauchard, Emeline; Hartwell, Karen J; McRae-Clark, Aimee L; Sherman, Brian J; Gorelick, David A

2018-02-22

Cannabis withdrawal has not been studied in adults with attention-deficit/hyperactivity disorder (ADHD) who have high rates of cannabis use. We aimed to describe cannabis withdrawal, motivations to quit, and strategies to quit cannabis use in cannabis-dependent adults with ADHD. Twenty-three adults with ADHD enrolled in a controlled clinical trial of pharmacotherapy (atomoxetine) for cannabis dependence (DSM-IV criteria) completed the Marijuana Quit Questionnaire (MJQQ) to provide information on their "most serious" quit attempt made without formal treatment. The study was conducted between November 2005 and June 2008. Participants were predominantly male (82.6%, n = 19), with a mean (SD) age of 27.4 (8.5) years (range, 18-53) at the start of their index quit attempt. The most common motive for quitting cannabis was "to save money" (87%, n = 20); the most common strategy to maintain abstinence was "stopped associating with people who smoke marijuana" (43%, n = 10). Almost all (96%, n = 22) subjects reported ≥ 1 cannabis withdrawal symptom; 7 (30%) met DSM-5 diagnostic criteria for cannabis withdrawal syndrome. Participants with comorbid ADHD and cannabis dependence reported withdrawal symptoms similar to other samples of non-treatment-seeking cannabis-dependent adults with no psychiatric comorbidity. These findings suggest that ADHD does not influence cannabis withdrawal in the way that it does tobacco (nicotine) withdrawal. Data used in this secondary analysis came from ClinicalTrials.gov identifier: NCT00360269. © Copyright 2018 Physicians Postgraduate Press, Inc.

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

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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.

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

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

2016-01-01

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 oxyt...

Dopamine agonist withdrawal syndrome: implications for patient care.

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Nirenberg, Melissa J

2013-08-01

Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper.

The effects of the novel DA D3 receptor antagonist SR 21502 on cocaine reward, cocaine seeking and cocaine-induced locomotor activity in rats.

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Galaj, E; Ananthan, S; Saliba, M; Ranaldi, Robert

2014-02-01

There is a focus on developing D3 receptor antagonists as cocaine addiction treatments. We investigated the effects of a novel selective D3 receptor antagonist, SR 21502, on cocaine reward, cocaine-seeking, food reward, spontaneous locomotor activity and cocaine-induced locomotor activity in rats. In Experiment 1, rats were trained to self-administer cocaine under a progressive ratio (PR) schedule of reinforcement and tested with vehicle or one of three doses of SR 21502. In Experiment 2, animals were trained to self-administer cocaine under a fixed ratio schedule of reinforcement followed by extinction of the response. Then, animals were tested with vehicle or one of the SR 21502 doses on cue-induced reinstatement of responding. In Experiment 3, animals were trained to lever press for food under a PR schedule and tested with vehicle or one dose of the compound. In Experiments 4 and 5, in separate groups of animals, the vehicle and three doses of SR 21502 were tested on spontaneous or cocaine (10 mg/kg, IP)-induced locomotor activity, respectively. SR 21502 produced significant, dose-related (3.75, 7.5 and 15 mg/kg) reductions in breakpoint for cocaine self-administration, cue-induced reinstatement (3.75, 7.5 and 15 mg/kg) and cocaine-induced locomotor activity (3.75, 7.5 and 15 mg/kg) but failed to reduce food self-administration and spontaneous locomotor activity. SR 21502 decreases cocaine reward, cocaine-seeking and locomotor activity at doses that have no effect on food reward or spontaneous locomotor activity. These data suggest SR 21502 may selectively inhibit cocaine's rewarding, incentive motivational and stimulant effects.

Clinical management of alcohol withdrawal: A systematic review

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Shivanand Kattimani

2013-01-01

Full Text Available Alcohol withdrawal is commonly encountered in general hospital settings. It forms a major part of referrals received by a consultation-liaison psychiatrist. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on pharmacological management of alcohol withdrawal in humans with no limit on the date of publication. Articles not relevant to clinical management were excluded based on the titles and abstract available. Full-text articles were obtained from this list and the cross-references. There were four meta-analyses, 9 systematic reviews, 26 review articles and other type of publications like textbooks. Alcohol withdrawal syndrome is a clinical diagnosis. It may vary in severity. Complicated alcohol withdrawal presents with hallucinations, seizures or delirium tremens. Benzodiazepines have the best evidence base in the treatment of alcohol withdrawal, followed by anticonvulsants. Clinical institutes withdrawal assessment-alcohol revised is useful with pitfalls in patients with medical comorbidities. Evidence favors an approach of symptom-monitored loading for severe withdrawals where an initial dose is guided by risk factors for complicated withdrawals and further dosing may be guided by withdrawal severity. Supportive care and use of vitamins is also discussed.

N-Acetylcysteine reduces cocaine-cue attentional bias and differentially alters cocaine self-administration based on dosing order.

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Levi Bolin, B; Alcorn, Joseph L; Lile, Joshua A; Rush, Craig R; Rayapati, Abner O; Hays, Lon R; Stoops, William W

2017-09-01

Disrupted glutamate homeostasis is thought to contribute to cocaine-use disorder, in particular, by enhancing the incentive salience of cocaine stimuli. n-Acetylcysteine might be useful in cocaine-use disorder by normalizing glutamate function. In prior studies, n-acetylcysteine blocked the reinstatement of cocaine seeking in laboratory animals and reduced the salience of cocaine stimuli and delayed relapse in humans. The present study determined the ability of maintenance on n-acetylcysteine (0 or 2400mg/day, counterbalanced) to reduce the incentive salience of cocaine stimuli, as measured by an attentional bias task, and attenuate intranasal cocaine self-administration (0, 30, and 60mg). Fourteen individuals (N=14) who met criteria for cocaine abuse or dependence completed this within-subjects, double-blind, crossover-design study. Cocaine-cue attentional bias was greatest following administration of 0mg cocaine during placebo maintenance, and was attenuated by n-acetylcysteine. Cocaine maintained responding during placebo and n-acetylcysteine maintenance, but the reinforcing effects of cocaine were significantly attenuated across both maintenance conditions in participants maintained on n-acetylcysteine first compared to participants maintained on placebo first. These results collectively suggest that a reduction in the incentive salience of cocaine-related stimuli during n-acetylcysteine maintenance may be accompanied by reductions in cocaine self-administration. These results are in agreement with, and link, prior preclinical and clinical trial results suggesting that n-acetylcysteine might be useful for preventing cocaine relapse by attenuating the incentive salience of cocaine cues. Copyright © 2017 Elsevier B.V. All rights reserved.

Vascular disease in cocaine addiction.

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Bachi, Keren; Mani, Venkatesh; Jeyachandran, Devi; Fayad, Zahi A; Goldstein, Rita Z; Alia-Klein, Nelly

2017-07-01

Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by vascular pathology. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use disorder of that period, now aging. Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best. We review major postmortem and in vitro studies documenting cocaine-induced vascular toxicity. PubMed and Academic Search Complete were used with relevant terms. Findings consist of the major mechanisms of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine. The etiology underlying cocaine's acute and chronic vascular effects is multifactorial, spanning hypertension, impaired homeostasis and platelet function, thrombosis, thromboembolism, and alterations in blood flow. Early detection of vascular disease in cocaine addiction by multimodality imaging is discussed. Treatment may be similar to indications in patients with traditional risk-factors, with few exceptions such as enhanced supportive care and use of benzodiazepines and phentolamine for sedation, and avoiding β-blockers. Given the vascular toxicity cocaine induces, further compounded by smoking and alcohol comorbidity, and interacting with aging of the crack generation, there is a public health imperative to identify pre-symptomatic markers of vascular impairments in cocaine addiction and employ preventive treatment to reduce silent disease progression. Copyright © 2017 Elsevier B.V. All rights reserved.

[Cocaine - Characteristics and addiction].

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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.

Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats.

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Eagle, Andrew L; Singh, Robby; Kohler, Robert J; Friedman, Amy L; Liebowitz, Chelsea P; Galloway, Matthew P; Enman, Nicole M; Jutkiewicz, Emily M; Perrine, Shane A

2015-05-01

Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague-Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0, 10 or 20 mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, as expected. However, compared to control rats on Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. Copyright © 2015. Published by Elsevier B.V.

Demand-Withdraw Patterns in Marital Conflict in the Home.

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Papp, Lauren M; Kouros, Chrystyna D; Cummings, E Mark

2009-06-01

The present study extended laboratory-based findings of demand-withdraw communication into marital conflict in the home and further explored its linkages with spousal depression. U.S. couples (N = 116) provided diary reports of marital conflict and rated depressive symptoms. Hierarchical linear modeling results indicated that husband demand-wife withdraw and wife demand-husband withdraw occurred in the home at equal frequency, and both were more likely to occur when discussing topics that concerned the marital relationship. For both patterns, conflict initiator was positively linked to the demander role. Accounting for marital satisfaction, both demand-withdraw patterns predicted negative emotions and tactics during marital interactions and lower levels of conflict resolution. Spousal depression was linked to increased likelihood of husband demand-wife withdraw.

Safety of atomoxetine in combination with intravenous cocaine in cocaine-experienced participants.

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Cantilena, Louis; Kahn, Roberta; Duncan, Connie C; Li, Shou-Hua; Anderson, Ann; Elkashef, Ahmed

2012-12-01

Atomoxetine has been considered as an agonist replacement therapy for cocaine. We investigated the safety of the interaction of atomoxetine with cocaine and also whether cognitive function was affected by atomoxetine during short-term administration. In a double-blind placebo-controlled inpatient study of 20 cocaine-dependent volunteers, participants received atomoxetine 80 mg daily followed by 100 mg daily for 5 days each. On the fourth and fifth day at each dose, cocaine (20 and 40 mg) was infused intravenously in sequential daily sessions. Preinfusion mean systolic pressures showed a small but statistically significant difference between placebo and both doses of atomoxetine. Preinfusion mean diastolic pressures were significant between placebo and atomoxetine 80 mg only. The diastolic pressure response to 40 mg cocaine was statistically significant only between the 80- and 100-mg atomoxetine doses. All electrocardiogram parameters were unchanged. Visual Analog Scale (VAS) scores for "bad effect" in the atomoxetine group were significantly higher at baseline, then declined, and for "likely to use" declined with atomoxetine treatment. On the Addiction Research Center Inventory, the atomoxetine group scored significantly lower on amphetamine, euphoria, and energy subscales (P affect cocaine pharmacokinetics. In tests of working memory, sustained attention, cognitive flexibility, and decision-making, atomoxetine improved performance on the visual n-back task. There were no differences in any pharmacokinetic parameters for cocaine with atomoxetine. Atomoxetine was tolerated safely by all participants. Certain cognitive improvements and a dampening effect on VAS scores after cocaine were observed, but should be weighed against small but significant differences in hemodynamic responses after atomoxetine.

Flumazenil in treatment benzodiazepine withdrawal syndrome: Case report

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Ramah Aleksandar J.

2015-01-01

Full Text Available Background: Today in the world and in Serbia is growing number of people who are addicted to benzodiazepine. A particular problem is the process of detoxification and treatment of benzodiazepine withdrawal syndrome due to a recurrence of symptoms of anxiety disorder, availability of benzodiazepines, falling motivation. Standard procedures have often proved unsuccessful and the last decade, and the search for new protocols, including the flumazenil, benzodiazepine receptor antagonist, is actualized. Case report: The patient aged 48 years was admitted to the specialist psychiatric clinic, for treatment of benzodiazepine addiction. Anxiety disorder was diagnosed since adolescence perennial addiction on benzodiazepines and the initial withdrawal syndrome. Former motivated topical treatments for detoxification were unsuccessful. The presence of dual diagnosis, persistence of both disorders in perennial cycle, treatment resistance and actual motivation contributed to the decision to opt rapid detoxification from benzodiazepines by flumazenil application protocol, for hospital treatment by adjuvant therapy with lamotrigine. After discharge from hospital in stable condition it was with no signs of withdrawal syndrome and a rebound of anxiety symptoms. Lamotrigine medication continued including CBT, held during the one-year abstinence monitoring, with sufficient social functionality. Discussion: The efficacy and safety of flumazenil in the treatment of benzodiazepine withdrawal syndrome was investigated in numerous clinical trials, and the mechanism of action is complex, from the benzodiazepine antagonist to inverse agonist in certain circumstances, as well as 'up-regulation' receptors, which together leads to a reduction in symptoms of abstinence syndrome and anxiety in the longer term after treatment, thereby acting favorably to the adherence and remission. Conclusions: Flumazenil protocol is an efficient method in the treatment of the benzodiazepine

Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol.

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Becker, Jérôme A J; Kieffer, Brigitte L; Le Merrer, Julie

2017-09-01

Unified theories of addiction are challenged by differing drug-seeking behaviors and neurobiological adaptations across drug classes, particularly for narcotics and psychostimulants. We previously showed that protracted abstinence to opiates leads to despair behavior and social withdrawal in mice, and we identified a transcriptional signature in the extended amygdala that was also present in animals abstinent from nicotine, Δ9-tetrahydrocannabinol (THC) and alcohol. Here we examined whether protracted abstinence to these four drugs would also share common behavioral features, and eventually differ from abstinence to the prototypic psychostimulant cocaine. We found similar reduced social recognition, increased motor stereotypies and increased anxiety with relevant c-fos response alterations in morphine, nicotine, THC and alcohol abstinent mice. Protracted abstinence to cocaine, however, led to strikingly distinct, mostly opposing adaptations at all levels, including behavioral responses, neuronal activation and gene expression. Together, these data further document the existence of common hallmarks for protracted abstinence to opiates, nicotine, THC and alcohol that develop within motivation/emotion brain circuits. In our model, however, these do not apply to cocaine, supporting the notion of unique mechanisms in psychostimulant abuse. © 2016 Society for the Study of Addiction.

[11]Cocaine: PET studies of cocaine pharmacokinetics, dopamine transporter availability and dopamine transporter occupancy

International Nuclear Information System (INIS)

Fowler, Joanna S.; Volkow, Nora D.; Wang, Gene-Jack; Gatley, S. John; Logan, Jean

2001-01-01

Cocaine was initially labeled with carbon-11 in order to track the distribution and pharmacokinetics of this powerful stimulant and drug of abuse in the human brain and body. It was soon discovered that [ 11 C]cocaine was not only useful for measuring cocaine pharmacokinetics and its relationship to behavior but that it is also a sensitive radiotracer for dopamine transporter (DAT) availability. Measures of DAT availability were facilitated by the development of a graphical analysis method (Logan Plot) for reversible systems which streamlined kinetic analysis. This expanded the applications of [ 11 C]cocaine to studies of DAT availability in the human brain and allowed the first comparative measures of the degree of DAT occupancy by cocaine and another stimulant drug methylphenidate. This article will summarize preclinical and clinical research with [ 11 C]cocaine

Tramadol versus methadone for the management of acute opioid withdrawal: an add-on study

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M Salehi

2006-07-01

Full Text Available BACKGROUND: Opioid agonists such as methadone have been used widely in controlling opioid withdrawal symptoms. Tramadol, a partial opioid agonist, also has been prescribed to manage acute and chronic pain. We sought to compare the efficacy of tramadol and methadone in reducing the severity of opioid withdrawal symptoms. METHODS: In a double blind clinical trial 70 opioid dependent patients who used daily opium equal to 15 mg methadone randomly were assigned in two groups. In one group, methadone was started at 15 mg/day while in the other group 450 mg/day tramadol was prescribed. Both drugs were tapered in a week and placebo was prescribed in the 2nd week. The severity of withdrawal symptoms were assessed five times by short opioid withdrawal scale (SOWS. Data were analyzed by Repeated Measures Analysis of Variance, Mann-Whitney U, and Wilcoxon tests. RESULTS: There were statistically significant differences between two groups in the severity of anxiety (P = 0.015, irritability (P = 0.044, palpitation (P = 0.018, agitation (P = 0.037, and dysphoria (P = 0.044 that all were more common in methadone group. Comparison of side effects revealed statistically significant differences in sweating (P = 0.003 and drowsiness (P = 0.019 between two groups that were more frequent in methadone group. DISCUSSION: Tramadol was more efficacious in controlling opioid withdrawal symptoms with lower side effects. KEYWORDS: Methadone, tramadol, opioid withdrawal.

[Alcohol withdrawal syndrome dynamics during treatment with nooclerin (deanoli aceglumas)].

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Agibalova, T V; Buzik, O Zh; Rychkova, O V; Smyshlyaev, A V; Rumbesht, V V

2018-01-01

To study the efficacy of nooclerin (deanoli aceglumas) in alcohol withdrawal syndrome assessed by clinical and biochemical characteristics. A multicenter, open, randomized, comparative study of nooclerin in the complex treatment of alcohol withdrawal syndrome included 90 patients. The patients were randomized into nooclerin group (n=55) and control group (n=35). Nooclerin reduced alcohol withdrawal symptoms more significantly throughout the whole study period. There were significant between-group differences on the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) and the Multidimensional Fatigue Inventory (МFI-20). However, patients exhibited no excessive activity. No adverse side-effects were observed.

The Differential Role of Symptoms of Anxiety and Social Withdrawal in Chinese Children's Dependency on Their Teachers during the Transition to Nursery Care

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Zhang, Xiao

2015-01-01

Research Findings: Based on a short-term longitudinal sample of Chinese children, the present study examined the role of symptoms of anxiety and social withdrawal in dependency on teachers during the transition to nursery care. Children's dependency on their teachers was assessed first at 3 months after nursery entry (Time 1) and then at the end…

Safety of Atomoxetine in Combination with Intravenous Cocaine in Cocaine- Experienced Participants

Science.gov (United States)

Cantilena, Louis; Kahn, Roberta; Duncan, Connie C.; Li, Shou-Hua; Anderson, Ann; Elkashef, Ahmed

2012-01-01

Objectives Atomoxetine has been considered as an agonist replacement therapy for cocaine. We investigated the safety of the interaction of atomoxetine with cocaine, and also whether cognitive function was affected by atomoxetine during short-term administration. Methods In a double-blind placebo-controlled inpatient study of 20 cocaine-dependent volunteers, participants received atomoxetine 80 mg daily followed by 100 mg daily for 5 days each. On the fourth and fifth day at each dose, cocaine (20 mg and 40 mg) was infused intravenously in sequential daily sessions. Results Pre-infusion mean systolic pressures showed a small but statistically significant difference between placebo and both doses of atomoxetine. Pre-infusion mean diastolic pressures were significant between placebo and atomoxetine 80 mg only. The diastolic pressure response to 40 mg cocaine was statistically significant only between the 80 mg and 100 mg atomoxetine doses. All ECG parameters were unchanged. VAS scores for “bad effect” in the atomoxetine group were significantly higher at baseline, then declined, and for “likely to use” declined with atomoxetine treatment. On the ARCI the atomoxetine group scored significantly lower on amphetamine, euphoria and energy subscales (pAtomoxetine did not affect cocaine pharmacokinetics. In tests of working memory, sustained attention, cognitive flexibility, and decision-making, atomoxetine improved performance on the visual n-back task. There were no differences in any pharmacokinetic parameters for cocaine with atomoxetine. Conclusions Atomoxetine was tolerated safely by all participants. Certain cognitive improvements and a dampening effect on VAS scores after cocaine were observed, but should be weighed against small but significant differences in hemodynamic responses after atomoxetine. PMID:22987022

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

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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

Alcohol Withdrawal Mimicking Organophosphate Poisoning

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Nezihat Rana Disel

2014-02-01

Full Text Available Organophosphates, which can cause occupational poisoning due to inappropriate personal protective measures, are widely used insecticides in agricultural regions of southern Turkey. Therefore, the classical clinical findings of this cholinergic poisoning are myosis, excessive secretions, bradicardia and fasciculations are easy to be recognized by local medical stuff. Diseases and conditions related to alcoholism such as mental and social impairments, coma, toxicity, withdrawal, and delirium are frequent causes of emergency visits of chronic alcoholic patients. Here we present a case diagnosed and treated as organophosphate poisoning although it was an alcohol withdrawal in the beginning and became delirium tremens, due to similar symptoms.

A double blind, within subject comparison of spontaneous opioid withdrawal from buprenorphine versus morphine.

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Tompkins, D Andrew; Smith, Michael T; Mintzer, Miriam Z; Campbell, Claudia M; Strain, Eric C

2014-02-01

Preliminary evidence suggests that there is minimal withdrawal after the cessation of chronically administered buprenorphine and that opioid withdrawal symptoms are delayed compared with those of other opioids. The present study compared the time course and magnitude of buprenorphine withdrawal with a prototypical μ-opioid agonist, morphine. Healthy, out-of-treatment opioid-dependent residential volunteers (N = 7) were stabilized on either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses for 9 days. They then underwent an 18-day period of spontaneous withdrawal, during which four double-blind i.m. placebo injections were administered daily. Stabilization and spontaneous withdrawal were assessed for the second opioid using the same time course. Opioid withdrawal measures were collected eight times daily. Morphine withdrawal symptoms were significantly (P withdrawal as measured by mean peak ratings of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), all subscales of the Profile of Mood States (POMS), sick and pain (0-100) Visual Analog Scales, systolic and diastolic blood pressure, heart rate, respiratory rate, and pupil dilation. Peak ratings on COWS and SOWS occurred on day 2 of morphine withdrawal and were significantly greater than on day 2 of buprenorphine withdrawal. Subjective reports of morphine withdrawal resolved on average by day 7. There was minimal evidence of buprenorphine withdrawal on any measure. In conclusion, spontaneous withdrawal from high-dose buprenorphine appears subjectively and objectively milder compared with that of morphine for at least 18 days after drug cessation.

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.

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.

Buprenorphine/naloxone as a promising therapeutic option for opioid abusing patients with chronic pain: reduction of pain, opioid withdrawal symptoms, and abuse liability of oral oxycodone.

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Roux, Perrine; Sullivan, Maria A; Cohen, Julien; Fugon, Lionel; Jones, Jermaine D; Vosburg, Suzanne K; Cooper, Ziva D; Manubay, Jeanne M; Mogali, Shanthi; Comer, Sandra D

2013-08-01

Few studies have examined abuse of prescription opioids among individuals with chronic pain under buprenorphine/naloxone (Bup/Nx) maintenance. The current 7-week inpatient study assessed oral oxycodone self-administration by patients with chronic pain who had a history of opioid abuse. Participants (n=25) were transitioned from their preadmission prescribed opioid to Bup/Nx. All of the participants were tested under each of the sublingual Bup/Nx maintenance doses (2/0.5, 8/2 or 16/4 mg) in random order. During each maintenance period, participants could self-administer oxycodone orally (0, 10, 20, 40 or 60 mg prescription opioids) or receive money during laboratory sessions. Drug choice (percentage) was the primary dependent variable. Subjective ratings of clinical pain and withdrawal symptoms also were measured. Mann-Whitney tests compared percentage of drug choice for each active oxycodone dose to placebo. Logistic regression analyses identified correlates of oxycodone preference, defined as 60% or greater choice of oxycodone compared to money. Pain was significantly reduced while participants were maintained on Bup/Nx compared to preadmission ratings. No differences in percentage drug choice were observed between the active oxycodone doses and placebo under each Bup/Nx maintenance dose. However, factors associated with oxycodone preference were lower Bup/Nx maintenance dose, more withdrawal symptoms and more pain. These data suggest that Bup/Nx was effective in reducing pain and supplemental oxycodone use. Importantly, adequate management of pain and withdrawal symptoms by Bup/Nx may reduce oxycodone preference in this population. Published by Elsevier B.V.

Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers

OpenAIRE

Volkow, Nora D.; Wang, Gene-Jack; Tomasi, Dardo; Telang, Frank; Fowler, Joanna S.; Pradhan, Kith; Jayne, Millard; Logan, Jean; Goldstein, Rita Z.; Alia-Klein, Nelly; Wong, Christopher

2010-01-01

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...

Cocaine dependent individuals discount future rewards more than future losses for both cocaine and monetary outcomes.

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Johnson, Matthew W; Bruner, Natalie R; Johnson, Patrick S

2015-01-01

Cocaine dependence and other forms of drug dependence are associated with steeper devaluation of future outcomes (delay discounting). Although studies in this domain have typically assessed choices between monetary gains (e.g., receive less money now versus receive more money after a delay), delay discounting is also applicable to decisions involving losses (e.g., small loss now versus larger delayed loss), with gains typically discounted more than losses (the "sign effect"). It is also known that drugs are discounted more than equivalently valued money. In the context of drug dependence, however, relatively little is known about the discounting of delayed monetary and drug losses and the presence of the sign effect. In this within-subject, laboratory study, delay discounting for gains and losses was assessed for cocaine and money outcomes in cocaine-dependent individuals (n=89). Both cocaine and monetary gains were discounted at significantly greater rates than cocaine and monetary losses, respectively (i.e., the sign effect). Cocaine gains were discounted significantly more than monetary gains, but cocaine and monetary losses were discounted similarly. Results suggest that cocaine is discounted by cocaine-dependent individuals in a systematic manner similar to other rewards. Because the sign effect was shown for both cocaine and money, delayed aversive outcomes may generally have greater impact than delayed rewards in shaping present behavior in this population. Copyright © 2014. Published by Elsevier Ltd.

Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine.

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Fitzgerald, Paul J

2013-10-13

A wide range of commonly abused drugs have effects on the noradrenergic neurotransmitter system, including alterations during acute intoxication and chronic use of these drugs. It is not established, however, that individual differences in noradrenergic signaling, which may be present prior to use of drugs, predispose certain persons to substance abuse. This paper puts forth the novel hypothesis that elevated noradrenergic signaling, which may be raised largely due to genetics but also due to environmental factors, is an etiological factor in the abuse of a wide range of substances, including alcohol, nicotine, marijuana, heroin, cocaine, and caffeine. Data are reviewed for each of these drugs comprising their interaction with norepinephrine during acute intoxication, long-term use, subsequent withdrawal, and stress-induced relapse. In general, the data suggest that these drugs acutely boost noradrenergic signaling, whereas long-term use also affects this neurotransmitter system, possibly suppressing it. During acute withdrawal after chronic drug use, noradrenergic signaling tends to be elevated, consistent with the observation that norepinephrine lowering drugs such as clonidine reduce withdrawal symptoms. Since psychological stress can promote relapse of drug seeking in susceptible individuals and stress produces elevated norepinephrine release, this suggests that these drugs may be suppressing noradrenergic signaling during chronic use or instead elevating it only in reward circuits of the brain. If elevated noradrenergic signaling is an etiological factor in the abuse of a broad range of substances, then chronic use of pharmacological agents that reduce noradrenergic signaling, such as clonidine, guanfacine, lofexidine, propranolol, or prazosin, may help prevent or treat drug abuse in general.

Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine

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Paul J. Fitzgerald

2013-01-01

Full Text Available A wide range of commonly abused drugs have effects on the noradrenergic neurotransmitter system, including alterations during acute intoxication and chronic use of these drugs. It is not established, however, that individual differences in noradrenergic signaling, which may be present prior to use of drugs, predispose certain persons to substance abuse. This paper puts forth the novel hypothesis that elevated noradrenergic signaling, which may be raised largely due to genetics but also due to environmental factors, is an etiological factor in the abuse of a wide range of substances, including alcohol, nicotine, marijuana, heroin, cocaine, and caffeine. Data are reviewed for each of these drugs comprising their interaction with norepinephrine during acute intoxication, long-term use, subsequent withdrawal, and stress-induced relapse. In general, the data suggest that these drugs acutely boost noradrenergic signaling, whereas long-term use also affects this neurotransmitter system, possibly suppressing it. During acute withdrawal after chronic drug use, noradrenergic signaling tends to be elevated, consistent with the observation that norepinephrine lowering drugs such as clonidine reduce withdrawal symptoms. Since psychological stress can promote relapse of drug seeking in susceptible individuals and stress produces elevated norepinephrine release, this suggests that these drugs may be suppressing noradrenergic signaling during chronic use or instead elevating it only in reward circuits of the brain. If elevated noradrenergic signaling is an etiological factor in the abuse of a broad range of substances, then chronic use of pharmacological agents that reduce noradrenergic signaling, such as clonidine, guanfacine, lofexidine, propranolol, or prazosin, may help prevent or treat drug abuse in general.

Neural mechanisms underlying morphine withdrawal in addicted patients: a review

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Nima Babhadiashar

2015-06-01

Full Text Available Morphine is one of the most potent alkaloid in opium, which has substantial medical uses and needs and it is the first active principle purified from herbal source. Morphine has commonly been used for relief of moderate to severe pain as it acts directly on the central nervous system; nonetheless, its chronic abuse increases tolerance and physical dependence, which is commonly known as opiate addiction. Morphine withdrawal syndrome is physiological and behavioral symptoms that stem from prolonged exposure to morphine. A majority of brain regions are hypofunctional over prolonged abstinence and acute morphine withdrawal. Furthermore, several neural mechanisms are likely to contribute to morphine withdrawal. The present review summarizes the literature pertaining to neural mechanisms underlying morphine withdrawal. Despite the fact that morphine withdrawal is a complex process, it is suggested that neural mechanisms play key roles in morphine withdrawal.

Cocaine and crack cocaine abuse by pregnant or lactating mothers and analysis of its biomarkers in meconium and breast milk by LC-MS-A review.

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D'Avila, Felipe Bianchini; Limberger, Renata Pereira; Fröehlich, Pedro Eduardo

2016-09-01

Abusive use of drugs is a public health problem worldwide. The use of these substances by pregnant or lactating women can have many serious side effects in newborns. Among the commonest causes of addiction in drug users is cocaine in powdered form, inhaled, intravenously injected or smoked form (crack). Fast screening and a confirmation test using high specificity and sensitivity instruments such as LC-MS or GC/MS, can provide data to qualify and quantify chemical substances present in biological samples such as breast milk or meconium. Cocaine and/or crack can be detected through biomarkers or the unchanged molecule, enabling the form of cocaine use to be distinguished through the analytes. These methods must be carefully developed and validated according to internationally recognized guidelines. Thus, the study of biological matrices in which it can be detected through the development of simple and quick analytical methods can help prevent intoxication and diagnose the symptoms of dependency such as seizures, especially in babies, providing appropriate medical care. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Cue-induced craving in patients with cocaine use disorder predicts cognitive control deficits toward cocaine cues.

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DiGirolamo, Gregory J; Smelson, David; Guevremont, Nathan

2015-08-01

Cue-induced craving is a clinically important aspect of cocaine addiction influencing ongoing use and sobriety. However, little is known about the relationship between cue-induced craving and cognitive control toward cocaine cues. While studies suggest that cocaine users have an attentional bias toward cocaine cues, the present study extends this research by testing if cocaine use disorder patients (CDPs) can control their eye movements toward cocaine cues and whether their response varied by cue-induced craving intensity. Thirty CDPs underwent a cue exposure procedure to dichotomize them into high and low craving groups followed by a modified antisaccade task in which subjects were asked to control their eye movements toward either a cocaine or neutral drug cue by looking away from the suddenly presented cue. The relationship between breakdowns in cognitive control (as measured by eye errors) and cue-induced craving (changes in self-reported craving following cocaine cue exposure) was investigated. CDPs overall made significantly more errors toward cocaine cues compared to neutral cues, with higher cravers making significantly more errors than lower cravers even though they did not differ significantly in addiction severity, impulsivity, anxiety, or depression levels. Cue-induced craving was the only specific and significant predictor of subsequent errors toward cocaine cues. Cue-induced craving directly and specifically relates to breakdowns of cognitive control toward cocaine cues in CDPs, with higher cravers being more susceptible. Hence, it may be useful identifying high cravers and target treatment toward curbing craving to decrease the likelihood of a subsequent breakdown in control. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cocaine – Characteristics and addiction

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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

Cocaine use and the breastfeeding mother.

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Jones, Wendy

2015-01-01

Cocaine is the second most commonly used illicit drug. Use in pregnancy and breastfeeding may have severe consequences for the baby due to its pharmacokinetic properties. Midwives need to be aware of the prolonged action of cocaine and be alert to the possibility of cocaine toxicity if a baby is excessively irritable and tachycardic. Euphoric highs are brief but breast milk and urine remain positive for long periods. Infant urine following exposure to cocaine via breast milk may remain positive for up to 60 hours. Mothers who snort cocaine should pump and dump breast milk for 24-48 hours. Passive inhalation of crack cocaine smoke may also result in infants with positive toxicology screens. Cocaine powder should never be applied to the nipples of breastfeeding mothers.

Reduced Metabolism in Brain 'Control Networks' Following Cocaine-Cues Exposure in Female Cocaine Abusers

International Nuclear Information System (INIS)

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

2011-01-01

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 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.

A survey of the effects of Raha® and Berberin medicine in toxic and sub toxic doses compare with Clonidine medicine on reducing symptoms of morphine withdrawal

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Mohammad.J Khoshnood

2010-09-01

Full Text Available Background: Opiate withdrawal refers to the wide range of symptoms that occur after stopping or dramatically reducing opiate drugs after heavy and prolonged use. The aim of the present study was to determine the effects of Raha and Berberin medicine in toxic and sub toxic doses compare with Clonidine medicine on reducing symptoms of morphine withdrawal in Syrian mice.Materials and Method: 140 Syrian mice (weight range 70-90 gr were divided randomly into 2 groups; first group; n1=35(receiving drug =21, control=14 & second group; n2=105 (receiving drug=91, control=14. Animals were treated by injected increasing doses of morphine sulfate for physical dependence. Then withdrawal syndrome was induced by administration of Naloxone. In order to evaluate the effect of Raha Berberin and Clonidine on morphine withdrawal syndrome in Syrian mice and also amount of total alkaloids and Berberin value in the Raha® were measured.Result: Total of average of alkaloid and Berberin value was 120, 5.72 mg, respectively in 5 ml of the Raha®. The rate of alcohol in Raha® was shown by using the USP procedure which was 19.34 percent. Toxic doses of Raha® and Berberin were 4, 40 mg/kg, respectively. Results indicated that, Raha increases significantly the percent of occurrence of ptosis and immobility were compared with control group (distilled water receiver (p=0.016. The occurrence rate of sniffing, grooming and rearing behavior in Raha and Berberin treated groups compared with control group, within 15min period, was not found statistically significant (p=0.089.Conclusion: Based on our study both Raha® and Berberin in any dilution had no effect on reducing signs of opioid withdrawal syndrome. According to the lack of its effect in mice, further studies should be undertaken for prescription of this drug in human

Carbon Nanotube Membranes for use in the Transdermal Treatment of Nicotine Addiction and Opioid Withdrawal Symptoms

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Caroline L. Strasinger

2009-01-01

Full Text Available Transdermal systems are attractive methods of drug administration specifically when treating patients for drug addiction. Current systems however are deficient in therapies that allow variable flux values of drug, such as nicotine for smoking cessation or complex dosing regimens using clonidine when treating opioid withdrawal symptoms. Through the use of functionalized carbon nanotube (CNT membranes, drug delivery to the skin can be controlled by applying a small electrical bias to create a programmable drug delivery system. Clearly, a transdermal patch system that can be tailored to an individual's needs will increase patient compliance as well as provide much more efficient therapy. The purpose of this paper is to discuss the applicability of using carbon nanotube membranes in transdermal systems for treatment of drug abuse.

Marijuana withdrawal and aggression among a representative sample of U.S. marijuana users

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Smith, Philip H.; Homish, Gregory G.; Leonard, Kenneth E.; Collins, R. Lorraine

2013-01-01

Background Previous laboratory-based research suggests that withdrawal from marijuana may cause increased aggression. It is unclear whether this finding extends beyond the laboratory setting to the general population of marijuana users. The purpose of this study was to test a cross-sectional association between marijuana withdrawal symptoms and aggression among a representative sample of U.S. adult marijuana users, and to test whether this association was moderated by previous history of aggression. Methods Data were analyzed from the National Epidemiologic Survey on Alcohol and Related Conditions. Wave Two data (2004–2005) were used for all variables except for history of aggression, which was assessed during the Wave One interview (2001–2002). Two outcomes were examined: self-report general aggression and relationship aggression. Odds ratios for aggression based on withdrawal symptoms and the interaction between withdrawal symptoms and history of aggression were calculated using logistic regression, adjusting for covariates and accounting for the complex survey design. Results Among marijuana users with a history of aggression, marijuana withdrawal was associated with approximately 60% higher odds of past year relationship aggression (p aggression among those without a history of aggression, and no association with general aggression regardless of history of aggression. Conclusions The findings from this study support the notion that laboratory-based increases in aggression due to marijuana withdrawal extend to the general population of marijuana users who have a previous history of aggression. PMID:23380439

Effects of anti-cocaine vaccine and viral gene transfer of cocaine hydrolase in mice on cocaine toxicity including motor strength and liver damage.

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Gao, Yang; Geng, Liyi; Orson, Frank; Kinsey, Berma; Kosten, Thomas R; Shen, Xiaoyun; Brimijoin, Stephen

2013-03-25

In developing an vivo drug-interception therapy to treat cocaine abuse and hinder relapse into drug seeking provoked by re-encounter with cocaine, two promising agents are: (1) a cocaine hydrolase enzyme (CocH) derived from human butyrylcholinesterase and delivered by gene transfer; (2) an anti-cocaine antibody elicited by vaccination. Recent behavioral experiments showed that antibody and enzyme work in a complementary fashion to reduce cocaine-stimulated locomotor activity in rats and mice. Our present goal was to test protection against liver damage and muscle weakness in mice challenged with massive doses of cocaine at or near the LD50 level (100-120 mg/kg, i.p.). We found that, when the interceptor proteins were combined at doses that were only modestly protective in isolation (enzyme, 1mg/kg; antibody, 8 mg/kg), they provided complete protection of liver tissue and motor function. When the enzyme levels were ~400-fold higher, after in vivo transduction by adeno-associated viral vector, similar protection was observed from CocH alone. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Effects of inhibitory GABA-active neurosteroids on cocaine seeking and cocaine taking in rats.

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Schmoutz, Christopher D; Runyon, Scott P; Goeders, Nicholas E

2014-09-01

Several compounds that potentiate GABA-induced inhibitory currents also decrease stress, anxiety and addiction-related behaviors. Because of the well-established connection between stress and addiction, compounds that reduce stress-induced responses might be efficacious in treating addiction. Since endogenous neurosteroids such as allopregnanolone may function in a manner similar to benzodiazepines to reduce HPA axis activation and anxiety following stressful stimuli, we hypothesized that exogenously applied neurosteroids would reduce cocaine reinforcement in two animal models. Male Wistar rats were trained to self-administer cocaine and food under a concurrent alternating operant schedule of reinforcement. Two separate groups of rats were trained to self-administer cocaine or food pellets and were then exposed to similar cue-induced reinstatement paradigms. Both groups of rats were pretreated with various doses of neurosteroids. Allopregnanolone and 3α-hydroxy-3β-methyl-17β-nitro-5α-androstane (R6305-7, a synthetic neurosteroid) were ineffective in selectively decreasing cocaine relative to food self-administration. On the other hand, both allopregnanolone and R6305-7 significantly decreased the cue-induced reinstatement of extinguished cocaine seeking, confirmed by one-way ANOVA. These results suggest that neurosteroids may be effective in reducing the relapse to cocaine use without affecting ongoing cocaine self-administration.

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

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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 K M 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.

Repeated in vivo exposure of cocaine induces long-lasting synaptic plasticity in hypocretin/orexin-producing neurons in the lateral hypothalamus in mice.

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Rao, Yan; Mineur, Yann S; Gan, Geliang; Wang, Alex Hanxiang; Liu, Zhong-Wu; Wu, Xinyuan; Suyama, Shigetomo; de Lecea, Luis; Horvath, Tamas L; Picciotto, Marina R; Gao, Xiao-Bing

2013-04-01

Hypocretin (orexin), a neuropeptide synthesized exclusively in the perifornical/lateral hypothalamus, is critical for drug seeking and relapse, but it is not clear how the circuitry centred on hypocretin-producing neurons (hypocretin neurons) is modified by drugs of abuse and how changes in this circuit might alter behaviours related to drug addiction. In this study, we show that repeated, but not single, in vivo cocaine administration leads to a long-lasting, experience-dependent potentiation of glutamatergic synapses on hypocretin neurons in mice following a cocaine-conditioned place preference (CPP) protocol. The synaptic potentiation occurs postsynaptically and probably involves up-regulation of AMPA-type glutamate receptors on hypocretin neurons. Phosphorylation of cAMP response element-binding protein (CREB) is also significantly increased in hypocretin neurons in cocaine-treated animals, suggesting that CREB-mediated pathways may contribute to synaptic potentiation in these cells. Furthermore, the potentiation of synaptic efficacy in hypocretin neurons persists during cocaine withdrawal, but reverses to baseline levels after prolonged abstinence. Finally, the induction of long-term potentiation (LTP) triggered by a high-frequency stimulation is facilitated in hypocretin neurons in cocaine-treated mice, suggesting that long-lasting changes in synapses onto hypocretin neurons would probably be further potentiated by other stimuli (such as concurrent environmental cues) paired with the drug. In summary, we show here that hypocretin neurons undergo experience-dependent synaptic potentiation that is distinct from that reported in other reward systems, such as the ventral tegmental area, following exposure to cocaine. These findings support the idea that the hypocretin system is important for behavioural changes associated with cocaine administration in animals and humans.

Effects of phendimetrazine treatment on cocaine vs food choice and extended-access cocaine consumption in rhesus monkeys.

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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).

Evaluation of cocaine-induced hepatotoxicity

International Nuclear Information System (INIS)

Wang, G.J.; Som, P.; Volkow, N.D.; Oster, Z.H.

1991-01-01

The effect of repeated administrations (1,5 weeks) of cocaine on the liver was studied using two radiopharmaceuticals, 99m Tc sulfur colloid (SC) and 99m Tc DISIDA. Uptake and clearance kinetics as well as liver enzyme determinations and histopathology were compared. In cocaine-treated animals hepatomegaly was noted (36% increase in liver weight over non-treated animals), and SGPT levels were 5 times higher than in non-treated animals. Periportal necrosis, fatty infiltration, and inflammation were noted on histological sections. The total uptake of 99m Tc SC in cocaine-treated mice was 8% higher, but the concentration (% ID/gm) was 18% lower, than in non-treated animals. Decreased uptake and concentration of 99m Tc SC was seen in the spleen. In contrast, the uptake and clearance of 99m Tc DISIDA were not affected by cocaine treatment. It is concluded that in this model 99m Tc DISIDA was not a sensitive agent for evaluation of cocaine-induced hepatoxicity, and that 99m Tc SC was a more sensitive agent for the determination of hepatic and splenic toxicity due to cocaine. Cocaine-mediated hepato-splenic toxicity warrants further clinical investigations. (orig.) [de

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

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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.

Cocaine Promotes Coincidence Detection and Lowers Induction Threshold during Hebbian Associative Synaptic Potentiation in Prefrontal Cortex.

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Ruan, Hongyu; Yao, Wei-Dong

2017-01-25

Addictive drugs usurp neural plasticity mechanisms that normally serve reward-related learning and memory, primarily by evoking changes in glutamatergic synaptic strength in the mesocorticolimbic dopamine circuitry. Here, we show that repeated cocaine exposure in vivo does not alter synaptic strength in the mouse prefrontal cortex during an early period of withdrawal, but instead modifies a Hebbian quantitative synaptic learning rule by broadening the temporal window and lowers the induction threshold for spike-timing-dependent LTP (t-LTP). After repeated, but not single, daily cocaine injections, t-LTP in layer V pyramidal neurons is induced at +30 ms, a normally ineffective timing interval for t-LTP induction in saline-exposed mice. This cocaine-induced, extended-timing t-LTP lasts for ∼1 week after terminating cocaine and is accompanied by an increased susceptibility to potentiation by fewer pre-post spike pairs, indicating a reduced t-LTP induction threshold. Basal synaptic strength and the maximal attainable t-LTP magnitude remain unchanged after cocaine exposure. We further show that the cocaine facilitation of t-LTP induction is caused by sensitized D1-cAMP/protein kinase A dopamine signaling in pyramidal neurons, which then pathologically recruits voltage-gated l-type Ca 2+ channels that synergize with GluN2A-containing NMDA receptors to drive t-LTP at extended timing. Our results illustrate a mechanism by which cocaine, acting on a key neuromodulation pathway, modifies the coincidence detection window during Hebbian plasticity to facilitate associative synaptic potentiation in prefrontal excitatory circuits. By modifying rules that govern activity-dependent synaptic plasticity, addictive drugs can derail the experience-driven neural circuit remodeling process important for executive control of reward and addiction. It is believed that addictive drugs often render an addict's brain reward system hypersensitive, leaving the individual more susceptible to

Functional consequences of cocaine expectation: findings in a non-human primate model of cocaine self-administration.

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

2016-05-01

Exposure to stimuli and environments associated with drug use is considered one of the most important contributors to relapse among substance abusers. Neuroimaging studies have identified neural circuits underlying these responses in cocaine-dependent subjects. But these studies are often difficult to interpret because of the heterogeneity of the participants, substances abused, and differences in drug histories and social variables. Therefore, the goal of this study was to assess the functional effects of exposure to cocaine-associated stimuli in a non-human primate model of cocaine self-administration, providing precise control over these variables, with the 2-[(14) C]deoxyglucose method. Rhesus monkeys self-administered 0.3 mg/kg/injection cocaine (n = 4) under a fixed-interval 3-minute (FI 3-min) schedule of reinforcement (30 injections/session) for 100 sessions. Control animals (n = 4) underwent identical schedules of food reinforcement. Sessions were then discontinued for 30 days, after which time, monkeys were exposed to cocaine- or food-paired cues, and the 2-[(14) C]deoxyglucose experiment was conducted. The presentation of the cocaine-paired cues resulted in significant increases in functional activity within highly restricted circuits that included portions of the pre-commissural striatum, medial prefrontal cortex, rostral temporal cortex and limbic thalamus when compared with control animals presented with the food-paired cues. The presentation of cocaine-associated cues increased brain functional activity in contrast to the decreases observed after cocaine consumption. Furthermore, the topography of brain circuits engaged by the expectation of cocaine is similar to the distribution of effects during the earliest phases of cocaine self-administration, prior to the onset of neuroadaptations that accompany chronic cocaine exposure. © 2015 Society for the Study of Addiction.

High enhancer, downer, withdrawal helper: Multifunctional nonmedical benzodiazepine use among young adult opioid users in New York City.

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Mateu-Gelabert, Pedro; Jessell, Lauren; Goodbody, Elizabeth; Kim, Dongah; Gile, Krista; Teubl, Jennifer; Syckes, Cassandra; Ruggles, Kelly; Lazar, Jeffrey; Friedman, Sam; Guarino, Honoria

2017-08-01

Benzodiazepines are a widely prescribed psychoactive drug; in the U.S., both medical and nonmedical use of benzodiazepines has increased markedly in the past 15 years. Long-term use can lead to tolerance and dependence, and abrupt withdrawal can cause seizures or other life-threatening symptoms. Benzodiazepines are often used nonmedically in conjunction with other drugs, and with opioids in particular-a combination that can increase the risk for fatal and non-fatal overdose. This mixed-methods study examines nonmedical use of benzodiazepines among young adults in New York City and its relationship with opioid use. For qualitative analysis, 46 90-minute semi-structured interviews were conducted with young adult opioid users (ages 18-32). Interviews were transcribed and coded for key themes. For quantitative analysis, 464 young adult opioid users (ages 18-29) were recruited using Respondent-Driven Sampling and completed structured interviews. Benzodiazepine use was assessed via a self-report questionnaire that included measures related to nonmedical benzodiazepine and opioid use. Participants reported using benzodiazepines nonmedically for a wide variety of reasons, including: to increase the high of other drugs; to lessen withdrawal symptoms; and to come down from other drugs. Benzodiazepines were described as readily available and cheap. There was a high prevalence (93%) of nonmedical benzodiazepine use among nonmedical opioid users, with 57% reporting regular nonmedical use. In bivariate analyses, drug-related risk behaviours such as polysubstance use, drug binging, heroin injection and overdose were strongly associated with regular nonmedical benzodiazepine use. In multivariate analysis, growing up in a middle-income household (earning between $51,000 and $100,000 annually), lifetime overdose experience, having ever used cocaine regularly, having ever been prescribed benzodiazepines, recent drug binging, and encouraging fellow drug users to use benzodiazepines to

Atomoxetine Does Not Alter Cocaine Use in Cocaine Dependent Individuals: A Double Blind Randomized Trial

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Middleton, Lisa S.; Wong, Conrad J.; Nuzzo, Paul A.; Campbell, Charles L.; Rush, Craig R.; Lofwall, Michelle R.

2016-01-01

Background Cocaine abuse continues to be a significant public health problem associated with morbidity and mortality. To date, no pharmacotherapeutic approach has proven effective for treating cocaine use disorders. Preclinical and clinical evidence suggests that noradrenergic activity may play a role in mediating some effects of cocaine and may be a rational target for treatment. Methods This double blind, placebo-controlled randomized, parallel group, 12-week outpatient clinical trial enrolled cocaine dependent individuals seeking treatment to examine the potential efficacy of the selective norepinephrine reuptake inhibitor, atomoxetine (80 mg/day; p.o.; n=25), compared to placebo (n=25). Subjects were initially stratified on cocaine use (atomoxetine and placebo groups (X2=0.2, p=.66; OR=0.89 [95% CI 0.41 – 1.74). Atomoxetine was generally well tolerated in this population. Conclusions These data provide no support for the utility of atomoxetine in the treatment of cocaine dependence. PMID:23200303

Potential risk factors associated with risk for drop-out and relapse during and following withdrawal of opioid prescription medication.

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Heiwe, Susanne; Lönnquist, Ingeborg; Källmén, Håkan

2011-10-01

Withdrawal of opioid medication in patients with chronic pain has a drop-out and relapse problem. To evaluate if depressive symptoms, anxiety and pain intensity are potential risk factors for drop-out or relapse during the withdrawal process. Further, to assess internal consistency of scales for assessment of these potential risk factors. Twenty-nine patients were included. After 2 years 28 of these were followed-up. Those with depressive symptoms at baseline had a significant risk for drop-out from the withdrawal program (odds ratio 1.37) and relapse into use of opioids at follow-up (odds ratio 1.44). Drop-outs rated depressive symptoms significantly higher before detoxification. Those who relapsed rated significantly higher for pain intensity, depressive symptoms and abstinence prior to withdrawal. All scales had high reliability. To avoid drop-out and relapse clinical practice need to screen for depressive symptoms, pain intensity, and abstinence. This article presents significant reliability of scales useful within dependency centers. They can be used to identify these risk factors for drop-out and relapse, respectively, when initiating the withdrawal process. Taking these risk factors into consideration could improve the outcome of the withdrawal process by preventing drop-out and relapse. Copyright © 2011 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Cocaine and opiates use in pregnancy: detection of drugs in neonatal meconium and urine.

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López, P; Bermejo, A M; Tabernero, M J; Cabarcos, P; Alvarez, I; Fernández, P

2009-09-01

In this study, the case of a newborn with symptoms of hyperexcitability was analyzed. After it was confirmed in the hospital that the mother had consumed drugs during pregnancy using an enzyme multiplied immunoassay technique, samples of the newborn's urine and meconium were sent to our laboratory to observe the evolution in the distribution of cocaine and opiates during the days following birth. For urine analysis, screening was done with an immunoassay technique, and the confirmation was done by gas chromatography-mass spectrometry (GC-MS) according to a published method. A GC-MS method for simultaneous analysis of cocaine, benzoylecgonine, codeine, morphine, and 6-acetylmorphine in meconium is described. GC-MS confirmation of urine and meconium results showed consumption of cocaine and codeine during pregnancy and also showed the levels of drugs gradually declined, totally disappearing by the third day.

Manipulating a "cocaine engram" in mice.

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Hsiang, Hwa-Lin Liz; Epp, Jonathan R; van den Oever, Michel C; Yan, Chen; Rashid, Asim J; Insel, Nathan; Ye, Li; Niibori, Yosuke; Deisseroth, Karl; Frankland, Paul W; Josselyn, Sheena A

2014-10-15

Experience with drugs of abuse (such as cocaine) produces powerful, long-lasting memories that may be important in the development and persistence of drug addiction. The neural mechanisms that mediate how and where these cocaine memories are encoded, consolidated and stored are unknown. Here we used conditioned place preference in mice to examine the precise neural circuits that support the memory of a cocaine-cue association (the "cocaine memory trace" or "cocaine engram"). We found that a small population of neurons (∼10%) in the lateral nucleus of amygdala (LA) were recruited at the time of cocaine-conditioning to become part of this cocaine engram. Neurons with increased levels of the transcription factor CREB were preferentially recruited or allocated to the cocaine engram. Ablating or silencing neurons overexpressing CREB (but not a similar number of random LA neurons) before testing disrupted the expression of a previously acquired cocaine memory, suggesting that neurons overexpressing CREB become a critical hub in what is likely a larger cocaine memory engram. Consistent with theories that coordinated postencoding reactivation of neurons within an engram or cell assembly is crucial for memory consolidation (Marr, 1971; Buzsáki, 1989; Wilson and McNaughton, 1994; McClelland et al., 1995; Girardeau et al., 2009; Dupret et al., 2010; Carr et al., 2011), we also found that post-training suppression, or nondiscriminate activation, of CREB overexpressing neurons impaired consolidation of the cocaine memory. These findings reveal mechanisms underlying how and where drug memories are encoded and stored in the brain and may also inform the development of treatments for drug addiction. Copyright © 2014 the authors 0270-6474/14/3414115-13$15.00/0.

Cannabis Withdrawal Among Detained Adolescents: Exploring the Impact of Nicotine and Race.

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Soenksen, Shayna; Stein, L A R; Brown, Joanna D; Stengel, JoAnn R; Rossi, Joseph S; Lebeau, Rebecca

2015-04-01

Rates of marijuana use among detained youths are exceptionally high. Research suggests a cannabis withdrawal syndrome is valid and clinically significant; however, these studies have mostly been conducted in highly controlled laboratory settings with treatment-seeking, White adults. The present study analyzed archival data to explore the magnitude of cannabis withdrawal symptoms within a diverse sample of detained adolescents while controlling for tobacco use and investigating the impact of race on symptom reports. Adolescents recruited from a juvenile correctional facility (N=93) completed a background questionnaire and the Marijuana Withdrawal Checklist. Analyses revealed a significant main effect for level of tobacco use on severity of irritability, and for level of marijuana use on severity of craving to smoke marijuana and strange/wild dreams. Furthermore, a significant main effect for race was found with Black adolescents reporting lower withdrawal discomfort scores and experiencing less severe depressed mood, difficulty sleeping, nervousness/anxiety, and strange/wild dreams. Although exploratory, these findings may have significant clinical implications for providers in juvenile detention facilities, allowing the execution of proper medical and/or behavioral interventions to assist adolescents presenting with problematic cannabis and/or tobacco withdrawal.

The selective dopamine uptake inhibitor, D-84, suppresses cocaine self-administration, but does not occasion cocaine-like levels of generalization.

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Batman, Angela M; Dutta, Aloke K; Reith, Maarten E A; Beardsley, Patrick M

2010-12-01

A successful replacement pharmacotherapy for treating cocaine dependency would likely reduce cocaine's abuse, support a low abuse liability, overlap cocaine's subjective effects, and have a long duration of action. Inhibitors with varying selectivity at the dopamine transporter (DAT) have approximated these properties. The objective of the present study was to characterize the behavioural effects of an extremely selective DAT inhibitor, (+) trans-4-(2-Benzhydryloxyethyl)-1-(4-fluorobenzyl) piperadin-3-ol (D-84), a 3-hydroxy substituted piperidine derivative of GBR-12935, for its cocaine-like discriminative stimulus effects, its effects on cocaine self-administration, and for its own self-administration. During cocaine discrimination tests, cocaine occasioned the 10 mg/kg cocaine training stimulus with an ED(50) value of 3.13 (1.54-6.34) mg/kg, and reduced response rates with an ED(50) value of 20.39 (7.24-57.44) mg/kg. D-84 incompletely generalized to the cocaine stimulus occasioning a maximal 76% cocaine-lever responding, while reducing response rates with lower potency than cocaine (ED(50)=30.94 (12.34-77.60) mg/kg). Pretreatment with D-84 (9.6-30.4 mg/kg) significantly (P<0.05) reduced cocaine intake at 17.1 mg/kg D-84 when cocaine was self-administered at 0.5 mg/kg/infusion, and at 30.4 mg/kg D-84 when cocaine was self-administered at 0.1, 0.5 .and 1.0 mg/kg/infusion. During self-administration tests with D-84 (0.1-1 mg/kg/infusion), numbers of infusions significantly exceeded vehicle levels at 0.3 mg/kg/infusion. These results show that D-84 pretreatment can decrease cocaine intake especially when high doses of cocaine are being self-administered. This observation, combined with its incomplete generalization to the cocaine discriminative stimulus and its reported long duration of action, provides a profile consistent with a potential replacement therapy for treating cocaine-abusing patients. Copyright © 2010 Elsevier B.V. All rights reserved.

Mirtazapine attenuates cocaine seeking in rats.

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Barbosa-Méndez, Susana; Leff, Phillipe; Arías-Caballero, Adriana; Hernández-Miramontes, Ricardo; Heinze, Gerardo; Salazar-Juárez, Alberto

2017-09-01

Relapse to cocaine use is a major problem in the clinical treatment of cocaine addiction. Antidepressants have been studied for their therapeutic potential to treat cocaine use disorder. Research has suggested that antidepressants attenuate both drug craving and the re-acquisition of drug-seeking and drug-taking behaviors. This study examined the efficacy of mirtazapine, an antidepressant/anxiolytic, in decreasing cocaine seeking in rats. We used the cocaine self-administration paradigm to assess the effects of mirtazapine on rats trained to self-administer cocaine or food under a fixed-ratio schedule. Mirtazapine (30 mg/kg, i.p.) was administered during extinction. Mirtazapine significantly attenuated non-reinforced lever-press responses during extinction. Moreover, the mirtazapine dosed for 30 days during extinction produced sustained attenuation of lever-press responses during re-acquisition of cocaine self-administration, without changing food-seeking behavior. Our results showed that mirtazapine attenuated the re-acquisition of cocaine-seeking responses. Our study pointed to the efficacy of mirtazapine in reducing the risk of drug relapse during abstinence, suggesting for its potential use as a novel pharmacological agent to treat drug abuse. Copyright © 2017 Elsevier Ltd. All rights reserved.

Childhood Social Withdrawal, Interpersonal Impairment, and Young Adult Depression: A Mediational Model

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Katz, Shaina J.; Conway, Christopher C.; Hammen, Constance L.; Brennan, Patricia A.; Najmanm, Jake M.

2011-01-01

Building on interpersonal theories of depression, the current study sought to explore whether early childhood social withdrawal serves as a risk factor for depressive symptoms and diagnoses in young adulthood. The researchers hypothesized that social impairment at age 15 would mediate the association between social withdrawal at age 5 and…

Carbon Nanotube Membranes for use in the Transdermal Treatment of Nicotine Addiction and Opioid Withdrawal Symptoms

Directory of Open Access Journals (Sweden)

Audra L. Stinchcomb

2009-01-01

Full Text Available Transdermal systems are attractive methods of drug administration specifically when treating patients for drug addiction. Current systems however are deficient in therapies that allow variable flux values of drug, such as nicotine for smoking cessation or complex dosing regimens using clonidine when treating opioid withdrawal symptoms. Through the use of functionalized carbon nanotube (CNT membranes, drug delivery to the skin can be controlled by applying a small electrical bias to create a programmable drug delivery system. Clearly, a transdermal patch system that can be tailored to an individual’s needs will increase patient compliance as well as provide much more efficient therapy. The purpose of this paper is to discuss the applicability of using carbon nanotube membranes in transdermal systems for treatment of drug abuse.

Neurobiology of opioid withdrawal: Role of the endothelin system.

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Bhalla, Shaifali; Andurkar, Shridhar V; Gulati, Anil

2016-08-15

Morphine and oxycodone are potent opioid analgesics most commonly used for the management of moderate to severe acute and chronic pain. Their clinical utility is limited by undesired side effects like analgesic tolerance, dependence, and withdrawal. We have previously demonstrated that endothelin-A (ETA) receptor antagonists potentiate opioid analgesia and eliminate analgesic tolerance. Mechanistically, G proteins and regulatory proteins such as β-arrestins have shown to play an important role in mediating opioid tolerance, dependence, and withdrawal. Recently, the involvement of central ET mechanisms in opioid withdrawal was investigated. ETA receptor antagonist was shown to block majority of the signs and symptoms associated with opioid withdrawal. This review focuses on ET as one of the potential novel strategies to manage the challenge of opioid withdrawal. An overview of additional players in this process (G proteins and β-arrestin2), and the possible therapeutic implications of these findings are presented. Copyright © 2016 Elsevier Inc. All rights reserved.

Stories of Hell and Healing: Internet Users’ Construction of Benzodiazepine Distress and Withdrawal

OpenAIRE

Fixsen, Alison; Ridge, Damien T.

2017-01-01

Abstract Benzodiazepines are a group of drugs used mainly as sedatives, hypnotics, antiepileptics, and muscle relaxants. Consumption is recommended for 2 to 4 weeks only, due to fast onset of dependency and potentially distressing withdrawal symptoms. Few peer-review studies have drawn on the user experiences and language to appreciate firsthand experiences of benzodiazepine withdrawal or discontinuation syndrome. We looked extensively at patient stories of benzodiazepine withdrawal and recov...

Location-specific immunodetection of cocaine on banknotes.

Science.gov (United States)

van der Heide, Susan; Cunningham, Andrew; Hardwick, Sheila; Russell, David A

2016-10-17

A novel in-gel bioanalytical immunodetection method has been developed to determine both the presence and the location of cocaine on the surface of banknotes. The cocaine was 'fixed' to the surface of the banknote via a coating of a polyacrylamide gel matrix. Immunostaining of the immobilised cocaine on the banknote surface was performed using an anti-cocaine primary antibody, either pre-labelled with horse radish peroxidase (HRP) or in conjunction with a HRP-labelled secondary antibody. Visualisation of the location of the cocaine was achieved through chemiluminescence imaging of the banknote following application of a chemiluminescent substrate. The novel method was applied to the detection of cocaine on partial and whole banknote samples obtained from general circulation. Newly minted banknotes, with or without spiked cocaine, were used as positive and negative controls, respectively. The results obtained, for the first time, demonstrate the successful location-specific immunostaining of cocaine on banknotes. A preliminary analysis of six UK banknotes, obtained from general circulation, suggests that cocaine can be present at variable locations across the whole of the banknote.

Mephedrone interactions with cocaine: prior exposure to the 'bath salt' constituent enhances cocaine-induced locomotor activation in rats.

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Gregg, Ryan A; Tallarida, Christopher S; Reitz, Allen B; Rawls, Scott M

2013-12-01

Concurrent use of mephedrone (4-methylmethcathinone; MEPH) and established drugs of abuse is now commonplace, but knowledge about interactions between these drugs is sparse. The present study was designed to test the hypothesis that prior MEPH exposure enhances the locomotor-stimulant effects of cocaine and methamphetamine (METH). For cocaine experiments, rats pretreated with saline, cocaine (15 mg/kg), or MEPH (15 mg/kg) for 5 days were injected with cocaine after 10 days of drug absence. For METH experiments, rats pretreated with saline, METH (2 mg/kg), or MEPH (15 mg/kg) were injected with METH after 10 days of drug absence. Cocaine challenge produced greater locomotor activity after pretreatment with cocaine or MEPH than after pretreatment with saline. METH challenge produced greater locomotor activity after METH pretreatment than after saline pretreatment; however, locomotor activity in rats pretreated with MEPH or saline and then challenged with METH was not significantly different. The locomotor response to MEPH (15 mg/kg) was not significantly affected by pretreatment with cocaine (15 mg/kg) or METH (0.5, 2 mg/kg). The present demonstration that cocaine-induced locomotor activation is enhanced by prior MEPH exposure suggests that MEPH cross-sensitizes to cocaine and increases cocaine efficacy. Interestingly, MEPH cross-sensitization was not bidirectional and did not extend to METH, suggesting that the phenomenon is sensitive to specific psychostimulants.

Subthalamic nucleus high-frequency stimulation modulates neuronal reactivity to cocaine within the reward circuit.

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Hachem-Delaunay, Sabira; Fournier, Marie-Line; Cohen, Candie; Bonneau, Nicolas; Cador, Martine; Baunez, Christelle; Le Moine, Catherine

2015-08-01

The subthalamic nucleus (STN) is a critical component of a complex network controlling motor, associative and limbic functions. High-frequency stimulation (HFS) of the STN is an effective therapy for motor symptoms in Parkinsonian patients and can also reduce their treatment-induced addictive behaviors. Preclinical studies have shown that STN HFS decreases motivation for cocaine while increasing that for food, highlighting its influence on rewarding and motivational circuits. However, the cellular substrates of these effects remain unknown. Our objectives were to characterize the cellular consequences of STN HFS with a special focus on limbic structures and to elucidate how STN HFS may interfere with acute cocaine effects in these brain areas. Male Long-Evans rats were subjected to STN HFS (130 Hz, 60 μs, 50-150 μA) for 30 min before an acute cocaine injection (15 mg/kg) and sacrificed 10 min following the injection. Neuronal reactivity was analyzed through the expression of two immediate early genes (Arc and c-Fos) to decipher cellular responses to STN HFS and cocaine. STN HFS only activated c-Fos in the globus pallidus and the basolateral amygdala, highlighting a possible role on emotional processes via the amygdala, with a limited effect by itself in other structures. Interestingly, and despite some differential effects on Arc and c-Fos expression, STN HFS diminished the c-Fos response induced by acute cocaine in the striatum. By preventing the cellular effect of cocaine in the striatum, STN HFS might thus decrease the reinforcing properties of the drug, which is in line with the inhibitory effect of STN HFS on the rewarding and reinforcing properties of cocaine. Copyright © 2015 Elsevier Inc. All rights reserved.

Sodium Valproate Withdrawal Correlates with Reduced Aggression

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Pritchard, Duncan; Hoerger, Marguerite; Dyer, Tim; Graham, Nicola; Penney, Heather; Mace, F. Charles

2014-01-01

People with learning disabilities are sometimes prescribed psychotropic medication to help manage their challenging behaviour. This case study describes how a multicomponent behavioural intervention in conjunction with the systematic withdrawal of sodium valproate was strongly correlated with reduced aggression. No symptoms of bipolar disorder or…

A mathematical model of a recombinant humanized anti-cocaine monoclonal antibody's effects on cocaine pharmacokinetics in mice.

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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.

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

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Kutlu, Munir Gunes

2016-01-01

It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawal-induced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates. PMID:27634143

Psychometric evaluation of the Dutch version of the Subjective Opiate Withdrawal Scale (SOWS)

NARCIS (Netherlands)

Dijkstra, B.A.G.; Krabbe, P.F.M.; Riezebos, T.G.M.; Staak, C.P.F. van der; Jong, C.A.J. de

2007-01-01

AIM: To evaluate the psychometric properties of the Dutch version of the 16-item Subjective Opiate Withdrawal Scale (SOWS). The SOWS measures withdrawal symptoms at the time of assessment. METHODS: The Dutch SOWS was repeatedly administered to a sample of 272 opioid-dependent inpatients of four

Neonatal episodic hypoglycemia: a finding of valproic acid withdrawal.

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Çoban, Dilek; Kurtoğlu, Selim; Akın, Mustafa Ali; Akçakuş, Mustafa; Güneş, Tamer

2010-01-01

The treatment of epilepsy during pregnancy is a worldwide problem. Drugs need to be used to control seizures in the mothers. In utero, exposure to valproic acid (VPA) and phenytoin (PH) may cause congenital malformations and also withdrawal symptoms such as irritability, jitteriness and symptoms of hypoglycemia. We present here a newborn with episodic hypoglycemia due to in utero exposure to VPA and PH. The mother was diagnosed as having complex partial epilepsy and was treated with PH (200 mg/day) and VPA (600 mg/day). The offspring developed jitteriness on the second day of life. The infant was hypoglycemic (32 mg/dl). These findings were accepted as withdrawal symptoms, since serum levels of VPA and PH were 37.8 μg/ml (50-100 μg/ml) and 6.37 μg/dl (10-20 μg/ml), respectively. Measurement of blood glucose is important and should be carefully monitored in infants exposed to antiepileptics in utero.

The association between social anhedonia, withdrawal and psychotic experiences in general and high-risk populations.

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Velthorst, Eva; Meijer, Carin

2012-07-01

Social anhedonia (SA) and withdrawal are clinically relevant phenomena in schizophrenia. To examine the nature of the overlap between SA, withdrawal and positive symptoms, we investigated whether the co-occurrence of these phenotypes is more prominent in siblings of patients with a psychotic disorder compared to healthy controls, and if this association is independent of the amount of distress caused by psychotic experiences (PEs). Data were derived from 646 unaffected siblings and 326 healthy controls who were included in the Dutch Genetic Risk and Outcome in Psychosis (GROUP) study. PEs were assessed with the Community Assessment of Psychic Experiences and the Structured Interview for Schizotypy-Revised was used to examine social anhedonia and withdrawal. Our results show relatively small but significant cross-sectional associations between SA, withdrawal and PEs in unaffected siblings and none in the control group, irrespective of the level of distress caused by PEs. The findings of the present study suggest that the overlap between SA, withdrawal and psychotic symptoms often reported in schizophrenia patients, may at least partly reflect a shared genetic vulnerability, instead of merely being either a state marker of - or reaction to - acute psychotic symptoms. Copyright © 2012. Published by Elsevier B.V.

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

Motivated attention to cocaine and emotional cues in abstinent and current cocaine users--an ERP study.

Science.gov (United States)

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

2011-05-01

Event-related potentials (ERPs) are a direct measure of neural activity and are ideally suited to study the time-course of attentional engagement with emotional and drug-related stimuli in addiction. In particular, the late positive potential (LPP) appears to be enhanced following cocaine-related compared with neutral stimuli in human participants with cocaine use disorders (CUD). However, previous studies have not directly compared cocaine-related with emotional stimuli while examining potential differences between abstinent and current cocaine users. The present study examined ERPs in 55 CUD (27 abstinent and 28 current users) and 29 matched healthy controls while they passively viewed pleasant, unpleasant, neutral and cocaine-related pictures. To examine the time-course of attention to these stimuli, we analysed both an early and later window in the LPP as well as the early posterior negativity (EPN), established in assessing motivated attention. Cocaine pictures elicited increased electrocortical measures of motivated attention in ways similar to affectively pleasant and unpleasant pictures in all CUD, an effect that was no longer discernible during the late LPP window for the current users. This group also exhibited deficient processing of the other emotional stimuli (early LPP window - pleasant pictures; late LPP window - pleasant and unpleasant pictures). Results were unique to the LPP and not EPN. Taken together, results support a relatively early attention bias to cocaine stimuli in cocaine-addicted individuals, further suggesting that recent cocaine use decreases such attention bias during later stages of processing but at the expense of deficient processing of other emotional stimuli. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. No claim to original US government works.

Cocaine in the UK--1991.

Science.gov (United States)

Strang, J; Johns, A; Caan, W

1993-01-01

More than 100 years after Freud's original endorsement of the drug, the use of cocaine is a problem for both users and for society, which struggles to organise effective responses to the epidemic of the last decade. During the 1980s the rapid spread of smokeable cocaine (including 'crack') was seen in the Americas (particularly the US). The initial simple predictions of an identical European epidemic were mistaken. The available data on the extent of cocaine use and of cocaine problems in the UK are examined. New forms of cocaine have been developed by black-market entrepreneurs ('freebase' and 'crack'), and new technologies have emerged for their use; with these new technologies have come new effects and new problems. The general psychiatrist now needs a knowledge of directly and indirectly related psychopathology which has an increasing relevance to the diagnosis and management of the younger patient.

Assessing the effect of patterns of cocaine and alcohol use on the risk of adverse acute cocaine intoxication.

Science.gov (United States)

Santos, Sara; Brugal, M Teresa; Barrio, Gregorio; Castellano, Yolanda; Domingo-Salvany, Antonia; Espelt, Albert; Bravo, M Jose; de la Fuente, Luis

2012-06-01

Although, in the laboratory, most acute adverse effects of cocaine are dose-dependent and alcohol potentiates some of these effects, there are few observational studies, and scarce awareness that the risk of acute cocaine intoxication (ACI) can increase as the amounts of cocaine and alcohol consumed increase. Our objectives were to assess if the risk of ACI increases with the level cocaine use, both in chronic and binge use; and also to determine whether it increases when a cocaine binge is combined with binge drinking or with regular excessive drinking. Hypotheses were evaluated using logistic regression and case-crossover analyses in a sample of 720 young regular cocaine users who did not regularly use heroin, recruited at drug scenes in 2004-2006. All data on ACI, predictor and confounding variables were obtained through a computer-assisted personal interview. The annual prevalence of ACI was 21%. In the last year 10.3% of the participants reported cocaine binges (≥ 0.5 g in 4 h). ACI risk increased considerably in the 4 h following a cocaine binge (odds ratio = 34.6; 95% confidence interval 11.5-170.8). Also, it increased with increases in the average level of cocaine used over a long period and when users regularly drank excessively. Finally, the results suggest that the high risk of ACI associated with cocaine binge may increase even more when combined with binge drinking. Awareness of the dose-dependent effect of cocaine on ACI risk, as well as the possible synergistic effect of alcohol, ought to be incorporated into preventive and care strategies. © 2012 Australasian Professional Society on Alcohol and other Drugs.

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

Psychometric evaluation of the Dutch version of the Subjective Opiate Withdrawal Scale (SOWS).

Science.gov (United States)

Dijkstra, Boukje A G; Krabbe, Paul F M; Riezebos, Truus G M; van der Staak, Cees P F; De Jong, Cor A J

2007-01-01

To evaluate the psychometric properties of the Dutch version of the 16-item Subjective Opiate Withdrawal Scale (SOWS). The SOWS measures withdrawal symptoms at the time of assessment. The Dutch SOWS was repeatedly administered to a sample of 272 opioid-dependent inpatients of four addiction treatment centers during rapid detoxification with or without general anesthesia. Examination of the psychometric properties of the SOWS included exploratory factor analysis, internal consistency, test-retest reliability, and criterion validity. Exploratory factor analysis of the SOWS revealed a general pattern of four factors with three items not always clustered in the same factors at different points of measurement. After excluding these items from factor analysis four factors were identified during detoxification (temperature dysregulation, tractus locomotorius, tractus gastro-intestinalis and facial disinhibition). The 13-item SOWS shows high internal consistency and test-retest reliability and good validity at different stages of withdrawal. The 13-item SOWS is a reliable and valid instrument to assess opioid withdrawal during rapid detoxification. Three items were deleted because their content does not correspond directly with opioid withdrawal symptoms. Copyright (c) 2007 S. Karger AG, Basel.

Signs of Cocaine Abuse and Addiction

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... Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search Share You are here Home » Drugs That People Abuse » Cocaine (Coke, Crack) Facts » Signs of Cocaine Use and Addiction Signs of Cocaine Use and Addiction Listen ©istock. ...

Proteasome phosphorylation regulates cocaine-induced sensitization.

Science.gov (United States)

Gonzales, Frankie R; Howell, Kristin K; Dozier, Lara E; Anagnostaras, Stephan G; Patrick, Gentry N

2018-04-01

Repeated exposure to cocaine produces structural and functional modifications at synapses from neurons in several brain regions including the nucleus accumbens. These changes are thought to underlie cocaine-induced sensitization. The ubiquitin proteasome system plays a crucial role in the remodeling of synapses and has recently been implicated in addiction-related behavior. The ATPase Rpt6 subunit of the 26S proteasome is phosphorylated by Ca 2+ /calmodulin-dependent protein kinases II alpha at ser120 which is thought to regulate proteasome activity and distribution in neurons. Here, we demonstrate that Rpt6 phosphorylation is involved in cocaine-induced locomotor sensitization. Cocaine concomitantly increases proteasome activity and Rpt6 S120 phosphorylation in cultured neurons and in various brain regions of wild type mice including the nucleus accumbens and prefrontal cortex. In contrast, cocaine does not increase proteasome activity in Rpt6 phospho-mimetic (ser120Asp) mice. Strikingly, we found a complete absence of cocaine-induced locomotor sensitization in the Rpt6 ser120Asp mice. Together, these findings suggest a critical role for Rpt6 phosphorylation and proteasome function in the regulation cocaine-induced behavioral plasticity. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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.

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.

Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

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Oliver, Jason A; Evans, David E; Addicott, Merideth A; Potts, Geoffrey F; Brandon, Thomas H; Drobes, David J

2017-06-01

Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task. Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors. Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p nicotine dependence (p Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes. Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and

Multiple Gastrointestinal Complications of Crack Cocaine Abuse

Directory of Open Access Journals (Sweden)

Neal Carlin

2014-01-01

Full Text Available Cocaine and its alkaloid free base “crack-cocaine” have long since been substances of abuse. Drug abuse of cocaine via oral, inhalation, intravenous, and intranasal intake has famously been associated with a number of medical complications. Intestinal ischemia and perforation remain the most common manifestations of cocaine associated gastrointestinal disease and have historically been associated with oral intake of cocaine. Here we find a rare case of two relatively uncommon gastrointestinal complications of hemorrhage and pancreatitis presenting within a single admission in a chronic crack cocaine abuser.

Experience of the use of Ketamine to manage opioid withdrawal in an addicted woman: a case report.

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Lalanne, Laurence; Nicot, Chloe; Lang, Jean-Philippe; Bertschy, Gilles; Salvat, Eric

2016-11-10

Opioids are good painkillers, but many patients treated with opioids as painkillers developed a secondary addiction. These patients need to stop misusing opioids, but the mild-to-severe clinical symptoms associated with opioid withdrawal risk increasing their existing pain. In such cases, ketamine, which is used by anaesthetists and pain physicians to reduce opioid medication, may be an effective agent for managing opioid withdrawal. We describe the case of a woman who developed a severe secondary addiction to opioids in the context of lombo-sciatic pain. She presented a severe opioid addiction, and her physicians refused to prescribe such high doses of opioid treatment (oxycontin® extended-release 120 mg daily, oxycodone 60 mg daily, and acetaminophen/codeine 300 mg/25 mg 6 times per day). To assist her with her opioid withdrawal which risked increasing her existing pain, she received 1 mg/kg ketamine oral solution, and two days after ketamine initiation her opioid treatment was gradually reduced. The patient dramatically reduced the dosage of opioid painkillers and ketamine was withdrawn without any withdrawal symptoms. Ketamine displays many interesting qualities for dealing with all symptoms relating to opioid withdrawal. Accordingly, it could be used instead of many psychotropic treatments, which interact with each other, to help with opioid withdrawal. However, the literature describes addiction to ketamine. All in all, although potentially addictive, ketamine could be a good candidate for the pharmacological management of opioid withdrawal.

Adjunct Ketamine Use in the Management of Severe Ethanol Withdrawal.

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Pizon, Anthony F; Lynch, Michael J; Benedict, Neal J; Yanta, Joseph H; Frisch, Adam; Menke, Nathan B; Swartzentruber, Greg S; King, Andrew M; Abesamis, Michael G; Kane-Gill, Sandra L

2018-05-08

Ketamine offers a plausible mechanism with favorable kinetics in treatment of severe ethanol withdrawal. The purpose of this study is to determine if a treatment guideline using an adjunctive ketamine infusion improves outcomes in patients suffering from severe ethanol withdrawal. Retrospective observational cohort study. Academic tertiary care hospital. Patients admitted to the ICU and diagnosed with delirium tremens by Diagnostic and Statistical Manual of Mental Disorders V criteria. Pre and post guideline, all patients were treated in a symptom-triggered fashion with benzodiazepines and/or phenobarbital. Postguideline, standard symptom-triggered dosing continued as preguideline, plus, the patient was initiated on an IV ketamine infusion at 0.15-0.3 mg/kg/hr continuously until delirium resolved. Based upon withdrawal severity and degree of agitation, a ketamine bolus (0.3 mg/kg) was provided prior to continuous infusion in some patients. A total of 63 patients were included (29 preguideline; 34 postguideline). Patients treated with ketamine were less likely to be intubated (odds ratio, 0.14; p trend toward a shorter hospitalization.

Teachers' Withdrawal Behaviors: Integrating Theory and Findings

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Shapira-Lishchinsky, Orly

2012-01-01

Purpose: The article aims to investigate the relationships between different dimensions of organizational ethics and different withdrawal symptoms--lateness, absence, and intent to leave work. Design/methodology/approach: Participants were 1,016 school teachers from 35 high schools in Israel. A joint model of Glimmix procedure of SAS was used for…

Effects of 21-day d-amphetamine and risperidone treatment on cocaine vs food choice and extended-access cocaine intake in male rhesus monkeys.

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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.

[Sucrose reward promotes rats' motivation for cocaine].

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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.

Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification.

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Vernon, Margaret K; Reinders, Stefan; Mannix, Sally; Gullo, Kristen; Gorodetzky, Charles W; Clinch, Thomas

2016-09-01

The Short Opiate Withdrawal Scale (SOWS)-Gossop is a 10-item questionnaire developed to evaluate opioid withdrawal symptom severity. The scale was derived from the original 32-item Opiate Withdrawal Scale in order to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The objective of this study was to examine the psychometric properties and provide score interpretation guidelines for the SOWS-Gossop 10-item version. Blinded, pooled data from two trials assessing the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid detoxification were used to evaluate the quantitative psychometric properties and score interpretation of the SOWS-Gossop. Five hundred fifty-five (N=555) observations were available at baseline with numbers decreasing to n=213 at day 7. Mean (standard deviation) SOWS-Gossop scores were 10.4 (6.86) at baseline, 8.7 (6.49) on day 1, 10.5 (7.21) on day 2, and 3.1 (3.95) on day 7. Confirmatory factor analysis indicated that the SOWS-Gossop items loaded on a single factor consistent with a single total score. Intra-class correlations (95% confidence interval) were 0.78 (0.70-0.85) between baseline and day 1, 0.84 (0.79-0.89) between days 4 and 5, and 0.88 (0.83-0.91) between days 6 and 7, demonstrating good test-retest reliability. Mean SOWS-Gossop scores varied significantly (popioid withdrawal and has excellent psychometric properties. The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. Copyright © 2016 Elsevier Ltd. All rights reserved.

A cocaine-associated quadriplegia and motor aphasia after first use of cocaine.

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Sein Anand, Jacek; Chodorowski, Zygmunt; Wiśniewski, Marek; Gólska, Agnieszka

2007-01-01

A 31-year-old female who have snorted one "line" of cocaine hydrochloride (approximately 35 mg), for the first time in her life, was admitted to the hospital because of acute onset of right hemiplegia and left hemiparesis evolving into quadriplegia. Motor aphasia, right eye-ball divergent strabismus and right mouth recess lowering were also observed. A first time mucosal administration of cocaine hydrochloride even in low dose can cause severe neurological complications like quadriplegia and aphasia. Cocaine-associated stroke can be a diagnostic problem in the emergency room. Unconscious patients or those with acute onset of neurological disorders can form a real diagnostic challenge, especially when there is no evidence of previous drug taking.

The association between social anhedonia, withdrawal and psychotic experiences in general and high-risk populations

NARCIS (Netherlands)

Velthorst, Eva; Meijer, Carin; Kahn, René S.; Linszen, Don H.; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Krabbendam, Lydia; Myin-Germeys, Inez

2012-01-01

Background: Social anhedonia (SA) and withdrawal are clinically relevant phenomena in schizophrenia. To examine the nature of the overlap between SA, withdrawal and positive symptoms, we investigated whether the co-occurrence of these phenotypes is more prominent in siblings of patients with a

Development of a translational model to screen medications for cocaine use disorder I: Choice between cocaine and food in rhesus monkeys.

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Johnson, Amy R; Banks, Matthew L; Blough, Bruce E; Lile, Joshua A; Nicholson, Katherine L; Negus, S Stevens

2016-08-01

Homologous cocaine self-administration procedures in laboratory animals and humans may facilitate translational research for medications development to treat cocaine dependence. This study, therefore, sought to establish choice between cocaine and an alternative reinforcer in rhesus monkeys responding under a procedure back-translated from previous human studies and homologous to a human laboratory procedure described in a companion paper. Four rhesus monkeys with chronic indwelling intravenous catheters had access to cocaine injections (0, 0.043, 0.14, or 0.43mg/kg/injection) and food (0, 1, 3, or 10 1g banana-flavored food pellets). During daily 5h sessions, a single cocaine dose and a single food-reinforcer magnitude were available in 10 30-min trials. During the initial "sample" trial, the available cocaine and food reinforcer were delivered non-contingently. During each of the subsequent nine "choice" trials, responding could produce either the cocaine or food reinforcer under an independent concurrent progressive-ratio schedule. Preference was governed by the cocaine dose and food-reinforcer magnitude, and increasing cocaine doses produced dose-dependent increases in cocaine choice at all food-reinforcer magnitudes. Effects of the candidate medication lisdexamfetamine (0.32-3.2mg/kg/day) were then examined on choice between 0.14mg/kg/injection cocaine and 10 pellets. Under baseline conditions, this reinforcer pair maintained an average of approximately 6 cocaine and 3 food choices. Lisdexamfetamine dose-dependently decreased cocaine choice in all monkeys, but food choice was not significantly altered. These results support utility of this procedure in rhesus monkeys as one component of a platform for translational research on medications development to treat cocaine use disorder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Opium tincture versus methadone syrup in management of acute raw opium withdrawal: A randomized, double-blind, controlled trial.

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Tabassomi, Farzaneh; Zarghami, Mehran; Shiran, Mohammad-Reza; Farnia, Samaneh; Davoodi, Mohsen

2016-01-01

The aim of this study was to evaluate the effectiveness of opium tincture versus methadone syrup in the management of acute withdrawal syndrome in opium dependent patients during the detoxification period. In this double-blind randomized controlled study, a total of 74 adult male raw opium dependent patients were treated with opium tincture or methadone syrup 2 times daily for 5 consecutive days. Detoxification was initiated by tapered dose reductions to reach abstinence. At the end of the 10th day, the medications were discontinued. The Objective Opioid Withdrawal Scale was used to assess withdrawal symptoms every day. Significant decreases on the Objective Opioid Withdrawal Scale were found for both treatment methods during the study period (p Opium tincture can be considered as a potential substitute for methadone syrup for suppression of raw opium withdrawal symptoms, with minimal adverse effects.

Efficacy of Tramadol Extended-Release for Opioid Withdrawal: A Randomized Clinical Trial.

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Dunn, Kelly E; Tompkins, D Andrew; Bigelow, George E; Strain, Eric C

2017-09-01

Opioid use disorder (OUD) is a significant public health problem. Supervised withdrawal (ie, detoxification) from opioids using clonidine or buprenorphine hydrochloride is a widely used treatment. To evaluate whether tramadol hydrochloride extended-release (ER), an approved analgesic with opioid and nonopioid mechanisms of action and low abuse potential, is effective for use in supervised withdrawal settings. A randomized clinical trial was conducted in a residential research setting with 103 participants with OUD. Participants' treatment was stabilized with morphine, 30 mg, administered subcutaneously 4 times daily. A 7-day taper using clonidine (n = 36), tramadol ER (n = 36), or buprenorphine (n = 31) was then instituted, and patients were crossed-over to double-blind placebo during a post-taper period. The study was conducted from October 25, 2010, to June 23, 2015. Retention, withdrawal symptom management, concomitant medication utilization, and naltrexone induction. Results were analyzed over time and using area under the curve for the intention-to-treat and completer groups. Of the 103 participants, 88 (85.4%) were men and 43 (41.7%) were white; mean (SD) age was 28.9 (10.4) years. Buprenorphine participants (28 [90.3%]) were significantly more likely to be retained at the end of the taper compared with clonidine participants (22 [61.1%]); tramadol ER retention was intermediate and did not differ significantly from that of the other groups (26 [72.2%]; χ2 = 8.5, P = .01). Time-course analyses of withdrawal revealed significant effects of phase (taper, post taper) for the Clinical Opiate Withdrawal Scale (COWS) score (taper mean, 5.19 [SE, .26]; post-taper mean, 3.97 [SE, .23]; F2,170 = 3.6, P = .03) and Subjective Opiate Withdrawal Scale (SOWS) score (taper mean,8.81 [SE, .40]; post-taper mean, 4.14 [SE, .30]; F2,170 = 15.7, P withdrawal severity between the taper and post-taper periods for clonidine (taper mean, 13.1; post

MDMA reinstates cocaine-seeking behaviour in mice.

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

2009-06-01

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

Combining the audit questionnaire and biochemical markers to assess alcohol use and risk of alcohol withdrawal in medical inpatients.

Science.gov (United States)

Dolman, Jonathan M; Hawkes, Neil D

2005-01-01

Alcohol consumption is often under-reported in patients admitted to general hospitals with acute illness. For alcohol-dependent individuals hospital admission results in an enforced period of abstinence with potential alcohol withdrawal symptoms, and possible life threatening complications. Early detection of alcohol use is therefore beneficial to patients and health services. The purpose of this study was to investigate the performance of the alcohol use disorders identification test (AUDIT) questionnaire in the acute medical setting, and the effect of combining routine biological markers-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and mean corpuscular volume (MCV) on its performance in the early identification of in-patients with alcohol use disorders and at risk of developing symptoms of alcohol withdrawal. Prospective study in consecutive patients admitted to an acute medical admissions ward. All patients were screened using the AUDIT questionnaire and routine blood tests. Patients were then monitored for symptoms of withdrawal using clinical institute withdrawal assessment for alcohol (CIWA-Ar). Of the 874 patients screened using the AUDIT, 98 (11%) screened positive of whom 17 (2% of the 874) experienced clinically significant alcohol withdrawal symptoms, when using serial CIWA-Ar. The AUDIT and serial CIWA-Ar detected all patients who went on to manifest acute withdrawal symptoms. There was no loss of sensitivity at an AUDIT cut-off of 13 or more compared with the lower cut-off of 8 or more. A positive predictive value of 17.3% for an AUDIT score of 8 or more in the detection of withdrawal, increased to 47.1% when found in combination with at least two abnormal biological markers whilst maintaining a sensitivity of 94.1% and specificity of 97.9%. These findings confirm that AUDIT is a useful alcohol screen in general medical settings and that its ability to correctly predict which patients will experience alcohol withdrawal is

Cerebral vasculitis associated with cocaine abuse

International Nuclear Information System (INIS)

Kaye, B.R.; Fainstat, M.

1987-01-01

A case of cerebral vasculitis in a previously healthy 22-year-old man with a history of cocaine abuse is described. Cerebral angiograms showed evidence of vasculitis. A search for possible causes other than cocaine produced no results. The authors include cocaine with methamphetamines, heroin, and ephedrine as illicit drugs that can cause cerebral vasculitis

Cocaine

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

A Longitudinal Rejection Sensitivity Model of Depression and Aggression: Unique Roles of Anxiety, Anger, Blame, Withdrawal and Retribution.

Science.gov (United States)

Zimmer-Gembeck, Melanie J; Nesdale, Drew; Webb, Haley J; Khatibi, Mhasa; Downey, Geraldine

2016-10-01

In this longitudinal study, attributional and social processes involved in symptoms of mental health problems (depressive symptoms and aggressive behavior) were identified by investigating anxious and angry rejection sensitivity (RS), causal attributions of self-blame and peer-blame, and responses to rejection threat of withdrawal and retribution. Young adolescents (N = 713, grades 5-7) completed questionnaires three times in their regular classrooms over 14 months. Participants who reported more self-blame for rejection were more likely to withdraw in response to rejection threat, and withdrawal and anxious RS were associated with increased depressive symptoms at T3 relative to T1. In contrast, adolescents higher in the angry form of RS and who reported more peer-blame for rejection were more likely to seek retribution, which in turn was associated with more overt/relational aggressive behavior at T3 relative to T1. Depressive symptom level measured at T1 also was associated with later RS and coping with withdrawal, and aggressive behavior at T1 was associated with later retribution. Sex of the participants did not moderate any longitudinal associations, and only one prospective path, from T1 depressive symptoms to T2 RS anxious, was moderated by age.

Malignant hypertension-associated thrombotic microangiopathy following cocaine use.

Science.gov (United States)

Lamia, Rais; El Ati, Zohra; Ben Fatma, Lilia; Zouaghi, Karim; Smaoui, Wided; Rania, Khedher; Krid, Madiha; Ben Hmida, Fathi; Béji, Soumaya; Ben Moussa, Fatma

2016-01-01

Cocaine is one of the most commonly used illicit drugs with distribution and consumption throughout the world. Acute renal failure associated with rhabdomyolysis, direct vasoconstriction and hemodynamic alteration is well described in patients with cocaine intoxication. Cocaine use is associated with high blood pressure and may rarely induce malignant hypertension associated with thrombotic microangiopathy. We report the case of a patient who developed malignant hypertension associated with thrombotic microangiopathy after chronic consumption of cocaine. A kidney biopsy revealed thrombotic microangiopathy with fibrinoid necrosis of arterioles and glomerular tufts. He required dialysis sessions. Cocaine-mediated endothelial injury and platelet activation may play important pathogenetic roles in cocaine abusers who develop malignant hypertension associated with thrombotic microangiopathy. Clinicians need to be aware of this rare feature of cocaine intoxication.

Cannabis, Cocaine and Jobs

NARCIS (Netherlands)

van Ours, J.C.

2005-01-01

This paper uses a dataset collected among inhabitants of Amsterdam, to study the employment effects of the use of cannabis and cocaine.For females no negative effects of drug use on the employment rate are found.For males there is a negative correlation between past cannabis and cocaine use and

Sex differences in psychiatric comorbidity and plasma biomarkers for cocaine addiction in abstinent cocaine-addicted subjects in outpatient settings

Directory of Open Access Journals (Sweden)

MARIA ePEDRAZ

2015-02-01

Full Text Available 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.The results showed that the chemokine concentrations of CCL2/MCP-1 and CXCL12/SDF-1 were only affected by history of cocaine addiction. The plasma concentrations of IL-1β, IL-6, IL-10 and TNFα were higher in control women relative to men, but these concentrations were reduced in cocaine-addicted women. Cytokine concentrations were unaltered 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, POEA was only increased in cocaine-addicted women.Regarding psychiatric comorbidity in the cocaine group, women had lower incidence rates of comorbid substance use disorders than did men. For example, alcohol use disorders were found in 80% of men and 40% of women. In contrast, the addicted women had increased prevalences of comorbid psychiatric disorders (mood, anxiety and psychosis disorders.These results demonstrate the existence of a sex influence on plasma biomarkers for cocaine addiction and on the presence of

Efficacy of an Adenovirus-based Anti-cocaine Vaccine to Reduce Cocaine Self-administration and Reacqusition using a Choice Procedure in Rhesus Macaques

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Evans, Suzette M.; Foltin, Richard W.; Hicks, Martin J.; Rosenberg, Jonathan B.; De, Bishnu P.; Janda, Kim D.; Kaminsky, Stephen M.; Crystal, Ronald G.

2016-01-01

Immunopharmacotherapy offers an approach for treating cocaine abuse by specifically targeting the cocaine molecule and preventing its access to the CNS. dAd5GNE is a novel cocaine vaccine that attenuates the stimulant and the reinforcing effects of cocaine in rats. The goal of this study was to extend and validate dAd5GNE vaccine efficacy in non-human primates. Six experimentally naïve adult female rhesus monkeys (Macaca mulatta) were trained to self-administer 0.1 mg/kg/injection intravenous (i.v.) cocaine or receive candy; then 4 monkeys were administered the vaccine and 2 monkeys were administered vehicle intramuscularly, with additional vaccine boosts throughout the study. The reinforcing effects of cocaine were measured during self-administration, extinction, and reacquisition (relapse) phases. Serum antibody titers in the vaccinated monkeys remained high throughout the study. There was no change in the preference for cocaine over candy over a 20-week period in 5 of the 6 monkeys; only one of the 4 (25%) vaccinated monkeys showed a decrease in cocaine choice. All 6 monkeys extinguished responding for cocaine during saline extinction testing; vaccinated monkeys tended to take longer to extinguish responding than control monkeys (17.5 vs. 7.0 sessions). Vaccination substantially retarded reacquisition of cocaine self-administration; control monkeys resumed cocaine self-administration within 6–41 sessions and 1 vaccinated monkey resumed cocaine self-administration in 19 sessions. The other 3 vaccinated monkeys required between 57–94 sessions to resume cocaine self-administration even in the context of employing several manipulations to encourage cocaine reacquisition. These data suggest that the dAdGNE vaccine may have therapeutic potential for humans who achieve cocaine abstinence as part of a relapse prevention strategy. PMID:27697554

Pyrolysis and volatilization of cocaine

International Nuclear Information System (INIS)

Martin, B.R.; Lue, L.P.; Boni, J.P.

1989-01-01

The increasing popularity of inhaling cocaine vapor prompted the present study, to determine cocaine's fate during this process. The free base of [3H]cocaine (1 microCi/50 mg) was added to a glass pipe, which was then heated in a furnace to simulate freebasing. Negative pressure was used to draw the vapor through a series of glass wool, ethanol, acidic, and basic traps. Air flow rate and temperature were found to have profound effects on the volatilization and pyrolysis of cocaine. At a temperature of 260 degrees C and a flow rate of 400 mL/min, 37% of the radioactivity remained in the pipe, 39% was found in the glass wool trap, and less than 1% in the remainder of the volatilization apparatus after a 10-min volatilization. Reducing the air flow rate to 100 mL/min reduced the amount of radioactivity collected in the glass wool trap to less than 10% of the starting material and increased the amount that remained in the pipe to 58%. GC/MS analysis of the contents of the glass wool trap after volatilization at 260 degrees C and a flow rate of 400 mL/min revealed that 60% of the cocaine remained intact, while approximately 6 and 2% of the starting material was recovered as benzoic acid and methylecgonidine, respectively. As the temperature was increased to 650 degrees C, benzoic acid and methylecgonidine accounted for 83 and 89% of the starting material, respectively, whereas only 2% of the cocaine remained intact. Quantitation of cocaine in the vapor during the course of volatilization revealed high concentrations during the first two min and low concentrations for the remaining time

[Sigmund Freud and cocaine].

Science.gov (United States)

Lebzeltern, G

1983-11-11

The basic tenet proposed by J. V. Scheidt states that the narcotic drug, cocaine played a role in the development of psychoanalysis which has been underestimated up to the present day. It is a fact that Freud himself took cocaine (in small doses) for about two years, and that he began his dream interpretation approximately ten years later. Scheidt believes that a long, unconscious conflict related to the cocaine-induced states of euphoria (ten years later) suddenly led to the beginnings of dream interpretation. The question to be answered now is: Why did this happen precisely in 1895? The foundations of psychoanalysis had already been laid, the application of the new method to the treatment of nervous disorders (heart complaints, train phobias, etc.) was certainly obvious. During this self-analysis it became necessary, first of all, to come to terms with the self-reproaches-which lay on the surface and were more accessible to consciousness-related to Freud's cocaine period (Fleischl-Marxow becomes addicted to cocaine, the most terrible night ever experienced, death of this friend, Freud's warning came too late). It was only when Freud has come to terms with this phase of his life that the road to the deepest part, the discovery of the Oedipus complex in the fall of 1897, was cleared.

Bioavailability and Pharmacokinetics of Oral Cocaine in Humans.

Science.gov (United States)

Coe, Marion A; Jufer Phipps, Rebecca A; Cone, Edward J; Walsh, Sharon L

2018-06-01

The pharmacokinetic profile of oral cocaine has not been fully characterized and prospective data on oral bioavailability are limited. A within-subject study was performed to characterize the bioavailability and pharmacokinetics of oral cocaine. Fourteen healthy inpatient participants (six males) with current histories of cocaine use were administered two oral doses (100 and 200 mg) and one intravenous (IV) dose (40 mg) of cocaine during three separate dosing sessions. Plasma samples were collected for up to 24 h after dosing and analyzed for cocaine and metabolites by gas chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by non-compartmental analysis, and a two-factor model was used to assess for dose and sex differences. The mean ± SEM oral cocaine bioavailability was 0.32 ± 0.04 after 100 and 0.45 ± 0.06 after 200 mg oral cocaine. Volume of distribution (Vd) and clearance (CL) were both greatest after 100 mg oral (Vd = 4.2 L/kg; CL = 116.2 mL/[min kg]) compared to 200 mg oral (Vd = 2.9 L/kg; CL = 87.5 mL/[min kg]) and 40 mg IV (Vd = 1.3 L/kg; CL = 32.7 mL/[min kg]). Oral cocaine area-under-thecurve (AUC) and peak concentration increased in a dose-related manner. AUC metabolite-to-parent ratios of benzoylecgonine and ecgonine methyl ester were significantly higher after oral compared to IV administration and highest after the lower oral dose. In addition, minor metabolites were detected in higher concentrations after oral compared to IV cocaine. Oral cocaine produced a pharmacokinetic profile different from IV cocaine, which appears as a rightward and downward shift in the concentration-time profile. Cocaine bioavailability values were similar to previous estimates. Oral cocaine also produced a unique metabolic profile, with greater concentrations of major and minor metabolites.

SAJCH 734.indd

African Journals Online (AJOL)

alcohol (51%), cannabis (21%), cocaine (9.6%), heroin/ opiates (7.9%) ... to contain a combination of heroin, morphine, methamphetamine, ... NAS is a combination of signs and symptoms of withdrawal in a newborn as a ... Baby A was a term female infant with a birth weight of 2 165 g and ... On further history taken from the.

Effect of GABA agonists and GABA-A receptor modulators on cocaine- and food-maintained responding and cocaine discrimination in rats.

Science.gov (United States)

Barrett, Andrew C; Negus, S Stevens; Mello, Nancy K; Caine, S Barak

2005-11-01

Recent studies indicate that GABAergic ligands modulate abuse-related effects of cocaine. The goal of this study was to evaluate the effects of a mechanistically diverse group of GABAergic ligands on the discriminative stimulus and reinforcing effects of cocaine in rats. One group of rats was trained to discriminate 5.6 mg/kg cocaine from saline in a two-lever, food-reinforced, drug discrimination procedure. In two other groups, responding was maintained by cocaine (0-3.2 mg/kg/injection) or liquid food (0-100%) under a fixed ratio 5 schedule. Six GABA agonists were tested: the GABA-A receptor agonist muscimol, the GABA-B receptor agonist baclofen, the GABA transaminase inhibitor gamma-vinyl-GABA (GVG), and three GABA-A receptor modulators (the barbiturate pentobarbital, the high-efficacy benzodiazepine midazolam, and the low-efficacy benzodiazepine enazenil). When tested alone, none of the compounds substituted fully for the discriminative stimulus effects of cocaine. As acute pretreatments, select doses of midazolam and pentobarbital produced 2.2- to 3.6-fold rightward shifts in the cocaine dose-effect function. In contrast, muscimol, baclofen, GVG, and enazenil failed to alter the discriminative stimulus effects of cocaine. In assays of cocaine- and food-maintained responding, midazolam and pentobarbital decreased cocaine self-administration at doses 9.6- and 3.3-fold lower, respectively, than those that decreased food-maintained responding. In contrast, muscimol, baclofen, and GVG decreased cocaine self-administration at doses that also decreased food-maintained responding. Enazenil failed to alter cocaine self-administration. Together with previous studies, these data suggest that among mechanistically diverse GABA agonists, high-efficacy GABA-A modulators may be the most effective for modifying the abuse-related effects of cocaine.

Cocaine-induced cardiovascular effects: lack of evidence for a central nervous system site of action based on hemodynamic studies with cocaine methiodide.

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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.

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction.

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Kutlu, Munir Gunes; Gould, Thomas J

2016-10-01

It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawal-induced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates. © 2016 Kutlu and Gould; Published by Cold Spring Harbor Laboratory Press.

Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study.

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Rosenson, Jonathan; Clements, Carter; Simon, Barry; Vieaux, Jules; Graffman, Sarah; Vahidnia, Farnaz; Cisse, Bitou; Lam, Joseph; Alter, Harrison

2013-03-01

Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management. We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal. This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward). There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4-32). There were no differences in adverse events. A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

Cocaine and Pavlovian fear conditioning: dose-effect analysis.

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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.

Drug smuggling using clothing impregnated with cocaine.

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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.

A Phase 3 Placebo-Controlled, Double Blind, Multi-Site Trial of the alpha-2-adrenergic Agonist, Lofexidine, for Opioid Withdrawal

Science.gov (United States)

Yu, Elmer; Miotto, Karen; Akerele, Evaristo; Montgomery, Ann; Elkashef, Ahmed; Walsh, Robert; Montoya, Ivan; Fischman, Marian W.; Collins, Joseph; McSherry, Frances; Boardman, Kathy; Davies, David K.; O’Brien, Charles P.; Ling, Walter; Kleber, Herbert; Herman, Barbara H.

2008-01-01

Context Lofexidine is an alpha-2-A noradrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine. Objective To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally-defined opioid withdrawal symptoms in opioid dependent individuals undergoing medically supervised opioid detoxification as compared to placebo. Design An inpatient, Phase 3, placebo-controlled, double blind, randomized multi-site trial with three phases: (1) Opioid Agonist Stabilization Phase (days 1–3), (2) Detoxification/Medication or Placebo Phase (days 4–8), and (3) Post Detoxification/Medication Phase (days 9–11). Subjects Sixty-eight opioid dependent subjects were enrolled at three sites with 35 randomized to lofexidine and 33 to placebo. Main Outcome Measure Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study day 5 (2nd opioid detoxification treatment day). Results Due to significant findings, the study was terminated early. On the study day 5 MHOWS, subjects treated with lofexidine had significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (Least squares means 19.5 ± 2.1 versus 30.9 ± 2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01). Conclusions Lofexidine is well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification. Trial Registration trial registry name A Phase 3 Placebo-Controlled, Double-Blind Multi-Site Trial of Lofexidine for Opiate Withdrawal, registration number NCT00032942, URL for the registry http://clinicaltrials.gov/ct/show/NCT00032942?order=4. PMID:18508207

Cannabis withdrawal in chronic, frequent cannabis smokers during sustained abstinence within a closed residential environment.

Science.gov (United States)

Lee, Dayong; Schroeder, Jennifer R; Karschner, Erin L; Goodwin, Robert S; Hirvonen, Jussi; Gorelick, David A; Huestis, Marilyn A

2014-01-01

Chronic, frequent cannabis smokers may experience residual and offset effects, withdrawal, and craving when abstaining from the drug. We characterized the prevalence, duration, and intensity of these effects in chronic frequent cannabis smokers during abstinence on a closed research unit. Non-treatment-seeking participants (N = 29 on admission, 66% and 34% remaining after 2 and 4 weeks) provided subjective effects data. A battery of five instruments was computer-administered daily to measure psychological, sensory, and physical symptoms associated with cannabinoid intoxication and withdrawal. Plasma and oral fluid specimens were concurrently collected and analyzed for cannabinoids. Outcome variables were evaluated as change from admission (Day 0) with regression models. Most abstinence effects, including irritability and anxiety were greatest on Days 0-3 and decreased thereafter. Cannabis craving significantly decreased over time, whereas decreased appetite began to normalize on Day 4. Strange dreams and difficulty getting to sleep increased over time, suggesting intrinsic sleep problems in chronic cannabis smokers. Symptoms likely induced by residual drug effects were at maximum intensity on admission and positively correlated with plasma and oral fluid cannabinoid concentrations on admission but not afterward; these symptoms showed overall prevalence higher than cannabis withdrawal symptoms. The combined influence of residual/offset drug effects, withdrawal, and craving was observed in chronic cannabis smokers during monitored abstinence. Abstinence symptoms were generally more intense in the initial phase, implying importance of early intervention in cannabis quit attempts. Sleep disturbance persisting for an extended period suggests that hypnotic medications could be beneficial in treating cannabis dependence. © American Academy of Addiction Psychiatry.

Tolerance and withdrawal from prolonged opioid use in critically ill children.

Science.gov (United States)

Anand, Kanwaljeet J S; Willson, Douglas F; Berger, John; Harrison, Rick; Meert, Kathleen L; Zimmerman, Jerry; Carcillo, Joseph; Newth, Christopher J L; Prodhan, Parthak; Dean, J Michael; Nicholson, Carol

2010-05-01

After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. Relevant manuscripts published in the English language were searched in Medline by using search terms "opioid," "opiate," "sedation," "analgesia," "child," "infant-newborn," "tolerance," "dependency," "withdrawal," "analgesic," "receptor," and "individual opioid drugs." Clinical and preclinical studies were reviewed for data synthesis. Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal.

Hypocretin 1/orexin A in the ventral tegmental area enhances dopamine responses to cocaine and promotes cocaine self-administration.

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España, Rodrigo A; Melchior, James R; Roberts, David C S; Jones, Sara R

2011-03-01

Recent evidence indicates that the hypocretin/orexin system participates in the regulation of reinforcement and addiction processes. For example, manipulations that decrease hypocretin neurotransmission result in disruptions of neurochemical and behavioral responses to cocaine. To further assess the relationship between the hypocretin system and cocaine reinforcement, the current studies used microdialysis and in vivo voltammetry to examine the effects of hypocretin 1 on cocaine-induced enhancement of dopamine signaling in the nucleus accumbens core. Fixed ratio, discrete trials, and progressive ratio self-administration procedures were also used to assess whether hypocretin 1 promotes cocaine self-administration behavior. Infusions of hypocretin 1 into the ventral tegmental area increased the effects of cocaine on tonic and phasic dopamine signaling and increased the motivation to self-administer cocaine on the discrete trials and progressive ratio schedules. Together with previous observations demonstrating that a hypocretin 1 receptor antagonist disrupts dopamine signaling and reduces self-administration of cocaine, the current observations further indicate that the hypocretin system participates in reinforcement processes likely through modulation of the mesolimbic dopamine system.

Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans

Science.gov (United States)

Lile, Joshua A.; Stoops, William W.; Rush, Craig R.; Negus, S. Stevens; Glaser, Paul E. A.; Hatton, Kevin W.; Hays, Lon R.

2016-01-01

Background A medication for treating cocaine use disorder has yet to be approved. Laboratory-based evaluation of candidate medications in animals and humans is a valuable means to demonstrate safety, tolerability and initial efficacy of potential medications. However, animal-to-human translation has been hampered by a lack of coordination. Therefore, we designed homologous cocaine self-administration studies in rhesus monkeys (see companion article) and human subjects in an attempt to develop linked, functionally equivalent procedures for research on candidate medications for cocaine use disorder. Methods Eight (N=8) subjects with cocaine use disorder completed 12 experimental sessions in which they responded to receive money ($0.01, $1.00 and $3.00) or intravenous cocaine (0, 3, 10 and 30 mg/70 kg) under independent, concurrent progressive-ratio schedules. Prior to the completion of 9 choice trials, subjects sampled the cocaine dose available during that session and were informed of the monetary alternative value. Results The allocation of behavior varied systematically as a function of cocaine dose and money value. Moreover, a similar pattern of cocaine choice was demonstrated in rhesus monkeys and humans across different cocaine doses and magnitudes of the species-specific alternative reinforcers. The subjective and cardiovascular responses to IV cocaine were an orderly function of dose, although heart rate and blood pressure remained within safe limits. Conclusions These coordinated studies successfully established drug vs. non-drug choice procedures in humans and rhesus monkeys that yielded similar cocaine choice behavior across species. This translational research platform will be used in future research to enhance the efficiency of developing interventions to reduce cocaine use. PMID:27269368

Cocaine

Science.gov (United States)

... different competition is going on: the National Football League (NFL) vs. drug use. Read More » 92 Comments ... opioid abuse, cigarette and alcohol use among the nation’s youth. View Online Dirty Money and Cocaine Published: ...

Opponent process properties of self-administered cocaine.

Science.gov (United States)

Ettenberg, Aaron

2004-01-01

Over the past decade, data collected in our laboratory have demonstrated that self-administered cocaine produces Opponent-Process-like behavioral effects. Animals running a straight alley once each day for IV cocaine develop over trials an approach-avoidance conflict about re-entering the goal box. This conflict behavior is characterized by a stop in forward locomotion (usually at the very mouth of the goal box) followed by a turn and 'retreat' back toward the goal box. The results of a series of studies conducted over the past decade collectively suggest that the behavioral ambivalence exemplified by rats running the alley for IV cocaine stems from concurrent and opponent positive (rewarding) and negative (anxiogenic) properties of the drug--both of which are associated with the goal box. These opponent properties of cocaine have been shown to result from temporally distinct affective states. Using a conditioned place preference test, we have been able to demonstrate that while the initial immediate effects of IV cocaine are reinforcing, the state present 15 min post-injection is aversive. In our most recent work, the co-administration of IV cocaine with either oral ethanol or IV heroin was found to greatly diminish the development and occurrence of retreat behaviors in the runway. It may therefore be that the high incidence of co-abuse of cocaine with either ethanol or heroin, stems from the users' motivation to alleviate some of the negative side effects of cocaine. It would seem then that the Opponent Process Theory has provided a useful conceptual framework for the study of the behavioral consequences of self-administered cocaine including the notion that both positive and negative reinforcement mechanisms are involved in the development and maintenance of cocaine abuse.

Differentiating Delirium From Sedative/Hypnotic-Related Iatrogenic Withdrawal Syndrome: Lack of Specificity in Pediatric Critical Care Assessment Tools.

Science.gov (United States)

Madden, Kate; Burns, Michele M; Tasker, Robert C

2017-06-01

To identify available assessment tools for sedative/hypnotic iatrogenic withdrawal syndrome and delirium in PICU patients, the evidence supporting their use, and describe areas of overlap between the components of these tools and the symptoms of anticholinergic burden in children. Studies were identified using PubMed and EMBASE from the earliest available date until July 3, 2016, using a combination of MeSH terms "delirium," "substance withdrawal syndrome," and key words "opioids," "benzodiazepines," "critical illness," "ICU," and "intensive care." Review article references were also searched. Human studies reporting assessment of delirium or iatrogenic withdrawal syndrome in children 0-18 years undergoing critical care. Non-English language, exclusively adult, and neonatal intensive care studies were excluded. References cataloged by study type, population, and screening process. Iatrogenic withdrawal syndrome and delirium are both prevalent in the PICU population. Commonly used scales for delirium and iatrogenic withdrawal syndrome assess signs and symptoms in the motor, behavior, and state domains, and exhibit considerable overlap. In addition, signs and symptoms of an anticholinergic toxidrome (a risk associated with some common PICU medications) overlap with components of these scales, specifically in motor, cardiovascular, and psychiatric domains. Although important studies have demonstrated apparent high prevalence of iatrogenic withdrawal syndrome and delirium in the PICU population, the overlap in these scoring systems presents potential difficulty in distinguishing syndromes, both clinically and for research purposes.

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 CRF 1 receptor-deficient (CRF 1 -/-), 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 CRF 1 -/-, mice display CPP responses to a relatively high cocaine dose (20 mg/kg, i.p.), indicating that CRF 1 receptor-deficiency alters the rewarding effects of cocaine. Acute pharmacological antagonism of the CRF 1 receptor by antalarmin also eliminates cocaine reward. Nevertheless, CRF 1 -/- mice display higher stereotypy responses to cocaine than wild-type mice. Despite the very low plasma corticosterone concentration, CRF 1 -/- 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 CRF 1 -/- mice by exogenous corticosterone does not affect CRF 1 receptor-dependent cocaine reward but induces stereotypy responses to cocaine. These results indicate a critical role for the CRF 1 receptor in cocaine reward, independently of the closely related HPA axis activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cocaine addiction: the hidden dimension.

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Oswald, L M

1989-06-01

There is growing awareness within the nursing profession that nurses need to expand their knowledge about addiction and develop expertise in providing care for substance abusing clients. This report presents a discussion about cocaine abuse that is focused on evolving knowledge about the physiology of addiction. Researchers have recently described cocaine-induced neurochemical changes in the brain that may form the underpinnings for the behavioral manifestations and symptomatology that have been associated with cocaine addiction. These neurochemical alterations are described at the cellular level, and treatment implications for nurses are presented.

Dopaminergic sensitivity and cocaine abuse: response to apomorphine.

Science.gov (United States)

Hollander, E; Nunes, E; DeCaria, C M; Quitkin, F M; Cooper, T; Wager, S; Klein, D F

1990-08-01

Ten male patients with chronic cocaine abuse received a single dose of the dopamine agonist apomorphine. Self-ratings of cocaine craving, depression, and anxiety decreased in response to apomorphine. Neuroendocrine response was consistent with central dopaminergic stimulation. Patients in the "craving" phase of the cocaine abuse cycle differed in behavioral but not neuroendocrine response to apomorphine from patients in the "crash" phase. Decrease in cocaine craving correlated with decrease in plasma homovanillic acid (pHVA). Total cocaine consumption correlated negatively with baseline prolactin and pHVA levels and inversely with peak change in prolactin following apomorphine. Patients had blunted neuroendocrine response to apomorphine in comparison to historical normal controls. Implications for the "dopamine" hypothesis of cocaine abuse are discussed.

Cocaine use in nightlife in Slovenia and Italy

OpenAIRE

Sande, Matej; Purkart, Barbara

2011-01-01

According to the 2010 annual report on the state of the drugs problem in Europe published by the EMCDDA, seizures of cocaine as well as cocaine use in Europe have increased in the last decade. Cocaine is the second most commonly used illicit drug in Europe after marijuana (EMCDDA, 2010). Due to its growing popularity and decreasing price, traditional perceptions about cocaine users and the ways in which it is consumed no longer hold true. It is no longer the case that cocaine u...

Differential vulnerability to the punishment of cocaine related behaviours: effects of locus of punishment, cocaine taking history and alternative reinforcer availability.

Science.gov (United States)

Pelloux, Yann; Murray, Jennifer E; Everitt, Barry J

2015-01-01

The availability of alternative reinforcement has been shown to reduce drug use, but it remains unclear whether it facilitates a reduction or cessation of drug seeking or taking. We compared the effects of punishment of cocaine seeking or taking behaviour after brief or extended cocaine-taking histories when behavioural reallocation was facilitated or not by making available an alternative ingestive reinforcer (sucrose). In the first experiment, punishment of either seeking or taking responses was introduced immediately after training on the seeking-taking chained schedule. In the second experiment, punishment of cocaine seeking was introduced after 12 additional days of either 1 or 6 h daily access to cocaine self-administration. In both experiments, beginning 1 week before the introduction of punishment, a subset of rats had concurrent nose poke access to sucrose while seeking or taking cocaine. The presence of an alternative source of reinforcement markedly facilitated behavioural reallocation from punished cocaine taking after acquisition. It also facilitated punishment-induced suppression of cocaine seeking after an extensive cocaine self-administration history likely by prompting goal-directed motivational control over drug use. However, a significant proportion of rats were deemed compulsive-maintaining drug use after an extensive cocaine history despite the presence of abstinence-promoting positive and negative incentives. Making available an alternative reinforcer facilitates disengagement from punished cocaine use through at least two different processes but remains ineffective in a subpopulation of vulnerable animals, which continued to seek cocaine despite the aversive consequence of punishment and the presence of the alternative positive reinforcer.

Rats classified as low or high cocaine locomotor responders: A unique model involving striatal dopamine transporters that predicts cocaine addiction-like behaviors

Science.gov (United States)

Yamamoto, Dorothy J.; Nelson, Anna M.; Mandt, Bruce H.; Larson, Gaynor A.; Rorabaugh, Jacki M.; Ng, Christopher M.C.; Barcomb, Kelsey M.; Richards, Toni L.; Allen, Richard M.; Zahniser, Nancy R.

2013-01-01

Individual differences are a hallmark of drug addiction. Here, we describe a rat model based on differential initial responsiveness to low dose cocaine. Despite similar brain cocaine levels, individual outbred Sprague-Dawley rats exhibit markedly different magnitudes of acute cocaine-induced locomotor activity and, thereby, can be classified as low or high cocaine responders (LCRs or HCRs). LCRs and HCRs differ in drug-induced, but not novelty-associated, hyperactivity. LCRs have higher basal numbers of striatal dopamine transporters (DATs) than HCRs and exhibit marginal cocaine inhibition of in vivo DAT activity and cocaine-induced increases in extracellular DA. Importantly, lower initial cocaine response predicts greater locomotor sensitization, conditioned place preference and greater motivation to self-administer cocaine following low dose acquisition. Further, outbred Long-Evans rats classified as LCRs, versus HCRs, are more sensitive to cocaine’s discriminative stimulus effects. Overall, results to date with the LCR/HCR model underscore the contribution of striatal DATs to individual differences in initial cocaine responsiveness and the value of assessing the influence of initial drug response on subsequent expression of addiction-like behaviors. PMID:23850581

Anticonvulsants for cocaine dependence.

Science.gov (United States)

Minozzi, Silvia; Cinquini, Michela; Amato, Laura; Davoli, Marina; Farrell, Michael F; Pani, Pier Paolo; Vecchi, Simona

2015-04-17

Cocaine dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Although effective pharmacotherapy is available for alcohol and heroin dependence, none is currently available for cocaine dependence, despite two decades of clinical trials primarily involving antidepressant, anticonvulsivant and dopaminergic medications. Extensive consideration has been given to optimal pharmacological approaches to the treatment of individuals with cocaine dependence, and both dopamine antagonists and agonists have been considered. Anticonvulsants have been candidates for use in the treatment of addiction based on the hypothesis that seizure kindling-like mechanisms contribute to addiction. To evaluate the efficacy and safety of anticonvulsants for individuals with cocaine dependence. We searched the Cochrane Drugs and Alcohol Group Trials Register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (1966 to June 2014), EMBASE (1988 to June 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to June 2014), Web of Science (1991 to June 2014) and the reference lists of eligible articles. All randomised controlled trials and controlled clinical trials that focus on the use of anticonvulsant medications to treat individuals with cocaine dependence. We used the standard methodological procedures expected by The Cochrane Collaboration. We included a total of 20 studies with 2068 participants. We studied the anticonvulsant drugs carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate and vigabatrin. All studies compared anticonvulsants versus placebo. Only one study had one arm by which the anticonvulsant was compared with the antidepressant desipramine. Upon comparison of anticonvulsant versus placebo, we found no significant differences for any of the efficacy and safety measures. Dropouts: risk ratio (RR) 0.95, 95

Buprenorphine for managing opioid withdrawal.

Science.gov (United States)

Gowing, Linda; Ali, Robert; White, Jason M; Mbewe, Dalitso

2017-02-21

Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of substitution treatment. To assess the effects of buprenorphine versus tapered doses of methadone, alpha 2 -adrenergic agonists, symptomatic medications or placebo, or different buprenorphine regimens for managing opioid withdrawal, in terms of the intensity of the withdrawal syndrome experienced, duration and completion of treatment, and adverse effects. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 11, 2016), MEDLINE (1946 to December week 1, 2016), Embase (to 22 December 2016), PsycINFO (1806 to December week 3, 2016), and the Web of Science (to 22 December 2016) and handsearched the reference lists of articles. Randomised controlled trials of interventions using buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha 2 -adrenergic agonists (clonidine or lofexidine), symptomatic medications or placebo, and different buprenorphine-based regimens. We used standard methodological procedures expected by Cochrane. We included 27 studies involving 3048 participants. The main comparators were clonidine or lofexidine (14 studies). Six studies compared buprenorphine versus methadone, and seven compared different rates of buprenorphine dose reduction. We assessed 12 studies as being at high risk of bias in at least one of seven domains of methodological quality. Six of these studies compared buprenorphine with clonidine or lofexidine and two with methadone; the other four studies compared different rates of buprenorphine dose reduction.For the comparison of buprenorphine and methadone in tapered doses, meta-analysis was not possible for the outcomes of intensity of withdrawal or adverse effects. However, information reported by the individual studies was suggestive of buprenorphine and methadone having similar capacity to

Intentional intrathecal opioid detoxification in 3 patients: characterization of the intrathecal opioid withdrawal syndrome.

Science.gov (United States)

Jackson, Tracy P; Lonergan, Daniel F; Todd, R David; Martin, Peter R

2013-04-01

Intrathecal (IT) drug delivery systems for patients with chronic non-malignant pain are intended to improve pain and quality of life and reduce side effects of systemic use. A subset of patients may have escalating pain, functional decline, and/or intolerable side effects even as IT opioid doses are increased. Discontinuation of IT medications may represent a viable treatment option but strategies to accomplish this are needed. Three patients with intrathecal drug delivery systems (IDDS), inadequate pain control, and declining functionality underwent abrupt IT opioid cessation. This was accomplished through a standardized protocol with symptom-triggered administration of clonidine and buprenorphine, monitored using the clinical opiate withdrawal scale. Symptoms of IT withdrawal were similar in all patients and included diuresis, agitation, hyperalgesia, mild diarrhea, yawning, and taste and smell aversion. Hypertension and tachycardia were effectively controlled by clonidine administration. Classic symptoms of withdrawal, such as piloerection, chills, severe diarrhea, nausea, vomiting, diaphoresis, myoclonus, and mydriasis, were not noted. At 2 to 3 months follow-up, patients reported decreased, but ongoing pain, with improvements in functional capacity and quality of life. This preliminary work demonstrates the safety of abrupt IT opioid cessation utilizing standardized inpatient withdrawal protocols. To our knowledge, these are among the first reported cases of intentional, controlled IT opioid cessation without initiation of an opioid bridge: self-reported pain scores, functional capacity, and quality of life improved. The IT opioid withdrawal syndrome is characterized based upon our observations and a review of the literature. © 2012 The Authors. Pain Practice © 2012 World Institute of Pain.

Cocaine-Associated Seizures and Incidence of Status Epilepticus

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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.

No evidence that environmental enrichment during rearing protects against cocaine behavioral effects but as an intervention reduces an already established cocaine conditioned place preference.

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Galaj, E; Shukur, A; Manuszak, M; Newman, K; Ranaldi, R

2017-05-01

Environmental enrichment (EE) produces differential effects on psychostimulant-related behaviors. Therefore, we investigated whether the timing of EE exposure - during rearing and before cocaine exposure versus in adulthood and after cocaine exposure might be a determining factor. In Experiment 1, rats reared with EE or not (non-EE) were conditioned with cocaine (5, 10 or 20mg/kg) in one compartment of a CPP apparatus and saline in the other, and later tested for cocaine CPP. In Experiment 2, locomotor activity in response to repeated injections of saline or cocaine was measured in rats raised with EE or non-EE. In Experiment 3 we measured the effects of EE or non-EE during rearing on food-based conditioned approach learning. In Experiment 4, rats were exposed to cocaine CPP conditioning then underwent 60days of EE or non-EE treatment after which they were tested for cocaine CPP. Our results show that rearing in EE did not reduce cocaine CPP or cocaine-induced locomotor activity (Experiments 1 and 2) but significantly facilitated conditioned approach learning (Experiment 3). On the other hand, EE treatment introduced after cocaine conditioning significantly reduced the expression of cocaine CPP (Experiment 4). These findings suggest that EE does not protect against cocaine's rewarding and stimulant effects but can reduce already established cocaine effects, suggesting that EE might be an effective treatment for cocaine addiction-related behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

Early psychosis symptoms

International Nuclear Information System (INIS)

Naqvi, H.A.; Hussain, S.; Islam, M.

2014-01-01

Objective: To determine the prodromal symptoms of schizophrenia in the pathways to help-seeking. Study Design: A cross-sectional study. Place and Duration of Study: The Department of Psychiatry, the Aga Khan University, Karachi, from 2008 to 2009. Methodology: A total of 93 patients were interviewed in the pathways to care of schizophrenia. The diagnosis was based on ICD-10 criteria. The pathways to care were assessed through a semi-structured questionnaire. The onset, course and symptoms of psychosis were assessed through Interview for Retrospective Assessment at Age at Onset of Psychosis (IROAS). Results: Fifty five (59%) participants were male while 41% (n=38%) were female. Using IROAS, 108 symptoms were identified as concerning behaviour. Alternatively, 60 (55%) concerning behaviours were reported in the open-ended inquiry of the reasons for help seeking as assessed by the pathways to care questionnaire with a statistically significant difference between most symptoms category. The difference was most pronounced (p < 0.001) for depressed mood (66%), worries (65%), tension (63%), withdrawal/mistrust (54%) and loss of self-confidence (53%). Thought withdrawal (22%) and passivity (15%) were elicited only through structured interview (IROAS). When symptoms were categorized together, about 83% of the subjects presented with affective and non-specific prodromal symptoms. Roughly, 10% of the subjects presented with positive symptoms and 3% presented with the negative symptoms of psychosis. The non-specific, affective symptoms appear to predominate the prodromal phase of the illness. Conclusion: Prodromal symptoms of schizophrenia include non-specific, affective symptoms. Attention needs to be paid on identifying the prodromal symptoms and change in social functioning in order to identify those who are at risk of long term psychosis. (author)

Cannabis Withdrawal Among Detained Adolescents: Exploring the Impact of Nicotine and Race

OpenAIRE

Soenksen, Shayna; Stein, L.A.R.; Brown, Joanna D.; Stengel, JoAnn R.; Rossi, Joseph S.; Lebeau, Rebecca

2015-01-01

Rates of marijuana use among detained youths are exceptionally high. Research suggests a cannabis withdrawal syndrome is valid and clinically significant; however, these studies have mostly been conducted in highly controlled laboratory settings with treatment-seeking, White adults. The present study analyzed archival data to explore the magnitude of cannabis withdrawal symptoms within a diverse sample of detained adolescents while controlling for tobacco use and investigating the impact of r...

Clinical ratings and plasma HVA during cocaine abstinence.

Science.gov (United States)

Martin, S D; Yeragani, V K; Lodhi, R; Galloway, M P

1989-08-01

Six patients were evaluated over a 21-day period during inpatient recovery from chronic repeated cocaine use. Serial evaluations of Hamilton depression rating, cocaine craving, plasma homovanillic acid (pHVA), and plasma 3-methoxy-4-hydroxyphenylethyleneglycol (pMHPG) concentrations were determined. There was a distinct increase in cocaine craving between 1 and 2 weeks after the last cocaine use. Levels of pHVA also increased at the time of heightened craving. The data provide preliminary evidence to suggest that changes in cocaine craving during abstinence are positively correlated with changes in dopamine turnover.

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

Fetal cocaine exposure: analysis of vernix caseosa.

Science.gov (United States)

Moore, C; Dempsey, D; Deitermann, D; Lewis, D; Leikin, J

1996-10-01

Preliminary data regarding the use of vernix caseosa (VC) as an alternative to other biological specimens for the determination of fetal cocaine exposure are presented. Advantages of VC analysis include its presence on all newborn babies, historical record of drug exposure, and ease of collection and storage. Fifteen samples of vernix caseosa-five from babies known to be cocaine-exposed because of a positive benzoylecgonine result from the urine and umbilical cord blood and ten from nonexposed neonates-were analyzed for the presence of cocaine and metabolites. VC samples from three of the five neonates known to be cocaine-exposed were positive for cocaine or its metabolites, the other two had little or no remaining specimen. The remaining ten were negative.

Phencyclidine-induced social withdrawal results from deficient stimulation of cannabinoid CB₁ receptors: implications for schizophrenia.

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Seillier, Alexandre; Martinez, Alex A; Giuffrida, Andrea

2013-08-01

The neuronal mechanisms underlying social withdrawal, one of the core negative symptoms of schizophrenia, are not well understood. Recent studies suggest an involvement of the endocannabinoid system in the pathophysiology of schizophrenia and, in particular, of negative symptoms. We used biochemical, pharmacological, and behavioral approaches to investigate the role played by the endocannabinoid system in social withdrawal induced by sub-chronic administration of phencyclidine (PCP). Pharmacological enhancement of endocannabinoid levels via systemic administration of URB597, an inhibitor of endocannabinoid degradation, reversed social withdrawal in PCP-treated rats via stimulation of CB1 receptors, but reduced social interaction in control animals through activation of a cannabinoid/vanilloid-sensitive receptor. In addition, the potent CB agonist CP55,940 reversed PCP-induced social withdrawal in a CB₁-dependent manner, whereas pharmacological blockade of CB₁ receptors by either AM251 or SR141716 reduced the time spent in social interaction in control animals. PCP-induced social withdrawal was accompanied by a decrease of anandamide (AEA) levels in the amygdala and prefrontal cortex, and these deficits were reversed by URB597. As CB₁ receptors are predominantly expressed on GABAergic interneurons containing the anxiogenic peptide cholecystokinin (CCK), we also examined whether the PCP-induced social withdrawal resulted from deficient CB₁-mediated modulation of CCK transmission. The selective CCK2 antagonist LY225910 blocked both PCP- and AM251-induced social withdrawal, but not URB597 effect in control rats. Taken together, these findings indicate that AEA-mediated activation of CB₁ receptors is crucial for social interaction, and that PCP-induced social withdrawal results from deficient endocannabinoid transmission.

Intractable nausea caused by zolpidem withdrawal: a case report.

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Baruch, Edward; Vernon, Leonard F; Hasbun, Rafael J

2007-03-01

First launched in France in 1988, zolpidem (Ambien®) is a short-acting hypnotic agent. Early studies reported that that the development of physical dependence and tolerance to sedative-hypnotic drugs, such as the depressant and anticonvulsant effects evidenced with benzodiazepines, is not found with zolpidem. Direct to consumer advertising by the manufacturer continues to state that the risk for dependency is low; however, recent publications seem to contradict this. Additionally, adverse drug reactions affecting the central nervous system, gastrointestinal tract, and respiratory system have been reported. Other studies have examined the interactions of selective serotonin reuptake inhibitors and zolpidem as a possible cause of hallucinations. With continued physician marketing efforts touting the safety and efficacy of zolpidem, there is a high likelihood to overlook the risk of dependency and the symptoms related to zolpidem withdrawal. We report a case of a 41-year-old female who developed a dependency to zolpidem, who on her own decided to decrease her dosage, resulting in intractable nausea requiring hospitalization. Reported cases of zolpidem withdrawal have occurred with doses in excess of 160 mg per day, none of these have reported with intractable nausea as the sole symptom. In our reported case, although exceeding recommended dosage withdrawal phenomenon seemed to be severe after withdrawal from a comparatively low dose of zolpidem. Before zolpidem is prescribed, patient education should include warnings about the potential problems associated with dependency and abrupt discontinuation. Education about this common and likely underrecognized clinical phenomenon will help prevent future episodes and minimize the risk of misdiagnosis.

A Review Study on the Effect of Iranian Herbal Medicines on Opioid Withdrawal Syndrome.

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Ebrahimie, Marzieh; Bahmani, Mahmoud; Shirzad, Hedayatollah; Rafieian-Kopaei, Mahmoud; Saki, Kourosh

2015-10-01

Addiction is a chronic and recurring disease that recurrence phenomenon is the most important challenge in treatment of this disease. Recent experiences have shown that synthetic drugs have undesirable side effects. Recent studies on medicinal plants have shown that they might be effective in treatment of different stages of addiction with lower side effects and costs. The aim of this study was to review the effects of medicinal plants in the treatment of morphine addiction in experimental animals. In this review article, by using keywords of morphine, withdrawal, and plants or herbal medicine in databases of indexing cites, desired articles were obtained since 1994. Inclusion criteria for selecting articles were the articles related to application of medicinal plants in decreasing symptoms resulting from morphine withdrawal were selected. Results of this study on experimental studies have shown that medicinal plants such as Trachyspermum copticum L and Melissa officinalis decrease the symptoms of withdrawal syndrome in a dose-dependent. Also, medicinal plants like Avena sativa, Hypericum perforatu, Passiflora incarnate, Valeriana officinalis, Satureja hortensis L, and Mentha piperita can have effects on behavior, emotions, and other problems of addicts, decreasing withdrawal symptoms. Results of this study showed that medicinal plants can be effective in controlling deprivation, decreasing dependency creation, and possibly DETOXIFICATION: of opioid addicts. © The Author(s) 2015.

Executive cognitive dysfunction and ADHD in cocaine dependence: searching for a common cognitive endophenotype for addictive disorders

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Paulo Jannuzzi Cunha

2013-10-01

Full Text Available Background: Cocaine dependent individuals (CDI present executive cognitive function (ECF deficits, but the impact of psychiatric comorbidities such as Attention-Deficit Hyperactivity Disorder (ADHD on neuropsychological functioning is still poorly understood. The aim of this study was to investigate if CDI with ADHD (CDI+ADHD would have a distinct pattern of executive functioning when compared with CDI without ADHD (CDI. Methods: we evaluated 101 adults, including 69 cocaine dependent subjects and 32 controls. ECF domains were assessed with Digits Forward (DF, Digits Backward (DB, Stroop Color Word Test (SCWT, the Wisconsin Card Sorting Test (WCST, and the Frontal Assessment Battery (FAB. DSM-IV criteria for ADHD were used for diagnosis and previous ADHD symptoms (in the childhood were retrospectively assessed by the Wender-Utah Rating Scale (WURS. Results: there were no significant differences between CDI+ADHD, CDI and controls in estimated IQ, socioeconomic background, education (in years and premorbid IQ (p>0.05. SCWT and WCST scores did not differ across groups. Nevertheless, CDI and CDI+ADHD performed more poorly than controls in total score of the FAB. Also, CDI+ADHD did worse than CDI on DF, DB, Conceptualization/FAB, and Mental flexibility/FAB. We did not find correlations between cocaine use variables and neuropsychological functioning, but previous ADHD symptoms assessed by WURS were negatively associated with DF (p=0.016 and with the total score of the FAB. Conclusion: CDI+TDAH presented more pronounced executive alterations than CDI and CDI exhibited poorer cognitive functioning than controls. Pre-existing ADHD symptoms may have a significant negative impact on executive dysfunction in CDI. It remains to be investigated by future studies if symptoms such as impulsivity or a pre-existing ECF dysfunction could represent underlying cognitive endophenotypes that would substantially increase the risk for acquiring addictive disorders.

Theory of Mind Impairments in Women With Cocaine Addiction.

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Sanvicente-Vieira, Breno; Kluwe-Schiavon, Bruno; Corcoran, Rhiannon; Grassi-Oliveira, Rodrigo

2017-03-01

This study investigates the Theory of Mind performance of female cocaine-dependent users (CDUs) and possible associations between theory of mind performance and features of cocaine use. Sixty women controlled for age, education, individual income, and IQ participated in this study: 30 in the CDU group and 30 in the healthy control group. Participants were assessed for theory of mind with the Reading the Mind in the Eyes Test (RMET), a test of understanding of first-order and second-order false beliefs, and the Hinting task. Drug use parameters, clinical symptoms, and neuropsychological functioning were also assessed. Analyses of covariance indicated Theory of Mind impairments in negative mental states within the RMET and second-order false-belief understanding of Theory of Mind stories. In addition, Theory of Mind impairment was associated with drug use characteristics, including craving and number of hospitalizations. High-demand Theory of Mind is suggested to be impaired in CDU women, and the deficits appear to be related to drug addiction severity. We found associations between Theory of Mind deficits and worse clinical and social outcomes.

Prenatal Cocaine Exposure and Infant Cortisol Reactivity

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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,…

Relapse to cocaine seeking in an invertebrate.

Science.gov (United States)

Amaning-Kwarteng, Akua O; Asif-Malik, Aman; Pei, Yue; Canales, Juan J

2017-06-01

Addiction is characterised by cycles of compulsive drug taking, periods of abstinence and episodes of relapse. The extinction/reinstatement paradigm has been extensively used in rodents to model human relapse and explore underlying mechanisms and therapeutics. However, relapse to drug seeking behaviour has not been previously demonstrated in invertebrates. Here, we used a cocaine conditioned place preference (CPP) paradigm in the flatworm, planarian, followed by extinction and reinstatement of drug seeking. Once baseline preference was established for one of two distinctly textured environments (i.e. compartments with a coarse or smooth surface), planarian received pairings of cocaine (5μM) in the non-preferred, and vehicle in the most preferred, environment, and were tested for conditioning thereafter. Cocaine produced robust CPP, measured as a significant increase in the time spent in the cocaine-paired compartment. Subsequently, planarian underwent extinction training, reverting back to their original preference within three sessions. Brief exposure to cocaine (5μM) or methamphetamine (5μM) reinstated cocaine-seeking behaviour. By contrast, the high affinity dopamine transporter inhibitor, (N-(n-butyl)-3α-[bis (4-fluorophenyl) methoxy]-tropane) (JHW007), which in rodents exhibits a neurochemical and behavioural profile distinct from cocaine, was ineffective. The present findings demonstrate for the first time reinstatement of extinguished cocaine seeking in an invertebrate model and suggest that the long-term adaptations underlying drug conditioning and relapse are highly conserved through evolution. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of DCS-facilitated cue exposure therapy on brain activation to cocaine cues in cocaine dependence.

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Prisciandaro, James J; Myrick, Hugh; Henderson, Scott; McRae-Clark, Aimee L; Santa Ana, Elizabeth J; Saladin, Michael E; Brady, Kathleen T

2013-09-01

The development of addiction is marked by a pathological associative learning process that imbues incentive salience to stimuli associated with drug use. Recent efforts to treat addiction have targeted this learning process using cue exposure therapy augmented with d-cycloserine (DCS), a glutamatergic agent hypothesized to enhance extinction learning. To better understand the impact of DCS-facilitated extinction on neural reactivity to drug cues, the present study reports fMRI findings from a randomized, double-blind, placebo-controlled trial of DCS-facilitated cue exposure for cocaine dependence. Twenty-five participants completed two MRI sessions (before and after intervention), with a cocaine-cue reactivity fMRI task. The intervention consisted of 50mg of DCS or placebo, combined with two sessions of cocaine cue exposure and skills training. Participants demonstrated cocaine cue activation in a variety of brain regions at baseline. From the pre- to post-study scan, participants experienced decreased activation to cues in a number of regions (e.g., accumbens, caudate, frontal poles). Unexpectedly, placebo participants experienced decreases in activation to cues in the left angular and middle temporal gyri and the lateral occipital cortex, while DCS participants did not. Three trials of DCS-facilitated cue exposure therapy for cocaine dependence have found that DCS either increases or does not significantly impact response to cocaine cues. The present study adds to this literature by demonstrating that DCS may prevent extinction to cocaine cues in temporal and occipital brain regions. Although consistent with past research, results from the present study should be considered preliminary until replicated in larger samples. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Neurotensin Agonist Attenuates Nicotine Potentiation to Cocaine Sensitization

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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.

ProSAAS-derived peptides are regulated by cocaine and are required for sensitization to the locomotor effects of cocaine.

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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.

N-Acetylcysteine Reverses Cocaine Induced Metaplasticity

OpenAIRE

Moussawi, Khaled; Pacchioni, Alejandra; Moran, Megan; Olive, M. Foster; Gass, Justin T.; Lavin, Antonieta; Kalivas, Peter W

2009-01-01

Cocaine addiction is characterized by an impaired ability to develop adaptive behaviors that can compete with cocaine seeking, implying a deficit in the ability to induce plasticity in cortico-accumbens circuitry critical for regulating motivated behavior. RWe found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentation (LTP) and depression (LTD) in the nucleus accumbens core subregion following stimulation of prefront...

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.

Estradiol increases choice of cocaine over food in male rats.

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Bagley, Jared R; Adams, Julia; Bozadjian, Rachel V; Bubalo, Lana; Ploense, Kyle L; Kippin, Tod E

2017-10-19

Estradiol modulates the rewarding and reinforcing properties of cocaine in females, including an increase in selection of cocaine over alternative reinforcers. However, the effects of estradiol on male cocaine self-administration behavior are less studied despite equivalent levels of estradiol in the brains of adult males and females, estradiol effects on motivated behaviors in males that share underlying neural substrates with cocaine reinforcement as well as expression of estrogen receptors in the male brain. Therefore, we sought to characterize the effects of estradiol in males on choice between concurrently-available cocaine and food reinforcement as well as responding for cocaine or food in isolation. Male castrated rats (n=46) were treated daily with estradiol benzoate (EB) (5μg/0.1, S.C.) or vehicle (peanut oil) throughout operant acquisition of cocaine (1mg/kg, IV; FI20 sec) and food (3×45mg; FI20 sec) responding, choice during concurrent access and cocaine and food reinforcement under progressive ratio (PR) schedules. EB increased cocaine choice, both in terms of percent of trials on which cocaine was selected and the proportion of rats exhibiting a cocaine preference as well as increased cocaine, but not food, intake under PR. Additionally, within the EB treated group, cocaine-preferring rats exhibited enhanced acquisition of cocaine, but not food, reinforcement whereas no acquisition differences were observed across preferences in the vehicle treated group. These findings demonstrate that estradiol increases cocaine choice in males similarly to what is observed in females. Copyright © 2017 Elsevier Inc. All rights reserved.

Memantine reverses social withdrawal induced by ketamine in rats.

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Uribe, Ezequiel; Landaeta, José; Wix, Richard; Eblen, Antonio

2013-03-01

The objective of this study was to determine the effect of memantine on schizophrenia-like symptoms in a ketamine-induced social withdrawal model in rats. We examined therapeutic effects of memantine, an NMDA antagonist, and haloperidol, a classic antipsychotic drug, on this behavioral model. Administration of memantine (10 or 15 mg·kg(-1)) significantly reduced ketamine-induced social withdrawal, and this effect was more effective than that of haloperidol (0.25 mg·kg(-1)) by restoring the social interaction between rats with no modification in general motor activity. These results suggest that memantine could have a therapeutic potential for schizophrenia.

Neural correlates of social approach and withdrawal in patients with major depression.

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Derntl, Birgit; Seidel, Eva-Maria; Eickhoff, Simon B; Kellermann, Thilo; Gur, Ruben C; Schneider, Frank; Habel, Ute

2011-01-01

Successful human interaction is based on correct recognition, interpretation, and appropriate reaction to facial affect. In depression, social skill deficits are among the most restraining symptoms leading to social withdrawal, thereby aggravating social isolation and depressive affect. Dysfunctional approach and withdrawal tendencies to emotional stimuli have been documented, but the investigation of their neural underpinnings has received limited attention. We performed an fMRI study including 15 depressive patients and 15 matched, healthy controls. All subjects performed two tasks, an implicit joystick task as well as an explicit rating task, both using happy, neutral, and angry facial expressions. Behavioral data analysis indicated a significant group effect, with depressed patients showing more withdrawal than controls. Analysis of the functional data revealed significant group effects for both tasks. Among other regions, we observed significant group differences in amygdala activation, with patients showing less response particularly during approach to happy faces. Additionally, significant correlations of amygdala activation with psychopathology emerged, suggesting that more pronounced symptoms are accompanied by stronger decreases of amygdala activation. Hence, our results demonstrate that depressed patients show dysfunctional social approach and withdrawal behavior, which in turn may aggravate the disorder by negative social interactions contributing to isolation and reinforcing cognitive biases.

Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice.

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Lee, Bridgin G; Anastasia, Agustin; Hempstead, Barbara L; Lee, Francis S; Blendy, Julie A

2015-12-01

Nicotine withdrawal is characterized by both affective and cognitive symptoms. Identifying genetic polymorphisms that could affect the symptoms associated with nicotine withdrawal are important in predicting withdrawal sensitivity and identifying personalized cessation therapies. In the current study we used a mouse model of a non-synonymous single nucleotide polymorphism in the translated region of the brain-derived neurotrophic factor (BDNF) gene that substitutes a valine (Val) for a methionine (Met) amino acid (Val66Met) to examine the relationship between the Val66Met single nucleotide polymorphism and nicotine dependence. This study measured proBDNF and the BDNF prodomain levels following nicotine and nicotine withdrawal and examined a mouse model of a common polymorphism in this protein (BDNF(Met/Met)) in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test. Using the BDNF knock-in mouse containing the BDNF Val66Met polymorphism we found: (1) blunted anxiety-like behavior in BDNF(Met/Met) mice following withdrawal in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test; (2) the anxiolytic effects of chronic nicotine are absent in BDNF(Met/Met) mice; and (3) an increase in BDNF prodomain in BDNF(Met/Met) mice following nicotine withdrawal. Our study is the first to examine the effect of the BDNF Val66Met polymorphism on the affective symptoms of withdrawal from nicotine in mice. In these mice, a single-nucleotide polymorphism in the translated region of the BDNF gene can result in a blunted withdrawal, as measured by decreased anxiety-like behavior. The significant increase in the BDNF prodomain in BDNF(Met/Met) mice following nicotine cessation suggests a possible role of this ligand in the circuitry remodeling after withdrawal. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For

Positron emitting tracers for studies of cocaine

International Nuclear Information System (INIS)

Fowler, J.S.; Gatley, S.J.; MacGregor, R.R.; Wolf, A.P.; Yu, D.W.; Dewey, S.L.; Schlyer, D.J.; Volkow, N.D.; Bendriem, B.; Logan, J.

1990-01-01

The use of PET to study the behavior and mechanism of action of therapeutic drugs and substances of abuse can be approached from a number of perspectives. The most common approach is to measure the effect of a drug on some aspect of metabolism and requires well characterized radiotracers whose behavior in vivo can be related to a discrete biochemical transformation. A second approach is to study the labeled drug itself. This provides information on the drug's regional distribution and kinetics as well as its pharmacological profile and metabolism. Cocaine has been labeled in different positions with carbon-11 and with fluorine-18 and the stereoisomers of cocaine have also been labeled to characterize its binding and metabolism in human and baboon brain. Regional cocaine binding as measured by PET is consistent with reversible binding to striatal dopamine reuptake sites and its time course parallels the behavioral activation of cocaine. The behaviorally inactive enantiomer (+)-cocaine is rapidly metabolized in serum preventing its entry into the brain. These PET tracers are useful in understanding the neurochemical basis of cocaine's action

New Drugs of Abuse and Withdrawal Syndromes.

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Andrabi, Sara; Greene, Spencer; Moukaddam, Nidal; Moukkadam, Nidal; Li, Benjamin

2015-11-01

New drugs of abuse continue to emerge, including synthetic cannabinoids, synthetic cathinones, and hallucinogens. It is important to recognize their individual psychopharmacologic properties, symptoms of intoxication, and symptoms of withdrawal. Providers must be vigilant of acute medical or psychiatric complications that may arise from use of these substances. Treatment of the patient also includes recognition of any substance use disorders as well as comorbid psychiatric disorders. Although pharmacologic treatments for substance use disorder (of the drugs included in this article) are limited, there are a variety of psychotherapeutic modalities that may be of some benefit. Published by Elsevier Inc.

Snow Control - An RCT protocol for a web-based self-help therapy to reduce cocaine consumption in problematic cocaine users

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Sullivan Robin

2011-09-01

Full Text Available Abstract Background Cocaine use has increased in most European countries, including Switzerland, and many states worldwide. The international literature has described treatment models that target the general population. In addition to supplying informative measures at the level of primary and secondary prevention, the literature also offers web-based self-help tools for problematic substance users, which is in line with tertiary prevention. Such programs, however, have been primarily tested on individuals with problematic alcohol and cannabis consumption, but not on cocaine-dependent individuals. Methods/Design This paper presents the protocol of a randomised clinical trial to test the effectiveness of a web-based self-help therapy to reduce cocaine use in problematic cocaine users. The primary outcome is severity of cocaine dependence. Secondary outcome measures include cocaine craving, consumption of cocaine and other substances of abuse in the past month, and changes in depression characteristics. The therapy group will receive a 6-week self-help therapy to reduce cocaine consumption based on methods of Cognitive Behavioural Therapy, principles of Motivational Interviewing and self-control practices. The control group will be presented weekly psycho-educative information with a quiz. The predictive validity of participant characteristics on treatment retention and outcome will be explored. Discussion To the best of our knowledge, this will be the first randomised clinical trial to test the effectiveness of online self-help therapy to reduce or abstain from cocaine use. It will also investigate predictors of outcome and retention. This trial is registered at Current Controlled Trials and is traceable as NTR-ISRCTN93702927.

WITHDRAWN: Carbamazepine for cocaine dependence.

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Lima Reisser, Anelise A R L; Silva de Lima, Mauricio; Soares, Bernardo Garcia de Oliveira; Farrell, Michael

2009-01-21

Cocaine dependence has become a public health problem, developing a significant number of medical, psychological and social problems. Although there is no consensus regarding how to treat cocaine dependence, effective pharmacotherapy has a potentially major role to play as part of a broader treatment milieu. The anti-convulsant carbamazepine, a tricyclic medication that is widely used to treat a variety of neurological and psychiatric disorders, has been used for treatment of cocaine dependence, although its effectiveness has not been established. To determine whether carbamazepine is effective for the treatment of cocaine dependence. We searched: Cochrane Controlled Trials Register (Cochrane Library issue 1, 1999), MEDLINE (f1966 - October 1997), EMBASE (1980 - October 1997), PsycLIT (1974 - July 1997), Biological Abstracts and LILACS (1982 - 1997); scan of reference list of relevant articles; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. The specialised register of trials of Cochrane Group on Drugs and Alcohol until February 2003. All randomised controlled trials focused on the use of carbamazepine versus placebo on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. The reviewers extracted the data independently, Odds Ratios, weighted mean difference and number needed to treat were estimated. Qualitative assessments of the methodology of eligible studies were carried out using validated checklists. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. Where possible analysis was carried out according to the "intention to treat" principles. 5 studies were included (455 participants). No differences regarding positive urine sample for cocaine metabolites. Scores on Spielberg State Anxiety

Fatal cocaine intoxication in a body packer

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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.

Emergence of dormant conditioned incentive approach by conditioned withdrawal in nicotine addiction.

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Scott, Daniel; Hiroi, Noboru

2010-10-15

Nicotine is one of the determinants for the development of persistent smoking, and this maladaptive behavior is characterized by many symptoms, including withdrawal and nicotine seeking. The process by which withdrawal affects nicotine seeking is poorly understood. The impact of a withdrawal-associated cue on nicotine (.2 mg/kg)-conditioned place preference was assessed in male C57BL/6J mice (n = 8-17/group). To establish a cue selectively associated with withdrawal distinct from those associated with nicotine, a tone was paired with withdrawal in their home cages; mice were chronically exposed to nicotine (200 μg/mL for 15 days) from drinking water in their home cages and received the nicotinic acetylcholine receptor antagonist mecamylamine (2.5 mg/kg) to precipitate withdrawal in the presence of a tone. The effect of the withdrawal-associated tone on nicotine-conditioned place preference was then evaluated in the place-conditioning apparatus after a delay, when nicotine-conditioned place preference spontaneously disappeared. A cue associated with precipitated withdrawal reactivated the dormant effect of nicotine-associated cues on conditioned place preference. This effect occurred during continuous exposure to nicotine but not during abstinence. A conditioned withdrawal cue could directly amplify the incentive properties of cues associated with nicotine. This observation extends the contemporary incentive account of the role of withdrawal in addiction to cue-cue interaction. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

High affinity binding of [3H]cocaine to rat liver microsomes

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El-Maghrabi, E.A.; Calligaro, D.O.; Eldefrawi, M.E.

1988-01-01

] 3 H]cocaine bound reversible, with high affinity and stereospecificity to rat liver microsomes. Little binding was detected in the lysosomal, mitochondrial and nuclear fractions. The binding kinetics were slow and the kinetically calculated K/sub D/ was 2 nM. Induction of mixed function oxidases by phenobarbital did not produce significant change in [ 3 H]cocaine binding. On the other hand, chronic administration of cocaine reduced [ 3 H]cocaine binding drastically. Neither treatment affected the affinity of the liver binding protein for cocaine. Microsomes from mouse and human livers had less cocaine-binding protein and lower affinity for cocaine than those from rat liver. Binding of [ 3 H]cocaine to rat liver microsomes was insensitive to monovalent cations and > 10 fold less sensitive to biogenic amines than the cocaine receptor in rat striatum. However, the liver protein had higher affinity for cocaine and metabolites except for norcocaine. Amine uptake inhibitors displaced [ 3 H]cocaine binding to liver with a different rank order of potency than their displacement of [ 3 H]cocaine binding to striatum. This high affinity [ 3 H]cocaine binding protein in liver is not likely to be monooxygenase, but may have a role in cocaine-induced hepatotoxicity

Altered reward sensitivity in female offspring of cocaine-exposed fathers.

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Fischer, Delaney K; Rice, Richard C; Martinez Rivera, Arlene; Donohoe, Mary; Rajadhyaksha, Anjali M

2017-08-14

Recent rodent studies have demonstrated that parental cocaine exposure can influence offspring behavior, supporting the idea that environmental insults can impact subsequent generations. However, studies on the effects of paternal cocaine exposure are limited and multiple inconsistencies exist. In the current study, we behaviorally characterize the effects of paternal cocaine exposure in a C57BL/6J intergenerational mouse model. Male sires were administered cocaine hydrochloride (20mg/kg) or saline (0.01mL/g) once a day for 75days, and bred with drug naïve females twenty-four hours after the final injection. Offspring, separated by sex, were tested in a battery of behaviors. We found that paternal cocaine exposure altered sensitivity to the rewarding and stimulant effects of psychostimulants and natural reward (sucrose) in female offspring; female cocaine-sired offspring showed blunted cocaine preference using cocaine conditioned place preference (CPP) at a low dose (5mg/kg), but displayed similar preference at a higher dose (10mg/kg) compared to saline-sired controls. Additionally, cocaine-sired female offspring exhibited higher psychomotor sensitivity to cocaine (10mg/kg) and amphetamine (2mg/kg) and consumed more sucrose. Cocaine-sired males exhibited increased psychomotor effects of cocaine and amphetamine. Male offspring also displayed an anxiety-like phenotype. No effect of paternal cocaine exposure was observed on depressive-like, learning and memory or social behavior in male or female offspring. Collectively, our findings show that paternal, chronic cocaine exposure induces intergenerational behavioral effects in male and female offspring with greatest impact on sensitivity to psychostimulants and sucrose in females. Copyright © 2017 Elsevier B.V. All rights reserved.

Anxiety does not contribute to social withdrawal in the subchronic phencyclidine rat model of schizophrenia.

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Seillier, Alexandre; Giuffrida, Andrea

2017-10-01

Social withdrawal should not be considered a direct measure of the negative symptoms of schizophrenia as it may result not only from asociality (primary negative symptom) but also from other altered processes such as anxiety. To understand the contribution of these two factors to social deficit, we investigated whether the social withdrawal observed in the subchronic phencyclidine (PCP) rat model of schizophrenia could be attributed to increased anxiety. Compared to saline controls, PCP-treated rats (5 mg/kg, twice daily for 7 days, followed by a washout period) spent significantly less time in social interaction, but did not show anxiety-like behaviors in different relevant behavioral paradigms. In addition, their social deficit was not affected by a behavioral procedure known to reduce anxiety-like behavior (repeated exposure to the same partner) nor by systemic administration of the classical anxiolytic diazepam. In contrast, PCP-induced social withdrawal was reversed by the cannabinoid agonist CP55,940, a drug with known anxiogenic properties. Furthermore, when using the social approach task, PCP-treated animals performed similarly to control animals treated with diazepam, but not to those treated with the anxiogenic compound pentylenetetrazole. Taken together, our results indicate that PCP-induced social withdrawal cannot be attributed to increased anxiety. These data are discussed in the context of primary versus secondary negative symptoms and the deficit syndrome of schizophrenia.

Individual differences in cocaine addiction: maladaptive behavioural traits

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Homberg, J.R.; Karel, P.G.A.; Verheij, M.M.M.

2014-01-01

Cocaine use leads to addiction in only a subset of individuals. Understanding the mechanisms underlying these individual differences in the transition from cocaine use to cocaine abuse is important to develop treatment strategies. There is agreement that specific behavioural traits increase the risk

Limitations to the Generality of Cocaine Locomotor Sensitization

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Marusich, Julie A.; Branch, Marc N.; Dallery, Jesse

2008-01-01

Repeated exposure to cocaine often leads to tolerance to effects on operant behavior, whereas sensitization often develops to effects on locomotor activity. The purpose of the present set of experiments was to examine if locomotor sensitization to cocaine would develop in the presence or absence of an operant contingency in rats. In Experiment 1, rats lever pressed on an FR schedule of reinforcement, and were administered chronic cocaine. Tolerance to effects of cocaine on lever pressing deve...

COCAINE AND PAVLOVIAN FEAR CONDITIONING: DOSE-EFFECT ANALYSIS

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Wood, Suzanne C.; Fay, Jonathon; Sage, Jennifer R.; Anagnostaras, Stephan G.

2006-01-01

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 – 15 mg/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 (15 mg/kg) displayed significantly less cont...

Phenibut (β-Phenyl-γ-aminobutyric Acid) Dependence and Management of Withdrawal: Emerging Nootropics of Abuse.

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Ahuja, Tania; Mgbako, Ofole; Katzman, Caroline; Grossman, Allison

2018-01-01

This case report describes the development of withdrawal from phenibut, a gamma-aminobutyric acid-receptor type B agonist. Although phenibut is not an FDA-approved medication, it is available through online retailers as a nootropic supplement. There are reports of dependence in patients that misuse phenibut. We report a case in which a patient experienced withdrawal symptoms from phenibut and was successfully treated with a baclofen taper. This case report highlights the development of phenibut use disorder with coingestion of alcohol and potential management for phenibut withdrawal. We believe clinicians must be aware of how phenibut dependence may present and how to manage the withdrawal syndrome.

Phenibut (β-Phenyl-γ-aminobutyric Acid Dependence and Management of Withdrawal: Emerging Nootropics of Abuse

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Tania Ahuja

2018-01-01

Full Text Available This case report describes the development of withdrawal from phenibut, a gamma-aminobutyric acid-receptor type B agonist. Although phenibut is not an FDA-approved medication, it is available through online retailers as a nootropic supplement. There are reports of dependence in patients that misuse phenibut. We report a case in which a patient experienced withdrawal symptoms from phenibut and was successfully treated with a baclofen taper. This case report highlights the development of phenibut use disorder with coingestion of alcohol and potential management for phenibut withdrawal. We believe clinicians must be aware of how phenibut dependence may present and how to manage the withdrawal syndrome.

Comparative Evaluation of Partial α2 -Adrenoceptor Agonist and Pure α2 -Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice.

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Arora, Shivani; Vohora, Divya

2016-08-01

As an addictive drug, alcohol produces withdrawal symptoms if discontinued abruptly after chronic use. Clonidine (CLN), a partial α2 -adrenergic agonist, and mirtazapine (MRT), an antagonist of α2 -adrenoceptor, both clinically aid alcohol withdrawal. Considering different mechanisms of action of the two drugs, this study was designed to see how far these two mechanistically different drugs differ in their ability to decrease the severity of ethanol withdrawal syndrome. The effect of CLN and MRT on ethanol withdrawal-induced anxiety, depression and memory impairment was analysed using EPM, FST and PAR tests, respectively. Animals received distilled water, ethanol and/or either of the drugs (CLN and MRT) in different doses. Relapse to alcohol use was analysed by CPP test. Animals received ethanol as a conditioning drug and distilled water, CLN or MRT as test drug. CLN and MRT both alleviated anxiety in a dose-dependent manner. MRT (4 mg/kg) was more effective than CLN (0.1 mg/kg) in ameliorating the anxiogenic effect of alcohol withdrawal. However, CLN treatment increased depression. It significantly decreased swimming time and increased immobility time, whereas MRT treatment decreased immobility time and increased climbing and swimming time during abstinence. The effect was dose dependent for both drugs. The results of PAR test show that CLN treatment worsens working memory. Significant increase in SDE and TSZ and decrease in SDL were observed in CLN-treated animals. MRT treatment, on the other hand, improved working memory at both doses. Further, both CLN and MRT alleviated craving. A significant decrease in time spent in the ethanol-paired chamber was seen. MRT treatment at both doses showed better effect than CLN in preventing the development of preference in CPP test. These findings indicate a potential therapeutic use and better profile of mirtazapine over clonidine in improving memory, as well as in alleviating depression, anxiety and craving associated

Higher Impulsivity As a Distinctive Trait of Severe Cocaine Addiction among Individuals Treated for Cocaine or Alcohol Use Disorders

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Nuria García-Marchena

2018-02-01

Full Text Available AimsDespite alcohol being the most often used addictive substance among addicted patients, use of other substances such as cocaine has increased over recent years, and the combination of both drugs aggravates health impairment and complicates clinical assessment. The aim of this study is to identify and characterize heterogeneous subgroups of cocaine- and alcohol-addicted patients with common characteristics based on substance use disorders, psychiatric comorbidity and impulsivity.MethodsA total of 214 subjects with cocaine and/or alcohol use disorders were recruited from outpatient treatment programs and clinically assessed. A latent class analysis was used to establish phenotypic categories according to diagnosis of cocaine and alcohol use disorders, mental disorders, and impulsivity scores. Relevant variables were examined in the latent classes (LCs using correlation and analyses of variance and covariance.ResultsFour LCs of addicted patients were identified: Class 1 (45.3% formed by alcohol-dependent patients exhibiting lifetime mood disorder diagnosis and mild impulsivity; Class 2 (14% formed mainly by lifetime cocaine use disorder patients with low probability of comorbid mental disorders and mild impulsivity; Class 3 (10.7% formed by cocaine use disorder patients with elevated probability to course with lifetime anxiety, early and personality disorders, and greater impulsivity scores; and Class 4 (29.9% formed mainly by patients with alcohol and cocaine use disorders, with elevated probability in early and personality disorders and elevated impulsivity. Furthermore, there were significant differences among classes in terms of Diagnostic and Statistical Manual of Mental Disorders-4th Edition-Text Revision criteria for abuse and dependence: Class 3 showed more criteria for cocaine use disorders than other classes, while Class 1 and Class 4 showed more criteria for alcohol use disorders.ConclusionCocaine- and alcohol-addicted patients who

Neural effects of positive and negative incentives during marijuana withdrawal.

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Francesca M Filbey

Full Text Available In spite of evidence suggesting two possible mechanisms related to drug-seeking behavior, namely reward-seeking and harm avoidance, much of the addiction literature has focused largely on positive incentivization mechanisms associated with addiction. In this study, we examined the contributing neural mechanisms of avoidance of an aversive state to drug-seeking behavior during marijuana withdrawal. To that end, marijuana users were scanned while performing the monetary incentive delay task in order to assess positive and negative incentive processes. The results showed a group x incentive interaction, such that marijuana users had greater response in areas that underlie reward processes during positive incentives while controls showed greater response in the same areas, but to negative incentives. Furthermore, a negative correlation between withdrawal symptoms and response in the amygdala during negative incentives was found in the marijuana users. These findings suggest that although marijuana users have greater reward sensitivity and less harm avoidance than controls, that attenuated amygdala response, an area that underlies fear and avoidance, was present in marijuana users with greater marijuana withdrawal symptoms. This is concordant with models of drug addiction that involve multiple sources of reinforcement in substance use disorders, and suggests the importance of strategies that focus on respective mechanisms.

Psychiatric aspects of acute withdrawal from gamma-hydroxybutyrate (GHB) and its analogue gamma-butyrolactone (GBL): implications for psychiatry services in the general hospital.

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Choudhuri, Debajeet; Cross, Sean; Dargan, Paul I; Wood, David M; Ranjith, Gopinath

2013-06-01

The objective of this study was to describe the psychiatric symptoms, management and outcomes in a consecutive series of patients being managed medically for symptoms of withdrawal from gamma-hydroxybutyrate (GHB) and its analogue gamma-butyrolactone (GBL) in a general hospital setting. A toxicology database was used to identify patients presenting with a history suggestive of withdrawal from GHB and analogues. Electronic and paper medical records were searched for demographic features, neuropsychiatric symptoms, psychiatric management while in hospital and overall outcome. There were 31 presentations with withdrawal from the drugs involving 20 patients. Of these 17 (54%) were referred to and seen by the liaison psychiatry team. Anxiety (61.3%) and agitation (48.4%) were the most common symptoms. Of the 17 cases seen by the liaison psychiatry team, 52.9% required close constant observation by a mental health nurse and 29.4% required to be detained in hospital under mental health legislation. The significant proportion of patients presenting with neuropsychiatric symptoms and requiring intensive input from the liaison psychiatry team during withdrawal from GHB and its analogues points to the importance of close liaison between medical and psychiatric teams in managing these patients in the general hospital.

Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice.

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Kotagale, Nandkishor R; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

2015-05-05

Smoking cessation exhibits an aversive withdrawal syndrome characterized by both increases in somatic signs and affective behaviors including anxiety and depression. In present study, abrupt withdrawal of daily nicotine injections (2mg/kg, s.c., four times daily, for 10 days) significantly increased somatic signs viz. rearing, grooming, jumping, genital licking, leg licking, head shakes with associated depression (increased immobility in forced swim test) as well as anxiety (decreased the number of entries and time spent in open arm in elevated plus maze) in nicotine dependent animals. The peak effect was observed at 24h time point of nicotine withdrawal. Repeated administration of agmatine (40-80µg/mouse, i.c.v.) before the first daily dose of nicotine from day 5 to 10 attenuated the elevated scores of somatic signs and abolished the depression and anxiety like behavior induced by nicotine withdrawal in dependent animals. However, in separate groups, its acute administration 30min before behavior analysis of nicotine withdrawal was ineffective. This result clearly shows the role of agmatine in development of nicotine dependence and its withdrawal. In extension to behavioral experiments, brain agmatine analyses, carried out at 24h time point of nicotine withdrawal demonstrated marked decrease in basal brain agmatine concentration as compared to control animals. Taken together, these data support the role of agmatine as common biological substrate for somatic signs and affective symptoms of nicotine withdrawal. This data may project therapies based on agmatine in anxiety, depression and mood changes associated with tobacco withdrawal. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Overlapping patterns of brain activation to food and cocaine cues in cocaine abusers: association to striatal D2/D3 receptors

OpenAIRE

Tomasi, Dardo; Wang, Gene-Jack; Wang, Ruiliang; Caparelli, Elisabeth C.; Logan, Jean; Volkow, Nora D.

2014-01-01

Cocaine, through its activation of dopamine (DA) signaling, usurps pathways that process natural rewards. However, the extent to which there is overlap between the networks that process natural and drug rewards and whether DA signaling associated with cocaine abuse influences these networks have not been investigated in humans. We measured brain activation responses to food and cocaine cues with fMRI, and D2/D3 receptors in the striatum with [11C]raclopride and PET in 20 active cocaine abuser...

Prolonged-release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal

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Lemoine P

2011-07-01

Full Text Available Patrick Lemoine1, Doron Garfinkel2, Moshe Laudon3, Tali Nir3, Nava Zisapel3,41The Clinique Lyon-Lumière, Meyzieu, France; 2Geriatric-Palliative Department, Shoham Geriatric Medical Center, Pardes Hanna, Israel; 3Neurim Pharmaceuticals Ltd, Tel-Aviv, Israel; 4Department of Neurobiology Faculty of Life Sciences, Tel Aviv University, Tel Aviv, IsraelBackground: Prolonged-release melatonin (PRM 2 mg is indicated for insomnia in patients aged 55 years and older. A recent double-blind placebo-controlled study demonstrated 6-month efficacy and safety of PRM in insomnia patients aged 18–80 and lack of withdrawal and rebound symptoms upon discontinuation.Objective: To investigate the efficacy, safety, and withdrawal phenomena associated with 6–12 months PRM treatment.Methods: Data from a prospective 6–12-month open-label study of 244 community dwelling adults with primary insomnia, who had participated in a placebo-controlled, double-blind dose-ranging trial of PRM. Patients received PRM nightly, followed by a 2-week withdrawal period. Main outcome measures were patient-reported sleep quality ratings (diary, adverse events, vital signs, and laboratory tests recorded at each visit, and withdrawal symptoms (CHESS-84 [Check-list Evaluation of Somatic Symptoms]. Nocturnal urinary 6-sulfatoxymelatonin excretion, a measure of the endogenous melatonin production, was assessed upon discontinuing long-term PRM.Results: Of the 244 patients, 36 dropped out, 112 completed 6 months of treatment, and the other 96 completed 12 months of treatment. The mean number of nights by which patients reported sleep quality as "good" or "very good" was significantly higher during PRM than before treatment. There was no evidence of tolerance to PRM. Discontinuation of PRM was not associated with rebound insomnia or withdrawal symptoms; on the contrary, residual benefit was observed. PRM was well tolerated, and there was no suppression of endogenous melatonin production

Gender differences in cocaine pharmacokinetics in CF-1 mice.

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Visalli, Thomas; Turkall, Rita; Abdel-Rahman, Mohamed S

2005-01-15

Hepatocellular damage is thought to occur as a result of cytochrome P450-mediated oxidation of cocaine to norcocaine (NC), a precursor of the hepatotoxic nitrosonium ion. However, this damage occurs only in male mice, with females exhibiting minimal biochemical and histological signs of hepatocellular stress. The objective of this study was to determine the plasma time course and tissue disposition of cocaine and its metabolites to further investigate the role that metabolism may play in the gender difference observed. Male and female CF-1 mice were orally administered 20mg/kg cocaine hydrochloride once daily for 7 days. Blood samples were withdrawn at various time points post-injection and analyzed for cocaine and its metabolites benzoylecgonine (BE), norcocaine, ecgonine methyl ester (EME), and ecgonine (E). In addition, tissue concentrations of cocaine and its metabolites were determined in liver, heart, brain, and kidney tissue. The results demonstrated that the plasma elimination half-life of cocaine is nearly three times longer in males versus females. Non-hepatotoxic hydrolysis metabolites BE, EME, and E were higher in female tissues while norcocaine was detected in tissues of male animals only. This study revealed that differences in cocaine pharmacokinetics and the resultant differences in the biodisposition of cocaine and its metabolites in tissues contribute to the mechanism of gender difference seen in cocaine hepatotoxicity.

Adolescent cocaine exposure simplifies orbitofrontal cortical dendritic arbors

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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.

Initial validation of a proxy indicator of functioning as a potential tool for establishing a clinically meaningful cocaine use outcome.

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Kiluk, Brian D; Babuscio, Theresa A; Nich, Charla; Carroll, Kathleen M

2017-10-01

Establishing a non-abstinence cocaine use outcome as clinically meaningful has been elusive, in part due to the lack of association between cocaine use outcomes and meaningful indicators of long-term functioning. Using data pooled across 7 clinical trials evaluating treatments for cocaine (N=718), a dichotomous indicator of functioning was created to represent a meaningful outcome ('problem-free functioning' - PFF), defined as the absence of problems across non-substance-related domains on the Addiction Severity Index. Its validity was evaluated at multiple time points (baseline, end-of-treatment, terminal follow-up) and used to explore associations with cocaine use. The percentage of participants meeting PFF criteria increased over time (baseline=18%; end-of-treatment=32%; terminal follow-up=37%). At each time point, ANOVAs indicated those who met PFF criteria reported significantly less distress on the Brief Symptom Inventory and less perceived stress on the Perceived Stress Scale. Generalized linear models indicated categorical indices of self-reported cocaine use at the end of treatment were predictive of the probability of meeting PFF criteria during follow-up (β=-0.01, pcocaine use in the final month of treatment was associated with PFF during follow-up, with strongest associations between PFF and abstinence or 'occasional' use. Copyright © 2017 Elsevier B.V. All rights reserved.

Cocaine smuggling in the gastrointestinal tract resulting in mechanical pylorostenosis.

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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.

In vitro model to study cocaine and its contaminants.

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Steinmetz, Aline; Steffens, Luiza; Morás, Ana Moira; Prezzi, Flávia; Braganhol, Elizandra; Saffi, Jenifer; Ortiz, Rafael Scorsatto; Barros, Helena M T; Moura, Dinara Jaqueline

2018-04-01

Cocaine is one of the most popular illicit drug worldwide. Due its great addictive potential, which leads to euphoria and hyperactivity, it is considered a public health concern. At the central nervous system, the drug acts inhibiting catecholamine re-uptake. It is now known that in addition to the toxicity of the drug itself, the contaminants present in the street drug have raised concern about the harmful effects on health. Toxicological in vivo and in vitro studies have demonstrated the toxic effects of cocaine correlated with the generation of reactive oxygen species (ROS), which in turn lead to oxidative damage to the cells. Therefore the aim of this work was to propose an in vitro model that reunites the main parameters of toxicity of the cocaine already observed in the literature so far, and we tested this model using cocaine and seizure cocaine sample (SCS), kindly provided by Federal Police of Brazil. For that, we used a C6 glioblastoma cells and evaluated cell death, oxygen reactive species induction, oxidation of macromolecules as membrane lipids and DNA and loss of mitochondrial membrane potential after cocaine exposure. The results showed that cocaine can decrease cellular viability in a dose-dependent way in the C6 cell immortalized and astrocytes primary culture. Cocaine also induced cellular death by apoptosis. However, in the seizure cocaine sample (SCS), the predominant cell death was due to necrosis. Using dichlorofluorescein (DCF) assay, we confirmed ROS production after cocaine exposition. In agreement with these findings, occurred an increasing in MDA production, as well as increased superoxide dismutase (SOD) and catalase (CAT) activity. The induction of DNA damage was observed after cocaine. Our results demonstrate the occurrence of mitochondrial dysfunction by depolarization of mitochondrial membrane as a consequence of cocaine treatment. In summary, these results demonstrated that cocaine can induce reactive oxygen species formation

Financing Cocaine Use in a Homeless Population

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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.

Phencyclidine-Induced Social Withdrawal Results from Deficient Stimulation of Cannabinoid CB1 Receptors: Implications for Schizophrenia

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Seillier, Alexandre; Martinez, Alex A; Giuffrida, Andrea

2013-01-01

The neuronal mechanisms underlying social withdrawal, one of the core negative symptoms of schizophrenia, are not well understood. Recent studies suggest an involvement of the endocannabinoid system in the pathophysiology of schizophrenia and, in particular, of negative symptoms. We used biochemical, pharmacological, and behavioral approaches to investigate the role played by the endocannabinoid system in social withdrawal induced by sub-chronic administration of phencyclidine (PCP). Pharmacological enhancement of endocannabinoid levels via systemic administration of URB597, an inhibitor of endocannabinoid degradation, reversed social withdrawal in PCP-treated rats via stimulation of CB1 receptors, but reduced social interaction in control animals through activation of a cannabinoid/vanilloid-sensitive receptor. In addition, the potent CB agonist CP55,940 reversed PCP-induced social withdrawal in a CB1-dependent manner, whereas pharmacological blockade of CB1 receptors by either AM251 or SR141716 reduced the time spent in social interaction in control animals. PCP-induced social withdrawal was accompanied by a decrease of anandamide (AEA) levels in the amygdala and prefrontal cortex, and these deficits were reversed by URB597. As CB1 receptors are predominantly expressed on GABAergic interneurons containing the anxiogenic peptide cholecystokinin (CCK), we also examined whether the PCP-induced social withdrawal resulted from deficient CB1-mediated modulation of CCK transmission. The selective CCK2 antagonist LY225910 blocked both PCP- and AM251-induced social withdrawal, but not URB597 effect in control rats. Taken together, these findings indicate that AEA-mediated activation of CB1 receptors is crucial for social interaction, and that PCP-induced social withdrawal results from deficient endocannabinoid transmission. PMID:23563893

[Cocaine smuggling in the gastrointestinal tract--the case report with the review of literature].

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Ciszowski, Krzysztof; Hydzik, Piotr; Waldman, Wojciech; Sein Anand, Jacek

2005-01-01

Body-packing is the way of psychoactive substances smuggling by swallowing of carefully prepared packages with drugs into the gastrointestinal tract or by insertion them into the vagina or the rectum, especially in order to avoid finding them by the custom service. Cocaine, as well as opiates, is the one of the most often smuggled drugs by so called body-packers. In the present study the first case of the body-packer from Malopolska region in Poland, who was observed in the Toxicology Department of the Collegium Medicum UJ, was described. The 29-year-old man swallowed 60 packages containing cocaine with a total net weight of about 500 grams. The plain abdominal radiography revealed multiple shadows of foreign bodies in the gastrointestinal tract, but the results of blood and urine cocaine measurements were negative. During the 37-hours stay in our department the patient was monitored (blood pressure, heart rate, temperature), laxatives and oral fluids were administered. All the packages were evacuated through the natural way and it was followed up by the control abdominal radiography. No symptoms of acute cocaine intoxication or any other complications were observed. According to the case there is also the thorough review of literature presented including the kinds of body-packing, the diagnostic methods used in recognizing of body-packers and the ways of their treatment taking into consideration the conservative management as well as surgical methods.

Opioid withdrawal presenting only nausea during tapering of oxycodone after celiac plexus block: a case report.

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Sakamoto, Akiyuki; Takayama, Hiroto; Mamiya, Keiko; Koizumi, Tomonobu

2016-01-01

Celiac plexus block (CPB) is an effective treatment for patients suffering pain. CPB may allow for a reduction in opioid dosage, and may alleviate some of the unwanted side effects of these drugs. However, there is a substantial risk of withdrawal symptoms after reduction of opioid dose. We describe a case of pancreatic cancer developing opioid withdrawal after CPB, who presented only nausea. A 70-year-old man was referred to our hospital due to severe pancreatic cancer pain. He was administered oxycodone (oxycontin®) at 240 mg per day, and presented nausea and anorexia as side effects. CPB was performed due to insufficient pain relief. His pain disappeared on the same day as treatment. Oxycodone was reduced to 160 mg/day, and further reduced two days later to 80 mg/day. However, he complained of more severe nausea and loss of appetite even after tapering of oxycodone. Physical examination, blood chemistry examination, and brain computed tomography (CT) showed no abnormalities. Administration of fast-release oxycodone (Oxinome®) at a dose of 10 mg immediately improved his nausea. There have been no previous reports of nausea as the sole symptom of opioid withdrawal. The present case indicates that unless opioid side effects improve after dosage reduction, the possibility that they may be withdrawal symptoms should also be considered.

Examining supply changes in Australia's cocaine market.

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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.

Catatonia Secondary to Sudden Clozapine Withdrawal: A Case with Three Repeated Episodes and a Literature Review

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John Bilbily

2017-01-01

Full Text Available A literature search identified 9 previously published cases that were considered as possible cases of catatonia secondary to sudden clozapine withdrawal. Two of these 9 cases did not provide enough information to make a diagnosis of catatonia according to the Diagnostic and Statistical Manual, 5th Edition (DSM-5. The Liverpool Adverse Drug Reaction (ADR Causality Scale was modified to assess ADRs secondary to drug withdrawal. From the 7 published cases which met DSM-5 catatonia criteria, using the modified scale, we established that 3 were definitive and 4 were probable cases of catatonia secondary to clozapine withdrawal. A new definitive case is described with three catatonic episodes which (1 occurred after sudden discontinuation of clozapine in the context of decades of follow-up, (2 had ≥3 of 12 DSM-5 catatonic symptoms and serum creatinine kinase elevation, and (3 required medical hospitalization and intravenous fluids. Clozapine may be a gamma-aminobutyric acid (GABA receptor agonist; sudden clozapine withdrawal may explain a sudden decrease in GABA activity that may contribute to the development of catatonic symptoms in vulnerable patients. Based on the limited information from these cases, the pharmacological treatment for catatonia secondary to sudden clozapine withdrawal can include benzodiazepines and/or restarting clozapine.

Sex-Specific Brain Deficits in Auditory Processing in an Animal Model of Cocaine-Related Schizophrenic Disorders

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Patricia A. Broderick

2013-04-01

Full Text Available Cocaine is a psychostimulant in the pharmacological class of drugs called Local Anesthetics. Interestingly, cocaine is the only drug in this class that has a chemical formula comprised of a tropane ring and is, moreover, addictive. The correlation between tropane and addiction is well-studied. Another well-studied correlation is that between psychosis induced by cocaine and that psychosis endogenously present in the schizophrenic patient. Indeed, both of these psychoses exhibit much the same behavioral as well as neurochemical properties across species. Therefore, in order to study the link between schizophrenia and cocaine addiction, we used a behavioral paradigm called Acoustic Startle. We used this acoustic startle paradigm in female versus male Sprague-Dawley animals to discriminate possible sex differences in responses to startle. The startle method operates through auditory pathways in brain via a network of sensorimotor gating processes within auditory cortex, cochlear nuclei, inferior and superior colliculi, pontine reticular nuclei, in addition to mesocorticolimbic brain reward and nigrostriatal motor circuitries. This paper is the first to report sex differences to acoustic stimuli in Sprague-Dawley animals (Rattus norvegicus although such gender responses to acoustic startle have been reported in humans (Swerdlow et al. 1997 [1]. The startle method monitors pre-pulse inhibition (PPI as a measure of the loss of sensorimotor gating in the brain's neuronal auditory network; auditory deficiencies can lead to sensory overload and subsequently cognitive dysfunction. Cocaine addicts and schizophrenic patients as well as cocaine treated animals are reported to exhibit symptoms of defective PPI (Geyer et al., 2001 [2]. Key findings are: (a Cocaine significantly reduced PPI in both sexes. (b Females were significantly more sensitive than males; reduced PPI was greater in females than in males. (c Physiological saline had no effect on startle in

Cocaine contamination of banknotes: a review.

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

2017-12-01

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. © The Author 2017. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

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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.

Cocaine abuse that presents with acute scrotal pain and mimics testicular torsion

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José Tadeu Nunes Tamanini

Full Text Available ABSTRACT Report case (s relevant aspects: Man, 27 years old, complaining of acute testicular pain by 2 hours in the remaining left testicle. Denies fever, lower urinary tract symptoms such as dysuria, urinary frequency, concommitant or prior urethral discharge to the painful condition. He underwent right orchiectomy 13 years ago by testicular torsion. He is a chronic user of cocaine for 15 years and during the last three days the drug use was continuous and intense. Proposed premise substantiating case (s description: Initial diagnostic hypothesis: Syndromic: Acute Scrotum Syndrome (SEA Main Etiologic (testicular torsion Secondary Etiologic (acute orchiepididymitis Briefly delineates what might it add? Lines of research That Could be Addressed: In this challenging clinical case we presented an alternative and new etiologic diangosis for the acute scrotum which the main etiologic factor remains testicular torsion. This new diangosis is acute testicular ischemia as a complication of cocaine abuse.

Effects of chronic cocaine abuse on postsynaptic dopamine receptors

International Nuclear Information System (INIS)

Volkow, N.D.; Fowler, J.S.; Wolf, A.P.; Schlyer, D.; Shiue, C.Y.; Alpert, R.; Dewey, S.L.; Logan, J.; Bendriem, B.; Christman, D.

1990-01-01

To assess the effects of chronic cocaine intoxication on dopamine receptors in human subjects, the authors evaluated [ 18 F]N-methylspiroperidol binding using positron emission tomography in 10 cocaine abusers and 10 normal control subjects. Cocaine abusers who had been detoxified for 1 week or less showed significantly lower values for uptake of [ 18 F]N-methylspiroperidol in striatum than the normal subjects, whereas the cocaine abusers who had been detoxified for 1 month showed values comparable to those obtained from normal subjects. The authors conclude that postsynaptic dopamine receptor availability decreases with chronic cocaine abuse but may recover after a drug-free interval

Aloe vera Aqueous Extract Effect on Morphine Withdrawal Syndrome in Morphine-Dependent Female Rats.

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Shahraki, Mohammad Reza; Mirshekari, Hamideh; Sabri, Azame

2014-09-01

Aloe vera is a medicinal herb used as an anti-inflammatory and sedative agent. The current study aimed to evaluate the effect of Aloe vera aqueous extract on morphine withdrawal symptoms in morphine-dependent female rats. The current research was performed on 40 female Wista-Albino rats which were made dependent on morphine using Houshyar protocol and were randomly divided into five groups (A, B, C, D, and E). Group A did not receive any agent in the period of handling but other groups (B, C, D and E) received 5, 10, 20 and 40 mg/kg of Aloe vera aqueous extract by gavage, three times daily for a week, respectively. Withdrawal symptoms, stool form, agitation, disparity, floppy eyelids, and body mass variations were checked for 10 days. The obtained data were analyzed using SPSS v.11 software, and Friedman, Kruskal-Wallis, and Mann-Whitney statistical tests. Statistical difference was considered significant (P E were significantly higher than those of others groups; however, these symptoms in group C were significantly lower than those of the other groups. The results of the present study revealed that the Aloe vera aqueous extract had various effects on morphine withdrawal syndrome in morphine-dependent female rats .

Manipulating a "cocaine engram" in mice

NARCIS (Netherlands)

Hisang, H.L.; Epp, J.R.; van den Oever, M.C.; Yan, C.; Rashid, J.; Insel, N.; Ye, L.; Niibori, Y.; Deisseroth, K.; Frankland, P.W.; Josselyn, S.A.

2014-01-01

Experience with drugs of abuse (such as cocaine) produces powerful, long-lasting memories that may be important in the development and persistence of drug addiction. The neural mechanisms that mediate how and where these cocaine memories are encoded, consolidated and stored are unknown. Here we used

Stepwise withdrawal of inhaled corticosteroids in COPD patients receiving dual bronchodilation

DEFF Research Database (Denmark)

Magnussen, Helgo; Watz, Henrik; Kirsten, Anne

2014-01-01

-controlled fashion, one group of patients continues to receive tiotropium, salmeterol and fluticasone, while the second group initiates stepwise withdrawal of fluticasone. The primary end point is time to first moderate or severe exacerbation following randomized treatment over 52 weeks. Lung function, symptoms...

N-Acetylcysteine Reverses Cocaine Induced Metaplasticity

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Moussawi, Khaled; Pacchioni, Alejandra; Moran, Megan; Olive, M. Foster; Gass, Justin T.; Lavin, Antonieta; Kalivas, Peter W

2009-01-01

Cocaine addiction is characterized by an impaired ability to develop adaptive behaviors that can compete with cocaine seeking, implying a deficit in the ability to induce plasticity in cortico-accumbens circuitry critical for regulating motivated behavior. RWe found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentation (LTP) and depression (LTD) in the nucleus accumbens core subregion following stimulation of prefrontal cortex. N-acetylcysteine treatment prevents relapse in animal models and craving in humans by activating cystine-glutamate exchange and thereby stimulating extrasynaptic metabotropic glutamate receptors (mGluR). N-acetylcysteine treatment restored the ability to induce LTP and LTD by indirectly stimulating mGluR2/3 and mGluR5, respectively. Cocaine self-administration induces metaplasticity that inhibits the further induction of synaptic plasticity, and this impairment can be reversed by N-acetylcysteine, a drug that also prevents relapse. PMID:19136971

N-Acetylcysteine reverses cocaine-induced metaplasticity.

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Moussawi, Khaled; Pacchioni, Alejandra; Moran, Megan; Olive, M Foster; Gass, Justin T; Lavin, Antonieta; Kalivas, Peter W

2009-02-01

Cocaine addiction is characterized by an impaired ability to develop adaptive behaviors that can compete with cocaine seeking, implying a deficit in the ability to induce plasticity in cortico-accumbens circuitry crucial for regulating motivated behavior. We found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentiation (LTP) and long-term depression (LTD) in the nucleus accumbens core subregion after stimulation of the prefrontal cortex. N-acetylcysteine (NAC) treatment prevents relapse in animal models and craving in humans by activating cystine-glutamate exchange and thereby stimulating extrasynaptic metabotropic glutamate receptors (mGluR). NAC treatment of rats restored the ability to induce LTP and LTD by indirectly stimulating mGluR2/3 and mGluR5, respectively. Our findings show that cocaine self-administration induces metaplasticity that inhibits further induction of synaptic plasticity, and this impairment can be reversed by NAC, a drug that also prevents relapse.

Cocaine's appetite for fat and the consequences on body weight.

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Billing, Lawrence; Ersche, Karen D

2015-03-01

For many individuals in treatment for cocaine dependence, weight gain is a substantial problem during recovery. This weight gain causes significant distress and seems to increase the risk of relapse. The mechanisms underlying cocaine's effects on weight remain elusive. It is widely assumed that this weight gain reflects a metabolic or behavioural compensatory response to the cessation of cocaine use. Here we challenge this assumption and outline potential mechanisms by which chronic cocaine use produces disturbances in the regulation of fat intake and storage, through its effects on the central and peripheral nervous systems, specifically the sympathetic nervous system. We hypothesize that the cocaine-induced alteration in fat regulation results in cocaine users developing a pronounced appetite for fatty food but keeps their fat mass low. This altered fat appetite subsequently leads to excessive weight gain when individuals enter treatment and stop using cocaine. Our aim is to shed light on the neurobiological mechanisms that may underlie the alterations in eating and fat regulation in cocaine-dependent individuals, to open up potential new avenues to support these individuals in recovery.

Nicotine reward and affective nicotine withdrawal signs are attenuated in calcium/calmodulin-dependent protein kinase IV knockout mice.

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Kia J Jackson

Full Text Available The influx of Ca(2+ through calcium-permeable nicotinic acetylcholine receptors (nAChRs leads to activation of various downstream processes that may be relevant to nicotine-mediated behaviors. The calcium activated protein, calcium/calmodulin-dependent protein kinase IV (CaMKIV phosphorylates the downstream transcription factor cyclic AMP response element binding protein (CREB, which mediates nicotine responses; however the role of CaMKIV in nicotine dependence is unknown. Given the proposed role of CaMKIV in CREB activation, we hypothesized that CaMKIV might be a crucial molecular component in the development of nicotine dependence. Using male CaMKIV genetically modified mice, we found that nicotine reward is attenuated in CaMKIV knockout (-/- mice, but cocaine reward is enhanced in these mice. CaMKIV protein levels were also increased in the nucleus accumbens of C57Bl/6 mice after nicotine reward. In a nicotine withdrawal assessment, anxiety-related behavior, but not somatic signs or the hyperalgesia response are attenuated in CaMKIV -/- mice. To complement our animal studies, we also conducted a human genetic association analysis and found that variants in the CaMKIV gene are associated with a protective effect against nicotine dependence. Taken together, our results support an important role for CaMKIV in nicotine reward, and suggest that CaMKIV has opposing roles in nicotine and cocaine reward. Further, CaMKIV mediates affective, but not physical nicotine withdrawal signs, and has a protective effect against nicotine dependence in human genetic association studies. These findings further indicate the importance of calcium-dependent mechanisms in mediating behaviors associated with drugs of abuse.

Dancing on coke: smuggling cocaine dispersed in polyvinyl alcohol.

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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.

N-acetylcysteine amide (AD4) reduces cocaine-induced reinstatement.

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Jastrzębska, Joanna; Frankowska, Malgorzata; Filip, Malgorzata; Atlas, Daphne

2016-09-01

Chronic exposure to drugs of abuse changes glutamatergic transmission in human addicts and animal models. N-acetylcysteine (NAC) is a cysteine prodrug that indirectly activates cysteine-glutamate antiporters. In the extrasynaptic space, NAC restores basal glutamate levels during drug abstinence and normalizes increased glutamatergic tone in rats during reinstatement to drugs of abuse. In initial clinical trials, repeated NAC administration seems to be promising for reduced craving in cocaine addicts. In this study, NAC-amide, called AD4 or NACA, was examined in intravenous cocaine self-administration and extinction/reinstatement procedures in rats. We investigated the behavioral effects of AD4 in the olfactory bulbectomized (OBX) rats, considered an animal model of depression. Finally, we tested rats injected with AD4 or NAC during 10-daily extinction training sessions to examine subsequent cocaine seeking. AD4 (25-75 mg kg(-1)) given acutely did not alter the rewarding effects of cocaine in OBX rats and sham-operated controls. However, at 6.25-50 mg kg(-1), AD4 decreased dose-dependently cocaine seeking and relapse triggered by cocaine priming or drug-associated conditioned cues in both phenotypes. Furthermore, repeated treatment with AD4 (25 mg kg(-1)) or NAC (100 mg kg(-1)) during daily extinction trials reduced reinstatement of drug-seeking behavior in sham-operated controls. In the OBX rats only, AD4 effectively blocked cocaine-seeking behavior. Our results demonstrate that AD4 is effective at blocking cocaine-seeking behavior, highlighting its potential clinical use toward cocaine use disorder.

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

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-trimester ......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...... 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...

Socially anxious smokers experience greater negative affect and withdrawal during self-quit attempts.

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Buckner, Julia D; Langdon, Kirsten J; Jeffries, Emily R; Zvolensky, Michael J

2016-04-01

Despite evidence of a strong and consistent relation between smoking and elevated social anxiety, strikingly little empirical work has identified mechanisms underlying the smoking-social anxiety link. Persons with elevated social anxiety may rely on smoking to cope with more severe nicotine withdrawal and post-quit negative mood states; yet, no known studies have investigated the relation of social anxiety to withdrawal severity. The current study examined the relation of social anxiety to post-quit nicotine withdrawal severity among 51 (33.3% female, Mage = 34.6) community-recruited smokers during the first two weeks following an unaided (i.e., no treatment) cessation attempt. Ecological momentary assessment was used to collect multiple daily ratings of withdrawal and negative mood states. Baseline social anxiety was related to increases in negative affect during the monitoring period and remained significantly related to post-quit withdrawal after controlling for negative affect, gender, lapses, and substance use. Persons with elevated social anxiety experience more severe post-quit withdrawal symptoms and increases in negative affect during a cessation attempt and may therefore benefit from intervention and treatment strategies geared toward helping them learn to cope with withdrawal and negative affect to improve cessation rates among these vulnerable smokers.

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...

Optogenetic Central Amygdala Stimulation Intensifies and Narrows Motivation for Cocaine.

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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

Measuring Outcome in the Treatment of Cocaine Dependence

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Crits-Christoph, Paul; Gallop, Robert; Gibbons, Mary Beth Connolly; Sadicario, Jaclyn S.; Woody, George

2015-01-01

Background Little in known about the extent to which outcome measures used in studies of the treatment of cocaine dependence are associated with longer-term use and with broader measures of clinical improvement. The current study examined reductions in use, and abstinence-oriented measures, in relation to functioning and longer-term clinical benefits in the treatment of cocaine dependence. Methods Overall drug use, cocaine use, and functioning in a number of addiction-related domains for 487 patients diagnosed with DSM-IV cocaine dependence and treated with one of four psychosocial interventions in the NIDA Cocaine Collaborative Treatment Study were assessed monthly during 6 months of treatment and at 9, 12, 15, and 18 month follow-up. Results Measures of during-treatment reduction in use were moderately correlated with drug and cocaine use measures 12 months, but showed non-significant or small correlations with measures of functioning at 12 months. Highest correlations were evident for abstinence measures (maximum consecutive days abstinence and completely abstinent) during treatment in relation to sustained (3 month) abstinence at 12 months. Latent class analysis of patterns of change over time revealed that most patients initially (months 1 to 4 of treatment) either became abstinent immediately or continued to use every month. Over the couse of follow-up, patients either maintained abstinence or used regularly – intermittent use was less common. Conclusions There were generally small associations between various measures of cocaine use and longer-term clinical benefits, other than abstinence was associated with continued abstinence. No one method of measuring outcome of treatment of cocaine dependence appears superior to others. PMID:26366427

Neuroleptic malignant syndrome and subsequent clozapine-withdrawal effects in a patient with refractory schizophrenia

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Cheng MF

2016-03-01

Full Text Available Minfeng Cheng,* Huaying Gu,* Liangrong Zheng, Houliang Wang, Zhiyong Zhong, Shenglin Wen Department of Psychiatry, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Here, we report a female patient developing neuroleptic malignant syndrome following the use of a combination of clozapine and haloperidol. Subsequently, the patient presented withdrawal effects after an abrupt discontinuation of clozapine. Psychiatrists not aware of possible clozapine-withdrawal effects may misdiagnose as a part of the primary mental illness or as the initial symptoms worsening, if unrecognized. Keywords: clozapine, neuroleptic malignant syndrome, withdrawal effect, schizophrenia

Association of elevated ambient temperature with death from cocaine overdose.

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Auger, Nathalie; Bilodeau-Bertrand, Marianne; Labesse, Maud Emmanuelle; Kosatsky, Tom

2017-09-01

Ecologic data suggest that elevated outdoor temperature is correlated with mortality rates from cocaine overdose. Using non-aggregated death records, we studied the association of hot temperatures with risk of death from cocaine overdose. We carried out a case-crossover study of all deaths from cocaine or other drug overdose between the months of May and September, from 2000 through 2013 in Quebec, Canada. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between maximum outdoor temperature and death from cocaine or other drug overdose. The main outcome measure was death from cocaine overdose as a function of maximum temperature the day of death and the days immediately preceding death. There were 316 deaths from cocaine overdose and 446 from other drug overdoses during the study. Elevated temperature the preceding week was associated with the likelihood of death from cocaine but not other drug overdose. Compared with 20°C, a maximum weekly temperature of 30°C was associated with an OR of 2.07 for death from cocaine overdose (95% CI 1.15-3.73), but an OR of 1.03 for other drug overdoses (95% CI 0.60-1.75). Associations for cocaine overdose were present with maximum daily temperature the day of and each of the three days preceding death. Elevated ambient temperature is associated with the risk of death from cocaine overdose. Public health practitioners and drug users should be aware of the added risk of mortality when cocaine is used during hot days. Copyright © 2017 Elsevier B.V. All rights reserved.