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Sample records for opioid dependent individuals

  1. Comparison of craving for opioid in opioid-dependent individuals and people under methadone maintenance treatment

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    Azita Chehri

    2014-02-01

    Full Text Available Background: Methadone Maintenance Therapy (MMT is the most important treatment for opioid -dependency recurrence. The aim of this study was to compare the craving level in opioid-dependent individuals and people under methadone maintenance therapy. Methods: In this case – control study, 120 men with opioid dependency were selected through cluster sampling method. They were divided into two groups, 60 people in opioid-dependent group and 60 people in MMT group. Both groups were matched for age, sex, marital status, education, duration of opioid dependency and method of consumption. Then, they completed INCAS Substance Abuse Profile (ISAP, opiate withdrawal symptoms checklist, self–report of craving, Desire for Drug Questionnaire (DDQ, Obsessive Compulsive Drug Use Scale (OCDUS and visual cue-induced craving questionnaire. Data were analyzed by SPSS 15 using t-test and ANOVA. Results: Mean craving for drug significantly was lower in MMT group comparing opioid-dependent group (P<0.01. Conclusion: Methadone Maintenance Therapy decreased the craving for drugs and substances This can have an important role in relapse prevention.

  2. Non-medical use of opioids among HIV-infected opioid dependent individuals on opioid maintenance treatment: the need for a more comprehensive approach

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    Roux Perrine

    2011-11-01

    Full Text Available Abstract Background Opioid maintenance treatment (OMT has a positive impact on substance use and health outcomes among HIV-infected opioid dependent patients. The present study investigates non-medical use of opioids by HIV-infected opioid-dependent individuals treated with buprenorphine or methadone. Methods The MANIF 2000 study is a longitudinal study that enrolled a cohort of 476 HIV-infected opioid-dependent individuals. Data were collected in outpatient hospital services delivering HIV care in France. The sample comprised all patients receiving OMT (either methadone or buprenorphine who attended at least one follow-up visit with data on adherence to OMT (N = 235 patients, 1056 visits. Non-medical use of opioids during OMT was defined as having reported use of opioids in a non-medical context, and/or the misuse of the prescribed oral OMT by an inappropriate route of administration (injection or sniffing. After adjusting for the non-random assignment of OMT type, a model based on GEE was then used to identify predictors of non-medical use of opioids. Results Among the 235 patients, 144 (61.3% and 91 (38.9% patients were receiving buprenorphine and methadone, respectively, at baseline. Non-medical use of opioids was found in 41.6% of visits for 83% of individual patients. In the multivariate analysis, predictors of non-medical use of opioids were: cocaine, daily cannabis, and benzodiazepine use, experience of opioid withdrawal symptoms, and less time since OMT initiation. Conclusions Non-medical use of opioids was found to be comparable in OMT patients receiving methadone or buprenorphine. The presence of opioid withdrawal symptoms was a determinant of non-medical use of opioids and may serve as a clinical indicator of inadequate dosage, medication, or type of follow-up. Sustainability and continuity of care with adequate monitoring of withdrawal symptoms and polydrug use may contribute to reduced harms from ongoing non-medical use of opioids.

  3. Laboratory-Induced Stress and Craving among Individuals with Prescription Opioid Dependence

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    Back, Sudie E.; Gros, Daniel F.; Price, Matthew; LaRowe, Steve; Flanagan, Julianne; Brady, Kathleen T.; Davis, Charles; Jaconis, Maryanne; McCauley, Jenna L.

    2015-01-01

    Background Stress and conditioned drug cues have been implicated in the initiation, maintenance and relapse to substances of abuse. Although stress and drug cues are often encountered together, little research exists on whether stress potentiates the response to drug cues. Method Participants (N = 75) were 39 community recruited individuals with current prescription opioid (PO) dependence and 36 healthy controls. Participants stayed overnight in the hospital for one night and then completed laboratory testing the following morning. During laboratory testing, participants were randomly assigned to a stress task (Trier Social Stress Task; TSST) or a no-stress condition. Following the stress manipulation, all participants completed a PO cue paradigm. Immediately before and after the stress and cue tasks, the following were assessed: subjective (stress, craving, anger, sadness, happiness), physiological (heart rate, blood pressure, galvanic skin response), and neuroendocrine responses (cortisol and dehydroepiandrosterone). Results Internal validity of the stress task was demonstrated, as evidenced by significantly higher subjective stress, as well as cortisol, heart rate and blood pressure in the TSST compared to the no-stress group. Individuals with PO dependence evidenced significantly greater reactivity to the stress task than controls. Craving increased significantly in response to the drug cue task among PO participants. No stress × cue interaction was observed. Conclusions In this study, heightened stress reactivity was observed among individuals with PO dependence. Exposure to acute stress, however, did not potentiate craving in response to conditioned drug cues. PMID:26342626

  4. A method to diagnose opioid dependence resulting from heroin versus prescription opioids using the Composite International Diagnostic Interview.

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    Potter, Jennifer S; Prather, Kristi; Kropp, Frankie; Byrne, Mimmie; Sullivan, C Rollynn; Mohamedi, Nadia; Copersino, Marc L; Weiss, Roger D

    2010-03-01

    Treatment research with opioid-dependent populations has not traditionally distinguished between those dependent on prescription opioids versus dependent upon heroin. Evidence suggests there is a substantial subpopulation of individuals with opioid dependence resulting largely or exclusively from prescription opioid use. Because this subpopulation may respond to treatment differently from heroin users, a method for discriminating DSM-IV opioid dependence due to prescription opioid use would provide more precision when examining this population. This paper describes an innovative method using a currently available diagnostic instrument, to diagnose DSM-IV opioid dependence and distinguish between dependence resulting from prescription opioids versus dependence upon heroin.

  5. Attentional Bias For Prescription Opioid Cues Among Opioid Dependent Chronic Pain Patients

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    Garland, Eric L.; Froeliger, Brett; Passik, Steven D.; Howard, Matthew O.

    2012-01-01

    Recurrent use of prescription opioid analgesics by chronic pain patients may result in opioid dependence, which involves implicit neurocognitive operations that organize and impel craving states and compulsive drug taking behavior. Prior studies have identified an attentional bias (AB) towards heroin among heroin dependent individuals. The aim of this study was to determine whether opioid-dependent chronic pain patients exhibit an AB towards prescription opioidrelated cues. Opioid-dependent c...

  6. Attentional Bias For Prescription Opioid Cues Among Opioid Dependent Chronic Pain Patients

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    Garland, Eric L.; Froeliger, Brett; Passik, Steven D.; Howard, Matthew O.

    2012-01-01

    Recurrent use of prescription opioid analgesics by chronic pain patients may result in opioid dependence, which involves implicit neurocognitive operations that organize and impel craving states and compulsive drug taking behavior. Prior studies have identified an attentional bias (AB) towards heroin among heroin dependent individuals. The aim of this study was to determine whether opioid-dependent chronic pain patients exhibit an AB towards prescription opioidrelated cues. Opioid-dependent c...

  7. Mu opioid receptor (OPRM1 as a predictor of treatment outcome in opiate-dependent individuals of Arab descent

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    Tay GK

    2012-09-01

    Full Text Available Laith N AL-Eitan,1 Saied A Jaradat,2 Steve YS Su,3 Guan K Tay,1 Gary K Hulse4,51Centre for Forensic Science, 2Princess Haya Biotechnology Center, Jordan University of Science and Technology, Irbid, Jordan; 3School of Mathematics and Statistics, 4School of Psychiatry and Clinical Neurosciences, 5Unit for Research and Education in Alcohol and Drugs, Queen Elizabeth II Medical Centre, The University of Western Australia, Crawley, WA, AustraliaBackground: A number of research studies on the genetics of opiate dependence have focused on the µ-opioid receptor (OPRM1, which is a primary target for opiates. This study aims to identify genetic polymorphisms within the OPRM1 gene involved in response to the biopsychosocial treatment in opiate-dependent individuals of Arab descent.Methods: Unrelated Jordanian Nationals of Arab descent (N = 183 with opiate dependence were selected for this study. These individuals, all males, met the DSM-IV criteria for opiate dependence and were undergoing a voluntary 8-week treatment program at a Jordanian Drug Rehabilitation Centre. All individuals were genotyped for 22 single nucleotide polymorphisms (SNPs within the OPRM1 gene using the Sequenom MassARRAY® system (iPLEX GOLD. Statistical analyses were carried out using the R package.Results: Patients receiving biopsychosocial treatment showed that there was a significant difference in their OPRM1 SNPs’ genotyping distribution between good, moderate, and poor responders to the treatment at two sites (rs6912029 [G-172T], and rs12205732 [G-1510A], P < 0.05, Fisher’s exact test.Conclusion: This study is the first report of an association between the OPRM1 G-172T and G-1510A polymorphisms and treatment response for opiate dependence. Specifically, this study demonstrated that the OPRM1 GG-172 and GG-1510 genotypes were more frequent among patients who were nonresponders to the biopsychosocial treatment. However, further pharmacogenetic studies in a larger cohort of

  8. Using behavioral economics to predict opioid use during prescription opioid dependence treatment.

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    Worley, Matthew J; Shoptaw, Steven J; Bickel, Warren K; Ling, Walter

    2015-03-01

    Research grounded in behavioral economics has previously linked addictive behavior to disrupted decision-making and reward-processing, but these principles have not been examined in prescription opioid addiction, which is currently a major public health problem. This study examined whether pre-treatment drug reinforcement value predicted opioid use during outpatient treatment of prescription opioid addiction. Secondary analyses examined participants with prescription opioid dependence who received 12 weeks of buprenorphine-naloxone and counseling in a multi-site clinical trial (N=353). Baseline measures assessed opioid source and indices of drug reinforcement value, including the total amount and proportion of income spent on drugs. Weekly urine drug screens measured opioid use. Obtaining opioids from doctors was associated with lower pre-treatment drug spending, while obtaining opioids from dealers/patients was associated with greater spending. Controlling for demographics, opioid use history, and opioid source frequency, patients who spent a greater total amount (OR=1.30, peconomic resources to drugs, reflects propensity for continued opioid use during treatment among individuals with prescription opioid addiction. Future studies should examine disrupted decision-making and reward-processing in prescription opioid users more directly and test whether reinforcer pathology can be remediated in this population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Relapse to opioid use in opioid-dependent individuals released from compulsory drug detention centres compared with those from voluntary methadone treatment centres in Malaysia: a two-arm, prospective observational study.

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    Wegman, Martin P; Altice, Frederick L; Kaur, Sangeeth; Rajandaran, Vanesa; Osornprasop, Sutayut; Wilson, David; Wilson, David P; Kamarulzaman, Adeeba

    2017-02-01

    Detention of people who use drugs into compulsory drug detention centres (CDDCs) is common throughout East and Southeast Asia. Evidence-based pharmacological therapies for treating substance use disorders, such as opioid agonist treatments with methadone, are generally unavailable in these settings. We used a unique opportunity where CDDCs coexisted with voluntary drug treatment centres (VTCs) providing methadone in Malaysia to compare the timing and occurrence of opioid relapse (measured using urine drug testing) in individuals transitioning from CDDCs versus methadone maintenance in VTCs. We did a parallel, two-arm, prospective observational study of opioid-dependent individuals aged 18 years and older who were treated in Malaysia in the Klang Valley in two settings: CDDCs and VTCs. We used sequential sampling to recruit individuals. Assessed individuals in CDDCs were required to participate in services such as counselling sessions and manual labour. Assessed individuals in VTCs could voluntarily access many of the components available in CDDCs, in addition to methadone therapy. We undertook urinary drug tests and behavioural interviews to assess individuals at baseline and at 1, 3, 6, 9, and 12 months post-release. The primary outcome was time to opioid relapse post-release in the community confirmed by urinary drug testing in individuals who had undergone baseline interviewing and at least one urine drug test (our analytic sample). Relapse rates between the groups were compared using time-to-event methods. This study is registered at ClinicalTrials.gov (NCT02698098). Between July 17, 2012, and August 21, 2014, we screened 168 CDDC attendees and 113 VTC inpatients; of these, 89 from CDDCs and 95 from VTCs were included in our analytic sample. The baseline characteristics of the two groups were similar. In unadjusted analyses, CDDC participants had significantly more rapid relapse to opioid use post-release compared with VTC participants (median time to relapse

  10. Buprenorphine Sublingual and Buccal (opioid dependence)

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    ... buprenorphine and naloxone are used to treat opioid dependence (addiction to opioid drugs, including heroin and narcotic ... as ketoconazole (Nizoral); medications for anxiety such as benzodiazepines; cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; ...

  11. Maintainence treatment of opioid dependence with tramadol

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    Siddharth Sarkar; Mohit Varshney; Vaibhav Patil; Rakesh Lal

    2017-01-01

    Background: Although tramadol has been used in the management of acute withdrawal in patients with opioid dependence, its use for maintenance treatment as a harm reduction approach has not been assessed systematically. This case series describes patients with opioid dependence who were treated with tramadol for long-term maintenance. Methods: Patients with opioid dependence who received treatment at the National Drug Dependence Treatment Centre of All India Institute of Medical Sciences, New ...

  12. Cue-induced craving in dependence upon prescription opioids and heroin.

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    McHugh, R Kathryn; Park, Sara; Weiss, Roger D

    2014-01-01

    Cues associated with heroin use (eg, needles, powder) elicit robust craving responses in individuals dependent upon heroin. Elevated cue-induced craving may be a risk factor for relapse and can persist after periods of drug abstinence. Despite the growing prevalence of opioid dependence involving prescription opioids, published studies have yet to examine whether cue-induced craving is also present in prescription opioid dependence. A sample of 50 adults diagnosed with opioid dependence (20 prescription opioid users, 25 heroin users, and 5 mixed opioid users) completed a cue reactivity assessment. Participants were administered a series of 90 pictures, including heroin-specific, prescription opioid-specific, and neutral images, and were asked to rate craving and cue salience after each image. Both the prescription opioid and heroin groups experienced significantly more craving to drug than to neutral stimuli. The prescription opioid group reported significantly less craving to prescription opioid stimuli than the heroin group to heroin stimuli; however, this effect was smaller and non-significant when controlling for group differences in cue salience. This study found evidence for cue-induced craving in individuals dependent upon prescription opioids. Further research is needed to better understand the role of cue reactivity in the course and treatment of opioid dependence involving prescription opioid use. As elevated craving reactivity to drug cues may reflect a risk factor for relapse, understanding the nature of cue-induced craving in individuals with opioid dependence is important to improving treatments for this population. © American Academy of Addiction Psychiatry.

  13. Treating opioid dependence. Growing implications for primary care.

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    Krantz, Mori J; Mehler, Philip S

    2004-02-01

    Almost 3 million Americans have abused heroin. The most effective treatment for this concerning epidemic is opioid replacement therapy. Although, from a historical perspective, acceptance of this therapy has been slow, growing evidence supports its efficacy. There are 3 approved medications for opioid maintenance therapy: methadone hydrochloride, levomethadyl acetate, and buprenorphine hydrochloride. Each has unique characteristics that determine its suitability for an individual patient. Cardiac arrhythmias have been reported with methadone and levomethadyl, but not with buprenorphine. Due to concerns about cardiac risk, levomethadyl use has declined and the product may ultimately be discontinued. These recent safety concerns, specifics about opioid detoxification and maintenance, and new federal initiatives were studied. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Although only a minority of eligible patients are engaged in treatment, opioid maintenance therapy appears to offer the greatest public health benefits. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. This model has gained wide acceptance in Europe and is now being implemented in the United States. The recent Drug Addiction Treatment Act enables qualified physicians to treat opioid-dependent patients with buprenorphine in an office-based setting. Mainstreaming opioid addiction treatment has many advantages; its success will depend on resolution of ethical and delivery system issues as well as improved and expanded training of physicians in addiction medicine.

  14. Opioid dependence treatment, including buprenorphine/naloxone.

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    Raisch, Dennis W; Fye, Carol L; Boardman, Kathy D; Sather, Mike R

    2002-02-01

    To review opioid dependence (OD) and its treatment. Pharmacologic treatments, including the use of buprenorphine/naloxone, are presented. Pharmaceutical care functions for outpatient OD treatment are discussed. Primary and review articles were identified by MEDLINE and HEALTHSTAR searches (from 1966 to November 2000) and through secondary sources. Tertiary sources were also reviewed regarding general concepts of OD and its treatment. Relevant articles were reviewed after identification from published abstracts. Articles were selected based on the objectives for this article. Studies of the treatment of OD with buprenorphine were selected based on the topic (pharmacology, pharmacokinetics, adverse reactions) and study design (randomized, controlled clinical trials in patients with OD with active/placebo comparisons and/or comparisons of active OD treatments). Articles regarding pharmacists' activities in the treatment and prevention of OD were reviewed for the pharmaceutical care section. OD is considered a medical disorder with costly adverse health outcomes. Although methadone maintenance treatment (MMT) is cost-effective for OD, only about 12% of individuals with OD receive this treatment. Psychological and pharmacologic modalities are used to treat OD, but patients often relapse. Drug therapy includes alpha 2-agonists for withdrawal symptoms, detoxification regimens with or without opioids, opioid antagonists, and opioid replacement including methadone, levomethadyl acetate, and buprenorphine. The Drug Addiction Treatment Act of 1999 allows for office-based opioid replacement therapies. Sublingual buprenorphine with naloxone can be used in this milieu. Buprenorphine with naloxone is currently under new drug application review with the Food and Drug Administration. Clinical research shows buprenorphine to be equal in effectiveness to methadone, but safer in overdose due to its ceiling effect on respiratory depression. It has lower abuse potential and fewer

  15. Maintainence Treatment of Opioid Dependence with Tramadol.

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    Sarkar, Siddharth; Varshney, Mohit; Patil, Vaibhav; Lal, Rakesh

    2017-08-01

    Although tramadol has been used in the management of acute withdrawal in patients with opioid dependence, its use for maintenance treatment as a harm reduction approach has not been assessed systematically. This case series describes patients with opioid dependence who were treated with tramadol for long-term maintenance. Patients with opioid dependence who received treatment at the National Drug Dependence Treatment Centre of All India Institute of Medical Sciences, New Delhi, were included in the study. Patients who received at least 6 months of tramadol and had follow-up adherence of more than 80% were included in the case series. A total of 25 cases were included, all of whom were males. The types of opioids being taken at the time of initiation of tramadol were natural opiates (poppy husk and raw opium), followed by heroin. The median dose of tramadol at initiation and maintenance was 300 mg/day. Nineteen patients were able to achieve complete abstinence to other opiates on tramadol. Tramadol may be an effective option in the long-term management of patients with opioid dependence. Further studies are required for establishing the efficacy of tramadol for agonist management of patients with opioid dependence.

  16. Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence

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    Randesi, Matthew; van den Brink, Wim; Levran, Orna; Blanken, Peter; Butelman, Eduardo R; Yuferov, Vadim; da Rosa, Joel Correa; Ott, Jurg; van Ree, Jan M; Kreek, Mary Jeanne

    2016-01-01

    BACKGROUND: Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence.

  17. Opioid-Induced Hyperalgesia - Worsening Pain in Opioid-Dependent Patients

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    2013-02-01

    other symptoms. His medical history was significant for posttraumatic stress disorder, anxiety, chronic pain , phantom limb pain , insomnia, and depression...FEB 2013 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Opioid-induced hyperalgesia--worsening pain in opioid-dependent...Report Opioid-induced hyperalgesia—worsening pain in opioid-dependent patients☆ Abstract Patients with chronic opioid use are commonly treated in the

  18. Five-factor model personality traits in opioid dependence

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    Nordvik Hilmar

    2007-08-01

    Full Text Available Abstract Background Personality traits may form a part of the aetiology of opioid dependence. For instance, opioid dependence may result from self-medication in emotionally unstable individuals, or from experimenting with drugs in sensation seekers. The five factor model (FFM has obtained a central position in contemporary personality trait theory. The five factors are: Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness. Few studies have examined whether there is a distinct personality pattern associated with opioid dependence. Methods We compared FFM personality traits in 65 opioid dependent persons (mean age 27 years, 34% females in outpatient counselling after a minimum of 5 weeks in buprenorphine replacement therapy, with those in a non-clinical, age- and sex-matched sample selected from a national database. Personality traits were assessed by a Norwegian version of the Revised NEO Personality Inventory (NEO PI-R, a 240-item self-report questionnaire. Cohen's d effect sizes were calculated for the differences in personality trait scores. Results The opioid-dependent sample scored higher on Neuroticism, lower on Extraversion and lower on Conscientiousness (d = -1.7, 1.2 and 1.7, respectively than the controls. Effects sizes were small for the difference between the groups in Openness to experience scores and Agreeableness scores. Conclusion We found differences of medium and large effect sizes between the opioid dependent group and the matched comparison group, suggesting that the personality traits of people with opioid dependence are in fact different from those of non-clinical peers.

  19. Sustained-release naltrexone for opioid dependence.

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    Lobmaier, P; Kornør, H; Kunøe, N; Bjørndal, A

    2008-04-16

    Naltrexone is an opioid antagonist which effectively blocks heroin effects. Since opioid dependence treatment with naltrexone tablets suffers from high dropout rates, several depot injections and implants are under investigation. Sustained-release formulations are claimed to be effective, but a systematic review of the literature is lacking. To evaluate the effectiveness of sustained-release naltrexone for opioid dependence and its adverse effects in different study populations. The following databases were searched from their inception to November 2007: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, LILACS, PsycINFO, ISI Web of Science, trial database at http://clinicaltrials.gov, available NIDA monographs, CPDD and AAAP conference proceedings. The reference lists of identified studies, published reviews and relevant web sides were searched manually. Study authors and drug companies were contacted to obtain any unpublished material or missing data. To evaluate effectiveness only RCTs were included. To evaluate safety, any clinical trial reporting adverse effects was assessed. Treatment condition was extended to include alcohol dependent subjects and healthy volunteers. Reviewers independently evaluated the reports, rated methodological quality and extracted data. Analyses were performed separately for opioid dependent, alcohol dependent and healthy participants. Foe effectiveness, one report met inclusion criteria. Two dosages of naltrexone depot injections (192 and 384 mg) were compared to placebo. High-dose significantly increased days in treatment compared to placebo (WMD 21.00, 95% CI 10.68 to 31.32, p<0.0001). High-dose compared to low-dose significantly increased days in treatment (WMD 12.00, 95% CI 1.69 to 22.31, p=0.02). Number of patients retained in treatment did not show significant differences between groups. For adverse effects, seventeen reports met inclusion criteria analyses, six were RCTs. Side effects were significantly

  20. Interaction of the mu-opioid receptor with GPR177 (Wntless) inhibits Wnt secretion: potential implications for opioid dependence

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    Stagljar Igor; Van Bockstaele Elisabeth J; Reyes Beverly AS; Wong Victoria; Kittanakom Saranya; Jin Jay; Berrettini Wade; Levenson Robert

    2010-01-01

    Abstract Background Opioid agonist drugs produce analgesia. However, long-term exposure to opioid agonists may lead to opioid dependence. The analgesic and addictive properties of opioid agonist drugs are mediated primarily via the mu-opioid receptor (MOR). Opioid agonists appear to alter neuronal morphology in key brain regions implicated in the development of opioid dependence. However, the precise role of the MOR in the development of these neuronal alterations remains elusive. We hypothes...

  1. Memory function in opioid-dependent patients treated with methadone or buprenorphine along with benzodiazepine: longitudinal change in comparison to healthy individuals

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    Rapeli Pekka

    2009-04-01

    Full Text Available Abstract Background Opioid-substitution treatment (OST for opioid dependence (OD has proven effective in retaining patients in treatment and reducing illegal opiate abuse and crime. Consequently, the World Health Organization (WHO has listed the opioid agonists methadone and buprenorphine as essential drugs for OD that should be available worldwide. In many areas of the world, OD is often associated with concomitant benzodiazepine (BZD dependence and abuse, which complicates treatment. However, possible changes in the cognitive functioning of these patients are not well-known. The present study is the first to examine longitudinal stability of memory function in OST patients with BZD use, thus providing a new tool for health policy authorities in evaluating the usefulness of OST. Methods Within the first two months (T1 and between 6–9 months (T2 after OST admission, we followed the working memory, immediate verbal memory, and memory consolidation of 13 methadone- and 15 buprenorphine- or buprenorphine/naloxone-treated patients with BZD dependence or abuse disorder. The results were compared to those of fifteen normal comparison participants. All participants also completed a self-reported memory complaint questionnaire on both occasions. Results Both patient groups performed statistically significantly worse than normal comparison participants in working memory at time points T1 and T2. In immediate verbal memory, as measured by list learning at T1, patients scored lower than normal comparison participants. Both patient groups reported significantly more subjective memory problems than normal comparison participants. Patients with more memory complaints recalled fewer items at T2 from the verbal list they had learned at T1 than those patients with fewer memory complaints. The significance of the main analyses remained nearly the same when the statistical tests were performed without buprenorphine-only patients leaving 12 patients to

  2. Arguments in favour of compulsory treatment of opioid dependence.

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    Wu, Zunyou

    2013-02-01

    Twelve agencies of the United Nations, including the World Health Organization, have issued a joint statement that calls on Member States to replace the compulsory detention of people who use opioids in treatment centres with voluntary, evidence-informed and rights-based health and social services. The arguments in favour of this position fall into three broad categories: Compulsory treatment centres infringe on an individual's liberty, they put human beings at risk of harm, and evidence of their effectiveness against opioid dependence has not been generated. The United Nations statement underscores that although countries apply different criteria for sending individuals to compulsory treatment centres, detention often takes place without due process, legal safeguards or judicial review. This clearly violates internationally recognized human rights standards. Furthermore, people who are committed to these centres are often exposed to physical and sexual violence, forced labour and sub-standard living conditions. They are often denied health care, despite their heightened vulnerability to HIV infection and tuberculosis. Finally, there is no evidence, according to the statement, that these centres offer an environment that is conducive to recovery from opioid dependence or to the rehabilitation of commercial sex workers or of children who have suffered sexual exploitation, abuse or lack of care and protection. The author of this paper sets forth several arguments that counter the position taken by the United Nations and argues in favour of compulsory treatment within a broader harm reduction strategy aimed at protecting society as well as the individual concerned.

  3. Evaluation and Management of Opioid Dependence in Pregnancy

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    Park, Eliza M; Meltzer-Brody, Samantha; Suzuki, Joji

    2017-01-01

    Background Opioid use disorders are a growing public health problem in the United States. Most women who are opioid dependent are of childbearing age and management of opioid dependence during pregnancy poses unique challenges. Assessment includes evaluation for addiction, withdrawal syndromes, and co-morbid psychiatric diagnoses. Consultation-liaison psychiatrists may also be involved in acute pain management, perinatal medication management, buprenorphine induction and stabilization. For the past four decades, the standard of care has included methadone maintenance, but the increasing use of buprenorphine creates new treatment issues and opportunities. Objective To educate consultation-liaison psychiatrists in emergency and obstetrical settings about the appropriate approach toward the evaluation and basic management of women with opioid dependence in pregnancy. Method The authors reviewed the consensus literature and all new treatment options on opioid dependence during pregnancy. Discussion In this review, the authors summarize known and emerging management strategies for opioid dependence in pregnancy pertinent to consultation-liaison psychiatrists. PMID:22902085

  4. Opioid-Induced Glial Activation: Mechanisms of Activation and Implications for Opioid Analgesia, Dependence, and Reward

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    Mark R. Hutchinson

    2007-01-01

    Full Text Available This review will introduce the concept of toll-like receptor (TLR–mediated glial activation as central to all of the following: neuropathic pain, compromised acute opioid analgesia, and unwanted opioid side effects (tolerance, dependence, and reward. Attenuation of glial activation has previously been demonstrated both to alleviate exaggerated pain states induced by experimental pain models and to reduce the development of opioid tolerance. Here we demonstrate that selective acute antagonism of TLR4 results in reversal of neuropathic pain as well as potentiation of opioid analgesia. Attenuating central nervous system glial activation was also found to reduce the development of opioid dependence, and opioid reward at a behavioral (conditioned place preference and neurochemical (nucleus accumbens microdialysis of morphine-induced elevations in dopamine level of analysis. Moreover, a novel antagonism of TLR4 by (+- and (˗-isomer opioid antagonists has now been characterized, and both antiallodynic and morphine analgesia potentiating activity shown. Opioid agonists were found to also possess TLR4 agonistic activity, predictive of glial activation. Targeting glial activation is a novel and as yet clinically unexploited method for treatment of neuropathic pain. Moreover, these data indicate that attenuation of glial activation, by general or selective TLR antagonistic mechanisms, may also be a clinical method for separating the beneficial (analgesia and unwanted (tolerance, dependence, and reward actions of opioids, thereby improving the safety and efficacy of their use.

  5. Opioid Dependence Can Start in Just a Few Days

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    ... https://medlineplus.gov/news/fullstory_164133.html Opioid Dependence Can Start in Just a Few Days Prescribing ... less may help patients avoid the dangers of dependence and addiction, a new study suggests. Among patients ...

  6. Cue-Induced Craving to Paraphernalia and Drug Images in Opioid Dependence

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    McHugh, R. Kathryn; Fulciniti, Francesca; Mashhoon, Yasmin; Weiss, Roger D.

    2016-01-01

    Background and Objectives Stimuli that are repeatedly paired with substance use, such as drug paraphernalia, can themselves elicit drug craving. The aim of this study was to examine whether particular cue types elicit greater craving responses than others among individuals with opioid dependence. Methods Participants seeking inpatient treatment for opioid dependence were recruited for a study of cue-induced craving. This sample (N=50), included 25 primary heroin users, 20 primary prescription opioid users, and 5 users of heroin and prescription opioids equally. Participants completed a cue reactivity task, in which images of drug-related stimuli were presented on a computer screen, each followed by a question assessing state drug craving. Results Overall, participants reported higher craving following paraphernalia stimuli relative to drug stimuli. However, this was moderated by opioid type; there was significantly higher craving in response to images of paraphernalia cues in the heroin group, and higher craving in response to drug cues in the prescription opioid group. Discussion and Conclusions These findings highlight potential differences in cue reactivity to opioid paraphernalia and drug cues, which appears to be moderated by drug type. Scientific Significance Cue-induced craving is an important factor in relapse. This study adds further to the literature on cue-induced craving in opioid dependence, suggesting that craving may vary based on both cue type and opioid type. Future studies designed to discriminate the impact of substance of abuse, route of administration, and cue type will help to further understand cue-induced craving in this population. PMID:26848719

  7. Review of perioperative pain management of opioid-dependent patients.

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    Vadivelu, Nalini; Mitra, Sukanya; Kai, Alice M; Kodumudi, Gopal; Gritsenko, Karina

    2016-01-01

    Opioid dependence can occur due to prescription opioid use, recreational opioid use, or as a result of opioid use for the treatment of drug addiction. Pain control in these patients is truly a challenge. It is important to understand the patient's condition such as the phenomenon of drug dependence, drug addiction, and pseudoaddiction to provide effective analgesia. This may be accomplished using appropriate multimodal therapies and by treatment of coexisting diseases such as anxiety. The goal is to provide effective analgesia, prevent cognitive and emotional problems, and produce a positive postoperative rehabilitation process. Multimodal options include pharmacological and nonpharmacological approaches, psychological support, and interventional pain procedures, all focused toward providing optimal pain control while preventing undertreatment, withdrawal symptoms, and other complications.

  8. An intronic variant in OPRD1 predicts treatment outcome for opioid dependence in African-Americans.

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    Crist, Richard C; Clarke, Toni-Kim; Ang, Alfonso; Ambrose-Lanci, Lisa M; Lohoff, Falk W; Saxon, Andrew J; Ling, Walter; Hillhouse, Maureen P; Bruce, R Douglas; Woody, George; Berrettini, Wade H

    2013-09-01

    Although buprenorphine and methadone are both effective treatments for opioid dependence, their efficacy can vary significantly among patients. Genetic differences may explain some of the variability in treatment outcome. Understanding the interactions between genetic background and pharmacotherapy may result in more informed treatment decisions. This study is a pharmacogenetic analysis of the effects of genetic variants in OPRD1, the gene encoding the δ-opioid receptor, on the prevalence of opioid-positive urine tests in African-Americans (n=77) or European-Americans (n=566) undergoing treatment for opioid dependence. Patients were randomly assigned to treatment with either methadone or buprenorphine/naloxone (Suboxone) over a 24-week open-label clinical trial, in which illicit opioid use was measured by weekly urinalysis. In African-Americans, the intronic SNP rs678849 predicted treatment outcome for both medications. Methadone patients with the CC genotype were less likely to have opioid-positive urine tests than those in the combined CT and TT genotypes group (relative risk (RR)=0.52, 95% confidence interval (CI)=0.44-0.60, p=0.001). In the buprenorphine treatment group, however, individuals with the CC genotype were more likely to have positive opioid drug screens than individuals in the combined CT and TT genotypes group (RR=2.17, 95% CI=1.95-2.68, p=0.008). These findings indicate that the genotype at rs678849 predicts African-American patient response to two common treatments for opioid dependence, suggesting that matching patients to treatment type based on the genotype at this locus may improve overall treatment efficacy. This observation requires confirmation in an independent population.

  9. Neurobiology of opioid dependence in creating addiction vulnerability.

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    Evans, Christopher J; Cahill, Catherine M

    2016-01-01

    Opioid drugs are potent modulators of many physiological and psychological processes. When given acutely, they can elicit the signature responses of euphoria and analgesia that societies have coveted for centuries. Repeated, or chronic, use of opioids induces adaptive or allostatic changes that modify neuronal circuitry and create an altered normality - the "drug-dependent" state. This state, at least that exhibited by those maintained continuously on long-acting opioid drugs such as methadone or buprenorphine, is generally indistinguishable from the drug-naïve state for most overt behaviors. The consequences of the allostatic changes (cellular, circuit, and system adaptations) that accompany the drug-dependent state are revealed during drug withdrawal. Drug cessation triggers a temporally orchestrated allostatic re-establishment of neuronal systems, which is manifested as opposing physiological and psychological effects to those exhibited by acute drug intoxication. Some withdrawal symptoms, such as physical symptoms (sweating, shaking, and diarrhea) resolve within days, whilst others, such as dysphoria, insomnia, and anxiety, can linger for months, and some adaptations, such as learned associations, may be established for life. We will briefly discuss the cellular mechanisms and neural circuitry that contribute to the opioid drug-dependent state, inferring an emerging role for neuroinflammation. We will argue that opioid addictive behaviors result from a learned relationship between opioids and relief from an existing or withdrawal-induced anxiogenic and/or dysphoric state. Furthermore, a future stressful life event can recall the memory that opioid drugs alleviate negative affect (despair, sadness, and anxiety) and thereby precipitate craving, resulting in relapse. A learned association of relief of aversive states would fuel drug craving in vulnerable people living in an increasingly stressful society. We suggest that this route to addiction is contributive to

  10. A systematic review of health economic models of opioid agonist therapies in maintenance treatment of non-prescription opioid dependence.

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    Chetty, Mersha; Kenworthy, James J; Langham, Sue; Walker, Andrew; Dunlop, William C N

    2017-02-24

    Opioid dependence is a chronic condition with substantial health, economic and social costs. The study objective was to conduct a systematic review of published health-economic models of opioid agonist therapy for non-prescription opioid dependence, to review the different modelling approaches identified, and to inform future modelling studies. Literature searches were conducted in March 2015 in eight electronic databases, supplemented by hand-searching reference lists and searches on six National Health Technology Assessment Agency websites. Studies were included if they: investigated populations that were dependent on non-prescription opioids and were receiving opioid agonist or maintenance therapy; compared any pharmacological maintenance intervention with any other maintenance regimen (including placebo or no treatment); and were health-economic models of any type. A total of 18 unique models were included. These used a range of modelling approaches, including Markov models (n = 4), decision tree with Monte Carlo simulations (n = 3), decision analysis (n = 3), dynamic transmission models (n = 3), decision tree (n = 1), cohort simulation (n = 1), Bayesian (n = 1), and Monte Carlo simulations (n = 2). Time horizons ranged from 6 months to lifetime. The most common evaluation was cost-utility analysis reporting cost per quality-adjusted life-year (n = 11), followed by cost-effectiveness analysis (n = 4), budget-impact analysis/cost comparison (n = 2) and cost-benefit analysis (n = 1). Most studies took the healthcare provider's perspective. Only a few models included some wider societal costs, such as productivity loss or costs of drug-related crime, disorder and antisocial behaviour. Costs to individuals and impacts on family and social networks were not included in any model. A relatively small number of studies of varying quality were found. Strengths and weaknesses relating to model structure, inputs and approach were identified across

  11. Long term substitution treatment (maintenance treatment of opioid dependent persons

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    Wirl, Charlotte

    2007-03-01

    . Concerning the improvement of life and health situation the results of the studies are contradictory. The results show that retention rate of substitution treatment is higher than retention rate of abstinence oriented treatment. Regarding economical aspects substitution treatment is efficient in avoiding secondary illnesses (infections and decreasing criminality. From the perspective of medical ethics substitution treatment as well as medical prescription of heroin is in principle acceptable. Discussion and conclusions: Based on these results, it can be recommended that substitution treatment in principle should be made available for all opioid dependent persons. The decision whether substitution treatment or another treatment (e. g. abstinence oriented treatment is more promising has to take into account the individual situation of the client. In addition a combination of substitution treatment and abstinence oriented treatment might be promising although there is a lack of studies about this approach. In any case the decision concerning a certain form of treatment should leave aside pseudo-moralic concerns and should be made on the base of established medical ethic principles - like the interest of the patient - taking into account the specific situation of the client.

  12. Differences in Early Maladaptive Schemas in a Sample of Alcohol and Opioid Dependent Women: Do Schemas Vary Across Disorders?

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    Shorey, Ryan C.; Stuart, Gregory L.; Anderson, Scott

    2012-01-01

    Research suggests that there may be differences between individuals diagnosed with alcohol dependence and individuals diagnosed with opioid dependence on co-morbid mental health problems (e.g., personality disorders, mood disorders, etc.). The current study examined whether there were differences in early maladaptive schemas, which are theorized to underlie mental health problems, among women diagnosed with alcohol dependence or opioid dependence who were seeking treatment for their substance use (N = 420). Results showed that opioid dependent women scored higher on 2 of the 18 early maladaptive schemas, particularly the schemas of dependence and punitiveness. Overall, these findings suggest that early maladaptive schemas may be largely consistent across women diagnosed with alcohol or opioid dependence. Implications of these findings for future research and treatment are discussed. PMID:23494129

  13. Use of Pharmacotherapies in the Treatment of Alcohol Use Disorders and Opioid Dependence in Primary Care

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    Jinhee Lee

    2015-01-01

    Full Text Available Substance-related and addictive disorders are chronic relapsing conditions that substantially impact public health. Effective treatments for these disorders require addressing substance use/dependence comprehensively as well as other associated comorbidities. Comprehensive addressing of substance use in a medical setting involves screening for substance use, addressing substance use directly with the patient, and formulating an appropriate intervention. For alcohol dependence and opioid dependence, pharmacotherapies are available that are safe and effective when utilized in a comprehensive treatment paradigm, such as medication assisted treatment. In primary care, substance use disorders involving alcohol, illicit opioids, and prescription opioid abuse are common among patients who seek primary care services. Primary care providers report low levels of preparedness and confidence in identifying substance-related and addictive disorders and providing appropriate care and treatment. However, new models of service delivery in primary care for individuals with substance-related and addictive disorders are being developed to promote screening, care and treatment, and relapse prevention. The education and training of primary care providers utilizing approved medications for the treatment of alcohol use disorders and opioid dependence in a primary care setting would have important public health impact and reduce the burden of alcohol abuse and opioid dependence.

  14. Opioid Analgesics.

    Science.gov (United States)

    Jamison, Robert N; Mao, Jianren

    2015-07-01

    Chronic pain is an international health issue of immense importance that is influenced by both physical and psychological factors. Opioids are useful in treating chronic pain but have accompanying complications. It is important for clinicians to understand the basics of opioid pharmacology, the benefits and adverse effects of opioids, and related problematic issues of tolerance, dependence, and opioid-induced hyperalgesia. In this article, the role of psychiatric comorbidity and the use of validated assessment tools to identify individuals who are at the greatest risk for opioid misuse are discussed. Additionally, interventional treatment strategies for patients with chronic pain who are at risk for opioid misuse are presented. Specific behavioral interventions designed to improve adherence with prescription opioids among persons treated for chronic pain, such as frequent monitoring, periodic urine screens, opioid therapy agreements, opioid checklists, and motivational counseling, are also reviewed. Use of state-sponsored prescription drug monitoring programs is also encouraged. Areas requiring additional investigation are identified, and the future role of abuse-deterrent opioids and innovative technology in addressing issues of opioid therapy and pain are presented. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  15. Retention in naltrexone implant treatment for opioid dependence.

    Science.gov (United States)

    Kunøe, Nikolaj; Lobmaier, Philipp; Vederhus, John Kåre; Hjerkinn, Bjørg; Hegstad, Solfrid; Gossop, Michael; Kristensen, Oistein; Waal, Helge

    2010-09-01

    Naltrexone's usefulness in the treatment of opioid dependence stems from its ability to block the action of heroin and other opioids. However, many patients are ambivalent towards naltrexone and often drop out of treatment with orally administered naltrexone. Sustained release naltrexone seems promising in reducing opioid use, but the extent to which patients remain in treatment beyond the first dosage of naltrexone is not clear. Patients (n=61) receving treatment with sustained release naltrexone implants were offered a second naltrexone implant after 6 months. Patients who remained in treatment were compared to those who did not, on drug use, mental health, and social problems before and during naltrexone implant treatment. Information was obtained on other treatments sought by patients who discontinued naltrexone. Blood samples were used to verify naltrexone release, and hair samples to confirm opioid intake. Of the patients who received the first naltrexone implant, 51% (n=31) remained in naltrexone implant treatment. Among those who discontinued treatment, 21% expressed a wish to reimplant but failed to attend for reimplantation and 28% declined reimplantation: 6 non-retained patients initiated maintenance or residential treatment. Remaining in naltrexone treatment was related to pre-study length of employment, illicit drug use, and concern for family problems. Higher levels of substance misuse and criminal activity during naltrexone treatment were negatively related to subsequent retention. Rates of retention among opioid-dependent patients receiving naltrexone implant treatment are encouraging and support this as a feasible long-term treatment option. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  16. Molecular and cellular mechanisms of the age-dependency of opioid analgesia and tolerance

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    Zhao Jing

    2012-05-01

    Full Text Available Abstract The age-dependency of opioid analgesia and tolerance has been noticed in both clinical observation and laboratory studies. Evidence shows that many molecular and cellular events that play essential roles in opioid analgesia and tolerance are actually age-dependent. For example, the expression and functions of endogenous opioid peptides, multiple types of opioid receptors, G protein subunits that couple to opioid receptors, and regulators of G protein signaling (RGS proteins change with development and age. Other signaling systems that are critical to opioid tolerance development, such as N-methyl-D-aspartic acid (NMDA receptors, also undergo age-related changes. It is plausible that the age-dependent expression and functions of molecules within and related to the opioid signaling pathways, as well as age-dependent cellular activity such as agonist-induced opioid receptor internalization and desensitization, eventually lead to significant age-dependent changes in opioid analgesia and tolerance development.

  17. The Need for Psychosocial Interventions to Facilitate the Transition to Extended-Release Naltrexone (XR-NTX) Treatment for Opioid Dependence: A Concise Review of the Literature

    Science.gov (United States)

    Ramsey, Susan E.; Rounsaville, Dan; Hoskinson, Randall; Park, Tae Woo; Ames, Evan G.; Neirinckx, Victor D.; Friedmann, Peter

    2016-01-01

    Given the increase of opioid dependence and opioid-related morbidity and mortality, improving treatment options for individuals with opioid dependence warrants increased attention. This article provides a concise review of work in this area. Remission from opioid dependence can be very difficult to sustain, particularly in the absence of opioid replacement or opioid antagonist therapy. For those who wish to transition from opioid use or opioid replacement therapy to opioid antagonist therapy, a significant challenge can be the period of withdrawal symptoms that must be endured prior to the initiation of opioid antagonist therapy. Studies that have incorporated psychosocial interventions into detoxification protocols have found that they can result in improved treatment outcomes. Interventions based on Acceptance and Commitment Therapy have shown promise in the treatment of clinical disorders that present with symptoms similar to those of opioid withdrawal and have been found to positively impact outcomes among those tapering from methadone. However, the use of an Acceptance and Commitment Therapy-based intervention has yet to be studied among opioid-dependent patients transitioning to XR-NTX, and its value to those transitioning to XR-NTX is currently unknown. PMID:27512336

  18. Cognitive function during early abstinence from opioid dependence: a comparison to age, gender, and verbal intelligence matched controls

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    Kähkönen Seppo

    2006-02-01

    Full Text Available Abstract Background Individuals with opioid dependence have cognitive deficits during abuse period in attention, working memory, episodic memory, and executive function. After protracted abstinence consistent cognitive deficit has been found only in executive function. However, few studies have explored cognitive function during first weeks of abstinence. The purpose of this study was to study cognitive function of individuals with opioid dependence during early abstinence. It was hypothesized that cognitive deficits are pronounced immediately after peak withdrawal symptoms have passed and then partially recover. Methods Fifteen patients with opioid dependence and fifteen controls matched for, age, gender, and verbal intelligence were tested with a cognitive test battery When patients performed worse than controls correlations between cognitive performance and days of withdrawal, duration of opioid abuse, duration of any substance abuse, or opioid withdrawal symptom inventory score (Short Opiate Withdrawal Scale were analyzed. Results Early abstinent opioid dependent patients performed statistically significantly worse than controls in tests measuring complex working memory, executive function, and fluid intelligence. Their complex working memory and fluid intelligence performances correlated statistically significantly with days of withdrawal. Conclusion The results indicate a rather general neurocognitive deficit in higher order cognition. It is suggested that cognitive deficit during early abstinence from opioid dependence is related to withdrawal induced neural dysregulation in the prefrontal cortex and is partly transient.

  19. Prediction formulas for individual opioid analgesic requirements based on genetic polymorphism analyses.

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    Kaori Yoshida

    Full Text Available The analgesic efficacy of opioids is well known to vary widely among individuals, and various factors related to individual differences in opioid sensitivity have been identified. However, a prediction model to calculate appropriate opioid analgesic requirements has not yet been established. The present study sought to construct prediction formulas for individual opioid analgesic requirements based on genetic polymorphisms and clinical data from patients who underwent cosmetic orthognathic surgery and validate the utility of the prediction formulas in patients who underwent major open abdominal surgery.To construct the prediction formulas, we performed multiple linear regression analyses using data from subjects who underwent cosmetic orthognathic surgery. The dependent variable was 24-h postoperative or perioperative fentanyl use, and the independent variables were age, gender, height, weight, pain perception latencies (PPL, and genotype data of five single-nucleotide polymorphisms (SNPs. To examine the utility of the prediction formulas, we performed simple linear regression analyses using subjects who underwent major open abdominal surgery. Actual 24-h postoperative or perioperative analgesic use and the predicted values that were calculated using the multiple regression equations were incorporated as dependent and independent variables, respectively.Multiple linear regression analyses showed that the four SNPs, PPL, and weight were retained as independent predictors of 24-h postoperative fentanyl use (R² = 0.145, P = 5.66 × 10⁻¹⁰ and the two SNPs and weight were retained as independent predictors of perioperative fentanyl use (R² = 0.185, P = 1.99 × 10⁻¹⁵. Simple linear regression analyses showed that the predicted values were retained as an independent predictor of actual 24-h postoperative analgesic use (R² = 0.033, P = 0.030 and perioperative analgesic use (R² = 0.100, P = 1.09 × 10⁻⁴, respectively.We constructed

  20. DYNAMICS OF OPIOID SUBSTITUTION TREATMENTIN DIFFERENT INITIAL SUBSTANCE USER OPIOID DEPENDENT PATIENTS.

    Science.gov (United States)

    Todadze, Kh; Mosia, S

    2016-05-01

    Injecting drug user size estimation studies carried out in 2009, 2012 and 2015 revealed growing trends of drug abuse in Georgia:estimated number of people who inject drugs (PWID) have been increased from 40000 and 45000 to 50000. Since Soviet period the most popular injective narcotics have been opioids: home-made opium, heroine, buprenorphine and home-made desomorphine ("Krokodile") replacing each other on the black market. Self-made desomorphine typically contains big amounts of different toxic substances and causes significant somatic disorders, especially skin, bone, blood infections, liver and kidney failure; is highly addictive, associates with frequent injections that enhance injecting-related harm, including the risk of HIV transmission, in comparison with typical opioids. The aim of the study was to determine the effectiveness of opioid substitution treatment (OST) on depression and anxiety in opioid dependent clients with history of different opioid substance use. 104 opioid drug users undergoing OST with intensive psychological counseling have been divided in 5 groups according to the principal opioid drug that was abused during past 6 months before starting treatment: heroine, desomorphine, illicit methadone injectors, illicit buprenorphine injectors, and multiple drug abusers consuming opioids as primary drugs. Level of depression (Beck Depression Inventory), anxiety (Spielberger Anxiety Inventory) as well as clinical symptoms, risky behavior, quality of life (WHO), and other data were measured before starting and after 3, 9, 15, 21 months of treatment. The illegal use of psychotropic-narcotics was checked through random urine-testing 1-2 times per patient per month. In all five groups remarkable decrease of depression and anxiety was observed in comparison with the starting data. Before inclusion desomorphine and poly-drug users had the highest scores of depression and anxiety while buprenorphine users manifested the lowest rate. Improvement of

  1. Opioid dependence and pregnancy: minimizing stress on the fetal brain.

    Science.gov (United States)

    McCarthy, John J; Leamon, Martin H; Finnegan, Loretta P; Fassbender, Catherine

    2017-03-01

    Increase in the number of opioid-dependent pregnant women delivering babies at risk for neonatal abstinence syndrome prompted a US Government Accountability Office report documenting deficits in research and provider knowledge about care of the maternal/fetal unit and the neonate. There are 3 general sources of dependence: untreated opioid use disorder, pain management, and medication-assisted treatment with methadone or buprenorphine. A survey of methadone patients' experiences when telling a physician of their pregnancy and opioid dependence demonstrated physician confusion about proper care, frequent negative interactions with the mother, and failures to provide appropriate referral. Patients in pain management were discharged without referral when the physician was told of the pregnancy. Methadone and buprenorphine were frequently seen negatively because they "caused" neonatal abstinence syndrome. Most mothers surveyed had to find opioid treatment on their own. How dependence is managed medically is a critical determinant of the level of stress on both mother and fetus, and therefore another determinant of neonatal health. The effects of both opioid withdrawal stress and maternal emotional stress on neonatal and developmental outcomes are reviewed. Currently, there have been efforts to criminalize maternal opioid dependence and to encourage or coerce pregnant women to undergo withdrawal. This practice poses both acute risks of fetal hypoxia and long-term risks of adverse epigenetic programming related to catecholamine and corticosteroid surges during withdrawal. Contemporary studies of the effects of withdrawal stress on the developing fetal brain are urgently needed to elucidate and quantify the risks of such practices. At birth, inconsistencies in the hospital management of neonates at risk for neonatal abstinence syndrome have been observed. Neglect of the critical role of maternal comforting in neonatal abstinence syndrome management is an iatrogenic and

  2. Mu opioid mediated discriminative-stimulus effects of tramadol: an individual subjects analysis.

    Science.gov (United States)

    Strickland, Justin C; Rush, Craig R; Stoops, William W

    2015-03-01

    Drug discrimination procedures use dose-dependent generalization, substitution, and pretreatment with selective agonists and antagonists to evaluate receptor systems mediating interoceptive effects of drugs. Despite the extensive use of these techniques in the nonhuman animal literature, few studies have used human participants. Specifically, human studies have not routinely used antagonist administration as a pharmacological tool to elucidate the mechanisms mediating the discriminative stimulus effects of drugs. This study evaluated the discriminative-stimulus effects of tramadol, an atypical analgesic with monoamine and mu opioid activity. Three human participants first learned to discriminate 100 mg tramadol from placebo. A range of tramadol doses (25 to 150 mg) and hydromorphone (4 mg) with and without naltrexone pretreatment (50 mg) were then administered to participants after they acquired the discrimination. Tramadol produced dose-dependent increases in drug-appropriate responding and hydromorphone partially or fully substituted for tramadol in all participants. These effects were attenuated by naltrexone. Individual participant records indicated a relationship between mu opioid activity (i.e., miosis) and drug discrimination performance. Our findings indicate that mu opioid activity may mediate the discriminative-stimulus effects of tramadol in humans. The correspondence of generalization, substitution, and pretreatment findings with the animal literature supports the neuropharmacological specificity of the drug discrimination procedure. © Society for the Experimental Analysis of Behavior.

  3. Restless legs syndrome in opioid dependent patients

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    Abhishek Ghosh

    2014-01-01

    Full Text Available Although frequently underdiagnosed, several epidemiological studies have estimated the prevalence of restless legs syndrome (RLS in western countries at 5-15% of the general population. The diagnosis is usually made on a clinical basis, according to the criteria established by the international RLS study group. There are case reports of transient RLS in opiate withdrawal. We describe three opiate (dextropropoxyphene (DPP dependent young male patients; two of them had DPP intoxication/withdrawal seizure developing RLS during opiate withdrawal. However, their RLS persisted even after the remission of other withdrawal symptoms. Thyroid function test, hemogram, serum ferritin were normal in all of them. The cases responded well to a treatment with ropinirole. Hence, there might be a causal association, which required further well-designed studies to substantiate. The sleep disturbances and use of benzodiazepines can be minimized by increasing clinician′s sensitivity to diagnose RLS.

  4. Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence.

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    Elkader, Alexander; Sproule, Beth

    2005-01-01

    Buprenorphine is a semi-synthetic opioid derived from thebaine, a naturally occurring alkaloid of the opium poppy, Papaver somniferum. The pharmacology of buprenorphine is unique in that it is a partial agonist at the opioid mu receptor. Buprenorphine undergoes extensive first-pass metabolism and therefore has very low oral bioavailability; however, its bioavailability sublingually is extensive enough to make this a feasible route of administration for the treatment of opioid dependence. The mean time to maximum plasma concentration following sublingual administration is variable, ranging from 40 minutes to 3.5 hours. Buprenorphine has a large volume of distribution and is highly protein bound (96%). It is extensively metabolised by N-dealkylation to norbuprenorphine primarily through cytochrome P450 (CYP) 3A4. The terminal elimination half-life of buprenorphine is long and there is considerable variation in reported values (mean values ranging from 3 to 44 hours). Most of a dose of buprenorphine is eliminated in the faeces, with approximately 10-30% excreted in urine. Naloxone has been added to a sublingual formulation of buprenorphine to reduce the abuse liability of the product. The presence of naloxone does not appear to influence the pharmacokinetics of buprenorphine. Buprenorphine crosses the placenta during pregnancy and also crosses into breast milk. Buprenorphine dosage does not need to be significantly adjusted in patients with renal impairment; however, since CYP3A activity may be decreased in patients with severe chronic liver disease, it is possible that the metabolism of buprenorphine will be altered in these patients. Although there is limited evidence in the literature to date, drugs that are known to inhibit or induce CYP3A4 have the potential to diminish or enhance buprenorphine N-dealkylation. It appears that the interaction between buprenorphine and benzodiazepines is more likely to be a pharmacodynamic (additive or synergistic) than a

  5. Interaction of the mu-opioid receptor with GPR177 (Wntless inhibits Wnt secretion: potential implications for opioid dependence

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    Stagljar Igor

    2010-03-01

    Full Text Available Abstract Background Opioid agonist drugs produce analgesia. However, long-term exposure to opioid agonists may lead to opioid dependence. The analgesic and addictive properties of opioid agonist drugs are mediated primarily via the mu-opioid receptor (MOR. Opioid agonists appear to alter neuronal morphology in key brain regions implicated in the development of opioid dependence. However, the precise role of the MOR in the development of these neuronal alterations remains elusive. We hypothesize that identifying and characterizing novel MOR interacting proteins (MORIPs may help to elucidate the underlying mechanisms involved in the development of opioid dependence. Results GPR177, the mammalian ortholog of Drosophila Wntless/Evi/Sprinter, was identified as a MORIP in a modified split ubiquitin yeast two-hybrid screen. GPR177 is an evolutionarily conserved protein that plays a critical role in mediating Wnt protein secretion from Wnt producing cells. The MOR/GPR177 interaction was validated in pulldown, coimmunoprecipitation, and colocalization studies using mammalian tissue culture cells. The interaction was also observed in rodent brain, where MOR and GPR177 were coexpressed in close spatial proximity within striatal neurons. At the cellular level, morphine treatment caused a shift in the distribution of GPR177 from cytosol to the cell surface, leading to enhanced MOR/GPR177 complex formation at the cell periphery and the inhibition of Wnt protein secretion. Conclusions It is known that chronic morphine treatment decreases dendritic arborization and hippocampal neurogenesis, and Wnt proteins are essential for these processes. We therefore propose that the morphine-mediated MOR/GPR177 interaction may result in decreased Wnt secretion in the CNS, resulting in atrophy of dendritic arbors and decreased neurogenesis. Our results demonstrate a previously unrecognized role for GPR177 in regulating cellular response to opioid drugs.

  6. Phytotherapy of opioid dependence and withdrawal syndrome: a review.

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    Tabatabai, Seyed Meghdad; Dashti, Saeedeh; Doosti, Fatemeh; Hosseinzadeh, Hossein

    2014-06-01

    Development of tolerance and dependence is a major problem associated with opioid treatment. Withdrawal syndrome is common between medical and illicit users of these agents. Phytomedicine has shown promise in the treatment of this complicated psychosomatic condition. In this study, the effects of plant extracts and active components on morphine dependence and withdrawal syndrome are discussed. Proper keywords were used to search through PubMed, Google Scholar, and SciVerse, as well as two local scientific databases, www.iranmedex.com and www.SID.com. All relevant results (original articles, meeting abstracts, patents, etc.) published from 2000 to 2013 were chosen for final review. A total of 35 plant species were studied on this subject. Plants from Lamiaceae, Ranunculaceae, and Apiaceae families were especially effective. A few studies were carried out on human subjects and the rest in animal models. Opioid dependence and withdrawal syndrome remain an intimidating challenge. Nonetheless, plants and their derivatives are suitable sources for their treatment. Although there are several plants shown to be effective in animal models, few clinical studies are available.

  7. Sexual dysfunction in patients with alcohol and opioid dependence

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    Sandeep Grover

    2014-01-01

    Full Text Available There are limited numbers of studies which have evaluated the sexual dysfunction (SD in patients with alcohol and opioids dependence. This article reviews the existing literature. Electronic searches were carried out using the PubMed, Google Scholar, and ScienceDirect to locate the relevant literature. Subjects addicted to heroin or on methadone maintenance treatment (MMT or buprenorphine maintenance treatment (BMT show higher rates of SD in comparison to the general population. SD rates have ranged 34-85% for heroin addicts, 14-81% for MMT, 36-83% for BMT, and 90% for naltrexone maintenance. The rates of SD in alcohol-dependent population have ranged 40-95.2%, with rates being consistently much higher in alcohol-dependent population than in the healthy controls or social drinkers. The common SDs reported have been erectile dysfunction followed by premature ejaculation, retarded ejaculation and decreased sexual desire among men, and dyspareunia and vaginal dryness among women. This review suggests that long-term use of alcohol and opioids are associated with SD in almost all domains of sexual functioning. There is a need to increase the awareness of clinicians about this association as many times SD in patients with substance abuse lead to poor treatment compliance and relapse. Further, there is a need to carry out more number of studies to understand the relationship in a better way.

  8. Smoking history, nicotine dependence and opioid use in patients with chronic non-malignant pain

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    Plesner, K; Jensen, H I; Højsted, J

    2016-01-01

    BACKGROUND: Previous studies have demonstrated a positive association between smoking and addiction to opioids in patients with chronic non-malignant pain. This could be explained by a susceptibility in some patients to develop addiction. Another explanation could be that nicotine influences both...... pain and the opioid system. The objective of the study was to investigate whether smoking, former smoking ± nicotine use and nicotine dependence in patients with chronic non-malignant pain were associated with opioid use and addiction to opioids. METHODS: The study was a cross-sectional study carried...... as in the general population. The prevalence of patients using opioids was 54% and the prevalence of addiction to opioids was 6%. No significant differences in addiction were found between the different smoking groups, but smokers and former smokers using nicotine tended to use opioids more frequently and at higher...

  9. Combining stepped-care approaches with behavioral reinforcement to motivate employment in opioid-dependent outpatients.

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    Kidorf, Michael; Neufeld, Karin; Brooner, Robert K

    2004-01-01

    Employment is associated with improved treatment outcome for opioid-dependent outpatients receiving methadone (e.g., Platt, 1995). Opioid-dependent individuals typically enter treatment unemployed and many remain unemployed despite reductions in heroin use. Additional interventions are needed to motivate employment seeking behaviors and outcome. This article reports on a promising approach to reduce the chronic unemployment commonplace in treatment-seeking, opioid-dependent patients--a "stepped care" service delivery intervention that incorporates multiple behavioral reinforcements to motivate patient participation in and adherence to the treatment plan. This therapeutic approach (Motivated Stepped Care--MSC; Brooner and Kidorf (2002) was refined and modified to motivate and support a range of positive treatment behaviors and outcomes in patients with opioid-dependence (Kidorf et al. 1999), including job-seeking and acquisition. Patients who are unemployed after one year of treatment are systematically advanced to more intensive steps of weekly counseling and remain there until employment is attained. Those who remain unemployed despite exposure to at least 4 weeks of counseling at the highest step of care (Step 3, which is 9 h weekly of counseling) are started on a methadone taper in preparation for discharge, which is reversible upon attaining a job. This article describes the MSC approach and presents rates of employment for patients who were judged capable of working (n = 228). A review of medical and billing records during August--September 2002 revealed that the great majority of these patients were employed (93%), usually in full-time positions. Employment was associated with less frequent advancement to higher intensities of weekly counseling because of drug use. Further, multiple indices of improved employment stability and functioning, including months of work, hours of work, and annualized salary, were associated with better drug use outcomes. These data

  10. Methadone induction in primary care for opioid dependence: a pragmatic randomized trial (ANRS Methaville.

    Directory of Open Access Journals (Sweden)

    Patrizia Maria Carrieri

    Full Text Available Methadone coverage is poor in many countries due in part to methadone induction being possible only in specialized care (SC. This multicenter pragmatic trial compared the effectiveness of methadone treatment between two induction models: primary care (PC and SC.In this study, registered at ClinicalTrials.Gov (NCT00657397, opioid-dependent individuals not on methadone treatment for at least one month or receiving buprenorphine but needing to switch were randomly assigned to start methadone in PC (N = 155 or in SC (N = 66 in 10 sites in France. Visits were scheduled at months M0, M3, M6 and M12. The primary outcome was self-reported abstinence from street-opioids at 12 months (M12 (with an underlying 15% non-inferiority hypothesis for PC. Secondary outcomes were abstinence during follow-up, engagement in treatment (i.e. completing the induction period, retention and satisfaction with the explanations provided by the physician. Primary analysis used intention to treat (ITT. Mixed models and the log-rank test were used to assess the arm effect (PC vs. SC on the course of abstinence and retention, respectively.In the ITT analysis (n = 155 in PC, 66 in SC, which compared the proportions of street-opioid abstinent participants, 85/155 (55% and 22/66 (33% of the participants were classified as street-opioid abstinent at M12 in PC and SC, respectively. This ITT analysis showed the non-inferiority of PC (21.5 [7.7; 35.3]. Engagement in treatment and satisfaction with the explanations provided by the physician were significantly higher in PC than SC. Retention in methadone and abstinence during follow-up were comparable in both arms (p = 0.47, p = 0.39, respectively.Under appropriate conditions, methadone induction in primary care is feasible and acceptable to both physicians and patients. It is as effective as induction in specialized care in reducing street-opioid use and ensuring engagement and retention in treatment for opioid dependence.Number Eudract

  11. Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system

    Science.gov (United States)

    Berrendero, Fernando; Robledo, Patricia; Trigo, José Manuel; Martín-García, Elena; Maldonado, Rafael

    2010-01-01

    Nicotine is the primary component of tobacco that maintains the smoking habit and develops addiction. The adaptive changes of nicotinic acetylcholine receptors produced by repeated exposure to nicotine play a crucial role in the establishment of dependence. However, other neurochemical systems also participate in the addictive effects of nicotine including glutamate, cannabinoids, GABA and opioids. This review will cover the involvement of these neurotransmitters in nicotine addictive properties, with a special emphasis on the endogenous opioid system. Thus, endogenous enkephalins and beta-endorphins acting on mu-opioid receptors are involved in nicotine rewarding effects, whereas opioid peptides derived from prodynorphin participate in nicotine aversive responses. An upregulation of mu-opioid receptors has been reported after chronic nicotine treatment that could counteract the development of nicotine tolerance, whereas the downregulation induced on kappa-opioid receptors seems to facilitate nicotine tolerance. Endogenous enkephalins acting on mu-opioid receptors also play a role in the development of physical dependence to nicotine. In agreement with these actions of the endogenous opioid system, the opioid antagonist naltrexone has shown to be effective for smoking cessation in certain subpopulations of smokers. PMID:20170672

  12. Do gender differences in depression remain after controlling for early maladaptive schemas? An examination in a sample of opioid dependent treatment seeking adults.

    Science.gov (United States)

    Shorey, Ryan C; Stuart, Gregory L; Anderson, Scott

    2013-01-01

    The abuse of opioids is a serious and prevalent problem and research is needed on factors that may place individuals at risk for misusing opioids. Depression is a common co-morbid mental health problem among opioid users. Theory and research suggest that early maladaptive schemas may underlie mental health problems including depression and substance abuse. The current study sought to determine whether early maladaptive schemas were associated with depression among a treatment seeking sample of male and female opioid users (n = 194). We also examined whether depression, as assessed by the Minnesota Multiphasic Personality Inventory, Second Edition, varied by gender and whether gender differences in depression remained after controlling for early maladaptive schemas. Results showed that women scored significantly higher than men on three of the five early maladaptive schema domains and that gender did not predict depression after controlling for schema domains. Early maladaptive schemas were also more strongly associated with depression for men than women. Implications of these findings for interventions and future research are discussed. Individuals with opioid dependence have a number of early maladaptive schemas that may be contributing to the onset and maintenance of substance use. Although there are generally broad gender differences in major depression, findings from the current study suggest that early maladaptive schemas are a better predictor of depressive symptoms than gender among opioid dependent adults. The treatment of opioid dependence, with or without co-morbid depressive symptoms, should target early maladaptive schemas. Copyright © 2012 John Wiley & Sons, Ltd.

  13. Vulnerability for cocaine dependence / Involvement of µ-opioid receptors

    NARCIS (Netherlands)

    Lesscher, Heidi Maria Bonifacio

    2004-01-01

    Drug dependence is a major health issue worldwide, which is characterised by its persistence and high rates of relapse. Individual differences exist in the vulnerability for drug dependence after first exposure to drugs of abuse like cocaine. A likely risk factor for drug dependence is the

  14. Vulnerability for cocaine dependence / Involvement of µ-opioid receptors

    NARCIS (Netherlands)

    Lesscher, Heidi Maria Bonifacio

    2004-01-01

    Drug dependence is a major health issue worldwide, which is characterised by its persistence and high rates of relapse. Individual differences exist in the vulnerability for drug dependence after first exposure to drugs of abuse like cocaine. A likely risk factor for drug dependence is the sensitivi

  15. Increased opioid dependence in a mouse model of panic disorder

    Directory of Open Access Journals (Sweden)

    Xavier Gallego

    2010-02-01

    Full Text Available Panic disorder is a highly prevalent neuropsychiatric disorder that shows co-occurrence with substance abuse. Here, we demonstrate that TrkC, the high affinity receptor for neurotrophin-3, is a key molecule involved in panic disorder and opiate dependence, using a transgenic mouse model (TgNTRK3. Constitutive TrkC overexpression in TgNTRK3 mice dramatically alters spontaneous firing rates of locus coeruleus neurons and the response of the noradrenergic system to chronic opiate exposure, possibly related to the altered regulation of neurotrophic peptides observed. Notably, TgNTRK3 locus coeruleus neurons showed an increased firing rate in saline-treated conditions and profound abnormalities in their response to met5-enkephalin. Behaviorally, chronic morphine administration induced a significantly increased withdrawal syndrome in TgNTRK3 mice. In conclusion, we show here that the NT-3/TrkC system is an important regulator of neuronal firing in locus coeruleus and could contribute to the adaptations of the noradrenergic system in response to chronic opiate exposure. Moreover, our results indicate that TrkC is involved in the molecular and cellular changes in noradrenergic neurons underlying both panic attacks and opiate dependence and support a functional endogenous opioid deficit in panic disorder patients.

  16. Individual variation in the motivational and neurobiological effects of an opioid cue.

    Science.gov (United States)

    Yager, Lindsay M; Pitchers, Kyle K; Flagel, Shelly B; Robinson, Terry E

    2015-03-13

    A discrete cue associated with intravenous injections of cocaine acquires greater control over motivated behavior in some rats ('sign-trackers', STs) than others ('goal-trackers', GTs). It is not known, however, if such variation generalizes to cues associated with other drugs. We asked, therefore, whether a discrete cue (a light) associated with the intravenous administration of an opioid drug (the short-acting mu receptor agonist, remifentanil) acquires incentive motivational properties differently in STs and GTs, as indicated by tests of Pavlovian conditioned approach and conditioned reinforcement. Consistent with studies using cocaine, STs approached a classically conditioned opioid cue more readily than GTs, and in a test of conditioned reinforcement worked more avidly to get it. Interestingly, STs and GTs did not differ in the acquisition of a conditioned orienting response. In addition, the performance of conditioned approach behavior, but not conditioned orientation, was attenuated by pretreatment with the dopamine receptor antagonist, flupenthixol, into the core of the nucleus accumbens. Lastly, food and opioid cues engaged similar amygdalo-striatal-thalamic circuitry to a much greater extent in STs than GTs, as indicated by Fos expression. Taken together, these data demonstrate that, similar to food and cocaine cues: (1) a discrete opioid cue attains greater incentive motivational value in STs than GTs; (2) the attribution of incentive motivational properties to an opioid cue is dopamine dependent; and (3) an opioid cue engages the so-called 'motive circuit' only if it is imbued with incentive salience.

  17. New developments in the management of opioid dependence: focus on sublingual buprenorphine–naloxone

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    Soyka M

    2015-01-01

    Full Text Available Michael Soyka1,21Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany; 2Private Hospital Meiringen, Meiringen, SwitzerlandAbstract: Opioid maintenance therapy is a well-established first-line treatment approach in opioid dependence. Buprenorphine, a partial opioid agonist, has been found by numerous studies to be an effective and safe medication in the treatment of opioid dependence. At present, buprenorphine is available as a monodrug or in a fixed 4:1 ratio combination with naloxone. A diminished risk of diversion and abuse for the buprenorphine–naloxone combination is likely but not firmly established. Conventional formulations are given sublingually to avoid the hepatic first-pass effect. A novel film tablet is available only in the US and Australia. Other novel, sustained-release formulations (implant, depot are currently being developed and tested. Recent studies, including a Cochrane meta-analysis, suggest that the retention with buprenorphine is lower than for methadone, but that buprenorphine may be associated with less drug use. Higher doses of buprenorphine are associated with better retention rates. Buprenorphine has a ceiling effect at the opioid receptor with regard to respiratory depression, and may cause fewer fatal intoxications than methadone. Possible antidepressant effects of buprenorphine and its use in comorbid psychiatric patients has not been studied in much detail. Clinical implications are discussed.Keywords: buprenorphine, methadone, naloxone, opioids, opioid dependence, therapy

  18. Opioid-induced constipation: rationale for the role of norbuprenorphine in buprenorphine-treated individuals

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    Webster LR

    2016-06-01

    Full Text Available Lynn R Webster,1 Michael Camilleri,2 Andrew Finn3 1PRA Health Sciences, Salt Lake City, UT, 2Mayo Clinic Rochester, MN, 3BioDelivery Sciences, Inc., Raleigh, NC, USA Abstract: Buprenorphine and buprenorphine–naloxone fixed combinations are effective for managing patients with opioid dependence, but constipation is one of the most common side effects. Evidence indicates that the rate of constipation is lower when patients are switched from sublingual buprenorphine–naloxone tablets or films to a bilayered bioerodible mucoadhesive buccal film formulation, and while the bilayered buccal film promotes unidirectional drug flow across the buccal mucosa, the mechanism for the reduced constipation is unclear. Pharmacokinetic simulations indicate that chronic dosing of sublingually administered buprenorphine may expose patients to higher concentrations of norbuprenorphine than buprenorphine, while chronic dosing of the buccal formulation results in higher buprenorphine concentrations than norbuprenorphine. Because norbuprenorphine is a potent full agonist at mu-opioid receptors, the differences in norbuprenorphine exposure may explain the observed differences in treatment-emergent constipation between the sublingual formulation and the buccal film formulation of buprenorphine–naloxone. To facilitate the understanding and management of opioid-dependent patients at risk of developing opioid-induced constipation, the clinical profiles of these formulations of buprenorphine and buprenorphine-naloxone are summarized, and the incidence of treatment-emergent constipation in clinical trials is reviewed. These data are used to propose a potential role for exposure to norbuprenorphine, an active metabolite of buprenorphine, in the pathophysiology of opioid-induced constipation. Keywords: opioid, safety, buccal, sublingual, dependence, maintenance

  19. Naltrexone depot formulations for opioid and alcohol dependence: a systematic review.

    Science.gov (United States)

    Lobmaier, Philipp P; Kunøe, Nikolaj; Gossop, Michael; Waal, Helge

    2011-12-01

    Naltrexone is an opioid receptor antagonist that blocks the reinforcing effects of opioids and reduces alcohol consumption and craving. It has no abuse potential, mild and transient side effects, and thus appears an ideal pharmacotherapy for opioid dependence. Its effectiveness in alcohol dependence is less evident, but compliance with naltrexone combined with psychosocial support has been repeatedly shown to improve drinking outcomes. Limited compliance with oral naltrexone treatment is a known drawback. Several naltrexone implant and injectable depot formulations are being investigated and provide naltrexone release for at least 1 month. Studies among opioid-dependent patients indicate significant reductions in heroin use, but sample sizes are usually small. In alcohol dependence, two large multicenter trials report alcohol and craving reductions for naltrexone and placebo groups, indicating a significant but moderate effect. The pharmacokinetic profile of the injectable formulation indicates reliable naltrexone release over 1 month at therapeutic levels. Implant formulations releasing naltrexone up to 7 months are reported. Findings on safety and tolerability confirm the generally mild adverse effects described for naltrexone tablets. However, further research on therapeutic levels (i.e., opioid blocking) is warranted. The majority of naltrexone implants lacks approval for regular clinical use and larger longitudinal studies are needed. The available naltrexone depot formulations have the potential to significantly improve medication compliance in opioid and alcohol dependence. In certain circumstances, they may constitute a promising new treatment option. © 2010 Blackwell Publishing Ltd.

  20. Opioid Dependent and Pregnant: What Are the Best Options for Mothers and Neonates?

    Directory of Open Access Journals (Sweden)

    Annemarie Unger

    2012-01-01

    Full Text Available Pregnancy in opioid-dependent women is a major public health issue. Women who are afflicted by opioid addiction are a highly vulnerable group of patients frequently becoming pregnant unplanned and at risk of adverse pregnancy outcomes and peri-natal complications. Opioid agonist maintenance treatment is the best option for the majority of women. Ideally, early and closely monitored treatment in an interdisciplinary team approach including social workers, nurses, psychologists, psychiatrists, gynecologists, anesthesiologists, and pediatricians should be provided. The treatment of comorbid psychiatric conditions, the resolution of financial, legal, and housing issues, and the psychosocial support provided have a significant effect on optimizing pregnancy outcomes. This paper aims to update health professionals in the field of gynecology and obstetrics on the latest optimal treatment approaches for mothers suffering from opioid dependence and their neonates.

  1. Does naltrexone affect craving in abstinent opioid-dependent patients?

    NARCIS (Netherlands)

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

    2007-01-01

    Naltrexone blocks the opioid receptors that modulate the release of dopamine in the brain reward system and therefore blocks the rewarding effects of heroin and alcohol. It is generally assumed that naltrexone leads to reduction of craving, but few studies have been performed to prove this. The purp

  2. Does naltrexone affect craving in abstinent opioid-dependent patients?

    NARCIS (Netherlands)

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

    2007-01-01

    Naltrexone blocks the opioid receptors that modulate the release of dopamine in the brain reward system and therefore blocks the rewarding effects of heroin and alcohol. It is generally assumed that naltrexone leads to reduction of craving, but few studies have been performed to prove this. The

  3. State-dependent µ-opioid Modulation of Social Motivation – a model

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    Guro Engvig Loseth

    2014-12-01

    Full Text Available Social mammals engage in affiliative interactions both when seeking relief from negative affect and when searching for pleasure and joy. These two motivational states are both modulated by µ-opioid transmission. The µ-opioid receptor (MOR system in the brain mediates pain relief and reward behaviours, and is implicated in social reward processing and affiliative bonding across mammalian species. However, pharmacological manipulation of the µ-opioid system has yielded opposite effects on rodents and primates: in rodents, social motivation is generally increased by MOR agonists and reduced by antagonists, whereas the opposite pattern has been shown in primates. Here, we address this paradox by taking into account differences in motivational state. We first review evidence for µ-opioid mediation of reward processing, emotion regulation, and affiliation in humans, non-human primates, rodents and other species. Based on the consistent cross-species similarities in opioid functioning, we propose a unified, state-dependent model for µ-opioid modulation of affiliation across the mammalian species. Finally, we show that this state-dependent model is supported by evidence from both rodent and primate studies, when species and age differences in social separation response are taken into account.

  4. Studies on the adrenomedullary dependence of kappa-opioid agonist-induced diuresis in conscious rats.

    Science.gov (United States)

    Borkowski, K. R.

    1989-01-01

    1. The dependence of kappa-opioid agonist-induced diuresis, upon an intact and functional adrenal medulla in conscious rats, was investigated in order to test the hypothesis that the diuresis is mediated by a blood-borne 'diuretic factor', of adrenomedullary origin, released by kappa-opioid receptor stimulation. 2. Confirming previous observations, adrenal demedullation significantly attenuated diuretic responses to the kappa-opioid agonists U50488H, ethylketocyclazocine (EKC) and tifluadom, but did not affect basal urine output, furosemide-induced diuresis or the antidiuretic response to the mu-opioid agonist, buprenorphine. Naloxone abolished U50488H-induced diuresis, confirming an involvement of opioid receptors. 3. Transfusion studies established that blood, from intact rats treated with U50488H, induced diuresis in intact and demedullated recipient rats, whether or not the recipients had been pretreated with naloxone. However, blood from demedullated rats treated with U50448H was unable to induce diuresis when administered to intact or demedullated recipients. 4. It is concluded that kappa-opioid agonist-induced diuresis is dependent upon an intact and functional adrenal medulla and appears to be mediated by a blood-borne 'diuretic factor' of adrenomedullary origin. PMID:2558758

  5. Casein kinase 1-epsilon deletion increases mu opioid receptor-dependent behaviors and binge eating1.

    Science.gov (United States)

    Goldberg, L R; Kirkpatrick, S L; Yazdani, N; Luttik, K P; Lacki, O A; Keith Babbs, R; Jenkins, D F; Evan Johnson, W; Bryant, C D

    2017-09-01

    Genetic and pharmacological studies indicate that casein kinase 1 epsilon (Csnk1e) contributes to psychostimulant, opioid, and ethanol motivated behaviors. We previously used pharmacological inhibition to demonstrate that Csnk1e negatively regulates the locomotor stimulant properties of opioids and psychostimulants. Here, we tested the hypothesis that Csnk1e negatively regulates opioid and psychostimulant reward using genetic inhibition and the conditioned place preference assay in Csnk1e knockout mice. Similar to pharmacological inhibition, Csnk1e knockout mice showed enhanced opioid-induced locomotor activity with the mu opioid receptor agonist fentanyl (0.2 mg/kg i.p.) as well as enhanced sensitivity to low-dose fentanyl reward (0.05 mg/kg). Interestingly, female knockout mice also showed a markedly greater escalation in consumption of sweetened palatable food - a behavioral pattern consistent with binge eating that also depends on mu opioid receptor activation. No difference was observed in fentanyl analgesia in the 52.5°C hot plate assay (0-0.4 mg/kg), naloxone conditioned place aversion (4 mg/kg), or methamphetamine conditioned place preference (0-4 mg/kg). To identify molecular adaptations associated with increased drug and food behaviors in knockout mice, we completed transcriptome analysis via mRNA sequencing of the striatum. Enrichment analysis identified terms associated with myelination and axon guidance and pathway analysis identified a differentially expressed gene set predicted to be regulated by the Wnt signaling transcription factor, Tcf7l2. To summarize, Csnk1e deletion increased mu opioid receptor-dependent behaviors, supporting previous studies indicating an endogenous negative regulatory role of Csnk1e in opioid behavior. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  6. Neurobiology of opioid dependence in creating addiction vulnerability [version 1; referees: 3 approved

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    Christopher J. Evans

    2016-07-01

    Full Text Available Opioid drugs are potent modulators of many physiological and psychological processes. When given acutely, they can elicit the signature responses of euphoria and analgesia that societies have coveted for centuries. Repeated, or chronic, use of opioids induces adaptive or allostatic changes that modify neuronal circuitry and create an altered normality — the “drug-dependent” state. This state, at least that exhibited by those maintained continuously on long-acting opioid drugs such as methadone or buprenorphine, is generally indistinguishable from the drug-naïve state for most overt behaviors. The consequences of the allostatic changes (cellular, circuit, and system adaptations that accompany the drug-dependent state are revealed during drug withdrawal. Drug cessation triggers a temporally orchestrated allostatic re-establishment of neuronal systems, which is manifested as opposing physiological and psychological effects to those exhibited by acute drug intoxication. Some withdrawal symptoms, such as physical symptoms (sweating, shaking, and diarrhea resolve within days, whilst others, such as dysphoria, insomnia, and anxiety, can linger for months, and some adaptations, such as learned associations, may be established for life. We will briefly discuss the cellular mechanisms and neural circuitry that contribute to the opioid drug-dependent state, inferring an emerging role for neuroinflammation. We will argue that opioid addictive behaviors result from a learned relationship between opioids and relief from an existing or withdrawal-induced anxiogenic and/or dysphoric state. Furthermore, a future stressful life event can recall the memory that opioid drugs alleviate negative affect (despair, sadness, and anxiety and thereby precipitate craving, resulting in relapse. A learned association of relief of aversive states would fuel drug craving in vulnerable people living in an increasingly stressful society. We suggest that this route to

  7. Mu Opioid Receptor Gene: New Point Mutations in Opioid Addicts

    OpenAIRE

    Dinarvand, Amin; Goodarzi, Ali; Vousooghi, Nasim; Hashemi, Mehrdad; Dinarvand, Rasoul; Ostadzadeh, Fahimeh; Khoshzaban, Ahad; Zarrindast, Mohammad-Reza

    2014-01-01

    Introduction Association between single-nucleotide polymorphisms (SNPs) in mu opioid receptor gene and drug addiction has been shown in various studies. Here, we have evaluated the existence of polymorphisms in exon 3 of this gene in Iranian population and investigated the possible association between these mutations and opioid addiction. Methods 79 opioid-dependent subjects (55 males, 24 females) and 134 non-addict or control individuals (74 males, 60 females) participated in the study. Geno...

  8. Impact of treatment for opioid dependence on fatal drug‐related poisoning: a national cohort study in England

    Science.gov (United States)

    Pierce, Matthias; Bird, Sheila M.; Hickman, Matthew; Marsden, John; Dunn, Graham; Jones, Andrew

    2015-01-01

    Abstract Aims To compare the change in illicit opioid users’ risk of fatal drug‐related poisoning (DRP) associated with opioid agonist pharmacotherapy (OAP) and psychological support, and investigate the modifying effect of patient characteristics, criminal justice system (CJS) referral and treatment completion. Design National data linkage cohort study of the English National Drug Treatment Monitoring System and the Office for National Statistics national mortality database. Data were analysed using survival methods. Setting All services in England that provide publicly funded, structured treatment for illicit opioid users. Participants Adults treated for opioid dependence during April 2005 to March 2009: 151 983 individuals; 69% male; median age 32.6 with 442 950 person‐years of observation. Measurements The outcome was fatal DRP occurring during periods in or out of treatment, with adjustment for age, gender, substances used, injecting status and CJS referral. Findings There were 1499 DRP deaths [3.4 per 1000 person‐years, 95% confidence interval (CI) = 3.2–3.6]. DRP risk increased while patients were not enrolled in any treatment [adjusted hazard ratio (aHR) = 1.73, 95% CI = 1.55–1.92]. Risk when enrolled only in a psychological intervention was double that during OAP (aHR = 2.07, 95% CI = 1.75–2.46). The increased risk when out of treatment was greater for men (aHR = 1.88, 95% CI = 1.67–2.12), illicit drug injectors (aHR = 2.27, 95% CI = 1.97–2.62) and those reporting problematic alcohol use (aHR = 2.37, 95% CI = 1.90–2.98). Conclusions Patients who received only psychological support for opioid dependence in England appear to be at greater risk of fatal opioid poisoning than those who received opioid agonist pharmacotherapy. PMID:26452239

  9. Baclofen for maintenance treatment of opioid dependence: A randomized double-blind placebo-controlled clinical trial [ISRCTN32121581

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    Ahmadi-Abhari Seyed Ali

    2003-11-01

    Full Text Available Abstract Background Results of preclinical studies suggest that the GABAB receptor agonist baclofen may be useful in treatment of opioid dependence. This study was aimed at assessing the possible efficacy of baclofen for maintenance treatment of opioid dependence. Methods A total of 40 opioid-dependent patients were detoxified and randomly assigned to receive baclofen (60 mg/day or placebo in a 12-week, double blind, parallel-group trial. Primary outcome measure was retention in treatment. Secondary outcome measures included opioids and alcohol use according to urinalysis and self-report ratings, intensity of opioid craving assessed with a visual analogue scale, opioid withdrawal symptoms as measured by the Short Opiate Withdrawal Scale and depression scores on the Hamilton inventory. Results Treatment retention was significantly higher in the baclofen group. Baclofen also showed a significant superiority over placebo in terms of opiate withdrawal syndrome and depressive symptoms. Non-significant, but generally favorable responses were seen in the baclofen group with other outcome measures including intensity of opioid craving and self-reported opioid and alcohol use. However, no significant difference was seen in the rates of opioid-positive urine tests. Additionally, the drug side effects of the two groups were not significantly different. Conclusion The results support further study of baclofen in the maintenance treatment of opioid dependence.

  10. Opioid receptor types involved in the development of nicotine physical dependence in an invertebrate (Planaria) model.

    Science.gov (United States)

    Raffa, Robert B; Baron, Steve; Bhandal, Jaspreet S; Brown, Tevin; Song, Kevin; Tallarida, Christopher S; Rawls, Scott M

    2013-11-01

    Recent data suggest that opioid receptors are involved in the development of nicotine physical dependence in mammals. Evidence in support of a similar involvement in an invertebrate (Planaria) is presented using the selective opioid receptor antagonist naloxone, and the more receptor subtype-selective antagonists CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) (μ, MOR), naltrindole (δ, DOR), and nor-BNI (norbinaltorphimine) (κ, KOR). Induction of physical dependence was achieved by 60-min pre-exposure of planarians to nicotine and was quantified by abstinence-induced withdrawal (reduction in spontaneous locomotor activity). Known MOR and DOR subtype-selective opioid receptor antagonists attenuated the withdrawal, as did the non-selective antagonist naloxone, but a KOR subtype-selective antagonist did not. An involvement of MOR and DOR, but not KOR, in the development of nicotine physical dependence or in abstinence-induced withdrawal was thus demonstrated in a sensitive and facile invertebrate model.

  11. From Resistance to Existence-Experiences of Medication-Assisted Treatment as Disclosed by People with Opioid Dependence.

    Science.gov (United States)

    Lindgren, Britt-Marie; Eklund, Margita; Melin, Ylva; Graneheim, Ulla Hällgren

    2015-01-01

    This study aimed to describe the lived experiences of participating in a medication-assisted treatment as disclosed by individuals with opioid dependence. Eleven narrative interviews were conducted and subjected to qualitative content analysis. The experiences of participating in the programme were described as a process from resistance to existence. The participants seized the chance to claim a life lived with dignity, struggled with hidden challenges, and eventually were freed from their pasts and were grateful for an existence with dignity. The recovery process was a long-term commitment and participants asked for a more individual and flexible process based on personal needs and values.

  12. Clinical and course indicators of bipolar disorder type I with and without opioid dependence

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    Amir Shabani

    2010-01-01

    Full Text Available Background: The existing evidence about the clinical situations of the bipolar patients with opioid dependence is scarce. The present study was carried out to compare the clinical features and course of the bipolar disorder type I re-garding the two subgroups of opioid dependent and non- dependent. Methods: There were 178 adult patients with bipolar disorder type I consecutively referred to the Iran Hospital of Psy-chiatry, Tehran, Iran, from January 2008 to January 2009 who enrolled in the study. The Persian Structured Clinical Interview for DSM- IV axis I disorders (SCID- I, HDRS- 17, and Y- MRS were administered for all patients. Other clini-cal information was gathered through the face- to- face interviews with the probands and the hospital records. The T test, Chi square test and logistic regression were used to analyze the data. Results: The mean age of probands were 33.6 ± 11.1 years old and they were mostly male. Among the evaluated indi-ces, the factors gender, anxiety disorders comorbidity, non- adherence, and positive family history were different sig-nificantly and independently from the other studied factors between opioid dependent and non- dependent bipolar pa-tients. Conclusions: Despite some differences, the opioid dependent and non- dependent bipolar patients did not have any significant difference regarding most of the examined clinical and course indices.

  13. The Early Maladaptive Schemas of an Opioid Dependent Sample of Treatment Seeking Young Adults: A Descriptive Investigation

    Science.gov (United States)

    Shorey, Ryan C.; Stuart, Gregory L.; Anderson, Scott

    2011-01-01

    Opioid dependence is an increasingly prevalent problem throughout the world, particularly for young adults (e.g., ages 17–25). Opioid dependence is associated with a wealth of negative consequences and is often a chronic, relapsing condition. Research on factors that may contribute to the etiology of opioid dependence could result in improved treatment outcomes. Using pre-existing patient records, the current study examined the early maladaptive schemas among young adult opioid dependent residential treatment patients (N = 169), as it is theorized that early maladaptive schemas may underlie or maintain substance use. Results showed that all 18 early maladaptive schemas were endorsed at various levels among male and female patients, with insufficient self-control being the most prevalent schema. In addition, females scored significantly higher than males on 11 of the 18 schemas. Findings from the current study are discussed in terms of future research and implications for the treatment of opioid dependence. PMID:22014405

  14. Opioid Tolerance and Physical Dependence: Role of Spinal Neuropeptides, Excitatory Amino Acids and Their Messengers

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    Khem Jhamandas

    2000-01-01

    Full Text Available Chronic opioid treatment results in the development of tolerance and physical dependence. The mechanisms underlying opioid tolerance and/or physical dependence are unclear. Recent studies suggest that opioid receptor or nociceptive, neural network-based adaptations contribute to this phenomenon. At the spinal level, the genesis of tolerance and physical dependence is associated with increased excitatory amino acid activity expressed through N-methyl-D-aspartate receptors in the dorsal horn. However, recent evidence also implicates spinal neuropeptide transmitters such as calcitonin gene-related peptide (CGRP and  substance P in the development of opioid tolerance. Long term spinal morphine treatment increases CGRP-like immunostaining in the dorsal horn, and coadministration of morphine with CGRP8-37, a competitive CGRP1 receptor antagonist, prevents this response as well as loss of the analgesic potency. CGRP8-37, like N-methyl-D-aspartate receptor antagonists, has the potential to restore morphine potency in experimental animals who are already tolerant to the opioid agonist. Recent evidence suggests that the effects of excitatory amino acid and neuropeptide receptor activity may be expressed through the generation of messengers such as nitric oxide and prostanoids. Agents that inhibit the synthesis of nitric oxide and prostanoids have the potential to inhibit and reverse spinal opioid tolerance, suggesting that this phenomenon may be expressed through the activity of these mediators. Nociceptive transmission in the dorsal horn of the spinal cord also involves activity of a number of other mediators including morphine modulatory neuropeptides, neuropeptide FF  and neuropeptide SF. The role of these mediators and their relationship with other factors implicated in tolerance remain to be determined.

  15. Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent youth☆

    Science.gov (United States)

    Warden, Diane; Subramaniam, Geetha A.; Carmody, Thomas; Woody, George E.; Minhajuddin, Abu; Poole, Sabrina A.; Potter, Jennifer; Fishman, Marc; Bogenschutz, Michael; Patkar, Ashwin; Trivedi, Madhukar H.

    2012-01-01

    Background In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment. Methods Opioid dependent adolescents and young adults (n=152), aged 15–21, were randomized to 12 weeks (BUP, n=74) or 2 weeks of detoxification (DETOX, n=78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment. Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression. Results In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition. Conclusions Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/ Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics. PMID:22626890

  16. Long term outcomes of pharmacological treatments for opioid dependence: does methadone still lead the pack?

    Science.gov (United States)

    Garcia-Portilla, Maria Paz; Bobes-Bascaran, Maria Teresa; Bascaran, Maria Teresa; Saiz, Pilar Alejandra; Bobes, Julio

    2014-02-01

    The aim of this review was to update and summarize the scientific knowledge on the long term outcomes of the different pharmacological treatment options for opioid dependence currently available and to provide a critical discussion on the different treatment options based on these results. We performed a literature search using the PubMed databases and the reference lists of the identified articles. Data from research show that the three pharmacological options reviewed are effective treatments for opioid dependence with positive long term outcomes. However, each one has its specific target population and setting. While methadone and buprenorphine are first line options, heroin-assisted treatment is a second line option for those patients refractory to treatment with methadone with concomitant severe physical, mental, social and/or functional problems. Buprenorphine seems to be the best option for use in primary care offices. The field of opioid dependence treatment is poised to undergo a process of reinforcement and transformation. Further efforts from researchers, clinicians and authorities should be made to turn new pharmacological options into clinical reality and to overcome the structural and functional obstacles that maintenance programmes face in combatting opioid dependence.

  17. Millon Clinical Multiaxial Inventory-III Subtypes of Opioid Dependence: Validity and Matching to Behavioral Therapies

    Science.gov (United States)

    Ball, Samuel A.; Nich, Charla; Rounsaville, Bruce J.; Eagan, Dorothy; Carroll, Kathleen M.

    2004-01-01

    The concurrent and predictive validity of 2 different methods of Millon Clinical Multiaxial Inventory-III subtyping (protocol sorting, cluster analysis) was evaluated in 125 recently detoxified opioid-dependent outpatients in a 12-week randomized clinical trial. Participants received naltrexone and relapse prevention group counseling and were…

  18. How Does Cognitive Behaviour Therapy Work with Opioid-Dependent Clients? Results of the UKCBTMM Study

    Science.gov (United States)

    Kouimtsidis, Christos; Reynolds, Martina; Coulton, Simon; Drummond, Colin

    2012-01-01

    Introduction: Process research in psychotherapy is important to understand how treatment works. The National Institute of Clinical Excellence guidelines suggest that in methadone maintenance treatment (MMT) for opioid dependence, drug key-working should be based on cognitive behavioural therapy (CBT) principles. This article reports the findings…

  19. Female Sexual Dysfunction Among the Wives of Opioid-Dependent Males in Iran

    Directory of Open Access Journals (Sweden)

    Anvar Abnavi

    2016-02-01

    Full Text Available Background Opiate abuse in males has significant effects on their sexual functions. In contrast, sexuality in females is a multidimensional issue that can strongly be affected by several factors in their partners. However, only a limited number of studies have assessed the role of males’ opioid dependency in their female partners’ sexual function. Objectives The present study aimed to evaluate the effect of males’ opioid dependency on their wives’ sexual function compared to the sexual function of the females whose husbands were not opioid dependent. Patients and Methods This study included 340 women who were selected through convenience sampling and divided into a control (females whose husbands were not opioid dependent and a case group (women whose husbands were opioid dependent. The data were collected through an interview according to the DSM-IV-R criteria for female sexual dysfunctions by a senior female medical student who was one of the researchers. Finally, the data were entered into the SPSS statistical software (v. 15 and analyzed using the t-test and chi-square test. Results According to the results, the frequency of hypoactive sexual desire disorder and sexual aversion disorder in the control group was significantly higher than that of the case group (P < 0.05. Conclusions The results showed that having an addicted husband could strongly affect some sexual domains in women. It could change the pattern of desire and motivation for sexual contact in females and alter their attitude toward the sexual relationship, thereby causing disturbances in the females’ normal sexual function.

  20. Naltrexone implants after in-patient treatment for opioid dependence: randomised controlled trial.

    Science.gov (United States)

    Kunøe, Nikolaj; Lobmaier, Philipp; Vederhus, John Kåre; Hjerkinn, Bjørg; Hegstad, Solfrid; Gossop, Michael; Kristensen, Øistein; Waal, Helge

    2009-06-01

    Naltrexone has considerable potential in helping to prevent relapse in heroin dependency. A longer-lasting formulation for naltrexone treatment is desirable to further reduce non-adherence and relapse during treatment of opiate dependence. To evaluate the safety and effectiveness of a 6-month naltrexone implant in reducing opioid use after in-patient treatment. A group of 56 abstinence-oriented patients who completed in-patient treatment for opioid dependence were randomly and openly assigned to receive either a 6-month naltrexone implant or their usual aftercare. Drug use and other outcomes were assessed at 6-month follow-up. Patients receiving naltrexone had on average 45 days less heroin use and 60 days less opioid use than controls in the 180-day period (both P<0.05). Blood tests showed naltrexone levels above 1 ng/ml for the duration of 6 months. Two patients died, neither of whom had received an implant. Naltrexone implant treatment safely and significantly reduces opioid use in a motivated population of patients.

  1. Predictors of Abstinence: National Institute of Drug Abuse Multisite Buprenorphine/Naloxone Treatment Trial in Opioid-Dependent Youth

    Science.gov (United States)

    Subramaniam, Geetha A.; Warden, Diane; Minhajuddin, Abu; Fishman, Marc J.; Stitzer, Maxine L.; Adinoff, Bryon; Trivedi, Madhukar; Weiss, Roger; Potter, Jennifer; Poole, Sabrina A.; Woody, George E.

    2011-01-01

    Objective: To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal)-assisted psychosocial treatment for opioid-dependent youth. Method: Secondary analyses were performed of data from 152 youth (15-21 years old) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification with weekly…

  2. Utilizing buprenorphine–naloxone to treat illicit and prescription-opioid dependence

    Directory of Open Access Journals (Sweden)

    Mauger S

    2014-04-01

    Full Text Available Sofie Mauger,1 Ronald Fraser1,2 Kathryn Gill1,2 1Department of Psychiatry, McGill University, Montreal, QC, Canada; 2Addictions Unit, McGill University Health Centre, Montreal, QC, Canada Objectives: To review current evidence on buprenorphine–naloxone (bup/nx for the treatment of opioid-use disorders, with a focus on strategies for clinical management and office-based patient care. Quality of evidence: Medline and the Cochrane Database of Systematic Reviews were searched. Consensus reports, guidelines published, and other authoritative sources were also included in this review. Apart from expert guidelines, data included in this review constitute level 1 evidence. Findings: Bup/nx is a partial µ-opioid agonist combined with the opioid antagonist naloxone in a 4:1 ratio. It has a lower abuse potential, carries less stigma, and allows for more flexibility than methadone. Bup/nx is indicated for both inpatient and ambulatory medically assisted withdrawal (acute detoxification and long-term substitution treatment (maintenance of patients who have a mild-to-moderate physical dependence. A stepwise long-term substitution treatment with regular monitoring and follow-up assessment is usually preferred, as it has better outcomes in reducing illicit opioid use, minimizing concomitant risks such as human immunodeficiency virus and hepatitis C transmission, retaining patients in treatment and improving global functioning. Conclusion: Bup/nx is safe and effective for opioid detoxification and substitution treatment. Its unique pharmaceutical properties make it particularly suitable for office-based maintenance treatment of opioid-use disorder. Keywords: Zubsolv, Suboxone, methadone, opiate detoxification, opiate substitution, clinical management

  3. Hyperalgesia in Heroin Dependent Patients and the Effects of Opioid Substitution Therapy

    OpenAIRE

    2012-01-01

    Evidence suggests that patients on opiate maintenance therapy for the treatment of addiction present with opioid-induced hyperalgesia (OIH). This study compared the experimental (cold-pressor, electrical stimulation) pain responses of 82 treatment-seeking heroin-dependent adults randomized to methadone (METH, n = 11) or buprenorphine (BUP, n = 64) therapy, with matched drug free controls (n = 21). Heroin-dependent participants were evaluated at baseline (treatment entry), medication (METH or ...

  4. The μ-opioid receptor gene and smoking initiation and nicotine dependence

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    Kendler Kenneth S

    2006-08-01

    Full Text Available Abstract The gene encoding the mu-opioid receptor (OPRM1 is reported to be associated with a range of substance dependence. Experiments in knockout mice indicate that the mu-opioid receptor may mediate reinforcing effects of nicotine. In humans, opioid antagonist naltrexone may reduce the reinforcing effects of tobacco smoking. Additionally, the OPRM1 gene is located in a region showing linkage to nicotine dependence. The OPRM1 is thus a plausible candidate gene for smoking behavior. To investigate whether OPRM1 contributes to the susceptibility of smoking initiation and nicotine dependence, we genotyped 11 SNPs in the gene for 688 Caucasian subjects of lifetime smokers and nonsmokers. Three SNPs showed nominal significance for smoking initiation and one reached significance for nicotine dependence. The global test for three-marker (rs9479757-rs2075572-rs10485057 haplotypes was significant for smoking initiation (p = 0.0022. The same three-marker haplotype test was marginal (p = 0.0514 for nicotine dependence. These results suggest that OPRM1 may be involved in smoking initiation and nicotine dependence.

  5. [Personality changes in opioid-dependent subjects in a methadone maintenance treatment program].

    Science.gov (United States)

    Trémeau, F; Darreye, A; Leroy, B; Renckly, V; Ertlé, S; Weibel, H; Khidichian, F; Macher, J-P

    2003-01-01

    Personality disorders and particularly antisocial personality disorders (APD) are quite frequent in opioid-dependent subjects. They show various personality traits: high neuroticism, high impulsivity, higher extraversion than the general population. Previous studies have reported that some but not all personality traits improved with treatment. In a previous study, we found a low rate of APD in a French population of opioid-dependent subjects. For this reason, we evaluated personality traits at intake and during maintenance treatment with methadone. Methods - The form A of the Eysenck Personality Inventory (EPI) was given to opioid addicts at intake and after 6 and 12 months of methadone treatment. Results - 134 subjects (96 males and 38 females) took the test at intake, 60 completed 12 months of treatment. After 12 months, the EPI Neuroticism (N) and the Extraversion-introversion (E) scale scores decreased significantly. The N score improved in the first 6 months, while the E score improved only during the second 6 months of treatment. Compared to a reference group of French normal controls, male and female opioid addicts showed high N and E scores. Demographic data and EPI scores of patients who stayed in treatment for 12 months did not differ significantly from those of dropouts (n=23). Patients with a history of suicide attempts (SA) started to use heroin at an earlier age and they showed a higher E score and a tendency for a higher N score at intake. Discussion - The two personality dimensions of the EPI changed during MMT, and the N score converged towards the score of normal controls. Opioid addicts differ from normal controls mostly in their N score. The EPI did not help to differentiate 12-month completers from dropouts. Higher E scores in patients with an SA history might reflect a higher impulsivity, which has been linked to suicidality in other patient groups.

  6. Choice between delayed food and immediate opioids in rats: treatment effects and individual differences.

    Science.gov (United States)

    Panlilio, Leigh V; Secci, Maria E; Schindler, Charles W; Bradberry, Charles W

    2017-09-04

    Addiction involves maladaptive choice behavior in which immediate drug effects are valued more than delayed nondrug rewards. To model this behavior and extend our earlier work with the prescription opioid oxycodone, we allowed rats to choose between immediate intravenous delivery of the short-acting opioid remifentanil and delayed delivery of highly palatable food pellets. Treatment drugs were tested on a baseline where remifentanil was preferred over food. Treatment with a high dose of the opioid antagonist naltrexone decreased but did not reverse the preference for remifentanil. Treatment with the serotonin 5-HT2C agonist lorcaserin decreased remifentanil and food self-administration nonselectively. Across conditions in which the alternative to delayed food was either a moderate dose of oxycodone, a moderate or high dose of remifentanil, a smaller more immediate delivery of food, or timeout with no primary reinforcement, choice was determined by both the length of the delay and the nature of the alternative option. Delayed food was discounted most steeply when the alternative was a high dose of remifentanil, which was preferred over food when food was delayed by 30 s or more. Within-subject comparisons showed no evidence for trait-like impulsivity or sensitivity to delay across these conditions. Choice was determined more by the current contingencies of reinforcement than by innate individual differences. This finding suggests that people might develop steep delay-discounting functions because of the contingencies in their environment, and it supports the use of contingency management to enhance the relative value of delayed nondrug reinforcers.

  7. The role of perceived belongingness to a drug subculture among opioid-dependent patients.

    Science.gov (United States)

    Moshier, Samantha J; McHugh, R Kathryn; Calkins, Amanda W; Hearon, Bridget A; Rosellini, Anthony J; Weitzman, Meara L; Otto, Michael W

    2012-12-01

    Illicit drug use frequently occurs in a context of a drug subculture characterized by social ties with other drug users, feelings of excitement and effectiveness deriving from illicit activities, and alienation from mainstream society. Identification with this subculture is recognized anecdotally as a barrier to recovery, but clear quantification of individual differences in perceived belongingness to the drug subculture has been absent from the literature. The purpose of this study was to describe the development and psychometric properties of a brief self-report measure designed to assess this construct, the Belongingness to Drug Culture Questionnaire (BDCQ). Ninety-six opioid-dependent, methadone-maintained participants completed the BDCQ, related self-report measures, and assessment of drug use patterns. The BDCQ demonstrated high internal consistency (α = .88) and was significantly associated with self-reported days of drug use in the past 30 days, desire to quit, impulsivity, psychopathy, and social, enhancement, and coping drug use motives. These findings encourage continued psychometric evaluation of the BDCQ and study of the role of belongingness in the development and maintenance of substance use disorders.

  8. Use and dependence on opioid drugs in the Spanish population with chronic pain: Prevalence and differences according to sex.

    Science.gov (United States)

    Coloma-Carmona, A; Carballo, J L; Rodríguez-Marín, J; Pérez-Carbonell, A

    To analyse the prevalence in the use and dependence on opioid drugs in the Spanish population with chronic pain and evaluate the differences according to sex. The demographic variables, opioid treatment characteristics and use of other substances were assessed in 229 users of opioid drugs. A descriptive bivariate analysis of the data was performed. Forty-six percent of the patients met the criteria of dependence on opioid drugs (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition [DSM-IV-TR]). Alcohol and cannabis consumption was greater in the men. The rates of dependence on the use of opioid drugs were significantly higher in the extended treatments. Planning for treatments with opioids and strategies for preventing inappropriate use should not depend on the patient's sex. We need further studies on the medical and psychological variables related to the use of and dependence on opioids. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  9. Six-Year Outcome of Opioid Maintenance Treatment in Heroin-Dependent Patients: Results from a Naturalistic Study in a Nationally Representative Sample.

    Science.gov (United States)

    Soyka, Michael; Strehle, Jens; Rehm, Jürgen; Bühringer, Gerhard; Wittchen, Hans-Ulrich

    2017-01-01

    In many countries, the opioid agonists, buprenorphine and methadone, are licensed for maintenance treatment of opioid dependence. Many short-term studies have been performed, but little is known about long-term effects. Therefore, this study described over 6 years (1) mortality, retention and abstinence rates and (2) changes in concomitant drug use and somatic and mental health. A prevalence sample of n = 2,694 maintenance patients, recruited from a nationally representative sample of n = 223 substitution doctors, was evaluated in a 6-year prospective-longitudinal naturalistic study. At 72 months, n = 1,624 patients were assessed for outcome; 1,147 had full outcome data, 346 primary outcome data and 131 had died; 660 individuals were lost to follow-up. The 6-year retention rate was 76.6%; the average mortality rate was 1.1%. During follow-up, 9.4% of patients became "abstinent" and 1.9% were referred for drug-free addiction treatment. Concomitant drug use decreased and somatic health status and social parameters improved. The study provides further evidence for the efficacy and safety of maintenance treatment with opioid agonists. In the long term, the number of opioid-free patients is low and most patients are more or less continuously under opioid maintenance therapy. Further implications are discussed. © 2017 S. Karger AG, Basel.

  10. Individualizing Opioid Use Disorder (OUD Treatment: Time to Fully Embrace a Chronic Disease Model

    Directory of Open Access Journals (Sweden)

    Richard Gustin

    2015-02-01

    Full Text Available The current opioid epidemic in the United States is changing our perceptions of the face of addiction. Opioid Use Disorder (OUD has become pervasive and is affecting all ethnicities, races, socioeconomic classes, the young and the old. In 2015, 46 people will lose their life each day to a chronic brain disease that is going unnoticed and undertreated. Over the last five decades, numerous scientific and clinical breakthroughs have allowed for a better understanding of the mechanisms underlying addiction, and the development of medications that can help support a patient’s long-term recovery. All of those that have contributed to these advancements have aided in redefining addiction as a primary, chronic disease of the brain reward, motivation, memory and related circuitry; however, our treatment strategies have not necessarily advanced to the same extent as our current understanding of the disease. This commentary will explore how personal philosophies can bias treatments strategies and definitions of treatment success, and prevent adoption of chronic disease treatment models that would significantly improve the quality of life of those suffering with OUD. This is a challenge to consider how our views and stigma can impact a patient’s recovery. We are currently losing a battle with a disease that is taking the lives of 46 individuals daily; it is time to fully embrace a chronic disease model which comprises an integrated pharmacopsychosocial approach for treating the biopsychosocial disorder that is addiction to reverse these trends.

  11. Modified ‘Joyce model’ of opioid dependence/withdrawal

    OpenAIRE

    Raffa, Robert B.; Tallarida, Ronald J.

    2006-01-01

    By comprehensive and detailed measurement of the time course of withdrawal signs in rats, Joyce et al. (J. Theo. Biol. 240:531–537, 2006) recently provided a creative quantitative model of onset of drug-dependence based on the requirement of protein synthesis. Because the initial model fit the data imperfectly over the full time course, the authors postulated that additional features would be needed. We report excellent fit of the data (R2 = 0.96) by adding: (1) a transient early phase, and (...

  12. Modified ‘Joyce model’ of opioid dependence/withdrawal

    Science.gov (United States)

    Raffa, Robert B.; Tallarida, Ronald J.

    2006-01-01

    By comprehensive and detailed measurement of the time course of withdrawal signs in rats, Joyce et al. (J. Theo. Biol. 240:531–537, 2006) recently provided a creative quantitative model of onset of drug-dependence based on the requirement of protein synthesis. Because the initial model fit the data imperfectly over the full time course, the authors postulated that additional features would be needed. We report excellent fit of the data (R2 = 0.96) by adding: (1) a transient early phase, and (2) a delay in the buildup of protein. PMID:17045985

  13. Modified 'Joyce model' of opioid dependence/withdrawal.

    Science.gov (United States)

    Raffa, Robert B; Tallarida, Ronald J

    2006-12-03

    By comprehensive and detailed measurement of the time course of withdrawal signs in rats, Joyce et al. (J. Theo. Biol. 240:531-537, 2006) recently provided a creative quantitative model of the onset of drug dependence based on the requirement of protein synthesis. Because the initial model fit the data imperfectly over the full time course, those authors postulated that additional features would be needed. We report excellent fit of the data (R(2)=0.96) by adding: (1) a transient early phase, and (2) a delay in the buildup of protein.

  14. The abnormal Wnt/β-cateninsignalingpathway in injury induced by opioid dependence and alleviations of adanon

    Institute of Scientific and Technical Information of China (English)

    Shi-Chao Xu; Peng Huang

    2015-01-01

    Objective:The present research aimed to explore the abnormal Wnt/β-Catenin signaling pathway in injury induced by opioid dependence and alleviations of adanon.Methods:80 cases of opioid dependence patients who received adanon treatment in our hospital were analyzed. The expression of Wnt/β-Catenin signaling pathway key proteins and TNF-αα as well as IL2/4 was detected by western blotting. 40 cases of healthy subjects in our hospital were taken as the internal the control group.Results:The expression of Wnt4,β-Catenin, TNF-α as well as IL2/4 was up-regulated greatly in patients before treatment with a statistical difference. Those abnormalities were alleviated after medication of adanon which also signified a statistical difference when compared with the level before medication.Conclusion:Over-activated Wnt/β-Catenin and up-regulated TNF-α as well as IL2/4 were involved in the injury induced by opioid and adanon exerts injury restoration by normalizing these abnormal expressions.

  15. Opioid antinociception, tolerance and dependence: interactions with the N-methyl-D-aspartate system in mice.

    Science.gov (United States)

    Dykstra, Linda A; Fischer, Bradford D; Balter, Rebecca E; Henry, Fredrick E; Schmidt, Karl T; Miller, Laurence L

    2011-09-01

    This study explored the involvement of N-methyl-D-aspartate (NMDA) in the effects of μ-opioid agonists. A hot-plate procedure was used to assess antinociception and tolerance in mice in which the NR1 subunit of the NMDA receptor was reduced [knockdown (KD)] to approximately 10%, and in mice treated with the NMDA antagonist, (-)-6-phosphonomethyl-deca-hydroisoquinoline-3-carboxylic acid (LY235959). The μ opioid agonists, morphine, l-methadone and fentanyl, were approximately three-fold less potent in the NR1 KD mice than in wild-type (WT) controls; however, the development of morphine tolerance and dependence did not differ markedly in the NR1 KD and the WT mice. Acute administration of the NMDA antagonist, LY235959, produced dose-dependent, leftward shifts in the morphine dose-effect curve in the WT mice, but not in the NR1 KD mice. Chronic administration of LY235959 during the morphine tolerance regimen did not attenuate the development of tolerance in the NR1 KD or the WT mice. These results indicate that the NR1 subunit of the NMDA receptor does not play a prominent role in μ opioid tolerance.

  16. A comparison of independent depression and substance-induced depression in cannabis-, cocaine-, and opioid-dependent treatment seekers.

    Science.gov (United States)

    Dakwar, Elias; Nunes, Edward V; Bisaga, Adam; Carpenter, Kenneth C; Mariani, John P; Sullivan, Maria A; Raby, Wilfrid N; Levin, Frances R

    2011-01-01

    Depressive symptoms often coexist with substance use disorders (SUDs). The DSM-IV has identified two distinct categories for depression coexisting with SUDs-independent depression and substance-induced depression. While this distinction has important therapeutic and prognostic implications, it remains difficult to make in clinical practice; the differentiation is often guided by chronological and symptom severity criteria that patients may be unable to precisely provide. Furthermore, it is unclear whether the various substances commonly abused-cannabis, cocaine, and opioids-are equally associated with the two types of depression. Predictors, associations, and other markers may be helpful in guiding the diagnostic process. We, therefore, examined the differences between cannabis-, cocaine-, and opioid-dependent individuals contending with independent depression and those contending with substance-induced depression in regard to several variables, hypothesizing that independent depression is more commonly found in females, and that it is associated with higher symptom severity and psychiatric comorbidity. Cocaine-, cannabis-, and/or opioid-dependent, treatment-seeking individuals underwent a structured clinical interview for DSM-IV-TR disorders after providing consent at our clinical research site; those with co-existing primary depression or substance-induced depression diagnoses were provided with further questionnaires and were entered into this analysis (n= 242). Pair-wise comparisons were conducted between the groups classified as independent versus substance-induced depression with 2-by-2 tables and chi-square tests for dichotomous independent variables, and t-tests for continuous variables. Binomial logistic regression was performed in order to ascertain which of the variables were significant predictors. Women were more likely than men to have independent depression (pCannabis dependence was highly associated with independent depression (pdepression

  17. Differences in onset and abuse/dependence episodes between prescription opioids and heroin: results from the National Epidemiologic Survey on Alcohol and Related Conditions

    Directory of Open Access Journals (Sweden)

    Mannelli P

    2011-05-01

    Full Text Available Li-Tzy Wu1, George E Woody2, Chongming Yang3, Paolo Mannelli1, Dan G Blazer11Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Duke University Medical Center, Durham, NC, USA; 2Department of Psychiatry, University of Pennsylvania School of Medicine, University of Pennsylvania and Treatment Research Institute, Philadelphia, PA, USA; 3Social Science Research Institute, Duke University, Durham, NC, USAObjectives: To examine patterns of onset and abuse/dependence episodes of prescription opioid (PO and heroin use disorders in a national sample of adults, and to explore differences by gender and substance abuse treatment status.Methods: Analyses of data from the 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093.Results: Of all respondents, 5% (n = 1815 reported a history of nonmedical PO use (NMPOU and 0.3% (n = 150 a history of heroin use. Abuse was more prevalent than dependence among NMPOUs (PO abuse, 29%; dependence, 7% and heroin users (heroin abuse, 63%; dependence, 28%. Heroin users reported a short mean interval from first use to onset of abuse (1.5 years or dependence (2.0 years, and a lengthy mean duration for the longest episode of abuse (66 months or dependence (59 months; the corresponding mean estimates for PO abuse and dependence among NMPOUs were 2.6 and 2.9 years, respectively, and 31 and 49 months, respectively. The mean number of years from first use to remission from the most recent episode was 6.9 years for PO abuse and 8.1 years for dependence; the mean number of years from first heroin use to remission from the most recent episode was 8.5 years for heroin abuse and 9.7 years for dependence. Most individuals with PO or heroin use disorders were remitted from the most recent episode. Treated individuals, whether their problem was heroin or POs, tended to have a longer mean duration of an episode than untreated individuals.Conclusion: Periodic remissions

  18. Traditional Chinese and Indian medicine in the treatment of opioid-dependence: a review

    Directory of Open Access Journals (Sweden)

    Fatemeh Doosti

    2013-05-01

    Full Text Available Objective: In this study, the current literatures on the use of herbs and herbal preparations of Traditional Chinese and Indian Medicine for the treatment of opioid addiction were reviewed. Methods: Search was done in databases such as Pub Med, Science Direct, Scopus, Springer Link, and Google Scholar. Results: Among 18 retrieved studies, 3 studies were about asafetida extract, an approved preparation for ameliorating drug abstinence in China. Chinese preparations including Composite Dong Yuan Gao, Qingjunyin and TJ-97 (a water extract of dai-bofu-to as well as Indian ones, Mentate and Shilajit, were reported to have positive effects against opioid withdrawal, dependence, and tolerance. Moreover, Levo-tetrahydropalmatine and L-Stepholidine, in addition to extracts of Caulis Sinomenii and Sinomenium acutum showed similar effects. Banxia Houpu Decoction, Fu-Yuan pellet, Jinniu capsules, Qingjunyin, Tai-Kang-Ning capsule, and Xuan Xia Qudu Jiaonang (WeiniCom from Chinese preparations, showed anti-addiction effects in randomized, double-blind and, in some studies, multicenter clinical trials. Conclusion: Traditional herbal preparations of China and India have anti-addiction effects with less adverse effects than alpha2-adrenergic or opioid agonists.

  19. Traditional Chinese and Indian medicine in the treatment of opioid-dependence: a review

    Science.gov (United States)

    Doosti, Fatemeh; Dashti, Saeedeh; Tabatabai, Seyed Meghdad; Hosseinzadeh, Hossein

    2013-01-01

    Objective: In this study, the current literatures on the use of herbs and herbal preparations of Traditional Chinese and Indian Medicine for the treatment of opioid addiction were reviewed. Matherials and Methods: Search was done in databases such as Pub Med, Science Direct, Scopus, Springer Link, and Google Scholar. Results: Among 18 retrieved studies, 3 studies were about asafetida extract, an approved preparation for ameliorating drug abstinence in China. Chinese preparations including Composite Dong Yuan Gao, Qingjunyin and TJ-97 (a water extract of dai-bofu-to) as well as Indian ones, Mentate and Shilajit, were reported to have positive effects against opioid withdrawal, dependence, and tolerance. Moreover, Levo-tetrahydropalmatine and L-Stepholidine, in addition to extracts of Caulis Sinomenii and Sinomenium acutum showed similar effects. Banxia Houpu Decoction, Fu-Yuan pellet, Jinniu capsules, Qingjunyin, Tai-Kang-Ning capsule, and Xuan Xia Qudu Jiaonang (WeiniCom) from Chinese preparations, showed anti-addiction effects in randomized, double-blind and, in some studies, multicenter clinical trials. Conclusion : Traditional herbal preparations of China and India have anti-addiction effects with less adverse effects than alpha2-adrenergic or opioid agonists. PMID:25050276

  20. Clinical Management of the Breast-Feeding Mother-Infant Dyad in Recovery From Opioid Dependence.

    Science.gov (United States)

    Busch, Deborah W

    2016-01-01

    Human milk is one of the most health-promoting and cost-effective nutritional substances known to humankind. Breastmilk provides substantial and remarkable physiological and psychological health benefits. Within the last decade, there has been a resurgence of breast-feeding in the United States and worldwide and an increased awareness of the immense health benefits for mothers, infants, and societies that support it. Each mother-baby dyad is a unique pair, with distinct relationships, biases, barriers, and obstacles. This article aims to address clinical management for the opioid-recovering breast-feeding dyad and to translate current evidenced-based practice findings, recommendations, and resources to best support this unique population. The recovering breast-feeding mother and newborn with opioid dependence deserve special consideration and expert care to foster their recovery and breast-feeding efforts. It is our moral and ethical responsibility as healthcare professionals to enable, foster, and promote breast-feeding among all families, especially those who stand to benefit the greatest. Substance recovery cannot be treated in isolation, nor can breast-feeding efforts; an interdisciplinary professional team effort promises the greatest chances for recovery success. With appropriate evidence-based practice support, training, and intervention by knowledgeable professionals, many women can overcome the biases and obstacles associated with opioid recovery to successfully breast-feed their babies.

  1. The mu-opioid receptor gene-dose dependent reductions in G-protein activation in the pons/medulla and antinociception induced by endomorphins in mu-opioid receptor knockout mice.

    Science.gov (United States)

    Mizoguchi, H; Narita, M; Oji, D E; Suganuma, C; Nagase, H; Sora, I; Uhl, G R; Cheng, E Y; Tseng, L F

    1999-01-01

    There appear to be different relationships between mu-opioid receptor densities and the acute and neuroadaptive mu-opioid agonist-induced responses of the multiple opioid neuronal systems, including important pons/medulla circuits. The recent success in creating mu-opioid receptor knockout mice allows studies of mu-opioid agonist-induced pharmacological and physiological effects in animals that express no, one or two copies of the mu-opioid receptor gene. We now report that the binding of mu-opioid receptor ligand, [3H][D-Ala2,NHPhe4,Gly-ol]enkephalin to membrane preparations of the pons/medulla was reduced by half in heterozygous mu-opioid receptor knockout mice and eliminated in homozygous mu-opioid receptor knockout mice. The endogenous mu-opioid agonist peptides endomorphin-1 and -2 activate G-proteins in the pons/medulla from wild-type mice in a concentration-dependent fashion, as assessed using [35S]guanosine-5'-o-(3-thio)triphosphate binding. This stimulation was reduced to half of the wild-type levels in heterozygous mice and eliminated in homozygous knockout mice. The intracerebroventricular injection of either endomorphin-1 or endomorphin-2 produced marked antinociception in the hot-plate and tail-flick tests in wild-type mice. These antinociceptive actions were significantly reduced in heterozygous mu-opioid receptor knockout mice, and virtually abolished in homozygous knockout mice. The mu-opioid receptors are the principal molecular targets for endomorphin-induced G-protein activation in the pons/medulla and the antinociception caused by the intracerebroventricular administration of mu-opioid agonists. These data support the notion that there are limited physiological mu-opioid receptor reserves for inducing G-protein activation in the pons/medulla and for the nociceptive modulation induced by the central administration of endomorphin-1 and -2.

  2. Activation of Peripheral κ-Opioid Receptors Normalizes Caffeine Effects Modified in Nicotine-Dependent Rats during Nicotine Withdrawal.

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    Sudakov, S K; Bogdanova, N G

    2016-10-01

    The study examined the effect of peripheral (intragastric) ICI-204,448, an agonist of gastric κ-opioid receptors, on the psychostimulating and anxiolytic effects of caffeine in nicotinedependent rats at the stage of nicotine withdrawal. In these rats, the effects of caffeine (10 mg/kg) were perverted. In nicotine-dependent rats, caffeine produced an anxiolytic effect accompanied by pronounced stimulation of motor activity, in contrast to anxiogenic effect induced by caffeine in intact rats without nicotine dependence. During nicotine withdrawal, nicotine-dependent rats demonstrated enhanced sensitivity to nicotine. Intragastric administration of κ-opioid receptor agonist ICI-204,448 normalized the effect of caffeine in nicotinedependent rats. We have previously demonstrated that activation of peripheral κ-opioid receptors inhibited central κ-opioid activity and eliminated manifestations of nicotine withdrawal syndrome in nicotine-dependent rats, e.g. metabolism activation, stimulation of motor activity, and enhancement of food consumption. In its turn, inhibition of central κ-opioid structures activates the brain adenosine system, which can attenuate the caffeine-induced effects in nicotine-dependent rats.

  3. Impaired pre-attentive auditory processing in opioid dependence with and without benzodiazepine co-dependence revealed by combined magnetoencephalography and electroencephalography.

    Science.gov (United States)

    Kivisaari, Reetta; Lehtinen, Reia; Autti, Taina; Puuskari, Varpu; Jokela, Olga; Ahveninen, Jyrki; Rapeli, Pekka; Kähkönen, Seppo

    2007-10-01

    Cognitive dysfunctions may be a significant factor in drug-seeking behavior, reducing the efficiency of rehabilitation in opioid dependence. Neurophysiological basis of these dysfunctions is poorly understood. 21 opioid-dependent patients and 15 healthy controls with no experience of illicit drugs were studied with simultaneous electroencephalography (EEG) and magnetoencephalography (MEG). Among opioid dependents 15 were benzodiazepine co-dependent. In a passive oddball paradigm, a train of 700-Hz standard tones (80%), presented to the left ear, was occasionally interrupted by infrequent deviants, which were either 600-Hz or 400-Hz pure tones or complex novel sounds. The auditory evoked potentials (AEP) and fields (AEF) were analyzed. The strength of the N1m dipoles was enhanced in patients with benzodiazepine co-dependence, but the latency of the response or the source location was not changed. A delay of mismatch negativity (MMN) response of novel tones in EEG, and delay of P3am response on the contralateral hemisphere to stimulated ear in MEG in opioid-dependent patients were observed. There were no differences in source locations or strengths of the dipoles for P1m, MMNm, and P3am determined using equivalent current dipoles. There were no group differences in EEG amplitude measures. In conclusion, our results suggest delayed pre-attentive auditory processing of novel information in opioid dependence. Benzodiazepine co-dependence modulated N1m response.

  4. Chronic Opioid Therapy and Opioid Tolerance: A New Hypothesis

    Directory of Open Access Journals (Sweden)

    Joel S. Goldberg

    2013-01-01

    Full Text Available Opioids are efficacious and cost-effective analgesics, but tolerance limits their effectiveness. This paper does not present any new clinical or experimental data but demonstrates that there exist ascending sensory pathways that contain few opioid receptors. These pathways are located by brain PET scans and spinal cord autoradiography. These nonopioid ascending pathways include portions of the ventral spinal thalamic tract originating in Rexed layers VI–VIII, thalamocortical fibers that project to the primary somatosensory cortex (S1, and possibly a midline dorsal column visceral pathway. One hypothesis is that opioid tolerance and opioid-induced hyperalgesia may be caused by homeostatic upregulation during opioid exposure of nonopioid-dependent ascending pain pathways. Upregulation of sensory pathways is not a new concept and has been demonstrated in individuals impaired with deafness or blindness. A second hypothesis is that adjuvant nonopioid therapies may inhibit ascending nonopioid-dependent pathways and support the clinical observations that monotherapy with opioids usually fails. The uniqueness of opioid tolerance compared to tolerance associated with other central nervous system medications and lack of tolerance from excess hormone production is discussed. Experimental work that could prove or disprove the concepts as well as flaws in the concepts is discussed.

  5. Opioid Basics: Prescription Opioids

    Science.gov (United States)

    ... Injury Violence Prevention WISQARS (Injury & Death Data) Prescription Opioids Recommend on Facebook Tweet Share Compartir Prescription opioids ... overdose before they start. Risk Factors for Prescription Opioid Abuse and Overdose Research shows that some risk ...

  6. Effectiveness of Mindfulness-Based Group Therapy Compared to the Usual Opioid Dependence Treatment

    Directory of Open Access Journals (Sweden)

    Saeed Imani

    2015-11-01

    Full Text Available  Objective: This study investigated the effectiveness of mindfulness-based group therapy (MBGT compared to the usual opioid dependence treatment (TAU.Thirty outpatients meeting the DSM-IV-TR criteria for opioid dependence from Iranian National Center for Addiction Studies (INCAS were randomly assigned into experimental (Mindfulness-Based Group Therapy and control groups (the Usual Treatment.The experimental group undertook eight weeks of intervention, but the control group received the usual treatment according to the INCAS program.  Methods:The Five Factor Mindfulness Questionnaire (FFMQ and the Addiction Sevier Index (ASI were administered at pre-treatment and post-treatment assessment periods. Thirteen patients from the experimental group and 15 from the control group completed post-test assessments. Results:The results of MANCOVA revealed an increase in mean scores in observing, describing, acting with awareness, non-judging, non-reacting, and decrease in mean scores of alcohol and opium in MBGT patient group. Conclusion:The effectiveness of MBGT, compared to the usual treatment, was discussed in this paper as a selective protocol in the health care setting for substance use disorders.

  7. Methadone disposition in oral fluid during pharmacotherapy for opioid-dependence

    Science.gov (United States)

    Gray, Teresa R.; Dams, Riet; Choo, Robin E.; Jones, Hendree E.; Huestis, Marilyn A.

    2010-01-01

    Introduction Oral fluid testing is widely used for detecting drug exposure, but data describing methadone and metabolites in oral fluid during pharmacotherapy for opioid-dependence are relatively limited. Method 414 oral fluid specimens from 16 opioid-dependent pregnant women receiving daily methadone were analyzed for methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), and methadol by liquid chromatography-mass spectrometry. Results All oral fluid specimens contained methadone greater than 1 ng/mL; 88% were positive for EDDP and 12% for methadol. Over 95% of oral fluid specimens exceeded the 20 ng/mL methadone cutoff set by the European Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) study. Methadone and EDDP oral fluid concentrations were highly variable within and between participants, did not predict methadone dose, but were negatively correlated with pH. Conclusion Methadone was readily identified in oral fluid at concentrations greater than 20 ng/mL following daily 30–110 mg/day methadone pharmacotherapy. As no specimens contained only EDDP or methadol, there was no advantage to including these analytes for identification of methadone exposure. As nearly all oral fluid specimens from methadone-maintained patients exceeded the DRUID guideline, the 20 ng/mL cutoff appears to be sensitive enough to detect daily methadone exposure; however, additional indicators of behavioral and/or motor impairment would be necessary to provide evidence of driving impairment. PMID:20667673

  8. Regulation of μ and δ opioid receptor functions: involvement of cyclin-dependent kinase 5

    Science.gov (United States)

    Beaudry, H; Mercier-Blais, A-A; Delaygue, C; Lavoie, C; Parent, J-L; Neugebauer, W; Gendron, L

    2015-01-01

    Background and Purpose Phosphorylation of δ opioid receptors (DOP receptors) by cyclin-dependent kinase 5 (CDK5) was shown to regulate the trafficking of this receptor. Therefore, we aimed to determine the role of CDK5 in regulating DOP receptors in rats treated with morphine or with complete Freund's adjuvant (CFA). As μ (MOP) and DOP receptors are known to be co-regulated, we also sought to determine if CDK5-mediated regulation of DOP receptors also affects MOP receptor functions. Experimental Approach The role of CDK5 in regulating opioid receptors in CFA- and morphine-treated rats was studied using roscovitine as a CDK inhibitor and a cell-penetrant peptide mimicking the second intracellular loop of DOP receptors (C11-DOPri2). Opioid receptor functions were assessed in vivo in a series of behavioural experiments and correlated by measuring ERK1/2 activity in dorsal root ganglia homogenates. Key Results Chronic roscovitine treatment reduced the antinociceptive and antihyperalgesic effects of deltorphin II (Dlt II) in morphine- and CFA-treated rats respectively. Repeated administrations of C11-DOPri2 also robustly decreased Dlt II-induced analgesia. Interestingly, DAMGO-induced analgesia was significantly increased by roscovitine and C11-DOPri2. Concomitantly, in roscovitine-treated rats the Dlt II-induced ERK1/2 activation was decreased, whereas the DAMGO-induced ERK1/2 activation was increased. An acute roscovitine treatment had no effect on Dlt II- or DAMGO-induced analgesia. Conclusions and Implications Together, our results demonstrate that CDK5 is a key player in the regulation of DOP receptors in morphine- and CFA-treated rats and that the regulation of DOP receptors by CDK5 is sufficient to modulate MOP receptor functions through an indirect process. PMID:25598508

  9. A randomized, controlled trial of the efficacy of an interoceptive exposure-based CBT for treatment-refractory outpatients with opioid dependence.

    Science.gov (United States)

    Otto, Michael W; Hearon, Bridget A; McHugh, R Kathryn; Calkins, Amanda W; Pratt, Elizabeth; Murray, Heather W; Safren, Steven A; Pollack, Mark H

    2014-01-01

    Many patients diagnosed with opioid dependence do not adequately respond to pharmacologic, psychosocial, or combination treatment, highlighting the importance of novel treatment strategies for this population. The current study examined the efficacy of a novel behavioral treatment focusing on internal cues for drug use (Cognitive Behavioral Therapy for Interoceptive Cues; CBT-IC) relative to an active comparison condition, Individual Drug Counseling (IDC), when added to methadone maintenance treatment (MMT) among those who had not responded to MMT. Participants (N=78) were randomly assigned to receive 15 sessions of CBT-IC or IDC as an adjunct to ongoing MMT and counseling. Oral toxicology screens were the primary outcome. Results indicated no treatment differences between CBT-IC and IDC and a small, significant reduction of self-reported drug use, but no change on toxicology screens. Tests of potential moderators, including sex, anxiety sensitivity, and coping motives for drug use, did not yield significant interactions. Among opioid-dependent outpatients who have not responded to MMT and counseling, the addition of IDC or CBT-IC did not result in additive outcome benefits. These results highlight the need for more potent treatment strategies for opioid dependence, particularly among those who do not fully respond to frontline treatment.

  10. Quantitative encoding of a partial agonist effect on individual opioid receptors by multi-site phosphorylation and threshold detection

    OpenAIRE

    Lau, Elaine K.; Trester-Zedlitz, Michelle; Trinidad, Jonathan C.; Kotowski, Sarah J.; Krutchinsky, Andrew N.; Burlingame, Alma L; von Zastrow, Mark

    2011-01-01

    Many drugs act as partial agonists of seven-transmembrane signaling receptors when compared to endogenous ligands. Partial agonism is well described as a 'macroscopic' property manifest at the level of physiological systems or cell populations, but it is not known whether partial agonists encode discrete regulatory information at the 'microscopic' level of individual receptors. We addressed this question by focusing on morphine, a partial agonist drug for µ-type opioid peptide receptors, and ...

  11. Pharmacotherapy for opioid dependence in jails and prisons: research review update and future directions

    Directory of Open Access Journals (Sweden)

    Sharma A

    2016-04-01

    Full Text Available Anjalee Sharma,1 Kevin E O'Grady,1,2 Sharon M Kelly,1 Jan Gryczynski,1 Shannon Gwin Mitchell,1 Robert P Schwartz1 1Friends Research Institute, Baltimore, 2Department of Psychology, University of Maryland, College Park, MD, USA Purpose: The World Health Organization recommends the initiation of opioid agonists prior to release from incarceration to prevent relapse or overdose. Many countries in the world employ these strategies. This paper considers the evidence to support these recommendations and the factors that have slowed their adoption in the US. Methods: We reviewed randomized controlled trials (RCTs and longitudinal/observational studies that examine participant outcomes associated with the initiation or continuation of opioid agonists (methadone, buprenorphine or antagonists (naltrexone during incarceration. Papers were identified through a literature search of PubMed with an examination of their references and were included if they reported outcomes for methadone, buprenorphine, or naltrexone continued during incarceration or initiated prior to release in a correctional institution. Results: Fourteen studies were identified, including eight RCTs and six observational studies. One RCT found that patients treated with methadone who were continued on versus tapered off methadone during brief incarceration were more likely to return to treatment upon release. A second RCT found that the group starting methadone treatment in prison versus a waiting list was less likely to report using heroin and sharing syringes during incarceration. A third RCT found no differences in postrelease heroin use or reincarceration between individuals initiating treatment with methadone versus those initiating treatment with buprenorphine during relatively brief incarcerations. Findings from four additional RCTs indicate that starting opioid agonist treatment during incarceration versus after release was associated with higher rates of entry into community

  12. Impact of Illicit Drug Use on Health-Related Quality of Life in Opioid Dependent Patients Undergoing HIV Treatment

    Science.gov (United States)

    Aden, Brandon; Dunning, Allison; Nosyk, Bohdan; Wittenberg, Eve; Bray, Jeremy W.; Schackman, Bruce R.

    2015-01-01

    Objective To assess the impact of illicit drug use on health-related quality of life (health utility) among opioid-dependent, HIV-infected patients. Design Secondary analyses of data from the Buprenorphine-HIV Evaluation and Support (BHIVES) cohort of HIV-infected patients with opioid dependence in 9 U.S. HIV clinics between 2004 and 2009. Health status (Short Form-12 (SF-12)), combination antiretroviral treatment (ART) status, CD4 cell count, HCV antibody status, current drug use, and demographics were assessed at an initial visit and quarterly follow-up visits for up to one year. Short Form-6D health utility scores were derived from the SF-12. Multivariate mixed effects regression models were used to assess the impact of illicit drug use on health utility controlling for demographic, clinical and social characteristics. Results Health utility was assessed among 307 participants, 67% male, with median age 46 at 1089 quarterly assessments. In multivariate analyses, illicit opioid use, non-opioid illicit drug use, not being on ART and being on ART with poor adherence were associated with lower health utility. The observed decrement in health utility associated with illicit opioid use was larger for those on ART with good adherence (beta = −0.067; popioid drug use are negatively associated with health utility in patients with HIV, however the relative effect of illicit opioid use is smaller than that of not being on ART. Postponing ART until initiation of opioid substitution therapy or abstinence may have limited benefits from the perspective of maximizing health utility. PMID:26218410

  13. Nonmedical Use of Antihistaminergic Anxiolytics and Other Prescription Drugs among Persons with Opioid Dependence

    Science.gov (United States)

    Abrahamsson, Tove; Kral, Alex H.

    2016-01-01

    Background. Nonmedical prescription drug use (NMPDU) is an increasing problem, insufficiently studied among people in opioid maintenance treatment (OMT). This study investigates the prevalence of and factors associated with NMPDU for drug classes insufficiently described in opioid-dependent populations, including antihistaminergic anxiolytics and central stimulants. Methods. Study participants were recruited at two OMT clinics in Malmo, Sweden, between October 2014 and December 2015 (N = 73) and interviewed about their use, motivations for use, and acquisition and administration of prescription drugs. Results. The majority of the sample reported lifetime NMPDU: 60% for benzodiazepine-like hypnotics (z-drugs), 21% for pregabalin, 19% for stimulants, and 12%–15% for antihistaminergic anxiolytics. Lower age was associated with nonmedical benzodiazepine use (Adjusted Odds Ratio = 0.89; 95% Confidence Interval = 0.82–0.97). Illicit acquisition was reported by 61% of people using z-drugs, 46% of people using pregabalin, and 38% of people using prescription stimulants, but only by 6–10% of people using antihistaminergic anxiolytics. Conclusions. The substantial nonmedical use of pregabalin, z-drugs, and prescription stimulants found in this study suggests that clinicians should prescribe these drugs with great caution. Nonmedical use of antihistaminergic anxiolytics does not seem to be a clinical issue among people in OMT in a Swedish setting, but we propose future studies to monitor their use. PMID:28097037

  14. Nonmedical Use of Antihistaminergic Anxiolytics and Other Prescription Drugs among Persons with Opioid Dependence

    Directory of Open Access Journals (Sweden)

    Disa Dahlman

    2016-01-01

    Full Text Available Background. Nonmedical prescription drug use (NMPDU is an increasing problem, insufficiently studied among people in opioid maintenance treatment (OMT. This study investigates the prevalence of and factors associated with NMPDU for drug classes insufficiently described in opioid-dependent populations, including antihistaminergic anxiolytics and central stimulants. Methods. Study participants were recruited at two OMT clinics in Malmo, Sweden, between October 2014 and December 2015 (N=73 and interviewed about their use, motivations for use, and acquisition and administration of prescription drugs. Results. The majority of the sample reported lifetime NMPDU: 60% for benzodiazepine-like hypnotics (z-drugs, 21% for pregabalin, 19% for stimulants, and 12%–15% for antihistaminergic anxiolytics. Lower age was associated with nonmedical benzodiazepine use (Adjusted Odds Ratio = 0.89; 95% Confidence Interval = 0.82–0.97. Illicit acquisition was reported by 61% of people using z-drugs, 46% of people using pregabalin, and 38% of people using prescription stimulants, but only by 6–10% of people using antihistaminergic anxiolytics. Conclusions. The substantial nonmedical use of pregabalin, z-drugs, and prescription stimulants found in this study suggests that clinicians should prescribe these drugs with great caution. Nonmedical use of antihistaminergic anxiolytics does not seem to be a clinical issue among people in OMT in a Swedish setting, but we propose future studies to monitor their use.

  15. Gender dependent rate of metabolism of the opioid receptor-PET ligand [{sup 18}F]fluoroethyl-diprenorphine

    Energy Technology Data Exchange (ETDEWEB)

    Henriksen, G.; Spilker, M.E.; Hauser, A.I.; Boecker, H.; Schwaiger, M.; Wester, H.J. [Technische Univ. Muenchen, Garching (Germany). Dept. of Nuclear Medicine; Sprenger, T.; Platzer, S.; Toelle, T.R. [Technische Univ. Muenchen, Garching (Germany). Klinikum rechts der Isar, Neurology

    2006-07-01

    Aim: The morphinane-derivate 6-O-(2-[{sup 18}F]fluoroethyl)-6-O-desmethyldiprenorphine ([{sup 18}F]FDPN) is a non-selective opioid receptor ligand currently used in positron emission tomography (PET). Correction for plasma metabolites of the arterial input function is necessary for quantitative measurements of [{sup 18}]FDPN binding. A study was undertaken to investigate if there are gender dependent differences in the rate of metabolism of [{sup 18}F]FDPN. Methods: The rate of metabolism of [{sup 18}F]FDPN was mathematically quantified by fitting a bi-exponential function to each individual's dynamic metabolite data. Results: No statistically significant gender differences were found for age, weight, body mass index or dose. However, significant differences (p<0.01) in two of the four kinetic parameters describing the rate of metabolism were found between the two groups, with women metabolizing [{sup 18}F]FDPN faster than men. These differences were found in the contribution of the fast and slow kinetic components of the model describing the distribution of radioactive species in plasma, indicating a higher rate of enzyme-dependent degradation of [{sup 18}F]FDPN in women than in men. Conclusion: The findings reinforce the need for individualized metabolite correction during [{sup 18}F]FDPN-PET scans and also indicate that in certain cases, grouping according to gender could be performed in order to minimize methodological errors of the input function prior to kinetic analyses. (orig.)

  16. Quantitative encoding of a partial agonist effect on individual opioid receptors by multi-site phosphorylation and threshold detection

    Science.gov (United States)

    Lau, Elaine K.; Trester-Zedlitz, Michelle; Trinidad, Jonathan C.; Kotowski, Sarah J.; Krutchinsky, Andrew N.; Burlingame, Alma L.; von Zastrow, Mark

    2013-01-01

    Many drugs act as partial agonists of seven-transmembrane signaling receptors when compared to endogenous ligands. Partial agonism is well described as a 'macroscopic' property manifest at the level of physiological systems or cell populations, but it is not known whether partial agonists encode discrete regulatory information at the 'microscopic' level of individual receptors. We addressed this question by focusing on morphine, a partial agonist drug for µ-type opioid peptide receptors, and combining quantitative mass spectrometry with cell biological analysis to investigate morphine's reduced efficacy for promoting receptor endocytosis when compared to a peptide full agonist. We show that these chemically distinct ligands produce a complex, and qualitatively similar mixture of phosphorylated opioid receptor forms in intact cells. Quantitatively, however, the agonists promote markedly disproportional production of multi-site phosphorylation involving a specific Ser/Thr motif, whose modification at more than one residue is essential for efficient recruitment of the adaptor protein β-arrestin to clathrin-coated pits that mediate subsequent endocytosis of MORs. These results reveal quantitative encoding of agonist-selective endocytosis at the level of individual opioid receptors, based on the conserved biochemical principles of multi-site phosphorylation and threshold detection. PMID:21868358

  17. Featured Article: Nuclear export of opioid growth factor receptor is CRM1 dependent.

    Science.gov (United States)

    Kren, Nancy P; Zagon, Ian S; McLaughlin, Patricia J

    2016-02-01

    Opioid growth factor receptor (OGFr) facilitates growth inhibition in the presence of its specific ligand opioid growth factor (OGF), chemically termed [Met(5)]-enkephalin. The function of the OGF-OGFr axis requires the receptor to translocate to the nucleus. However, the mechanism of nuclear export of OGFr is unknown. In this study, endogenous OGFr, as well as exogenously expressed OGFr-EGFP, demonstrated significant nuclear accumulation in response to leptomycin B (LMB), an inhibitor of CRM1-dependent nuclear export, suggesting that OGFr is exported in a CRM1-dependent manner. One consensus sequence for a nuclear export signal (NES) was identified. Mutation of the associated leucines, L217 L220 L223 and L225, to alanine resulted in decreased nuclear accumulation. NES-EGFP responded to LMB, indicating that this sequence is capable of functioning as an export signal in isolation. To determine why the sequence functions differently in isolation than as a full length protein, the localization of subNES was evaluated in the presence and absence of MG132, a potent inhibitor of proteosomal degradation. MG132 had no effect of subNES localization. The role of tandem repeats located at the C-terminus of OGFr was examined for their role in nuclear trafficking. Six of seven tandem repeats were removed to form deltaTR. DeltaTR localized exclusively to the nucleus indicating that the tandem repeats may contribute to the localization of the receptor. Similar to the loss of cellular proliferation activity (i.e. inhibition) recorded with subNES, deltaTR also demonstrated a significant loss of inhibitory activity indicating that the repeats may be integral to receptor function. These experiments reveal that OGFr contains one functional NES, L217 L220 L223 and L225 and can be exported from the nucleus in a CRM1-dependent manner.

  18. Efficacy of treatment in an opioid -dependent population group using the Maudsley Addiction Profile (MAP) tool.

    Science.gov (United States)

    Collins, Ruth; Boggs, Bob; Taggart, Noel; Kelly, Martin; Drillington, Aileen; Swanton, Ivy; Patterson, Diane

    2009-01-01

    A pilot study was performed to assess the effectiveness of treatment in an opioid dependent population using the Maudsley Addiction Profile (MAP) tool1.The primary outcome of the study was to assess if treatment had an effect on 1. Substance use (quantity and frequency of use), 2. Health risk behaviour (injecting and sharing injecting equipment), 3. Health symptoms (physical and psychological) and 4. Personal /Social functioning (relationships, employment and crime). A secondary outcome was also sought.The study took place in 2007 in an inner city Belfast hospital specialising in the treatment of addiction, over a two month period. Fifteen patients, all opioid dependent and receiving outpatient community treatment, were interviewed at baseline (prior to the commencement of treatment) and at eight weeks follow up.Three patients were lost to follow up. Two patients stopped using altogether. Of the remaining patients, improvements were seen in most areas. There was a decrease in the use of heroin (71.28%), cocaine (99.72%), crack cocaine (100%), cannabis (99.94%) and alcohol (33.17%). There was a reduction in injecting behaviour (60.93%). Improvements were observed in health with a reduction in physical (41.35%) and psychological (35%) symptoms. Overall personal and social functioning improved regarding interactions with family and friends. A reduction in crime was also observed (75%).Opinions and views of staff involved in the study were generally positive.This patient population presents with multiple and complex needs. Effective treatment needs to address these needs and not just drug addiction alone. The Maudsley Addiction Profile tool highlights this.

  19. μ-Opioid Agonist Inhibition of κ-Opioid Receptor-Stimulated Extracellular Signal-Regulated Kinase Phosphorylation Is Dynamin-Dependent in C6 Glioma Cells

    OpenAIRE

    Bohn, Laura M.; Belcheva, Mariana M.; Coscia, Carmine J.

    2000-01-01

    In previous studies we found that μ-opioids, acting via μ-opioid receptors, inhibit endothelin-stimulated C6 glioma cell growth. In the preceding article we show that the κ-selective opioid agonist U69,593 acts as a mitogen with a potency similar to that of endothelin in the same astrocytic model system. Here we report that C6 cell treatment with μ-opioid agonists for 1 h results in the inhibition of κ-opioid mitogenic signaling. The μ-selective agonist endomorphin-1 attenuates κ-opioid-stimu...

  20. Effects of Ibudilast on the Subjective, Reinforcing, and Analgesic Effects of Oxycodone in Recently Detoxified Adults with Opioid Dependence.

    Science.gov (United States)

    Metz, Verena E; Jones, Jermaine D; Manubay, Jeanne; Sullivan, Maria A; Mogali, Shanthi; Segoshi, Andrew; Madera, Gabriela; Johnson, Kirk W; Comer, Sandra D

    2017-08-01

    Ibudilast, a nonselective phosphodiesterase inhibitor, is used clinically in Asia for the treatment of asthma and poststroke dizziness. Recent preclinical studies have suggested that it also inhibits glial cell activation in rodents, and may alter opioid-mediated effects, including analgesia and withdrawal symptoms. The effects of ibudilast on the abuse potential of opioids in humans are largely unknown. The present study was designed to examine the influence of ibudilast on subjective (including drug craving), reinforcing, and analgesic effects of oxycodone in human volunteers diagnosed with opioid dependence (equivalent to moderate-severe opioid use disorder). Non-treatment-seeking opioid-dependent male volunteers (n=11) underwent an in-patient detoxification with morphine, followed by maintenance on placebo (0 mg b.i.d.) and active ibudilast (50 mg b.i.d.). Under each maintenance dose, six experimental sample and choice sessions were completed involving oral oxycodone administration (0, 15, and 30 mg/70 kg, p.o.). Subjective effects of oxycodone and drug craving were measured with visual analog scales (VAS) and a Drug Effects Questionnaire. The cold pressor test was used to produce pain, and a modified progressive-ratio choice procedure was used to measure the reinforcing effects of oxycodone. Under the active ibudilast condition compared with the placebo condition, ratings of drug liking following 15 mg of oxycodone were decreased significantly. The mean drug breakpoint value was also significantly lower in the active vs the placebo ibudilast condition under the 15 mg oxycodone condition, but not significantly lower under the 30 mg oxycodone condition. Heroin craving was significantly reduced under active ibudilast vs placebo, and similar effects were observed for tobacco and cocaine craving. Furthermore, mean subjective ratings of pain were lower in the active ibudilast condition. Our data suggest that ibudilast may be useful for treating opioid

  1. Effects of Disulfiram on QTc Interval in non-Opioid Dependent and Methadone-Treated Cocaine Dependent Patients

    Science.gov (United States)

    Atkinson, Thomas S.; Sanders, Nichole; Mancino, Michael; Oliveto, Alison

    2013-01-01

    Objectives Methadone and cocaine are each known to prolong the QTc interval, a risk factor for developing potentially fatal cardiac arrhythmias. Disulfiram, often administered in the context of methadone maintenance to facilitate alcohol abstinence, has been shown to have some efficacy for cocaine dependence. Disulfiram has differential effects on cocaine and methadone metabolism, but its impact on methadone- or cocaine-induced changes in QTc interval is unclear. Thus, the effects of disulfiram on QTc interval in a subset of cocaine dependent patients participating in a 14 week, randomized, double blind, placebo-controlled clinical trial of disulfiram was prospectively determined. Methods Opioid dependent participants were inducted onto methadone (wks 1-2; MT) and both MT and nonopioid dependent (UT) participants were randomized to receive disulfiram (wks 3-14) at one of the following doses: 0, 250, 375, or 500 mg/day. Electrocardiograms (ECGs) were obtained prior to study entry and during weeks 2 and 4. Results Complete QTc interval data in 23 MT and 18 UT participants were analyzed. QTc interval tended to be higher in MT relative to UT dependent participants, regardless of disulfiram dose and time point, but disulfiram did not differentially alter QTc interval. QTc interval was, however, significantly greater in participants with recent cocaine use than those with no recent use. Conclusions These results suggest that cocaine use and possibly MT status, but not disulfiram, are risk factors for QTc prolongation. PMID:23648640

  2. Child Maltreatment as a Risk Factor for Opioid Dependence: Comparison of Family Characteristics and Type and Severity of Child Maltreatment with a Matched Control Group

    Science.gov (United States)

    Conroy, Elizabeth; Degenhardt, Louisa; Mattick, Richard P.; Nelson, Elliot C.

    2009-01-01

    Objective: To examine the prevalence, characteristics and risk factors for child maltreatment among opioid-dependent persons compared to a community sample of similar social disadvantage. Method: The study employed a case-control design. Cases had a history of opioid pharmacotherapy. Controls were frequency matched to cases with regard to age, sex…

  3. Methadone for the treatment of Prescription Opioids Dependence. A retrospective chart review.

    Science.gov (United States)

    Barrio, Pablo; Ezzeldin, Mohamed; Bruguera, Pol; Pérez, Ana; Mansilla, Sara; Fàbrega, Marina; Lligoña, Anna; Mondón, Sílvia; Balcells, Mercè

    2016-06-14

    Prescription opioids (PO) addiction is increasing to an epidemic level. Few studies exist regarding its treatment. Although buprenorphine has been the mainstay so far, other treatment options might be considered, such as methadone. We conducted a retrospective assessment of all patients admitted to a psychiatry ward for PO detoxification using methadone between 2010 and 2013. The assessment and description was carried out during a 3-month follow-up period after their discharge. Although this is a retrospective chart review, our exploration included sociodemographic and treatment variables in addition to the abstinence rates for the whole sample. Eleven patients were included, mostly women (81.8%), with a median age of 50 years. The median duration of dependence was 8 years. Dependence on other substances and psychiatric comorbidities were high. Eight patients were monitored during three months. Of these, 7 (87.5%) were abstinent after that period. The results suggest that methadone deserves further exploration as a potentially efficacious treatment option for PO dependence.

  4. Do drug treatment variables predict cognitive performance in multidrug-treated opioid-dependent patients? A regression analysis study

    Directory of Open Access Journals (Sweden)

    Rapeli Pekka

    2012-11-01

    Full Text Available Abstract Background Cognitive deficits and multiple psychoactive drug regimens are both common in patients treated for opioid-dependence. Therefore, we examined whether the cognitive performance of patients in opioid-substitution treatment (OST is associated with their drug treatment variables. Methods Opioid-dependent patients (N = 104 who were treated either with buprenorphine or methadone (n = 52 in both groups were given attention, working memory, verbal, and visual memory tests after they had been a minimum of six months in treatment. Group-wise results were analysed by analysis of variance. Predictors of cognitive performance were examined by hierarchical regression analysis. Results Buprenorphine-treated patients performed statistically significantly better in a simple reaction time test than methadone-treated ones. No other significant differences between groups in cognitive performance were found. In each OST drug group, approximately 10% of the attention performance could be predicted by drug treatment variables. Use of benzodiazepine medication predicted about 10% of performance variance in working memory. Treatment with more than one other psychoactive drug (than opioid or BZD and frequent substance abuse during the past month predicted about 20% of verbal memory performance. Conclusions Although this study does not prove a causal relationship between multiple prescription drug use and poor cognitive functioning, the results are relevant for psychosocial recovery, vocational rehabilitation, and psychological treatment of OST patients. Especially for patients with BZD treatment, other treatment options should be actively sought.

  5. A case report on the treatment of complex chronic pain and opioid dependence by a multidisciplinary transitional pain service using the ACT Matrix and buprenorphine/naloxone

    Science.gov (United States)

    Weinrib, Aliza Z; Burns, Lindsay C; Mu, Alex; Azam, Muhammad Abid; Ladak, Salima SJ; McRae, Karen; Katznelson, Rita; Azargive, Saam; Tran, Cieran; Katz, Joel; Clarke, Hance

    2017-01-01

    In an era of growing concern about opioid prescribing, the postsurgical period remains a critical window with the risk of significant opioid dose escalation, particularly in patients with a history of chronic pain and presurgical opioid use. The purpose of this case report is to describe the multidisciplinary care of a complex, postsurgical pain patient by an innovative transitional pain service (TPS). A 59-year-old male with complex chronic pain, as well as escalating long-term opioid use, presented with a bleeding duodenal ulcer requiring emergency surgery. After surgery, the TPS provided integrated pharmacological and behavioral treatment, including buprenorphine combined with naloxone and acceptance and commitment therapy (ACT) using the ACT Matrix. The result was dramatic pain reduction and improved functioning and quality of life after 40+ years of chronic pain, thus changing the pain trajectory of a chronic, complex, opioid-dependent patient.

  6. Addiction in developmental perspective: influence of conduct disorder severity, subtype, and attention-deficit hyperactivity disorder on problem severity and comorbidity in adults with opioid dependence.

    NARCIS (Netherlands)

    Carpentier, P.J.; Knapen, L.J.; Gogh, M.T. van; Buitelaar, J.K.; Jong, C.A.J. de

    2012-01-01

    This retrospective cross-sectional study examines whether conduct disorder and attention deficit hyperactivity disorder are associated with problem severity and psychiatric comorbidity in 193 middle-aged, opioid-dependent patients. Conduct disorder history, attention deficit hyperactivity disorder,

  7. Addiction in developmental perspective: influence of conduct disorder severity, subtype, and attention-deficit hyperactivity disorder on problem severity and comorbidity in adults with opioid dependence.

    NARCIS (Netherlands)

    Carpentier, P.J.; Knapen, L.J.; Gogh, M.T. van; Buitelaar, J.K.; Jong, C.A.J. de

    2012-01-01

    This retrospective cross-sectional study examines whether conduct disorder and attention deficit hyperactivity disorder are associated with problem severity and psychiatric comorbidity in 193 middle-aged, opioid-dependent patients. Conduct disorder history, attention deficit hyperactivity disorder,

  8. Development of pharmaceutical heroin preparations for medical co-prescription to opioid dependent patients.

    Science.gov (United States)

    Klous, Marjolein G; Van den Brink, Wim; Van Ree, Jan M; Beijnen, Jos H

    2005-12-12

    Presently, there is a considerable interest in heroin-assisted treatment: co-prescription of heroin to certain subgroups of chronic, treatment-resistant, opioid dependent patients. In 2002, nine countries had planned (Australia, Belgium, Canada, France, Spain) or ongoing (Germany, The Netherlands, Switzerland, United Kingdom) clinical trials on this subject. These trials (and the routine heroin-assisted treatment programs that might result) will need pharmaceutical heroin (diacetylmorphine) to prescribe to the patients. Research into the development of pharmaceutical forms of heroin for prescription to addicts can benefit from the large amount of knowledge that already exists regarding this substance. Therefore, in this paper we review the physicochemical and pharmaceutical properties of diacetylmorphine and the clinically investigated routes of administration, as well as routes of administration utilised on the street in the context of developing pharmaceutical heroin formulations for prescription to addicts. Patient acceptability of the formulation is essential, because heroin-assisted treatment is aimed at treatment-resistant addicts, who often have to be encouraged to participate (or to maintain participation) in a treatment program. This means that the most suitable products would have pharmacokinetic profiles mimicking that of diacetylmorphine for injection, with rapid peak concentrations of diacetylmorphine and 6-acetylmorphine, ensuring the 'rush effect' and the sustained presence of morphine(-6-glucuronide) creating the prolonged euphoria. Diacetylmorphine for inhalation after volatilisation (via 'chasing the dragon') seems to be a suitable candidate, while intranasal and oral diacetylmorphine are currently thought to be unsuitable. However, oral and intranasal delivery systems might be improved and become suitable for use by heroin dependent patients.

  9. Suicidal ideation is associated with individual differences in prescription opioid craving and cue-reactivity among chronic pain patients.

    Science.gov (United States)

    Garland, Eric L; Riquino, Michael R; Priddy, Sarah E; Bryan, Craig J

    2017-01-01

    Given that chronic pain patients experience significant rates of suicidal ideation and suicide attempts, access to prescription opioids compounds the risk of death by suicide. These patients may experience heightened opioid craving and exhibit increased cue-reactivity to stimuli associated with past opioid use when suicidal ideation produces negative affective states. Because both opioids and suicidal behavior are used to alleviate emotional and physical pain through a process of negative reinforcement, elucidating factors that mediate this association may yield insight into suicide risk among chronic pain patients. This study examined the relationship between suicidal ideation and opioid craving and cue-reactivity, and tested opioid self-medication as a mediator of associations between those factors after controlling for the impact of pain severity. A sample of 115 chronic pain patients provided demographic and clinical information on the Obsessive Compulsive Drug Use Scale, the Current Opioid Misuse Measure, and the Brief Pain Inventory before completing an opioid dot probe task in which heart rate variability was recorded. As hypothesized, suicidal ideation was positively correlated with subjective opioid craving and physiological cue-reactivity. Self-medication significantly mediated the association between suicidal ideation, craving, and cue-reactivity. As opioids relieve the emotional pain linked with suicidal thoughts, chronic pain patients with higher levels of suicidal ideation may experience more intense opioid craving and exhibit heightened physiological cue-reactivity when compared to patients with low levels of suicidal ideation.

  10. Effects of long-term sustained naltrexone release onthe optic center in opioid-dependent patients Case-control study in four provinces of China

    Institute of Scientific and Technical Information of China (English)

    Shengxi He; Longchuan Yu; Shaowei Jia; Qing Chen; Dongmei Wang; Shu Hu

    2011-01-01

    Very little is known about visual functional recovery following long-term naltrexone administration in opioid-dependent patients. In the present study, a portable event-related potential (ERP) working system was utilized to collect and record ERP in opioid-dependent patients and normal controls in visual half-field testing. In addition, the influence of long-term sustained naltrexone release on the visual nervous system was observed in opioid-dependent patients. Results revealed a significant main group effect in reaction time to visual signal stimulations. The reaction time of normal controls was shortest, but longest in opioid-dependent patients. The reaction time of long-term sustained naltrexone release group and compulsory detoxification group was similar to normal controls. A significant main group effect was also observed in P100 latency, and P100 latency in normal controls and the compulsory detoxification group was significantly decreased compared with the opioid-dependent patients. P100 amplitude at the Oz-electrode resulted in a significant main group effect. In particular, normal controls exhibited significant differences compared with long-term sustained release naltrexone and compulsory detoxification groups. These findings demonstrated that long-term sustained naltrexone release effectively ameliorated optic center function and improved visual sensitivity and reactions in opioid-dependent patients.

  11. A case report on the treatment of complex chronic pain and opioid dependence by a multidisciplinary transitional pain service using the ACT Matrix and buprenorphine/naloxone

    Directory of Open Access Journals (Sweden)

    Weinrib AZ

    2017-03-01

    Full Text Available Aliza Z Weinrib,1,2 Lindsay C Burns,1,2 Alex Mu,1 Muhammad Abid Azam,1,2 Salima SJ Ladak,1 Karen McRae,1,3 Rita Katznelson,1,3 Saam Azargive,1 Cieran Tran,1 Joel Katz,1–3 Hance Clarke1,3 1Pain Research Unit, Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, 2Department of Psychology, York University, 3Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada Abstract: In an era of growing concern about opioid prescribing, the postsurgical period remains a critical window with the risk of significant opioid dose escalation, particularly in patients with a history of chronic pain and presurgical opioid use. The purpose of this case report is to describe the multidisciplinary care of a complex, postsurgical pain patient by an innovative transitional pain service (TPS. A 59-year-old male with complex chronic pain, as well as escalating long-term opioid use, presented with a bleeding duodenal ulcer requiring emergency surgery. After surgery, the TPS provided integrated pharmacological and behavioral treatment, including buprenorphine combined with naloxone and acceptance and commitment therapy (ACT using the ACT Matrix. The result was dramatic pain reduction and improved functioning and quality of life after 40+ years of chronic pain, thus changing the pain trajectory of a chronic, complex, opioid-dependent patient. Keywords: transitional pain service, postsurgical pain, chronic pain, opioid dependence, opioid weaning, acceptance and commitment therapy

  12. Client satisfaction among participants in a randomized trial comparing oral methadone and injectable diacetylmorphine for long-term opioid-dependency

    Directory of Open Access Journals (Sweden)

    Brissette Suzanne

    2011-07-01

    149 (60.3% participants; concerns about the randomization process and the study ending were most commonly reported by participants receiving the oral and injectable medications, respectively. Conclusions The higher satisfaction among those receiving medically prescribed injectable diacetylmorphine (or hydromorphone supports current evidence regarding the attractiveness of this treatment for long-term, opioid-dependent individuals not benefiting sufficiently from other treatments. In addition, the measurement of treatment satisfaction provides valuable information about participants at risk of relapse and in need of additional services. Trial Registration ClinicalTrials.gov Identifier: NCT00175357

  13. Sprcial discussion: Future Roles for Tincture of Opium in Medical Intervention for Opioid Dependence Treads and Hopes

    Directory of Open Access Journals (Sweden)

    2009-02-01

    Full Text Available Opium tincture or tincture of opium (TOP, also known as Laudanum, is an alcoholic herbal preparation of opium. It is made by combining ethanol with opium latex or powder. After works of Paracelsus, the 16th century Swiss-German alchemist, who discovered that the alkaloids in opium are far more soluble in alcohol compared to water and named Opium tincture as Laudanum, this drug has been found a broad range of applications as the drug of choice for practically every ailment through 17th to 19th centuries. The early 20th century brought increased regulation of all manner of narcotics, including laudanum, as the addictive properties of opium became more widely understood. By the late 20th century, TOP's use was almost exclusively confined to treating severe diarrhea. During these thirty years, The efficacy and cost-effectiveness of opioid substitution therapy for the treatment of opioid addiction has been well documented by methadone and buprenorphine. Based on the idea of substitution therapy, TOP and slow releasing oral morphine (SROM have been proposed as the new alternatives. TOP could be used in three different ways in interventions for opioid dependency, first, as a supportive drug to reduce withdrawal syndrome during detoxification programs, second, as a substitution drug in long term maintenance, third, as a legal form of opioid drugs for harm reduction purposes. A little but growing evidences are supporting effectiveness of TOP for detoxification programs, in Iran, some preliminary open label studies showed effectiveness of TOP as a detoxifying drug in three to six month program, Now another open label study is evaluating TOP in a specific detoxification program with monthly evaluation and providing long term follow up after reaching to abstinence. There are a strong debate among the policy makers and clinicians on implementation of TOP in Iranian National Substance Abuse Treatment Facilities. In this article, We reviewed the proposed

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

    Science.gov (United States)

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

    2014-02-01

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

  15. Opioid intoxication

    Science.gov (United States)

    ... easily result in intoxication. The provider prescribes a sleep medicine (sedative) in addition to the opioid. The provider ... an opioid with certain other drugs, such as sleep medicines or alcohol Taking the opioid in ways not ...

  16. Escitalopram is associated with reductions in pain severity and pain interference in opioid dependent patients with depressive symptoms.

    Science.gov (United States)

    Tsui, Judith I; Herman, Debra S; Kettavong, Malyna; Anderson, Bradley J; Stein, Michael D

    2011-11-01

    Pain is common among opioid-dependent patients, yet pharmacologic strategies are limited. The aim of this study was to explore whether escitalopram, a selective serotonin reuptake inhibitor, was associated with reductions in pain. The study used longitudinal data from a randomized, controlled trial that evaluated the effects of escitalopram on treatment retention in patients with depressive symptoms who were initiating buprenorphine/naloxone for treatment of opioid dependence. Participants were randomized to receive escitalopram 10 mg or placebo daily. Changes in pain severity, pain interference, and depression were assessed at 1-, 2-, and 3-month visits with the visual analog scale, Brief Pain Inventory, and the Beck Depression Inventory II, respectively. Fixed-effects estimators for panel regression models were used to assess the effects of intervention on changes in outcomes over time. Additional models were estimated to explore whether the intervention effect was mediated by within-person changes in depression. In this sample of 147 adults, we found that participants randomized to escitalopram had significantly larger reductions on both pain severity (b=-14.34, t=-2.66, P<.01) and pain interference (b=-1.20, t=-2.23, P<.05) between baseline and follow-up. After adjusting for within-subject changes in depression, the estimated effects of escitalopram on pain severity and pain interference were virtually identical to the unadjusted effects. This study of opioid-dependent patients with depressive symptoms found that treatment with escitalopram was associated with clinically meaningful reductions in pain severity and pain interference during the first 3 months of therapy.

  17. Relationship between cold pressor pain-sensitivity and sleep quality in opioid-dependent males on methadone treatment

    OpenAIRE

    2015-01-01

    Aim. Poor sleep quality due to pain has been reported among opioid-dependent male patients on methadone maintenance therapy (MMT) but objective pain data are lacking. This study aimed to investigate the rate of pain-sensitivity using cold pressor test (CPT) and the relationship between pain-sensitivity and sleep quality in this population. Methods. A total of 168 male participants were included into the study. Objective pain-tolerance was evaluated at 0 h and at 24 h after the first CPT. ...

  18. Effectiveness of Mindfulness-Based Relapse Prevention in opioid Dependence Treatment &Mental Health

    Directory of Open Access Journals (Sweden)

    2008-11-01

    Findings: therapy compliance, retention in treatment, decrease in somatic symptoms, anxiety, social dysfunction and increase in health was significantly in both combination of psychological intervention method than the Naltroxan group. Mindfulness-based on relapse prevention was more effective than CBT relapse prevention in decreasing of, social dysfunction, relapse prevention, increase of therapy compliance, and health. Results: Mindfulness based relapse prevention was superior to CBT and Naltroxan and considerably increased effectiveness of opioid relapse prevention therapy.

  19. Regional differences in mu-opioid receptor-dependent modulation of basal dopamine transmission in rat striatum.

    Science.gov (United States)

    Campos-Jurado, Y; Martí-Prats, L; Zornoza, T; Polache, A; Granero, L; Cano-Cebrián, M J

    2017-01-18

    The nigrostriatal dopamine system is implicated in the regulation of reward and motor activity. Dopamine (DA) release in dorsal striatum (DS) is controlled by the firing rate of DA neurons in substantia nigra pars compacta. However, influences at terminal level, such as those involving activation of mu opioid receptors (MORs), can play a key role in determining DA levels in striatum. Nonetheless, published data also suggest that the effect of opioid drugs on DA levels may differ depending on the DS subregion analyzed. In this study, in vivo microdialysis in rats was used to explore this regional dependence. Changes in basal DA levels induced by local retrodialysis application of DAMGO (selective MORs agonist) in three different subregions of DS along the rostro-caudal axis were studied. Our results indicate that whereas administration of 10μM DAMGO into the rostral and caudal DS significantly reduced DA levels, in medial DS an increase in DA levels was observed. These data reveal a regional-dependent MOR modulation of DA release in DS, similar to that described in the ventral striatum. Our findings may lead to a better understanding of the nigrostriatal DA system regulation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Urine analysis of 3,4-methylenedioxypyrovalerone in opioid-dependent patients by gas chromatography-mass spectrometry.

    Science.gov (United States)

    Ojanperä, Ilkka Antero; Heikman, Pertti Kalevi; Rasanen, Ilpo Juhani

    2011-04-01

    A gas chromatography-mass spectrometry (GCMS) procedure was developed for the quantitative analysis of the new designer drug methylenedioxypyrovalerone (MDPV) in urine together with the common stimulants amphetamine, methamphetamine, and methylenedioxymethamphetamine (MDMA). The procedure involved electron ionization (EI) GCMS in the selected ion monitoring (SIM) mode after liquid-liquid extraction with toluene and derivatization with heptafluorobutyric acid anhydride. All MDPV findings were confirmed by positive chemical ionization GCMS in SIM mode. Positive chemical ionization-GCMS allowed the protonated molecule M+H+ m/z 276 to be used as a target ion with 3 abundant fragments as qualifier ions. By electron ionization-GCMS, the limit of quantification (LOQ) for MDPV was 0.02 mg/L; and for amphetamine, methamphetamine, and MDMA, the LOQ was 0.05 mg/L. The method was applied to monitoring urine samples from opioid-dependent patients undergoing opioid substitution treatment. Nine of the 34 urine samples (26%) analyzed were MDPV positive by the GCMS procedure. The positive samples were obtained from 2 female and 7 male patients with a mean age of 31 years. The median (range) MDPV concentration was 0.16 mg/L (0.04-3.9 mg/L) based on the 7 samples for which a numeric value was obtained, whereas the concentration was below the LOQ but above the limit of detection in 2 samples. The method revealed amphetamine in approximately 40% of the cases, and there was no statistical difference between the MDPV-positive and MDPV-negative groups. Urine amphetamine concentrations were on average 10 times higher than those of MDPV. The opioid-dependent patients used MDPV mainly as a substitute for amphetamine, judging from the laboratory findings of this study and the information from our patients.

  1. Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations.

    Science.gov (United States)

    Arout, Caroline A; Edens, Ellen; Petrakis, Ismene L; Sofuoglu, Mehmet

    2015-06-01

    Opioid analgesics have become a cornerstone in the treatment of moderate to severe pain, resulting in a steady rise of opioid prescriptions. Subsequently, there has been a striking increase in the number of opioid-dependent individuals, opioid-related overdoses, and fatalities. Clinical use of opioids is further complicated by an increasingly deleterious profile of side effects beyond addiction, including tolerance and opioid-induced hyperalgesia (OIH), where OIH is defined as an increased sensitivity to already painful stimuli. This paradoxical state of increased nociception results from acute and long-term exposure to opioids, and appears to develop in a substantial subset of patients using opioids. Recently, there has been considerable interest in developing an efficacious treatment regimen for acute and chronic pain. However, there are currently no well-established treatments for OIH. Several substrates have emerged as potential modulators of OIH, including the N-methyl-D-aspartate and γ-aminobutyric acid receptors, and most notably, the innate neuroimmune system. This review summarizes the neurobiology of OIH in the context of clinical treatment; specifically, we review evidence for several pathways that show promise for the treatment of pain going forward, as prospective adjuvants to opioid analgesics. Overall, we suggest that this paradoxical state be considered an additional target of clinical treatment for chronic pain.

  2. Binding affinity to and dependence on some opioidsin Sf9 insect cells expressing human μ-opioid receptor

    Institute of Scientific and Technical Information of China (English)

    LIUZhong-Hua; HEYou; JINWen-Qiao; CHENXin-Jian; ZHANGHong-Ping; SHENQing-Xiang; CHIZhi-Qiang

    2003-01-01

    AIM: To investigate the receptor binding affinity and naloxone-precipitated cAMP overshoot of dihydroetorphine,fentanyl, heroin, and pethidine in Sf9 insect cells expressing human μ-opioid receptor (Sf9-μ cells). METHODS:Competitive binding assay of [3H]ohmefentanyl was used to reveal the affinity for μ-opioid receptor in Sf9-μ cells.[3H]cAMP RIA was used to determine cAMP level. Antinociceptive activity was evaluated using 55℃ mouse hotplate test. Naloxone-precipitated withdrawal jumping was used to reflect physical dependence in mice. RESULTS:All drugs displayed antinociceptive activity and produced physical dependence in mice. The Ki values ofdihydroetorphine, fentanyl, heroin, and pethidine in competitive binding assay were (0.85±0.20)nmol, (59.1±11.7)nmol, (0.36±0.13)μmol, and (12.2±3.8) μmol respectively. The binding affinities of these drugs for μ-opioidreceptor in Sf9-μ cells were paralleled to their antinociceptive activities in mice. After chronic pretreatment withthese drugs, naloxone induced cAMP withdrawal overshoot in Sf9-μ cells. The dependence index in Sf9-μ cellswas calculated as Ki value in competitive binding assay over ECs0 value in naloxone-precipitated cAMP assay, Thephysical dependence index in mice was calculated as antinociceptive ED50/withdrawal jumping cumulative EDs0.There was a good linear correlation between dependence index in Sf9-μ cells and physical dependence index inmice. CONCLUSION: The Sf9-μ cells could be used as a cell model to evaluate the receptor binding affinity andphysical dependent liability of analgesic agents.

  3. Characterization of Individuals Seeking Treatment for Caffeine Dependence

    OpenAIRE

    Juliano, Laura M.; Evatt, Daniel P.; Richards, Brian D.; Griffiths, Roland R.

    2012-01-01

    Previous investigations have identified individuals who meet criteria for DSM-IV-TR substance dependence as applied to caffeine, but there is little research on treatments for caffeine dependence. This study aimed to thoroughly characterize individuals who are seeking treatment for problematic caffeine use. Ninety-four individuals who identified as being psychologically or physically dependent on caffeine, or who had tried unsuccessfully to modify caffeine consumption participated in a face-t...

  4. Neocortical prodynorphin expression is transiently increased with learning: Implications for time- and learning-dependent neocortical kappa opioid receptor activation.

    Science.gov (United States)

    Loh, Ryan; Collins, Sean; Galvez, Roberto

    2017-09-29

    There are several lines of evidence that indicate a prominent role for the opioid system in the acquisition and consolidation of learned associations. Specifically, kappa opioid receptor (KOR) modulation has been demonstrated to alter various behavioral tasks including whisker trace eyeblink conditioning (WTEB). WTEB is an associative conditioning paradigm in which a neutral conditioned stimulus (CS; Whisker stimulation) is paired following a short stimulus free trace interval with a salient unconditioned stimulus that elicits a blink response (US; Eye shock). Work from our laboratory has shown that WTEB conditioning is dependent upon and induces plasticity in primary somatosensory cortex (S1), a likely site for memory storage. Our subsequent studies have shown that WTEB acquisition or consolidation are impaired when the initial or later phase of KOR activation in S1 is respectively blocked. Interestingly, this mechanism by which KOR is activated in S1 during learning remains unexplored. Dynorphin (DYN), KOR's endogenous ligand, is synthesized from the precursor prodynorphin (PD) that is synthesized from preprodynorphin (PPD). In S1, most PPD is found in inhibitory GABAergic somatostatin interneurons (SOM), suggesting that these SOM interneurons are upstream regulators of learning induced KOR activation. Using immunofluorescence to investigate the expression of PD and SOM, the current study found that PD/SOM expression was transiently increased in S1 during learning. Interestingly, these findings have direct implications towards a time- and learning-dependent role for KOR activation in neocortical mechanisms mediating learning. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Preliminary buprenorphine sublingual tablet pharmacokinetic data in plasma, oral fluid and sweat during treatment of opioid-dependent pregnant women

    Science.gov (United States)

    Concheiro, Marta; Jones, Hendreé E.; Johnson, Rolley E.; Choo, Robin; Huestis, Marilyn A.

    2011-01-01

    Background Buprenorphine is currently under investigation as a pharmacotherapy to treat pregnant women for opioid dependence. This research evaluates buprenorphine (BUP), norbuprenophine (NBUP), buprenorphine-glucuronide (BUP-Gluc) and norbuprenorphine-glucuronide (NBUP-Gluc) pharmacokinetics after high dose (14–20 mg) BUP sublingual tablet administration in three opioid-dependent pregnant women. Methods Oral fluid and sweat specimens were collected in addition to plasma specimens for 24 h during gestation weeks 28 or 29 and 34, and 2 months after delivery. Tmax was not affected by pregnancy; however, BUP and NBUP Cmax and AUC0–24h tended to be lower during pregnancy compared to postpartum levels. Results Statistically significant but weak positive correlations were found for BUP plasma and OF concentrations, and BUP/NBUP ratios in plasma and OF. Conclusion Statistically significant negative correlations were observed for times of specimen collection and BUP and NBUP OF/plasma ratios. BUP-Gluc and NBUP-Gluc were detected in only 5% of OF specimens. In sweat, BUP and NBUP were detected in only 4 of 25 (12 or 24 h) specimens in low concentrations (<2.4 ng/patch). These preliminary data describe BUP and metabolite pharmacokinetics in pregnant women and suggest that, like methadone, upward dose adjustments may be needed with advancing gestation. PMID:21860340

  6. Expanding treatment capacity for opioid dependence with office-based treatment with buprenorphine: National surveys of physicians.

    Science.gov (United States)

    Arfken, Cynthia L; Johanson, Chris-Ellyn; di Menza, Salvatore; Schuster, Charles Roberts

    2010-09-01

    Office-based treatment of opioid dependence with buprenorphine has the potential to expand treatment capacity in the United States. However, nationally, little is known about the number, characteristics, and experiences of physicians certified to prescribe buprenorphine. Moreover, little is known about the impact of easing federal regulations on the number of patients a physician is allowed to treat concurrently. To address these questions, surveys of national samples of physicians certified to prescribe buprenorphine (2004-2008) were analyzed (N = 6,892). There has been a continual increase in the number of physicians certified to prescribe buprenorphine, increase in the mean number of patients treated by physicians, and decrease in patients turned away, coinciding temporally with easing of federal regulations. In addition, most physicians prescribed buprenorphine outside of traditional treatment settings. The U.S. experiment in expanding Schedule III-V medications for opioid dependence to physicians outside of formal substance abuse treatment facilities appears to have resulted in expanded capacity. Copyright 2010 Elsevier Inc. All rights reserved.

  7. Co-prescription of opioids with benzodiazepine and other co-medications among opioid users: differential in opioid doses

    Science.gov (United States)

    Zin, Che Suraya; Ismail, Fadhilah

    2017-01-01

    Purpose This study investigated the patterns of opioid co-prescription with benzodiazepine and other concomitant medications among opioid users. Opioid dose in each type of co-prescription was also examined. Patients and methods This cross-sectional study was conducted among opioid users receiving concomitant medications at an outpatient tertiary hospital setting in Malaysia. Opioid prescriptions (morphine, fentanyl, oxycodone, dihydrocodeine and tramadol) that were co-prescribed with other medications (opioid + benzodiazepines, opioid + antidepressants, opioid + anticonvulsants, opioid + antipsychotics and opioid + hypnotics) dispensed from January 2013 to December 2014 were identified. The number of patients, number of co-prescriptions and the individual mean opioid daily dose in each type of co-prescription were calculated. Results A total of 276 patients receiving 1059 co-prescription opioids with benzodiazepine and other co-medications were identified during the study period. Of these, 12.3% of patients received co-prescriptions of opioid + benzodiazepine, 19.3% received opioid + anticonvulsant, 6.3% received opioid + antidepressant and 10.9% received other co-prescriptions, including antipsychotics and hypnotics. The individual mean opioid dose was <100 mg/d of morphine equivalents in all types of co-prescriptions, and the dose ranged from 31 to 66 mg/d in the co-prescriptions of opioid + benzodiazepine. Conclusion Among the opioid users receiving concomitant medications, the co-prescriptions of opioid with benzodiazepine were prescribed to 12.3% of patients, and the individual opioid dose in this co-prescription was moderate. Other co-medications were also commonly used, and their opioid doses were within the recommended dose. Future studies are warranted to evaluate the adverse effect and clinical outcomes of the co-medications particularly in long-term opioid users with chronic non-cancer pain. PMID:28182128

  8. Differences between opioids

    DEFF Research Database (Denmark)

    Drewes, Asbjørn; Jensen, Rasmus D.; Nielsen, Lecia M.;

    2013-01-01

    Clinical studies comparing the response and side effects of various opioids have not been able to show robust differences between drugs. Hence, recommendations of the regulatory authorities have been driven by costs with a general tendency in many countries to restrict physician's use of opioids...... to morphine. Although this approach is recognized as cost-effective in most cases there is solid evidence that, on an individual patient basis, opioids are not all equal. Therefore it is important to have an armamentarium of strong analgesics in clinical practice to ensure a personalized approach in patients...... who do not respond to standard treatment. In this review we highlight differences between opioids in human studies from a pharmacological, experimental, clinical and health economics point of view. We provide evidence that individuals respond differently to opioids, and that general differences...

  9. Healthcare utilization in adults with opioid dependence receiving extended release naltrexone compared to treatment as usual.

    Science.gov (United States)

    Soares, William E; Wilson, Donna; Rathlev, Niels; Lee, Joshua D; Gordon, Michael; Nunes, Edward V; O'Brien, Charles P; Friedmann, Peter D

    2017-05-12

    Opioid use disorders have reached epidemic proportions, with overdose now the leading cause of accidental death in the United States. Extended release naltrexone (XR-NTX) has emerged as a medication treatment that reduces opioid use and craving. However, the effect of XR-NTX therapy on acute healthcare utilization, including emergency department visits and inpatient hospitalizations, remains uncertain. The objective of the current study is to evaluate hospital-based healthcare resource utilization in adults involved in the criminal justice system with a history of opioid use disorder randomized to XR-NTX therapy compared with treatment as usual (TAU) during a 6-month treatment phase and 12months post-treatment follow up. This retrospective exploratory analysis uses data collected in a published randomized trial. Comparisons of the number of emergency department visits and hospital admissions (for drug detox, psychiatric care and other medical reasons) were performed using chi square tests for any admission and negative binomial models for number of admissions. Of the 308 participants randomized, 96% had utilization data (76% complete 6months, 67% complete follow up). No significant differences were seen in overall healthcare utilization (IRR=0.88, 95%CI 0.63-1.23, p=0.45), or substance use-related drug detox hospitalizations (IRR=0.83, 95%CI 0.32-2.16, p=0.71). Despite having more participants report chronic medical problems at baseline (43% vs. 32%, p=0.05), those receiving XR-NTX generally experienced equivalent or lower rates of healthcare utilization compared to TAU. The XR-NTX group had significantly lower medical/surgical related hospital admissions (IRR=0.55, 95%CI 0.30-1.00, p=0.05) during the course of the entire study. XR-NTX did not significantly increase rates of healthcare utilization compared to TAU. Provider concerns regarding healthcare utilization should not preclude the consideration of XR-NTX as therapy for opioid use disorders. Copyright © 2017

  10. Opioid analgesics: does potency matter?

    Science.gov (United States)

    Passik, Steven D; Webster, Lynn

    2014-01-01

    Prescription opioid analgesics with a wide range of potencies are currently used for the treatment of chronic pain. Yet understanding the clinical relevance and therapeutic consequences of opioid potency remains ill defined. Both patients and clinicians alike have misperceptions about opioid potency, expecting that less-potent opioids will be less effective or fearing that more-potent opioids are more dangerous or more likely to be abused. In this review, common myths about the potency of opioid analgesics will be discussed. Clinicians should understand that pharmacologic potency per se does not necessarily imply more effective analgesia or higher abuse liability. Published dose conversion tables may not accurately calculate the dose for effective and safe rotation from one opioid to another in patients receiving long-term opioid therapy because they are based on limited data that may not apply to chronic pain. Differences in pharmacologic potency are largely accounted for by the actual doses prescribed, according to individualized patient need. Factors for achieving effective analgesia and reducing the risks involved with opioid use include careful medication selection based on patient characteristics, appropriate dosing titration and opioid rotation practices, knowledge of product formulation characteristics (eg, extended release, immediate release, and tamper-resistant features), and an awareness of differences in opioid pharmacokinetics and metabolism. Clinicians should remain vigilant in monitoring patients on any opioid medication, regardless of classification along the opioid potency continuum.

  11. Profile of female patients seeking in-patient treatment for prescription opioid abuse from a tertiary care drug dependence treatment centre from India

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    Prabhoo Dayal

    2016-01-01

    Full Text Available Background & objectives: There has been a limited focus on prescription drug abuse among women in the country. Choice of psychoactive substance, reasons for initiation and co-occurring disorders have been found to be different among men and women. The current study was aimed at studying the profile of female patients seeking in-patient treatment for prescription drug use over a period of five years at a tertiary care drug dependence treatment centre in India. Methods: Case records of all female patients admitted with substance use disorder at a national level drug dependence treatment centre in north India across five years (between January 2008 and December 2012 were reviewed retrospectively to study their socio-demographic and clinical profile. The information was gathered using a semi-structured proforma and detailed case records. Abstinence, relapse and retention rates were calculated. Results: Over the five years, 31 female patients were admitted with prescription drug abuse. Of them, 12 (39% used prescription opioids and 11 (36% used prescription opioid along with benzodiazepines. Commonest prescription opioid was pentazocine used by 87 per cent of the women. Twenty two (71% women were introduced to opioid by medical practitioners and commonest reason for introduction was pain (among 48%. Common co-occurring psychiatric diagnoses were depressive disorder (26%, cluster B traits/disorder (19% and somatoform disorder (13%. Eight women did not complete treatment and left against medical advice. Thirteen women were advised maintenance treatment, and 70 per cent of them were retained for at least six months. Interpretation & conclusions: Our findings revealed a link between mental illness, pain and non-medical use of prescription opioids among women. Majority of these women received opioids as a legitimate prescription form physician. Therefore, these legitimate prescribers should be trained for pain management to facilitate proper treatment of

  12. Antinociceptive Activity of Stephanolepis hispidus Skin Aqueous Extract Depends Partly on Opioid System Activation

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    Hugo Castro-Faria-Neto

    2013-04-01

    Full Text Available Stephanolepis hispidus is one of the most common filefish species in Brazil. Its skin is traditionally used as a complementary treatment for inflammatory disorders. However, there are very few studies on chemical and pharmacological properties using the skin of this fish. This study was undertaken in order to investigate the effect of aqueous crude extract of S. hispidus skin (SAE in different nociception models. Here, we report that intraperitoneal administration of SAE inhibited the abdominal constrictions induced by acetic acid in mice. In addition to the effect seen in the abdominal constriction model, SAE was also able to inhibit the hyperalgesia induced by carrageenan and prostaglandin E2 (PGE2 in mice. This potent antinociceptive effect was observed in the hot plate model too, but not in tail-flick test. Naloxone, an opioid receptor antagonist, was able to block the antinociceptive effect of SAE in the abdominal constriction and hot plate models. In addition, SAE did not present cytotoxic or genotoxic effect in human peripheral blood cells. Our results suggest that aqueous crude extract from S. hispidus skin has antinociceptive activity in close relationship with the partial activation of opioid receptors in the nervous system. Moreover, aqueous crude extract from S. hispidus skin does not present toxicity and is therefore endowed with the potential for pharmacological control of pain.

  13. Correlates of Nine-Month Retention following Interim Buprenorphine-Naloxone Treatment in Opioid Dependence: A Pilot Study

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    A. Håkansson

    2016-01-01

    Full Text Available Interim medication-only treatment has been suggested for the initiation of opioid maintenance treatment (OMT in opioid-dependent subjects, but this rarely has been studied using buprenorphine instead of methadone. Following a pilot trial assessing interim buprenorphine-naloxone treatment in order to facilitate transfer into OMT, we here aimed to study retention, and potential correlates of retention, in full-scale treatment. Thirty-six patients successfully referred from a waiting list through an interim treatment phase were followed for nine months in OMT. Baseline characteristics, as well as urine analyses during the interim phase and during full-scale OMT, were studied as potential correlates of retention. The nine-month retention in OMT was 83 percent (n=30. While interim-phase urine samples positive for benzodiazepines did not significantly predict dropout from full-scale OMT (p=0.09, urine samples positive for benzodiazepines within full-scale OMT were significantly associated with dropout (p<0.01, in contrast to other substances and baseline characteristics. Retention remained high through nine months in this pilot study sample of patients referred through buprenorphine-naloxone interim treatment, but use of benzodiazepines is problematic, and the present data suggest that it may be associated with treatment dropout.

  14. Food-dependent individual growth and population dynamics in fishes

    NARCIS (Netherlands)

    L. Persson; A.M. de Roos

    2006-01-01

    It is long since well established that growth and development in fish individuals are heavily dependent on food intake. Yet, this dependence of individual development on food levels has only to a limited extent been taken into consideration when studying fish population and community processes. Usin

  15. Pedofilia, transtorno bipolar e dependência de álcool e opioides Paedophilia, bipolar disorder and alcohol and opioid dependence

    OpenAIRE

    Vanessa Fabiane Machado Gomes Marsden

    2009-01-01

    Diversos estudos investigaram a relação entre psicopatologia e parafilias, especialmente pedofilia. Transtornos de humor e ansiedade, seguidos de transtornos relacionados ao uso de substâncias, são as comorbidades mais prevalentes em pacientes com parafilias. Apresentou- se o caso de um paciente em tratamento para dependência de substâncias (álcool e heroína), transtorno bipolar e pedofilia. É importante frisar que poucos casos relatando comorbidades como essas foram descritos na literatura.M...

  16. Prevalence of DSM-IV and DSM-5 Alcohol, Cocaine, Opioid, and Cannabis Use Disorders in a Largely Substance Dependent Sample

    Science.gov (United States)

    Peer, Kyle; Rennert, Lior; Lynch, Kevin G.; Farrer, Lindsay; Gelernter, Joel; Kranzler, Henry R.

    2012-01-01

    BACKGROUND The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) will soon replace the DSM-IV, which has existed for nearly two decades. The changes in diagnostic criteria have important implications for research and for the clinical care of individuals with Substance Use Disorders (SUDs). METHODS We used the Semi-Structured Assessment for Drug Dependence and Alcoholism to evaluate the lifetime presence of DSM-IV abuse and dependence diagnoses and DSM-5 mild, moderate, or severe SUDs for alcohol, cocaine, opioids, and cannabis in a sample of 7,543 individuals recruited to participate in genetic studies of substance dependence. RESULTS Switches between diagnostic systems consistently resulted in a modestly greater prevalence for DSM-5 SUDs, based largely on the assignment of DSM-5 diagnoses to DSM-IV “diagnostic ophans” (i.e., individuals meeting one or two criteria for dependence and none for abuse, and thus not receiving a DSM-IV SUD diagnosis). The vast majority of these diagnostic switches were attributable to the requirement that only two of 11 criteria be met for a DSM-5 SUD diagnosis. We found evidence to support the omission from DSM-5 of the legal criterion due to its limited diagnostic utility. The addition of craving as a criterion in DSM-5 did not substantially affect the likelihood of an SUD diagnosis. CONCLUSION The greatest advantage of DSM-5 appears to be its ability to capture diagnostic orphans. In this sample, changes reflected in DSM-5 had a minimal impact on the prevalence of SUD diagnoses. PMID:22884164

  17. Opioid Receptors.

    Science.gov (United States)

    Stein, Christoph

    2016-01-01

    Opioids are the oldest and most potent drugs for the treatment of severe pain. Their clinical application is undisputed in acute (e.g., postoperative) and cancer pain, but their long-term use in chronic pain has met increasing scrutiny. This article reviews mechanisms underlying opioid analgesia and other opioid actions. It discusses the structure, function, and plasticity of opioid receptors; the central and peripheral sites of analgesic actions and side effects; endogenous and exogenous opioid receptor ligands; and conventional and novel opioid compounds. Challenging clinical situations, such as the tension between chronic pain and addiction, are also illustrated.

  18. Pedofilia, transtorno bipolar e dependência de álcool e opioides Paedophilia, bipolar disorder and alcohol and opioid dependence

    Directory of Open Access Journals (Sweden)

    Vanessa Fabiane Machado Gomes Marsden

    2009-01-01

    Full Text Available Diversos estudos investigaram a relação entre psicopatologia e parafilias, especialmente pedofilia. Transtornos de humor e ansiedade, seguidos de transtornos relacionados ao uso de substâncias, são as comorbidades mais prevalentes em pacientes com parafilias. Apresentou- se o caso de um paciente em tratamento para dependência de substâncias (álcool e heroína, transtorno bipolar e pedofilia. É importante frisar que poucos casos relatando comorbidades como essas foram descritos na literatura.Many studies have investigated the relationship between psychopathology and paraphilias, specifically paedophilia. Mood disorders, anxiety disorders, followed by substance use were the most prevalent disorders comorbid in these patients. We present the case of a patient in treatment for substance misuse (alcohol and heroin, bipolar disorder and paedophilia. To our knowledge few cases were reported describing cases of comorbidity such as this.

  19. Pharmacokinetics and pharmacodynamics of high doses of pharmaceutically prepared heroin, by intravenous or by inhalation route in opioid-dependent patients

    NARCIS (Netherlands)

    E.J. Rook; J.M. van Ree; W. van den Brink; M.J.X. Hillebrand; A.D.R. Huitema; V.M. Hendriks; J.H. Beijnen

    2006-01-01

    A pharmacokinetic-pharmacodynamic study was performed in opioid-dependent patients in the Netherlands, who were currently treated with high doses of pharmaceutically prepared heroin on medical prescription. Besides intravenous heroin, heroin was prescribed for inhalation by "chasing the dragon" meth

  20. Electrophoretic Profile of Albumin, α1, α2, β and γ Globulin in Sera of Opioid Dependants and Non-dependants

    Directory of Open Access Journals (Sweden)

    koros Div-salaar

    2008-02-01

    Full Text Available Div-salaar K1, Saravani R2, Shamsi-e-meimandi M3, Taei M4, Sheikholeslami A5 1. MSc. Staff member of Neurology Sciences Research Center, Kerman University of Medical Sciences 2. Instructor, Department of Biochemistry, Faculty of Medicine, Zahedan University of Medical Sciences 3. Instructor, Department of Physiology and Pharmacology, Faculty of Medicine, Neurology Sciences Research Center, Karman University of Medical Sciences 4. Researcher, Neurology Sciences Research Center, Karman University of Medical Sciences 5. B.Sc in Environmental Hygiene, Kerman University of Medical Sciences Abstract Background: The prevalence rate of opioids consumption is high in Iran. The latest research approach related to substance abuse considers the role of plasma proteins in novel treatments of addiction. Since long-term consumption of opioids has some effects on liver function and plasma transfer systems, the present study was designed to determine the electrophoretic profile of plasma proteins in opiates-addict subjects. Materials and methods: In this cross-control study, the sample groups consisted of 42 opium consumers and 35 heroine dependents as case group and 35 non-addict volunteers as control group. The control group was matched with addicts for age and sex. Opioid consumption was confirmed by laboratory diagnostic tests on urine samples such as immunochromatography (RSA, rapidosis and complementary tests including liquid-solid column chromatography and thin layer chromatography (TLC. After blood collection and serum preparation, serum electrophoresis was performed. Data were presented as mean±SEM and analyzed by SPSS ver.11.5. The comparison of groups was done by using parametric tests and p<0.01 was considered as statistically significant. Results: There was no significant difference in the amounts of albumin, alpha-1-globulin, alpha-2-globulin and beta-globulin between groups. Gamma-globulin concentration was not significantly different between

  1. Dopamine-dependent behavioural stimulation by non-peptide delta opioids BW373U86 and SNC 80: 1. Locomotion, rearing and stereotypies in intact rats.

    Science.gov (United States)

    Spina, L; Longoni, R; Mulas, A; Chang, K J; Di Chiara, G

    1998-02-01

    The unconditioned behavioural effects of two non-peptide delta-opioid receptor agonists, BW 373U86 and SNC 80, were studied in the intact rat. BW 373U86 (0.1-2.5 mg/kg s.c.) and SNC 80 (2.5-10 mg/kg s.c.) dose-dependently elicited locomotion, rearing, stereotyped sniffing, licking and gnawing. These effects were abolished by pretreatment with the delta-opioid receptor antagonist naltrindole (5.0 mg/kg s.c.). In view of the phenomenological similarities between this syndrome and that elicited by dopamine-receptor agonists, the role played by dopamine receptors was investigated. The specific dopamine D1 receptor antagonist SCH 23390 and the specific dopamine D2/D3 receptor antagonist raclopride reduced or even abolished the behavioural stimulation induced by lower doses of BW 373U86 and SNC 80. When higher doses of BW 373U86 were used (2.5 mg/kg), however, raclopride, even at high cataleptic doses (6.0 mg/kg), only partly prevented the behavioural stimulation induced by the delta-opioid receptor agonist. The behavioural stimulation remaining after high doses of raclopride was abolished by the administration of SCH 23390. These results show that delta-opioid receptor stimulation elicits dopamine-dependent behavioural activation in the rat that depends on dopamine receptors, particularly of the D1 subtype.

  2. Retention on buprenorphine is associated with high levels of maximal viral suppression among HIV-infected opioid dependent released prisoners.

    Directory of Open Access Journals (Sweden)

    Sandra A Springer

    Full Text Available INTRODUCTION: HIV-infected prisoners lose viral suppression within the 12 weeks after release to the community. This prospective study evaluates the use of buprenorphine/naloxone (BPN/NLX as a method to reduce relapse to opioid use and sustain viral suppression among released HIV-infected prisoners meeting criteria for opioid dependence (OD. METHODS: From 2005-2010, 94 subjects meeting DSM-IV criteria for OD were recruited from a 24-week prospective trial of directly administered antiretroviral therapy (DAART for released HIV-infected prisoners; 50 (53% selected BPN/NLX and were eligible to receive it for 6 months; the remaining 44 (47% selected no BPN/NLX therapy. Maximum viral suppression (MVS, defined as HIV-1 RNA<50 copies/mL, was compared for the BPN/NLX and non-BPN/NLX (N = 44 groups. RESULTS: The two groups were similar, except the BPN/NLX group was significantly more likely to be Hispanic (56.0% v 20.4%, from Hartford (74.4% v 47.7% and have higher mean global health quality of life indicator scores (54.18 v 51.40. MVS after 24 weeks of being released was statistically correlated with 24-week retention on BPN/NLX [AOR = 5.37 (1.15, 25.1], having MVS at the time of prison-release [AOR = 10.5 (3.21, 34.1] and negatively with being Black [AOR = 0.13 (0.03, 0.68]. Receiving DAART or methadone did not correlate with MVS. CONCLUSIONS: In recognition that OD is a chronic relapsing disease, strategies that initiate and retain HIV-infected prisoners with OD on BPN/NLX is an important strategy for improving HIV treatment outcomes as a community transition strategy.

  3. Ligand- and cell-dependent determinants of internalization and cAMP modulation by delta opioid receptor (DOR) agonists.

    Science.gov (United States)

    Charfi, Iness; Nagi, Karim; Mnie-Filali, Ouissame; Thibault, Dominic; Balboni, Gianfranco; Schiller, Peter W; Trudeau, Louis-Eric; Pineyro, Graciela

    2014-04-01

    Signaling bias refers to G protein-coupled receptor ligand ability to preferentially activate one type of signal over another. Bias to evoke signaling as opposed to sequestration has been proposed as a predictor of opioid ligand potential for generating tolerance. Here we measured whether delta opioid receptor agonists preferentially inhibited cyclase activity over internalization in HEK cells. Efficacy (τ) and affinity (KA) values were estimated from functional data and bias was calculated from efficiency coefficients (log τ/KA). This approach better represented the data as compared to alternative methods that estimate bias exclusively from τ values. Log (τ/KA) coefficients indicated that SNC-80 and UFP-512 promoted cyclase inhibition more efficiently than DOR internalization as compared to DPDPE (bias factor for SNC-80: 50 and for UFP-512: 132). Molecular determinants of internalization were different in HEK293 cells and neurons with βarrs contributing to internalization in both cell types, while PKC and GRK2 activities were only involved in neurons. Rank orders of ligand ability to engage different internalization mechanisms in neurons were compared to rank order of E max values for cyclase assays in HEK cells. Comparison revealed a significant reversal in rank order for cyclase E max values and βarr-dependent internalization in neurons, indicating that these responses were ligand-specific. Despite this evidence, and because kinases involved in internalization were not the same across cellular backgrounds, it is not possible to assert if the magnitude and nature of bias revealed by rank orders of maximal responses is the same as the one measured in HEK cells.

  4. Ca2+/calmodulin-dependent protein kinase II alpha is required for the initiation and maintenance of opioid-induced hyperalgesia.

    Science.gov (United States)

    Chen, Yan; Yang, Cheng; Wang, Zaijie Jim

    2010-01-01

    Repeated administration of opioids not only leads to tolerance and dependence, but also results in nociceptive enhancement called opioid-induced hyperalgesia (OIH). Nociceptive mediators involved in OIH generation remain poorly understood. In the present study, we tested the hypothesis that Ca(2+)/calmodulin-depent protein kinase II (CaMKIIalpha) is critical for OIH. Opioid-induced hyperalgesia was produced by repeated morphine administration or pellet implantation in mice. Correlating with the development of tactile allodynia and thermal hyperalgesia, spinal CaMKIIalpha activity was significantly increased in OIH. KN93, a CaMKII inhibitor, dose- and time-dependently reversed OIH and CaMKII activation without impairing locomotor coordination. To elucidate the specific CaMKII isoform involved, we targeted CaMKIIalpha by using small interfering RNA and demonstrated that knockdown of spinal CaMKIIalpha attenuated OIH. Furthermore, morphine failed to induce OIH in CaMKIIalpha(T286A) point mutant mice, although wild-type littermate mice developed robust OIH after repeated treatments with morphine. These data implicate, for the first time, an essential role of CaMKIIalpha as a cellular mechanism leading to and maintaining opioid-induced hyperalgesia.

  5. Who Benefits from Chronic Opioid Therapy? Rethinking the Question of Opioid Misuse Risk

    Directory of Open Access Journals (Sweden)

    Elizabeth Huber

    2016-05-01

    Full Text Available Beginning in the late 1990s, a movement began within the pain management field focused upon the underutilization of opioids, thought to be a potentially safe and effective class of pain medication. Concern for addiction and misuse were present at the start of this shift within pain medicine, and an emphasis was placed on developing reliable and valid methods and measures of identifying those at risk for opioid misuse. Since that time, the evidence for the safety and effectiveness of chronic opioid therapy (COT has not been established. Rather, the harmful, dose-dependent deleterious effects have become clearer, including addiction, increased risk of injuries, respiratory depression, opioid induced hyperalgesia, and death. Still, many individuals on low doses of opioids for long periods of time appear to have good pain control and retain social and occupational functioning. Therefore, we propose that the question, “Who is at risk of opioid misuse?” should evolve to, “Who may benefit from COT?” in light of the current evidence.

  6. Emotional Intelligence Components in Alcohol Dependent and Mentally Healthy Individuals

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    Arash Mohagheghi

    2015-01-01

    Full Text Available Objective. Emotional intelligence might play an important role in the onset and persistence of different psychopathologies. This study investigated the relationship between emotional intelligence and alcohol dependence. Methods. In this case-control study, participants included alcohol dependent individuals and mentally healthy inpatients. Each group consisted of 40 individuals (male/female: 1. The diagnosis was based on the criteria of the DSM-IV-TR using the Structured Clinical Interview for DSM-IV (SCID-IV. All the participants completed Bar-On emotional intelligence test. Results. 20 males and 20 females were included in each group. Mean age of alcohol dependent participants and controls was 31.28 ± 7.82 and 34.93 ± 9.83 years in that order. The analyses showed that the alcohol dependent individuals had a significant difference compared with the control group and received lower scores in empathy, responsibility, impulse control, self-esteem, optimism, emotional consciousness, stress tolerance, autonomy, problem-solving, and total score of emotional intelligence components. Conclusion. Patients with alcohol dependence have deficits in components of emotional intelligence. Identifying and targeted training of the individuals with lower scores in components of emotional intelligence may be effective in prevention of alcohol dependence.

  7. Buprenorphine-containing treatments: place in the management of opioid addiction.

    Science.gov (United States)

    Robinson, Susan E

    2006-01-01

    Although the synthetic opioid buprenorphine has been available clinically for almost 30 years, its use has only recently become much more widespread for the treatment of opioid addiction. The pharmacodynamic and pharmacokinetic profiles of buprenorphine make it unique in the armamentarium of drugs for the treatment of opioid addiction. Buprenorphine has partial mu-opioid receptor agonist activity and is a kappa-opioid receptor antagonist; hence, it can substitute for other micro-opioid receptor agonists, yet is less apt to produce overdose reactions or dysphoria. On the other hand, buprenorphine can block the effects of opioids such as heroin (diamorphine) and morphine, and can even precipitate withdrawal in individuals physically dependent upon these drugs. Buprenorphine has significant sublingual bioavailability and a long half-life, making administration on a less than daily basis possible. Furthermore, its discontinuation is associated with only a mild withdrawal syndrome. Clinical trials have demonstrated that sublingual buprenorphine is effective in both maintenance therapy and detoxification of individuals addicted to opioids. The introduction of a sublingual formulation combining naloxone with buprenorphine further reduces the risk of diversion to illicit intravenous use. Because of its relative safety and lower risk of illegal diversion, buprenorphine has been made available in several countries for treating opioid addiction in the private office setting, greatly enhancing treatment options for this condition.

  8. Opioid craving and seeking behavior in physically dependent volunteers: effects of acute withdrawal and drug reinforcement opportunity.

    Science.gov (United States)

    Greenwald, Mark K

    2005-02-01

    This study examined whether acute opioid withdrawal and drug reinforcement opportunity increase opioid craving and seeking behavior. The author used a 3 x 2 within-subject randomized crossover design to assess craving and operant behavioral effects of 3 pretreatments (naloxone 0.1 mg/70 kg, fentanyl 0.75 mg/70 kg, or saline iv) and drug or money reinforcement opportunity in 8 methadone-maintained volunteers. Each pretreatment was paired with response-contingent (15 x fixed-ratio 100) delivery of drug (fentanyl 1.5 mg/70 kg iv) and money (rated equivalent of fentanyl) in different sessions. Naloxone significantly increased opioid craving, withdrawal signs, and symptoms, but not operant behavior, relative to saline and fentanyl pretreatment. However, drug versus money reinforcement opportunity did not significantly increase opioid craving or seeking behavior.

  9. Characterization of Individuals Seeking Treatment for Caffeine Dependence

    Science.gov (United States)

    Juliano, Laura M.; Evatt, Daniel P.; Richards, Brian D.; Griffiths, Roland R.

    2013-01-01

    Previous investigations have identified individuals who meet criteria for DSM-IV-TR substance dependence as applied to caffeine, but there is little research on treatments for caffeine dependence. This study aimed to thoroughly characterize individuals who are seeking treatment for problematic caffeine use. Ninety-four individuals who identified as being psychologically or physically dependent on caffeine, or who had tried unsuccessfully to modify caffeine consumption participated in a face-to-face diagnostic clinical interview. They also completed measures concerning caffeine use and quitting history, reasons for seeking treatment, and standardized self-report measures of psychological functioning. Caffeine treatment seekers (mean age 41 yrs, 55% women) consumed an average of 548 mg caffeine per day. The primary source of caffeine was coffee for 50% of the sample and soft drinks for 37%. Eighty-eight percent reported prior serious attempts to modify caffeine use (mean 2.7 prior attempts) and 43% reported being advised by a medical professional to reduce or eliminate caffeine. Ninety-three percent met criteria for caffeine dependence when generic DSM-IV-TR substance dependence criteria were applied to caffeine use. The most commonly endorsed criteria were withdrawal (96%), persistent desire or unsuccessful efforts to control use (89%), and use despite knowledge of physical or psychological problems caused by caffeine (87%). The most common reasons for wanting to modify caffeine use were health-related (59%) and not wanting to be dependent on caffeine (35%). This investigation reveals that there are individuals with problematic caffeine use who are seeking treatment, and suggests that there is a need for effective caffeine dependence treatments. PMID:22369218

  10. μ-Opioid receptor antibody reveals tissue-dependent specific staining and increased neuronal μ-receptor immunoreactivity at the injured nerve trunk in mice.

    Directory of Open Access Journals (Sweden)

    Yvonne Schmidt

    Full Text Available Neuropathic pain is a debilitating chronic disease often resulting from damage to peripheral nerves. Activation of opioid receptors on peripheral sensory neurons can attenuate pain without central nervous system side effects. Here we aimed to analyze the distribution of neuronal μ-opioid receptors, the most relevant opioid receptors in the control of clinical pain, along the peripheral neuronal pathways in neuropathy. Hence, following a chronic constriction injury of the sciatic nerve in mice, we used immunohistochemistry to quantify the μ-receptor protein expression in the dorsal root ganglia (DRG, directly at the injured nerve trunk, and at its peripheral endings in the hind paw skin. We also thoroughly examined the μ-receptor antibody staining specificity. We found that the antibody specifically labeled μ-receptors in human embryonic kidney 293 cells as well as in neuronal processes of the sciatic nerve and hind paw skin dermis, but surprisingly not in the DRG, as judged by the use of μ/δ/κ-opioid receptor knockout mice. Therefore, a reliable quantitative analysis of μ-receptor expression in the DRG was not possible. However, we demonstrate that the μ-receptor immunoreactivity was strongly enhanced proximally to the injury at the nerve trunk, but was unaltered in paws, on days 2 and 14 following injury. Thus, μ-opioid receptors at the site of axonal damage might be a promising target for the control of painful neuropathies. Furthermore, our findings suggest a rigorous tissue-dependent characterization of antibodies' specificity, preferably using knockout animals.

  11. A Preliminary Study of Sexual Dysfunction in Male Opioid-Dependants under Methadone Maintenance Treatment

    Directory of Open Access Journals (Sweden)

    Masoudeh Babakhanian

    2011-08-01

    Full Text Available Introduction: Sexual dysfunction is one of the prevalent problems of opiate-dependent patients. The current preliminarily study examines sexual dysfunction in a group of opiate-dependent patients before and after 6 months of MMT. Methods: The current study is a cross-sectional study. The numbers of 30 opiate-dependent patients were selected of Cheraghiyan clinic in Damghan, Iran. Demographics questionnaire and the International Index of Erectile Function were administered before and after treatment. Results: Erectile function showed an increase and intercourse satisfactions completely improved. Sexual desire and overall satisfaction increased, showing slight improvement while orgasmic function increased showing no improvement. Discussion: The findings revealed the prevalence of sexual dysfunction and improvement of some component in patients after treatment. Future studies are needed to explore the roles of other factors.

  12. Pedofilia, transtorno bipolar e dependência de álcool e opioides

    OpenAIRE

    Marsden,Vanessa Fabiane Machado Gomes

    2009-01-01

    Diversos estudos investigaram a relação entre psicopatologia e parafilias, especialmente pedofilia. Transtornos de humor e ansiedade, seguidos de transtornos relacionados ao uso de substâncias, são as comorbidades mais prevalentes em pacientes com parafilias. Apresentou- se o caso de um paciente em tratamento para dependência de substâncias (álcool e heroína), transtorno bipolar e pedofilia. É importante frisar que poucos casos relatando comorbidades como essas foram descritos na literatura....

  13. Pedofilia, transtorno bipolar e dependência de álcool e opioides

    OpenAIRE

    Vanessa Fabiane Machado Gomes Marsden

    2009-01-01

    Diversos estudos investigaram a relação entre psicopatologia e parafilias, especialmente pedofilia. Transtornos de humor e ansiedade, seguidos de transtornos relacionados ao uso de substâncias, são as comorbidades mais prevalentes em pacientes com parafilias. Apresentou- se o caso de um paciente em tratamento para dependência de substâncias (álcool e heroína), transtorno bipolar e pedofilia. É importante frisar que poucos casos relatando comorbidades como essas foram descritos na literatura.M...

  14. Opioid Attentional Bias and Cue-Elicited Craving Predict Future Risk of Prescription Opioid Misuse Among Chronic Pain Patients*

    Science.gov (United States)

    Garland, Eric L.; Howard, Matthew O.

    2014-01-01

    Background Some chronic pain patients receiving long-term opioid analgesic pharmacotherapy are at risk for misusing opioids. Like other addictive behaviors, risk of opioid misuse may be signaled by an attentional bias (AB) towards drug-related cues. The purpose of this study was to examine opioid AB as a potential predictor of opioid misuse among chronic pain patients following behavioral treatment. Methods Chronic pain patients taking long-term opioid analgesics (N = 47) completed a dot probe task designed to assess opioid AB, as well as self-report measures of opioid misuse and pain severity, and then participated in behavioral treatment. Regression analyses examined opioid AB and cue-elicited craving as predictors of opioid misuse at 3-months posttreatment follow-up. Results Patients who scored high on a measure of opioid misuse risk following treatment exhibited significantly greater opioid AB scores than patients at low risk for opioid misuse. Opioid AB for 200 ms cues and cue-elicited craving significantly predicted opioid misuse risk 20 weeks later, even after controlling for pre-treatment opioid dependence diagnosis, opioid misuse, and pain severity (Model R2 = .50). Conclusion Biased initial attentional orienting to prescription opioid cues and cue-elicited craving may reliably signal future opioid misuse risk following treatment. These measures may therefore provide potential prognostic indicators of treatment outcome. PMID:25282309

  15. Extinction of drug cue reactivity in methamphetamine-dependent individuals.

    Science.gov (United States)

    Price, Kimber L; Saladin, Michael E; Baker, Nathaniel L; Tolliver, Bryan K; DeSantis, Stacia M; McRae-Clark, Aimee L; Brady, Kathleen T

    2010-09-01

    Conditioned responses to drug-related environmental cues (such as craving) play a critical role in relapse to drug use. Animal models demonstrate that repeated exposure to drug-associated cues in the absence of drug administration leads to the extinction of conditioned responses, but the few existing clinical trials focused on extinction of conditioned responses to drug-related cues in drug-dependent individuals show equivocal results. The current study examined drug-related cue reactivity and response extinction in a laboratory setting in methamphetamine-dependent individuals. Methamphetamine cue-elicited craving was extinguished during two sessions of repeated (3) within-session exposures to multi-modal (picture, video, and in-vivo) cues, with no evidence of spontaneous recovery between sessions. A trend was noted for a greater attenuation of response in participants with longer (4-7 day) inter-session intervals. These results indicate that extinction of drug cue conditioned responding occurs in methamphetamine-dependent individuals, offering promise for the development of extinction- based treatment strategies. 2010 Elsevier Ltd. All rights reserved.

  16. Extinction of Drug Cue Reactivity in Methamphetamine-Dependent Individuals

    Science.gov (United States)

    Price, Kimber L.; Saladin, Michael E.; Baker, Nathaniel L.; Tolliver, Bryan K.; DeSantis, Stacia M.; McRae-Clark, Aimee L.; Brady, Kathleen T.

    2010-01-01

    Conditioned responses to drug-related environmental cues (such as craving) play a critical role in relapse to drug use. Animal models demonstrate that repeated exposure to drug-associated cues in the absence of drug administration leads to the extinction of conditioned responses, but the few existing clinical trials focused on extinction of conditioned responses to drug-related cues in drug-dependent individuals show equivocal results. The current study examined drug-related cue reactivity and response extinction in a laboratory setting in methamphetamine-dependent individuals. Methamphetamine cue-elicited craving was extinguished during two sessions of repeated (3) within-session exposures to multi-modal (picture, video, and in-vivo) cues, with no evidence of spontaneous recovery between sessions. A trend was noted for a greater attenuation of response in participants with longer (4-7 day) inter-session intervals. These results indicate that extinction of drug-cue conditioned responding occurs in methamphetamine-dependent individuals, offering promise for the development of extinction- based treatment strategies. PMID:20538262

  17. Individualism in plant populations: using stochastic differential equations to model individual neighbourhood-dependent plant growth.

    Science.gov (United States)

    Lv, Qiming; Schneider, Manuel K; Pitchford, Jonathan W

    2008-08-01

    We study individual plant growth and size hierarchy formation in an experimental population of Arabidopsis thaliana, within an integrated analysis that explicitly accounts for size-dependent growth, size- and space-dependent competition, and environmental stochasticity. It is shown that a Gompertz-type stochastic differential equation (SDE) model, involving asymmetric competition kernels and a stochastic term which decreases with the logarithm of plant weight, efficiently describes individual plant growth, competition, and variability in the studied population. The model is evaluated within a Bayesian framework and compared to its deterministic counterpart, and to several simplified stochastic models, using distributional validation. We show that stochasticity is an important determinant of size hierarchy and that SDE models outperform the deterministic model if and only if structural components of competition (asymmetry; size- and space-dependence) are accounted for. Implications of these results are discussed in the context of plant ecology and in more general modelling situations.

  18. Salvinorin A regulates dopamine transporter function via a kappa opioid receptor and ERK1/2-dependent mechanism.

    Science.gov (United States)

    Kivell, Bronwyn; Uzelac, Zeljko; Sundaramurthy, Santhanalakshmi; Rajamanickam, Jeyaganesh; Ewald, Amy; Chefer, Vladimir; Jaligam, Vanaja; Bolan, Elizabeth; Simonson, Bridget; Annamalai, Balasubramaniam; Mannangatti, Padmanabhan; Prisinzano, Thomas E; Gomes, Ivone; Devi, Lakshmi A; Jayanthi, Lankupalle D; Sitte, Harald H; Ramamoorthy, Sammanda; Shippenberg, Toni S

    2014-11-01

    Salvinorin A (SalA), a selective κ-opioid receptor (KOR) agonist, produces dysphoria and pro-depressant like effects. These actions have been attributed to inhibition of striatal dopamine release. The dopamine transporter (DAT) regulates dopamine transmission via uptake of released neurotransmitter. KORs are apposed to DAT in dopamine nerve terminals suggesting an additional target by which SalA modulates dopamine transmission. SalA produced a concentration-dependent, nor-binaltorphimine (BNI)- and pertussis toxin-sensitive increase of ASP(+) accumulation in EM4 cells coexpressing myc-KOR and YFP-DAT, using live cell imaging and the fluorescent monoamine transporter substrate, trans 4-(4-(dimethylamino)-styryl)-N-methylpyridinium) (ASP(+)). Other KOR agonists also increased DAT activity that was abolished by BNI pretreatment. While SalA increased DAT activity, SalA treatment decreased serotonin transporter (SERT) activity and had no effect on norepinephrine transporter (NET) activity. In striatum, SalA increased the Vmax for DAT mediated DA transport and DAT surface expression. SalA up-regulation of DAT function is mediated by KOR activation and the KOR-linked extracellular signal regulated kinase-½ (ERK1/2) pathway. Co-immunoprecipitation and BRET studies revealed that DAT and KOR exist in a complex. In live cells, DAT and KOR exhibited robust FRET signals under basal conditions. SalA exposure caused a rapid and significant increase of the FRET signal. This suggests that the formation of KOR and DAT complexes is promoted in response to KOR activation. Together, these data suggest that enhanced DA transport and decreased DA release resulting in decreased dopamine signalling may contribute to the dysphoric and pro-depressant like effects of SalA and other KOR agonists. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Co-occurring amphetamine use and associated medical and psychiatric comorbidity among opioid-dependent adults: results from the Clinical Trials Network

    Directory of Open Access Journals (Sweden)

    Blazer DG

    2011-07-01

    Full Text Available Daniel J Pilowsky1, Li-Tzy Wu2, Bruce Burchett2, Dan G Blazer2, George E Woody3, Walter Ling41Departments of Epidemiology and Psychiatry, Columbia University, and the New York State Psychiatric Institute, New York City, NY; 2Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University Medical Center, Durham, NC; 3Department of Psychiatry, School of Medicine, University of Pennsylvania and Treatment Research Institute, Philadelphia, PA; 4David Geffen School of Medicine, NPI/Integrated Substance Abuse Programs, University of California, Los Angeles, CA, USABackground: In response to the rising rate of treatment admissions related to illicit use of amphetamines (eg, methamphetamine, we examined the prevalence of amphetamine use among treatment-seeking, opioid-dependent adults, explored whether amphetamine users were as likely as nonamphetamine users to enroll in opioid-dependence treatment trials, and determined whether amphetamine users manifested greater levels of medical and psychiatric comorbidity than nonusers.Methods: The sample included 1257 opioid-dependent adults screened for participation in threemultisite studies of the National Drug Abuse Treatment Clinical Trials Network (CTN001-003, which studied the effectiveness of buprenorphine for opioid detoxification under varying treatment conditions. Patients were recruited from 23 addiction treatment programs across the US. Medical and psychiatric comorbidity were examined by past-month amphetamine use (current vs former and route of administration. Five mutually exclusive groups were examined, ie, nonusers, current amphetamine injectors, current amphetamine noninjectors, former amphetamine injectors, and former amphetamine noninjectors.Results: Of the sample (n = 1257, 22.3% had a history of regular amphetamine use. Of the 280 amphetamine users, 30.3% reported injection as their primary route. Amphetamine users were more likely than nonusers to be white and use more

  20. Affective temperaments in nicotine-dependent and non-nicotine-dependent individuals

    Directory of Open Access Journals (Sweden)

    Włodzimierz Oniszczenko

    2016-07-01

    Full Text Available Background One of the smoking risk factors influencing nicotine dependency may be human personality; however, few studies have examined the association between Akiskal’s affective temperaments and smoking in adults. Our study aims to evaluate the associations between nicotine dependence and affective temperaments using the TEMPS-A. Participants and procedure The sample in this study consisted of 678 healthy Caucasian adults aged from 17 to 69 years, including 134 self-declared nicotine-dependent subjects (89 females and 45 males and 544 self-declared non-nicotine-dependent subjects (352 females and 192 males. The Polish version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A was used to assess affective temperaments (depressive, cyclothymic, hyperthymic, irritable and anxious. Results Nicotine-dependent individuals scored higher on cyclothymic, irritable and anxious temperaments than non-nicotine-dependents (no significant differences with regard to depressive and hyperthymic temperaments. Among the nicotine-dependent individuals, females scored higher on anxious temperaments than males (no differences with regard to the other affective temperaments, and among the non-nicotine-dependent individuals, females exhibited more depressive, cyclothymic and anxious temperaments than males, while males exhibited more hyperthymic temperaments than females. Conclusions The results suggest that affective, cyclothymic and irritable temperaments in both genders and anxious temperaments in females may be predictors of nicotine dependence in adults.

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

    Science.gov (United States)

    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.

  2. Prescription Pain Medications (Opioids)

    Science.gov (United States)

    ... the brain? Opioids attach to specific proteins, called opioid receptors, on nerve cells in the brain, spinal cord, ... essential functions like breathing when they attach to opioid receptors in a brain area that controls respiration. Opioid ...

  3. The risk for problematic opioid use in chronic pain: What can we learn from studies of pain and reward?

    Science.gov (United States)

    Finan, Patrick H; Remeniuk, Bethany; Dunn, Kelly E

    2017-08-01

    Problematic prescription opioid use is cited as a primary contributor to the current 'opioid epidemic' in the United States, which is characterized by recent rapid increases in individuals seeking treatment for opioid dependence and staggering rates of opioid overdose deaths. Individuals with chronic pain are commonly prescribed opioids to treat pain, and by this mere exposure are at increased risk for the development of problematic opioid use. However, the factors contributing to variation in risk across patients have only recently begun to be unraveled. In the present review, we describe the recent and expanding literature on interactions between pain and reward system function in an effort to inform our understanding of risk for problematic opioid use in chronic pain. To that end, we describe the limited experimental evidence regarding opioid abuse liability under conditions of pain, and offer suggestions for how to advance a research agenda that better informs clinicians about the factors contributing to opioid addiction risk in patients with chronic pain. We raise mechanistic hypotheses by highlighting the primary conclusions of several recent reviews on the neurobiology of pain and reward, with an emphasis on describing dopamine deficits in chronic pain, the role of the reward system in mediating the affective and motivational components of pain, and the role of opponent reward/anti-reward processes in the perpetuation of pain states and the development of problematic opioid use behaviors. Finally, we also argue that positive affect-which is directly regulated by the mesolimbic reward system-is a key pain inhibitory factor that, when deficient, may increase risk for problematic opioid use, and present a model that integrates the potential contributions of pain, reward system function, and positive affect to problematic opioid use risk. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Methadone versus buprenorphine for the treatment of opioid abuse in pregnancy: science and stigma.

    Science.gov (United States)

    Holbrook, Amber M

    2015-01-01

    The past decade has seen an increase in rates of opioid abuse during pregnancy. This clinical challenge has been met with debate regarding whether or not illicit and prescription opioid-dependent individuals require different treatment approaches; whether detoxification is preferable to maintenance; and the efficacy of methadone versus buprenorphine as treatment options during pregnancy. The clinical recommendations resulting from these discussions are frequently influenced by the comparative stigma attached to heroin abuse and methadone maintenance versus prescription opioid abuse and maintenance treatment with buprenorphine. While some studies have suggested that a subset of individuals who abuse prescription opioids may have different characteristics than heroin users, there is currently no evidence to suggest that buprenorphine is better suited to treatment of prescription opioid abuse than methadone. Similarly, despite its perennial popularity, there is no evidence to recommend detoxification as an efficacious approach to treatment of opioid dependence during pregnancy. While increased access to treatment is important, particularly in rural areas, there are multiple medical and psychosocial reasons to recommend comprehensive substance abuse treatment for pregnant women suffering from substance use disorders rather than office-based provision of maintenance medication. Both methadone and buprenorphine are important treatment options for opioid abuse during pregnancy. Methadone may still remain the preferred treatment choice for some women who require higher doses for stabilization, have a higher risk of treatment discontinuation, or who have had unsuccessful treatment attempts with buprenorphine. As treatment providers, we should advocate to expand available treatment options for pregnant women in all States.

  5. Opioids in Preclinical and Clinical Trials

    Science.gov (United States)

    Nagase, Hiroshi; Fujii, Hideaki

    Since 1952, when Gates determined the stereo structure of morphine, numerous groups have focused on discovering a nonnarcotic opioid drug [1]. Although several natural, semisynthetic, and synthetic opioid ligands (alkaloids and peptides) have been developed in clinical studies, very few were nonnarcotic opioid drugs [2]. One of the most important studies in the opioid field appeared in 1976, when Martin and colleagues [3] established types of opioid receptors (these are now classified into μ, δ, and κ types). Later, Portoghese discovered a highly selective μ type opioid receptor antagonist, β-funaltrexamine [4]. This led to the finding that the μ type opioid receptor was correlated to drug dependence [5]. Consequently, δ, and particularly κ, opioid agonists were expected to lead to ideal opioid drugs. Moreover, opioid antagonists were evaluated for the treatment of symptoms related to undesirable opioid system activation. In this chapter, we provide a short survey of opioid ligands in development and describe the discovery of the two most promising drugs, TRK-851 [6] and TRK-820 (nalfurafine hydrochloride) [7].

  6. Are experiences of sexual violence related to special needs in patients with substance use disorders? A study in opioid-dependent patients.

    Science.gov (United States)

    Schäfer, Ingo; Gromus, Lil; Atabaki, Armita; Pawils, Silke; Verthein, Uwe; Reimer, Jens; Schulte, Bernd; Martens, Marcus

    2014-12-01

    A history of sexual violence has been related to more complex treatment needs in patients with substance use disorders (SUD). Most of the existing studies, however, included patients with various types of SUD, did not examine gender differences and focused on a small range of clinical domains. Our sample consisted of opioid-dependent outpatients treated during a three-year period in a German metropolitan region. The analysis was based on a local case register and included all patients for whom information on lifetime sexual violence was available (N=3531; 68.3% males). In a case-control design, patients with a history of sexual violence were compared to patients without these experiences regarding a wide range of clinical and social factors indicative of potential needs. Almost two thirds (65.6%) of the female patients and 10.9% of the males reported experiences of sexual violence. Victims differed from non-victims across a variety of domains, including more psychiatric symptoms and suicide attempts, more legal problems, financial and family problems, as well as a higher use of services. In contrast to a previous study among alcohol-dependent patients, no gender differences became apparent. Our findings suggest that experiences of sexual violence are an indicator for more complex needs in opioid-dependent patients of both genders. In addition to integrated trauma-informed approaches, an effort needs to be made to link addiction facilities to further institutions to meet these complex needs.

  7. Ramp length/grade prescriptions for wheelchair dependent individuals.

    Science.gov (United States)

    Canale, I; Felici, F; Marchetti, M; Ricci, B

    1991-09-01

    The aim of this work was to provide well defined criteria for ramp construction for wheelchair dependent individuals (WDI). Force capability was measured in a large sample (140) of WDI, who presented different levels of motor impairment. Levels of impairment were established on the basis of the answers given in a questionnaire regarding the degree of self sufficiency at home as well as outside the home and active participation in sports events. Taking into account those WDI who exhibited at least a minimal level of self-sufficiency, the following prescriptions are indicated. For a 1 metre ramp length, allowable maximal incline 15%; up to 3 metre ramp length, maximal incline 10%. The reliability of such prescriptions was confirmed by having a test ramp traversed by 43 WDI. These values are suggested as confidence limits when faced with public building accommodations. Special prescriptions could be adopted for selected populations of WDI.

  8. The μ opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway

    Directory of Open Access Journals (Sweden)

    Roberts-Thomson Sarah J

    2006-07-01

    Full Text Available Abstract Background The vanilloid receptor 1 (TRPV1 is critical in the development of inflammatory hyperalgesia. Several receptors including G-protein coupled prostaglandin receptors have been reported to functionally interact with the TRPV1 through a cAMP-dependent protein kinase A (PKA pathway to potentiate TRPV1-mediated capsaicin responses. Such regulation may have significance in inflammatory pain. However, few functional receptor interactions that inhibit PKA-mediated potentiation of TRPV1 responses have been described. Results In the present studies we investigated the hypothesis that the μ opioid receptor (MOP agonist morphine can modulate forskolin-potentiated capsaicin responses through a cAMP-dependent PKA pathway. HEK293 cells were stably transfected with TRPV1 and MOP, and calcium (Ca2+ responses to injection of the TRPV1 agonist capsaicin were monitored in Fluo-3-loaded cells. Pre-treatment with morphine did not inhibit unpotentiated capsaicin-induced Ca2+ responses but significantly altered capsaicin responses potentiated by forskolin. TRPV1-mediated Ca2+ responses potentiated by the direct PKA activator 8-Br-cAMP and the PKC activator Phorbol-12-myristate-13-acetatewere not modulated by morphine. Immunohistochemical studies confirmed that the TRPV1 and MOP are co-expressed on cultured Dorsal Root Ganglion neurones, pointing towards the existence of a functional relationship between the G-protein coupled MOP and nociceptive TRPV1. Conclusion The results presented here indicate that the opioid receptor agonist morphine acts via inhibition of adenylate cyclase to inhibit PKA-potentiated TRPV1 responses. Targeting of peripheral opioid receptors may therefore have therapeutic potential as an intervention to prevent potentiation of TRPV1 responses through the PKA pathway in inflammation.

  9. Comparing methadone and buprenorphine maintenance with methadone-assisted withdrawal for the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes

    Directory of Open Access Journals (Sweden)

    Lund IO

    2012-02-01

    Full Text Available Ingunn O Lund1, Heather Fitzsimons2, Michelle Tuten2, Margaret S Chisolm2, Kevin E O’Grady3, Hendrée E Jones2,41SERAF-Norwegian Centre for Addiction Research, University of Oslo, Oslo, Norway; 2Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD; 3Department of Psychology, University of Maryland, College Park, MD; 4Substance Abuse Treatment Evaluations and Interventions Research Program, RTI International, Research Triangle Park, NC, USAAbstract: Pregnancy can motivate opioid-dependent women to seek substance abuse treatment. Research has demonstrated that although prenatal exposure to buprenorphine results in less severe neonatal abstinence syndrome (NAS relative to prenatal methadone exposure, the maternal and other neonatal outcomes are similar for the two medications. Maternal and neonatal outcomes for opioid-dependent pregnant women receiving these medications have not been systematically compared with methadone-assisted withdrawal. The present study provides an initial assessment of the relative efficacy of both methadone and buprenorphine maintenance versus methadone-assisted withdrawal in terms of neonatal and maternal delivery outcomes. Data were derived from (1 the MOTHER (Maternal Opioid Treatment: Human Experimental Research study at the Johns Hopkins University Bayview Medical Center (JHBMC, or (2 retrospective records review of women who underwent methadone-assisted withdrawal at the JHBMC during the time period in which participants were enrolled in the MOTHER study. Compared with the methadone maintenance group, the methadone-assisted withdrawal group had a significantly lower mean NAS peak score (Means = 13.7 vs 7.0; P = 0.002, required a significantly lower mean amount of morphine to treat NAS (Means = 82.8 vs 0.2; P < 0.001, had significantly fewer days medicated for NAS (Means = 31.5 vs 3.9; P < 0.001, and remained in the hospital for a significantly fewer number of

  10. Strain Dependence of Photoluminescense of Individual Carbon Nanotubes

    Science.gov (United States)

    Nikolaev, Pavel N.; Leeuw, Tonya K.; Tsyboulski, Dmitri A.; Bachilo, Sergei M.; Weisman, Bruce; Arepalli, Sivaram

    2007-01-01

    We have investigated strain dependence of photoluminescense (PL) spectra of single wall carbon nanotubes (SWNT). Nanotubes were sparsely dispersed in a thin PMMA film applied to acrylic bar, and strained in both compression and extension by bending this bar in either direction in a homebuilt four-point bending rig. The average surface strain was measured with high accuracy by a resistive strain gage applied on top of the film. The near infrared imaging and spectroscopy were performed on the inverted microscope equipped with high numerical aperture reflective objective lens and InGaAs CCD cameras. PL was excited with a diode laser at either 658, 730 or 785 nm, linearly polarized in the direction of the strain. We were able to measure (n,m) types and orientation of individual nanotubes with respect to strain direction and strain dependence of their PL maxima. It was found that PL peak shifts with respect to the values measured in SDS micelles are a sum of three components. First, a small environmental shift due to difference in the dielectric constant of the surrounding media, that is constant and independent of the nanotube type. Second, shift due to isotropic compression of the film during drying. Third, shifts produced by the uniaxial loading of the film in the experiment. Second and third shifts follow expression based on the first-order expansion of the TB hamiltonian. Their magnitude is proportional to the nanotube chiral angle and strain, and direction is determined by the nanotube quantum number. PL strain dependence measured for a number of various nanotube types allows to estimate TB carbon-carbon transfer integral.

  11. Management of opioid-induced constipation.

    Science.gov (United States)

    Prichard, David; Norton, Christine; Bharucha, Adil E

    Up to 40% of patients taking opioids develop constipation. Opioid-induced constipation (OIC) may limit the adequate dosing of opioids for pain relief and reduce quality of life. Health professionals must therefore inquire about bowel function in patients receiving opioids. The management of OIC includes carefully re-evaluating the necessity, type and dose of opioids at each visit. Lifestyle modification and alteration of aggravating factors, the use of simple laxatives and, when essential, the addition of newer laxatives or opioid antagonists (naloxone, naloxegol or methylnaltrexone) can be used to treat OIC. This review discusses the recent literature regarding the management of OIC and provides a rational approach to assessing and managing constipation in individuals receiving opioids.

  12. Demand Curves for Hypothetical Cocaine in Cocaine-Dependent Individuals

    Science.gov (United States)

    Bruner, Natalie R.; Johnson, Matthew W.

    2013-01-01

    Rationale 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. Objectives This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. Methods 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. Results 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 Omax (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, Pmax, were significantly correlated with real-world cocaine use. Conclusions Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use. PMID:24217899

  13. 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.

  14. Density dependence of clutch size: habitat heterogeneity or individual adjustment?

    NARCIS (Netherlands)

    Both, C.

    1998-01-01

    1. Two hypotheses have been proposed to explain density- dependent patterns in reproduction. The habitat heterogeneity hypothesis (HHH) explains density-dependent reproduction at the population level from poorer quality territories in heterogeneous environments only being occupied at high densities.

  15. Review of naloxone safety for opioid overdose: practical considerations for new technology and expanded public access.

    Science.gov (United States)

    Wermeling, Daniel P

    2015-02-01

    Opioid overdose and mortality have increased at an alarming rate prompting new public health initiatives to reduce drug poisoning. One initiative is to expand access to the opioid antidote naloxone. Naloxone has a long history of safe and effective use by organized healthcare systems and providers in the treatment of opioid overdose by paramedics/emergency medicine technicians, emergency medicine physicians and anesthesiologists. The safety of naloxone in a prehospital setting administered by nonhealthcare professionals has not been formally established but will likely parallel medically supervised experiences. Naloxone dose and route of administration can produce variable intensity of potential adverse reactions and opioid withdrawal symptoms: intravenous administration and higher doses produce more adverse events and more severe withdrawal symptoms in those individuals who are opioid dependent. More serious adverse reactions after naloxone administration occur rarely and may be confounded by the effects of other co-intoxicants and the effects of prolonged hypoxia. One component of the new opioid harm reduction initiative is to expand naloxone access to high-risk individuals (addicts, abusers, or patients taking high-dose or extended-release opioids for pain) and their close family or household contacts. Patients or their close contacts receive a naloxone prescription to have the medication on their person or in the home for use during an emergency. Contacts are trained on overdose recognition, rescue breathing and administration of naloxone by intramuscular injection or nasal spraying of the injection prior to the arrival of emergency medical personnel. The safety profile of naloxone in traditional medical use must be considered in this new context of outpatient prescribing, dispensing and treatment of overdose prior to paramedic arrival. New naloxone delivery products are being developed for this prehospital application of naloxone in treatment of opioid

  16. Co-relationship between sexual dysfunction and high-risk sexual behavior in patients receiving buprenorphine and naltrexone maintenance therapy for opioid dependence

    Directory of Open Access Journals (Sweden)

    Santosh Ramdurg

    2015-01-01

    Full Text Available Introduction: People suffering from substance dependence suffer from various sexual dysfunctions and are at risk for indulging in various high-risk sexual behaviors and thus are vulnerable to acquire various infections such as HIV/AIDS and other sexually transmitted infections. AIM: The aim of the study was to evaluate the correlation between sexual dysfunction and high-risk sexual behavior in opioid-dependent men receiving buprenorphine and naltrexone maintenance therapy. Materials and Methods: Semi-structured questionnaire, brief male sexual functioning inventory and HIV-risk taking behavior scale was administered to a sample of 60 sexually active men, receiving buprenorphine (n = 30 and naltrexone (n = 30 maintenance therapy for opioid dependence. Results: The main outcomes are correlation between severity of sexual dysfunction and HIV-risk taking behavior. The study results showed 83% of the men on buprenorphine and 90% on naltrexone reported at least one of the sexual dysfunction symptoms. There was a negative correlation between sexual dysfunction and HIV-risk taking behavior that suggest severe the dysfunction, higher the risk taking behavior. Significant correlation was present with overall sexual dysfunction and HIV-risk taking behavior (P = 0.028 and in naltrexone receiving group premature ejaculation versus HIV-risk taking behavior however, (P = 0.022, P < 0.05 there were no significant differences among both the groups except above findings. Conclusion: Conclusion was treatment is associated with sexual dysfunctions and HIV-risk taking behavior, which has clinical implication. Future research should explore this further using biochemical analyses.

  17. SUBSTITUTION TREATMENT FOR OPIOID DEPENDENTS IN GERMANY%德国的阿片类依赖替代治疗

    Institute of Scientific and Technical Information of China (English)

    Ingo Ilja MICHELS; Heino ST(O)VER2; Ralf GERLACH

    2007-01-01

    After a long and controversial debate methadone maintenance treatment (MMT) was first introduced in Germany in 1987. The number of patients in MMT first low because of strict admission criteria - has increased considerably since the 1990s up to 61 000 at the end of 2005. In Germany every general practitioner (GP), who has completed an additional training on addiction medicine, is allowed to prescribe substitution drugs to opioid dependent patients. 2700 GPs are currently prescribing substitution drugs. Psychosocial care should be offered to every MMT patient. The results of research studies and practical experiences indicate that clients benefit substantially from MMT with improvements in physical and psychological health. MMT has high retention rates (65% -85% ) and plays a major role in accessing and maintaining ongoing medical treatment for HIV and hepatitis. MMT is also seen as a vital factor in the social re - integration process. MMT also plays an important role in the reduction of drug related harms such as mortality, morbidity and prevention of infection diseases. Some 10% of MMT clients become drug- free in the long run. Mostly methadone is the most commonly prescribed substitution medication, although buprenorphine is attaining more and more importance. Access to MMT in rural areas is very patchy and therefore constitutes a problem. Also employment opportunities are scare for patients in MMT, although labor is recognized unanimously as a positive factor of the treatment.Substitution treatment in German prisons is heterogeneous in access and treatment modalities. Access is very patchy and the number of inmates in treatment is limited. Nevertheless, substitution treatment plays a substantial part in the health care system provided to drug users in Germany.%经过漫长而激烈的争论,德国于1987年首次引进了美沙酮维持治疗.最初,由于入治标准严格,接受治疗的人数很少,但自1990年后接受治疗的人数迅速上升,到2005

  18. Opioid Basics: Fentanyl

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Opioid Overdose Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Opioid Overdose Opioid Basics Understanding the Epidemic Commonly Used ...

  19. Opioid Abuse and Addiction

    Science.gov (United States)

    Opioids, sometimes called narcotics, are a type of drug. They include strong prescription pain relievers, such as ... tramadol. The illegal drug heroin is also an opioid. Some opioids are made from the opium plant, ...

  20. The role of beta-arrestin2 in the severity of antinociceptive tolerance and physical dependence induced by different opioid pain therapeutics.

    Science.gov (United States)

    Raehal, Kirsten M; Bohn, Laura M

    2011-01-01

    Ligands acting at the same receptor can differentially activate distinct signal transduction pathways, which in turn, can have diverse functional consequences. Further, receptors expressed in different tissues may utilize intracellular signaling proteins in response to a ligand differently as well. The mu opioid receptor (MOR), which mediates many of the pharmacological actions of opiate therapeutics, is also subject to differential signaling in response to diverse agonists. To study the effect of diverse agonists on MOR signaling, we examined the effects of chronic opiate treatment on two distinct physiological endpoints, antinociceptive tolerance and physical dependence, in mice lacking the intracellular regulatory molecule, βarrestin2. While βarrestin2 knockout (βarr2-KO) mice do not become tolerant to the antinociceptive effects of chronic morphine in a hot plate test, tolerance develops to the same degree in both wild type and βarr2-KO mice following chronic infusion with methadone, fentanyl, and oxycodone. Studies here also assess the severity of withdrawal signs precipitated by naloxone following chronic infusions at three different doses of each opiate agonist. While there are no differences in withdrawal responses between genotypes at the highest dose of morphine tested (48 mg/kg/day), the βarr2-KO mice display several less severe withdrawal responses when the infusion dose is lowered (12 or 24 mg/kg/day). Chronic infusion of methadone, fentanyl, and oxycodone all lead to equivalent naloxone-precipitated withdrawal responses in both genotypes at all doses tested. These results lend further evidence that distinct agonists can differentially impact on opioid-mediated responses in vivo in a βarrestin2-dependent manner.

  1. Density dependence of clutch size : habitat heterogeneity or individual adjustment?

    NARCIS (Netherlands)

    Both, Christiaan

    1998-01-01

    1.   Two hypotheses have been proposed to explain density-dependent patterns in reproduction. The habitat heterogeneity hypothesis (HHH) explains density-dependent reproduction at the population level from poorer quality territories in hetero geneous environments only being occupied at high

  2. Diretrizes para o tratamento de pacientes com síndrome de dependência de opióides no Brasil Brazilian guideline for the treatment of patients with opioids dependence syndrome

    Directory of Open Access Journals (Sweden)

    Danilo Antonio Baltieri

    2004-12-01

    Full Text Available Existe uma prevalência relativamente baixa do uso de ópioides no Brasil, em particular envolvendo o uso não médico da codeína e de xaropes que contêm opióides. No entanto, a síndrome de dependência apresenta um significativo impacto total na mortalidade e morbidade. Nos últimos 20 anos, o avanço científico tem modificado nosso entendimento sobre a natureza da adição aos opióides e os variados tratamentos possíveis. A adição é uma doença crônica tratável se o tratamento for realizado e adaptado tendo em vista as necessidades do paciente específico. Há, de um fato, um conjunto de tratamentos que podem efetivamente reduzir o uso da droga, ajudar a gerenciar a fissura pela droga, prevenir recaídas e recuperar as pessoas para o funcionamento social produtivo. O tratamento da dependência de drogas será parte de perspectivas de longo prazo do ponto de vista médico, psicológico e social. Esta diretriz almeja fornecer um guia para os psiquiatras e outros profissionais de saúde que tratam de pacientes com Síndrome de Dependência de Opióides. Ela tece comentários sobre o tratamento somático e psicossocial que é utilizado nesses pacientes e revisa as evidências científicas e seu poder. Da mesma forma, os aspectos históricos, epidemiológicos e neurobiológicos da dependência de opióides são revisados.There is a relatively low prevalence of opioid use in Brazil, particularly involving the non-medical use of codeine and opiate-containing syrups. However, opioid dependence syndrome shows a significant total impact on mortality and morbidity. Over the past 20 years, scientific progress has changed our understanding of the nature of opioid addiction and its various possible treatments. Addiction is a chronic illness treatable if the treatment is well-delivered and tailored to the needs of the particular patient. There is indeed an array of treatments that can effectively reduce drug use, help manage drug cravings

  3. Context-dependent individual behavioral consistency in Daphnia

    DEFF Research Database (Denmark)

    Heuschele, Jan; Ekvall, Mikael T.; Bianco, Giuseppe

    2017-01-01

    , whereas studies focusing on smaller aquatic organisms are still rare. Here, we show individual differences in the swimming behavior of Daphnia magna, a clonal freshwater invertebrate, before, during, and after being exposed to a lethal threat, ultraviolet radiation (UVR). We show consistency in swimming...

  4. Donations and dependence: Individual contributor strategies in house elections.

    Science.gov (United States)

    Heerwig, Jennifer A

    2016-11-01

    Despite the importance of individual contributors to financing federal candidates, past work has largely neglected this crucial financial constituency in favor of research on corporate and trade political action committees (PACs). By contrast, in this study I offer the first analysis of aggregate contributions from the population of individual contributors to House candidates. Using an original big dataset constructed from over fifteen million Federal Election Commission (FEC) disclosure records, I identify individual contributors (rather than contributions) and trace the variation in their strategies across types of House candidates. I distinguish between frequent donors, who are theorized to have more contact with members of Congress, versus infrequent donors in these elections. I find evidence that the character of aggregate donations from repeat donors is more access-oriented even while controlling for other salient candidate characteristics. Funds from infrequent donors, in contrast, appear more ideologically motivated. By also examining the percentage of funds that House candidates receive from repeat donors, I show that the fundraising coalitions of candidates may reproduce reliance on more access-oriented, repeat donors despite the influx of dollars from infrequent donors. I suggest that my findings provide a persuasive case for re-evaluating the diversity of roles individual contributors play in the campaign finance system, and for systematically analyzing variation in contributor strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Prohormone convertase 2 (PC2) null mice have increased mu opioid receptor levels accompanied by altered morphine-induced antinociception, tolerance and dependence.

    Science.gov (United States)

    Lutfy, K; Parikh, D; Lee, D L; Liu, Y; Ferrini, M G; Hamid, A; Friedman, T C

    2016-08-04

    Chronic morphine treatment increases the levels of prohormone convertase 2 (PC2) in brain regions involved in nociception, tolerance and dependence. Thus, we tested if PC2 null mice exhibit altered morphine-induced antinociception, tolerance and dependence. PC2 null mice and their wild-type controls were tested for baseline hot plate latency, injected with morphine (1.25-10mg/kg) and tested for antinociception 30min later. For tolerance studies, mice were tested in the hot plate test before and 30min following morphine (5mg/kg) on day 1. Mice then received an additional dose so that the final dose of morphine was 10mg/kg on this day. On days 2-4, mice received additional doses of morphine (20, 40 and 80mg/kg on days 1, 2, 3, and 4, respectively). On day 5, mice were tested in the hot plate test before and 30min following morphine (5mg/kg). For withdrawal studies, mice were treated with the escalating doses of morphine (10, 20, 40 and 80mg/kg) for 4days, implanted with a morphine pellet on day 5 and 3 days later injected with naloxone (1mg/kg) and signs of withdrawal were recorded. Morphine dose-dependently induced antinociception and the magnitude of this response was greater in PC2 null mice. Tolerance to morphine was observed in wild-type mice and this phenomenon was blunted in PC2 null mice. Withdrawal signs were also reduced in PC2 null mice. Immunohistochemical studies showed up-regulation of the mu opioid receptor (MOP) protein expression in the periaqueductal gray area, ventral tegmental area, lateral hypothalamus, medial hypothalamus, nucleus accumbens, and somatosensory cortex in PC2 null mice. Likewise, naloxone specific binding was increased in the brains of these mice compared to their wild-type controls. The results suggest that the PC2-derived peptides may play a functional role in morphine-induced antinociception, tolerance and dependence. Alternatively, lack of opioid peptides led to up-regulation of the MOP and altered morphine

  6. Determination of substance overdose in two Iranian centers: comparison between opioids and non-opioids.

    Science.gov (United States)

    Taghaddosinejad, Fakhreddin; Arefi, Mohammad; Fayaz, Amir Farshid; Tanhaeivash, Roozbeh

    2013-04-01

    Recently, new trend toward non-opioid substances is observed in Iran. This is, therefore, to compare overdose of opioids and non-opioids origin. We performed this investigation to provide more detailed information so that preventive actions are taken in future. Over 18 month, 1876 individuals with opioid (opium, heroin, compact-heroin, buprenorphine and opiates) or non-opioid (MDMA (ecstasy), LSD, hashish and cocaine) overdose were selected. They have been compared regarding sex, age, reason of overdose, method of substance use, occupation, marital status, history of addiction in parents/siblings, duration of hospital admission and educational level. There were 1782 and 94 persons with opioid and non-opioid, respectively. Inhalation was the method of choice and women were found to have more tendencies to hallucinogens rather opioids. Moreover, use of non-opioids was observed more in individuals with university education and moreover in whom none of whose parents/siblings was addict. Policies should be planned by the governments to prevent further addictions especially to non-opioids. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  7. Which potent opioid? Important criteria for selection.

    Science.gov (United States)

    Bovill, J G

    1987-05-01

    Opioids remain the drugs of choice for the treatment of severe pain. In recent years several new potent opioids have become available for clinical use. These newer drugs are generally safer than the older morphine-like compounds and their differing pharmacological and pharmacokinetic properties allow the physician to choose an appropriate drug according to the clinical situation and need of an individual patient. These drugs are classified according to their activity at the opioid receptors. The opioid agonists produce their pharmacological effect by an almost exclusive action at mu-receptors. The agonist-antagonist group are kappa-receptor agonists and either competitive antagonists at the mu-receptor or weak mu-agonists. The use of the potent opioid agonists, because of their potential for causing respiratory depression, is restricted to hospitals. Fentanyl, the oldest drug of this class, is extensively used as a supplement to general anaesthesia, or in high doses as a 'complete' anaesthetic for patients undergoing cardiac surgery. Alfentanil and sufentanil are newer fentanyl derivatives. Alfentanil is unique in having a very short elimination half-life. This is a particular advantage during short operations and for day-case surgery. For longer operations alfentanil can be given as a continuous infusion to supplement nitrous oxide anaesthesia. Sufentanil is about 10 times more potent than fentanyl and is more rapidly eliminated. Initial reports suggest that it may be more effective than fentanyl as an anaesthetic supplement and that recovery may be more rapid. Both sufentanil and alfentanil are also used in cardiac anaesthesia. The newer agonist-antagonist opioids, butorphanol, nalbuphine and buprenorphine, have largely replaced pentazocine in clinical practice. Unlike pentazocine, they cause a low incidence of dysphoric side effects. Like the pure agonists, they cause respiratory depression; however, in contrast to the pure agonists this is not dose related

  8. Mutations in antiquitin in individuals with pyridoxine-dependent seizures.

    NARCIS (Netherlands)

    Mills, P.B.; Struys, E.A.; Jakobs, C.; Plecko, B.; Baxter, P.; Baumgartner, M.; Willemsen, M.A.A.P.; Omran, H.; Tacke, U.; Uhlenberg, B.; Weschke, B.; Clayton, P.T.

    2006-01-01

    We show here that children with pyridoxine-dependent seizures (PDS) have mutations in the ALDH7A1 gene, which encodes antiquitin; these mutations abolish the activity of antiquitin as a delta1-piperideine-6-carboxylate (P6C)-alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase. The accumulating

  9. Investigating expectation and reward in human opioid addiction with [(11) C]raclopride PET.

    Science.gov (United States)

    Watson, Ben J; Taylor, Lindsay G; Reid, Alastair G; Wilson, Sue J; Stokes, Paul R; Brooks, David J; Myers, James F; Turkheimer, Federico E; Nutt, David J; Lingford-Hughes, Anne R

    2014-11-01

    The rewarding properties of some abused drugs are thought to reside in their ability to increase striatal dopamine levels. Similar increases have been shown in response to expectation of a positive drug effect. The actions of opioid drugs on striatal dopamine release are less well characterized. We examined whether heroin and the expectation of heroin reward increases striatal dopamine levels in human opioid addiction. Ten opioid-dependent participants maintained on either methadone or buprenorphine underwent [(11) C]raclopride positron emission tomography imaging. Opioid-dependent participants were scanned three times, receiving reward from 50-mg intravenous heroin (diamorphine; pharmaceutical heroin) during the first scan to generate expectation of the same reward at the second scan, during which they only received 0.1-mg intravenous heroin. There was no heroin injection during the third scan. Intravenous 50-mg heroin during the first scan induced pronounced effects leading to high levels of expectation at the second scan. There was no detectable increase in striatal dopamine levels to either heroin reward or expectation of reward. We believe this is the first human study to examine whether expectation of heroin reward increases striatal dopamine levels in opioid addiction. The absence of detectable increased dopamine levels to both the expectation and delivery of a heroin-related reward may have been due to the impact of substitute medication. It does however contrast with the changes seen in abstinent stimulant users, suggesting that striatal dopamine release alone may not play such a pivotal role in opioid-maintained individuals.

  10. Invasive cane toads: social facilitation depends upon an individual's personality.

    Science.gov (United States)

    González-Bernal, Edna; Brown, Gregory P; Shine, Richard

    2014-01-01

    Individual variation in behavioural traits (including responses to social cues) may influence the success of invasive populations. We studied the relationship between sociality and personality in invasive cane toads (Rhinella marina) from a recently established population in tropical Australia. In our field experiments, we manipulated social cues (the presence of a feeding conspecific) near a food source. We captured and compared toads that only approached feeding sites where another toad was already present, with conspecifics that approached unoccupied feeding sites. Subsequent laboratory trials showed correlated personality differences (behavioural syndromes) between these two groups of toads. For example, toads that approached already-occupied rather than unoccupied feeding sites in the field, took longer to emerge from a shelter-site in standardized trials, suggesting these individuals are 'shy' (whereas toads that approached unoccupied feeding stations tended to be 'bold'). Manipulating hunger levels did not abolish this difference. In feeding trials, a bold toad typically outcompeted a shy toad under conditions of low prey availability, but the outcome was reversed when multiple prey items were present. Thus, both personality types may be favored under different circumstances. This invasive population of toads contains individuals that exhibit a range of personalities, hinting at the existence of a wide range of social dynamics in taxa traditionally considered to be asocial.

  11. Berberine Improves Intestinal Motility and Visceral Pain in the Mouse Models Mimicking Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D Symptoms in an Opioid-Receptor Dependent Manner.

    Directory of Open Access Journals (Sweden)

    Chunqiu Chen

    Full Text Available Berberine and its derivatives display potent analgesic, anti-inflammatory and anticancer activity. Here we aimed at characterizing the mechanism of action of berberine in the gastrointestinal (GI tract and cortical neurons using animal models and in vitro tests.The effect of berberine was characterized in murine models mimicking diarrhea-predominant irritable bowel syndrome (IBS-D symptoms. Then the opioid antagonists were used to identify the receptors involved. Furthermore, the effect of berberineon opioid receptors expression was established in the mouse intestine and rat fetal cortical neurons.In mouse models, berberine prolonged GI transit and time to diarrhea in a dose-dependent manner, and significantly reduced visceral pain. In physiological conditions the effects of berberine were mediated by mu- (MOR and delta- (DOR opioid receptors; hypermotility, excessive secretion and nociception were reversed by berberine through MOR and DOR-dependent action. We also found that berberine increased the expression of MOR and DOR in the mouse bowel and rat fetal cortical neurons.Berberine significantly improved IBS-D symptoms in animal models, possibly through mu- and delta- opioid receptors. Berberine may become a new drug candidate for the successful treatment of IBS-D in clinical conditions.

  12. Buprenorphine and methadone treatment for opioid dependence by income, ethnicity and race of neighborhoods in New York City

    Science.gov (United States)

    Hansen, Helena; Siegel, Carole; Wanderling, Joseph; DiRocco, Danae

    2016-01-01

    Background Geographic and demographic variation in buprenorphine and methadone treatment use in U.S. cities has not been assessed. Identifying variance in opioid maintenance is essential to improving treatment access and equity. Purpose To examine the differential uptake of buprenorphine treatment in comparison to methadone treatment between 2004 and 2013 in neighborhoods in New York City characterized by income, race and ethnicity. Methods Social area (SA) analysis of residential zip codes of methadone and buprenorphine patients in NYC, which aggregated zip codes into five social areas with similar percentages of residents below poverty, identifying as Black non-Hispanic and as Hispanic, to examine whether treatment rates differed significantly among social areas over time. For each rate, mixed model analyses of variance were run with fixed effects for social area, year and the interaction of social area by year. Results Buprenorphine treatment increased in all social areas over time with a significantly higher rate of increase in the social area with the highest income and the lowest percentage of Black, Hispanic, and low-income residents. Methadone treatment decreased slightly in all social areas until 2011 and then increased bringing rates back to 2004 levels. Treatment patterns varied by social area. Conclusions Buprenorphine treatment rates are increasing in all social areas, with slower uptake in moderate income mixed ethnicity areas. Methadone rates have remained stable over time. Targeted investments to promote public sector buprenorphine prescription may be necessary to reduce disparities in buprenorphine treatment and to realize its potential as a public health measure. PMID:27179822

  13. Opioid receptor trafficking and interaction in nociceptors

    Science.gov (United States)

    Zhang, X; Bao, L; Li, S

    2015-01-01

    Opiate analgesics such as morphine are often used for pain therapy. However, antinociceptive tolerance and dependence may develop with long-term use of these drugs. It was found that μ-opioid receptors can interact with δ-opioid receptors, and morphine antinociceptive tolerance can be reduced by blocking δ-opioid receptors. Recent studies have shown that μ- and δ-opioid receptors are co-expressed in a considerable number of small neurons in the dorsal root ganglion. The interaction of μ-opioid receptors with δ-opioid receptors in the nociceptive afferents is facilitated by the stimulus-induced cell-surface expression of δ-opioid receptors, and contributes to morphine tolerance. Further analysis of the molecular, cellular and neural circuit mechanisms that regulate the trafficking and interaction of opioid receptors and related signalling molecules in the pain pathway would help to elucidate the mechanism of opiate analgesia and improve pain therapy. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24611685

  14. Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation.

    Science.gov (United States)

    Cahill, Catherine M; Walwyn, Wendy; Taylor, Anna M W; Pradhan, Amynah A A; Evans, Christopher J

    2016-11-01

    Mechanisms of opioid tolerance have focused on adaptive modifications within cells containing opioid receptors, defined here as cellular allostasis, emphasizing regulation of the opioid receptor signalosome. We review additional regulatory and opponent processes involved in behavioral tolerance, and include mechanistic differences both between agonists (agonist bias), and between μ- and δ-opioid receptors. In a process we will refer to as pass-forward allostasis, cells modified directly by opioid drugs impute allostatic changes to downstream circuitry. Because of the broad distribution of opioid systems, every brain cell may be touched by pass-forward allostasis in the opioid-dependent/tolerant state. We will implicate neurons and microglia as interactive contributors to the cumulative allostatic processes creating analgesic and hedonic tolerance to opioid drugs. Copyright © 2016. Published by Elsevier Ltd.

  15. Understanding the Opioid Overdose Epidemic

    Science.gov (United States)

    ... can happen when someone takes more than prescribed, combines opioids with depressants (such as Xanax ® ) or alcohol, ... suffering with chronic pain.” Read More "Understanding Opioids" Articles Understanding The Opioid Overdose Epidemic / Beyond Opioids: Mind ...

  16. Development and preliminary validation of the Opioid Abuse Risk Screener.

    Science.gov (United States)

    Henrie-Barrus, Patricia; Averill, Lynnette A; Sudweeks, Richard R; Averill, Christopher L; Mota, Natalie

    2016-01-01

    Prescription opioid drug abuse has reached epidemic proportions. Individuals with chronic pain represent a large population at considerable risk of abusing opioids. The Opioid Abuse Risk Screener was developed as a comprehensive self-administered measure of potential risk that includes a wide range of critical elements noted in the literature to be relevant to opioid risk. The creation, refinement, and preliminary modeling of the item pool, establishment of preliminary concurrent validity, and the determination of the factor structure are presented. The initial development and validation of the Opioid Abuse Risk Screener shows promise for effective risk stratification.

  17. Development and preliminary validation of the Opioid Abuse Risk Screener

    Directory of Open Access Journals (Sweden)

    Patricia Henrie-Barrus

    2016-05-01

    Full Text Available Prescription opioid drug abuse has reached epidemic proportions. Individuals with chronic pain represent a large population at considerable risk of abusing opioids. The Opioid Abuse Risk Screener was developed as a comprehensive self-administered measure of potential risk that includes a wide range of critical elements noted in the literature to be relevant to opioid risk. The creation, refinement, and preliminary modeling of the item pool, establishment of preliminary concurrent validity, and the determination of the factor structure are presented. The initial development and validation of the Opioid Abuse Risk Screener shows promise for effective risk stratification.

  18. 42 CFR 440.185 - Respiratory care for ventilator-dependent individuals.

    Science.gov (United States)

    2010-10-01

    ... care professional trained in respiratory therapy (as determined by the State) to an individual who— (1... 42 Public Health 4 2010-10-01 2010-10-01 false Respiratory care for ventilator-dependent... Definitions § 440.185 Respiratory care for ventilator-dependent individuals. (a) “Respiratory care...

  19. Opioid Analgesics and Nicotine: More Than Blowing Smoke.

    Science.gov (United States)

    Yoon, Jin H; Lane, Scott D; Weaver, Michael F

    2015-09-01

    Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs-including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs.

  20. Prescription opioid analgesic use among adults: United States, 1999-2012.

    Science.gov (United States)

    Frenk, Steven M; Porter, Kathryn S; Paulozzi, Leonard J

    2015-02-01

    Prescription opioid analgesics are used to treat pain from surgery, injury, and health conditions such as cancer. Opioid dependence and opioid-related deaths are growing public health problems. Opioid analgesic sales (in kilograms per 10,000) quadrupled from 1999 to 2010 (1), and from 1999 to 2012, opioid-related deaths (per 100,000) more than tripled (2). During 1999–2002, 4.2% of persons aged 18 and over used a prescription opioid analgesic in the past 30 days (3). This report provides updated estimates and trends in prescription opioid analgesic use among adults aged 20 and over, overall and by selected subgroups.

  1. Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis.

    Science.gov (United States)

    Tekieh, E; Zaringhalam, Jalal; Manaheji, H; Maghsoudi, N; Alani, B; Zardooz, H

    2011-01-01

    Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14(th) and 21(st) days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment.

  2. 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

  3. Psychotherapeutic benefits of opioid agonist therapy.

    Science.gov (United States)

    Tenore, Peter L

    2008-01-01

    Opioids have been used for centuries to treat a variety of psychiatric conditions with much success. The so-called "opium cure" lost popularity in the early 1950s with the development of non-addictive tricyclic antidepressants and monoamine oxidase inhibitors. Nonetheless, recent literature supports the potent role of methadone, buprenorphine, tramadol, morphine, and other opioids as effective, durable, and rapid therapeutic agents for anxiety and depression. This article reviews the medical literature on the treatment of psychiatric disorders with opioids (notably, methadone and buprenorphine) in both the non-opioid-dependent population and in the opioid-dependent methadone maintenance population. The most recent neurotransmitter theories on the origin of depression and anxiety will be reviewed, including current information on the role of serotonin, N-Methyl d-Aspartate, glutamate, cortisol, catecholamine, and dopamine in psychiatric disorders. The observation that methadone maintenance patients with co-existing psychiatric morbidity (so called dual diagnosis patients) require substantially higher methadone dosages by between 20% and 50% will be explored and qualified. The role of methadone and other opioids as beneficial psychiatric medications that are independent of their drug abuse mitigating properties will be discussed. The mechanisms by which methadone and other opioids can favorably modulate the neurotransmitter systems controlling mood will also be discussed.

  4. Kappa-opioid receptor signaling in the striatum as a potential modulator of dopamine transmission in cocaine dependence

    Directory of Open Access Journals (Sweden)

    Pierre eTrifilieff

    2013-06-01

    Full Text Available Cocaine addiction is accompanied by a decrease in striatal dopamine signaling, measured as a decrease in dopamine D2 receptor binding as well as blunted dopamine release in the striatum. These alterations in dopamine transmission have clinical relevance, and have been shown to correlate with cocaine-seeking behavior and response to treatment for cocaine dependence. However, the mechanisms contributing to the hypodopaminergic state in cocaine addiction remain unknown. Here we review the Positron Emission Tomography (PET imaging studies showing alterations in D2 receptor binding potential and dopamine transmission in cocaine abusers and their significance in cocaine-seeking behavior. Based on animal and human studies, we propose that the kappa receptor/dynorphin system, because of its impact on dopamine transmission and upregulation following cocaine exposure, could contribute to the hypodopaminergic state reported in cocaine addiction, and could thus be a relevant target for treatment development.

  5. Cell death sensitization of leukemia cells by opioid receptor activation

    Science.gov (United States)

    Friesen, Claudia; Roscher, Mareike; Hormann, Inis; Fichtner, Iduna; Alt, Andreas; Hilger, Ralf A.; Debatin, Klaus-Michael; Miltner, Erich

    2013-01-01

    Cyclic AMP (cAMP) regulates a number of cellular processes and modulates cell death induction. cAMP levels are altered upon stimulation of specific G-protein-coupled receptors inhibiting or activating adenylyl cyclases. Opioid receptor stimulation can activate inhibitory Gi-proteins which in turn block adenylyl cyclase activity reducing cAMP. Opioids such as D,L-methadone induce cell death in leukemia cells. However, the mechanism how opioids trigger apoptosis and activate caspases in leukemia cells is not understood. In this study, we demonstrate that downregulation of cAMP induced by opioid receptor activation using the opioid D,L-methadone kills and sensitizes leukemia cells for doxorubicin treatment. Enhancing cAMP levels by blocking opioid-receptor signaling strongly reduced D,L-methadone-induced apoptosis, caspase activation and doxorubicin-sensitivity. Induction of cell death in leukemia cells by activation of opioid receptors using the opioid D,L-methadone depends on critical levels of opioid receptor expression on the cell surface. Doxorubicin increased opioid receptor expression in leukemia cells. In addition, the opioid D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux in leukemia cells, suggesting that the opioid D,L-methadone as well as doxorubicin mutually increase their cytotoxic potential. Furthermore, we found that opioid receptor activation using D,L-methadone alone or in addition to doxorubicin inhibits tumor growth significantly in vivo. These results demonstrate that opioid receptor activation via triggering the downregulation of cAMP induces apoptosis, activates caspases and sensitizes leukemia cells for doxorubicin treatment. Hence, opioid receptor activation seems to be a promising strategy to improve anticancer therapies. PMID:23633472

  6. Implicit and Explicit Memory Bias in Opiate Dependent, Abstinent and Normal Individuals

    Directory of Open Access Journals (Sweden)

    Jafar Hasani

    2013-07-01

    Full Text Available Objective: The aim of current research was to assess implicit and explicit memory bias to drug related stimuli in opiate Dependent, abstinent and normal Individuals. Method: Three groups including opiate Dependent, abstinent and normal Individuals (n=25 were selected by available sampling method. After matching on the base of age, education level and type of substance use all participants assessed by recognition task (explicit memory bias and stem completion task (implicit memory bias. Results: The analysis of data showed that opiate dependent and abstinent groups in comparison with normal individual had implicit memory bias, whereas in explicit memory only opiate dependent individuals showed bias. Conclusion: The identification of explicit and implicit memory governing addiction may have practical implications in diagnosis, treatment and prevention of substance abuse.

  7. Anger management style, opioid analgesic use, and chronic pain severity: a test of the opioid-deficit hypothesis.

    Science.gov (United States)

    Burns, John W; Bruehl, Stephen

    2005-12-01

    Anger management style is related to both acute and chronic pain. Recent research suggests that individuals who predominantly express anger (anger-out) may report heightened chronic pain severity due in part to endogenous opioid antinociceptive dysfunction. If exogenous opioids serve to remediate opioid deficits, we predicted that regular use of opioid analgesics by chronic pain patients would alter these relationships such that anger-out would be related to chronic pain severity only among opioid-free patients. For 136 chronic pain patients, anger management style, depression, anxiety, pain severity, and use of opioid and antidepressant medication was assessed. Results of hierarchical multiple regressions to predict chronic pain severity showed: (a) a significant Anger-out x Opioid use interaction such that high Anger-out was associated with high pain severity only among patients not taking opioids; (b) controlling for depressed affect and anxiety did not affect this association; (c) the Anger-out x Antidepressant use interaction was nonsignificant; (d) Anger-in did not interact with use of any medication to affect pain severity. Results are consistent with an opioid-deficit hypothesis and suggest that regular use of opioid medications by patients high in anger expression may compensate for an endogenous opioid deficit, and mitigate the effects of elevated anger expression on chronic pain intensity.

  8. Opioid-induced hyperalgesia and burn pain.

    Science.gov (United States)

    Holtman, Joseph R; Jellish, W Scott

    2012-01-01

    The treatment of pain produced during the management of burn injury has been an ongoing problem for physicians caring for these patients. The main therapeutic option for analgesia has been the repeated and prolonged use of opioids. The adverse effects of opioids are well known but the long term use of opioids which produces tolerance with accompanying dose escalation and dependence is most problematic. Another potentially important consequence of opioid exposure that sometimes masks as tolerance is that of opioid induced hyperalgesia. This syndrome is manifest as enhanced pain, sensitivity and loss of analgesic efficacy in patients treated with opioids who actually become sensitized to painful stimuli. This article focuses on the treatment of burn pain and how current analgesic therapies with opioids may cause hyperalgesia and affect the adequacy of treatment for burn pain. This article also provides possible modalities to help therapeutically manage these patients and considers future analgesic strategies which may help to improve pain management in this complicated patient population.

  9. The Limit Behavior of a Stochastic Logistic Model with Individual Time-Dependent Rates

    Directory of Open Access Journals (Sweden)

    Yilun Shang

    2013-01-01

    Full Text Available We investigate a variant of the stochastic logistic model that allows individual variation and time-dependent infection and recovery rates. The model is described as a heterogeneous density dependent Markov chain. We show that the process can be approximated by a deterministic process defined by an integral equation as the population size grows.

  10. Sex and age-dependent effects of a maternal junk food diet on the mu-opioid receptor in rat offspring.

    Science.gov (United States)

    Gugusheff, Jessica R; Bae, Sung Eun; Rao, Alexandra; Clarke, Iain J; Poston, Lucilla; Taylor, Paul D; Coen, Clive W; Muhlhausler, Beverly S

    2016-03-15

    Perinatal junk food exposure increases the preference for palatable diets in juvenile and adult rat offspring. Previous studies have implicated reduced sensitivity of the opioid pathway in the programming of food preferences; however it is not known when during development these changes in opioid signalling first emerge. This study aimed to determine the impact of a maternal junk food (JF) diet on mu-opioid receptor (MuR) expression and ligand binding in two key regions of the reward pathway, the nucleus accumbens (NAc) and the ventral tegmental area (VTA) in rats during the early suckling (postnatal day (PND) 1 and 7) and late suckling/early post-weaning (PND 21 and 28) periods. Female rats were fed either a JF or a control diet for two weeks prior to mating and throughout pregnancy and lactation. MuR expression in the VTA was significantly reduced in female JF offspring on PND 21 and 28 (by 32% and 57% respectively, Pjunk food exposure on MuR mRNA expression or binding were detected at these time points in male offspring. These findings provide evidence that the opioid signalling system is a target of developmental programming by the end of the third postnatal week in females, but not in males. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Potential misuse and inappropriate prescription practices involving opioid analgesics.

    Science.gov (United States)

    Liu, Ying; Logan, Joseph E; Paulozzi, Leonard J; Zhang, Kun; Jones, Christopher M

    2013-08-01

    Opioid misuse and abuse are growing concerns among the medical and public health communities. To examine the prevalence of indicators for potential opioid misuse in a large, commercially insured adult population. We adapted existing indicators developed by expert panels to include having overlapping opioid prescriptions, overlapping opioid and benzodiazepine prescriptions, long-acting/ extended release (LA/ER) opioids for acute pain,and high daily doses of opioids (>100 morphine milligram equivalents). These indicators were assessed among continuously enrolled individuals aged 18-64 years from the 2009 Truven Health MarketScan databases. Analyses were stratified by sex. We identified 3,391,599 eligible enrollees who received at least 1 opioid prescription. On average, enrollees obtained 3.3 opioid prescriptions, and the average annual days of supply was 47 days. Twice as many enrollees received opioid prescriptions for acute pain as for chronic pain. About a quarter of the enrollees had at least 1 indicator of either potential misuse by patients or inappropriate prescription practices by providers. About 15% of enrollees had high daily doses;7.8% had opioid overlap; and 7.9% had opioid and benzodiazepine overlap. Among those prescribed LA/ER opioids, 24.3% were treated for acute pain. Overlap indicators were more common among women. Our findings underscore the critical need to develop programs aimed at promoting appropriate use of opioids. Retrospective opioid utilization reviews similar to our analyses can potentially help managed care organizations and healthcare providers improve patient care and reduce the risk of adverse outcomes related to these medications.

  12. Dose dependency and individual variability of the lipopolysaccharide-induced bovine acute phase protein response

    DEFF Research Database (Denmark)

    Jacobsen, S.; Andersen, P.H.; Tølbøll, T.

    2004-01-01

    In order to investigate the dose dependency and the individual variability of the lipopolysaccharide (LPS)-induced acute phase protein response in cattle, 8 nonlactating, nonpregnant Danish Holstein cows were challenged 3 times each by intravenous injection of increasing doses (10, 100, and 1000 ng...... for several days after each LPS injection, and their increase or decrease was significantly related to LPS dose. In addition to dose dependency, the response was also dependent on the individual, as APP concentrations differed significantly among cows. To compare APP production in 2 consecutive challenges...

  13. Sex differences in HIV effects on visual memory among substance-dependent individuals.

    Science.gov (United States)

    Keutmann, Michael K; Gonzalez, Raul; Maki, Pauline M; Rubin, Leah H; Vassileva, Jasmin; Martin, Eileen M

    2016-11-13

    HIV's effects on episodic memory have not been compared systematically between male and female substance-dependent individuals. We administered the Brief Visuospatial Memory Test-Revised (BVMT-R) to 280 substance-dependent HIV+ and HIV- men and women. Groups were comparable on demographic, substance use, and comorbid characteristics. There were no significant main effects of sex or HIV serostatus on BVMT-R performance, but HIV+ women performed significantly more poorly on delayed recall. This effect was most prominent among cocaine-dependent HIV+ women. Our findings are consistent with recent speculation that memory impairment may be more common among HIV+ women, particularly those with a history of cocaine dependence.

  14. Opioid Abuse after TBI

    Science.gov (United States)

    2014-07-01

    AD_________________ Award Number: W81XWH-11-1-0373 TITLE: " Opioid Abuse after TBI...2014 2. REPORT TYPE Annual 3. DATES COVERED 1 July 2013 - 30 June 2014 4. TITLE AND SUBTITLE " Opioid Abuse after TBI" 5a. CONTRACT NUMBER 5b...the brain’s reward circuitry which may make an injured brain more susceptible to the rewarding effects of opioids . We are currently conducting

  15. Nicotine effects and the endogenous opioid system.

    Science.gov (United States)

    Kishioka, Shiroh; Kiguchi, Norikazu; Kobayashi, Yuka; Saika, Fumihiro

    2014-01-01

    Nicotine (NIC) is an exogenous ligand of the nicotinic acetylcholine receptor (nAChR), and it influences various functions in the central nervous system. Systemic administration of NIC elicits the release of endogenous opioids (endorphins, enkephalins, and dynorphins) in the supraspinal cord. Additionally, systemic NIC administration induces the release of methionine-enkephalin in the spinal dorsal horn. NIC has acute neurophysiological actions, including antinociceptive effects, and the ability to activate the hypothalamic-pituitary-adrenal (HPA) axis. The endogenous opioid system participates in NIC-induced antinociception, but not HPA axis activation. Moreover, NIC-induced antinociception is mediated by α4β2 and α7 nAChRs, while NIC-induced HPA axis activation is mediated by α4β2, not α7, suggesting that the effects of NIC on the endogenous opioid system are mediated by α7, not α4β2. NIC has substantial physical dependence liability. The opioid-receptor antagonist naloxone (NLX) elicits NIC withdrawal after repeated NIC administration, and NLX-induced NIC withdrawal is inhibited by concomitant administration of an opioid-receptor antagonist. NLX-induced NIC withdrawal is also inhibited by concomitant administration of an α7 antagonist, but not an α4β2 antagonist. Taken together, these findings suggest that NIC-induced antinociception and the development of physical dependence are mediated by the endogenous opioid system, via the α7 nAChR.

  16. Emotional Dependency and Dysfunctional Relationship Beliefs as Predictors of Married Turkish Individuals' Relationship Satisfaction.

    Science.gov (United States)

    Kemer, Gülşah; Çetinkaya Yıldız, Evrim; Bulgan, Gökçe

    2016-11-02

    In this study, we examined married individuals' relationship satisfaction in relation to their emotional dependency and dysfunctional relationship beliefs. Our participants consisted of 203 female and 181 male, a total of 384 married individuals from urban cities of Turkey. Controlling the effects of gender and length of marriage, we performed a hierarchical regression analysis. Results revealed that married Turkish individuals' relationship satisfaction was significantly explained by their emotional dependency (sr 2 = .300, p relationship expectations (sr 2 = .028, p .05). When compared to perceptions of interpersonal rejection and unrealistic relationship expectations, emotional dependency had the largest role in explaining participants' satisfaction with their marriages. We discuss the results in light of current literature as well as cultural relevance. We also provide implications for future research and mental health practices.

  17. Psychometric properties of the IES-R in traumatized substance dependent individuals with and without PTSD.

    Science.gov (United States)

    Rash, Carla J; Coffey, Scott F; Baschnagel, Joseph S; Drobes, David J; Saladin, Michael E

    2008-08-01

    Posttraumatic stress disorder (PTSD) is common among treatment-seeking substance abusers. Despite the high prevalence of these co-occurring conditions, few PTSD screening tools have been evaluated for their utility in identifying PTSD in substance use disorder (SUD) populations. The present study evaluated the psychometric properties of the Impact of Event Scale-Revised (IES-R) in a sample of 124 substance dependent individuals. All participants had a history of a DSM-IV Criterion A traumatic event, and 71 individuals met diagnostic criteria for PTSD. Participants with comorbid PTSD reported significantly more symptoms of anxiety, depression, and PTSD compared to substance dependent individuals without PTSD. Acceptable internal consistency and convergent validity of the IES-R were established among a substance dependent sample. Examination of diagnostic effectiveness suggested a cutoff value of 22 as optimal for a substance using population, resulting in adequate classification accuracy, sensitivity, and specificity.

  18. Sex and HIV serostatus differences in decision making under risk among substance-dependent individuals.

    Science.gov (United States)

    Martin, Eileen; Gonzalez, Raul; Vassileva, Jasmin; Maki, Pauline M; Bechara, Antoine; Brand, Matthias

    2016-01-01

    HIV+ individuals with and without substance use disorders make significantly poorer decisions when information about the probability and magnitude of wins and losses is not available. We administered the Game of Dice Task, a measure of decision making under risk that provides this information explicitly, to 92 HIV+ and 134 HIV- substance-dependent men and women. HIV+ participants made significantly poorer decisions than HIV- participants, but this deficit appeared more prominent among HIV+ women. These data indicate that decision making under risk is impaired among HIV+ substance-dependent individuals (SDIs). Potential factors for the HIV+ women's relatively greater impairment are discussed.

  19. Polydrug abuse among opioid maintenance treatment patients is related to inadequate dose of maintenance treatment medicine.

    Science.gov (United States)

    Heikman, Pertti Kalevi; Muhonen, Leea Hellevi; Ojanperä, Ilkka Antero

    2017-07-06

    Polydrug abuse is a known problem among opioid-dependent patients receiving opioid maintenance treatment (OMT). However, improved laboratory diagnostics is required to reveal polydrug abuse in its current scope. Furthermore, there are few studies focusing on the relationship between polydrug abuse and adequacy of the dose of OMT medicine. This study aimed to evaluate the polydrug abuse among opioid-dependent patients receiving OMT with inadequate (Group IA) and adequate (Group A) doses of OMT medicine as experienced by the patients. Craving for opioids and withdrawal symptoms were evaluated as indicators of the adequacy rating. This is a retrospective register-based study of 60 OMT patients on either methadone or sublingual buprenorphine/naloxone medication, whose polydrug abuse was studied from urine samples by means of a comprehensive high-resolution mass spectrometry method. Inadequate doses of the OMT medicines were associated with higher subjective withdrawal scores and craving for opioids. Six groups of abused substances (benzodiazepines, amphetamines, opioids, cannabis, new psychoactive substances, and non-prescribed psychotropic medicines) were found among OMT patients. Group IA patients showed significantly more abuse of benzodiazepines and amphetamines than the Group A patients. All the new psychoactive substances and most of the non-prescribed psychotropic medicines were detected from the Group IA patients. There was no difference in the doses of the OMT medicine between Groups IA and A patients. Polydrug abuse, detected by definitive laboratory methods, was widespread and more common among Group IA than Group A patients, emphasizing the requirement for individual OMT medicine dose adjustment.

  20. Motivational influences on impression formation: outcome dependency, accuracy-driven attention, and individuating processes.

    Science.gov (United States)

    Neuberg, S L; Fiske, S T

    1987-09-01

    How might being outcome dependent on another person influence the processes that one uses to form impressions of that person? We designed three experiments to investigate this question with respect to short-term, task-oriented outcome dependency. In all three experiments, subjects expected to interact with a young man formerly hospitalized as a schizophrenic, and they received information about the person's attributes in either written profiles or videotapes. In Experiment 1, short-term, task-oriented outcome dependency led subjects to use relatively individuating processes (i.e., to base their impressions of the patient on his particular attributes), even under conditions that typically lead subjects to use relatively category-based processes (i.e., to base their impressions on the patient's schizophrenic label). Moreover, in the conditions that elicited individuating processes, subjects spent more time attending to the patient's particular attribute information. Experiment 2 demonstrated that the attention effects in Experiment 1 were not merely a function of impression positivity and that outcome dependency did not influence the impression formation process when attribute information in addition to category-level information was unavailable. Finally, Experiment 3 manipulated not outcome dependency but the attentional goal of forming an accurate impression. We found that accuracy-driven attention to attribute information also led to individuating processes. The results of the three experiments indicate that there are important influences of outcome dependency on impression formation. These results are consistent with a model in which the tendency for short-term, task-oriented outcome dependency to facilitate individuating impression formation processes is mediated by an increase in accuracy-driven attention to attribute information.

  1. Internet addictive individuals share impulsivity and executive dysfunction with alcohol-dependent patients

    Directory of Open Access Journals (Sweden)

    Zhenhe eZhou

    2014-08-01

    Full Text Available Internet addiction disorder (IAD should belong to a kind of behavioral addiction. Previous studies indicated that there are many similarities in the neurobiology of behavior and substance addictions. Up to date, although individuals with IAD have difficulty suppressing their excessive online behaviors in real life, little is known about the patho-physiological and cognitive mechanisms responsible for IAD. Neuropsychological test studies have contributed significantly to our understanding of the effect of IAD on the cognitive function. The purpose of the present study was to examine whether Internet addictive individuals share impulsivity and executive dysfunction with alcohol-dependent individuals. Participants include 22 Internet addictive individuals, 22 alcohol-dependent patients (AD and 22 normal controls (NC. All participants were measured with BIS- 11, go/no-go task, WCST and Digit span task under the same experimental condition. Results showed that BIS-11 scores, false alarm rate, the total response errors, perseverative errors, failure to maintain set of IAD and AD group were significantly higher than that of NC group, and hit rate, percentage of conceptual level responses, the number of categories completed, forwards scores and backwards scores of IAD and AD group were significantly lower than that of NC group, however, no differences in above variables between IAD group and AD group were observed. These results revealed that the existence of impulsivity, deficiencies in executive function and working memory in an IAD and an AD sample, namely, Internet addictive individuals share impulsivity and executive dysfunction with alcohol-dependent patients.

  2. δ-OPIOID RECEPTOR ADAPTATION IN NEUROBLASTOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    D-M,Chuang; M.Belchers; J.Barg; J.Rowinski; G.Clark; C.A.Gloeckner; A.Ho; X-M.Gao; C.J.Coscia

    1993-01-01

    The mechanisms underlying tolerance and dependence arising from chronic opioid exposure are poorly understood. However, the development of neuroblastoma and neurohybrid cell culturea, has provided a simplified model for the atudy of opioid receptor adaptation. Using neuroblastoma NG108-15 cells,

  3. Russia: district court upholds legal ban on opioid substitution treatment.

    Science.gov (United States)

    Golichenko

    2011-10-01

    On 27 May 2011, the Leninsky district court of Kaliningrad Region upheld the refusal of the Ministry of Health of Kaliningrad Region to ensure access to opioid substitution therapy (OST) as an effective treatment for opioid dependence and an effective intervention for HIV prevention among people who inject drugs.

  4. How to measure load-dependent kinetics of individual motor molecules without a force clamp

    DEFF Research Database (Denmark)

    Sung, J.; Mortensen, Kim; Spudich, J.A.;

    2017-01-01

    functions at the single molecule level, such as conformational changes and force-generation of individual motor proteins or force-dependent kinetics in molecular interactions. Here, we describe a new method, “Harmonic Force Spectroscopy (HFS).” With a conventional dual-beam optical trap and a simple...... the molecular basis of muscle contraction and intracellular cargo transport along cytoskeletal filamentous proteins. Optical trapping is among the most sophisticated single-molecule techniques. With exceptionally high spatial and temporal resolutions, it has been extensively utilized to understand biological...... harmonic oscillation of the sample stage, HFS can measure the load-dependent kinetics of transient molecular interactions, such as a human β-cardiac myosin II interacting with an actin filament. We demonstrate that the ADP release rate of an individual human β-cardiac myosin II molecule depends...

  5. Differentiation of Opioid Drug Effects by Hierarchical Multi-Site Phosphorylation

    OpenAIRE

    Just, Sascha; Illing, Susann; Trester-Zedlitz, Michelle; Lau, Elaine K.; Kotowski, Sarah J.; Miess, Elke; Mann, Anika; Doll, Christian; Trinidad, Jonathan C.; Burlingame, Alma L; von Zastrow, Mark; Schulz, Stefan

    2013-01-01

    Differences in the ability of opioid drugs to promote regulated endocytosis of μ-opioid receptors are related to their tendency to produce drug tolerance and dependence. Here we show that drug-specific differences in receptor internalization are determined by a conserved, 10-residue sequence in the receptor’s carboxyl-terminal cytoplasmic tail. Diverse opioids induce receptor phosphorylation at serine (S)375, present in the middle of this sequence, but opioids differ markedly in their ability...

  6. Reduced emotional and corticosterone responses to stress in μ-opioid receptor knockout mice

    OpenAIRE

    Ide, Soichiro; Sora,Ichiro; Ikeda, Kazutaka; Minami, Masabumi; Uhl, George R.; Ishihara, Kumatoshi

    2009-01-01

    The detailed mechanisms of emotional modulation in the nervous system by opioids remain to be elucidated, although the opioid system is well known to play important roles in the mechanisms of analgesia and drug dependence. In the present study, we conducted behavioral tests of anxiety and depression and measured corticosterone concentrations in both male and female μ-opioid receptor knockout (MOP-KO) mice to reveal the involvement of μ-opioid receptors in stress-induced emotional responses. M...

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

    Directory of Open Access Journals (Sweden)

    George H. Trksak

    2013-01-01

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

  8. Opioid equianalgesic tables: are they all equally dangerous?

    Science.gov (United States)

    Shaheen, Philip E; Walsh, Declan; Lasheen, Wael; Davis, Mellar P; Lagman, Ruth L

    2009-09-01

    Pain is one of the most common symptoms in cancer patients. Opioids are widely prescribed for this and other purposes. Properly used, they are safe, but they have serious and potentially lethal side effects. Successful use of opioids to manage cancer pain requires adequate knowledge about opioid pharmacology and equianalgesia for the purpose of both drug rotation and route conversion. The aim of this study was to demonstrate variations in equianalgesic ratios, as quoted in equianalgesic tables and various educational materials widely available to practicing physicians. We surveyed commercially available educational materials in package inserts, teaching materials provided by pharmaceutical companies, and the Physicians' Desk Reference for equianalgesic tables of commonly used opioids. We found inconsistent and variable equianalgesic ratios recommended for both opioid rotation and conversion. Multiple factors like inter- and intraindividual differences in opioid pharmacology may influence the accuracy of dose calculations, as does the heterogeneity of study design used to derive equianalgesic ratios. Equianalgesic tables should only serve as a general guideline to estimate equivalent opioid doses. Clinical judgment should be used and individual patient characteristics considered when applying any table. Professional organizations and regulators should establish a rotation and conversion consensus concerning opioid equianalgesic ratios. Systematic research on equianalgesic opioid dose calculation is recommended to avoid adverse public health consequences of incorrect or inappropriate dosing. Current information in equianalgesic tables is confusing for physicians, and dangerous to the public.

  9. Changes of μ-opioid receptor in the brain tissues of morphine-dependent and abstinent rats%吗啡依赖与戒断大鼠脑组织μ阿片受体的变化

    Institute of Scientific and Technical Information of China (English)

    傅强; 王新华; 邹最; 宋建刚; 陈杞; 蒋健强

    2004-01-01

    BACKGROUND: The alteration of endogenous opioid peptide system is one of the important mechanisms for opioid dependence, μ opioid receptor antagonist or activator can regulate opioid receptor in vitro, but the results from the animal experiment vary greatly.OBJECTIVE: To study the locahzation and quantitative changes of μ-opioid receptor in the brain tissues of morphine-dependent and abstinent rats.DESIGN: A completely randomized controlled experimental study.SETTING and MATERIALS: The experiment was conducted in the Depurtment of Anaesthesiology, Changzheng Hospital, Second Military Medical University using 30 male SD rats provided by the Experimental Animal Center, Second Military Medical University.INTERVENTIONS: Thirty SD rats were divided randomly into 3 groups( n =10) . Intraperitoneal injection with morphine was given to the rats in morphine-dependent group and abstinent group to produce morphine - dependent models, and 3 hours after the model establishment, the rats in the abstinent group were injected with naloxone(5 mg/kg) to induce the withdrawal syndromes. The rats in the control group received only injection with saline. All rats were sacrificed by decapitation 24 hours after the last injection of morphine, and the coronal sections of discrete brain regions(namely the frontal cortex, hippocampus, striatum, thalamus, and hypothalamus) were prepared.MAIN OUTCOME MEASURES: The localization and density of μ-opioid receptor in the specified brain regions of rats in all the 3 groups were measured by autoradiography.RESULTS: In morphine dependent group, the density ofμ-opioid receptor in the frontal cortex, hippocampus, striatum, thalamus, and hypothalamus were significantly lowered by 22%, 49%, 21% and 28%, respectively( t = 11.54,17.82, 15.80, 8.35, 13.78, respectively, P < 0. 01) in comparison with the control group. In morphine abstinent group, the densities of μ opioid receptor in those brain regions were significantly higher by 10%, 38%, 12%, 13

  10. The Opposing Roles of IVS2+691 CC Genotype and AC/AG Diplotype of 118A>G and IVS2+691G>C of OPRM1 Polymorphisms in Cold Pain Tolerance Among Opioid-Dependent Malay Males on Methadone Therapy

    OpenAIRE

    2015-01-01

    Introduction We recently reported that a majority of opioid-dependent Malay males on methadone therapy are cold pain sensitive. It is postulated that common OPRM1 polymorphisms may be responsible. This study investigated the association between 118A>G (dbSNP rs1799971) and IVS2+691G>C (dbSNP rs2075572) variants on cold pain responses among opioid-dependent Malay males on methadone maintenance therapy. Methods Cold pain responses including pain threshold, pain tolerance, and pain intensity wer...

  11. Elemental or contextual? It depends: Individual difference in the hippocampal dependence of associative learning for a simple sensory stimulus

    Directory of Open Access Journals (Sweden)

    Kyung Jennifer Lee

    2014-06-01

    Full Text Available Learning theories categorize learning systems into elemental and contextual systems, the former being processed by non-hippocampal regions and the latter being processed in the hippocampus. A set of complex stimuli such as a visual background is often considered a contextual stimulus and simple sensory stimuli such as pure tone and light are considered elemental stimuli. However, this elemental-contextual categorization scheme has only been tested in limited behavioral paradigms and it is largely unknown whether it can be generalized across different learning situations. By requiring rats to respond differently to a common object in association with various types of sensory cues including contextual and elemental stimuli, we tested whether different types of elemental and contextual sensory stimuli depended on the hippocampus to different degrees. In most rats, a surrounding visual background and a tactile stimulus served as contextual (hippocampal dependent and elemental (non-hippocampal dependent stimuli, respectively. However, simple tone and light stimuli frequently used as elemental cues in traditional experiments required the hippocampus to varying degrees among rats. Specifically, one group of rats showed a normal contextual bias when both contextual and elemental cues were present. These rats effectively switched to using elemental cues when the hippocampus was inactivated. The other group showed a strong contextual bias (and hippocampal dependence because these rats were not able to use elemental cues when the hippocampus was unavailable. It is possible that the latter group of rats might have interpreted the elemental cues (light and tone as background stimuli and depended more on the hippocampus in associating the cues with choice responses. Although exact mechanisms underlying these individual variances are unclear, our findings recommend a caution for adopting a simple sensory stimulus as a non-hippocampal sensory cue only based on

  12. Elemental or contextual? It depends: individual difference in the hippocampal dependence of associative learning for a simple sensory stimulus

    Science.gov (United States)

    Lee, Kyung J.; Park, Seong-Beom; Lee, Inah

    2014-01-01

    Learning theories categorize learning systems into elemental and contextual systems, the former being processed by non-hippocampal regions and the latter being processed in the hippocampus. A set of complex stimuli such as a visual background is often considered a contextual stimulus and simple sensory stimuli such as pure tone and light are considered elemental stimuli. However, this elemental-contextual categorization scheme has only been tested in limited behavioral paradigms and it is largely unknown whether it can be generalized across different learning situations. By requiring rats to respond differently to a common object in association with various types of sensory cues including contextual and elemental stimuli, we tested whether different types of elemental and contextual sensory stimuli depended on the hippocampus to different degrees. In most rats, a surrounding visual background and a tactile stimulus served as contextual (hippocampal dependent) and elemental (non-hippocampal dependent) stimuli, respectively. However, simple tone and light stimuli frequently used as elemental cues in traditional experiments required the hippocampus to varying degrees among rats. Specifically, one group of rats showed a normal contextual bias when both contextual and elemental cues were present. These rats effectively switched to using elemental cues when the hippocampus was inactivated. The other group showed a strong contextual bias (and hippocampal dependence) because these rats were not able to use elemental cues when the hippocampus was unavailable. It is possible that the latter group of rats might have interpreted the elemental cues (light and tone) as background stimuli and depended more on the hippocampus in associating the cues with choice responses. Although exact mechanisms underlying these individual variances are unclear, our findings recommend a caution for adopting a simple sensory stimulus as a non-hippocampal sensory cue only based on the literature

  13. Pharmacogenomic considerations in opioid analgesia

    Directory of Open Access Journals (Sweden)

    Vuilleumier PH

    2012-08-01

    Full Text Available Pascal H Vuilleumier,1 Ulrike M Stamer,1 Ruth Landau21Klinik für Anästhesiologie und Schmerztherapie, Inselspital Universität Bern, Switzerland; 2Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, WA, USAAbstract: Translating pharmacogenetics to clinical practice has been particularly challenging in the context of pain, due to the complexity of this multifaceted phenotype and the overall subjective nature of pain perception and response to analgesia. Overall, numerous genes involved with the pharmacokinetics and dynamics of opioids response are candidate genes in the context of opioid analgesia. The clinical relevance of CYP2D6 genotyping to predict analgesic outcomes is still relatively unknown; the two extremes in CYP2D6 genotype (ultrarapid and poor metabolism seem to predict pain response and/or adverse effects. Overall, the level of evidence linking genetic variability (CYP2D6 and CYP3A4 to oxycodone response and phenotype (altered biotransformation of oxycodone into oxymorphone and overall clearance of oxycodone and oxymorphone is strong; however, there has been no randomized clinical trial on the benefits of genetic testing prior to oxycodone therapy. On the other hand, predicting the analgesic response to morphine based on pharmacogenetic testing is more complex; though there was hope that simple genetic testing would allow tailoring morphine doses to provide optimal analgesia, this is unlikely to occur. A variety of polymorphisms clearly influence pain perception and behavior in response to pain. However, the response to analgesics also differs depending on the pain modality and the potential for repeated noxious stimuli, the opioid prescribed, and even its route of administration.Keywords: pain perception, opioid analgesia, genetic variation, pharmacogenetics

  14. Screening and Treatment for Alcohol, Tobacco and Opioid Use Disorders: A Survey of Family Physicians across Ontario.

    Directory of Open Access Journals (Sweden)

    Genane Loheswaran

    Full Text Available As a primary point of contact within the health care system, family physicians are able to play a vital role in identifying individuals with substance use disorders and connecting them to the appropriate treatment. However, there is very little data available on whether family physicians are actively screening for and treating substance use disorders. The objective of the current survey was to assess whether family physicians in Ontario are screening for alcohol, opioid and tobacco use disorders, using validated tools and providing treatment.An online survey consisting of a series of 38 primarily close-ended questions was circulated to family physicians in Ontario. Rates of screening for alcohol, opioid and tobacco dependence, use of validated tools for screening, providing treatment for dependent individuals and the current barriers to the prescription of pharmacotherapies for these drug dependences were assessed.The use of validated screening tools was limited for all three substances. Screening by family physicians for the substance use disorders among adolescents was much lower than screening among adults. Pharmacotherapy was more commonly used as an intervention for tobacco dependence than for alcohol and opioid dependence. This was explained by the lack of knowledge among family physicians on the pharmacotherapies for alcohol and opioid dependence.Findings from the current study suggest there is a need for family physicians to integrate screening for substance use disorders using validated tools into their standard medical practice. Furthermore, there is a need for increased knowledge on pharmacotherapies for alcohol and opioid use disorders. It is important to note that the low response rate is a major limitation to this study. One possible reason for this low response rate may be a lack of interest and awareness among family physicians on the importance of screening and treatment of substance use disorders in Ontario.

  15. Spinal Tolerance and Dependence: Some Observations on the Role of Spinal N-Methyl-D-Aspartate Receptors and Phosphorylation in the Loss of Opioid Analgesic Responses

    Directory of Open Access Journals (Sweden)

    Tony L Yaksh

    2000-01-01

    Full Text Available The continuous delivery of opiates can lead to a reduction in analgesic effects. In humans, as in other animals, some component of this change in sensitivity seems likely to have a strong pharmacodynamic component. Such loss of effect, deemed to be tolerance in the present article, can be readily demonstrated in animals with repeated bolus and continuous intrathecal infusion of mu and delta opioids and alpha-2 adrenergic agonists. Research has shown that this loss of effect can be diminished by concurrent treatment with N-methyl-D-aspartate (NMDA receptor antagonists and by the suppression of the activity of spinal protein kinase C (PKC. This suggests in part the probable role of PKC-mediated phosphorylation in the right shift in the dose-effect curves observed with continuous opiate or adrenergic exposure. Importantly, this right shift is seen to occur in parallel with an increase in the phosphorylating activity in the dorsal horn and in the expression of several PKC isozymes. The target of this phosphorylation is not certain. Phosphorylation of the NMDA receptor enhances its functionality, while phosphorylation of the opioid receptor or associated channels seems to diminish their activity or to enhance internalization. While the focus is on several specific components, the accumulating data emphasize the biological complexity of these changes in spinal drug reactivity.

  16. In vitro packaging of individual genomic segments of bacteriophage phi 6 RNA: serial dependence relationships.

    OpenAIRE

    Qiao, X; Casini, G.; Qiao, J; Mindich, L

    1995-01-01

    Bacteriophage phi 6 has a genome of three segments of double-stranded RNA enclosed in a procapsid composed of four different proteins. The preformed procapsid is capable of packaging plus-strand transcripts of the genomic segments in an in vitro reaction. The packaging of the three segments shows a strong order of dependence in that segment S packages alone, but segment M requires S and and segment L requires S and M for efficient packaging. Packaging of individual segments is dependent on un...

  17. Non-analgesic effects of opioids: cardiovascular effects of opioids and their receptor systems.

    Science.gov (United States)

    Headrick, John P; Pepe, Salvatore; Peart, Jason N

    2012-01-01

    Opioid peptides and their G protein-coupled receptors (GPCRs) are important regulators within the cardiovascular system, implicated in modulation of electrophysiological function, heart rate, myocardial inotropy, vascular function, and cellular stress resistance. The opioid system is also involved in cardiovascular development, adaptation to injury and effects of advanced age. The significant roles of opioids are emphasized by the observation that the heart produces prodynorphin and proenkephalin, which are enzymatically processed from small to large active polypeptides. Indeed, depending on species, cardiac preproenkephalin mRNA levels are comparable to or higher than those found in the central nervous system. This review highlights and discusses current knowledge and recent findings regarding physiological and pathophysiological modulation of the heart and vessels by the opioid receptor system.

  18. Sequential Learning Models for the Wisconsin Card Sort Task: Assessing Processes in Substance Dependent Individuals

    Science.gov (United States)

    Bishara, Anthony J.; Kruschke, John K.; Stout, Julie C.; Bechara, Antoine; McCabe, David P.; Busemeyer, Jerome R.

    2010-01-01

    The Wisconsin Card Sort Task (WCST) is a commonly used neuropsychological test of executive or frontal lobe functioning. Traditional behavioral measures from the task (e.g., perseverative errors) distinguish healthy controls from clinical populations, but such measures can be difficult to interpret. In an attempt to supplement traditional measures, we developed and tested a family of sequential learning models that allowed for estimation of processes at the individual subject level in the WCST. Testing the model with substance dependent individuals and healthy controls, the model parameters significantly predicted group membership even when controlling for traditional behavioral measures from the task. Substance dependence was associated with a) slower attention shifting following punished trials and b) reduced decision consistency. Results suggest that model parameters may offer both incremental content validity and incremental predictive validity. PMID:20495607

  19. New opioid prescribing guidelines favor non-opioid alternatives.

    Science.gov (United States)

    2016-05-01

    Determined to make a dent in the growing problem of opioid addiction, the CDC has unveiled new guidelines for opioid prescribing for chronic pain. The recommendations urge providers to be more judicious in their prescribing, opting for opioids only after carefully weighing substantial risks and benefits. Public health authorities note the rampant use and misuse of opioids have "blurred the lines" between prescription opioids and illicit opioids. The new guidelines are designed to help frontline providers balance the need to manage their patients' chronic pain with the duty to curb dangerous prescribing practices. The recommendations are built around three principles: favor non-opioid alternatives for most cases of chronic pain, use the lowest effective dose when prescribing opioids, and exercise caution/monitor patients who are treated with opioids.

  20. Are peripheral opioid antagonists the solution to opioid side effects?

    LENUS (Irish Health Repository)

    Bates, John J

    2012-02-03

    Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

  1. Opioids for restless legs syndrome.

    Science.gov (United States)

    de Oliveira, César Osório; Carvalho, Luciane Bc; Carlos, Karla; Conti, Cristiane; de Oliveira, Marcio M; Prado, Lucila Bf; Prado, Gilmar F

    2016-06-29

    Restless legs syndrome (RLS) is a distressing and common neurological disorder that may have a huge impact in the quality of life of those with frequent and intense symptoms. Patients complain of unpleasant sensations in the legs, at or before bedtime, and feel an urge to move the legs, which improves with movement, such as walking. Symptoms start with the patient at rest (e.g. sitting or lying down), and follow a circadian pattern, increasing during the evening or at night. Many pharmacological intervention are available for RLS, including drugs used to treat Parkinson's disease (L-Dopa and dopaminergic agonists), epilepsy (anticonvulsants), anxiety (benzodiazepines), and pain (opioids). Dopaminergic drugs are those most frequently used for treatment of RLS, but some patients do not respond effectively and require other medication. Opioids, a class of medications used to treat severe pain, seem to be effective in treating RLS symptoms, and are recommended for patients with severe symptoms, because RLS and pain appear to share the same mechanism in the central nervous system. All available drugs are associated to some degree with side effects, which can impede treatment. Opioids are associated with adverse events such as constipation, tolerance, and dependence. This justifies the conduct of a systematic review to ascertain whether opioids are safe and effective for treatment of RLS. To asses the effects of opioids compared to placebo treatment for restless legs syndrome in adults. We searched the Cochrane Central Register of Controlled trials, CENTRAL 2016, issue 4 and MEDLINE, EMBASE, and LILACS up to April 2016, using a search strategy adapted by Cochraneto identify randomised clinical trials. We checked the references of each study and established personal communication with other authors to identify any additional studies. We considered publications in all languages. Randomised controlled clinical trials of opioid treatment in adults with idiopathic RLS. Two

  2. Cocaine dependent individuals with attenuated striatal activation during reinforcement learning are more susceptible to relapse.

    Science.gov (United States)

    Stewart, Jennifer L; Connolly, Colm G; May, April C; Tapert, Susan F; Wittmann, Marc; Paulus, Martin P

    2014-08-30

    Cocaine-dependent individuals show altered brain activation during decision making. It is unclear, however, whether these activation differences are related to relapse vulnerability. This study tested the hypothesis that brain-activation patterns during reinforcement learning are linked to relapse 1 year later in individuals entering treatment for cocaine dependence. Subjects performed a Paper-Scissors-Rock task during functional magnetic resonance imaging (fMRI). A year later, we examined whether subjects had remained abstinent (n=15) or relapsed (n=15). Although the groups did not differ on demographic characteristics, behavioral performance, or lifetime substance use, abstinent patients reported greater motivation to win than relapsed patients. The fMRI results indicated that compared with abstinent individuals, relapsed users exhibited lower activation in (1) bilateral inferior frontal gyrus and striatum during decision making more generally; and (2) bilateral middle frontal gyrus and anterior insula during reward contingency learning in particular. Moreover, whereas abstinent patients exhibited greater left middle frontal and striatal activation to wins than losses, relapsed users did not demonstrate modulation in these regions as a function of outcome valence. Thus, individuals at high risk for relapse relative to those who are able to abstain allocate fewer neural resources to action-outcome contingency formation and decision making, as well as having less motivation to win on a laboratory-based task.

  3. Comparison between ability and performance: a study on the functionality of dependent elderly individuals

    Directory of Open Access Journals (Sweden)

    Flávia Nunes Machado

    2013-12-01

    Full Text Available OBJECTIVE: to compare the ability and performance of Basic Activities of Daily Living of dependent elderly individuals cared for in a geriatric healthcare center. METHOD: cross-sectional, observational study with quantitative approach. The Functional Independence Measure (FIM was applied in 109 elderly individuals cared for in a geriatric healthcare center. Of these, 60 individuals were classified as dependent in the case of basic activities of daily living described according to the International Classification of Functionality, Disability and Health (ICF. The process of triangulation reinforced reliability of data, which included information provided by patients and caregivers and that contained in medical files and objective assessment. RESULTS: the average age was 81.0±7.1 with a predominance of women. The difference between ability and performance was statistically significant (p<0.05 in most daily tasks. CONCLUSION: the contribution of this study in using ICF was semi-quantitatively interpreting its qualifiers, which enabled more objective comparisons and inferences, and revealed a clear distance between the performance and ability of these individuals in most of the assessed activities.

  4. CYP2A6 Polymorphisms May Strengthen Individualized Treatment for Nicotine Dependence

    Directory of Open Access Journals (Sweden)

    Yawo Mawuli Akrodou

    2015-01-01

    Full Text Available Each CYP2A6 gene variant metabolizes nicotine differently depending on its enzymatic activities. The normal nicotine metabolizer CYP2A6*1A is associated with high scores of nicotine dependence (5–10 on the Fagerström Test for Nicotine Dependence (FTND scale because it encodes for enzymes that catalyze nicotine 100%. Slow nicotine metabolizers (i.e., CYP2A6*1H, CYP2A6*4A, CYP2A6*9, and CYP2A6*12A are associated with underrated nicotine metabolizing activity (50%–75%, linking them to low scores for nicotine dependence (0–4 on the FTND scale. In a clinical trial involving the use of bupropion, people who were carriers of slow nicotine metabolizers were found to have a tendency to maintain abstinence 1.7 times longer than people with normal nicotine metabolizers. An overview of CYP2A6 polymorphism enzymatic activities in nicotine dependence etiology and treatment revealed that slow nicotine metabolizers may strengthen the individualized treatment of nicotine dependence.

  5. The Risk of Individual Stocks’ Tail Dependence with the Market and Its Effect on Stock Returns

    Directory of Open Access Journals (Sweden)

    Guobin Fan

    2015-01-01

    Full Text Available Traditional beta is only a linear measure of overall market risk and places equal emphasis on upside and downside risks, but actually the latter is always much stronger probably due to the trading mechanism like short-sale constraints. Therefore, this paper employs the nonlinear measure, tail dependence, to measure the extreme downside risks that individual stocks crash together with the whole market and investigates whether such tail dependence risks will affect stock returns. Our empirical evidence based on Shanghai A shares confirms that most stocks display nonnegligible tail dependence with the whole market, and, more importantly, such tail dependence risks can indeed provide additional information beyond beta and other factors for asset pricing. In cross-sectional regression, it is proved that this tail dependence does help to explain monthly returns on Shanghai A shares, whereas the time-series regression further indicates that mimicking portfolio returns for tail dependence can capture strong common variation of Shanghai A stock returns.

  6. Harmonic force spectroscopy measures load-dependent kinetics of individual human β-cardiac myosin molecules

    Science.gov (United States)

    Sung, Jongmin; Nag, Suman; Mortensen, Kim I.; Vestergaard, Christian L.; Sutton, Shirley; Ruppel, Kathleen; Flyvbjerg, Henrik; Spudich, James A.

    2015-08-01

    Molecular motors are responsible for numerous cellular processes from cargo transport to heart contraction. Their interactions with other cellular components are often transient and exhibit kinetics that depend on load. Here, we measure such interactions using `harmonic force spectroscopy'. In this method, harmonic oscillation of the sample stage of a laser trap immediately, automatically and randomly applies sinusoidally varying loads to a single motor molecule interacting with a single track along which it moves. The experimental protocol and the data analysis are simple, fast and efficient. The protocol accumulates statistics fast enough to deliver single-molecule results from single-molecule experiments. We demonstrate the method's performance by measuring the force-dependent kinetics of individual human β-cardiac myosin molecules interacting with an actin filament at physiological ATP concentration. We show that a molecule's ADP release rate depends exponentially on the applied load, in qualitative agreement with cardiac muscle, which contracts with a velocity inversely proportional to external load.

  7. Understanding the Opioid Epidemic

    Science.gov (United States)

    ... Brain Injury Awareness Home and Recreational Safety Motor Vehicle Safety Parents Are The Key to Safe Teen Drivers ... give health care providers information to improve patient safety and prevent ... high-risk prescribing and prevent opioid overdose. Improve detection of ...

  8. Probabilistic inference: Task dependency and individual differences of probability weighting revealed by hierarchical Bayesian modelling

    Directory of Open Access Journals (Sweden)

    Moritz eBoos

    2016-05-01

    Full Text Available Cognitive determinants of probabilistic inference were examined using hierarchical Bayesian modelling techniques. A classic urn-ball paradigm served as experimental strategy, involving a factorial two (prior probabilities by two (likelihoods design. Five computational models of cognitive processes were compared with the observed behaviour. Parameter-free Bayesian posterior probabilities and parameter-free base rate neglect provided inadequate models of probabilistic inference. The introduction of distorted subjective probabilities yielded more robust and generalizable results. A general class of (inverted S-shaped probability weighting functions had been proposed; however, the possibility of large differences in probability distortions not only across experimental conditions, but also across individuals, seems critical for the model’s success. It also seems advantageous to consider individual differences in parameters of probability weighting as being sampled from weakly informative prior distributions of individual parameter values. Thus, the results from hierarchical Bayesian modelling converge with previous results in revealing that probability weighting parameters show considerable task dependency and individual differences. Methodologically, this work exemplifies the usefulness of hierarchical Bayesian modelling techniques for cognitive psychology. Theoretically, human probabilistic inference might be best described as the application of individualized strategic policies for Bayesian belief revision.

  9. Probabilistic Inference: Task Dependency and Individual Differences of Probability Weighting Revealed by Hierarchical Bayesian Modeling.

    Science.gov (United States)

    Boos, Moritz; Seer, Caroline; Lange, Florian; Kopp, Bruno

    2016-01-01

    Cognitive determinants of probabilistic inference were examined using hierarchical Bayesian modeling techniques. A classic urn-ball paradigm served as experimental strategy, involving a factorial two (prior probabilities) by two (likelihoods) design. Five computational models of cognitive processes were compared with the observed behavior. Parameter-free Bayesian posterior probabilities and parameter-free base rate neglect provided inadequate models of probabilistic inference. The introduction of distorted subjective probabilities yielded more robust and generalizable results. A general class of (inverted) S-shaped probability weighting functions had been proposed; however, the possibility of large differences in probability distortions not only across experimental conditions, but also across individuals, seems critical for the model's success. It also seems advantageous to consider individual differences in parameters of probability weighting as being sampled from weakly informative prior distributions of individual parameter values. Thus, the results from hierarchical Bayesian modeling converge with previous results in revealing that probability weighting parameters show considerable task dependency and individual differences. Methodologically, this work exemplifies the usefulness of hierarchical Bayesian modeling techniques for cognitive psychology. Theoretically, human probabilistic inference might be best described as the application of individualized strategic policies for Bayesian belief revision.

  10. Sensitive plant (Mimosa pudica) hiding time depends on individual and state.

    Science.gov (United States)

    Reed-Guy, Sarah; Gehris, Connor; Shi, Meng; Blumstein, Daniel T

    2017-01-01

    The decisions animals make to adjust their antipredator behavior to rapidly changing conditions have been well studied. Inducible defenses in plants are an antipredator behavior that acts on a longer time scale, but sensitive plants, Mimosa pudica, have a much more rapid antipredator response; they temporarily close their leaves when touched. The time they remain closed is defined as hiding time. We studied hiding time in sensitive plants and found that individual plants differed significantly in their hiding times. We then showed that the effect of individual explained substantial variation in hiding time on a short time scale. Finally, on a longer time scale, individuality persisted but the amount of variation attributed to individual decreased. We hypothesized that variation in plant condition might explain this change. We therefore manipulated sunlight availability and quantified hiding time. When deprived of light for 6 h, sensitive plants significantly shortened their hiding times. But when only half a plant was deprived of light, hiding times on the deprived half and light exposed half were not significantly different. This suggests that overall condition best explains variation in sensitive plant antipredator behavior. Just like in animals, sensitive plant antipredator behavior is condition dependent, and, just like in animals, a substantial amount of the remaining variation is explained by individual differences between plants. Thus, models designed to predict plasticity in animal behavior may be successfully applied to understand behavior in other organisms, including plants.

  11. Sensitive plant (Mimosa pudica hiding time depends on individual and state

    Directory of Open Access Journals (Sweden)

    Sarah Reed-Guy

    2017-07-01

    Full Text Available The decisions animals make to adjust their antipredator behavior to rapidly changing conditions have been well studied. Inducible defenses in plants are an antipredator behavior that acts on a longer time scale, but sensitive plants, Mimosa pudica, have a much more rapid antipredator response; they temporarily close their leaves when touched. The time they remain closed is defined as hiding time. We studied hiding time in sensitive plants and found that individual plants differed significantly in their hiding times. We then showed that the effect of individual explained substantial variation in hiding time on a short time scale. Finally, on a longer time scale, individuality persisted but the amount of variation attributed to individual decreased. We hypothesized that variation in plant condition might explain this change. We therefore manipulated sunlight availability and quantified hiding time. When deprived of light for 6 h, sensitive plants significantly shortened their hiding times. But when only half a plant was deprived of light, hiding times on the deprived half and light exposed half were not significantly different. This suggests that overall condition best explains variation in sensitive plant antipredator behavior. Just like in animals, sensitive plant antipredator behavior is condition dependent, and, just like in animals, a substantial amount of the remaining variation is explained by individual differences between plants. Thus, models designed to predict plasticity in animal behavior may be successfully applied to understand behavior in other organisms, including plants.

  12. Remifentanil: a new opioid.

    Science.gov (United States)

    Glass, P S

    1995-11-01

    Remifentanil appears to have pharmacodynamic properties similar to other potent mu opioid agonists. It does, however, have unique pharmacokinetic properties, with a rapid onset and rapid offset of effect, irrespective of the duration of its administration. With this property, remifentanil appears to be a very titratable opioid that will make it suitable for administration for either very brief periods, in which analgesia is required, or over prolonged periods, without the concern for prolonged recovery.

  13. 几种阿片类药物在表达人μ阿片受体Sf9昆虫细胞中的受体亲和力及依赖性%Binding affinity to and dependence on some opioids in Sf9 insect cells expressing humanμ-opioid receptor

    Institute of Scientific and Technical Information of China (English)

    刘忠华; 和友; 金文桥; 陈新建; 张鸿萍; 申庆祥; 池志强

    2003-01-01

    目的:用表达人μ受体的Sf9昆虫细胞(Sf9-μ细胞)研究二氢埃托啡、芬太尼、海洛因和哌替啶对μ受体亲和力与依赖性.方法:竞争结合实验检测受体亲和力;放免法测定cAMP;热板法测痛;纳洛酮催促跳跃评价身体依赖性.结果:Sf9-μ细胞经上述药物孵育后,纳洛酮引起cAMP超射.以结合实验中Ki值与cAMP超射实验中的EC50值之比作为药物在Sf9-μ细胞的依赖性指数.以镇痛ED50与戒断反应中累积剂量的ED50之比作为小鼠身体依赖性指数.上述药物的两种依赖性指数之间以及受体亲和力与镇痛活性之间有较好的相关性.结论:Sf9-μ细胞可用来评价阿片类药物的受体亲和力及依赖潜能.%AIM: To investigate the receptor binding affinity and naloxone-precipitated cAMP overshoot of dihydroetorphine,fentanyl, heroin, and pethidine in Sf9 insect cells expressing human μ-opioid receptor (Sf9-μ cells). METHODS:Competitive binding assay of [3H]ohmefentanyl was used to reveal the affinity for μ-opioid receptor in Sf9-μ cells.[3H]cAMP RIA was used to determine cAMP level. Antinociceptive activity was evaluated using 55 ℃ mouse hot plate test. Naloxone-precipitated withdrawal jumping was used to reflect physical dependence in mice. RESULTS:All drugs displayed antinociceptive activity and produced physical dependence in mice. The Ki values of dihydroetorphine, fentanyl, heroin, and pethidine in competitive binding assay were (0.85±0.20) nmol, (59.1± 11.7)nmol, (0.36±0.13) μmol, and (12.2±3.8) μmol respectively. The binding affinities of these drugs for μ-opioid receptor in Sf9-μ cells were paralleled to their antinociceptive activities in mice. After chronic pretreatment with these drugs, naloxone induced cAMP withdrawal overshoot in Sf9-μ cells. The dependence index in Sf9-μ cells was calculated as Ki value in competitive binding assay over ECs0 value in naloxone-precipitated cAMP assay. The physical dependence index in mice

  14. Correlates of overdose risk perception among illicit opioid users.

    Science.gov (United States)

    Rowe, Christopher; Santos, Glenn-Milo; Behar, Emily; Coffin, Philip O

    2016-02-01

    Opioid-related mortality continues to increase in the United States. The current study assesses demographic and behavioral predictors of perceived overdose risk among individuals who use opioids illicitly. By examining these correlates in the context of established overdose risk factors, we aim to assess whether characteristics and behaviors that have been associated with actual overdose risk translate to higher perception of risk. We conducted a cross-sectional survey of 172 adult illicit opioid users in San Francisco, CA and used multivariable logistic regression to identify predictors of perception of high risk for opioid overdose. Age (aOR=0.96, 95%CI=0.93-1.00) and number of injection days per month (0.91, 0.86-0.97) were associated with a lower odds of perceived high overdose risk. There was no independent association between use of opioid analgesics, concurrent use of opioids and benzodiazepines or cocaine, or HIV status and overdose risk perception. Opioid users who injected more frequently and those who were older were less likely to perceive themselves as being at risk of overdose, notwithstanding that those who inject more are at higher risk of overdose and those who are older are at higher risk overdose mortality. In addition, despite being established overdose risk factors, there was no relationship between use of opioid analgesics, concurrent use of opioids and cocaine or benzodiazepines, or self-reported HIV status and overdose risk perception. These findings highlight key populations of opioid users and established risk factors that may merit focused attention as part of education-based overdose prevention and opioid management strategies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Medical cannabis and chronic opioid therapy.

    Science.gov (United States)

    Reisfield, Gary M

    2010-12-01

    Fourteen states and the District of Columbia have legalized the use of cannabis for medical purposes. A small, high-quality literature supports the efficacy of medical cannabis for the treatment of neuropathic pain. The smoked botanical product, however, is associated with a number of adverse medical and psychiatric consequences. Furthermore, experimental data indicate that acute use of cannabis results in impairment of every important metric related to the safe operation of a motor vehicle. Epidemiological data show associations between recent cannabis use and both psychomotor impairment and motor vehicle crashes, associations that are strengthened by the concomitant use of alcohol and other central nervous system depressants. Finally, data from pain clinics reveals an unusually high prevalence of cannabis use in nearly all age groups and an association between cannabis use and opioid and other substance misuse. Based on available data and expert opinion, concomitant use of cannabis and opioids is an absolute contraindication to the operation of a motor vehicle. In patients who use cannabis and are prescribed opioids, heightened vigilance for opioid- and other substance-related problems is warranted. It is appropriate to refrain from prescribing opioids to individuals using medical cannabis if there is reasonable suspicion that the combination will pose a risk to the patient or others.

  16. Stress- and cue-elicited craving and reactivity in marijuana-dependent individuals.

    Science.gov (United States)

    McRae-Clark, Aimee L; Carter, Rickey E; Price, Kimber L; Baker, Nathaniel L; Thomas, Suzanne; Saladin, Michael E; Giarla, Kathleen; Nicholas, Katherine; Brady, Kathleen T

    2011-11-01

    Cue-elicited craving and stress responses have been identified as predictors of relapse in drug dependence, but little research exists on the contribution of these factors to marijuana use specifically. The aims of the present study were to evaluate (1) responses to a psychological stressor, (2) responses to marijuana-related cues, and (3) if an exposure to a psychological stressor augmented craving subsequently elicited by marijuana-related cue exposure in marijuana-dependent individuals. Subjective (craving, stress), neuroendocrine (adrenocorticotropic hormone (ACTH), cortisol), and physiologic responses to the presentation of neutral and marijuana cues were assessed after randomization to a stress (Trier Social Stress Task (TSST)) or non-stress control condition in marijuana-dependent individuals. Outcome measures were assessed at baseline, post-stressor/pre-neutral cue, post-neutral cue, and post-marijuana cue. Eighty-seven participants completed procedures (stress group, n = 45; non-stress group, n = 42). The stress group had a significant increase over the non-stress group in stress rating (p < 0.001), craving (p = 0.028), cortisol (p < 0.001), and ACTH (p < 0.001) after the completion of the TSST. An increased craving response for all participants was seen following the presentation of the marijuana cues (p = 0.005). Following the TSST or non-stress condition, the non-stress group had an increase in craving to marijuana cues as compared to neutral cues (p = 0.002); an increase in craving was not observed in the stress group (p = 0.404). Marijuana cue exposure and a social stressor increased craving in marijuana-dependent individuals. Completion of the TSST did not increase craving response to subsequent marijuana cue exposure.

  17. STRESS AND CUE-ELICITED CRAVING AND REACTIVITY IN MARIJUANA-DEPENDENT INDIVIDUALS

    Science.gov (United States)

    McRae-Clark, Aimee L.; Carter, Rickey E.; Price, Kimber L.; Baker, Nathaniel L.; Thomas, Suzanne; Saladin, Michael E.; Giarla, Kathleen; Nicholas, Katherine; Brady, Kathleen T.

    2011-01-01

    Rationale Cue-elicited craving and stress responses have been identified as predictors of relapse in drug dependence, but little research exists on the contribution of these factors to marijuana use specifically. Objectives The aims of the present study were to evaluate (1) responses to a psychological stressor, (2) responses to marijuana-related cues, and (3) if an exposure to a psychological stressor augmented craving subsequently elicited by marijuana-related cue exposure in marijuana-dependent individuals. Methods Subjective (craving, stress), neuroendocrine (ACTH, cortisol), and physiologic responses to the presentation of neutral and marijuana cues were assessed after randomization to a stress (Trier Social Stress Task; TSST) or no-stress control condition in marijuana-dependent individuals. Outcome measures were assessed at baseline, post-stressor/pre-neutral cue, post-neutral cue, and post marijuana cue. Results 87 participants completed procedures (stress group, n=45; non-stress group, n=42). The stress group had a significant increase over the non-stressed group in stress rating (p<0.001), craving (p=0.028), cortisol (p<0.001), and ACTH (p<0.001) after completion of the TSST. An increased craving response for all participants was seen following presentation of the marijuana cues (p=0.005). Following the TSST or no-stress condition, the non-stressed group had an increase in craving to marijuana cues as compared to neutral cues (p=0.002); an increase in craving was not observed in the stress group (p=0.404). Conclusions Marijuana cue exposure and a social stressor increased craving in marijuana-dependent individuals. Completion of the TSST did not increase craving response to subsequent marijuana-cue exposure. PMID:21710170

  18. Dopamine-dependent behavioural stimulation by non-peptide delta opioids BW373U86 and SNC 80: 2. Place-preference and brain microdialysis studies in rats.

    Science.gov (United States)

    Longoni, R; Cadoni, C; Mulas, A; Di Chiara, G; Spina, L

    1998-02-01

    The motivational properties of the non-peptide delta-opioid receptor agonists BW373U86 and SNC 80 were investigated using the place-conditioning paradigm. BW373U86 (0.5-1.0 mg/kg s.c.) and SNC 80 (1.25-5.0 mg/kg s.c.) elicited significant preference for the drug-paired compartment, in a dose-related fashion. Naltrindole (5.0 mg/kg s.c.) pretreatment, while failing to modify preference when given alone, completely prevented place-preference induced by BW373U86 (1.0 mg/kg s.c.) and SNC 80 (1.25 mg/kg s.c.). The dopamine D1 receptor antagonist SCH23390, given at doses that do not affect place-preference (0.012 mg/kg s.c.), completely prevented the place-preference induced by BW373U86 and SNC 80. At the doses effective in eliciting place-preference, BW373U86 and SNC 80 failed to modify extracellular dopamine in the medial nucleus accumbens, while in the dorso-lateral caudate-putamen BW373U86 (1.0 and 2.5 mg/kg s.c.) reduced extracellular dopamine, and this effect was prevented by naltrindole (5.0 mg/kg s.c.). SNC 80, only at the dose of 5 mg/kg s.c., significantly reduced extracellular DA in the dorso-lateral caudate-putamen. The results indicate that stimulation of delta-opioid receptors has incentive properties that might be related to an indirect amplification of post-synaptic dopamine transmission.

  19. Context dependency of baseline glucocorticoids as indicators of individual quality in a capital breeder.

    Science.gov (United States)

    Jaatinen, Kim; Seltmann, Martin W; Hollmén, Tuula; Atkinson, Shannon; Mashburn, Kendall; Öst, Markus

    2013-09-15

    Identifying markers of individual quality is a central goal of life-history theory and conservation biology. The 'corticosterone (CORT)-fitness hypothesis' postulates that low fitness signals impaired ability to cope with the environment, resulting in elevated baseline CORT levels. CORT can, however, be negatively, positively or neutrally related to fitness, depending on the context. In order to clarify this controversial issue, we elucidate the utility of using baseline CORT as a correlate of individual fitness in incubating female eiders across variable environments. An increase in serum CORT with decreasing body condition was evident in older, more experienced breeders, while increased clutch mass was associated with elevated serum CORT in females breeding late in the season. For faecal CORT, the expected negative association with body condition was observed only in early breeders. We found a strong increase in faecal CORT with increasing baseline body temperature, indicating the utility of body temperature as a complementary stress indicator. Females in good body condition had a lower baseline body temperature, but this effect was only observed on open islands, a harsher breeding habitat less buffered against weather variability. Females with higher reproductive investment also maintained a lower baseline body temperature. Nest success strongly decreased with increasing serum and faecal CORT concentrations, and individual stress hormone and body temperature profiles were repeatable over years. Although our data support the tenet that baseline CORT is negatively related to fitness, the complex context-dependent effects call for cautious interpretation of relationships between stress physiology and phenotypic quality.

  20. Disrupted Resting-State Default Mode Network in Betel Quid-Dependent Individuals

    Science.gov (United States)

    Zhu, Xueling; Zhu, Qiuling; Jiang, Canhua; Shen, Huaizhen; Wang, Furong; Liao, Weihua; Yuan, Fulai

    2017-01-01

    Recent studies have shown that substance dependence (addiction) is accompanied with altered activity patterns of the default mode network (DMN). However, the neural correlates of the resting-state DMN and betel quid dependence (BQD)-related physiopathological characteristics still remain unclear. Resting-state functional magnetic resonance imaging images were obtained from 26 BQD individuals and 28 matched healthy control subjects. Group independent component analysis was performed to analyze the resting state images into spatially independent components. Gray matter volume was examined as covariate with voxel-based morphometry to rule out its effect on the functional results. The severity of BQD was assessed by the BQD Scale (BQDS). We observed decreased functional connectivity in anterior part of the DMN including ventral medial prefrontal cortex, orbital MPFC (OMPFC)/anterior cingulate cortex (ACC). Furthermore, the functional connectivity within the OMPFC/ACC in BQD individuals was negatively correlated with BQDS (p = 0.01, r = -0.49). We reported decreased functional connectivity within anterior part of the DMN in BQD individuals, which provides new evidence for the role of the DMN in the pathophysiology of BQD. PMID:28194128

  1. Does alexithymia explain variation in cue-elicited craving reported by methamphetamine-dependent individuals?

    Science.gov (United States)

    Saladin, Michael E; Santa Ana, Elizabeth J; LaRowe, Steven D; Simpson, Annie N; Tolliver, Bryan K; Price, Kimber L; McRae-Clark, Aimee L; Brady, Kathleen T

    2012-01-01

    Drug craving is an important motivational phenomenon among addicted individuals, and successful management of craving is essential to both the initiation and maintenance of abstinence. Although craving in response to drug cues is common in drug-dependent individuals, it is not universal. At the present time, it is not known why approximately 20-30% of all addicted persons fail to report appreciable craving in laboratory-based cue reactivity studies. This study examined the possibility that alexithymia, a personality attribute characterized by a difficulty identifying and describing emotions, may contribute to the impoverished cue-elicited craving experienced by some addicts. Specifically, we tested the hypothesis that alexithymia, as measured by the Toronto Alexithymia Scale (TAS), would be inversely related to the magnitude of cue-elicited craving obtained in a cue reactivity protocol. Forty methamphetamine-dependent individuals completed the TAS and provided craving ratings for methamphetamine after presentation of methamphetamine-associated cues. Thirteen participants (32%) reported no methamphetamine cue-elicited craving. Contrary to expectation, TAS factor 1 (a measure of difficulty identifying feelings) scores were positively associated with cue-elicited craving. Thus, the results suggest that increasing difficulty-identifying feelings may be associated with higher cue-elicited craving. Clinical implications for this finding are discussed.

  2. PSYCHOLOGICAL ASSESSMENT OF OPIOID DRUG ABUSE

    Directory of Open Access Journals (Sweden)

    José Luis Carballo

    2016-01-01

    Full Text Available The increase in the prescription of opioid analgesics is related to increased rates of opioid abuse and the negative consequences of medication misuse. Several international health organisations recommend comprehensive and multidisciplinary patient assessment for the duration of the opioid treatment in order to identify and prevent medication abuse. Due to the lack of specific clinical guidelines in the Spanish National Health System, the aim of this paper is to present a proposal for psychological assessment based on the main psychological tools currently available for assessing opioid abuse. The assessment guidelines have been established based on the psychological variables that can predict and prolong the abuse, classifying all of the variables depending on the current stage of the therapeutic process for each patient. Although there are instruments with good psychometric properties, further research is necessary to adapt, translate and validate these instruments for use in the Spanish population. Future studies are also needed to investigate intervention and prevention strategies in depth in order to reduce the likelihood of abuse in patients treated with opioids.

  3. Doctor shopping reveals geographical variations in opioid abuse.

    Science.gov (United States)

    Nordmann, Sandra; Pradel, Vincent; Lapeyre-Mestre, Maryse; Frauger, Elisabeth; Pauly, Vanessa; Thirion, Xavier; Mallaret, Michel; Jouanjus, Emilie; Micallef, Joëlle

    2013-01-01

    Prescription opioid abuse is not homogeneous due to varying patterns of use and different geographic preferences. Because doctor shopping is one of the main sources of diversion, it has previously been used to estimate drug abuse. The aim of this study was to describe and compare opioid abuse in 2008 using doctor shopping to estimate abuse in 3 French regions. Data for this study came from the General Health Insurance (GHI) reimbursement database, which covers 77% of the French population. All individuals living in Provence-Alpes-Cote d'Azur-Corse (PACA), Rhone-Alpes (RA), or Midi-Pyrenees (MP) that received at least one reimbursement for oral opioids from the GHI in 2008 were included. Oral opioids under study were opioids for mild to moderate pain (dextropropoxyphene, codeine, tramadol, dihydrocodeine), opoids for moderately severe to severe pain (oral morphine, oxycodone, buprenorphine painkiller, hydromorphone), and opioid maintenance treatments (buprenorphine maintenance, methadone). For a given opioid, the Doctor Shopping Quantity (DSQ) is the quantity obtained by overlapping prescriptions from several prescribers. It is used to estimate the magnitude of abuse. The Doctor Shopping Indicator (DSI) is the DSQ divided by the total dispensed quantity. It is used to estimate the abuse corrected for use. The total DSQ for opioids in PACA (213.3 DDD/1,000 inhabitants) was twofold superior to that in RA (115.1 DDD/1,000) and in MP (106.2 DDD/1,000). The DSQ of opioids for mild to moderate pain was 75.5DDD/1000 (DSI=1.1%), 19.7DDD/1,000 (DSI=5.0%) for opioids for moderately severe to severe pain, and 55.3DDD/1,000 (DSI=6.2%) for opioid maintenance treatments. Emergent signals of abuse have been observed at a regional level for oxycodone in MP and dihydrocodeine in RA and MP. The main limitation of this study is that the GHI reimbursement database provides information about dispensed and reimbursed prescription drugs, and not necessarily the actual quantity used. These

  4. A Moderated Mediation Model of HIV-Related Stigma, Depression, and Social Support on Health-Related Quality of Life among Incarcerated Malaysian Men with HIV and Opioid Dependence.

    Science.gov (United States)

    Shrestha, Roman; Copenhaver, Michael; Bazazi, Alexander R; Huedo-Medina, Tania B; Krishnan, Archana; Altice, Frederick L

    2017-04-01

    Although it is well established that HIV-related stigma, depression, and lack of social support are negatively associated with health-related quality of life (HRQoL) among people living with HIV (PLH), no studies to date have examined how these psychosocial factors interact with each other and affect HRQoL among incarcerated PLH. We, therefore, incorporated a moderated mediation model (MMM) to explore whether depression mediates the effect of HIV-related stigma on HRQoL as a function of the underlying level of social support. Incarcerated HIV-infected men with opioid dependence (N = 301) were recruited from the HIV units in Kajang prison in Malaysia. Participants completed surveys assessing demographic characteristics, HIV-related stigma, depression, social support, and HRQoL. Results showed that the effect of HIV-related stigma on HRQoL was mediated via depression (a1:β = 0.1463, p PLH.

  5. Prediction of withdrawal symptoms during opioid detoxification

    NARCIS (Netherlands)

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

    2008-01-01

    OBJECTIVE: The severity of self-reported withdrawal symptoms varies during detoxification of opioid-dependent patients. The aim of this study is to identify subgroups of withdrawal symptoms within the detoxification trajectory and to predict the severity of withdrawal symptoms on the basis of

  6. Population dynamics of minimally cognitive individuals. Part 2: Dynamics of time-dependent knowledge

    Energy Technology Data Exchange (ETDEWEB)

    Schmieder, R.W.

    1995-07-01

    The dynamical principle for a population of interacting individuals with mutual pairwise knowledge, presented by the author in a previous paper for the case of constant knowledge, is extended to include the possibility that the knowledge is time-dependent. Several mechanisms are presented by which the mutual knowledge, represented by a matrix K, can be altered, leading to dynamical equations for K(t). The author presents various examples of the transient and long time asymptotic behavior of K(t) for populations of relatively isolated individuals interacting infrequently in local binary collisions. Among the effects observed in the numerical experiments are knowledge diffusion, learning transients, and fluctuating equilibria. This approach will be most appropriate to small populations of complex individuals such as simple animals, robots, computer networks, agent-mediated traffic, simple ecosystems, and games. Evidence of metastable states and intermittent switching leads them to envision a spectroscopy associated with such transitions that is independent of the specific physical individuals and the population. Such spectra may serve as good lumped descriptors of the collective emergent behavior of large classes of populations in which mutual knowledge is an important part of the dynamics.

  7. Opioids for cancer pain: the challenge of optimizing treatment.

    Science.gov (United States)

    Plante, Gérard E; VanItallie, Theodore B

    2010-10-01

    During 2007, 11.7 million US men and women of all ages suffered from some form of invasive cancer. During their illness, at least 70% (8.2 million) will experience pain sufficiently severe to require chronic opioid treatment. Cancer-induced pain is usually described under 3 headings: acute pain, chronic pain, and breakthrough pain. Among patients with chronic, persistent cancer pain controlled by around-the-clock analgesics, there is a high prevalence of breakthrough pain-often precipitated by some form of physical activity. Breakthrough pain seems best treated by a powerful, fast-acting opioid such as intravenous morphine or transmucosal fentanyl. At present, opioids are virtually the only analgesics capable of controlling moderate and severe cancer pain. In recent years, a veritable arsenal of opioids with a wide range of pharmacologic properties has become available for use in different pain situations. The World Health Organization has developed a 3-step "analgesic ladder" to guide management of cancer pain, based on the pain's severity, estimated by means of a 1 to 10 numeric rating scale. As the severity of the pain escalates, more potent (World Health Organization Step III) opioids are used. When faced with a difficult case of cancer pain, the physician must choose-from an array of options-the safest and most effective opioid analgesic and the most appropriate delivery system. Such decisions require an adequate understanding of the available opioids and experience with their use. The pharmacodynamic response to a given opioid depends on the nature of the receptor to which the opioid binds and its affinity for the receptor. Morphine activates the μ-opioid receptors, resulting in not only analgesia and sedation, but also euphoria, respiratory depression, constipation, and pruritus. The existence of a number of opioid receptor subtypes, each with its own repertoire of responses, has given rise to the hope (as yet unrealized) that an opioid can be found (or

  8. Sex and HIV serostatus differences in decision making under risk among substance dependent individuals

    Science.gov (United States)

    Martin, Eileen; Gonzalez, Raul; Vassileva, Jasmin; Maki, Pauline M.; Bechara, Antoine; Brand, Matthias

    2016-01-01

    HIV+ individuals with and without substance use disorders make significantly poorer decisions when information about the probability and magnitude of wins and losses is not available. We administered the Game of Dice Task, a measure of decision making under risk that provides this information explicitly, to 92 HIV+ and 134 HIV− substance dependent men and women. HIV+ participants made significantly poorer decisions compared with HIV− participants, but this deficit appeared more prominent among HIV+ women. These data indicate that decision making under risk is impaired among HIV+ SDIs. Potential factors for the HIV+ women’s relatively greater impairment are discussed. PMID:26882176

  9. Learning and generalization from reward and punishment in opioid addiction.

    Science.gov (United States)

    Myers, Catherine E; Rego, Janice; Haber, Paul; Morley, Kirsten; Beck, Kevin D; Hogarth, Lee; Moustafa, Ahmed A

    2017-01-15

    This study adapts a widely-used acquired equivalence paradigm to investigate how opioid-addicted individuals learn from positive and negative feedback, and how they generalize this learning. The opioid-addicted group consisted of 33 participants with a history of heroin dependency currently in a methadone maintenance program; the control group consisted of 32 healthy participants without a history of drug addiction. All participants performed a novel variant of the acquired equivalence task, where they learned to map some stimuli to correct outcomes in order to obtain reward, and to map other stimuli to correct outcomes in order to avoid punishment; some stimuli were implicitly "equivalent" in the sense of being paired with the same outcome. On the initial training phase, both groups performed similarly on learning to obtain reward, but as memory load grew, the control group outperformed the addicted group on learning to avoid punishment. On a subsequent testing phase, the addicted and control groups performed similarly on retention trials involving previously-trained stimulus-outcome pairs, as well as on generalization trials to assess acquired equivalence. Since prior work with acquired equivalence tasks has associated stimulus-outcome learning with the nigrostriatal dopamine system, and generalization with the hippocampal region, the current results are consistent with basal ganglia dysfunction in the opioid-addicted patients. Further, a selective deficit in learning from punishment could contribute to processes by which addicted individuals continue to pursue drug use even at the cost of negative consequences such as loss of income and the opportunity to engage in other life activities.

  10. Overview of genetic analysis of human opioid receptors.

    Science.gov (United States)

    Spampinato, Santi M

    2015-01-01

    The human μ-opioid receptor gene (OPRM1), due to its genetic and structural variation, has been a target of interest in several pharmacogenetic studies. The μ-opioid receptor (MOR), encoded by OPRM1, contributes to regulate the analgesic response to pain and also controls the rewarding effects of many drugs of abuse, including opioids, nicotine, and alcohol. Genetic polymorphisms of opioid receptors are candidates for the variability of clinical opioid effects. The non-synonymous polymorphism A118G of the OPRM1 has been repeatedly associated with the efficacy of opioid treatments for pain and various types of dependence. Genetic analysis of human opioid receptors has evidenced the presence of numerous polymorphisms either in exonic or in intronic sequences as well as the presence of synonymous coding variants that may have important effects on transcription, mRNA stability, and splicing, thus affecting gene function despite not directly disrupting any specific residue. Genotyping of opioid receptors is still in its infancy and a relevant progress in this field can be achieved by using advanced gene sequencing techniques described in this review that allow the researchers to obtain vast quantities of data on human genomes and transcriptomes in a brief period of time and with affordable costs.

  11. Age-and gender-dependent obesity in individuals with 16p11.2 deletion

    Institute of Scientific and Technical Information of China (English)

    Yongguo Yu; Haitao Zhu; David T. Miller; James F. Gusella; Orah S. Platt; Bai-Lin Wu; Yiping Shen

    2011-01-01

    Recurrent genomic imbalances at 16p11.2 are genetic risk factors of variable penetrance for developmental delay and autism.Recently,16p11.2 (chr16:29.5 Mb-30.1 Mb) deletion has also been detected in individuals with early-onset severe obesity.The penetrance of 16p11.2deletion as a genetic risk factor for obesity is unknown.We evaluated the growth and body mass characteristics of 28 individuals with 16p11.2(chr16:29.5 Mb-30.1 Mb) deletion originally ascertained for their developmental disorders by reviewing their medical records.We found that nine individuals could be classilied as obese and six as overweight.These individuals generally had early feeding and growth difficulties,and started to gain excessive weight around 5-6 years of age.Thirteen out of the 18 deletion carriers aged 5 years and older (72%) were overweight or obese,whereas only two of 10 deletion carriers (20%) younger than five were overweight or obese.Males exhibited more severe obesity than females.Thus,the obesity phenotype of 16p11.2 deletion carriers is of juvenile onset,exhibited an age.and gender-dependent penetrance.16p11.2 deletion appears to predispose individuals to juvenile onset obesity and in this case are similar to the well-described Prader-Willi syndrome (PWS).Early detection of this deletion will provide opportunity to prevent obesity.

  12. Gene Variants Reduce Opioid Risks

    Science.gov (United States)

    ... Opioids Prescription Drugs & Cold Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine ... variant of the gene for the μ-opioid receptor (OPRM1) with a decreased risk for addiction to ...

  13. Spontaneous harm reduction: a barrier for substance-dependent individuals seeking treatment?

    Directory of Open Access Journals (Sweden)

    Bruno José Barcellos Fontanella

    2005-12-01

    Full Text Available OBJETIVE: Greater information regarding motivations and treatment barriers faced by substance-dependent individuals has clinical and public health implications. This study aimed to formulate hypotheses regarding psychological, social and family variables that can be constructed as motivations or subjective barriers for the early seeking of formal treatment. METHODS: A qualitative study was conducted in an intentional sample (selected through saturation and variety of types of 13 substance-dependent individuals who sought treatment. In-depth, semi-structured interviews were conducted using open questions, and the transcribed data were subjected to qualitative analysis. RESULTS: Four types of spontaneous harm reduction measures were identified, according to the subjective logic of each participant: having some periods at rest (not using and recovering from adverse effects; caretaking by close acquaintances (relatives, partners, drug dealers and alcoholic beverage sellers; selectivity regarding substance source, type and means of administration; establishing "healthy" limits of ingestion. CONCLUSIONS: The measures identified might represent barriers to the early seeking of treatment but might also represent spontaneous learning of abilities beneficial to future treatment. Health care professionals should take into consideration their existence and should address them in clinical settings. Issues representative of the formulated categories should be presented in structured questionnaires used in future quantitative studies of barriers to treatment in this population.

  14. Spontaneous harm reduction: a barrier for substance-dependent individuals seeking treatment?

    Directory of Open Access Journals (Sweden)

    Fontanella Bruno José Barcellos

    2005-01-01

    Full Text Available OBJETIVE: Greater information regarding motivations and treatment barriers faced by substance-dependent individuals has clinical and public health implications. This study aimed to formulate hypotheses regarding psychological, social and family variables that can be constructed as motivations or subjective barriers for the early seeking of formal treatment. METHODS: A qualitative study was conducted in an intentional sample (selected through saturation and variety of types of 13 substance-dependent individuals who sought treatment. In-depth, semi-structured interviews were conducted using open questions, and the transcribed data were subjected to qualitative analysis. RESULTS: Four types of spontaneous harm reduction measures were identified, according to the subjective logic of each participant: having some periods at rest (not using and recovering from adverse effects; caretaking by close acquaintances (relatives, partners, drug dealers and alcoholic beverage sellers; selectivity regarding substance source, type and means of administration; establishing "healthy" limits of ingestion. CONCLUSIONS: The measures identified might represent barriers to the early seeking of treatment but might also represent spontaneous learning of abilities beneficial to future treatment. Health care professionals should take into consideration their existence and should address them in clinical settings. Issues representative of the formulated categories should be presented in structured questionnaires used in future quantitative studies of barriers to treatment in this population.

  15. Variation in opioid prescribing patterns between ED providers.

    Science.gov (United States)

    Smulowitz, Peter B; Cary, Chris; Boyle, Katherine L; Novack, Victor; Jagminas, Liudvikas

    2016-12-01

    Abuse of opioid prescription drugs has become an epidemic across the developed world. Despite the fact that emergency physicians overall account for a small proportion of total opioids prescribed, the number of prescriptions has risen dramatically in the past decade and, to some degree, contributes to the available supply of opioids in the community, some of which are diverted for non-medical use. Since successfully reducing opioid prescribing on the individual level first requires knowledge of current prescribing patterns, we sought to determine to what extent variation exists in opioid prescribing patterns at our institution. This was a single-institution observational study at a community hospital with an annual ED volume of 47,000 visits. We determined the number of prescriptions written by each provider, both total number and accounting for the number of patients seen. Our primary outcome measure was the level of variation at the physician level for number of prescriptions written per patient. We also identified the mean number of pills written per prescription. We analyzed data from November 13, 2014 through July 31, 2015 for 21 full-time providers. There were a total of 2211 prescriptions for opioids written over this time period for a total of 17,382 patients seen. On a per-patient basis, the rate of opioid prescriptions written per patient during this period was 127 per 1000 visits (95 % CI 122-132). There was a variation on the individual provider level, with rates ranging from 33 per to 332 per 1000 visits. There was also substantial variation by provider in the number of pills written per prescription with coefficient of variation (standard deviation divided by mean) averaged over different opioids ranging from 16 to 40 %. There was significant variation in opioid prescribing patterns at the individual physician level, even when accounting for the number of patients seen.

  16. Learning a novel phonological contrast depends on interactions between individual differences and training paradigm design.

    Science.gov (United States)

    Perrachione, Tyler K; Lee, Jiyeon; Ha, Louisa Y Y; Wong, Patrick C M

    2011-07-01

    Studies evaluating phonological contrast learning typically investigate either the predictiveness of specific pretraining aptitude measures or the efficacy of different instructional paradigms. However, little research considers how these factors interact--whether different students learn better from different types of instruction--and what the psychological basis for any interaction might be. The present study demonstrates that successfully learning a foreign-language phonological contrast for pitch depends on an interaction between individual differences in perceptual abilities and the design of the training paradigm. Training from stimuli with high acoustic-phonetic variability is generally thought to improve learning; however, we found high-variability training enhanced learning only for individuals with strong perceptual abilities. Learners with weaker perceptual abilities were actually impaired by high-variability training relative to a low-variability condition. A second experiment assessing variations on the high-variability training design determined that the property of this learning environment most detrimental to perceptually weak learners is the amount of trial-by-trial variability. Learners' perceptual limitations can thus override the benefits of high-variability training where trial-by-trial variability in other irrelevant acoustic-phonetic features obfuscates access to the target feature. These results demonstrate the importance of considering individual differences in pretraining aptitudes when evaluating the efficacy of any speech training paradigm. © 2011 Acoustical Society of America

  17. Progressive white matter microstructure damage in male chronic heroin dependent individuals: a DTI and TBSS study.

    Directory of Open Access Journals (Sweden)

    Yingwei Qiu

    Full Text Available BACKGROUND: To investigate the WM microstructure deficits in heroin dependent individuals (HDIs with different length of heroin dependence, and to investigate whether these WM deficits can be related to the duration of heroin use and to decision-making deficits in HDIs. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-six HDIs [including eighteen sHDIs (duration of heroin dependent is less than 10 years and eighteen lHDIs (duration of dependent is between 10:20 years] and sixteen healthy controls participated in this study. Whole brain voxel-wise analysis of fractional anisotropy (FA, mean diffusivity (MD, axial diffusivity (Da and radial diffusivity (Dr were performed by tract-based spatial statistics (TBSS to localize abnormal WM regions among groups. TBSS demonstrated that sHDIs had significantly lower FA than controls in right orbito-frontal WM, bilateral temporal WM and right parietal WM. The lHDIs had significantly lower FA throughout the brain compared with the controls and sHDIs. The lHDIs had significantly lower Da than controls in bilateral inferior frontaloccipital fasciculus, bilateral splenium of corpus callosum, left inferior longitudinal fasciculus, and had significantly higher Dr than controls in bilateral uncinatus fasciculus, bilateral inferior frontaloccipital fasciculus and bilateral cortical spinal fasciculus. Volume-of-interest (VOI analyses detect the changes of diffusivity indices in the regions with FA abnormalities revealed by control vs sHDIs. In most VOIs, FA reductions were caused by the increase in Dr as well as the decrease in Da. Correlation analysis was used to assess the relationship between FA and behavioral measures in HDIs and controls available. Significantly positively correlations were found between the FA values in the right orbital-frontal WM, right parietal WM and IGT performance. CONCLUSIONS: The extent and severity of WM integrity deficits in HDIs was associated with the length of heroin dependent. Furthermore

  18. Striatal μ-opioid receptor availability predicts cold pressor pain threshold in healthy human subjects

    DEFF Research Database (Denmark)

    Hagelberg, Nora; Aalto, Sargo; Tuominen, Lauri;

    2012-01-01

    Previous PET studies in healthy humans have shown that brain μ-opioid receptor activation during experimental pain is associated with reductions in the sensory and affective ratings of the individual pain experience. The aim of this study was to find out whether brain μ-opioid receptor binding...... at the resting state, in absence of painful stimulation, can be a long-term predictor of experimental pain sensitivity. We measured μ-opioid receptor binding potential (BP(ND)) with μ-opioid receptor selective radiotracer [(11)C]carfentanil and positron emission tomography (PET) in 12 healthy male subjects...... the potential associations between μ-opioid receptor BP(ND) and psychophysical measures. The results show that striatal μ-opioid receptor BP(ND) predicts cold pressor pain threshold, but not cold pressor pain tolerance or tactile sensitivity. This finding suggests that striatal μ-opioid receptor density...

  19. Management of opioid-dependent patients: comparison of the cost associated with use of buprenorphine/naloxone or methadone, and their interactions with concomitant treatments for infectious or psychiatric comorbidities.

    Science.gov (United States)

    Roncero, Carlos; Domínguez-Hernández, Raquel; Díaz, Tomás; Fernández, José Manuel; Forcada, Rafael; Martínez, José Manuel; Seijo, Pedro; Terán, Antonio; Oyagüez, Itziar

    2015-09-15

    The objective was to estimate the annual interaction management cost of agonist opioid treatment (AOT) for opioid-dependent (OD) patients with buprenorphine-naloxone (Suboxone®) (B/N) or methadone associated with concomitant treatments for infectious (HIV) or psychiatric comorbidities. A costs analysis model was developed to calculate the associated cost of AOT and interaction management. The AOT cost included pharmaceutical costs, drug preparation, distribution and dispensing, based on intake regimen (healthcare center or take-home) and type and frequency of dispensing (healthcare center or pharmacy), and medical visits. The cost of methadone also included single-dose bottles, monthly costs of custody at pharmacy, urine toxicology drug screenings and nursing visits. Potential interactions between AOT and concomitant treatments (antivirals, antibacterials/antifungals, antipsychotics, anxiolytics, antidepressant and anticonvulsants), were identified to determine the additional use of healthcare resources for each interaction management. The annual cost per patient of AOT was €1,525.97 for B/N and €1,467.29 for methadone. The average annual cost per patient of interaction management was €257.07 (infectious comorbidities), €114.03 (psychiatric comorbidities) and €185.55 (double comorbidity) with methadone and €7.90 with B/N in psychiatric comorbidities. Total annual costs of B/N were €1,525.97, €1,533.87 and €1,533.87 compared to €1,724.35, €1,581.32 and €1,652.84 for methadone per patient with infectious, psychiatric or double comorbidity respectively.Compared to methadone, the total cost per patient with OD was lower with B/N (€47.45-€198.38 per year). This is due to the differences in interaction management costs associated with the concomitant treatment of infectious and/or psychiatric comorbidities.

  20. Clinically employed opioid analgesics produce antinociception via μ-δ opioid receptor heteromers in Rhesus monkeys.

    Science.gov (United States)

    Yekkirala, Ajay S; Banks, Matthew L; Lunzer, Mary M; Negus, Stevens S; Rice, Kenner C; Portoghese, Philip S

    2012-09-19

    Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans.

  1. Individual Differences and State-Dependent Responses in Transcranial Direct Current Stimulation.

    Science.gov (United States)

    Hsu, Tzu-Yu; Juan, Chi-Hung; Tseng, Philip

    2016-01-01

    Transcranial direct current stimulation (tDCS) has been extensively used to examine whether neural activities can be selectively increased or decreased with manipulations of current polarity. Recently, the field has reevaluated the traditional anodal-increase and cathodal-decrease assumption due to the growing number of mixed findings that report the effects of the opposite directions. Therefore, the directionality of tDCS polarities and how it affects each individual still remain unclear. In this study, we used a visual working memory (VWM) paradigm and systematically manipulated tDCS polarities, types of different independent baseline measures, and task difficulty to investigate how these factors interact to determine the outcome effect of tDCS. We observed that only low-performers, as defined by their no-tDCS corsi block tapping (CBT) performance, persistently showed a decrement in VWM performance after anodal stimulation, whereas no tDCS effect was found when participants were divided by their performance in digit span. In addition, only the optimal level of task difficulty revealed any significant tDCS effect. All these findings were consistent across different blocks, suggesting that the tDCS effect was stable across a short period of time. Lastly, there was a high degree of intra-individual consistency in one's responsiveness to tDCS, namely that participants who showed positive or negative effect to anodal stimulation are also more likely to show the same direction of effects for cathodal stimulation. Together, these findings imply that tDCS effect is interactive and state dependent: task difficulty and consistent individual differences modulate one's responsiveness to tDCS, while researchers' choices of independent behavioral baseline measures can also critically affect how the effect of tDCS is evaluated. These factors together are likely the key contributors to the wide range of "noises" in tDCS effects between individuals, between stimulation protocols

  2. Opioid Therapy Pharmacogenomics for Noncancer Pain: Efficacy, Adverse Events, and Costs

    Directory of Open Access Journals (Sweden)

    Yan Xu

    2013-01-01

    Full Text Available Chronic non-cancer pain is a debilitating condition associated with high individual and societal costs. While opioid treatment for pain has been available for centuries, it is associated with high variability in outcome, and a considerable proportion of patients is unable to attain relief from symptoms while suffering adverse events and developing medication dependence. We performed a review of the efficacy of pharmacogenomic markers and their abilities to predict adverse events, dependence, and associated economic costs, focusing on two genes: OPRM1 and CYP2D6. Data sources were articles indexed by PubMed on or before August 6, 2013. Articles were first selected after review of their titles and abstracts, and full papers were read to confirm eligibility. Initially, fifty-two articles were identified. Of these, 17 were relevant to biological actions of pharmacogenomic markers and their effect on therapeutic efficacy, 16 to adverse events, 15 to opioid dependence, and eight to economic costs. In conclusion, increasing costs of opioid therapy have made the advances in pharmacogenomics an attractive solution to personalize care with unclear repercussions related to the impact on costs, morbidity, and outcomes. This intersection of pharmacoeconomics and pharmacogenomics presents a unique platform to further examine current advances in clinical medicine and their utility in cost-effective treatment of chronic pain.

  3. ACTIVATION AND INTERNALIZATION OF THE μ-OPIOID RECEPTOR BY THE NEWLY DISCOVERED ENDOGENOUS AGONISTS, ENDOMORPHIN-1 AND ENDOMORPHIN-2

    OpenAIRE

    McConalogue, K; Grady, E. F.; MINNIS, J.; Balestra, B; Tonini, M; Brecha, N C; Bunnett, N. W.; Sternini, C.

    1999-01-01

    The multiple effects of opiate alkaloids, important therapeutic drugs used for pain control, are mediated by the neuronal μ-opioid receptor. Among the side effects of these drugs is a profound impairment of gastrointestinal transit. Endomorphins are opioid peptides recently isolated from the nervous system, which have high affinity and selectivity for μ-opioid receptors. Since the μ-opioid receptor undergoes ligand-induced receptor endocytosis in an agonist-dependent manner, we compared the a...

  4. The evolution of vertebrate opioid receptors

    OpenAIRE

    Stevens, Craig W.

    2009-01-01

    The proteins that mediate the analgesic and other effects of opioid drugs and endogenous opioid peptides are known as opioid receptors. Opioid receptors consist of a family of four closely-related proteins belonging to the large superfamily of G-protein coupled receptors. The three types of opioid receptors shown unequivocally to mediate analgesia in animal models are the mu (MOR), delta (DOR), and kappa (KOR) opioid receptor proteins. The role of the fourth member of the opioid receptor fami...

  5. Prognostic factors in the development of opioid addiction

    Directory of Open Access Journals (Sweden)

    Vasila Talimbekova

    2011-04-01

    Full Text Available In 145 patients with opioid addiction were studied prognostic factors of the formation of the disease and their medical and social consequences. In the examined patients duration of the narcotization was from 1 year to 15 years. Analysis of studies showed that the most significant adverse prognostic factors, determining formation rate of medical and social consequences in opioid addiction, may include: perinatal pathology, personality deviation in the premorbid; early age of onset of drug use; hereditary load addictive and mental illness; condition of upbringing; alcohol abuse prior to narcotization; prescription of narcotization. These constitutionally-biological factors are informative indicators in the predicting the formation of opioid dependence.

  6. Opioid rotation: the science and the limitations of the equianalgesic dose table.

    Science.gov (United States)

    Knotkova, Helena; Fine, Perry G; Portenoy, Russell K

    2009-09-01

    Opioid rotation refers to a switch from one opioid to another in an effort to improve the response to analgesic therapy or reduce adverse effects. It is a common method to address the problem of poor opioid responsiveness despite optimal dose titration. Guidelines for opioid rotation are empirical and begin with the selection of a safe and reasonably effective starting dose for the new opioid, followed by dose adjustment to optimize the balance between analgesia and side effects. The selection of a starting dose must be based on an estimate of the relative potency between the existing opioid and the new one. Potency, which is defined as the dose required to produce a given effect, differs widely among opioids, and among individuals under varying conditions. To effectively rotate from one opioid to another, the new opioid must be started at a dose that will cause neither toxicity nor abstinence, and will be sufficiently efficacious in that pain is no worse than before the change. The estimate of relative potency used in calculating this starting dose has been codified on "equianalgesic dose tables," which historically have been based on the best science available and have been used with little modification for more than 40 years. These tables, and the clinical protocols used to apply them to opioid rotation, may need revision, however, as the science underlying relative potency evolves. Review of these issues informs the use of opioid rotation in the clinical setting and defines key areas for future research.

  7. Opioid shopping behavior: how often, how soon, which drugs, and what payment method.

    Science.gov (United States)

    Cepeda, M Soledad; Fife, Daniel; Chow, Wing; Mastrogiovanni, Gregory; Henderson, Scott C

    2013-01-01

    Doctor shopping (obtaining opioid prescriptions from multiple prescribers) is one example of opioid abuse and diversion. The authors assessed how soon shopping behavior was observed after opioid exposure, number of events per shopper, preferred opioids, and method of payment. This was a cohort study. Individuals with ≤1 dispensing for any opioid in 2008 were followed for 18 months. Shopping behavior was defined as ≤2 prescriptions by different prescribers with ≤1 day of overlap and filled at ≤3 pharmacies. Of 25,161,024 subjects, 0.30% exhibited shopping behavior. Opioid-experienced subjects were 13.7 times more likely to exhibit shopping behavior and had more shopping episodes than opioid-naive subjects. Time to first shopping event was 246.90 ± 163.61 days. Number of episodes was 2.74 ± 4.66. Most subjects with shopping behavior (55.27%) had 1 shopping episode, whereas 9.52% had ≤6 episodes; 88.99% had ≤4 prescribers. Subjects with shopping behavior filled schedule II opioids more often than subjects without shopping behavior (19.51% vs 10.89%) and more often paid in cash (44.85% vs 18.54%). Three of 1000 people exposed to opioids exhibit shopping behavior, on average, 8 months after exposure. Opioid shoppers seek strong opioids, avoid combination products, often pay cash, and obtain prescriptions from few prescribers. © 2012 The Author(s).

  8. Improving personality/character traits in individuals with alcohol dependence: the influence of mindfulness-oriented meditation.

    Science.gov (United States)

    Crescentini, Cristiano; Matiz, Alessio; Fabbro, Franco

    2015-01-01

    The study of personality is critical to enhance current knowledge of the psychological characteristics of alcohol dependence. Recent evidence shows that mindfulness-oriented meditation positively influences healthy individuals' character. Here, it was assessed whether 8-week mindfulness-oriented meditation promotes similar changes in a group of alcohol-dependent individuals. A control group with alcohol dependence was also tested. Mindfulness-oriented meditation participants showed an increase in the character scores of the temperament and character inventory together with reduced risks of relapse. These longitudinal data highlight the importance of assessing personality in alcohol-dependent individuals and support the utility of therapeutic interventions for alcohol dependence aimed at enhancing individuals' character.

  9. Individual whey protein components influence lipid oxidation dependent on pH

    DEFF Research Database (Denmark)

    Horn, Anna Frisenfeldt; Nielsen, Nina Skall; Jacobsen, Charlotte

    amounts of the two. Emulsions were prepared at pH4 and pH7. Emulsions were characterized by their droplet sizes, viscosities, and contents of proteins in the water phase. Lipid oxidation was assessed by PV and secondary volatile oxidation products. Results showed that pH greatly influenced the oxidative......In emulsions, lipid oxidation is expected to be initiated at the oil-water interface. The properties of the emulsifier used and the composition at the interface is therefore expected to be of great importance for the resulting oxidation. Previous studies have shown that individual whey protein...... components (α-lactalbumin and β-lactoglobulin) adsorb differently to the interface depending on pH. In addition, differences has been shown to exists between the oxidative stability provided by α-lactalbumin and β-lactoglobulin. The hypothesis is that pH influences the oxidative stability of emulsions...

  10. Multifunctional and context-dependent control of vocal acoustics by individual muscles

    DEFF Research Database (Denmark)

    Srivastava, Kyle H; Elemans, Coen P H; Sober, Samuel J

    2015-01-01

    The relationship between muscle activity and behavioral output determines how the brain controls and modifies complex skills. In vocal control, ensembles of muscles are used to precisely tune single acoustic parameters such as fundamental frequency and sound amplitude. If individual vocal muscles...... a context-dependent scheme would require the brain to calculate different motor modifications in each case. We tested the hypothesis that single muscles control multiple acoustic parameters and that the function of single muscles varies across gestures using three complementary approaches. First, we...... recorded electromyographic data from vocal muscles in singing Bengalese finches. Second, we electrically perturbed the activity of single muscles during song. Third, we developed an ex vivo technique to analyze the biomechanical and acoustic consequences of single-muscle perturbations. We found that single...

  11. Temperature dependence of the emission spectra of individual self-assembled quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Zora, A; Simserides, C; Triberis, G P, E-mail: azora@phys.uoa.g [University of Athens, Physics Department, Panepistimiopolis, Zografos, GR-15784, Athens (Greece)

    2010-09-01

    We have developed a quantum-mechanical theory for the interaction of light and electron-hole excitations in semiconductor quantum dots. Our theoretical analysis results in an expression for the photoluminescence intensity in the non-linear regime. The validity of the theoretical results is tested analyzing experimental data reported for the temperature dependence of the emission spectra of an individual lens-shaped In{sub 0.4}Ga{sub 0.6}As self-assembled quantum dot in a wide temperature range up to 300 K. Our theoretical predictions for the redshift of the emission peak with increasing temperature, in the range 2-300 K, agree with the experiment.

  12. A population-based cohort study on chronic pain: the role of opioids

    DEFF Research Database (Denmark)

    Sjøgren, Per; Grønbæk, Morten; Peuckmann, Vera

    2010-01-01

    . In addition, use of strong opioids was associated with poor health-related quality of life. Furthermore, the results indicated that individuals with chronic pain using strong opioids pain had a higher risk of death than individuals without chronic pain (HR: 1.67; 95% CI: 1.03-2.70). However, this study cannot...

  13. Intraoperative Use of Remifentanil and Opioid Induced Hyperalgesia/Acute Opioid Tolerance - Systematic review

    Directory of Open Access Journals (Sweden)

    Sang Hun eKim

    2014-05-01

    Full Text Available IntroductionThe use of opioids has been increasing in operating room and intensive care unit to provide perioperative analgesia as well as stable hemodynamics. However, many authors have suggested that the use of opioids is associated with the expression of acute opioid tolerance (AOT and opioid-induced hyperalgesia (OIH in experimental studies and clinical observations in dose and/or time dependent exposure even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management during anesthesia as well as in the intensive care units because of its rapid onset and offset. ObjectivesSearch of the available literature to assess remifentanil AOT and OIH based on available published data.MethodsWe reviewed articles analyzing remifentanil AOT and OIH, and focused our literature search on evidence based information. Experimental and clinical studies were identified using electronic searches of Medline (PubMed, Ovid, Springer, and Elsevier, ClinicalKey. ResultsOur results showed that the development of remifentanil AOT and OIH is a clinically significant phenomenon requiring further research.Discussions and ConclusionsAOT - defined as an increase in the required opioid dose to maintain adequate analgesia, and OIH - defined as decreased pain threshold, should be suspected with any unexplained pain report unassociated with the disease progression.The clinical significance of these findings was evaluated taking into account multiple methodological issues including the dose and duration of opioids administration, the different infusion mode, the co-administrated anesthetic drug’s effect, method assessing pain sensitivity, and the repetitive and potentially tissue damaging nature of the stimuli used to determine the threshold during opioid infusion.Future studies need to investigate the contribution of remifentanil induced hyperalgesia to chronic pain and the role of pharmacological modulation to reverse this process.

  14. The association of psychedelic use and opioid use disorders among illicit users in the United States.

    Science.gov (United States)

    Pisano, Vincent D; Putnam, Nathaniel P; Kramer, Hannah M; Franciotti, Kevin J; Halpern, John H; Holden, Selma C

    2017-05-01

    Preliminary studies show psychedelic compounds administered with psychotherapy are potentially effective and durable substance misuse interventions. However, little is known about the association between psychedelic use and substance misuse in the general population. This study investigated the association between psychedelic use and past year opioid use disorders within illicit opioid users. While controlling for socio-demographic covariates and the use of other substances, the relationship between classic psychedelic use and past year opioid use disorders was analyzed within 44,000 illicit opioid users who completed the National Survey on Drug Use and Health from 2008 to 2013. Among respondents with a history of illicit opioid use, psychedelic drug use is associated with 27% reduced risk of past year opioid dependence (weighted risk ratio = 0.73 (0.60-0.89) p = 0.002) and 40% reduced risk of past year opioid abuse (weighted risk ratio = 0.60 (0.41-0.86) p = 0.006). Other than marijuana use, which was associated with 55% reduced risk of past year opioid abuse (weighted risk ratio = 0.45 (0.30-0.66) p psychedelic drugs is associated with decreased risk of opioid abuse and dependence. Conversely, other illicit drug use history is largely associated with increased risk of opioid abuse and dependence. These findings suggest that psychedelics are associated with positive psychological characteristics and are consistent with prior reports suggesting efficacy in treatment of substance use disorders.

  15. Dietary methyl content regulates opioid responses in mice

    Directory of Open Access Journals (Sweden)

    Liang DY

    2013-03-01

    Full Text Available De-Yong Liang,1,2 Yuan Sun,1,2 J David Clark1,2 1Department of Anesthesiology, Veterans Affairs Palo Alto Health Care System, Palo Alto, 2Stanford University School of Medicine, Stanford, CA, USA Background: Large interindividual differences in clinical responses to opioids and the variable susceptibility to abuse of this class of drugs make their use problematic. We lack a full understanding of the factors responsible for these differences. Dietary factors including methyl donor content have been noted to alter multiple physiological and behavioral characteristics of laboratory animals. The purpose of this research was to determine the effects of dietary methyl donor content on opioid responses in mice. Methods: Groups of male C57BL/6J mice were treated with high and low methyl donor diets either in the perinatal period or after weaning. Analgesic responses to morphine, as well as tolerance, opioid-induced hyperalgesia, and physical dependence were assessed. Results: Mice fed high and low methyl donor diets showed equal weight gain over the course of the experiments. Exposure to a high methyl donor diet in the perinatal period enhanced physical dependence. Dietary methyl donor content also altered analgesic responses to low doses of morphine when the dietary treatments were given to the mice after weaning. Opioid-induced hyperalgesia was unaltered by dietary methyl donor content. Conclusion: High and low methyl donor diet treatment has selective effects on opioid responses depending on the timing of exposure. These findings suggest that examination of DNA methylation patterns in specific brain regions linked to opioid analgesia and dependence may provide specific explanations for dietary effects on opioid responses. Keywords: opioid, methylation, tolerance, hyperalgesia, dependence

  16. Fe biomineralization mirrors individual metabolic activity in a nitrate-dependent Fe(II-oxidizer

    Directory of Open Access Journals (Sweden)

    Jennyfer eMIOT

    2015-09-01

    Full Text Available Microbial biomineralization sometimes leads to periplasmic encrustation, which is predicted to enhance microorganism preservation in the fossil record. Mineral precipitation within the periplasm is however thought to induce death, as a result of permeability loss preventing nutrient and waste transit across the cell wall. This hypothesis had however never been investigated down to the single cell level. Here, we cultured the nitrate reducing Fe(II oxidizing bacteria Acidovorax sp. strain BoFeN1 that have been previously shown to promote the precipitation of a diversity of Fe minerals (lepidocrocite, goethite, Fe phosphate encrusting the periplasm. We investigated the connection of Fe biomineralization with carbon assimilation at the single cell level, using a combination of electron microscopy and Nano-Secondary Ion Mass Spectrometry (NanoSIMS. Our analyses revealed strong individual heterogeneities of Fe biomineralization. Noteworthy, a small proportion of cells remaining free of any precipitate persisted even at advanced stages of biomineralization. Using pulse chase experiments with 13C-acetate, we provide evidences of individual phenotypic heterogeneities of carbon assimilation, correlated with the level of Fe biomineralization. Whereas non- and moderately encrusted cells were able to assimilate acetate, higher levels of periplasm encrustation prevented any carbon incorporation. Carbon assimilation only depended on the level of Fe encrustation and not on the nature of Fe minerals precipitated in the cell wall. Carbon assimilation decreased exponentially with increasing cell-associated Fe content. Persistence of a small proportion of non-mineralized and metabolically active cells might constitute a strategy of survival in highly ferruginous environments. Eventually, our results suggest that periplasmic Fe biomineralization may provide a signature of individual metabolic status, which could be looked for in the fossil record and in modern

  17. Fe biomineralization mirrors individual metabolic activity in a nitrate-dependent Fe(II)-oxidizer

    Science.gov (United States)

    Miot, Jennyfer; Remusat, Laurent; Duprat, Elodie; Gonzalez, Adriana; Pont, Sylvain; Poinsot, Mélanie

    2015-01-01

    Microbial biomineralization sometimes leads to periplasmic encrustation, which is predicted to enhance microorganism preservation in the fossil record. Mineral precipitation within the periplasm is, however, thought to induce death, as a result of permeability loss preventing nutrient and waste transit across the cell wall. This hypothesis had, however, never been investigated down to the single cell level. Here, we cultured the nitrate reducing Fe(II) oxidizing bacteria Acidovorax sp. strain BoFeN1 that have been previously shown to promote the precipitation of a diversity of Fe minerals (lepidocrocite, goethite, Fe phosphate) encrusting the periplasm. We investigated the connection of Fe biomineralization with carbon assimilation at the single cell level, using a combination of electron microscopy and Nano-Secondary Ion Mass Spectrometry. Our analyses revealed strong individual heterogeneities of Fe biomineralization. Noteworthy, a small proportion of cells remaining free of any precipitate persisted even at advanced stages of biomineralization. Using pulse chase experiments with 13C-acetate, we provide evidence of individual phenotypic heterogeneities of carbon assimilation, correlated with the level of Fe biomineralization. Whereas non- and moderately encrusted cells were able to assimilate acetate, higher levels of periplasmic encrustation prevented any carbon incorporation. Carbon assimilation only depended on the level of Fe encrustation and not on the nature of Fe minerals precipitated in the cell wall. Carbon assimilation decreased exponentially with increasing cell-associated Fe content. Persistence of a small proportion of non-mineralized and metabolically active cells might constitute a survival strategy in highly ferruginous environments. Eventually, our results suggest that periplasmic Fe biomineralization may provide a signature of individual metabolic status, which could be looked for in the fossil record and in modern environmental samples. PMID

  18. Laboratory testing for prescription opioids.

    Science.gov (United States)

    Milone, Michael C

    2012-12-01

    Opioid analgesic misuse has risen significantly over the past two decades, and these drugs now represent the most commonly abused class of prescription medications. They are a major cause of poisoning deaths in the USA exceeding heroin and cocaine. Laboratory testing plays a role in the detection of opioid misuse and the evaluation of patients with opioid intoxication. Laboratories use both immunoassay and chromatographic methods (e.g., liquid chromatography with mass spectrometry detection), often in combination, to yield high detection sensitivity and drug specificity. Testing methods for opioids originated in the workplace-testing arena and focused on detection of illicit heroin use. Analysis for a wide range of opioids is now required in the context of the prescription opioid epidemic. Testing methods have also been primarily based upon urine screening; however, methods for analyzing alternative samples such as saliva, sweat, and hair are available. Application of testing to monitor prescription opioid drug therapy is an increasingly important use of drug testing, and this area of testing introduces new interpretative challenges. In particular, drug metabolism may transform one clinically available opioid into another. The sensitivity of testing methods also varies considerably across the spectrum of opioid drugs. An understanding of opioid metabolism and method sensitivity towards different opioid drugs is therefore essential to effective use of these tests. Improved testing algorithms and more research into the effective use of drug testing in the clinical setting, particularly in pain medicine and substance abuse, are needed.

  19. State-dependent modulation of functional connectivity in early blind individuals.

    Science.gov (United States)

    Pelland, Maxime; Orban, Pierre; Dansereau, Christian; Lepore, Franco; Bellec, Pierre; Collignon, Olivier

    2017-02-15

    Resting-state functional connectivity (RSFC) studies have provided strong evidences that visual deprivation influences the brain's functional architecture. In particular, reduced RSFC coupling between occipital (visual) and temporal (auditory) regions has been reliably observed in early blind individuals (EB) at rest. In contrast, task-dependent activation studies have repeatedly demonstrated enhanced co-activation and connectivity of occipital and temporal regions during auditory processing in EB. To investigate this apparent discrepancy, the functional coupling between temporal and occipital networks at rest was directly compared to that of an auditory task in both EB and sighted controls (SC). Functional brain clusters shared across groups and cognitive states (rest and auditory task) were defined. In EBs, we observed higher occipito-temporal correlations in activity during the task than at rest. The reverse pattern was observed in SC. We also observed higher temporal variability of occipito-temporal RSFC in EB suggesting that occipital regions in this population may play the role of a multiple demand system. Our study reveals how the connectivity profile of sighted and early blind people is differentially influenced by their cognitive state, bridging the gap between previous task-dependent and RSFC studies. Our results also highlight how inferring group-differences in functional brain architecture solely based on resting-state acquisition has to be considered with caution.

  20. Multifunctional and Context-Dependent Control of Vocal Acoustics by Individual Muscles.

    Science.gov (United States)

    Srivastava, Kyle H; Elemans, Coen P H; Sober, Samuel J

    2015-10-21

    The relationship between muscle activity and behavioral output determines how the brain controls and modifies complex skills. In vocal control, ensembles of muscles are used to precisely tune single acoustic parameters such as fundamental frequency and sound amplitude. If individual vocal muscles were dedicated to the control of single parameters, then the brain could control each parameter independently by modulating the appropriate muscle or muscles. Alternatively, if each muscle influenced multiple parameters, a more complex control strategy would be required to selectively modulate a single parameter. Additionally, it is unknown whether the function of single muscles is fixed or varies across different vocal gestures. A fixed relationship would allow the brain to use the same changes in muscle activation to, for example, increase the fundamental frequency of different vocal gestures, whereas a context-dependent scheme would require the brain to calculate different motor modifications in each case. We tested the hypothesis that single muscles control multiple acoustic parameters and that the function of single muscles varies across gestures using three complementary approaches. First, we recorded electromyographic data from vocal muscles in singing Bengalese finches. Second, we electrically perturbed the activity of single muscles during song. Third, we developed an ex vivo technique to analyze the biomechanical and acoustic consequences of single-muscle perturbations. We found that single muscles drive changes in multiple parameters and that the function of single muscles differs across vocal gestures, suggesting that the brain uses a complex, gesture-dependent control scheme to regulate vocal output.

  1. Diameter-dependent bending modulus of individual multiwall boron nitride nanotubes.

    Science.gov (United States)

    Tanur, Adrienne E; Wang, Jiesheng; Reddy, Arava L M; Lamont, Daniel N; Yap, Yoke Khin; Walker, Gilbert C

    2013-04-25

    The mechanical properties of individual multiwall boron nitride nanotubes (MWBNNTs) synthesized by a growth-vapor-trapping chemical vapor deposition method are investigated by a three-point bending technique via atomic force microscopy. Multiple locations on suspended tubes are probed in order to determine the boundary conditions of the supported tube ends. The bending moduli (EB) calculated for 20 tubes with diameters ranging from 18 to 58 nm confirm the exceptional mechanical properties of MWBNNTs, with an average EB of 760 ± 30 GPa. For the first time, the bending moduli of MWBNNTs are observed to increase with decreasing diameter, ranging from 100 ± 20 GPa to as high as 1800 ± 300 GPa. This diameter dependence is evaluated by Timoshenko beam theory. The Young's modulus and shear modulus were determined to be 1800 ± 300 and 7 ± 1 GPa, respectively, for a trimmed data set of 16 tubes. The low shear modulus of MWBNNTs is the reason for the detected diameter-dependent bending modulus and is likely due to the presence of interwall shearing between the crystalline and faceted helical nanotube structures of MWBNNTs.

  2. The Useage of Opioids and their Adverse Effects in Gastrointestinal Practice: A Review

    Science.gov (United States)

    Khansari, MahmoudReza; Sohrabi, MasourReza; Zamani, Farhad

    2013-01-01

    Opium is one of the oldest herbal medicines currently used as an analgesic, sedative and antidiarrheal treatment. The effects of opium are principally mediated by the μ-, κ- and δ-opioid receptors. Opioid substances consist of all natural and synthetic alkaloids that are derived from opium. Most of their effects on gastrointestinal motility and secretion result from suppression of neural activity. Inhibition of gastric emptying, increase in sphincter tone, changes in motor patterns, and blockage of peristalsis result from opioid use. Common adverse effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, dependency and tolerance, and respiratory depression. The most common adverse effect of opioid use is constipation. Although stool softeners are frequently used to decrease opioid-induced bowel dysfunction, however they are not efficacious. Possibly, the use of specific opioid receptor antagonists is a more suitable approach. Opioid antagonists, both central and peripheral, could affect gastrointestinal function and visceromotor sensitivity, which suggests an important role for endogenous opioid peptides in the control of gastrointestinal physiology. Underlying diseases or medications known to influence the central nervous system (CNS) often accelerate the opioid’s adverse effects. However, changing the opioid and/or route of administration could also decrease their adverse effects. Appropriate patient selection, patient education and discussion regarding potential adverse effects may assist physicians in maximizing the effectiveness of opioids, while reducing the number and severity of adverse effects. PMID:24829664

  3. Opioid Antagonist Impedes Exposure.

    Science.gov (United States)

    Merluzzi, Thomas V.; And Others

    1991-01-01

    Thirty spider-phobic adults underwent exposure to 17 phobic-related, graded performance tests. Fifteen subjects were assigned to naltrexone, an opioid antagonist, and 15 were assigned to placebo. Naltrexone had a significant effect on exposure, with naltrexone subjects taking significantly longer to complete first 10 steps of exposure and with…

  4. Opioid Prescribing PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2017-07-06

    This 60 second public service announcement is based on the July 2017 CDC Vital Signs report. Higher opioid prescribing puts patients at risk for addiction and overdose. Learn what can be done about this serious problem.  Created: 7/6/2017 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/6/2017.

  5. Clinical interpretation of opioid tolerance versus opioid-induced hyperalgesia.

    Science.gov (United States)

    Chen, Lucy; Sein, Michael; Vo, Trang; Amhmed, Shihab; Zhang, Yi; Hilaire, Kristin St; Houghton, Mary; Mao, Jianren

    2014-01-01

    Opioid analgesics are commonly used to manage moderate to severe pain. However, the long-term use of opioids could lead to opioid tolerance (OT) and opioid-induced hyperalgesia (OIH). Distinguishing OIH from OT would impact the practice of opioid therapy because opioid dose adjustment may differentially influence OT and OIH. Currently, there are no standard criteria of OT versus OIH causing considerable ambiguity in clinical interpretation and management of these conditions. The authors designed a practitioner-based survey consisting of 20 targeted questions. Answering these questions would require responders' actual clinical experiences with opioid therapy. The survey was conducted between 2011 and 2012 through direct mails or e-mails to 1,408 physicians who are currently practicing in the United States. The authors find that certain clinical characteristics (eg, increased pain despite opioid dose escalation) are often used by practitioners to make differential diagnosis of OT and OIH despite some overlap in their clinical presentation. A key difference in clinical outcome is that OT and OIH could be improved and exacerbated by opioid dose escalation, respectively. Our survey results revealed a significant knowledge gap in some responders regarding differential diagnosis and management of OT and OIH. The results also identified several issues, such as opioid dose adjustment and clinical comorbidities related to OT and OIH, which require future patient-based studies.

  6. Role of opioid receptors in the reinstatement of opioid-seeking behavior: an overview.

    Science.gov (United States)

    Fattore, Liana; Fadda, Paola; Antinori, Silvia; Fratta, Walter

    2015-01-01

    Opioid abuse in humans is characterized by discontinuous periods of drug use and abstinence. With time, the probability of falling into renewed drug consumption becomes particularly high and constitutes a considerable problem in the management of heroin addicts. The major problem in the treatment of opioid dependence still remains the occurrence of relapse, to which stressful life events, renewed use of heroin, and exposure to drug-associated environmental cues are all positively correlated. To study the neurobiology of relapse, many research groups currently use the reinstatement animal model, which greatly contributed to disentangle the mechanisms underlying relapse to drug-seeking in laboratory animals. The use of this model is becoming increasingly popular worldwide, and new versions have been recently developed to better appreciate the differential contribution of each opioid receptor subtype to the relapse phenomenon. In this chapter we review the state of the art of our knowledge on the specific role of the opioid receptors as unrevealed by the reinstatement animal model of opioid-seeking behavior.

  7. The Effect of a Payer-Mandated Decrease in Buprenorphine Dose on Aberrant Drug Tests and Treatment Retention Among Patients with Opioid Dependence.

    Science.gov (United States)

    Accurso, Anthony J; Rastegar, Darius A

    2016-02-01

    The optimal dose for office-based buprenorphine therapy is not known. This study reports on the effect of a change in payer policy, in which the insurer of a subset of patients in an office-based practice imposed a maximum sublingual buprenorphine dose of 16 mg/day, thereby forcing those patients on higher daily doses to decrease their dose. This situation created conditions for a natural experiment, in which treatment outcomes for patients experiencing this dose decrease could be compared to patients with other insurance who were not challenged with a dose decrease. Subjects were 297 patients with opioid use disorder in a primary care practice who were prescribed buprenorphine continuously for at least 3 months. Medical records were retrospectively reviewed for urine drug test results and treatment retention. Rates of aberrant urine drug tests were calculated in the period before the dose decrease and compared to rate after it with patients serving as their own controls. Comparison groups were formed from patients with the same insurance on buprenorphine doses of 16 mg/day or lower, patients with different insurance on 16 mg/day or lower, and patients with different insurance on greater than 16 mg/day. Rates of aberrant drug tests and treatment retention of patients on 16 mg/day or less of buprenorphine were compared to that of patients on higher daily doses. The rate of aberrant urine drug tests among patients who experienced a dose decrease rose from 27.5% to 34.2% (p=0.043). No comparison group showed any significant change in aberrant drug test rates. Moreover, all groups who were prescribed buprenorphine doses greater than 16 mg/day displayed lower rates of aberrant urine drug tests than groups prescribed lower doses. Retention in treatment was also highest among those prescribed greater than 16 mg/day (100% vs. 86.8%, 90.1%, and 84.4% p=0.010). An imposed buprenorphine dose decrease was associated with an increase in aberrant drug tests. Patients in a

  8. Opioid regulation of Pavlovian overshadowing in fear conditioning.

    Science.gov (United States)

    Zelikowsky, Moriel; Fanselow, Michael S

    2010-08-01

    In Pavlovian overshadowing, a stimulus that predicts a biologically important event reduces conditioning to another, equally predictive stimulus. We tested the effects of an opioid antagonist and dopamine agonist on the ability of a salient white noise to overshadow a less salient light. Rats were conditioned to fear a light or a noise-light compound using a mild footshock. Compound-conditioned rats trained under the saline vehicle revealed significant overshadowing of the light by the noise. This overshadowing effect was significantly attenuated in rats trained under the opioid antagonist naltrexone, consistent with an opioid-mediated negative feedback model of conditioning. In line with predictions made by negative feedback-type models, we failed to obtain overshadowing with few trials, suggesting that the processes underlying conditioning during initial trials do not contribute to the opioid-dependent Pavlovian overshadowing obtained in our preparation. Lastly, we compared the involvement of dopamine-mediated and opioid-mediated processes in overshadowing by conditioning rats under the partial dopamine D1 receptor agonist SKF 38393 or the opioid antagonist naltrexone. Both naltrexone and SKF 38393 were found to attenuate overshadowing; however, the behavioral profiles produced by each pharmacological manipulation were distinct. Collectively, these studies demonstrate an important role for both opioid- and dopamine-mediated processes in multiple-trial overshadowing.

  9. Complications of long-term opioid therapy for management of chronic pain: the paradox of opioid-induced hyperalgesia.

    Science.gov (United States)

    Brush, D Eric

    2012-12-01

    While opioids remain a valid and effective analgesic strategy for patients suffering from a wide variety of painful conditions, they are not a panacea. Increasingly, physicians must balance patient expectations of adequate pain control with known limitations of opioid pharmaceuticals including adverse effects, tolerance, addiction, withdrawal, and drug diversion. Further complicating the issue over the last decade is a growing body of evidence suggesting chronic opioid use may unexpectedly worsen the perception of pain in some individuals. This syndrome, termed opioid-induced hyperalgesia (OIH), fundamentally changes our understanding of opioid pharmacodynamics and may influence our approach to management of chronic pain. This manuscript describes the concept OIH and provides an overview of basic science and clinical research to date attempting to characterize this syndrome, as well as ascertain its clinical relevance. The potential existence of OIH in humans is framed within the context of our current understanding of opioids and our prescribing patterns so that physicians may begin to incorporate these ideas into their philosophy of pain management as further information develops. Animal studies reliably validate OIH in controlled models. Rigorous research protocols in humans are lacking, and we cannot yet confidently conclude that OIH manifests in clinically significant ways. However, clinicians should consider the possibility of OIH when evaluating outcomes of patients on chronic opioid therapy.

  10. Unused opioid analgesics and drug disposal following outpatient dental surgery: A randomized controlled trial.

    Science.gov (United States)

    Maughan, Brandon C; Hersh, Elliot V; Shofer, Frances S; Wanner, Kathryn J; Archer, Elizabeth; Carrasco, Lee R; Rhodes, Karin V

    2016-11-01

    Individuals who abuse prescription opioids often use leftover pills that were prescribed for friends or family members. Dental surgery has been identified as a common source of opioid prescriptions. We measured rates of used and unused opioids after dental surgery for a pilot program to promote safe drug disposal. We conducted a randomized controlled trial of opioid use patterns among patients undergoing surgical tooth extraction at a university-affiliated oral surgery practice. The primary objective was to describe opioid prescribing and consumption patterns, with the number of unused opioid pills remaining on postoperative day 21 serving as the primary outcome. The secondary aim was to measure the effect of a behavioral intervention (informing patients of a pharmacy-based opioid disposal program) on the proportion of patients who disposed or reported intent to dispose of unused opioids. (NCT02814305) Results: We enrolled 79 patients, of whom 72 filled opioid prescriptions. On average, patients received 28 opioid pills and had 15 pills (54%) left over, for a total of 1010 unused pills among the cohort. The behavioral intervention was associated with a 22% absolute increase in the proportion of patients who disposed or reported intent to dispose of unused opioids (Fisher's exact p=0.11). Fifty-four percent of opioids prescribed in this pilot study were not used. The pharmacy-based drug disposal intervention showed a robust effect size but did not achieve statistical significance. Dentists and oral surgeons could potentially reduce opioid diversion by moderately reducing the quantity of opioid analgesics prescribed after surgery. Copyright © 2016. Published by Elsevier Ireland Ltd.

  11. Advances in the treatment of opioid use disorders

    Science.gov (United States)

    Woody, George E.

    2017-01-01

    The development of medications for treating persons with opioid use disorders has expanded the number of evidence-based treatment options, particularly for persons with the most severe disorders. It has also improved outcomes compared to psychosocial treatment alone and expanded treatment availability by increasing the number of physicians involved in treatment and the settings where patients can be treated. The medications include methadone, buprenorphine, buprenorphine/naloxone, and extended-release injectable naltrexone. Studies have shown that they are most effective when used over an extended, but as-yet-unspecified, period of time and with counseling and other services, particularly for the many with psychosocial problems. Though controversial in some cultures, well-designed studies in Switzerland, the Netherlands, Germany, and Canada have demonstrated the efficacy of supervised heroin injecting for persons who responded poorly to other treatments, and this treatment option has been approved by Switzerland and a few other E.U. countries. The degree to which medication-assisted therapies are available is dependent on many variables, including national and local regulations, preferences of individual providers and their geographical location, treatment costs, and insurance policies. Greater availability of medication-assisted therapies has become a major focus in the U.S. and Canada, where there has been a marked increase in deaths associated with heroin and prescription opioid use. This paper provides a brief summary of these developments. PMID:28184294

  12. Opioid activation of Toll-Like receptor 4 contributes to drug reinforcement

    OpenAIRE

    Hutchinson, M R; Northcutt, A.L.; Hiranita, T.; WANG, X; Lewis, S.; Thomas, J.; van Steeg, K.; Kopajtic, T.A.; L. Loram; Sfregola, C.; Galer, E.; Miles, N.E.; Bland, S.T.; AMAT, J.; Rozeske, R.R.

    2012-01-01

    Opioid action was thought to exert reinforcing effects solely via the initial agonism of opioid receptors. Here we present evidence for an additional novel contributor to opioid reward: the innate immune pattern-recognition receptor, Toll-like receptor 4 (TLR4), and its MyD88-dependent signaling. Blockade of TLR4/MD2 by administration of the non-opioid, unnatural isomer of naloxone, (+)-naloxone (rats), or two independent genetic knockouts of MyD88-TLR4-dependent signaling (mice), suppressed ...

  13. Cortisol-dependent stress effects on cell distribution in healthy individuals and individuals suffering from chronic adrenal insufficiency.

    Science.gov (United States)

    Geiger, Ashley M; Pitts, Kenneth P; Feldkamp, Joachim; Kirschbaum, Clemens; Wolf, Jutta M

    2015-11-01

    Chronic adrenal insufficiency (CAI) is characterized by a lack of glucocorticoid and mineralocorticoid production due to destroyed adrenal cortex cells. However, elevated cortisol secretion is thought to be a central part in a well-orchestrated immune response to stress. This raises the question to what extent lack of cortisol in CAI affects stress-related changes in immune processes. To address this question, 28 CAI patients (20 females) and 18 healthy individuals (11 females) (age: 44.3 ± 8.4 years) were exposed to a psychosocial stress test (Trier Social Stress Test: TSST). Half the patients received a 0.03 mg/kg body weight injection of hydrocortisone (HC) post-TSST to mimic a healthy cortisol stress response. Catecholamines and immune cell composition were assessed in peripheral blood and free cortisol measured in saliva collected before and repeatedly after TSST. CAI patients showed norepinephrine (NE) stress responses similar to healthy participants, however, epinephrine (E) as well as cortisol levels were significantly lower. HC treatment post-TSST resulted in cortisol increases comparable to those observed in healthy participants (interaction effects--NE: F=1.05, p=.41; E: F=2.56, p=.045; cortisol: F=13.28, pcortisol's central involvement in post-stress lymphocyte migration from blood into immune-relevant body compartments. As such, future studies should investigate whether psychosocial stress exposure may put CAI patients at an increased health risk due to attenuated immune responses to pathogens.

  14. Cingulate cortex functional connectivity predicts future relapse in alcohol dependent individuals

    Directory of Open Access Journals (Sweden)

    Yasmin Zakiniaeiz

    2017-01-01

    Full Text Available Alcohol dependence is a chronic relapsing illness. Alcohol and stress cues have consistently been shown to increase craving and relapse risk in recovering alcohol dependent (AUD patients. However, differences in functional connectivity in response to these cues have not been studied using data-driven approaches. Here, voxel-wise connectivity is used in a whole-brain investigation of functional connectivity differences associated with alcohol and stress cues and to examine whether these differences are related to subsequent relapse. In Study 1, 45, 4- to 8-week abstinent, recovering AUD patients underwent functional magnetic resonance imaging during individualized imagery of alcohol, stress, and neutral cues. Relapse measures were collected prospectively for 90 days post-discharge from inpatient treatment. AUD patients showed blunted anterior (ACC, mid (MCC and posterior cingulate cortex (PCC, voxel-wise connectivity responses to stress compared to neutral cues and blunted PCC response to alcohol compared to neutral cues. Using Cox proportional hazard regression, weaker connectivity in ACC and MCC during neutral exposure was associated with longer time to relapse (better recovery outcome. Similarly, greater connectivity in PCC during alcohol-cue compared to stress cue was associated with longer time to relapse. In Study 2, a sub-group of 30 AUD patients were demographically-matched to 30 healthy control (HC participants for group comparisons. AUD compared to HC participants showed reduced cingulate connectivity during alcohol and stress cues. Using novel data-driven approaches, the cingulate cortex emerged as a key region in the disruption of functional connectivity during alcohol and stress-cue processing in AUD patients and as a marker of subsequent alcohol relapse.

  15. Managing Opioid Abuse in Older Adults: Clinical Considerations and Challenges.

    Science.gov (United States)

    Loreck, David; Brandt, Nicole J; DiPaula, Bethany

    2016-04-01

    Opioid use disorder is a public health epidemic. There is increasing attention being given to opioid abuse and overdose in the United States. The overall use of illicit substances by older adults is on the rise and in part can be attributed to the aging of Baby Boomers. Furthermore, much attention is being given to prescription opioid drug overdose, but it is important to note that heroin-related deaths have also increased sharply. Heroin use is part of a larger substance abuse problem, with more than nine in 10 individuals who use heroin also using at least one other drug (e.g., cocaine, prescription opioid medication). The current article highlights treatment approaches, namely buprenorphine, buprenorphine/naloxone, and naltrexone; insurance considerations; and resources to aid in understanding and managing this public health crisis.

  16. Risk of All-Cause Mortality in Alcohol-Dependent Individuals: A Systematic Literature Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Philippe Laramée

    2015-10-01

    Interpretation: AD was found to significantly increase an individual's risk of all-cause mortality. While abstinence in alcohol-dependent subjects led to greater mortality reduction than non-abstinence, this study suggests that alcohol-dependent subjects can significantly reduce their mortality risk by reducing alcohol consumption.

  17. Characteristics of prospective memory deficits in HIV-seropositive substance-dependent individuals: preliminary observations.

    Science.gov (United States)

    Martin, Eileen M; Nixon, Heather; Pitrak, David L; Weddington, William; Rains, Niles A; Nunnally, Gerald; Grbesic, Silvana; Gonzalez, Raul; Jacobus, Joanna; Bechara, Antoine

    2007-07-01

    The construct of "prospective memory" (PM) refers to a type of episodic memory for a future intention or "remembering what one must do." This function has been proposed as a candidate mechanism underlying behaviors of critical importance in HIV disease, including adherence with medication regimens and continued engagement in risk behavior. We administered tasks of time-based and event-based prospective memory and control tasks of retrospective and working memory to 31 HIV-seropositive and 35 HIV-seronegative substance-dependent individuals (SDIs). We found that compared with HIV- controls HIV+ participants showed deficits in time-based but not event-based PM. Retrospective, but not working, memory performance correlated significantly with time-based PM performance. In addition, performance on the time-based PM task was a significant predictor of scores on a self-report measure of risky sexual and injection practices. These preliminary data provide new and unique findings regarding the components of executive function mediated by prefrontal cortical systems that are impaired among HIV+ SDIs and their relevance to "real-world" behaviors.

  18. Primary care management of opioid use disorders

    Science.gov (United States)

    Srivastava, Anita; Kahan, Meldon; Nader, Maya

    2017-01-01

    level of opioid tolerance, and those at high risk of prolonged QT interval (level III evidence). Conclusion Individual patient characteristics and preferences should be taken into consideration when choosing a first-line opioid agonist treatment. For patients at high risk of dropout (such as adolescents and socially unstable patients), treatment retention should take precedence over other clinical considerations. For patients with high risk of toxicity (such as patients with heavy alcohol or benzodiazepine use), safety would likely be the first consideration. However, the most important factor to consider is that opioid agonist treatment is far more effective than abstinence-based treatment. PMID:28292795

  19. Comparison of pain models to detect opioid-induced hyperalgesia

    Directory of Open Access Journals (Sweden)

    Krishnan S

    2012-04-01

    Full Text Available Sumithra Krishnan1, Amy Salter2, Thomas Sullivan2, Melanie Gentgall3, Jason White4, Paul Rolan11Discipline of Pharmacology, School of Medical Sciences, The University of Adelaide, 2Discipline of Public Health, The University of Adelaide, 3Pain and Anesthesia Research Clinic, Royal Adelaide Hospital, 4Pharmacy School, University of South Australia, Adelaide, South Australia, AustraliaObjective: Chronic opioid therapy may be associated with hyperalgesia. Our objective was to determine if opioid-induced hyperalgesia detection sensitivity is dependent on the stimulus used to detect it.Methods: This open design study compared the detection of hyperalgesia in opioid-dependent subjects (n = 16 and healthy control subjects (n = 16 using the following pain stimuli: cold pain, electrical stimulation, mechanical pressure, and ischemic pain. The opioid-dependent subjects were maintained on either methadone (n = 8 or buprenorphine (n = 8 for at least 3 months. None of the controls was dependent on opioids or other drugs of abuse.Results: The opioid-dependent subjects were markedly more sensitive than controls to the cold pain test. Compared with the control group, the hazard ratio for ceasing the test due to intolerable pain was 7.7 (95% confidence interval [CI] 2.6–23.3 in the buprenorphine group and 4.5 (95% CI 1.7–15.6 in the methadone group, with similar data for the cold pain threshold. Of the remaining tests, there were differences only for the electrical pain threshold between treatment groups, with the geometric mean threshold in the buprenorphine group being 1.5 (95% CI 1.1–1.9-fold higher (ie, less sensitive than that of the controls; the geometric mean for the methadone group was 1.3 (95% CI 1.04–1.7-fold higher than that of the controls. There were no significant differences between buprenorphine and methadone patients in test responses. Women were more sensitive to the cold pain (hazard ratio for tolerance, 3.1 [95% CI 1.4–7.3] and

  20. Individual recognition of social rank and social memory performance depends on a functional circadian system.

    Science.gov (United States)

    Müller, L; Weinert, D

    2016-11-01

    In a natural environment, social abilities of an animal are important for its survival. Particularly, it must recognize its own social rank and the social rank of a conspecific and have a good social memory. While the role of the circadian system for object and spatial recognition and memory is well known, the impact of the social rank and circadian disruptions on social recognition and memory were not investigated so far. In the present study, individual recognition of social rank and social memory performance of Djungarian hamsters revealing different circadian phenotypes were investigated. Wild type (WT) animals show a clear and well-synchronized daily activity rhythm, whereas in arrhythmic (AR) hamsters, the suprachiasmatic nuclei (SCN) do not generate a circadian signal. The aim of the study was to investigate putative consequences of these deteriorations in the circadian system for animalś cognitive abilities. Hamsters were bred and kept under standardized housing conditions with food and water ad libitum and a 14l/10 D lighting regimen. Experimental animals were assigned to different groups (WT and AR) according to their activity pattern obtained by means of infrared motion sensors. Before the experiments, the animals were given to develop a dominant-subordinate relationship in a dyadic encounter. Experiment 1 dealt with individual recognition of social rank. Subordinate and dominant hamsters were tested in an open arena for their behavioral responses towards a familiar (known from the agonistic encounters) or an unfamiliar hamster (from another agonistic encounter) which had the same or an opposite social rank. The investigation time depended on the social rank of the WT subject hamster and its familiarity with the stimulus animal. Both subordinate and dominant WT hamsters preferred an unfamiliar subordinate stimulus animal. In contrast, neither subordinate nor dominant AR hamsters preferred any of the stimulus animals. Thus, disruptions in circadian

  1. When Is an Opioid Safe to Take?

    Science.gov (United States)

    ... gov/news/fullstory_166872.html When Is an Opioid Safe to Take? Doctors say it can treat ... Society of Anesthesiologists (ASA): Why was I prescribed opioids? Did the doctor assume opioids are the strongest ...

  2. Beyond Opioids: Mind and Body Practices

    Science.gov (United States)

    ... that tai chi, a traditional Chinese practice that combines meditation with deep breathing, relaxation, and gentle movements, ... Tide Rx: turnthetiderx.org Read More "Understanding Opioids" Articles Understanding The Opioid Overdose Epidemic / Beyond Opioids: Mind ...

  3. Dextromethorphan differentially affects opioid antinociception in rats

    OpenAIRE

    2005-01-01

    Opioid drugs such as morphine and meperidine are widely used in clinical pain management, although they can cause some adverse effects. A number of studies indicate that N-methyl-D-aspartate (NMDA) receptors may play a role in the mechanism of morphine analgesia, tolerance and dependence. Being an antitussive with NMDA antagonist properties, dextromethorphan (DM) may have some therapeutic benefits when coadministered with morphine. In the present study, we investigated the effects of DM on th...

  4. Laboratory Testing for Prescription Opioids

    OpenAIRE

    Milone, Michael C.

    2012-01-01

    Opioid analgesic misuse has risen significantly over the past two decades, and these drugs now represent the most commonly abused class of prescription medications. They are a major cause of poisoning deaths in the USA exceeding heroin and cocaine. Laboratory testing plays a role in the detection of opioid misuse and the evaluation of patients with opioid intoxication. Laboratories use both immunoassay and chromatographic methods (e.g., liquid chromatography with mass spectrometry detection),...

  5. Endomorphins fully activate a cloned human mu opioid receptor.

    Science.gov (United States)

    Gong, J; Strong, J A; Zhang, S; Yue, X; DeHaven, R N; Daubert, J D; Cassel, J A; Yu, G; Mansson, E; Yu, L

    1998-11-13

    Endomorphins were recently identified as endogenous ligands with high selectivity for mu opioid receptors. We have characterized the ability of endomorphins to bind to and functionally activate the cloned human mu opioid receptor. Both endomorphin-1 and endomorphin-2 exhibited binding selectivity for the mu opioid receptor over the delta and kappa opioid receptors. Both agonists inhibited forskolin-stimulated increase of cAMP in a dose-dependent fashion. When the mu opioid receptor was coexpressed in Xenopus oocytes with G protein-activated K+ channels, application of either endomorphin activated an inward K+ current. This activation was dose-dependent and blocked by naloxone. Both endomorphins acted as full agonists with efficacy similar to that of [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin (DAMGO). These data indicate that endomorphins act as full agonists at the human mu opioid receptor, capable of stimulating the receptor to inhibit the cAMP/adenylyl cyclase pathway and activate G-protein-activated inwardly rectifying potassium (GIRK) channels.

  6. Peripheral Opioid Analgesia

    Science.gov (United States)

    1999-07-16

    noxious insult . These substances include serotonin. bradykinin. and histamine . Serotonin (5-hydroxylryptamine [5-HT]) is derived from platelets in...IL-IP) and substance P, releases histamine which increases Ca·" permeability resulting in the release of certain neuropeptides (Falus and Meretey...i.p. injection than by intracerebroventricular injection. The effects of delta, mu, and kappa opioid agonists were investigated by Stein et al

  7. Mental Disorders in Substance Dependent Individuals as Compared to Non-Substance Dependent People in Hamadan, Iran

    Directory of Open Access Journals (Sweden)

    A. Heidari Pahlavian

    2011-10-01

    Full Text Available Introduction & Objective: There are several close links between substance dependency and mental disorders. Many people who regularly abuse drugs are also diagnosed with psychiatric disorders and vice versa. The high prevalence of this comorbidity has been documented in several studies, although most of the research has been carried out in only a few countries and the cultural validity of the data is unknown. Thus the aim of this study was the comparative investigation of mental disorders in drug dependent and non drug dependent persons in city of Hamadan.Materials & Methods: This study was a descriptive comparative research. 106 men aged 18 to 51 who sought treatment at addiction rehabilitation department of Hamadan were recruited in this study. Also 106 men in the same age range were matched with the first group. Data were collected through structured clinical interview for DSM-IV-TR and SCL 90-R questionnaire. Data were analyzed using t-test and correlation coefficient test.Results: The rate and severity of mental disorders in 9 studied Categories of disorders—phobia, anxiety, somatization, psychotism, depression, paranoid thoughts, aggression, interpersonal sensitivity and obsession-compulsion—were significantly higher among the addicts than the normal group.The level of severity was higher in depression, paranoid thoughts and interpersonal sensitivity than the other disorders. 63.5% of addicts suffered from some psychological disorders while the figures for no addicts were 28.8%. The prevalence of co-morbid psychiatric disorders varied with the pattern of addicts.Conclusion: This study showed that persons with substance dependence display more signs of psycho pathology and mental disorders in comparison with non- substance dependent people.(Sci J Hamadan Univ Med Sci 2011;18(3:22-28

  8. Opioid induced nausea and vomiting.

    Science.gov (United States)

    Smith, Howard S; Laufer, Andras

    2014-01-05

    Opioids are broad spectrum analgesics that are an integral part of the therapeutic armamentarium to combat pain in the palliative care population. Unfortunately, among the adverse effects of opioids that may be experienced along with analgesia is nausea, vomiting, and/or retching. Although it is conceivable that in the future, using combination agents (opioids combined with agents which may nullify emetic effects), currently nausea/vomiting remains a significant issue for certain patients. However, there exists potential current strategies that may be useful in efforts to diminish the frequency and/or intensity of opioid-induced nausea/vomiting (OINV).

  9. Relapse to opioid use in opioid-dependent individuals released from compulsory drug detention centres compared with those from voluntary methadone treatment centres in Malaysia: a two-arm, prospective observational study

    Directory of Open Access Journals (Sweden)

    Martin P Wegman, BSc

    2017-02-01

    Funding: The World Bank Group, Doris Duke Charitable Foundation, National Institute on Drug Abuse, Australian National Health & Medical Research Council, National Institute of Mental Health, and the University of Malaya-Malaysian Ministry of Higher Education High Impact Research Grant.

  10. Aberrant default-mode functional and structural connectivity in heroin-dependent individuals.

    Directory of Open Access Journals (Sweden)

    Xiaofen Ma

    Full Text Available Little is known about connectivity within the default mode network (DMN in heroin-dependent individuals (HDIs. In the current study, diffusion-tensor imaging (DTI and resting-state functional MRI (rs-fMRI were combined to investigate both structural and functional connectivity within the DMN in HDIs.Fourteen HDIs and 14 controls participated in the study. Structural (path length, tracts count, (fractional anisotropy FA and (mean diffusivity MD derived from DTI tractographyand functional (temporal correlation coefficient derived from rs-fMRI DMN connectivity changes were examined in HDIs. Pearson correlation analysis was performed to compare the structural/functional indices and duration of heroin use/Iowa gambling task(IGT performance in HDIs.HDIs had lower FA and higher MD in the tract connecting the posterior cingulate cortex/precuneus (PCC/PCUN to right parahippocampal gyrus (PHG, compared to the controls. HDIs also had decreased FA and track count in the tract connecting the PCC/PCUN and medial prefrontal cortex (MPFC, as well as decreased functional connectivity between the PCC/PCUN and bilateral PHG and MPFC, compared to controls. FA values for the tract connecting PCC/PCUN to the right PHG and connecting PCC/PCUN to the MPFC were negatively correlated to the duration of heroin use. The temporal correlation coefficients between the PCC/PCUN and the MPFC, and the FA values for the tract connecting the PCC/PCUN to the MPFC were positively correlated to IGT performance in HDIs.Structural and functional connectivity within the DMN are both disturbed in HDIs. This disturbance progresses as duration of heroin use increases and is related to deficits in decision making in HDIs.

  11. Frequency of Opioid Use in a Population of Cancer Patients During the Trajectory of the Disease

    DEFF Research Database (Denmark)

    Jarlbaek, L.; Hansen, D.G.; Bruera, E.

    2010-01-01

    Aims: Bearing in mind that Denmark has one of the world's highest legal uses of strong opioids per capita, the aim of the present study was to describe the frequency of opioid use in a complete, population-based cohort of cancer patients at different time points during the trajectory of the disease......, and to analyse the influence of different factors on opioid use close to death. Materials and methods: All incident cancer patients registered in 1997-1998 (n = 4006) from a population of 470 000 were followed individually from diagnosis to death (non-survivors) or for 5 years (survivors). The use of opioids...... was obtained from a prescription database covering the whole population. Results: Among the 43% cancer patients who survived for 5 years, 12% used opioids at diagnosis, 38% during follow-up and 10% after 5 years. For the non-survivors, 80% used opioids sometime during follow-up. At diagnosis, use related...

  12. Local peripheral opioid effects and expression of opioid genes in the spinal cord and dorsal root ganglia in neuropathic and inflammatory pain.

    Science.gov (United States)

    Obara, Ilona; Parkitna, Jan Rodriguez; Korostynski, Michal; Makuch, Wioletta; Kaminska, Dorota; Przewlocka, Barbara; Przewlocki, Ryszard

    2009-02-01

    We investigated the efficacy of local intraplantar (i.pl.) injection of peptide and non-peptide mu-, delta- and kappa-opioid receptor agonists in rat models of inflammatory and neuropathic pain. Locally applied agonists dose-dependently reduced formalin-induced flinching of the inflamed paw and induced antiallodynic and antihyperalgesic effects in sciatic nerve ligation-induced neuropathic pain. These effects were mediated by peripheral opioid receptors localized at the side of tissue/nerve injury, as was demonstrated by selective and non-selective opioid receptors antagonists. The ED(50) dose range of mu- and kappa-agonists required to induce analgesia in neuropathy was much higher than the ED(50) for inflammation; moreover, only delta-agonists were effective in the same dose range in both pain models. Additionally, effective antinociception was achieved at a lower dose of peptide, compared to non-peptide, opioids. Such findings support the use of the peripheral administration of opioid peptides, especially delta-agonists, in treating chronic pain. Furthermore, in order to assess whether adaptations in the expression of opioid genes could underlie the clinical observation of reduced opioid effectiveness in neuropathic pain, we analyzed the abundance of opioid transcripts in the spinal cord and dorsal root ganglia (DRG) during the neuropathy and inflammation. Nerve injury down-regulated mRNA for all types of opioid receptors in the DRG, which is predicted to decrease in the synthesis of opioid receptors to possibly account for the reduced effectiveness of locally administered opioids in neuropathy. The obtained results differentiate inflammatory and neuropathic pain and provide a novel insight into the peripheral effectiveness of opioids in both types of pain.

  13. Comparison of the risks of shopping behavior and opioid abuse between tapentadol and oxycodone and association of shopping behavior and opioid abuse.

    Science.gov (United States)

    Cepeda, M Soledad; Fife, Daniel; Kihm, Mary A; Mastrogiovanni, Greg; Yuan, Yingli

    2014-12-01

    This study compared the risks of opioid shopping behavior and opioid abuse between tapentadol immediate release and oxycodone immediate release and, to validate the definition of shopping, examined the association between opioid shopping and opioid abuse further. This retrospective cohort study using linked dispensing and diagnosis databases followed opioid-naive patients for development of shopping behavior and/or opioid abuse during 1 year after initial exposure to tapentadol or oxycodone. Shopping was defined by having overlapping opioid prescriptions from >1 prescriber filled at ≥3 pharmacies; abuse by having International Classification of Diseases, 9th revision diagnoses reflecting opioid abuse, addiction, or dependence. To determine their association, we cross-tabulated shopping and opioid abuse and calculated odds ratios. Risks of developing each outcome were estimated using logistic regression. Among 277,401 participants initiating opioid use with tapentadol (39,524) or oxycodone (237,877), 0.6% developed shopping behavior, 0.75% developed abuse. Higher proportions of patients in the oxycodone group developed shopping behavior and abuse than in the tapentadol group (shopping: adjusted odds ratio [95% confidence interval], 0.45 [0.36-0.55]; abuse: 0.44 [0.37-0.54]). Shopping behavior and abuse were associated; of those with shopping behavior, 6.5% had abuse. Age (18 to 64 y), sex (male), prior benzodiazepine use, paying cash, and history (mood disorders, abuse of nonopioid medications, and back pain) were risk factors for developing either outcome. Shopping behavior and abuse measure complementary, but associated, constructs, which further validates the current definition of shopping. The risk of developing either is lower among patients who initiate opioid use with tapentadol than those who initiate opioid use with oxycodone.

  14. [Comorbidity of opioid addiction and alcoholism in patients of young age: clinical variants of the double diagnosis].

    Science.gov (United States)

    Bokhan, N A; Blagov, L N; Kurgak, D I

    2012-01-01

    A study included 115 male patients with opioid addiction, aged from 17 to 27 years. Comorbidity of opioid addiction and alcoholism in patients of young age was represented by two main variants distinguishing between primary dependence on opioid or alcohol. In the first variant, additional variants of vicarious alcoholization and replacement of addiction form were singled out. In the second case, alcoholism preceded opioid addiction that developed as a form of polyaddiction and the formation of preliminary (primary) alcoholism was considered as a protracted stage of searching narcotism with the transition from alcoholism to opioid addiction. Stages and differential criteria of the variants of double disorders are described.

  15. Neural response in obsessive-compulsive washers depends on individual fit of triggers

    Directory of Open Access Journals (Sweden)

    Ali eBaioui

    2013-04-01

    Full Text Available BackgroundPatients with obsessive-compulsive disorder (OCD have highly idiosyncratic triggers. To fully understand which role this idiosyncrasy plays in the neurobiological mechanisms behind OCD, it is necessary to elucidate the impact of individualization regarding the applied investigation methods.This functional magnetic resonance imaging (fMRI study explores the neural correlates of contamination/washing-related OCD with a highly individualized symptom provocation paradigm. Additionally, it is the first study to directly compare individualized and standardized symptom provocation. MethodsNineteen patients with washing compulsions created individual OCD hierarchies, which later served as instructions to photograph their own individualized stimulus sets. The patients and 19 case-by-case matched healthy controls participated in a symptom provocation fMRI experiment with individualized and standardized stimulus sets created for each patient. ResultsOCD patients compared to healthy controls displayed stronger activation in the basal ganglia (nucleus accumbens, nucleus caudatus, pallidum for individualized symptom provocation. Using standardized symptom provocation, this group comparison led to stronger activation in the nucleus caudatus. The direct comparison of between-group effects for both symptom provocation approaches revealed stronger activation of the orbitofronto-striatal network for individualized symptom provocation.ConclusionsThe present study provides insight into the differential impact of individualized and standardized symptom provocation on the orbitofronto-striatal network of OCD washers. Behavioral and neural responses imply a higher symptom-specificity of individualized symptom provocation.

  16. Trends in average days' supply of opioid medications in Medicaid and commercial insurance.

    Science.gov (United States)

    Tehrani, Ali Bonakdar; Henke, Rachel Mosher; Ali, Mir M; Mutter, Ryan; Mark, Tami L

    2017-08-19

    To calculate trends in adult average days' supply for six commonly prescribed opioids: hydrocodone, hydromorphone, morphine, oxycodone, oxymorphone, and tapentadol to assess whether physicians changed prescribing practices at the time of the intensifying epidemic. We used 2005-2015 Truven Health MarketScan Commercial Claims and Encounters data to measure trends in opioid average days' supply among commercially insured individuals and 2005-2014 MarketScan Multi-State Medicaid data to measure trends in opioid average days' supply among Medicaid beneficiaries. For Medicaid, we found an increase in days' supply for all drugs except morphine. The largest percentage increase was for oxycodone, which increased 4.5days (37%). Opioid days' supply for individuals with commercial insurance exhibited similar but steeper trends. The largest increase was also for oxycodone, which increased 6days (56%). Between 2013 and 2015, when the opioid epidemic had begun to be widely publicized, there was no decline in the median days supplied for any of the opioids. Our results find that days' supply of opioids are increasing despite public health campaigns and media attention on the risks of opioid prescribing. More effective interventions to curb opioid prescribing are needed to reverse these trends. Published by Elsevier Ltd.

  17. Differentiation of opioid drug effects by hierarchical multi-site phosphorylation.

    Science.gov (United States)

    Just, Sascha; Illing, Susann; Trester-Zedlitz, Michelle; Lau, Elaine K; Kotowski, Sarah J; Miess, Elke; Mann, Anika; Doll, Christian; Trinidad, Jonathan C; Burlingame, Alma L; von Zastrow, Mark; Schulz, Stefan

    2013-03-01

    Differences in the ability of opioid drugs to promote regulated endocytosis of μ-opioid receptors are related to their tendency to produce drug tolerance and dependence. Here we show that drug-specific differences in receptor internalization are determined by a conserved, 10-residue sequence in the receptor's carboxyl-terminal cytoplasmic tail. Diverse opioids induce receptor phosphorylation at serine (S)375, present in the middle of this sequence, but opioids differ markedly in their ability to drive higher-order phosphorylation on flanking residues [threonine (T)370, T376, and T379]. Multi-phosphorylation is required for the endocytosis-promoting activity of this sequence and occurs both sequentially and hierarchically, with S375 representing the initiating site. Higher-order phosphorylation involving T370, T376, and T379 specifically requires GRK2/3 isoforms, and the same sequence controls opioid receptor internalization in neurons. These results reveal a biochemical mechanism differentiating the endocytic activity of opioid drugs.

  18. Opioid Overdose Deaths in the City and County of San Francisco: Prevalence, Distribution, and Disparities.

    Science.gov (United States)

    Visconti, Adam J; Santos, Glenn-Milo; Lemos, Nikolas P; Burke, Catherine; Coffin, Phillip O

    2015-08-01

    Drug overdose is now the leading cause of unintentional death nationwide, driven by increased prescription opioid overdoses. To better understand urban opioid overdose deaths, this paper examines geographic, demographic, and clinical differences between heroin-related decedents and prescription opioid decedents in San Francisco from 2010 to 2012. During this time period, 331 individuals died from accidental overdose caused by opioids (310 involving prescription opioids and 31 involving heroin). Deaths most commonly involved methadone (45.9%), morphine (26.9%), and oxycodone (21.8%). Most deaths also involved other substances (74.9%), most commonly cocaine (35.3%), benzodiazepines (27.5%), antidepressants (22.7%), and alcohol (19.6%). Deaths were concentrated in a small, high-poverty, central area of San Francisco and disproportionately affected African-American individuals. Decedents in high-poverty areas were significantly more likely to die from methadone and cocaine, whereas individuals from more affluent areas were more likely die from oxycodone and benzodiazepines. Heroin decedents were more likely to be within a younger age demographic, die in public spaces, and have illicit substances rather than other prescription opioids. Overall, heroin overdose death, previously common in San Francisco, is now rare. Prescription opioid overdose has emerged as a significant concern, particularly among individuals in high-poverty areas. Deaths in poor and affluent regions involve different causative opioids and co-occurring substances.

  19. [Difference of acute ketone body metabolism between insulin-dependent diabetic and non-insulin-dependent diabetic individuals].

    Science.gov (United States)

    Mayumi, K; Suzuki, S; Takuma, T; Gomi, Y; Kondo, Y; Sakamaki, T; Kokei, S; Inoue, T; Iino, S

    1992-10-20

    The difference in the acute metabolic change in ketone bodies between patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) was investigated in this study. The subjects employed were 7 patients with IDDM losing residual insulin secretion and 7 patients with NIDDM matched to the former patients for age, body mass index, duration of diabetes, daily insulin dosage, fasting plasma glucose and HbA1c. Blood samples were drawn at 3A.M. and 7A.M. on the same day, and plasma glucose, acetoacetic acid (AcAc), 3-beta-hydroxybutylic acid (3-OHBA), free fatty acid (FFA), glycerol, cortisol and growth hormone (GH) concentrations were determined. Plasma total ketone bodies (AcAc and 3-OHBA), 3-OHBA and FFA concentrations at 7A.M. were significantly higher in the patients with IDDM than in those with NIDDM (p ketone bodies, AcAc and 3-OHBA concentrations were also more significantly elevated in the patients with IDDM than in those with NIDDM. It was observed that the ratio of 3-OHBA was more than 2.0 in all of the patients with IDDM and less than 2.0 in all of the patients with NIDDM, the difference being significant with p < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. The effect of various morphine weaning regimens on the sequelae of opioid tolerance involving physical dependency, anxiety and hippocampus cell neurodegeneration in rats.

    Science.gov (United States)

    Motaghinejad, Majid; Karimian, Seyed Morteza; Motaghinejad, Ozra; Shabab, Behnaz; Asadighaleni, Majid; Fatima, Sulail

    2015-06-01

    Chronic consumption of morphine induces physical dependency, anxiety, and neurodegeneration. In this study, morphine on its own has been used for the management of morphine-induced dependency, oxidative stress, and apoptosis. Forty-eight male rats were randomly divided into six groups. Rats in groups 1-5 were made morphine dependent by an increasing manner of morphine for 7 days (15-45 mg/kg). For the next 14 days, morphine was administered using the following regimen: (i) once daily 45 mg/kg (positive controls), (ii) the same dose at additional intervals (6 h longer than the previous intervals each time), (iii) 45 mg/kg of morphine at irregular intervals like of 12, 24, 36 h, (iv) decreasing dose once daily (every time 2.5 mg/kg less than the former dosage). Group 5 received 45 mg/kg of morphine and 10 mg/kg of SOD mimetic agent (M40401) injection per day. Group 6 (negative control) received saline solution only. On day 22, all animals received naloxone (3 mg/kg) and their Total Withdrawal Index (TWI) and blood cortisol levels were measured. After drug treatment, hippocampus cells were isolated, and oxidative, antioxidative, and apoptotic factors were evaluated. Various regimens of morphine reduced TWI, cortisol levels, Bax activity, caspase-3, caspase-9, TNF-α, and IL-1β and lipid peroxidation. In all treatment groups, GSH level, superoxide dismutase, glutathione peroxidase, and Bcl-2 activity were significantly increased. Furthermore, SOD mimetic agent c diminished morphine effect on SOD activity. Thus, varying the dosage regimen of morphine can reduce the severity of morphine-induced dependency and neurodegeneration.

  1. Effectiveness of opioid analgesics in chronic noncancer pain.

    Science.gov (United States)

    Ferrari, Renata; Zanolin, Maria E; Duse, Genni; Visentin, Marco

    2015-03-01

    There is general agreement about the need to perform a screening test to assess the risk of opioid misuse prior to starting a long-term opioid treatment for chronic noncancer pain. The evidence supporting the effectiveness of opioid long-term treatment is weak, and no predictors of its usefulness have been assessed. The aim of this study was to assess the effect on pain and quality of life of chronic opioid treatment, and detect the possible predictors of its effectiveness. This observational, prospective study was conducted in 2 Italian Pain Relief Units on 77 patients affected by intractable chronic pain. Patients were submitted to psycho-logical tests, investigating the individual pain experience, risk of opioid misuse, mood states, quality of life, and personality characteristics prior to starting treatment and at 2,4, and 6-month follow-up. Both maximum and habitual pain, as measured with VAS, underwent a statistically significant reduction at 2, 4, and 6-month follow-up. In multivariate analysis, lower scores in the Pain Medication Questionnaire (PMQ) were predictive of a major reduction in maximum VAS (P = 0.005). Both low PMQ and MMPI-cynicism scores were predictive of habitual VAS decrease (P = 0.012 and P = 0.028, respectively). The results indicate that pain relief significantly improved over a 6-month period of opioid treatment, together with quality of life. The outcome was better in patients with a pretreatment low risk of opioid misuse, low scores in the Cynicism scale of MMPI-2, and no aberrant drug behaviors at follow-up. Therefore, a psychological screening and support is crucial for a good outcome of opioid therapy for chronic noncancer pain patients.

  2. Decision-Making and the Iowa Gambling Task: Ecological validity in individuals with substance dependence

    Directory of Open Access Journals (Sweden)

    Antonio Verdejo-Garcia

    2006-03-01

    Full Text Available Substance Dependent Individuals (SDIs usually show deficits in real-life decision-making, as illustrated by their persistence in drug use despite a rise in undesirable consequences. The Iowa Gambling Task (IGT is an instrument that factors a number of aspects of real-life decision-making. Although most SDIs are impaired on the IGT, there is a subgroup of them who perform normally on this task. One possible explanation for this differential performance is that impairment in decision-making is largely detected on the IGT when the use of drugs escalates in the face of rising adverse consequences. The aim of this study is to test this hypothesis, by examining if several real-life indices associated with escalation of addiction severity (as measured by the Addiction Severity Index -ASI- are predictive of risky decisions, as revealed by impaired performance on different versions of the IGT. We administered the ASI and different versions of the IGT (the main IGT version, a variant IGT version, and two parallel versions of each to a large sample of SDI. We used regression models to examine the predictive effects of the seven real-life domains assessed by the ASI on decision-making performance as measured by the IGT. We included in regression models both ASI-derived objective and subjective measures of each problem domain. Results showed (i that several aspects of real-life functioning associated with addiction severity were moderate predictors of IGT decision-making performance; (ii that the combined assessment of decision-making using different versions of the IGT yielded better predictive measures than assessment using isolated versions of the IGT; and (iii that objective measures of real-life functioning were better predictors of decision-making performance on the IGT than subjective measures based on SDI's insight about their problems. These results support the notion that decision-making deficits as measured by the IGT are associated with a rise in

  3. Opioid receptors and cardioprotection - 'opioidergic conditioning' of the heart.

    Science.gov (United States)

    Headrick, John P; See Hoe, Louise E; Du Toit, Eugene F; Peart, Jason N

    2015-04-01

    Ischaemic heart disease (IHD) remains a major cause of morbidity/mortality globally, firmly established in Westernized or 'developed' countries and rising in prevalence in developing nations. Thus, cardioprotective therapies to limit myocardial damage with associated ischaemia-reperfusion (I-R), during infarction or surgical ischaemia, is a very important, although still elusive, clinical goal. The opioid receptor system, encompassing the δ (vas deferens), κ (ketocyclazocine) and μ (morphine) opioid receptors and their endogenous opioid ligands (endorphins, dynorphins, enkephalins), appears as a logical candidate for such exploitation. This regulatory system may orchestrate organism and organ responses to stress, induces mammalian hibernation and associated metabolic protection, triggers powerful adaptive stress resistance in response to ischaemia/hypoxia (preconditioning), and mediates cardiac benefit stemming from physical activity. In addition to direct myocardial actions, central opioid receptor signalling may also enhance the ability of the heart to withstand I-R injury. The δ- and κ-opioid receptors are strongly implicated in cardioprotection across models and species (including anti-infarct and anti-arrhythmic actions), with mixed evidence for μ opioid receptor-dependent protection in animal and human tissues. A small number of clinical trials have provided evidence of cardiac benefit from morphine or remifentanil in cardiopulmonary bypass or coronary angioplasty patients, although further trials of subtype-specific opioid receptor agonists are needed. The precise roles and utility of this GPCR family in healthy and diseased human myocardium, and in mediating central and peripheral survival responses, warrant further investigation, as do the putative negative influences of ageing, IHD co-morbidities, and relevant drugs on opioid receptor signalling and protective responses.

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

    Directory of Open Access Journals (Sweden)

    Cleo Lina Crunelle

    2014-01-01

    Full Text Available In cocaine-dependent patients, grey matter (GM volume reductions have been observed in the frontal lobes that are associated with 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 (VBM. Additionally, within the group of non-treatment-seeking cocaine-dependent individuals, we explored the role of frequently co-occurring features such as of trait impulsivity (Barratt Impulsivity Score, BIS, smoking, depressive symptoms (Beck Depression Inventory (BDI, 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 OFC, 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.

  5. 阿片类物质对机体免疫系统的影响%The Effects of Opioids on Immune System

    Institute of Scientific and Technical Information of China (English)

    姜美俊; 郝伟

    2002-01-01

    The abuse and dependence of opioids can seriously damage the users' health physically and psychologically. The authors reviewed the inhibitory effects of opioid on the immune system and related mechanisms involving cellular, humoral, and unspecific immune processes, which would cast light on the treatment of opioid-induced immunodeficiency and infectious diseases in clinical practice.

  6. An Individual Based Model of Arctic cod ( Boreogadus saida) early life in Arctic polynyas: II. Length-dependent and growth-dependent mortality

    Science.gov (United States)

    Thanassekos, Stéphane; Robert, Dominique; Fortier, Louis

    2012-05-01

    A bioenergetics individual based model (IBM) of early growth is used to investigate the relative importance of length-dependent and growth-dependent mortality during the early life (0-45 d) of Arctic cod in the Northeast Water (NEW) in 1993 and the North Water (NOW) in 1998. In the model, individual growth is forced by the observed temperature and prey concentration histories as prescribed by the hatch date of a larva. The IBM reproduced well the observed length-at-age and revealed large ontogenetic and interregional fluctuations in instantaneous growth. Four mortality scenarios were compared for each population: (1) constant mortality (estimated from catch-at-age data); (2) length-dependent mortality; (3) growth-dependent mortality; and (4) combined length- and growth-dependent mortality. Scenarios 2, 3, and 4 were parameterized to achieve the final survival produced by the constant mortality rates estimated from observations (scenario 1). Scenario 2 accounted well for declining mortality with size but not for the large variations in growth-dependent mortality. Scenario 3 failed to capture the decreasing vulnerability of surviving larvae to predation. Only scenario 4 accounted for both the large fluctuations in growth-dependent mortality and the progressive shift in dominance from length-dependent to growth-dependent mortality as the survivors increased in size. Sub-sampling the model output to reproduce the limited temporal resolution of sampling at sea improved the fit between observed and modeled frequencies-at-age, and pointed to the under-sampling of the smallest larvae as a major sampling bias.

  7. Opioids and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P

    2015-01-01

    BACKGROUND: Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence. METHODS: Patients with incident, early stage breast cancer who were diagnosed during 1996 through...... 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death......, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months...

  8. Opioid Receptors Mediate Direct Predictive Fear Learning: Evidence from One-Trial Blocking

    Science.gov (United States)

    Cole, Sindy; McNally, Gavan P.

    2007-01-01

    Pavlovian fear learning depends on predictive error, so that fear learning occurs when the actual outcome of a conditioning trial exceeds the expected outcome. Previous research has shown that opioid receptors, including [mu]-opioid receptors in the ventrolateral quadrant of the midbrain periaqueductal gray (vlPAG), mediate such predictive fear…

  9. The impact of size-dependent predation on population dynamcis and individual life history

    NARCIS (Netherlands)

    Claessen, D.; van Oss, C.; de Roos, A.M.; Persson, L.

    2002-01-01

    In size-structured predator-prey systems, capture success depends on the sizes of both predator and prey. We study the population-dynamic consequences of size-dependent predation using a model of a size-structured, cannibalistic fish population with one shared, alternative resource. We assume that a

  10. Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-labouring myometrium.

    LENUS (Irish Health Repository)

    Fanning, Rebecca A

    2013-01-05

    The existence of opioid receptors in mammalian myometrial tissue is now widely accepted. Previously enkephalin degrading enzymes have been shown to be elevated in pregnant rat uterus and a met-enkephalin analogue has been shown to alter spontaneous contractility of rat myometrium. Here we have undertaken studies to determine the effects of met-enkephalin on in vitro human myometrial contractility and investigate the expression of opioid receptors in pregnant myometrium. Myometrial biopsies were taken from women undergoing elective caesarean delivery at term. Organ bath experiments were used to investigate the effect of the met-enkephalin analogue [d-Ala 2, d-met 5] enkephalin (DAMEA) on spontaneous contractility. A confocal immunofluorescent technique and real time PCR were used to determine the expression of protein and mRNA, respectively for two opioid receptor subtypes, mu and delta. DAMEA had a concentration dependent inhibitory effect on contractile activity (1 × 10(-7)M-1 × 10(-4)M; 54% reduction in contractile activity, P<0.001 at 1 × 10(-4)M concentration). Mu and delta opioid receptor protein sub-types and their respective mRNA were identified in all tissues sampled. This is the first report of opioid receptor expression and of an opioid mediated uterorelaxant action in term human non-labouring myometrium in vitro.

  11. Emotional and Social Loneliness in Individuals With and Without Substance Dependence Disorder

    OpenAIRE

    Hosseinbor, Mohsen; Yassini Ardekani, Seyed Mojtaba; Bakhshani, Saeed; Bakhshani, Somayeh

    2014-01-01

    Background: Loneliness is one of the psychological variables related to high risk behaviors that should be investigated more. Objectives: The current study aimed to assess emotional, social, romantic, and familial dimensions of loneliness in drug abuser and nondrug abuser individuals. Patients and Methods: Two hundred and twenty eight individuals were enrolled in this cross sectional study. Hundred and eighteen drug abusers were recruited through random sampling among the clients referred to ...

  12. Remifentanil-acute opioid tolerance and opioid-induced hyperalgesia: a systematic review.

    Science.gov (United States)

    Kim, Sang Hun; Stoicea, Nicoleta; Soghomonyan, Suren; Bergese, Sergio D

    2015-01-01

    The use of opioids may seem to be a double-edged sword; they provide straight analgesic and antihyperalgesic effects initially, but subsequently are associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) that have been reported in experimental studies and clinical observations. It has been suggested that opioids can induce an acute tolerance and hyperalgesia in dose- and/or time-dependent manners even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management in clinical anesthesia and in the intensive care units because of its rapid onset and offset. We reviewed articles analyzing AOT and/or OIH by remifentanil and focused on the following issues: (1) evidence of remifentanil inducing AOT and/or OIH and (2) importance of AOT and/or OIH in considering the reduction of remifentanil dosage or adopting preventive modulations. Twenty-four experimental and clinical studies were identified using electronic searches of MEDLINE (PubMed, Ovid, Springer, and Elsevier). However, the development of AOT and OIH by remifentanil administration remains controversial. There is no sufficient evidence to support or refute the existence of OIH in humans.

  13. Intra-individual Neurocognitive Variability Confers Risk of Dependence in Activities of Daily Living among HIV-Seropositive Individuals without HIV-Associated Neurocognitive Disorders

    Science.gov (United States)

    Morgan, Erin E.; Woods, Steven Paul; Grant, Igor

    2012-01-01

    Although HIV-associated neurocognitive disorders (HAND) are the strong predictors of everyday functioning difficulties, approximately half of all functionally impaired individuals are labeled “neurocognitively normal” according to the standard neuropsychological measures, suggesting that novel predictors of functional problems in this prevalent subgroup are needed. The present study hypothesized that increased neurocognitive intra-individual variability as indexed by dispersion would be associated with poor daily functioning among 82 persons with HIV infection who did not meet research criteria for HAND. An intra-individual standard deviation was calculated across the demographically adjusted T-scores of 13 standard neuropsychological tests to represent dispersion, and functional outcomes included self-reported declines in basic and instrumental activities of daily functioning (basic activity of daily living [BADL] and instrumental activity of daily living [IADL], respectively) and medication management. Dispersion was a significant predictor of medication adherence and dependence in both BADL and IADL, even when other known predictors of functional status (i.e., age, affective distress, and indices of disease severity) were included in the models. As a significant and unique predictor of a performance on the range of daily functioning activities, neurocognitive dispersion may be indicative of deficient cognitive control expressed as inefficient regulation of neurocognitive resources in the context of competing functional demands. As such, dispersion may have clinical utility in detecting risk for functional problems among HIV-infected individuals without HAND. PMID:22337933

  14. Opioid-Induced Constipation and Bowel Dysfunction

    DEFF Research Database (Denmark)

    Müller-Lissner, Stefan; Bassotti, Gabrio; Coffin, Benoit

    2016-01-01

    OBJECTIVE:  To formulate timely evidence-based guidelines for the management of opioid-induced bowel dysfunction. SETTING:  Constipation is a major untoward effect of opioids. Increasing prescription of opioids has correlated to increased incidence of opioid-induced constipation. However, the inh...

  15. Outpatient Provider Contact Prior to Unintentional Opioid Overdose Among VHA Service Users.

    Science.gov (United States)

    Lin, Lewei Allison; Bohnert, Amy S B; Ilgen, Mark A; Pfeiffer, Paul N; Ganoczy, Dara; Blow, Frederic C

    2015-11-01

    Prescription opioid medications are the most commonly implicated substances in unintentional overdoses. Outpatient health care encounters represent a potential opportunity to intervene to reduce opioid overdose risk. This study assessed the timing and type of outpatient provider contacts prior to death from unintentional prescription opioid overdose. This study examined all adult patients nationally in the Veterans Health Administration (VHA) who died from unintentional prescription opioid overdose in fiscal years 2004-2007 and who used VHA services anytime within two years of their deaths (N=1,813). For those whose final treatment contact was in an outpatient setting (N=1,457), demographic, clinical, and treatment characteristics were compared among patients categorized by the location of their last contact. Among individuals last seen in outpatient settings, 33% were seen within one week of their overdose and 62% within one month of their overdose. A substantial proportion of patients (30%) were last seen within one month of death in mental health or substance use disorder outpatient settings. The majority of patients (86%) did not fill an opioid prescription on their last outpatient visit prior to death from unintentional opioid overdose. Most patients who died by unintentional prescription opioid overdose were seen in outpatient settings within a month of their overdose. These settings may provide an opportunity to prevent patients from dying from prescription opioid overdoses. Interventions to reduce risk should not be limited to visits during which an opioid is prescribed.

  16. The Opioid Epidemic: What Does it Mean for Nurses?

    Science.gov (United States)

    Leahy, Laura G

    2017-01-01

    The United States is facing a major crisis with the current opioid epidemic. Tens of thousands of individuals are dying each year due to abuse and misuse of heroin and prescription opiate drugs. Nurses play an integral role in these aspects of health care and offer solutions by providing education; preventive measures; treatments, including medication-assisted treatments (MATs); and ongoing recovery options for individuals with opioid use disorders. Nurses provide education, issue prescriptions and dispense medications, and provide overall physical and mental health care to patients struggling with this "disease of the brain," and with the signing of the Comprehensive Addiction and Recovery Act, advanced practice RNs will soon be able to include MATs related to buprenorphine as part of their treatment plan. The current article explores the anatomy, physiology, and genetics of addiction and how they relate to the pharmacological MATs used to treat opioid use disorders. [Journal of Psychosocial Nursing and Mental Health Services, 55(1), 18-23.].

  17. Chronic pain, opioid prescriptions, and mortality in Denmark

    DEFF Research Database (Denmark)

    Ekholm, Ola; Kurita, Geana Paula; Højsted, Jette

    2014-01-01

    This study aimed to investigate the risk of death, development of cancer, and hospital inpatient admissions resulting from injuries and toxicity/poisoning among opioid users with chronic noncancer pain. A population-based cohort of 13,127 adults, who have participated in the Danish Health Interview...... Surveys in 2000 or 2005 and have been followed up prospectively by registers until the end of 2011, were classified according to the absence or presence of chronic pain (ie, pain lasting ⩾ 6 months) and long-term or short-term opioid use (individuals using at least 1 prescription per month for 6 months...... in the previous year and at least 1 prescription in the previous year, respectively). The risk of all-cause mortality was 1.72 (95% confidence interval [CI]=1.23-2.41) times higher among long-term opioid users than among individuals without chronic pain. The risk of death was lower, but still significantly higher...

  18. Harmonic Force Spectroscopy measures load-dependent kinetics of individual human β-cardiac myosin molecules

    DEFF Research Database (Denmark)

    Sung, Jongmin; Nag, Suman; Mortensen, Kim

    2015-01-01

    Molecular motors are responsible for numerous cellular processes from cargo transport to heart contraction. Their interactions with other cellular components are often transient and exhibit kinetics that depend on load. Here, we measure such interactions using ‘harmonic force spectroscopy...... concentration. We show that a molecule’s ADP release rate depends exponentially on the applied load, in qualitative agreement with cardiac muscle, which contracts with a velocity inversely proportional to external load....

  19. Loneliness in elderly individuals, level of dependence in activities of daily living (ADL) and influential factors.

    Science.gov (United States)

    Hacihasanoğlu, Rabia; Yildirim, Arzu; Karakurt, Papatya

    2012-01-01

    This study has been carried out to investigate the level of loneliness, determine the level of dependence in the ADL and influential factors in the elderly people. This descriptive, cross-sectional study was conducted in 5 Family Healthcare Centers (FHC) located in central Erzincan, Turkey between March and June 2010. The data of the research was collected using a questionnaire that determined the descriptive and UCLA Loneliness Scale (UCLA-LS). Mean score of the UCLA-LS was determined as 51.59 ± 4.44. It was determined that 2% of the elderly ADL were completely dependent, 14.5% were semi-dependent. Factors such as being old, a widow/divorced, having a lower level of education and/or income, living alone, having a chronic disease, poor self-perceived health, lack of visits by relatives or acquaintances, dissatisfaction with the place of living, and being fully dependent while performing daily activities were determined as factors which increased the level of loneliness. Furthermore, factors such as being old, a female, a widow/divorced, living together with a daughter/son, having a chronic disease and poor self-perceived health were found to be influential in dependency. Elderly people who are alone and dependent in fulfilling their ADL should be monitored more closely.

  20. Benchmark study of the length dependent thermal conductivity of individual suspended, pristine SWCNTs.

    Science.gov (United States)

    Liu, Jinhui; Li, Tianyi; Hu, Yudong; Zhang, Xing

    2017-01-26

    The thermal conductivity of individual suspended single-walled carbon nanotubes (SWCNTs) has been theoretically predicated to increase with length but this has never been verified experimentally. This then leads to the question of whether the thermal conductivity saturates to a finite constant value in ultra-long SWCNTs. This paper reports on experimental measurements of the thermal conductivity of individual suspended SWCNTs as a function of the characteristic thermal transport length using the same individual suspended SWCNT sample. Interestingly, at around 360 K, the thermal conductivity first increases with increasing characteristic length and then saturates to a finite constant value at a characteristic length of ∼10 μm. These experimental results provide a fundamental understanding of the phonon transport characteristics in suspended, pristine SWCNTs.

  1. Designing Opioids That Deter Abuse

    Directory of Open Access Journals (Sweden)

    Robert B. Raffa

    2012-01-01

    Full Text Available Prescription opioid formulations designed to resist or deter abuse are an important step in reducing opioid abuse. In creating these new formulations, the paradigm of drug development target should be introduced. Biological targets relating to the nature of addiction may pose insurmountable hurdles based on our current knowledge and technology, but products that use behavioral targets seem logical and feasible. The population of opioid abusers is large and diverse so behavioral targets are more challenging than they appear at first glance. Furthermore, we need to find ways to correlate behavioral observations of drug liking to actual use and abuse patterns. This may involve revisiting some pharmacodynamic concepts in light of drug effect rather than peak concentration. In this paper we present several new opioid analgesic agents designed to resist or deter abuse using physical barriers, the inclusion of an opioid agonist or antagonist, an aversive agent, and a prodrug formulation. Further, this paper also provides insight into the challenges facing drug discovery in this field. Designing and screening for opioids intended to resist or deter abuse is an important step to meet the public health challenge of burgeoning prescription opioid abuse.

  2. Readiness for Change and Treatment Outcome among Individuals with Alcohol Dependency.

    Science.gov (United States)

    Hewes, Robert L.; Janikowski, Timothy P.

    1998-01-01

    Uses the Addiction Severity Index and Stage of Change Readiness and Treatment Eagerness Scale to evaluate individuals with primary alcohol-abuse problems involved in treatment programs. Results indicate that participants showed significant improvement in problems related to alcohol use. No significant differences were found between participants…

  3. Molecular mechanism for opioid dichotomy: bidirectional effect of μ-opioid receptors on P2X₃ receptor currents in rat sensory neurones.

    Science.gov (United States)

    Chizhmakov, Igor; Kulyk, Vyacheslav; Khasabova, Iryna; Khasabov, Sergey; Simone, Donald; Bakalkin, Georgy; Gordienko, Dmitri; Verkhratsky, Alexei; Krishtal, Oleg

    2015-06-01

    Here, we describe a molecular switch associated with opioid receptors-linked signalling cascades that provides a dual opioid control over P2X3 purinoceptor in sensory neurones. Leu-enkephalin inhibited P2X3-mediated currents with IC50 ~10 nM in ~25% of small nociceptive rat dorsal root ganglion (DRG) neurones. In contrast, in neurones pretreated with pertussis toxin leu-enkephalin produced stable and significant increase of P2X3 currents. All effects of opioid were abolished by selective μ-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), nonselective inhibitor naloxone, and by PLC inhibitor U73122. Thus, we discovered a dual link between purinoceptors and μ-opioid receptors: the latter exert both inhibitory (pertussis toxin-sensitive) and stimulatory (pertussis toxin-insensitive) actions on P2X3 receptors through phospholipase C (PLC)-dependent pathways. This dual opioid control of P2X3 receptors may provide a molecular explanation for dichotomy of opioid therapy. Pharmacological control of this newly identified facilitation/inhibition switch may open new perspectives for the adequate medical use of opioids, the most powerful pain-killing agents known today.

  4. Opioid rotation with extended-release opioids: where should we begin?

    Science.gov (United States)

    Nalamachu, Srinivas

    2012-01-01

    Opioid rotation is a common and necessary clinical practice in the management of chronic non-cancer pain to improve therapeutic efficacy with the lowest opioid dose. When dose escalations fail to achieve adequate analgesia or are associated with intolerable side effects, a trial of a new opioid should be considered. Much of the scientific rationale of opioid rotation is based on the wide interindividual variability in sensitivity to opioid analgesics and the novel patient response observed when introducing an opioid-tolerant patient to a new opioid. This article discusses patient indicators for opioid rotation, the conversion process between opioid medications, and additional practical considerations for increasing the effectiveness of opioid therapy during a trial of a new opioid. A Patient vignette that demonstrates a step-wise approach to opioid rotation is also presented.

  5. Assessing opioid shopping behaviour: a large cohort study from a medication dispensing database in the US.

    Science.gov (United States)

    Cepeda, M Soledad; Fife, Daniel; Chow, Wing; Mastrogiovanni, Gregory; Henderson, Scott C

    2012-04-01

    : Risks of abuse, misuse and diversion of opioids are of concern. Obtaining opioid prescriptions from multiple prescribers, known as opioid shopping, is a way in which opioids may be abused and diverted. Previous studies relied on counting the number of prescribers or number of pharmacies a subject goes to in a year to define shopping behaviour, but did not distinguish successive prescribers from concomitant prescribers. : The aim of the study was to assess the frequency of opioid overlapping prescriptions from different prescribers, compare it with diuretics and benzodiazepines, and provide a definition of shopping behaviour that differentiates opioids from diuretics, avoiding the inappropriate flagging of individuals with legitimate use of opioids. : Population-based cohort study using the IMS LRx database. This database covers 65% of all retail prescriptions in the US and includes mail service and specialty pharmacy provider prescriptions independent of the method of payment. : Ambulatory. : Subjects with at least one dispensing for any type of opioid in 2008. Similar cohorts were created for subjects exposed to benzodiazepines or diuretics. Analyses were performed separately for naïve subjects and those with prior use. : Frequency of overlapping prescriptions defined as at least 1 day of overlapping dispensing of prescriptions written by two or more different prescribers at any time during an 18-month period. : A total of 25 161 024 subjects exposed to opioids were included, of whom 13.1% exhibited at least one episode of overlapping prescriptions during 18 months of follow-up. Almost 10% of subjects exposed to benzodiazepines and 13.8% of subjects exposed to diuretics exhibited a similar behaviour. Having overlapping prescriptions dispensed by three or more pharmacies differentiates opioids from the other medication classes. Using that criterion, the overall risk of shopping behaviour was 0.18% in subjects exposed to opioids, 0.10% in subjects exposed to

  6. Psychometric Evaluation of the Life Orientation Test-Revised in Treated Opiate Dependent Individuals

    Science.gov (United States)

    Hirsch, Jameson K.; Britton, Peter C.; Conner, Kenneth R.

    2010-01-01

    We examined internal consistency and test-retest reliability of a measure of dispositional optimism, the Life Orientation Test-Revised, in 121 opiate-dependent patients seeking methadone treatment. Internal consistency was adequate at baseline (alpha = 0.69) and follow-up (alpha = 0.72). Low socioeconomic status and being on disability were…

  7. Individual Learner Differences in CALL: The Field Independence/Dependence (FID) Construct

    Science.gov (United States)

    Chapelle, Carol A.; Heift, Trude

    2009-01-01

    In Spring semester 2006, we conducted a study with 50 learners of German to investigate the use of a new measure (Cardenas-Claros, 2005) for research on the field independent/dependent (FID) cognitive style and CALL use. After the measure was administered, students worked on a CALL program for German that logs interaction. This paper reports the…

  8. Oxytocin attenuates feelings of hostility depending on emotional context and individuals' characteristics

    Science.gov (United States)

    Hirosawa, Tetsu; Kikuchi, Mitsuru; Higashida, Haruhiro; Okumura, Eiichi; Ueno, Sanae; Shitamichi, Kiyomi; Yoshimura, Yuko; Munesue, Toshio; Tsubokawa, Tsunehisa; Haruta, Yasuhiro; Nakatani, Hideo; Hashimoto, Takanori; Minabe, Yoshio

    2012-01-01

    In humans, oxytocin (OT) enhances prosocial behaviour. However, it is still unclear how the prosocial effects of OT are modulated by emotional features and/or individuals' characteristics. In a placebo-controlled design, we tested 20 healthy male volunteers to investigate these behavioural and neurophysiological modulations using magnetoencephalography. As an index of the individuals' characteristics, we used the empathy quotient (EQ), the autism spectrum quotient (AQ), and the systemising quotient (SQ). Only during the perception of another person's angry face was a higher SQ a significant predictor of OT-induced prosocial change, both in the behavioural and neurophysiological indicators. In addition, a lower EQ was only a significant predictor of OT-induced prosocial changes in the neurophysiological indicators during the perception of angry faces. Both on the behavioural and the neurophysiological level, the effects of OT were specific for anger and correlated with a higher SQ. PMID:22540030

  9. Oxytocin facilitation of acceptance of social advice is dependent upon the perceived trustworthiness of individual advisors.

    Science.gov (United States)

    Luo, Ruixue; Xu, Lei; Zhao, Weihua; Ma, Xiaole; Xu, Xiaolei; Kou, Juan; Gao, Zhao; Becker, Benjamin; Kendrick, Keith M

    2017-09-01

    The neuropeptide oxytocin may increase social cohesion by making us more willing to trust others and/or to conform to their opinions. Here we investigated whether intranasal oxytocin can influence acceptance of advice given on solving everyday social problems by either individual expert (psychologist) or non-expert advisors with or without influencing their perceived likeability or trustworthiness. In a double-blind, between-subject, placebo-control design study in 160 male and female subjects, intranasal oxytocin (24IU) only significantly enhanced acceptance of advice given by female psychologists who were rated as the most trustworthy advisors. However, oxytocin itself did not alter either trustworthiness or likeability ratings. The oxytocin effect on acceptance of the female psychologist's advice was not maintained after a week, with subjects mainly reverting to their original solutions. These findings suggest that while oxytocin can transiently increase acceptance of advice from the most trustworthy individuals this is because it makes subjects more likely to conform to their opinions rather than enhancing their perceived trustworthiness or likeability. Thus in every day contexts oxytocin may primarily promote social cohesion by facilitating conformity towards the opinions of the most trusted individuals. Copyright © 2017. Published by Elsevier Ltd.

  10. Chronic Opioid Therapy and Opioid Tolerance: A New Hypothesis

    OpenAIRE

    Goldberg, Joel S.

    2013-01-01

    Opioids are efficacious and cost-effective analgesics, but tolerance limits their effectiveness. This paper does not present any new clinical or experimental data but demonstrates that there exist ascending sensory pathways that contain few opioid receptors. These pathways are located by brain PET scans and spinal cord autoradiography. These nonopioid ascending pathways include portions of the ventral spinal thalamic tract originating in Rexed layers VI–VIII, thalamocortical fibers that proje...

  11. Educational Outreach to Opioid Prescribers: The Case for Academic Detailing.

    Science.gov (United States)

    Trotter Davis, Margot; Bateman, Brian; Avorn, Jerry

    2017-02-01

    Nonmedical use of opioid medications constitutes a serious health threat as the rates of addiction, overdoses, and deaths have risen in recent years. Increasingly, inappropriate and excessively liberal prescribing of opioids by physicians is understood to be a central part of the crisis. Public health officials, hospital systems, and legislators are developing programs and regulations to address the problem in sustained and systematic ways that both insures effective treatment of pain and appropriate limits on the availability of opioids. Three approaches have obtained prominence as means of avoiding excessive and inappropriate prescribing, including: providing financial incentives to physicians to change their clinical decision through pay-for-performance contracts, monitoring patient medications through Prescription Drug Monitoring Programs, and educational outreach to physicians. A promising approach to educational outreach to physicians is an intervention known as "academic detailing." It was developed in the 1980s to provide one-on-one educational outreach to physicians using similar methods as the pharmaceutical industry that sends "detailers" to market their products to physician practices. Core to academic detailing, however, is the idea that medical decisions should be based on evidence-based information, including managing conditions with updated assessment measures, behavioral, and nonpharmacological interventions. With the pharmaceutical industry spending billions of dollars to advertise their products, individual practitioners can have difficulty gathering unbiased information, especially as the number of approved medications grows each year. Academic detailing has successfully affected the management of health conditions, such as atrial fibrillation, chronic obstructive pulmonary disease, and recently, has targeted physicians who prescribe opioids. This article discusses the approach as a potentially effective preventative intervention to address the

  12. Addictive behaviors related to opioid use for chronic pain

    DEFF Research Database (Denmark)

    Højsted, Jette; Ekholm, Kim Ola Michael; Kurita, Geana Paula

    2013-01-01

    ,281 individuals were analyzed through multiple logistic regression analyses to assess the association between chronic pain (lasting ⩾6 months), opioid use, health behavior, and body mass index. Six potential addictive behaviors were identified: daily smoking; high alcohol intake; illicit drug use in the past year...

  13. Environmental and synthesis-dependent luminescence properties of individual single-walled carbon nanotubes.

    Science.gov (United States)

    Duque, Juan G; Pasquali, Matteo; Cognet, Laurent; Lounis, Brahim

    2009-08-25

    Luminescence properties of individual (6,5) single-walled carbon nanotubes (SWNTs) were studied using continuous wave and time-resolved spectroscopy. Nanotubes synthesized by different methods (HiPco and CoMoCat) and dispersed in two different ionic surfactants were examined either in aqueous environments or deposited on surfaces. SWNT preparations leading to the highest luminescence intensities and narrowest spectral widths exhibit the longest luminescence decay times. This highlights the role of the nanotube environment and synthesis methods in the nonradiative relaxation processes of the excitonic recombination. Samples of HiPco nanotubes dispersed in sodium deoxycholate contained the brightest nanotubes in aqueous environments.

  14. Condition-dependent individual decision-making determines cyprinid partial migration

    DEFF Research Database (Denmark)

    Brodersen, J.; Nilsson, P.A.; Hansson, L.A.;

    2008-01-01

    migration. Hence, our main conclusion is that individual decision-making is based on assessment of own condition which offers a mechanistic explanation to partial migration. Moreover, this may be of high importance for understanding population responses to environmental variation as well as ecosystem......Partial migration is a common phenomenon among many animals and occurs in many types of ecosystems. Understanding the mechanisms behind partial migration is of major importance for the understanding of population dynamics and, eventually, ecosystem processes. We studied the effects of food...

  15. Amnesia Affecting Some Opioid Abusers

    Science.gov (United States)

    ... they had used opioids. These drugs include prescription painkillers, such as oxycodone (Oxycontin) and oxycodone and acetaminophen ( ... attributed to a stroke or dementia. Moreover, the brain abnormalities seen on the MRI scans appear to ...

  16. Opioids and their peripheral receptors

    Directory of Open Access Journals (Sweden)

    Francesco Amato

    2012-12-01

    Full Text Available The inflammation of peripheral tissues leads the primary afferent neurons, in particular at the cell bodies level located in the DRG (dorsal root ganglia, to an increased synthesis of opioid receptors: determining an “up-regulation”. After that opioid receptors are transported at the level of the nociceptive terminals, they are incorporated into the neuronal membrane becoming functional receptors. The above receptor proteins bind to opioid produced by immune cells or the exogenous ones. This leads to a direct or indirect suppression of the Ca2+ currents induced by TRPV1 or the currents of the Na+, resulting in neuronal reduced excitability and in transmitted signals decrease. The observation that the immune system is able to modulate the pain by ligands that interact with the opioid receptors located on sensory neurons, may have broad implications for the development of innovative and safer pain drugs.

  17. Newer approaches to opioid detoxification

    Directory of Open Access Journals (Sweden)

    Siddharth Sarkar

    2012-01-01

    Full Text Available Opioid use disorders present with distressing withdrawal symptoms at the time of detoxification. The pharmacological agents and methods currently in use for detoxification mainly include buprenorphine, methadone, and clonidine. Many other pharmacological agents have been tried for opioid detoxification. This review takes a look at the newer pharmacological options, both opioid agonists and non-agonist medications that have been utilized for detoxification. Peer reviewed articles were identified using PubMed and PsychInfo databases. The keywords included for the search were a combination of ′opioid′ and ′detoxification′ and their synonyms. All the articles published in the last 10 years were screened for. Relevant data was extracted from identified studies. Many newer pharmacological agents have been tried in detoxification of opioids. However, the quest for a safe, efficacious, cost-effective pharmacological option which requires minimal monitoring still continues. The role of non-pharmacological measures and alternative medicine needs further evaluation.

  18. Towards safer use of opioids.

    LENUS (Irish Health Repository)

    Carson, R W R

    2009-09-01

    The main aim of our work was to improve the safety of opioid use in our institution, an acute generalhospital with 620 beds. Initially, all reported opioid errors from 2001 - 2006 were audited. The findings directed a range of multidisciplinary staff educational inputs to improve opioid prescribing and administration practice, and encourage drug error reporting. 448 drug errors were reported, of which 54 (12%) involved opioids; of these, 43 (79%) involved codeine, morphine or oxycodone. 31 of the errors (57%) were associated with administration, followed by 12 (22%) with dispensing and 11 (20%) with prescribing. There were 2 reports of definite patient harm. A subsequent audit examined a 17-month period following the introduction of the above teaching: 17 errors were noted, of which 14 (83%) involved codeine, morphine or oxycodone. Again, drug administration was most error-prone, comprising 11 (65%) of reports. However, just 2 (12%) of the reported errors now involved prescribing, which was a reduction.

  19. Critical issues on opioids in chronic non-cancer pain

    DEFF Research Database (Denmark)

    Eriksen, Jørgen; Sjøgren, Per; Bruera, Eduardo

    2006-01-01

    quality of life (SF-36), use of the health care system, functional capabilities, satisfaction with medical pain treatment and regular or continuous use of medications. Participants reporting pain were divided into opioid and non-opioid users. The analyses were adjusted for age, gender, concomitant use...... random sample of 16,684 individuals (>16 years of age), 10,066 took part in an interview and completed a self-administered questionnaire. Cancer patients were excluded. The interview and the self-administered questionnaire included questions on chronic/long-lasting pain (>6 months), health-related...

  20. Temperature-Dependent Charge Transport through Individually Contacted DNA Origami-Based Au Nanowires.

    Science.gov (United States)

    Teschome, Bezu; Facsko, Stefan; Schönherr, Tommy; Kerbusch, Jochen; Keller, Adrian; Erbe, Artur

    2016-10-11

    DNA origami nanostructures have been used extensively as scaffolds for numerous applications such as for organizing both organic and inorganic nanomaterials, studying single molecule reactions, and fabricating photonic devices. Yet, little has been done toward the integration of DNA origami nanostructures into nanoelectronic devices. Among other challenges, the technical difficulties in producing well-defined electrical contacts between macroscopic electrodes and individual DNA origami-based nanodevices represent a serious bottleneck that hinders the thorough characterization of such devices. Therefore, in this work, we have developed a method to electrically contact individual DNA origami-based metallic nanowires using electron beam lithography. We then characterize the charge transport of such nanowires in the temperature range from room temperature down to 4.2 K. The room temperature charge transport measurements exhibit ohmic behavior, whereas at lower temperatures, multiple charge transport mechanisms such as tunneling and thermally assisted transport start to dominate. Our results confirm that charge transport along metallized DNA origami nanostructures may deviate from pure metallic behavior due to several factors including partial metallization, seed inhomogeneities, impurities, and weak electronic coupling among AuNPs. Besides, this study further elucidates the importance of variable temperature measurements for determining the dominant charge transport mechanisms for conductive nanostructures made by self-assembly approaches.

  1. Sex-Dependent Individual Differences and the Correlational Relationship Between Proprioceptive and Verbal Tests

    Directory of Open Access Journals (Sweden)

    Liutsko Liudmila

    2014-09-01

    Full Text Available Introduction. The aim of the study was to analyze the relationship between proprioceptive and verbal tests on personality in both sexes separately due to existing proprioceptive differences in fine motor behavior between men and women in our previous studies [1, 2, 3]. Material and methods. 114 middle-aged participants from Belarus completed verbal tests (personality: Eysenck's EPQ, Big Five in Hromov's Russian adaptation, and Rosenberg's Self-esteem together with Proprioceptive Diagnostics of Temperament and Character (by Tous. Complementary information, such as tests of time perception, was collected and used in correlative and ANOVA analyses with the use of SPSS v.19. Results. The relationship between proprioceptive variables in personality and individual differences, time perception and the results of verbal tests were determined for each sex subgroup and discussed. ANOVA results reflected the corresponding differences and similarities between men and women in the variables of each test. Time perception was found to be significantly correlated to all five dimensions of the Big Five Test in both sexes, and both had a significant relationship to the same variables of the DP-TC test. Conclusions. Time perception can be used as an indirect indicator of personality. Existing individual and personality differences should be taken into account in coaching and education to obtain more effective results.

  2. Comorbid psychiatric diagnoses among individuals presenting to an addiction treatment program for alcohol dependence.

    LENUS (Irish Health Repository)

    Lyne, John Paul

    2011-01-01

    A retrospective patient record review was conducted to examine comorbid psychiatric diagnoses, and comorbid substance use, among 465 patients below 45 years of age, presenting to a national alcohol addiction treatment unit in Dublin, between 1995 and 2006. Rates were high for depressive disorder (25.3%) particularly among females (35.4%). Lifetime reported use of substances other than alcohol was 39.2%, and further analysis showed significantly higher rates of deliberate self-harm among this group. Lifetime reported use of ecstasy was also significantly associated with depression in this alcohol-dependent population using logistic regression analysis. Implications and limitations of the findings are discussed.

  3. Positron Emission Tomography (PET) Imaging of Opioid Receptors

    NARCIS (Netherlands)

    van Waarde, Aren; Absalom, Anthony; Visser, Anniek; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; De Vries, Erik FJ; Van Waarde, Aren; Luiten, Paul GM

    2014-01-01

    The opioid system consists of opioid receptors (which mediate the actions of opium), their endogenous ligands (the enkephalins, endorphins, endomorphins, dynorphin, and nociceptin), and the proteins involved in opioid production, transport, and degradation. PET tracers for the various opioid recepto

  4. Positron Emission Tomography (PET) Imaging of Opioid Receptors

    NARCIS (Netherlands)

    van Waarde, Aren; Absalom, Anthony; Visser, Anniek; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; De Vries, Erik FJ; Van Waarde, Aren; Luiten, Paul GM

    2014-01-01

    The opioid system consists of opioid receptors (which mediate the actions of opium), their endogenous ligands (the enkephalins, endorphins, endomorphins, dynorphin, and nociceptin), and the proteins involved in opioid production, transport, and degradation. PET tracers for the various opioid

  5. PD-L1 Blockade Differentially Impacts Regulatory T Cells from HIV-Infected Individuals Depending on Plasma Viremia.

    Directory of Open Access Journals (Sweden)

    Cristina Peligero

    2015-12-01

    Full Text Available Blocking the PD-1/PD-L1 pathway has emerged as a potential therapy to restore impaired immune responses in human immunodeficiency virus (HIV-infected individuals. Most reports have studied the impact of the PD-L1 blockade on effector cells and neglected possible effects on regulatory T cells (Treg cells, which play an essential role in balancing immunopathology and antiviral effector responses. The aim of this study was to define the consequences of ex vivo PD-L1 blockade on Treg cells from HIV-infected individuals. We observed that HIV infection led to an increase in PD-1+ and PD-L1+ Treg cells. This upregulation correlated with disease progression and decreased under antiretroviral treatment. Treg cells from viremic individuals had a particularly high PD-1 expression and impaired proliferative capacity in comparison with Treg cells from individuals under antiretroviral treatment. PD-L1 blockade restored the proliferative capacity of Treg cells from viremic individuals but had no effect on its suppressive capacity. Moreover, it increased the viral production in cell cultures from viremic individuals. This increase in viral production correlated with an increase in Treg cell percentage and a reduction in the CD4/Treg and CD8/Treg cell ratios. In contrast to the effect of the PD-L1 blockade on Treg cells from viremic individuals, we did not observe a significant effect on the proliferative capacity of Treg cells from individuals in whom viremia was controlled (either spontaneously or by antiretroviral treatment. However, PD-L1 blockade resulted in an increased proliferative capacity of HIV-specific-CD8 T cells in all subjects. Taken together, our findings suggest that manipulating PD-L1 in vivo can be expected to influence the net gain of effector function depending on the subject's plasma viremia.

  6. Climate change and temperature-dependent sex determination: can individual plasticity in nesting phenology prevent extreme sex ratios?

    Science.gov (United States)

    Schwanz, Lisa E; Janzen, Fredric J

    2008-01-01

    Under temperature-dependent sex determination (TSD), temperatures experienced by embryos during development determine the sex of the offspring. Consequently, populations of organisms with TSD have the potential to be strongly impacted by climatic warming that could bias offspring sex ratio, a fundamental demographic parameter involved in population dynamics. Moreover, many taxa with TSD are imperiled, so research on this phenomenon, particularly long-term field study, has assumed great urgency. Recently, turtles with TSD have joined the diverse list of taxa that have demonstrated population-level changes in breeding phenology in response to recent climate change. This raises the possibility that any adverse impacts of climate change on populations may be alleviated by individual plasticity in nesting phenology. Here, we examine data from a long-term study on a population of painted turtles (Chrysemys picta) to determine whether changes in phenology are due to individual plasticity and whether individual plasticity in the timing of nesting has the capacity to offset the sex ratio effects of a rise in climatic temperature. We find that individual females show plasticity in the date of first nesting each year, and that this plasticity depends on the climate from the previous winter. First nesting date is not repeatable within individuals, suggesting that it would not respond to selection. Sex ratios of hatchlings within a nest declined nonsignificantly over the nesting season. However, small increases in summer temperature had a much stronger effect on nest sex ratios than did laying nests earlier in the season. For this and other reasons, it seems unlikely that individual plasticity in the timing of nesting will offset the effects of climate change on sex ratios in this population, and we hypothesize that this conclusion applies to other populations with TSD.

  7. Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531 influences the analgesic response to the short acting opioid Remifentanil in humans

    Directory of Open Access Journals (Sweden)

    Schalling Martin

    2009-07-01

    Full Text Available Abstract Background There is evidence from animal studies that serotonin (5-HT can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531. The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on μ-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS. All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders. Results At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG as compared to those with high expression(LA/LA, p Conclusion This is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of

  8. Consumer attitudes about opioid addiction treatment: a focus group study in New York City.

    Science.gov (United States)

    Sohler, Nancy L; Weiss, Linda; Egan, James E; López, Carolina M; Favaro, Jamie; Cordero, Robert; Cunningham, Chinazo O

    2013-01-01

    To develop effective programs for people who are opioid dependent and to impact the opioid epidemic in New York City, it is crucial to monitor attitudes about opioid addiction treatments among opioid users who have experienced barriers to engagement and retention in addiction treatment. The authors conducted a qualitative study using focus groups. Six focus groups in three needle exchanges in New York City were audio recorded, transcribed, and systematically coded. The authors report on the main themes related to the study objectives. Participants of each needle exchange who were opioid dependent and had some knowledge of both methadone and buprenorphine were eligible. There were four main findings. Participants felt the following: 1) buprenorphine is an appropriate option for those heroin users who are motivated to stop using, 2) they have less control over their addiction treatment with methadone than they would have with buprenorphine, 3) buprenorphine treatment is not accessible to many New York City residents who would benefit from this treatment, and 4) lack of access to buprenorphine treatment is a cause of treatment-related diversion. Both methadone maintenance and buprenorphine treatment opportunities are necessary to address the diverse treatment needs of opioid-dependent people in New York City. However, the current medical model of buprenorphine treatment may be too restrictive for some opioid-dependent people and may be contributing to the use of illicit buprenorphine. New models to deliver buprenorphine treatment may address these problems.

  9. Impact of capillary flow hydrodynamics on carrier-mediated transport of opioid derivatives at the blood-brain barrier, based on pH-dependent Michaelis-Menten and Crone-Renkin analyses.

    Science.gov (United States)

    Yusof, Siti R; Abbott, N Joan; Avdeef, Alex

    2017-08-30

    Most studies of blood-brain barrier (BBB) permeability and transport are conducted at a single pH, but more detailed information can be revealed by using multiple pH values. A pH-dependent biophysical model was applied to the mechanistic analysis of published pH-dependent BBB luminal uptake data from three opioid derivatives in rat: pentazocine (Suzuki et al., 2002a, 2002b), naloxone (Suzuki et al., 2010a), and oxycodone (Okura et al., 2008). Two types of data were processed: in situ brain perfusion (ISBP) and brain uptake index (BUI). The published perfusion data were converted to apparent luminal permeability values, Papp, and analyzed by the pCEL-X program (Yusof et al., 2014), using the pH-dependent Crone-Renkin equation (pH-CRE) to determine the impact of cerebrovascular flow on the Michaelis-Menten transport parameters (Avdeef and Sun, 2011). For oxycodone, the ISBP data had been measured at pH7.4 and 8.4. The present analysis indicates a 7-fold lower value of the cerebrovascular flow velocity, Fpf, than that expected in the original study. From the pyrilamine-inhibited data, the flow-corrected passive intrinsic permeability value was determined to be P0=398×10(-6)cm·s(-1). The uptake data indicate that the neutral form of oxycodone is affected by a transporter at pH8.4. The extent of the cation uptake was less certain from the available data. For pentazocine, the brain uptake by the BUI method had been measured at pH5.5, 6.5, and 7.4, in a concentration range 0.1-40mM. Under similar conditions, ISBP data were also available. The pH-CRE determined values of Fpf from both methods were nearly the same, and were smaller than the expected value in the original publication. The transport of the cationic pentazocine was not fully saturated at pH5.5 at 40mM. The transport of the neutral species at pH7.4 appeared to reach saturation at 40mM pentazocine concentration, but not at 12mM. In the case of naloxone, a pH-dependent Michaelis-Menten equation (p

  10. Peripheral Sensitization Increases Opioid Receptor Expression and Activation by Crotalphine in Rats

    Science.gov (United States)

    Zambelli, Vanessa Olzon; Fernandes, Ana Carolina de Oliveira; Gutierrez, Vanessa Pacciari; Ferreira, Julio Cesar Batista; Parada, Carlos Amilcar; Mochly-Rosen, Daria; Cury, Yara

    2014-01-01

    Inflammation enhances the peripheral analgesic efficacy of opioid drugs, but the mechanisms involved in this phenomenon have not been fully elucidated. Crotalphine (CRP), a peptide that was first isolated from South American rattlesnake C.d. terrificus venom, induces a potent and long-lasting anti-nociceptive effect that is mediated by the activation of peripheral opioid receptors. Because the high efficacy of CRP is only observed in the presence of inflammation, we aimed to elucidate the mechanisms involved in the CRP anti-nociceptive effect induced by inflammation. Using real-time RT-PCR, western blot analysis and ELISA assays, we demonstrate that the intraplantar injection of prostaglandin E2 (PGE2) increases the mRNA and protein levels of the µ- and κ-opioid receptors in the dorsal root ganglia (DRG) and paw tissue of rats within 3 h of the injection. Using conformation state-sensitive antibodies that recognize activated opioid receptors, we show that PGE2, alone does not increase the activation of these opioid receptors but that in the presence of PGE2, the activation of specific opioid receptors by CRP and selective µ- and κ-opioid receptor agonists (positive controls) increases. Furthermore, PGE2 down-regulated the expression and activation of the δ-opioid receptor. CRP increased the level of activated mitogen-activated protein kinases in cultured DRG neurons, and this increase was dependent on the activation of protein kinase Cζ. This CRP effect was much more prominent when the cells were pretreated with PGE2. These results indicate that the expression and activation of peripheral opioid receptors by opioid-like drugs can be up- or down-regulated in the presence of an acute injury and that acute tissue injury enhances the efficacy of peripheral opioids. PMID:24594607

  11. Human exposure to acrolein: Time-dependence and individual variation in eye irritation.

    Science.gov (United States)

    Claeson, Anna-Sara; Lind, Nina

    2016-07-01

    The aim of the study was to examine the time dependence on sensory irritation detection following exposure to threshold levels of acrolein, in humans. The exposures occurred in an exposure chamber and the subjects were breathing fresh air through a mask that covered the nose and mouth. All participants participated in four exposure conditions, of which three consisted of a mixture of acrolein and heptane and one of only heptane. Exposure to acrolein at a concentration half of the TLV-C lead to sensory irritation. The perceived sensory irritation resulted in both increased detectability and sensory irritation after about 6.8min of exposure in 58% of the participants. The study confirm the previously suggested LOAEL of about 0.34mg/m(3) for eye irritation due to acrolein exposure. The sensory irritation was still significant 10min after exposure. These results have implications for risk assessment and limit setting in occupational hygiene.

  12. A randomized comparative trial in the management of Alcohol Dependence: Individualized Homoeopathy versus standard Allopathic Treatment

    Directory of Open Access Journals (Sweden)

    Raj K Manchanda

    2016-01-01

    Full Text Available Objectives: This study was undertaken to compare the effects of IH with standard allopathic (SA treatment. Methods: A randomized controlled, open-label, comparative trial, was conducted, in which alcohol dependents were screened verbally using the CAGE scale. The participants 80 patients fulfilling the inclusion criteria were randomized either IH (n=40 or SA (n=40 and treated cum followed up for 12 months. The primary outcome was more than 50% reduction in the Severity of Alcohol Dependence Questionnaire [SADQ] rating scale at 12 th month. Data analysis was done for both intention-to-treat (ITT and per-protocol (PP populations. Results: ITT analysis reflected 80% (n = 32 of the patients in IH and 37.5% (n = 15 of the patients in the SA responding to CI before 2.4 treatment with absolute difference was 42.5% (42.5 [95% confidence interval [CI]: 23.0, 61.6] and estimated effect: 6.6 (95% C.I: 2.4, 18.2, P = 0.0002. A significant difference favoring IH was also observed in three out of four domains of WHO QOL-BREF. Statistically significant difference was found in the number of drinking days (median difference: −24.00; CI: −39.0-−8.0; P = 0.001 and number of drinks per drinking day (median difference: −6.3 [95% CI: −11.3-−1.9]; P = 0.004, favoring IH. The results showed a similar trend in PP analysis. Medicines found useful were Sulphur, Lycopodium clavatum, Arsenicum album, Nux vomica, Phosphorus, and Lachesis. Conclusion: The results conclude that IH is not inferior to SA in the management of AD patients. More rigorous studies with large sample size are however desirable.

  13. Trends in opioid use and dosing among socio-economically disadvantaged patients

    Science.gov (United States)

    Gomes, Tara; Juurlink, David N; Dhalla, Irfan A; Mailis-Gagnon, Angela; Paterson, J Michael; Mamdani, Muhammad M

    2011-01-01

    Background Opioid therapy for patients with chronic nonmalignant pain remains controversial, primarily because of safety concerns and the potential for abuse. The objective of this study was to examine trends in opioid utilization for nonmalignant pain among recipients of social assistance and to explore the relation between dose of analgesic and mortality. Methods Using a cross-sectional study design, we characterized annual trends in prescriptions for and daily dose of opioid analgesics between 2003 and 2008 for beneficiaries (aged 15 to 64 years) of Ontario’s public drug plan. We defined moderate, high and very high dose thresholds as daily doses of up to 200, 201 to 400, and more than 400 mg oral morphine (or equivalent), respectively. In an exploratory cohort study, we followed, over a 2-year period, patients who received at least one prescription for an opioid in 2004 to investigate the relation between opioid dose and opioid-related mortality. Results Over the study period, opioid prescribing rates rose by 16.2%, and 180 974 individuals received nearly 1.5 million opioid prescriptions in 2008. Also by 2008, the daily dose dispensed exceeded 200 mg morphine equivalent for almost a third (32.6%) of recipients of long-acting oxycodone but only 20.3% of those treated with fentanyl or other long-acting opioids. Among patients for whom high or very high doses of opioids were dispensed in 2004, 19.3% of deaths during the subsequent 2 years were opioid-related, occurring at a median age of 46 years. Two-year opioid-related mortality rates were 1.63 per 1000 population (95% confidence interval [CI] 1.42–1.85) among people with moderate-dose prescriptions, 7.92 per 1000 population (95% CI 5.25–11.49) among those with high-dose prescriptions, and 9.94 per 1000 population (95% CI 2.78–25.12) among those with very-high-dose prescriptions. Interpretation Among socio-economically disadvantaged patients in Ontario, the use and dose of opioids for nonmalignant pain

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

    Science.gov (United States)

    Greenwald, Mark K.

    2008-01-01

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

  15. Unexpected opioid activity in a known class of drug.

    Science.gov (United States)

    Römer, D; Büscher, H H; Hill, R C; Maurer, R; Petcher, T J; Zeugner, H; Benson, W; Finner, E; Milkowski, W; Thies, P W

    Tifluadom, although structurally a 1,4 benzodiazepine, has no affinity for the 3H-flunitrazepam binding site, but is a potent displacer of 3H-bremazocine from its opioid binding site. Tifluadom is characterised as an opiate kappa-receptor agonist in vitro and in vivo with potent analgesic activity in animals and no dependence potential.

  16. "I'm not afraid of those ones just 'cause they've been prescribed": perceptions of risk among illicit users of pharmaceutical opioids.

    Science.gov (United States)

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

    2012-09-01

    There has been a rise in the illicit use of pharmaceutical opioids ("pain pills") in the United States. Conducted with young adult non-medical users of pharmaceutical opioids, this study uses qualitative methods and cultural consensus analysis to describe risk perceptions associated with pharmaceutical opioids and to determine patterns of cultural sharing and intra-cultural variation of these views. The qualitative sub-sample (n=47) was selected from a larger sample of 396 young adults (18-23 years old), who were participating in a natural history study of illicit pharmaceutical opioid use. Qualitative life history interviews, drug ranking task, and cultural consensus analysis were used to elicit participant views about risks and harms associated with pain pills and other drugs, as well as alcohol and tobacco. Cultural consensus analysis revealed that the participants shared a single cultural model of drug risks, but the level of agreement decreased with the increasing range of drugs ever used. Further, those with more extensive drug use histories differed from less "experienced" users in their views about OxyContin and some other drugs. Overall, pain pills were viewed as addicting and potentially deadly substances, but these properties were linked to the patterns and methods of use, as well as characteristics of an individual user. Further, risks associated with pharmaceutical opioids were further curtailed because they "came from the doctor," and thus had a legitimate aspect to their use. This study highlights potential problems with universal approaches to substance use prevention and intervention among young people since such approaches ignore the fact that substance use education messages may be experienced differently depending on an individual's drug use history and his/her perceptions of drug risks. Findings reported here may be useful in the development of prevention and intervention programs aimed at reducing the harm associated with illicit use of pain

  17. 阿片类药物所致呼吸抑制与基因多态性%Opioid induced respiratory depression and gene polymorphism

    Institute of Scientific and Technical Information of China (English)

    姜楠楠; 席宏杰

    2016-01-01

    Opioids is widely used in clinic,and the treatment of moderate to severe pain and most of the post-operative pain are largely dependent on the use of opioids. Most of the commonly used opioids have narrow therapeutic index with great individual differences,and are often accompanied by some serious tolerance and addiction,and even se-rious side effects such as respiratory depression. Research on opioid receptor gene polymorphisms helps to explain dif-ferent reaction to opioids individuals from the angle of molecular biology. Determination of the gene specificity helps to guide the clinical medication and reduce the incidence of side effects such as respiratory depression.%阿片类药物目前在临床上应用广泛,中度至重度疼痛以及大多数术后疼痛的治疗多依赖于阿片类药物的使用。目前临床上常用的吗啡等阿片类镇痛药治疗指数范围窄,个体差异较大,而且常常伴随着严重的耐受性和成瘾性,甚至呼吸抑制( RD)等严重不良反应。研究阿片受体的基因多态性有助于从分子生物学的角度解释个体间对阿片类药物反应存在的差异。确定基因特异性有助于指导临床用药,降低其呼吸抑制等不良反应的发生率。

  18. Stage movement following a 5A's intervention in tobacco dependent individuals with serious mental illness (SMI).

    Science.gov (United States)

    DiClemente, Carlo C; Delahanty, Janine C; Kofeldt, Miranda G; Dixon, Lisa; Goldberg, Richard; Lucksted, Alicia

    2011-03-01

    Smoking among individuals with serious mental illness (SMI) creates significant health problems. This study explored stage of change transitions over time among smokers with serious mental illness (SMI) and how dose of a brief intervention and other psychosocial variables were related to stage transitions. Participants were a subsample of 110 patients who participated in a larger controlled trial (Dixon, et al., 2009) examining whether psychiatrists in mental health clinics implementing the "5A's" (Ask, Advise, Assess, Assist, and Arrange) significantly reduced smoking among persons with SMI. Participants were classified into one of the Transtheoretical Model (TTM) Stages of Change for Smoking Cessation as well as classified into groups based upon the pattern of stage status transitions over time (i.e., Regressors, Stable, Inconsistent, Progressors with and without a successful quit). Modest quit rates for this brief intervention were found at one-year (6.4%) and the dose of the intervention was meaningfully related to positive stage transitions. Cessation outcomes from the controlled trial (Dixon, et al., 2009) indicated a small effect on smoking cessation, which is confirmed in this stage transition secondary analysis with a subset of these smokers. However, these results suggest that a brief intervention delivered by psychiatrists in a mental health treatment setting does seem to make an impact on these smokers.

  19. Degree of functionalisation dependence of individual Raman intensities in covalent graphene derivatives

    Science.gov (United States)

    Vecera, Philipp; Eigler, Siegfried; Koleśnik-Gray, Maria; Krstić, Vojislav; Vierck, Asmus; Maultzsch, Janina; Schäfer, Ricarda A.; Hauke, Frank; Hirsch, Andreas

    2017-01-01

    Covalent functionalisation of graphene is a continuously progressing field of research. The optical properties of such derivatives attract particular attention. In virtually all optical responses, however, an enhancement in peak intensity with increase of sp3 carbon content, and a vanishing of the peak position shift in monolayer compared to few-layer systems, is observed. The understanding of these seemingly connected phenomena is lacking. Here we demonstrate, using Raman spectroscopy and in situ electrostatic doping techniques, that the intensity is directly modulated by an additional contribution from photoluminescent π-conjugated domains surrounded by sp3 carbon regions in graphene monolayers. The findings are further underpinned by a model which correlates the individual Raman mode intensities to the degree of functionalisation. We also show that the position shift in the spectra of solvent-based and powdered functionalised graphene derivatives originates predominantly from the presence of edge-to-edge and edge-to-basal plane interactions and is by large functionalisation independent. PMID:28345640

  20. Addiction to opioids in chronic pain patients: a literature review

    DEFF Research Database (Denmark)

    Højsted, Jette; Sjøgren, Per

    2007-01-01

    Opioids have proven very useful for treatment of acute pain and cancer pain, and in the developed countries opioids are increasingly used for treatment of chronic non-malignant pain patients as well. This literature review aims at giving an overview of definitions, mechanisms, diagnostic criteria...... patients. The review indicates that the prevalence of addiction varied from 0% up to 50% in chronic non-malignant pain patients, and from 0% to 7.7% in cancer patients depending of the subpopulation studied and the criteria used. The risk of addiction has to be considered when initiating long-term opioid...... are concerned with the fact that pain may be under treated because of fear of addiction, and the guidelines in management of non-malignant pain patients include warnings of addiction. According to the literature, it seems appropriate and necessary to be aware of the problems associated with addiction during...

  1. Disparities in safe sex counseling & behavior among individuals with substance dependence: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    D’Amore Meredith M

    2012-12-01

    Full Text Available Abstract Background Despite the vast literature examining disparities in medical care, little is known about racial/ethnic and mental health disparities in sexual health care. The objective of this study was to assess disparities in safe sex counseling and resultant behavior among a patient population at risk of negative sexual health outcomes. Methods We conducted a cross-sectional analysis among a sample of substance dependent men and women in a metropolitan area in the United States. Multiple logistic regression models were used to explore the relationship between race/ethnicity (non-Hispanic black; Hispanic; non-Hispanic white and three indicators of mental illness (moderately severe to severe depression; any manic episodes; ≥3 psychotic symptoms with two self-reported outcomes: receipt of safe sex counseling from a primary care physician and having practiced safer sex because of counseling. Results Among 275 substance-dependent adults, approximately 71% (195/275 reported ever being counseled by their regular doctor about safe sex. Among these 195 subjects, 76% (149/195 reported practicing safer sex because of this advice. Blacks (adjusted odds ratio (AOR: 2.71; 95% confidence interval (CI: 1.36,5.42 and those reporting manic episodes (AOR: 2.41; 95% CI: 1.26,4.60 had higher odds of safe sex counseling. Neither race/ethnicity nor any indicator of mental illness was significantly associated with practicing safer sex because of counseling. Conclusions Those with past manic episodes reported more safe sex counseling, which is appropriate given that hypersexuality is a known symptom of mania. Black patients reported more safe sex counseling than white patients, despite controlling for sexual risk. One potential explanation is that counseling was conducted based on assumptions about sexual risk behaviors and patient race. There were no significant disparities in self-reported safer sex practices because of counseling, suggesting that increased

  2. Nucleus accumbens μ-opioid receptors mediate social reward.

    Science.gov (United States)

    Trezza, Viviana; Damsteegt, Ruth; Achterberg, E J Marijke; Vanderschuren, Louk J M J

    2011-04-27

    Positive social interactions are essential for emotional well-being and proper behavioral development of young individuals. Here, we studied the neural underpinnings of social reward by investigating the involvement of opioid neurotransmission in the nucleus accumbens (NAc) in social play behavior, a highly rewarding social interaction in adolescent rats. Intra-NAc infusion of morphine (0.05-0.1 μg) increased pinning and pouncing, characteristic elements of social play behavior in rats, and blockade of NAc opioid receptors with naloxone (0.5 μg) prevented the play-enhancing effects of systemic morphine (1 mg/kg, s.c.) administration. Thus, stimulation of opioid receptors in the NAc was necessary and sufficient for morphine to increase social play. Intra-NAc treatment with the selective μ-opioid receptor agonist [D-Ala(2),N-MePhe(4),Gly(5)-ol]enkephalin (DAMGO) (0.1-10 ng) and the μ-opioid receptor antagonist Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP) (0.3-3 μg) increased and decreased social play, respectively. The δ-opioid receptor agonist DPDPE ([D-Pen(2),D-Pen(5)]-enkephalin) (0.3-3 μg) had no effects, whereas the κ-opioid receptor agonist U69593 (N-methyl-2-phenyl-N-[(5R,7S,8S)-7-(pyrrolidin-1-yl)-1-oxaspiro[4.5]dec-8-yl]acetamide) (0.01-1 μg) decreased social play. Intra-NAc treatment with β-endorphin (0.01-1 μg) increased social play, but met-enkephalin (0.1-5 μg) and the enkephalinase inhibitor thiorphan (0.1-1 μg) were ineffective. DAMGO (0.1-10 ng) increased social play after infusion into both the shell and core subregions of the NAc. Last, intra-NAc infusion of CTAP (3 μg) prevented the development of social play-induced conditioned place preference. These findings identify NAc μ-opioid receptor stimulation as an important neural mechanism for the attribution of positive value to social interactions in adolescent rats. Altered NAc μ-opioid receptor function may underlie social impairments in psychiatric disorders such as autism

  3. Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual.

    Science.gov (United States)

    Khan, Lubina; Makhdoomi, Muzamil Ashraf; Kumar, Sanjeev; Nair, Ambili; Andrabi, Raiees; Clark, Brenda E; Auyeung, Kate; Bhattacharya, Jayanta; Vajpayee, Madhu; Wig, Naveet; Pantophlet, Ralph; Luthra, Kalpana

    2015-01-01

    Dissecting antibody specificities in the plasma of HIV-1 infected individuals that develop broadly neutralizing antibodies (bNAbs) is likely to provide useful information for refining target epitopes for vaccine design. Several studies have reported CD4-binding site (CD4bs) antibodies as neutralization determinants in the plasma of subtype B-infected individuals; however there is little information on the prevalence of CD4bs specificities in HIV-infected individuals in India. Here, we report on the presence of CD4bs antibodies and their contribution to virus neutralization in the plasma from a cohort of HIV-1 infected Indian individuals. Plasma from 11 of the 140 HIV-1 infected individuals (7.9%) studied here exhibited cross-neutralization activity against a panel of subtype B and C viruses. Analyses of these 11 plasma samples for the presence of CD4bs antibodies using two CD4bs-selective probes (antigenically resurfaced HXB2gp120 core protein RSC3 and hyperglycosylated JRFLgp120 mutant ΔN2mCHO) revealed that five (AIIMS 617, 619, 627, 642, 660) contained RSC3-reactive plasma antibodies and only one (AIIMS 660) contained ΔN2mCHO-reactive antibodies. Plasma antibody depletion and competition experiments confirmed that the neutralizing activity in the AIIMS 660 plasma was dependent on CD4bs antibodies. To the best of our knowledge, this is the first study to report specifically on the presence of CD4bs antibodies in the plasma of a cohort of HIV-1 infected Indian donors. The identification of CD4bs dependent neutralizing antibodies in an HIV-1 infected Indian donor is a salient finding of this study and is supportive of ongoing efforts to induce similar antibodies by immunization.

  4. Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual.

    Directory of Open Access Journals (Sweden)

    Lubina Khan

    Full Text Available Dissecting antibody specificities in the plasma of HIV-1 infected individuals that develop broadly neutralizing antibodies (bNAbs is likely to provide useful information for refining target epitopes for vaccine design. Several studies have reported CD4-binding site (CD4bs antibodies as neutralization determinants in the plasma of subtype B-infected individuals; however there is little information on the prevalence of CD4bs specificities in HIV-infected individuals in India. Here, we report on the presence of CD4bs antibodies and their contribution to virus neutralization in the plasma from a cohort of HIV-1 infected Indian individuals. Plasma from 11 of the 140 HIV-1 infected individuals (7.9% studied here exhibited cross-neutralization activity against a panel of subtype B and C viruses. Analyses of these 11 plasma samples for the presence of CD4bs antibodies using two CD4bs-selective probes (antigenically resurfaced HXB2gp120 core protein RSC3 and hyperglycosylated JRFLgp120 mutant ΔN2mCHO revealed that five (AIIMS 617, 619, 627, 642, 660 contained RSC3-reactive plasma antibodies and only one (AIIMS 660 contained ΔN2mCHO-reactive antibodies. Plasma antibody depletion and competition experiments confirmed that the neutralizing activity in the AIIMS 660 plasma was dependent on CD4bs antibodies. To the best of our knowledge, this is the first study to report specifically on the presence of CD4bs antibodies in the plasma of a cohort of HIV-1 infected Indian donors. The identification of CD4bs dependent neutralizing antibodies in an HIV-1 infected Indian donor is a salient finding of this study and is supportive of ongoing efforts to induce similar antibodies by immunization.

  5. Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-labouring myometrium.

    Science.gov (United States)

    Fanning, Rebecca A; McMorrow, Jason P; Campion, Deirdre P; Carey, Michael F; O'Connor, John J

    2013-01-05

    The existence of opioid receptors in mammalian myometrial tissue is now widely accepted. Previously enkephalin degrading enzymes have been shown to be elevated in pregnant rat uterus and a met-enkephalin analogue has been shown to alter spontaneous contractility of rat myometrium. Here we have undertaken studies to determine the effects of met-enkephalin on in vitro human myometrial contractility and investigate the expression of opioid receptors in pregnant myometrium. Myometrial biopsies were taken from women undergoing elective caesarean delivery at term. Organ bath experiments were used to investigate the effect of the met-enkephalin analogue [d-Ala 2, d-met 5] enkephalin (DAMEA) on spontaneous contractility. A confocal immunofluorescent technique and real time PCR were used to determine the expression of protein and mRNA, respectively for two opioid receptor subtypes, mu and delta. DAMEA had a concentration dependent inhibitory effect on contractile activity (1 × 10(-7)M-1 × 10(-4)M; 54% reduction in contractile activity, Popioid receptor protein sub-types and their respective mRNA were identified in all tissues sampled. This is the first report of opioid receptor expression and of an opioid mediated uterorelaxant action in term human non-labouring myometrium in vitro.

  6. Neural correlates of adherence to extended-release naltrexone pharmacotherapy in heroin dependence

    Science.gov (United States)

    Wang, A-L; Elman, I; Lowen, S B; Blady, S J; Lynch, K G; Hyatt, J M; O'Brien, C P; Langleben, D D

    2015-01-01

    Injectable extended-release naltrexone (XRNTX) presents an effective therapeutic strategy for opioid addiction, however its utility could be hampered by poor adherence. To gain a better insight into this phenomenon, we utilized blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) in conjunction with a validated cue-induced craving procedure to examine neural correlates of XRNTX adherence. We operationalized treatment adherence as the number of monthly XRNTX injections (range: 0–3) administered to a group of fully detoxified heroin-dependent subjects (n=32). Additional outcomes included urine toxicology screening and self-reported tobacco use. The presented heroin-related visual cues reliably elicited heroin craving in all tested subjects. Nine, five, three and 15 of the participants, respectively, received zero, one, two and three XRNTX injections, predicted by the individual baseline fMRI signal change in response to the cues in the medial prefrontal cortex, a brain region involved in inhibitory self-control and emotional appraisal. The incidence of opioid-positive urines during the XRNTX therapy was low and remained about half the pre-treatment rate after the XRNTX ended. During the treatment, cigarette smoking behaviors followed patterns of opioid use, while cocaine consumption was increased with reductions in opioid use. The present data support the hypothesis that medial prefrontal cortex functions are involved in adherence to opioid antagonist therapy. A potential role of concurrent non-opioid addictive substances consumption during the XRNTX pharmacotherapy warrants further investigation. Our findings set the stage for further bio-behavioral investigations of the mechanisms of relapse prevention in opioid dependence. PMID:25781230

  7. Continuous multimechanistic postoperative analgesia: a rationale for transitioning from intravenous acetaminophen and opioids to oral formulations.

    Science.gov (United States)

    Pergolizzi, Joseph V; Raffa, Robert B; Tallarida, Ronald; Taylor, Robert; Labhsetwar, Sumedha A

    2012-02-01

    Good surgical outcomes depend in part on good pain relief, allowing for early mobilization, optimal recovery, and patient satisfaction. Postsurgical pain has multiple mechanisms, and multimechanistic approaches to postoperative analgesia are recommended and may be associated with improved pain relief, lowered opioid doses, and sometimes a lower rate of opioid-associated side effects. Acetaminophen (paracetamol) is a familiar agent for treating many types of pain, including postsurgical pain. Oral acetaminophen has been shown to be safe and effective in a variety of acute pain models. Combination products using a fixed-dose of acetaminophen and an opioid have also been effective in treating postsurgical pain. Combination products with acetaminophen have demonstrated an opioid-sparing effect, which inconsistently results in a reduced rate of opioid-associated side effects. Intravenous (IV) acetaminophen and an opioid analgesic administered in the perioperative period may be followed by an oral acetaminophen and opioid combination in the postoperative period. Transitioning from an IV acetaminophen and opioid formulation to a similar but oral formulation of the same drugs appears to be a reasonable step in that both analgesic therapies are known to be safe and effective. For postsurgical analgesia with any acetaminophen product, patient education is necessary to be sure that the patient does not concurrently take any over-the-counter products containing acetaminophen and accidentally exceed dose limits.

  8. PK20, a new opioid-neurotensin hybrid peptide that exhibits central and peripheral antinociceptive effects

    Directory of Open Access Journals (Sweden)

    Tsuda Yuko

    2010-12-01

    Full Text Available Abstract Background The clinical treatment of various types of pain relies upon the use of opioid analgesics. However most of them produce, in addition to the analgesic effect, several side effects such as the development of dependence and addiction as well as sedation, dysphoria, and constipation. One solution to these problems are chimeric compounds in which the opioid pharmacophore is hybridized with another type of compound to incease antinociceptive effects. Neurotensin-induced antinociception is not mediated through the opioid system. Therefore, hybridizing neurotensin with opioid elements may result in a potent synergistic antinociceptor. Results Using the known structure-activity relationships of neurotensin we have synthesized a new chimeric opioid-neurotensin compound PK20 which is characterized by a very strong antinociceptive potency. The observation that the opioid antagonist naltrexone did not completely reverse the antinociceptive effect, indicates the partial involvement of the nonopioid component in PK20 in the produced analgesia. Conclusions The opioid-neurotensin hybrid analogue PK20, in which opioid and neurotensin pharmacophores overlap partially, expresses high antinociceptive tail-flick effects after central as well as peripheral applications.

  9. Subcortical grey matter alterations in cocaine dependent individuals with substance-induced psychosis compared to non-psychotic cocaine users.

    Science.gov (United States)

    Willi, Taylor S; Lang, Donna J; Honer, William G; Smith, Geoff N; Thornton, Allen E; Panenka, William J; Procyshyn, Ric M; Vila-Rodriguez, Fidel; Su, Wayne; Vertinsky, A Talia; Leonova, Olga; Rauscher, Alexander; MacEwan, G William; Barr, Alasdair M

    2016-10-01

    After prolonged psychostimulant abuse, transient psychotic symptoms referred to as "substance-induced psychosis" (SIP) can develop - closely resembling symptoms observed in schizophrenia spectrum disorders. The comparability in psychotic presentation between SIP and schizophrenias suggests that similar underlying neural deficits may contribute to the expression of psychosis across these disorders. To date, neuroanatomical characterization of grey matter structural alterations in SIP has been limited to methamphetamine associated psychosis, with no studies controlling for potential neurotoxic effects of the psychostimulant that precipitates psychosis. To investigate grey matter subcortical alterations in SIP, a voxel-based analysis of magnetic resonance images (MRI) was performed between a group of 74 cocaine dependent nonpsychotic individuals and a group of 29 individuals with cocaine-associated psychosis. The cocaine-associated psychosis group had significantly smaller volumes of the thalamus and left hippocampus, controlling for age, total brain volume, current methamphetamine dependence, and current marijuana dependence. No differences were present in bilateral caudate structures. The findings of reduced thalamic and hippocampal volumes agree with previous reports in the schizophrenia literature, suggesting alterations of these structures are not specific to schizophrenia, but may be common to multiple forms of psychosis.

  10. AIDS AS A CHALLENGE FOR THE DEVELOPMENT OF THE TREATMENT OF OPIOID DEPENDENTS IN CHINA Report on the 9th National Conference on Drug Dependence, MMT and HIV Prevention in Sanya/Hainan (VR China), 1-5 November 2006

    Institute of Scientific and Technical Information of China (English)

    Ingo Ilja Michels

    2007-01-01

    @@ Nearly 100 experts from all over China attended the Chinese National Conference on Drug Dependence in Sanya/Hainan. The participants came from drug abuse treatment centers, methadone clinics and drug research institutes. The conference's focus was on the question how drug abuse treatment shall and might be part of HIV prevention. CHINALi xiao(The Federal Drug Commissioner with the Federal Ministry of Health, Berlin)

  11. Medicare Part D Opioid Drug Mapping Tool

    Data.gov (United States)

    U.S. Department of Health & Human Services — The opioid prescribing rate interactive mapping tool shows geographic comparisons, at the state, county, and ZIP code levels, of de-identified Medicare Part D opioid...

  12. Opioids and Alcohol a Dangerous Cocktail

    Science.gov (United States)

    ... taken opioids previously. Oxycodone, an ingredient in the brand-name drugs OxyContin and Percocet, is widely prescribed ... in the journal Anesthesiology . "We hope to increase awareness regarding the dangers of prescription opioids, the increased ...

  13. Direct association of Mu-opioid and NMDA glutamate receptors supports their cross-regulation: molecular implications for opioid tolerance.

    Science.gov (United States)

    Garzón, Javier; Rodríguez-Muñoz, María; Sánchez-Blázquez, Pilar

    2012-09-01

    In the nervous system, the interaction of opioids like morphine and its derivatives, with the G protein-coupled Mu-opioid receptor (MOR) provokes the development of analgesic tolerance, as well as physical dependence. Tolerance implies that increasing doses of the drug are required to achieve the same effect, a phenomenon that contributes significantly to the social problems surrounding recreational opioid abuse. In recent years, our understanding of the mechanisms that control MOR function in the nervous system, and that eventually produce opioid tolerance, has increased greatly. Pharmacological studies have identified a number of signaling proteins involved in morphine-induced tolerance, including the N-methyl-D-aspartate acid glutamate receptor (NMDAR), nitric oxide synthase (NOS), protein kinase C (PKC), protein kinase A (PKA), calcium (Ca²⁺)/calmodulin (CaM)-dependent kinase II (CaMKII), delta-opioid receptor (DOR) and the regulators of G-protein signaling (RGS) proteins. There is general agreement on the critical role of the NMDAR/nNOS/CaMKII pathway in this process, which is supported by the recent demonstration of a physical association between MORs and NMDARs in post-synaptic structures. Indeed, it is feasible that treatments that diminish morphine tolerance may target distinct elements within the same regulatory MOR-NMDAR pathway. Accordingly, we propose a model that incorporates the most relevant signaling components implicated in opioid tolerance in which, certain signals originating from the activated MOR are perceived by the associated NMDAR, which in turn exerts a negative feedback effect on MOR signaling. MOR- and NMDAR-mediated signals work together in a sequential and interconnected manner to ultimately induce MOR desensitization. Future studies of these phenomena should focus on adding further components to this signaling pathway in order to better define the mechanism underlying MOR desensitization in neural cells.

  14. Nurses and opioids: results of a bi-national survey on mental models regarding opioid administration in hospitals

    Directory of Open Access Journals (Sweden)

    Guest C

    2017-03-01

    Full Text Available Charlotte Guest,1 Fabian Sobotka,2 Athina Karavasopoulou,3 Stephen Ward,3 Carsten Bantel4,5 1Pain Medicine, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK; 2Division of Epidemiology and Biometry, Department of Health Services Research, Faculty 6, Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany; 3Pain Service, Barts Health, St Bartholomew’s Hospital, London, UK; 4Department of Anaesthesiology, Intensive Care, Emergency Medicine and Pain Therapy, Oldenburg University, Klinikum Oldenburg Campus, Oldenburg, Germany; 5Department of Surgery and Cancer, Anaesthetics Section, Imperial College London, Chelsea and Westminster Hospital Campus, London, UK Objective: Pain remains insufficiently treated in hospitals. Increasing evidence suggests human factors contribute to this, due to nurses failing to administer opioids. This behavior might be the consequence of nurses’ mental models about opioids. As personal experience and conceptions shape these models, the aim of this prospective survey was to identify model-influencing factors. Material and methods: A questionnaire was developed comprising of 14 statements concerning ideations about opioids and seven questions concerning demographics, indicators of adult learning, and strength of religious beliefs. Latent variables that may underlie nurses’ mental models were identified using undirected graphical dependence models. Representative items of latent variables were employed for ordinal regression analysis. Questionnaires were distributed to 1,379 nurses in two London, UK, hospitals (n=580 and one German (n=799 hospital between September 2014 and February 2015. Results: A total of 511 (37.1% questionnaires were returned. Mean (standard deviation age of participants were 37 (11 years; 83.5% participants were female; 45.2% worked in critical care; and 51.5% had more than 10 years experience. Of the nurses, 84% were not scared of opioids, 87

  15. Opioid Peptides: Potential for Drug Development

    OpenAIRE

    Aldrich, Jane V.; McLaughlin, Jay P.

    2012-01-01

    Opioid receptors are important targets for the treatment of pain and potentially for other disease states (e.g. mood disorders and drug abuse) as well. Significant recent advances have been made in identifying opioid peptide analogs that exhibit promising in vivo activity for treatment of these maladies. This review focuses on the development and evaluation of opioid peptide analogs demonstrating activity after systemic administration, and recent clinical evaluations of opioid peptides for po...

  16. The relationship between temporal discounting and the prisoner's dilemma game in intranasal abusers of prescription opioids.

    Science.gov (United States)

    Yi, Richard; Buchhalter, August R; Gatchalian, Kirstin M; Bickel, Warren K

    2007-02-23

    Previous research on college students has found that cooperation in iterated prisoner's dilemma game is correlated with preference for delayed rewards in studies of temporal discounting. The present study attempted to replicate this finding in a drug-dependent population. Thirty-one individuals who intranasally abuse prescription opioids participated in temporal discounting and iterated prisoner's dilemma game procedures during intake for a treatment study. Rate of temporal discounting was determined for each participant at two hypothetical reward magnitudes, as well as proportion of cooperation in a 60-trial iterated prisoner's dilemma game versus a tit-for-tat strategy. Cooperation in the prisoner's dilemma game and temporal discounting rates were significantly correlated in the predicted direction: individuals who preferred delayed rewards in the temporal discounting task were more likely to cooperate in the prisoner's dilemma game.

  17. Fifty hertz magnetic fields individually affect chromatin conformation in human lymphocytes: dependence on amplitude, temperature, and initial chromatin state.

    Science.gov (United States)

    Sarimov, Ruslan; Alipov, Eugene D; Belyaev, Igor Y

    2011-10-01

    Effects of magnetic field (MF) at 50 Hz on chromatin conformation were studied by the method of anomalous viscosity time dependence (AVTD) in human lymphocytes from two healthy donors. MF within the peak amplitude range of 5-20 µT affected chromatin conformation. These MF effects differed significantly between studied donors, and depended on magnetic flux density and initial condensation of chromatin. While the initial state of chromatin was rather stable in one donor during one calendar year of measurements, the initial condensation varied significantly in cells from another donor. Both this variation and the MF effect depended on temperature during exposure. Despite these variations, the general rule was that MF condensed the relaxed chromatin and relaxed the condensed chromatin. Thus, in this study we show that individual effects of 50 Hz MF exposure at peak amplitudes within the range of 5-20 µT may be observed in human lymphocytes in dependence on the initial state of chromatin and temperature. Copyright © 2011 Wiley-Liss, Inc.

  18. Opioid-use disorder among patients on long-term opioid therapy: impact of final DSM-5 diagnostic criteria on prevalence and correlates

    Directory of Open Access Journals (Sweden)

    Boscarino JA

    2015-08-01

    Full Text Available Joseph A Boscarino,1 Stuart N Hoffman,1 John J Han2 1Center for Health Research, 2Department of Pain Medicine, Geisinger Clinic, Danville, PA, USAAims: Previously, we estimated the prevalence and risk factors for prescription opioid-use disorder among outpatients on opioid therapy using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5 and DSM-4 criteria. However, at the time, the DSM-5 criteria were not finalized. In the current study, we analyzed these data using the final DSM-5 criteria and compared these results.Methods: Using electronic records from a large US health care system, we identified outpatients receiving five or more prescription orders for opioid therapy in the past 12 months for noncancer pain (mean prescription orders =10.72; standard deviation =4.96. In 2008, we completed diagnostic interviews with 705 of these patients using the DSM-4 criteria. In the current study, we reassessed these results using the final DSM-5 criteria.Results: The lifetime prevalence of DSM-5 opioid-use disorders using the final DSM-5 criteria was 58.7% for no or few symptoms (<2, 28.1% for mild symptoms (2–3, 9.7% for moderate symptoms (4–5, and 3.5% for severe symptoms (six or more. Thus, the lifetime prevalence of “any” prescription opioid-use disorder in this cohort was 41.3% (95% confidence interval [CI] =37.6–45.0. A comparison to the DSM-4 criteria indicated that the majority of patients with lifetime DSM-4 opioid dependence were now classified as having mild opioid-use disorder, based on the DSM-5 criteria (53.6%; 95% CI =44.1–62.8. In ordinal logistic regression predicting no/few, mild, moderate, and severe opioid-use disorder, the best predictors were age <65 years, current pain impairment, trouble sleeping, suicidal thoughts, anxiety disorders, illicit drug use, and history of substance abuse treatment.Conclusion: Given the final DSM-5 criteria, including the elimination of tolerance and withdrawal, inclusion of

  19. Opioid Use in Fibromyalgia: A Cautionary Tale.

    Science.gov (United States)

    Goldenberg, Don L; Clauw, Daniel J; Palmer, Roy E; Clair, Andrew G

    2016-05-01

    Multiple pharmacotherapies are available for the treatment of fibromyalgia (FM), including opioid analgesics. We postulate that the mechanism of action of traditional opioids predicts their lack of efficacy in FM. Literature searches of the MEDLINE and Cochrane Library databases were conducted using the search term opioid AND fibromyalgia to identify relevant articles, with no date limitations set. Citation lists in returned articles and personal archives of references were also examined for additional relevant items, and articles were selected based on the expert opinions of the authors. We found no evidence from clinical trials that opioids are effective for the treatment of FM. Observational studies have found that patients with FM receiving opioids have poorer outcomes than patients receiving nonopioids, and FM guidelines recommend against the use of opioid analgesics. Despite this, and despite the availability of alternative Food and Drug Administration-approved pharmacotherapies and the efficacy of nonpharmacologic therapies, opioids are commonly used in the treatment of FM. Factors associated with opioid use include female sex; geographic variation; psychological factors; a history of opioid use, misuse, or abuse; and patient or physician preference. The long-term use of opioid analgesics is of particular concern in the United States given the ongoing public health emergency relating to excess prescription opioid consumption. The continued use of opioids to treat FM despite a proven lack of efficacy, lack of support from treatment guidelines, and the availability of approved pharmacotherapy options provides a cautionary tale for their use in other chronic pain conditions.

  20. Policies and events affecting prescription opioid use for non-cancer pain among an insured patient population.

    Science.gov (United States)

    Ahmedani, Brian K; Peterson, Edward L; Wells, Karen E; Lanfear, David E; Williams, L Keoki

    2014-01-01

    Rising prescription opioid use and abuse have prompted widespread concern. However, to date there have been few rigorous investigations into the policies and events which may have contributed to these trends. This study investigates trends in opioid use and related adverse events among individuals with non-cancer pain before and after implementation of major national policies. The study used a longitudinal prospective study design. The analysis was limited to adults (age = 18 years) without a recorded cancer diagnosis. Pharmacy claims were used to assess rates of prescription opioid use, the strength of opioids dispensed, the proportion using opioids chronically, and related adverse events. Time trend analysis was used to identify changes in these rates over time. The study was Institutional Review Board approved. Study patients were members of a large, health maintenance organization in southeast Michigan, with longitudinal records of prescription opioid use. The analysis comprised 523,623 individuals and 1,066,700 opioid pharmacy fills from January 1, 1997, to December 31, 2011. Contemporaneous with the implementation of health organization accreditation criteria requiring assessment and treatment of pain in all patients beginning January 2001, we observed a consistent and unabated increase in the rate of opioid fills and the proportion of chronic use. A parallel increase in the annual rate of adverse events was also observed. Similarly, we observed a continuous rise in the average strength of opioid fills following January 2001 with the exception of a single drop in December 2010, which was attributable to the withdrawal of propoxyphene from the U.S. market. This was an observational study and not a trial. Other long-term opioid-related benefits or harms, including functional status, quality of life, and substance use disorder, were not assessed. This study provides temporal evidence for a rise in prescription opioid use after implementation of health

  1. Patterns and Correlates of Prescription Opioid Use in OEF/OIF Veterans with Chronic Non-Cancer Pain

    Science.gov (United States)

    2011-10-01

    collected information regarding substance use disorder (defined as substance abuse/dependence diagnoses for alcohol, amphetamine, cannabis, cocaine , opioids...Author M anuscript N IH -PA Author M anuscript overdose or death [34]. Finally, although the use of urine drug screening was greater in the opioid users

  2. Cannabis as a Substitute for Opioid-Based Pain Medication: Patient Self-Report.

    Science.gov (United States)

    Reiman, Amanda; Welty, Mark; Solomon, Perry

    2017-01-01

    Introduction: Prescription drug overdoses are the leading cause of accidental death in the United States. Alternatives to opioids for the treatment of pain are necessary to address this issue. Cannabis can be an effective treatment for pain, greatly reduces the chance of dependence, and eliminates the risk of fatal overdose compared to opioid-based medications. Medical cannabis patients report that cannabis is just as effective, if not more, than opioid-based medications for pain. Materials and Methods: The current study examined the use of cannabis as a substitute for opioid-based pain medication by collecting survey data from 2897 medical cannabis patients. Discussion: Thirty-four percent of the sample reported using opioid-based pain medication in the past 6 months. Respondents overwhelmingly reported that cannabis provided relief on par with their other medications, but without the unwanted side effects. Ninety-seven percent of the sample "strongly agreed/agreed" that they are able to decrease the amount of opiates they consume when they also use cannabis, and 81% "strongly agreed/agreed" that taking cannabis by itself was more effective at treating their condition than taking cannabis with opioids. Results were similar for those using cannabis with nonopioid-based pain medications. Conclusion: Future research should track clinical outcomes where cannabis is offered as a viable substitute for pain treatment and examine the outcomes of using cannabis as a medication assisted treatment for opioid dependence.

  3. Pain volatility and prescription opioid addiction treatment outcomes in patients with chronic pain.

    Science.gov (United States)

    Worley, Matthew J; Heinzerling, Keith G; Shoptaw, Steven; Ling, Walter

    2015-12-01

    The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (n = 149) who received buprenorphine/naloxone (BUP/NLX) and counseling for 12 weeks in an outpatient, multisite clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least 2 of the previous 3 weeks. Pain severity significantly declined over time during treatment (b = -0.36, p treatment outcome (odds ratio = 0.55, p treatment provides observational support for the analgesic effects of BUP/NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk of returning to opioid use by the conclusion of an intensive treatment with BUP/NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain.

  4. NKTR-181: A Novel Mu-Opioid Analgesic with Inherently Low Abuse Potential.

    Science.gov (United States)

    Miyazaki, Takahiro; Choi, Irene Y; Rubas, Werner; Anand, Neel K; Ali, Cherie; Evans, Juli; Gursahani, Hema; Hennessy, Marlene; Kim, Grace; McWeeney, Daniel; Pfeiffer, Juergen; Quach, Phi; Gauvin, David; Riley, Timothy A; Riggs, Jennifer A; Gogas, Kathleen; Zalevsky, Jonathan; Doberstein, Stephen K

    2017-08-04

    The increasing availability of prescription opioid analgesics for the treatment of pain has been paralleled by an epidemic of opioid misuse, diversion, and overdose. The development of abuse-deterrent formulations (ADF) of conventional opioids such as oxycodone and morphine represents an advance in the field and has had a positive but insufficient impact, as most opioids are still prescribed in highly abusable, non-ADF forms, and abusers can tamper with ADF medications to liberate the abusable opioid within. The abuse liability of mu-opioid agonists appears to be dependent on their rapid rate of entry into the central nervous system (CNS) while analgesic activity appears to be a function of CNS exposure alone, suggesting that a new opioid agonist with an inherently low rate of influx across the blood-brain barrier could mediate analgesia with low abuse liability, regardless of formulation or route of administration. NKTR-181 is a novel, long-acting, selective mu-opioid agonist with structural properties that reduce its rate of entry across the blood-brain barrier compared with traditional mu-opioid agonists. NKTR-181 demonstrated maximum analgesic activity comparable to that of oxycodone in hot-plate latency and acetic acid writhing models. NKTR-181 was distinguishable from oxycodone by its reduced abuse potential in self-administration and progressive ratio break point models, with behavioral effects similar to those of saline, as well as reduced CNS side effects as measured by the modified Irwin test. The in vitro and in vivo studies presented here demonstrate that NKTR-181 is the first selective mu-opioid agonist to combine analgesic efficacy and reduced abuse liability through the alteration of brain-entry kinetics. The American Society for Pharmacology and Experimental Therapeutics.

  5. Endomorphins and related opioid peptides.

    Science.gov (United States)

    Okada, Yoshio; Tsuda, Yuko; Bryant, Sharon D; Lazarus, Lawrence H

    2002-01-01

    Opioid peptides and their G-protein-coupled receptors (delta, kappa, mu) are located in the central nervous system and peripheral tissues. The opioid system has been studied to determine the intrinsic mechanism of modulation of pain and to develop uniquely effective pain-control substances with minimal abuse potential and side effects. Two types of endogenous opioid peptides exist, one containing Try-Gly-Gly-Phe as the message domain (enkephalins, endorphins, dynorphins) and the other containing the Tyr-Pro-Phe/Trp sequence (endomorphins-1 and -2). Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2), which has high mu receptor affinity (Ki = 0.36 nM) and remarkable selectivity (4000- and 15,000-fold preference over the delta and kappa receptors, respectively), was isolated from bovine and human brain. In addition, endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), isolated from the same sources, exhibited high mu receptor affinity (Ki = 0.69 nM) and very high selectivity (13,000- and 7500-fold preference relative to delta and kappa receptors, respectively). Both opioids bind to mu-opioid receptors, thereby activating G-proteins, resulting in regulation of gastrointestinal motility, manifestation of antinociception, and effects on the vascular systems and memory. To develop novel analgesics with less addictive properties, evaluation of the structure-activity relationships of the endomorphins led to the design of more potent and stable analgesics. Opioidmimetics and opioid peptides containing the amino acid sequence of the message domain of endomorphins, Tyr-Pro-Phe/Trp, could exhibit unique binding activity and lead to the development of new therapeutic drugs for controlling pain.

  6. Post-traumatic stress disorder and opioid use disorder: A narrative review of conceptual models.

    Science.gov (United States)

    Danovitch, Itai

    2016-01-01

    Post-traumatic stress disorder is highly prevalent among individuals who suffer from opioid use disorder. Compared to individuals with opioid use disorder alone, those with post-traumatic stress disorder have a worse course of illness, occupational functioning, and physical health. The neurobiological pathways underlying each disorder overlap substantially, and there are multiple pathways through which these disorders may interact. This narrative review explores evidence underpinning 3 explanatory perspectives on comorbid post-traumatic stress disorder and opioid use disorder: The opioid susceptibility model (a.k.a.: the Self-Medication Hypothesis), the post-traumatic stress disorder susceptibility model, and the common factors model. Diagnostic implications, treatment implications, and directions for future research are discussed.

  7. Opioid Analgesic and Benzodiazepine Prescribing Among Medicaid-Enrollees with Opioid Use Disorders: The Influence of Provider Communities

    Science.gov (United States)

    Stein, Bradley D.; Mendelsohn, Joshua; Gordon, Adam J.; Dick, Andrew W.; Burns, Rachel M.; Sorbero, Mark; Shih, Regina A.; Pacula, Rosalie Liccardo

    2017-01-01

    Background Opioid analgesic and benzodiazepine use in individuals with opioid use disorders (OUDs) can increase the risk for medical consequences and relapse. Little is known about rates of use of these medications or prescribing patterns among communities of prescribers. Aims To examine rates of prescribing to Medicaid-enrollees in the calendar year after an OUD diagnosis, and to examine individual, county, and provider community factors associated with such prescribing. Methods We used 2008 Medicaid claims data from 12 states to identify enrollees diagnosed with OUDs, and 2009 claims data to identify rates of prescribing of each drug. We used social network analysis to identify provider communities and multivariate regression analyses to identify patient, county, and provider community level factors associated with prescribing these drugs. We also examined variation in rates of prescribing across provider communities. Results Among Medicaid-enrollees identified with an OUD, 45% filled a prescription for an opioid analgesic, 37% for a benzodiazepine, and 21% for both in the year following their diagnosis. Females, older individuals, individuals with pain syndromes, and individuals residing in counties with higher rates of poverty were more likely to fill prescriptions. Prescribing rates varied substantially across provider communities, with rates in the highest quartile of prescribing communities over 2.5 times the rates in the lowest prescribing communities. Discussion Prescribing opioid analgesics and benzodiazepines to individuals diagnosed with OUDs may increase risk of relapse and overdose. Interventions should be considered that target provider communities with the highest rates of prescribing and individuals at highest risk. PMID:27449904

  8. Efficacy of disulfiram and Twelve Step Facilitation in cocaine-dependent individuals maintained on methadone: A randomized placebo-controlled trial

    Science.gov (United States)

    Carroll, Kathleen M.; Nich, Charla; Shi, Julia M.; Eagan, Dorothy; Ball, Samuel A.

    2012-01-01

    Background Cocaine use remains a major problem within methadone maintenance programs. Disulfiram’s efficacy in reducing cocaine use has been demonstrated in several trials, but its relative efficacy among individuals who use versus abstain from alcohol remains unclear Treatment approaches which seek to enhance substance users’ involvement in self-help activities (Twelve Step Facilitation, TSF) have been associated with better outcomes among alcohol and cocaine users, but have rarely been evaluated among methadone-maintained cocaine-opioid users. Methods We conducted a randomized, placebo controlled, double blind (for medication condition), factorial (2×2) trial with 4 treatment conditions: Disulfiram plus TSF, disulfiram plus standard counseling only, placebo plus TSF, and placebo plus standard counseling in the context of a community-based methadone maintenance program. Participants (N=112) received either disulfiram (250 mg/d) or placebo in conjunction with daily methadone maintenance. Results Assignment to TSF was associated with less cocaine use throughout treatment and a higher number of cocaine-negative urines. While there were no significant main effects of disulfiram versus placebo, individuals without an alcohol use disorder demonstrated greater reductions in cocaine use over time when assigned to disulfiram. Conclusions TSF appears feasible in this methadone maintenance program and was associated with modest reductions in cocaine use, an often intractable problem in this setting. Support for the efficacy of disulfiram was weaker, as it appeared effective only for those without a current alcohol use disorder for this sample. PMID:22695473

  9. The impact of clinical and demographic variables on cognitive performance in methamphetamine-dependent individuals in rural South Carolina.

    Science.gov (United States)

    Price, Kimber L; DeSantis, Stacia M; Simpson, Annie N; Tolliver, Bryan K; McRae-Clark, Aimee L; Saladin, Michael E; Baker, Nathaniel L; Wagner, Mark T; Brady, Kathleen T

    2011-01-01

    Inconsistencies in reports on methamphetamine (METH) associated cognitive dysfunction may be attributed, at least in part, to the diversity of study sample features (eg, clinical and demographic characteristics). The current study assessed cognitive function in a METH-dependent population from rural South Carolina, and the impact of demographic and clinical characteristics on performance. Seventy-one male (28.2%) and female (71.8%) METH-dependent subjects were administered a battery of neurocognitive tests including the Test of Memory Malingering (TOMM), Shipley Institute of Living Scale, Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), Grooved Pegboard Test, California Verbal Learning Test (CVLT), and Wisconsin Card Sorting Test (WCST). Demographic and clinical characteristics (eg, gender, frequency of METH use) were examined as predictors of performance. Subjects scored significantly lower than expected on one test of attention and one of fine motor function, but performed adequately on all other tests. There were no predictors of performance on attention; however, more frequent METH use was associated with better performance for males and worse for females on fine motor skills. The METH-dependent individuals in this population exhibit very limited cognitive impairment. The marked differences in education, Intellectual Quotient (IQ), and gender in our sample when compared to the published literature may contribute to these findings. Characterization of the impact of clinical and/or demographic features on cognitive deficits could be important in guiding the development of treatment interventions. © American Academy of Addiction Psychiatry.

  10. Opioid rotation with extended-release opioids: where should we begin?

    Directory of Open Access Journals (Sweden)

    Nalamachu S

    2011-12-01

    Full Text Available Srinivas NalamachuInternational Clinical Research Institute and Pain Management Institute, Overland Park, KS, USAAbstract: Opioid rotation is a common and necessary clinical practice in the management of chronic non-cancer pain to improve therapeutic efficacy with the lowest opioid dose. When dose escalations fail to achieve adequate analgesia or are associated with intolerable side effects, a trial of a new opioid should be considered. Much of the scientific rationale of opioid rotation is based on the wide interindividual variability in sensitivity to opioid analgesics and the novel patient response observed when introducing an opioid-tolerant patient to a new opioid. This article discusses patient indicators for opioid rotation, the conversion process between opioid medications, and additional practical considerations for increasing the effectiveness of opioid therapy during a trial of a new opioid. A Patient vignette that demonstrates a step-wise approach to opioid rotation is also presented.Keywords: extended-release opioids, chronic pain, opioid rotation

  11. Non-analgesic effects of opioids: opioids and the endocrine system.

    Science.gov (United States)

    Elliott, Jennifer A; Opper, Susan E; Agarwal, Sonali; Fibuch, Eugene E

    2012-01-01

    Opioids are among the oldest known and most widely used analgesics. The application of opioids has expanded over the last few decades, especially in the treatment of chronic non-malignant pain. This upsurge in opioid use has been accompanied by the increasingly recognized occurrence of opioid-associated endocrinopathy. This may arise after exposure to enteral, parenteral, or neuraxial opioids. Opioid-associated endocrinopathy consists primarily of hypothalamic-pituitary-gonadal axis or hypothalamic-pituitary-adrenal axis dysfunction and may manifest with symptoms of hypogonadism, adrenal dysfunction, and other hormonal disturbances. Additionally, opioid related endocrine dysfunction may be coupled with such disorders as osteoporosis and mood disturbances including depression. Undesirable changes in pain sensitivity such as opioid-induced hyperalgesia, and reduced potency of opioid analgesia may also be potential consequences of chronic opioid consumption. Few studies to date have been able to establish what degree of opioid exposure, in terms of dose or duration of therapy, may predispose patients to opioid-associated endocrinopathy. This article will review the currently available literature concerning opioid-associated endocrinopathy and will provide recommendations for the evaluation, monitoring, and management of opioid-associated endocrinopathy and its other accompanying undesired effects.

  12. Cloning and characterization of Xen-dorphin prohormone from Xenopus laevis: a new opioid-like prohormone distinct from proenkephalin and prodynorphin.

    Science.gov (United States)

    Pattee, Patrick; Ilie, Alina-Elena; Benyhe, Sandor; Toth, Geza; Borsodi, Anna; Nagalla, Srinivasa R

    2003-12-26

    Opioid-like peptides mediate analgesia and induce behavioral effects such as tolerance and dependence by ligand-receptor-mediated mechanisms. The classical opioid prohormones can generate several bioactive peptides, and these divergent families of prohormones share a common well conserved ancestral opioid motif (Tyr-Gly-Gly-Phe). Evidence from pharmacological and molecular cloning studies indicates the presence of multiple isoforms of opioid ligands and receptors that are as yet uncharacterized. To identify potential new members we used the opioid motif as an anchor sequence and isolated two distinct isoforms (Xen-dorphins A and B) of an opioid prohormone from Xenopus laevis brain cDNA library. Xen-dorphin prohormones can generate multiple novel opioid ligands distinct from the known members of this family. Both isoforms are present in a wide variety of tissues including the brain. Two potential bioactive peptides, Xen-dorphin-1A and -1B, that were chemically synthesized showed opioid agonist activity in frog and rat brain membranes using a [35S]GTPgammaS assay. Initial radioligand binding experiments demonstrated that Xen-dorphin-1B binds with high affinity to opioid receptor(s) and with potential preference to the kappa-opioid receptor subtype. Cloning of the Xen-dorphin prohormone provides new evidence for the potential presence of other members in the opioid peptide superfamily.

  13. Opioid analgesics and P-glycoprotein efflux transporters: a potential systems-level contribution to analgesic tolerance.

    Science.gov (United States)

    Mercer, Susan L; Coop, Andrew

    2011-01-01

    Chronic clinical pain remains poorly treated. Despite attempts to develop novel analgesic agents, opioids remain the standard analgesics of choice in the clinical management of chronic and severe pain. However, mu opioid analgesics have undesired side effects including, but not limited to, respiratory depression, physical dependence and tolerance. A growing body of evidence suggests that P-glycoprotein (P-gp), an efflux transporter, may contribute a systems-level approach to the development of opioid tolerance. Herein, we describe current in vitro and in vivo methodology available to analyze interactions between opioids and P-gp and critically analyze P-gp data associated with six commonly used mu opioids to include morphine, methadone, loperamide, meperidine, oxycodone, and fentanyl. Recent studies focused on the development of opioids lacking P-gp substrate activity are explored, concentrating on structure-activity relationships to develop an optimal opioid analgesic lacking this systems-level contribution to tolerance development. Continued work in this area will potentially allow for delineation of the mechanism responsible for opioid-related P-gp up-regulation and provide further support for evidence based medicine supporting clinical opioid rotation.

  14. A new opioid designed multiple ligand derived from the micro opioid agonist endomorphin-2 and the delta opioid antagonist pharmacophore Dmt-Tic.

    Science.gov (United States)

    Salvadori, Severo; Trapella, Claudio; Fiorini, Stella; Negri, Lucia; Lattanzi, Roberta; Bryant, Sharon D; Jinsmaa, Yunden; Lazarus, Lawrence H; Balboni, Gianfranco

    2007-11-15

    Opioid compounds with mixed micro agonist/delta antagonist properties could be used as analgesics with low propensity to induce tolerance and dependence. Here we report the synthesis of a new designed multiple ligand deriving from the micro selective agonist endomorphin-2 and the delta selective antagonist pharmacophore Dmt-Tic. As predicted, the resulting bivalent ligand showed a micro agonist/delta antagonist profile deriving from the corresponding activities of each pharmacophore.

  15. Differential prescribing of opioid analgesics according to physician specialty for Medicaid patients with chronic noncancer pain diagnoses.

    Science.gov (United States)

    Ringwalt, Chris; Gugelmann, Hallam; Garrettson, Mariana; Dasgupta, Nabarun; Chung, Arlene E; Proescholdbell, Scott K; Skinner, Asheley Cockrell

    2014-01-01

    Despite >20 years of studies investigating the characteristics of patients seeking or receiving opioid analgesics, research characterizing factors associated with physicians' opioid prescribing practices has been inconclusive, and the role of practitioner specialty in opioid prescribing practices remains largely unknown. To examine the relationships between physicians' and other providers' primary specialties and their opioid prescribing practices among patients with chronic noncancer pain (CNCP). Prescriptions for opioids filled by 81,459 Medicaid patients with CNCP in North Carolina (USA), 18 to 64 years of age, enrolled at any point during a one-year study period were examined. χ2 statistics were used to examine bivariate differences in prescribing practices according to specialty. For multivariable analyses, maximum-likelihood logistic regression models were used to examine the effect of specialty on prescribing practices, controlling for patients' pain diagnoses and demographic characteristics. Of prescriptions filled by patients with CNCP, who constituted 6.4% of the total sample of 1.28 million individuals, 12.0% were for opioids. General practitioner⁄family medicine specialists and internists were least likely to prescribe opioids, and orthopedists were most likely. Across specialties, men were more likely to receive opioids than women, as were white individuals relative to other races⁄ethnicities. In multivariate analyses, all specialties except internal medicine had higher odds of prescribing an opioid than general practitioners: orthopedists, OR 7.1 (95% CI 6.7 to 7.5); dentists, OR 3.5 (95% CI 3.3 to 3.6); and emergency medicine physicians, OR 2.7 (95% CI 2.6 to 2.8). Significant differences in opioid prescribing practices across prescriber specialties may be reflective of differing norms concerning the appropriateness of opioids for the control of chronic pain. If so, sharing these norms across specialties may improve the care of patients with

  16. Opioid use in the elderly.

    NARCIS (Netherlands)

    Wilder-Smith, O.H.G.

    2005-01-01

    Pain treatment in the elderly is an important challenge to Western societies due to increasing numbers of old persons, their higher incidence of pain, and their greater susceptibility to adverse effects of pain medication. We provide an overview of the factors liable to influence opioid action in

  17. Opioid use in the elderly.

    NARCIS (Netherlands)

    Wilder-Smith, O.H.G.

    2005-01-01

    Pain treatment in the elderly is an important challenge to Western societies due to increasing numbers of old persons, their higher incidence of pain, and their greater susceptibility to adverse effects of pain medication. We provide an overview of the factors liable to influence opioid action in th

  18. Nurses and opioids: results of a bi-national survey on mental models regarding opioid administration in hospitals

    Science.gov (United States)

    Guest, Charlotte; Sobotka, Fabian; Karavasopoulou, Athina; Ward, Stephen; Bantel, Carsten

    2017-01-01

    Objective Pain remains insufficiently treated in hospitals. Increasing evidence suggests human factors contribute to this, due to nurses failing to administer opioids. This behavior might be the consequence of nurses’ mental models about opioids. As personal experience and conceptions shape these models, the aim of this prospective survey was to identify model-influencing factors. Material and methods A questionnaire was developed comprising of 14 statements concerning ideations about opioids and seven questions concerning demographics, indicators of adult learning, and strength of religious beliefs. Latent variables that may underlie nurses’ mental models were identified using undirected graphical dependence models. Representative items of latent variables were employed for ordinal regression analysis. Questionnaires were distributed to 1,379 nurses in two London, UK, hospitals (n=580) and one German (n=799) hospital between September 2014 and February 2015. Results A total of 511 (37.1%) questionnaires were returned. Mean (standard deviation) age of participants were 37 (11) years; 83.5% participants were female; 45.2% worked in critical care; and 51.5% had more than 10 years experience. Of the nurses, 84% were not scared of opioids, 87% did not regard opioids as drugs to help patients die, and 72% did not view them as drugs of abuse. More English (41%) than German (28%) nurses were afraid of criminal investigations and were constantly aware of side effects (UK, 94%; Germany, 38%) when using opioids. Four latent variables were identified which likely influence nurses’ mental models: “conscious decision-making”; “medication-related fears”; “practice-based observations”; and “risk assessment”. They were predicted by strength of religious beliefs and indicators of informal learning such as experience but not by indicators of formal learning such as conference attendance. Conclusion Nurses in both countries employ analytical and affective mental

  19. Opioids Switching with Transdermal Systems in Chronic Cancer Pain

    Directory of Open Access Journals (Sweden)

    Barbarisi M

    2009-05-01

    Full Text Available Abstract Background Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy Objective To assess the efficacy and tolerability of an alternative transdermally applied (TDS opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment. Methods A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks Results Pain relief as assessed by VAS, PPI, and PRI significantly improved (p Conclusion Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.

  20. Intra-individual variation of GH-dependent markers in athletes: comparison of population based and individual thresholds for detection of GH abuse in sports.

    Science.gov (United States)

    Kniess, Astrid; Ziegler, Eckart; Thieme, Detlef; Müller, R Klaus

    2013-10-01

    The GH-2000 discriminant functions, using insulin-like growth factor I (IGF-I) and the N-terminal propeptide of type III procollagen (PIIINP), enabled the detection of growth hormone (GH) doping despite the broad inter-individual normal range of both peptides. The sensitivity of the discriminant function-based methodology may perhaps be further increased in future by applying individual athlete profiles. The purpose of the present study was to evaluate the intra-individual variability of IGF-I, PIIINP and the GH-2000 scores in athletes. For this purpose a total of eight blood samples were taken from each of fifty male and female elite athletes over a period of up to 18 months. The IGF-I and PIIINP levels, we found, lay predominantly within the reference range for elite athletes. The intra-individual variability for IGF-I ranged between 6 and 26%, while that for PIIINP ranged between 6 and 33%. The intra-individual variations of both parameters were higher in female than in male subjects and were found to be mostly moderate. We found that the intra-individual variations of the GH-2000 test scores, expressed as CV, ranged from 4 to 36% and were in most of the subjects markedly smaller than the inter-individual variation. Individual cut-offs for the GH-2000 scores would be lower than population based ones in most of the cases.

  1. Involvement of opioid peptides in the regulation of reproduction in the prawn Penaeus indicus

    Science.gov (United States)

    Sreenivasula Reddy, P.

    The possible involvement of an endogenous opioid system in the regulation of ovarian development in the prawn Penaeus indicus was investigated. Injection of leucine-enkephalin significantly increased the ovarian index and oocyte diameter in a dose-dependent manner. In contrast, injection of methionine-enkephalin significantly decreased the ovarian index and oocyte diameters. These results provide evidence to support the hypothesis that an opioid system is involved in the regulation of reproduction in crustaceans.

  2. Quality Improvement Initiative to Decrease Variability of Emergency Physician Opioid Analgesic Prescribing

    Directory of Open Access Journals (Sweden)

    John H. Burton

    2016-05-01

    Full Text Available Introduction: Addressing pain is a crucial aspect of emergency medicine. Prescription opioids are commonly prescribed for moderate to severe pain in the emergency department (ED; unfortunately, prescribing practices are variable. High variability of opioid prescribing decisions suggests a lack of consensus and an opportunity to improve care. This quality improvement (QI initiative aimed to reduce variability in ED opioid analgesic prescribing. Methods: We evaluated the impact of a three-part QI initiative on ED opioid prescribing by physicians at seven sites. Stage 1: Retrospective baseline period (nine months. Stage 2: Physicians were informed that opioid prescribing information would be prospectively collected and feedback on their prescribing and that of the group would be shared at the end of the stage (three months. Stage 3: After physicians received their individual opioid prescribing data with blinded comparison to the group means (from Stage 2 they were informed that individual prescribing data would be unblinded and shared with the group after three months. The primary outcome was variability of the standard error of the mean and standard deviation of the opioid prescribing rate (defined as number of patients discharged with an opioid divided by total number of discharges for each provider. Secondary observations included mean quantity of pills per opioid prescription, and overall frequency of opioid prescribing. Results: The study group included 47 physicians with 149,884 ED patient encounters. The variability in prescribing decreased through each stage of the initiative as represented by the distributions for the opioid prescribing rate: Stage 1 mean 20%; Stage 2 mean 13% (46% reduction, p<0.01, and Stage 3 mean 8% (60% reduction, p<0.01. The mean quantity of pills prescribed per prescription was 16 pills in Stage 1, 14 pills in Stage 2 (18% reduction, p<0.01, and 13 pills in Stage 3 (18% reduction, p<0.01. The group mean

  3. It's MORe exciting than mu: crosstalk between mu opioid receptors and glutamatergic transmission in the mesolimbic dopamine system.

    Science.gov (United States)

    Chartoff, Elena H; Connery, Hilary S

    2014-01-01

    Opioids selective for the G protein-coupled mu opioid receptor (MOR) produce potent analgesia and euphoria. Heroin, a synthetic opioid, is considered one of the most addictive substances, and the recent exponential rise in opioid addiction and overdose deaths has made treatment development a national public health priority. Existing medications (methadone, buprenorphine, and naltrexone), when combined with psychosocial therapies, have proven efficacy in reducing aspects of opioid addiction. Unfortunately, these medications have critical limitations including those associated with opioid agonist therapies (e.g., sustained physiological dependence and opioid withdrawal leading to high relapse rates upon discontinuation), non-adherence to daily dosing, and non-renewal of monthly injection with extended-release naltrexone. Furthermore, current medications fail to ameliorate key aspects of addiction such as powerful conditioned associations that trigger relapse (e.g., cues, stress, the drug itself). Thus, there is a need for developing novel treatments that target neural processes corrupted with chronic opioid use. This requires a basic understanding of molecular and cellular mechanisms underlying effects of opioids on synaptic transmission and plasticity within reward-related neural circuits. The focus of this review is to discuss how crosstalk between MOR-associated G protein signaling and glutamatergic neurotransmission leads to immediate and long-term effects on emotional states (e.g., euphoria, depression) and motivated behavior (e.g., drug-seeking, relapse). Our goal is to integrate findings on how opioids modulate synaptic release of glutamate and postsynaptic transmission via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate receptors in the nucleus accumbens and ventral tegmental area with the clinical (neurobehavioral) progression of opioid dependence, as well as to identify gaps in knowledge that can be addressed in future studies.

  4. 42 CFR 8.11 - Opioid treatment program certification.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Opioid treatment program certification. 8.11... PROVISIONS CERTIFICATION OF OPIOID TREATMENT PROGRAMS Certification and Treatment Standards § 8.11 Opioid... Substances Act (21 U.S.C. 823(g)(1)) to dispense opioid drugs in the treatment of opioid addiction. An OTP...

  5. Epidural and opioid analgesia following the Nuss procedure

    Science.gov (United States)

    Walaszczyk, Malgorzata; Knapik, Piotr; Misiolek, Hanna; Korlacki, Wojciech

    2011-01-01

    Summary Background Parents have the right to decide on behalf of their children and deny consent to regional anaesthesia. The investigators decided to investigate quality of postoperative analgesia in adolescents undergoing epidural and opioid analgesia following the Nuss procedure. Material/Methods The study subjects were 61 adolescents aged 11–18 years who underwent pectus excavatum repair with the Nuss procedure. Patients were divided into epidural (n=41) and opioid (n=20) groups, depending on their parents’ consent to epidural catheter insertion. Intraoperatively, 0.5% epidural ropivacaine with fentanyl or intermittent intravenous injections of fentanyl were used. Postoperative analgesia was achieved with either epidural infusion of 0.1% ropivacaine with fentanyl, or subcutaneous morphine via an intraoperatively inserted “butterfly” cannula. Additionally, both groups received metamizol and paracetamol. Primary outcome variables were postoperative pain scores (Numeric Rating Scale and Prince Henry Hospital Pain Score). Secondary outcome variables included hemodynamic parameters, additional analgesia and side effects. Results Heart rate and blood pressure values in the postoperative period were significantly higher in the opioid group. Pain scores requiring intervention were noted almost exclusively in the opioid group. Conclusions Denial of parental consent to epidural analgesia following the Nuss procedure results in significantly worse control of postoperative pain. Our data may be useful when discussing with parents the available anaesthetic techniques for exceptionally painful procedures. PMID:22037752

  6. Opioid substitution treatment in New Zealand: a 40 year perspective.

    Science.gov (United States)

    Deering, Daryle; Sellman, J Douglas; Adamson, Simon

    2014-07-04

    We provide an overview of the history and philosophy of the treatment for opioid dependence, which has been dominated by methadone substitution treatment for the past 40 years in New Zealand. Although changes in approach have occurred over this time, influenced by various sociopolitical events and changing ideologies, opioid substitution treatment has still "not come of age". It remains undermined by stigma and risk concerns associated with methadone and has struggled to be accessible and attractive to illicit opioid drug users, comprehensive and integrated into mainstream health care. However, the introduction in 2012 of Pharmac-subsidised buprenorphine combined with naloxone (Suboxone) in the context of an emerging trend towards a broader recovery and well-being orientation could signal a new era in treatment. The availability of buprenorphine-naloxone may also facilitate a further shift in treatment from primarily siloed specialist addiction services to integrated primary care services. This shift will help reduce stigma, promote patient self-management and community integration and align opioid substitution treatment with treatment for other chronic health conditions such as diabetes and asthma.

  7. Effects of Combined Opioids on Pain and Mood in Mammals

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    Richard H. Rech

    2012-01-01

    Full Text Available The authors review the opioid literature for evidence of increased analgesia and reduced adverse side effects by combining mu-opioid-receptor (MOR agonists, kappa-opioid-receptor (KOR agonists, and nonselective low-dose-opioid antagonists (LD-Ant. We tested fentanyl (MOR agonist and spiradoline (KOR agonist, singly and combined, against somatic and visceral pain models. Combined agonists induced additive analgesia in somatic pain and synergistic analgesia in visceral pain. Other investigators report similar effects and reduced tolerance and dependence with combined MOR agonist and KOR agonist. LD-Ant added to either a MOR agonist or KOR agonist markedly enhanced analgesia of either agonist. In accordance with other place-conditioning (PC studies, our PC investigations showed fentanyl-induced place preference (CPP and spiradoline-induced place aversion (CPA. We reduced fentanyl CPP with a low dose of spiradoline and reduced spiradoline CPA with a low dose of fentanyl. We propose combined MOR agonist, KOR agonist, and LD-Ant to produce superior analgesia with reduced adverse side effects, particularly for visceral pain.

  8. Experimental verification of the individual energy dependencies of the partial L-shell photoionization cross sections of Pd and Mo.

    Science.gov (United States)

    Hönicke, Philipp; Kolbe, Michael; Müller, Matthias; Mantler, Michael; Krämer, Markus; Beckhoff, Burkhard

    2014-10-17

    An experimental method for the verification of the individually different energy dependencies of L(1)-, L(2)-, and L(3)- subshell photoionization cross sections is described. The results obtained for Pd and Mo are well in line with theory regarding both energy dependency and absolute values, and confirm the theoretically calculated cross sections by Scofield from the early 1970 s and, partially, more recent data by Trzhaskovskaya, Nefedov, and Yarzhemsky. The data also demonstrate the questionability of quantitative x-ray spectroscopical results based on the widely used fixed jump ratio approximated cross sections with energy independent ratios. The experiments are carried out by employing the radiometrically calibrated instrumentation of the Physikalisch-Technische Bundesanstalt at the electron storage ring BESSY II in Berlin; the obtained fluorescent intensities are thereby calibrated at an absolute level in reference to the International System of Units. Experimentally determined fixed fluorescence line ratios for each subshell are used for a reliable deconvolution of overlapping fluorescence lines. The relevant fundamental parameters of Mo and Pd are also determined experimentally in order to calculate the subshell photoionization cross sections independently of any database.

  9. Prefrontal hypoactivity associated with impaired inhibition in stimulant-dependent individuals but evidence for hyperactivation in their unaffected siblings.

    Science.gov (United States)

    Morein-Zamir, Sharon; Simon Jones, P; Bullmore, Edward T; Robbins, Trevor W; Ersche, Karen D

    2013-09-01

    A neurocognitive endophenotype has been proposed for stimulant dependence, based on behavioral measures of inhibitory response control associated with white matter changes in the frontal cortex. This study investigated the functional neuroimaging correlates of inhibitory response control, as functional activity serves as a more dynamic measure than brain structure, allowing refinement of the suggested endophenotype. Stimulant-dependent individuals (SDIs), their unaffected siblings (SIBs), and healthy controls (CTs) performed the stop-signal task, including stop-signal reaction time (SSRT) as a measure of response inhibition, while undergoing functional magnetic resonance imaging. SDIs had impaired response inhibition accompanied by hypoactivation in the ventrolateral prefrontal cortex (PFC). In addition, they demonstrated hypoactivation in the anterior cingulate when failing to stop. In contrast, no hypoactivations were noted in their unaffected SIBs. Rather, they exhibited increased activation in the dorsomedial PFC relative to controls, together with inhibitory performance that was intermediate between that of the stimulant group and the healthy CT group. Such hyperactivations within the neurocircuitry underlying response inhibition and control are suggestive of compensatory mechanisms that could be protective in nature or could reflect coping with a pre-existing vulnerability, thus expressing potential aspects of resilience. The functional activation associated with response inhibition and error monitoring showed differential patterns of results between SDIs and their unaffected first-degree relatives, suggesting that the proposed endophenotype does not generalize to functional brain activity.

  10. Probing the gate--voltage-dependent surface potential of individual InAs nanowires using random telegraph signals.

    Science.gov (United States)

    Salfi, Joe; Paradiso, Nicola; Roddaro, Stefano; Heun, Stefan; Nair, Selvakumar V; Savelyev, Igor G; Blumin, Marina; Beltram, Fabio; Ruda, Harry E

    2011-03-22

    We report a novel method for probing the gate-voltage dependence of the surface potential of individual semiconductor nanowires. The statistics of electronic occupation of a single defect on the surface of the nanowire, determined from a random telegraph signal, is used as a measure for the local potential. The method is demonstrated for the case of one or two switching defects in indium arsenide (InAs) nanowire field effect transistors at temperatures T=25-77 K. Comparison with a self-consistent model shows that surface potential variation is retarded in the conducting regime due to screening by surface states with density Dss≈10(12) cm(-2) eV(-1). Temperature-dependent dynamics of electron capture and emission producing the random telegraph signals are also analyzed, and multiphonon emission is identified as the process responsible for capture and emission of electrons from the surface traps. Two defects studied in detail had capture activation energies of EB≈50 meV and EB≈110 meV and cross sections of σ∞≈3×10(-19) cm2 and σ∞≈2×10(-17) cm2, respectively. A lattice relaxation energy of Sℏω=187±15 meV was found for the first defect.

  11. In vivo readout of CFTR function: ratiometric measurement of CFTR-dependent secretion by individual, identifiable human sweat glands.

    Directory of Open Access Journals (Sweden)

    Jeffrey J Wine

    Full Text Available To assess CFTR function in vivo, we developed a bioassay that monitors and compares CFTR-dependent and CFTR-independent sweat secretion in parallel for multiple (~50 individual, identified glands in each subject. Sweating was stimulated by intradermally injected agonists and quantified by optically measuring spherical sweat bubbles in an oil-layer t