Objectives Many addicted pregnant patients receiving buprenorphine medication-assisted therapy (MAT) wish to discontinue this medication while pregnant. This study was undertaken to determine whether outpatient detoxification from buprenorphine during pregnancy is safe and effective when confirmed with postdetoxification urine drug screens (UDSs). Methods This case series reports the maternal and neonatal outcomes for 21 patients who ended MAT with buprenorphine while pregnant. A retrospective chart review of both maternal and newborn electronic medical records was performed to obtain results. Newborn neonatal abstinence syndrome (NAS) diagnosis, need for morphine, maternal safety and fetal/newborn complications were assessed. Maternal sobriety was documented with UDSs at the time of admission for delivery. Umbilical cord blood also was assessed for substances of abuse. An additional 182 pregnant women who lowered their buprenorphine doses but did not decide to end MAT were assessed via routine quality assurance methods. Results None of the women who stopped buprenorphine during their pregnancy as confirmed by UDSs and umbilical cord sampling delivered neonates who had NAS. Eleven patients ended MAT with medical assistance and 10 ended MAT without medical assistance. No overdoses were reported for the 182 additional pregnant patients who indicated an intention to taper buprenorphine dosage while pregnant but who did not decide to end MAT; the neonatal benefits were obtained without any identified maternal harm. Conclusions The neonates of pregnant women enrolled in an outpatient buprenorphine MAT tapering program who are able to completely stop taking buprenorphine (as documented by negative urinary drug screen) are very unlikely to have NAS. Further research will be important.

A biological marker of the addictive state would be a major breakthrough in objectively assessing the efficacy of treatment outcomes. Given its role in the mesolimbic system and drug reward, most biological marker studies for addiction focus on measures related to dopamine (DA). Dopamine is also implicated in some disorders of visual attention and plays a modulatory role in the processing of color in the retinal DA pathway. For example, visual processing in the retina has been shown to co-vary with DA levels during cocaine withdrawal. In this electroencephalographic (EEG) study, we studied event related potentials (ERPs) and reaction time (RT) in opiate addicts—recruited from a community-based high intensity residential substance abuse and detoxification treatment program—and their age- and gender- matched controls. Using a visual color recognition Go/NoGo task with three similar blocks, participants responded in each block to a "Relevant" stimulus of one of three randomly-presented Red, Green or Blue light stimuli as instructed, while ignoring the other two "Irrelevant" stimuli. This simple task produced robust ERPs that were well-differentiated in the visual evoked potentials (VEPs) obtained by the Relevant stimulus compared to the VEPs from Irrelevant distractor stimuli. P300 ERP amplitudes from the color recognition task were significantly higher in males than females. Similar results were obtained with the frontal late positive (LP) potentials (i.e., 700 msec after stimulus onset), which occurred 200-300 msec after the average participant response/RT. While there were no significant RT differences between controls and addicts in the task, male controls had significantly greater P300 and LP potentials than female controls, suggesting sex differences in visual color processing. However, there were also significant differences in P300 amplitudes male controls and addiction participants—suggesting a difference in retinal DA production in opiate addiction. Further to the hypothesis of sex differences in visual color processing, P300s and LPs were not significantly different in female controls compared to female addicts. Changing the color wavelength of the Relevant stimulus did not significantly affect ERPs in males or females, controls or addicts at P300 but did at LP, particularly when the color blue was relevant. These findings suggest that there are significant sex differences in retinal DA production for opiate addicts and controls in visual processing for a simple Go/NoGo color recognition task.

No description available.

No description available.

Opiatberoende är ett allvarligt och svårt tillstånd och narkotikadödligheten i Sverige är mycket hög. Syftet med denna studie är att skaffa kunskap om och belysa hur missbrukshandläggare inom socialtjänsten i Dalarna ser på sitt arbete med personer med opiatberoende i relation till att behandlingsformen LARO ligger hos en annan huvudman. En kvalitativ studie har genomförts där missbrukshandläggare från fem olika kommuner i Dalarna har intervjuats. Det empiriska materialet har sedan analyserats i relation till tidigare forskning inom området samt teorier om domäner och professioner. Slutsatsen av studien visar att missbrukshandläggare i Dalarna upplever en del svårigheter i sitt arbete med opiatberoende klienter utifrån att det är två aktörer inblandade i att hjälpa dessa. Bland annat är långa köer till LARO samt svårigheter att få igenom tvångsvård för klienter som står i kö till eller är inskrivna på LARO problem som kan innebära en risk för klienternas liv. / Opiate addiction is a serious and difficult condition and drug mortality in Sweden is very high. The purpose of this study is to acquire knowledge and illustrate how staff working with drug addiction in social services in Dalarna look at their work with people with opiate addiction in relation to the fact that MAT lies with another operator. A qualitative study has been carried out where social workers who works with drug addiction from five different municipalities in Dalarna have been interviewed. The empirical data were analyzed in relation to previous research on the area and the theories of domains and professions. The conclusion of the study shows that the social workers in Dalarna experiencing some obstacles in their work with clients with opioid dependence since it is two operators involved. For example, the long queues to MAT and difficulties to get through forced addiction care were issues that may be a risk for clients lives.

Opioid overdose fatalities have quadrupled in the United States since the turn of the century, and are becoming increasingly recognized as a nationwide epidemic. While naloxone (narcan) has long been the standard treatment for overdose in clinical settings, it has not been issued to opioid users or their family members in the U.S. until relatively recently. As naloxone distribution and overdose training become more widespread, they are being incorporated into more and more abstinence-oriented settings including detoxes, halfway houses, and outpatient methadone and suboxone treatment programs. This qualitative study explored whether the staff at such programs found that training their patients to use naloxone was disruptive or controversial, and whether they found it difficult to reconcile these trainings’ basis in harm reduction with their personal and organizational philosophies about substance use and recovery. Ten subjects from Eastern and Central Massachusetts were interviewed about their experience introducing naloxone to their patients under the aegis of the Massachusetts Department of Public Health’s Opioid Overdose Prevention Pilot Program, and their interviews were analyzed from a descriptive phenomenological perspective. This approach seeks to distill the essence of a phenomenon by analyzing the narratives of those who have experienced it, and has been found especially useful when exploring questions that have not yet been studied in depth. The analysis identified eleven recurring themes, grouped into four broad domains (What is overdose prevention training? What is narcan? What is harm reduction? What is the goal of treatment?). These themes suggested that while subjects overwhelmingly experienced naloxone distribution and overdose prevention training as positive additions to their workplace, this experience did not necessarily lead to more engagement with the broader concept of harm reduction.

Eine langdauernde Vorinkubation des GPI bzw. des MVD mit Morphin-haltiger Nährlösung (unter in vitro-Bedingungen wird anstelle von Morphin häufig Normorphin verwendet) führte zur Entwicklung von Toleranz und im Falle des GPI zu einer zusätzlichen Abhängigkeits-ähnlichen Reaktion. Die Toleranz manifestierte sich als verminderte Ansprechbarkeit gegenüber dem in Anwesenheit des Morphins akut applizierten Normorphin, während die Gewebeabhängigkeit sich als starke Naloxon-induzierte Kontraktion bemerkbar machte. Diese Kontraktion beruhte auf einer massiven Ausschüttung von Acetylcholin aus den postganglionär parasympathischen Nervenendigungen. Als Erklärung wurde hinzugezogen, dass Naloxon das Morphin von seinen Rezeptoren verdrängt und eine entzugsähnliche Reaktion auslöst. Da nicht nur eine in vitro-Vorinkubation mit Morphin in den beiden Präparaten zur Empfindlichkeitsabnahme gegenüber Morphin/Normorphin führte sondern auch die mehrtägige, subkutane Implantation eines Morphin-Pellets oder einer Opioid-Lösung enthaltenden osmotischen Minipumpe, haben wir über den letzteren Weg selektive Toleranz gegenüber μ- (Morphin, Fentanyl), δ- (DADLE) und κ-Agonisten (Ethylketocyclazocin, MR 2034, MRZ) hervorgerufen. Nach in vivo-Behandlung mit den genannten Substanzen wurde das GPI präpariert, in einer Nährlösung, die den jeweiligen Agonisten in der ungefähr 80-fachen Toleranz-induzierenden Kon-zentration enthielt, aufgehängt und mit Feldelektroden elektrisch stimuliert. Die Reizparameter wurden so gewählt (supramaximale Spannung, 0.5 ms Reizbreite, 0.1 Hz Frequenz), dass ausschließlich das neuronale Gewebe stimuliert wurde, nicht aber der Glattmuskel. In vorhergehenden Experimenten konnte die Rezeptorausstattung des GPI nicht eindeutig identifiziert werden. Mit der Erzeugung der selektiven Toleranz an µ-Rezeptoren wurde die akute Wirkung von sowohl μ- als auch δ-Rezeptor-Agonisten wesentlich vermindert. Demgegenüber, übten κ-Rezeptor-Agonisten ihre Wirkung in unveränderter Intensität aus. Die vollständige Kreuz-Toleranz zwischen Morphin und DADLE schloss das Vorhandensein eines δ-Rezeptors aus, während die fehlende Kreuz-Toleranz zwischen Normorphin/DADLE einerseits und Ethylketocyclazocin andererseits das Vorhandensein eines κ-Rezeptors belegte. Es bedarf einer Erklärung, weshalb die in vivo-Behandlung mit Fentanyl nur geringe Toleranz gegenüber Normorphin auslöste und vice versa (wenig Kreuz-Toleranz), obwohl sich eine hochgradige Toleranz gegenüber derselben Substanz entwickelte. Es wurde geschlussfolgert, dass es verschiedene Subtypen von μ-Rezeptoren gibt, eines mit Empfindlichkeit gegenüber Morphin/Normorphin und ein anderes gegenüber Fentanyl.:Inhaltsverzeichnis Inhaltsverzeichnis…………………………………………………………………………… 2 Wissenschaftlicher Anteil der Promovendin an der Publikation……………………….. 3 Bibliographische Beschreibung……………………………………………………………. 4 I. Einleitung………………………………………………………………………………… 5 Grundlegende Erklärungen……………………………………………………………. 5 Multiple Opioidrezeptoren……………………………………………………………… 5 II. Wissenschaftlicher Hintergrund………………………………………………………..8 Eigene Publikationen…………………………………………………………………… 8 Fragestellungen der Dissertation………………………………………………………8 III. Zusammenfassung der Arbeit…………………………………………………………. 9 IV. Originalmitteilungen…………………………………………………………………... 3 V. Derzeitiger Stand der Opioidforschung……………………………………………31 Opioidrezeptortypen…………………………………………………………………… 31 Transduktionsmechanismen der Opioidrezeptoren; Toleranz und Abhängigkeit…………….. 32 Zentrale und periphere Opioidanalgesie…………………………………………….. 38 Schlussfolgerungen……………………………………………………………………. 39 VI. Literaturverzeichnis……………………………………………………………………. 40 Eigenständigkeitserklärung……………………………………………………………….. 44 Lebenslauf und Publikationsverzeichnis…………………………………………… 45 Danksagung………………………………………………………………………………… 49

Hintergrund: Die Datenlage zur Substitutionstherapie Opiatabhängiger ist defizitär. Vor diesem markant defizitären Erkenntnishintergrund erscheint es sinnvoll und notwendig, eine versorgungsepidemiologische Studie zur aktuellen Versorgungslage opiatabhängiger Substitutionspatienten durchzuführen, um offene Fragen zu klären. Hierfür haben wir ein mehrstufiges Forschungsprojekt unter dem Akronym COBRA initiiert. COBRA steht für "Cost-Benefit and Risk Appraisal of Substitution Treatments" und signalisiert, dass wir uns in umfassender Weise um eine Evaluation der Risiken, Vor- und Nachteile verschiedener Interventionsstrategien und Modalitäten in der Substitutions- und Versorgungspraxis Opiatabhängiger in Deutschland bemühen. Zielsetzungen des COBRA-Projekts sind: • Die Charakterisierung von bestehenden Einrichtungsformen und -modellen; • Die Charakterisierung von: – Merkmalen opiatabhängiger Patienten in diesen Einrichtungen (Schwere, Dauer/ Stadium, Komorbidität, Delinquenz, Desintegration etc.), – der Diagnostik sowie den Indikations- und Allokationsentscheidungen in der Versorgungsrealität sowie – den eingesetzten Interventionsmethoden (Substitutionsmittel, Therapie komorbider Störungen, psychotherapeutische und soziale Interventionen) • Die Ermittlung von Problemen der Substitutionstherapie bei verschiedenen Risikogruppen (z.B. Hepatitis-C- und HIVPatienten) • Die Beschreibung des Kurzzeitverlaufs und Outcomes hinsichtlich verschiedener klinischer und sozialer Kriterien Methodik: Die Studie teilt sich in einen deskriptiv-klinisch-epidemiologischen und einen analytisch-evaluativen Teil. Der deskriptive Teil soll zunächst darüber Auskunft geben, wie viele und welche Arten von Substitutionseinrichtungen in Deutschland wie viele Opiatabhängige erreichen und behandeln. Auf dieser Grundlage soll dann im evaluativen Teil an möglichst repräsentativen Einrichtungen und Patienten beurteilt werden, wie und mit welchen Methoden welche Arten von Patienten und Problemlagen versorgt werden. Durch Abgleich mit den wissenschaftlichen Bewertungsmaßstäben können daraus Defizite, Probleme und mögliche verbesserte Allokationsstrategien abgeleitet werden. Ergebnisse: Es werden erste Vorstudienbefunde und Ihre Design- Konsequenzen vorgestellt und diskutiert. / In the present paper, we will describe aims, methods, and design along with selected pre-study findings of an epidemiological study in a nationally representative sample of substitution doctors (N = 381) and their patients (n = 2500) in Germany. The project has three major components: (a) Pre-study: We sent mailed questionnaires to a sample of over 1000 substitution doctors to describe qualification and setting characteristics, treatment profiles and attitudes of substitution doctors in Germany. (b) Cross-sectional study: With a two-step epidemiological design (target day assessment of the patients, clinical appraisals by the doctors), our main aims were (1) to determine the number of opiate addicts treated by methadone or buprenorphine or other substitution drugs; (2) to find predictors and correlates for treatment, taking into account doctors, patients, and system variables; and (3) to evaluate cross-sectional differences between groups with regard to clinical presentation (comorbidity), clinical course, acceptance/compliance, critical incidences, and social integration. (c) Furthermore, the study includes a prospective-longitudinal cohort study of a total of 1000 patients sampled from this data base. The cohort will be followed-up over a period of three months to investigate whether buprenorphine patients have a more favorable course and outcome in terms of clinical, psychosocial, pharmaco-economic, and related measures. Selected pre-study findings are summarized, highlightening that current registers include a considerable proportion of doctors and a considerable heterogeneity of setting characteristics in terms of the number of patients, choice of substitution drugs and involvement in hepatitis- C treatment.

No description available.

The purpose of this study is to describe and analyze how health care providers, working at care facilities providing maintenance treatment programs for opiate dependence, perceive and manage the legal framework governing the treatment. The study is limited to a few particular rules within this framework which over the recent decade have been the subject matter of debate regarding i.a. their alleged lack of relation to scientific research and their frequently disastrous implications for program participants. The empirical material consists of interviews with five respondents working at four different care facilities and has been analyzed by using Lipskys theory on street-level bureaucrats as policymaking agents. The results of the study show that the rules are looked upon and dealt with in a liberal fashion and that the primary loyalty of the maintenance treatment staff is clearly directed towards promoting the well-being of their patients and helping them reach their treatment goals rather than strictly following the rules.