The United States is in the midst of an opioid epidemic. In addition to other system level interventions, almost all states have responded to the crisis by implementing prescription drug monitoring programs (PDMPs). PDMPs are state-level interventions that track the dispensing of Controlled Substances. Data generated at the time of medication dispensing is uploaded to a central data server that may be used to assist in identifying drug diversion, medication misuse, or potentially aberrant prescribing practices. Prior studies assessing the impact of PDMPs on trends in opioid-related morbidity have often failed to take into account the wide heterogeneity of program features and how the effectiveness of these features may be mitigated by insurance status. Previous research has also failed to differentiate the effects of these programs on prescription vs. illicit opioid-related morbidity. The studies in this dissertation attempt to address these gaps using epidemiological techniques to examine the associations between specific PDMP features and trends in prescription and illicit opioid-related poisonings in populations of different insurance beneficiaries. Results of these studies demonstrate that implementation of specific PDMP features is significantly associated with differential trends in prescription and illicit-opioid related poisonings and that the effectiveness of these features vary depending on the insurance status of the population studied. These results suggest that PDMPs offer a valuable tool in addressing the United States’ opioid epidemic, and may be used as empirical evidence to support PDMP best practices in the future.

This thesis shows that illicit drug consumers in Vietnam who administer product via injection are vulnerable actors in a paradoxical global/glocal phenomenon rooted in historical complexities of globalisation. Therefore, responsibility for HIV risks should be shifted upstream from the level of individuals toward institutional processes that manufacture environments of harm. At the global level, the UN Milennium Development Goals do not provide the required level of leadership on HIV prevention for drug injectors. Association between globalisation, opiates and blood-born disease in Vietnam is not new and is inseparable from historical transportation, migration and trade processes. As a key locale in the Cold War, after 1975, and 1979 in particular, Vietnam was 'at distance' from increasing intra-regional trade flows across its western frontiers and northern border. As a consequence, it was hermetically sealed to nearby HIV sub-epidemics unfolding among heroin cons umers. A latent HIV risk environment awaited Vietnam should geopolitical grievances be resolved and it became re-integrated among Mekong sub-regional flows. Neo-liberal financial flows returned to Vietnam in 1993 and the Mekong was spanned in 1994. In 1995 it normalised relations with the United States, joined ASEAN and announced the resurrection of transportation linkages across the northern border with China. Mid-decade, its borders were made more porous at the same time as local opium production was reduced as part of the UN global programme against drugs. Exploiting enhanced trans-boundary mobilities intended for goods, opiate traffickers quickly transformed Vietnam into a transit nation and a marke for high-quality heroin well suited to a youthful population experiencing socio-economic change including new consumerism. Following traditional pathways, a radical transformation in the fluidity of drug consumption environs ensued, enabling more widespread and efficient flows of blood across complex boundari es. Analysis reveals that a spatio-temporal confluence of structural factors has created conditions which enabled this process. These factors are overlapping and they range from global influences, such as the collapse of the USSR, to micro-economic reform such as privatisation and modernisation of the domestic pharmaceutical sector. The transformation in opiate consumption from injecting opium to heroin injecting occurred faster than expert-driven prevention systems responded, even in time and space where this was most forseeable. Although the opiate transformation was highly predictable, there has been a time-lag of almost a decade between risk transformations and policy responses equated with harm reduction principles. The thesis shows that blame for HIV sub-epidemics in Vietnam should not be attributed to vulnerable youths and young adults. Expert-driven economic transition associated with global inegration has manufactured circumstances in which drug availability has risen dramatically at a time when emp loyment growth has been insufficient and a commercial sex industry has expanded. This research confirms the cimportance of new methods of risk environment analyses, particularly in relation to trans-boundary hazards associated with global flows, including trade and human mobilities.

<p>Methadone Maintenance treatment of compulsive opioid addiction was started by the study of Dole and Nyswander (1965) and has subsequently been replicated in programs throughout the world. Methadone treatment has become the most effective modality for the treatment of chronic heroin addiction. </p><p>In 1966 a Swedish National methadone maintenance program was opened at the Psychiatric Research Center, Ulleråker hospital at Uppsala.</p><p>The aim of this thesis was to study the outcome of methadone treatment along various lines:</p><p>• An open randomised controlled study comparing the efficacy of methadone treatment and drug free treatment in 34 heroin addicts, 20-24 years of age. </p><p>• Before/after comparisons of rehabilitation among 345 heroin addicts admitted during the 23 years when this was a centralised National program.</p><p>• Retention in treatment.</p><p><b>Study subjects, methods and treatment goals: </b>Subjects underwent an admission procedure when background data was collected through hospital records, and personal interviews. Therapeutic efforts focused on vocational rehabilitation, i.e. a return to full-time work or studies, hoping to make patients abandon their drug addict’s life-style and make them socially accepted and self-supporting. </p><p><b>Results: </b>Thirty-four heroin addicts with a history of 4-8 years of heroin use were randomly assigned either to methadone treatment (17) or an untreated control group (17). The controls could not apply for methadone treatment until two years later. Outcome after six years observation showed that 81% became free of drug abuse, while the corresponding figure for the controls was only 1/17 (6%). The mean yearly death rate for the controls was 7.2%. Likewise, among the total material of 345 heroin addicts, 70-80% of the patients became engaged in work or studies, a significant increase compared with the situation before treatment (1.7%). The program was an effective reducer of illicit heroin use and criminality among its patients and prevented the occurrence of HIV infection among patients in long-term methadone treatment. The average one-year retention during 1967-1989 was 90% and cumulative retention showed that 29% were still in treatment 10 years after admission.</p><p><b>Conclusion: </b>The present results emphasise the importance of vocational rehabilitation and support in a treatment strategy based on long-term maintenance therapy.</p>

Methadone Maintenance treatment of compulsive opioid addiction was started by the study of Dole and Nyswander (1965) and has subsequently been replicated in programs throughout the world. Methadone treatment has become the most effective modality for the treatment of chronic heroin addiction. In 1966 a Swedish National methadone maintenance program was opened at the Psychiatric Research Center, Ulleråker hospital at Uppsala. The aim of this thesis was to study the outcome of methadone treatment along various lines: • An open randomised controlled study comparing the efficacy of methadone treatment and drug free treatment in 34 heroin addicts, 20-24 years of age. • Before/after comparisons of rehabilitation among 345 heroin addicts admitted during the 23 years when this was a centralised National program. • Retention in treatment. <b>Study subjects, methods and treatment goals: </b>Subjects underwent an admission procedure when background data was collected through hospital records, and personal interviews. Therapeutic efforts focused on vocational rehabilitation, i.e. a return to full-time work or studies, hoping to make patients abandon their drug addict’s life-style and make them socially accepted and self-supporting. <b>Results: </b>Thirty-four heroin addicts with a history of 4-8 years of heroin use were randomly assigned either to methadone treatment (17) or an untreated control group (17). The controls could not apply for methadone treatment until two years later. Outcome after six years observation showed that 81% became free of drug abuse, while the corresponding figure for the controls was only 1/17 (6%). The mean yearly death rate for the controls was 7.2%. Likewise, among the total material of 345 heroin addicts, 70-80% of the patients became engaged in work or studies, a significant increase compared with the situation before treatment (1.7%). The program was an effective reducer of illicit heroin use and criminality among its patients and prevented the occurrence of HIV infection among patients in long-term methadone treatment. The average one-year retention during 1967-1989 was 90% and cumulative retention showed that 29% were still in treatment 10 years after admission. <b>Conclusion: </b>The present results emphasise the importance of vocational rehabilitation and support in a treatment strategy based on long-term maintenance therapy.

Lo studio analizza la relazione tra i diversi prezzi delle droghe illegali, eroina e cocaina, e il livello di violenza sistemica in un territorio. L'ipotesi dello studio è che ad un aumento dei prezzi delle droghe illegali, si registra una maggiore violenza causata dal maggiore ritorno economico derivante dalla commissione della violenza. L'analisi empirica si riferisce agli anni ottanta e novanta negli Stati Uniti d'America. Lo studio di mostra la validità dell'ipotesi e propone nuove ambiti di ricerca. / The study analyzes the relation between the different prices of illegal drugs, heroin and cocaine, and the level of systemic violence recorded in a territory. The hypothesis of the study is that from an increase of the prices of illegal drugs, it is derived a greater level of violence caused by the greater menotary return derived by the commission of violence. The empirical analysis referred to the eighties and nineties in the United States of America. The study demonstrates the hypothesis and proposes new research paths.

本研究目的主要在探討海洛因成癮者是否具有決策判斷的問題與抑制控制能力缺損，利用數理認知模型的參數值檢驗受試者在新式Go/No-Go作業的表現，該作業結合IGT與原先Go/No-Go作業的特性，並將作業刺激改為中性與海洛因相關的圖片，探討海洛因成癮者在此作業的決策歷程與抑制反應功能，並與控制組作比較。另者，根據誘發─敏感化理論 ( Robinson & Berridge, 1993 ) 與誘發─習慣化模式 ( Di Chiara, 2000 ) 的預測，前者認為成癮越嚴重者的抑制缺損情形會越嚴重，對藥物相關刺激的注意力偏誤也越明顯；後者則認為藥物依賴階段的初期會發生較嚴重的注意力偏誤情形，但隨著依賴程度增加而對藥物相關刺激已習慣化，尋求藥物行為也已變成自動化反應，故注意力偏誤的情形反而會減少。因此，本研究試圖在加入藥物相關刺激的Go/No-Go作業中驗證這兩種理論的預測。 本研究以48位一般控制組、88位海洛因受戒治人為樣本，利用Go/No-Go作業與線索依賴學習模式 ( CD model ) 分析受試者對酬賞或處罰的注意力 ( w參數 )、學習率 ( 參數 )、反應一致性 ( c參數 )、以及海洛因圖片價值的影響 ( I_Heroin參數 )，結果發現，比起控制組，海洛因成癮者對酬賞的注意力較低、受到藥物相關刺激影響較明顯。另外，將戒治組分為物質高依賴組與低依賴組時，比起控制組，高依賴組對酬賞的注意力較低；而低依賴組受到海洛因圖片價值影響較明顯。結果證實當面對同時具有中性與藥物相關刺激時的情況下，海洛因成癮者與過去古柯鹼成癮者在決策作業上的表現不同，不僅受到酬賞或處罰的影響，藥物相關刺激本身亦帶有某種價值，影響成癮者的決策與抑制能力；另外，結果部分支持誘發─習慣化的預測。 / The purpose of present study was to investigate the decision making and inhibitory problem in heroin addicts, and to use the mathematics cognitive model parameters to examine performance in a new Go/No-Go Task of subjects. The task combined the characteristics of IGT and original Go/No-Go Task. We changed the task’s stimuli to neural and heroin related pictures, to explore the decision making and inhibitory reactive function in the task, and compared with control group. On the other hands, according to Incentive-sensitization theory (Robinson & Berridge, 1993) and ‘Incentive ─ habit’ model (Di Chiara, 2000), the incentive-sensitization thoery thought that people with increasing severity of addiction get more inhibitory problems and attentional bias toward drug related cues, but the incentive-habit model suggests that attentional bias for drug cues will be more severe in the early stage of drug dependence., but with the increase in dependence and habit to drug cues, drug-seeking behavior has become automatic reaction, so attentional bias will be attenuated when abusers get more dependence. Therefore, this study attempted to verify the prediction of two theories in the Go / No-Go Task with drug-related stimuli. This research was based on the data collected from the 48 normals and 88 heroin addicts, using Go/No-Go Task and Cue-dependence learning model ( CD model ) analysis their attention to reward or punishment ( parameter w ), learning rate ( ), reactive consistence ( c ), and valence of heroin pictures ( I_Heroin). The result revealed that compare to controls, heroin addicts had fewer attention to rewards, and more obvious influenced by drug related stimuli. Otherwise, to divided addicts group into high dependence group and low dependence group, compared to control group, the high dependence addicts had lower attention to reward, and the lower dependence addicts was higher influenced by drug related stimuli. It confirm that when heroin abusers faced to neural and drug related stimili, their performance in decision making task was different from cocaine abusers, it’s not only influenced from reward or punishment, but also from the valence of drug related cues. In addition, the result partially support the prediction of the incentive-habit model.

Based on the study of available literature in this thesis are defined easily accessible poisons, which are carbofuran, methanol, ethylene glycol, marijuana, methamphetamine, heroin and cocaine. The thesis is further defined by crime, with those readily available poisons committed on the territory of the Czech Republic. Defined easily accessible poisons were also associated with a particular crime that is committed to them and based on statistical outputs of the Czech Police and the National Drug Headquarters of the Police of the Czech Republic was conducted statistical research that is readily available to these poisons committing a crime on the territory of the Czech Republic, and whether there are differences in crime rates between different regions of the Czech Republic. The second part describes the methodology of work and research questions. The third part consists of the results which graphically compares crime committed with easily accessible poisons. The final part consists of discussions, where they are analyzed the achievements of work. To achieve the objectives in this work used data collection methods, analytical, mathematical and graphical. While writing this thesis I first considered studying literature in easily accessible poisons and study applicable laws, which serve as the legal basis for the definition of crimes. When I was writing a thesis based on research questions: They are easily accessible poisons available in the Czech Republic? There in the CR crime committed using readily available poisons? There are differences between individual regions in the Czech Republic? These research questions were answered by meeting our goals, namely the Czech Republic are readily available poisons available with them commit crime in the crimes committed there are differences between individual regions.

L’addiction aux drogues d’abus est un désordre psychiatrique caractérisé par une consommation compulsive de toxiques, au détriment d’activités alternatives plus bénéfiques à long terme, et malgré les conséquences négatives associées. Cette psychopathologie est ainsi de plus en plus conceptualisée comme le résultat d’une prise de décision pathologique, et l’un des plus grands enjeux de la recherche en addiction est de comprendre les bases neurobiologiques et physiopathologiques de ce dysfonctionnement. Devant les contraintes éthiques, techniques et pratiques inhérentes aux études neurobiologiques chez l’homme, il est important d’utiliser en parallèle des modèles animaux d’addiction. Malheureusement, la validité de la plupart de ces modèles est incertaine. En effet, la prise de drogue est bien trop souvent étudiée dans une situation où la drogue est la seule récompense disponible. Ainsi, dans ces conditions, il est difficile de déterminer si l’animal s’auto-administre une drogue par compulsion, ou simplement parce qu’il n’a pas d’autre activité alternative valable. Une série d’expériences menées dans notre laboratoire depuis plusieurs années a montré que lorsqu’un choix est donné entre une injection intraveineuse de cocaïne ou d’héroïne et un accès à une boisson sucrée, la vaste majorité des rats préfèrent l’eau sucrée. Une minorité de rats persévère cependant dans le choix de la drogue au détriment de l’accès à la boisson sucrée, et constituerait ainsi une population d’individus vulnérables à l’addiction. Au cours de ma thèse, mon principal objectif a été d’étudier les déterminants du choix entre prise de drogue (cocaïne et héroïne) et récompense alternative. Mes travaux de recherche ont permis de déterminer les mécanismes de choix utilisés par le rat, en testant la validité prédictive relative de plusieurs modèles de prise de décision. J’ai également contribué à la mise en évidence d’une interaction forte entre le contexte de choix, les effets directs de la drogue et les capacités cognitives spécifiques au rat. Cette interaction exerce une influence considérable sur le choix de la drogue chez le rat. Cette découverte pourrait conduire à une réinterprétation des expériences de choix menées chez le rat et soulève aussi des interrogations importantes sur la validité relative des procédures de choix pour modéliser l’addiction aux drogues. / Drug addiction is defined as a psychiatric disorder involving compulsive drug use, despite negative consequences, and is increasingly conceptualized as resulting from poor decision making with a preference bias towards the drug at the expense of other socially-valued behaviors. The most important challenge in current addiction research is to understand the physiopathology of this disorder. Animal models are important tools in addiction research, since they are less ethically and technically limited than human studies. However, preclinical research on drug addiction is typically performed in laboratory rats that are given ready access to drugs for intravenous self-administration but without other options. The lack of choice during drug access limits its validity for understanding the physiopathology of addiction. A series of studies from our laboratory has previously shown that when offered a mutually exclusive choice between pressing a lever to get sweet water or an alternative lever to receive an intravenous dose of cocaine or heroin, most rats prefer sweet water. Only a minority of rats persists in drug taking despite the availability of an alternative reward, and thus, appears to be more vulnerable to drug addiction. During my thesis, my main objective was to determine the psychological and behavioral determinants of choice between drugs of abuse (cocaine and heroin) and sweet water. This research allowed us to determine the decision-making processes underlying this choice, by testing the predictive validity of different decision-making models. Additionally, we evidenced a strong interaction between the choice setting, the drug’ direct effects and rats’ specific cognitive abilities that reliably influences drug choices in rats. This finding should lead to a novel interpretation of drug choice studies in rats and also raises important issues regarding the relative validity of choice procedures for modelling drug addiction.

American policy makers primarily embrace a deterrent-based policing agenda to curb illicit drug trafficking and use that relies on the principles of the economic price elasticity of demand (Boynum & Reuter, 2005). This counter-drug platform includes three fundamental programs: arresting offenders, seizing illicit drugs, and eradicating horticultural sources of illicit drugs (U.S. DEA, 2015). One of the main goals of these programs is to deter illegal trafficking and use by increasing the price of illicit substances so they are no longer attractive to consumers. The United States has weathered various drug use epidemics during its history, and currently it is facing a heroin and opioid epidemic (Dean, 2017). The present multi-dimensional study is guided by three broad goals: to assess the dynamics of illicit drug pricing and the economic price elasticity of demand perspective; to evaluate whether drug trafficking organizations respond to theoretically deterrence based counter-drug law enforcement efforts; and to assess why law enforcement activities are (or are not) effective in controlling illegal drug markets. To accomplish these three broad goals, four separate yet linked focal points comprised of quantitative, qualitative, and mixed-methods evaluations of official data are examined. The findings in the study call into question the current American counter-drug law enforcement agenda being used to address the ongoing heroin epidemic. Furthermore, the results shine light on various shortcomings in overall U.S. counter-drug policy. Finally, the study calls for a new approach to address illicit drug trafficking and use in the U.S.

Objective: The aim was to summarize the clinical literature on interactions between common illicit drugs and prescription therapies. Methods: Medline, Iowa Drug Information Service, International Pharmaceutical Abstracts, EBSCO Academic Search Premier, and Google Scholar were searched from date of origin of database to March 2011. Search terms were cocaine, marijuana, cannabis, methamphetamine, amphetamine, ecstasy, N-methyl-3,4- methylenedioxymethamphetamine, methylenedioxymethamphetamine, heroin, gamma-hydroxybutyrate, sodium oxybate, and combined with interactions, drug interactions, and drugdrug interactions. This review focuses on established clinical evidence. All applicable full-text English language articles and abstracts found were evaluated and included in the review as appropriate. Results: The interactions of illicit drugs with prescription therapies have the ability to potentiate or attenuate the effects of both the illicit agent and/or the prescription therapeutic agent, which can lead to toxic effects or a reduction in the prescription agent's therapeutic activity. Most texts and databases focus on theoretical or probable interactions due to the kinetic properties of the drugs and do not fully explore the pharmacodynamic and clinical implications of these interactions. Clinical trials with coadministration of illicit drugs and prescription drugs are discussed along with case reports that demonstrate a potential interaction between agents. The illicit drugs discussed are cocaine, marijuana, amphetamines, methylenedioxymethamphetamine, heroin, and sodium oxybate. Conclusion: Although the use of illicit drugs is widespread, there are little experimental or clinical data regarding the effects of these agents on common prescription therapies. Scientific Significance: Potential drug interactions between illicit drugs and prescription drugs are described and evaluated on the Drug Interaction Probability Scale by Horn and Hansten.