Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 237-252).

Ho Man Choi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 178-215). / Abstracts and appendices in English and Chinese. / ACKNOWLEDGEMENT --- p.ii / ABSTRACT --- p.iii / 研究摘要 --- p.vi / Chapter CHAPTER 1 --- INTRODUCTION / Chapter 1.1. --- Heroin --- p.1 / Chapter 1.1.1. --- Manufacture --- p.1 / Chapter 1.1.2. --- Administration --- p.2 / Chapter 1.1.3. --- Physical and Psychological Effects --- p.4 / Chapter 1.1.4. --- Heroin Metabolism --- p.5 / Chapter 1.1.5. --- Treatments for Heroin Dependence --- p.6 / Chapter 1.2. --- Opioids and Analgesia --- p.8 / Chapter 1.2.1. --- Pain Transmission --- p.8 / Chapter 1.2.2. --- Pain Modulation and Endogenous Opioid System --- p.9 / Chapter 1.2.3. --- Clinical Application of Opiates in Pain Management --- p.11 / Chapter 1.2.4. --- Narcotics and Pain --- p.11 / Chapter 1.3. --- Biological Basis of Drug Addiction --- p.12 / Chapter 1.3.1. --- Mesocorticolimbic Reward System --- p.13 / Chapter 1.3.2. --- Molecular Neurobiology of Drug Addiction --- p.16 / Chapter 1.3.2.1. --- "Cyclic Adenosine-3',5'-Monophosphate and Protein Kinase A" --- p.16 / Chapter 1.3.2.2. --- Transcription Factors: cAMP-Response Element Binding Protein and Delta-Fos B --- p.18 / Chapter 1.3.2.3. --- Neurotrophic Factors --- p.23 / Chapter 1.4. --- Biological Basis of Relapse --- p.25 / Chapter 1.4.1. --- Environmental Stimuli --- p.26 / Chapter 1.4.2. --- Drug Re-exposure/Priming --- p.26 / Chapter 1.4.3. --- Acute Stress Exposure --- p.27 / Chapter 1.5. --- Gene Polymorphisms and Opioid Dependence --- p.30 / Chapter 1.5.1. --- Opioidergic System --- p.31 / Chapter 1.5.2. --- Dopaminergic System --- p.36 / Chapter 1.5.3. --- Serotoninergic System --- p.41 / Chapter 1.5.4. --- Noradrenergic System --- p.43 / Chapter 1.5.5. --- GABAergic System --- p.44 / Chapter 1.6. --- Aim of Research --- p.45 / Chapter CHAPTER 2 --- METHODS OF STUDY / Chapter 2.1. --- Subject Recruitment and Demographic Data Collection --- p.49 / Chapter 2.1.1. --- Heroin-dependent Subjects --- p.49 / Chapter 2.1.1.1. --- Phenotype Assessment --- p.49 / Chapter 2.1.1.2. --- Socio-demographics Data and Substance Use History --- p.50 / Chapter 2.1.1.3. --- Addiction Severity Index (ASI) --- p.51 / Chapter 2.1.1.4. --- History of Detoxifications and Relapse --- p.51 / Chapter 2.1.2. --- Control Subjects --- p.51 / Chapter 2.2. --- Pain Response Assessment using Cold-Pressor Test (CPT) --- p.52 / Chapter 2.3. --- Personality Trait Assessment --- p.53 / Chapter 2.4. --- Genotype Analysis --- p.55 / Chapter 2.4.1. --- DNA Extraction --- p.55 / Chapter 2.4.2. --- Genotyping --- p.56 / Chapter 2.4.2.1. --- MORA118G --- p.56 / Chapter 2.4.2.2. --- DOR T921C --- p.56 / Chapter 2.4.2.3. --- COMTVal108/158Met --- p.57 / Chapter 2.4.2.4. --- Prodynorphin 68bp-VNTR --- p.58 / Chapter 2.4.2.5. --- DRD2 TaqI A --- p.59 / Chapter 2.4.2.6. --- DRD4 -521C/T --- p.59 / Chapter 2.4.2.7. --- 5HT1B G861C --- p.60 / Chapter 2.5. --- Saliva Collection and Salivary Cortisol Measurement --- p.61 / Chapter 2.6. --- Statistical Analysis --- p.62 / Chapter CHAPTER 3 --- RESULTS / Chapter 3.1. --- Demographics --- p.64 / Chapter 3.1.1. --- Age --- p.64 / Chapter 3.1.2. --- Ethnicity --- p.64 / Chapter 3.1.3. --- District of Residence and Type of Housing --- p.64 / Chapter 3.1.4. --- "Education, Employment and Income" --- p.68 / Chapter 3.1.5. --- ASI Scores --- p.71 / Chapter 3.1.5.1. --- Family/Social Relationship --- p.71 / Chapter 3.1.5.2. --- Employment and Support Status --- p.73 / Chapter 3.1.5.3. --- Medical Status --- p.73 / Chapter 3.1.5.4. --- Legal Status --- p.75 / Chapter 3.1.5.5. --- Psychiatric Status --- p.75 / Chapter 3.1.5.6. --- Drug Use Status --- p.76 / Chapter 3.1.5.7. --- Alcohol Use Status --- p.79 / Chapter 3.1.6. --- Tranquillizer Use Status --- p.79 / Chapter 3.1.7. --- Smoking Status --- p.81 / Chapter 3.1.8. --- Detoxification and Relapse --- p.83 / Chapter 3.2. --- Cold-Pressor Test (CPT) --- p.88 / Chapter 3.3. --- Personality Traits --- p.90 / Chapter 3.3.1. --- NEO PI-R --- p.90 / Chapter 3.3.2. --- BIS/BAS --- p.93 / Chapter 3.3.3. --- SSS-V --- p.93 / Chapter 3.4. --- Salivary Cortisol Levels --- p.93 / Chapter 3.5. --- Genotype and Allele Frequencies of Gene Polymorphisms --- p.96 / Chapter 3.5.1. --- MOR A118G Polymorphism --- p.96 / Chapter 3.5.2. --- DOR T921C Polymorphism --- p.96 / Chapter 3.5.3. --- COMT Val108/158Met Polymorphism --- p.99 / Chapter 3.5.4. --- Prodynorphin 68bp-VNTR --- p.99 / Chapter 3.5.5. --- DRD2 TαqI A Polymorphism --- p.102 / Chapter 3.5.6. --- DRD4 -521C/T Polymorphism --- p.102 / Chapter 3.5.7. --- 5HT1B G861C Polymorphism --- p.105 / Chapter 3.6. --- "Association of Gene Polymorphisms, Personality Traits and CPT" --- p.105 / Chapter 3.7. --- Association of Gene Polymorphisms and CPT --- p.108 / Chapter 3.7.1. --- COMT Val108/158Met Polymorphism --- p.108 / Chapter 3.7.2. --- DRD4 -521C/T Polymorphism --- p.108 / Chapter CHAPTER 4 --- DISCUSSIONS AND CONCLUSIONS / Chapter 4.1. --- Demographics and Potential Environmental Factors of Relapse --- p.111 / Chapter 4.1.1. --- Medical and Psychological Status --- p.114 / Chapter 4.1.2. --- Substance Use Status --- p.116 / Chapter 4.1.3. --- Detoxification and Relapse --- p.118 / Chapter 4.2. --- Cold-Pressor Test (CPT) --- p.121 / Chapter 4.3. --- Personality Traits --- p.123 / Chapter 4.4. --- Salivary Cortisol --- p.125 / Chapter 4.5. --- "Association of Gene Polymorphisms, Personality Traits and Cold-Pressor Test" --- p.127 / Chapter 4.5.1. --- MORA118G Polymorphism --- p.127 / Chapter 4.5.2. --- DOR T921C Polymorphism --- p.129 / Chapter 4.5.3. --- COMT Val108/158Met --- p.130 / Chapter 4.5.4. --- Prodynorphin (ProDYN) 68bp-VNTR --- p.133 / Chapter 4.5.5. --- DRD2 A Polymorphism --- p.134 / Chapter 4.5.6. --- DRD4 -521C/T Polymorphism --- p.138 / Chapter 4.5.7. --- 5HTlB G861C Polymorphism --- p.141 / Chapter 4.5.8. --- Personality Traits --- p.142 / Chapter 4.6. --- Limitations --- p.144 / Chapter 4.7. --- Potential Clinical Application --- p.145 / Chapter 4.8. --- Conclusion --- p.146 / APPENDIXES --- p.148 / APPENDIX 1 Addiction Severity Index (ASI) with Additional Questions for Heroin Users / APPENDIX 2 Detoxification and Relapse History Questionnaire / APPENDIX 3A Questionnaire for Control Subjects (Chinese version) / APPENDIX 3B Questionnaire for Control Subjects (English version) / APPENDIX 4A NEO PI-R (Chinese version) / APPENDIX 4B NEO PI-R (English version) / APPENDIX 5A BIS/BAS (Chinese version) / APPENDIX 5B BIS/BAS (English version) / APPENDIX 6A SSS- V (Chinese version) / APPENDIX 6B SSS- V (English version) / REFERENCES --- p.178

Szeto Yi Ki. / Thesis submitted in: December 2000. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 83-113). / Abstracts in English and Chinese. / Acknowledgement --- p.iv / Abstract --- p.v / List of Abbreviations --- p.ix / Chapter CHATPER ONE --- INTRODUCTION / Chapter 1.1 --- Heroin --- p.1 / Chapter 1.1.1 --- Historical Background --- p.2 / Chapter 1.1.2 --- Manufacturing of Heroin --- p.5 / Chapter 1.1.3 --- Route of Administration and Absorption Rate --- p.6 / Chapter 1.1.4 --- Metabolism of Heroin --- p.8 / Chapter 1.1.5 --- Physical and Psychological Effects of Heroin --- p.9 / Chapter 1.2 --- Opioid Receptors --- p.10 / Chapter 1.2.1 --- Mu Opioid Receptors (MOR) --- p.11 / Chapter 1.2.2 --- Kappa Opioid Receptors (KOR) --- p.14 / Chapter 1.2.3 --- Delta Opioid Receptors (DOR) --- p.15 / Chapter 1.3 --- Dopamine Receptors --- p.17 / Chapter 1.4 --- Dopamine Transporter (DAT) --- p.19 / Chapter 1.5 --- Gamma-Aminobutyric Acid (GABA) Receptors --- p.21 / Chapter 1.6 --- Mesocorticolimbic Pathway --- p.22 / Chapter 1.6.1 --- Neural Substrates of Drug Reinforcement --- p.25 / Chapter 1.6.2 --- Molecular and Cellular Basis of Addiction --- p.26 / Chapter 1.6.3 --- Intracellular Substrates of Relapse --- p.29 / Chapter 1.7 --- Environmental Factors in Drug Addiction --- p.30 / Chapter 1.8 --- Genetic Factors in Drug Addiction --- p.32 / Chapter 1.9 --- Aim of Project --- p.35 / Chapter CHAPTER TWO --- MATERIALS AND METHODS / Chapter 2.1 --- Recruitment of Subjects 、 --- p.39 / Chapter 2.1.1 --- Heroin-dependent Subjects --- p.39 / Chapter 2.1.1.1 --- Phenotype Assessment --- p.39 / Chapter 2.1.1.2 --- Establishment of Socio-demographic Data --- p.40 / Chapter 2.1.2 --- Control Subjects --- p.42 / Chapter 2.2 --- DNA Extraction --- p.42 / Chapter 2.3 --- Genotyping --- p.43 / Chapter 2.3.1 --- A118G Polymorphism in Exon 1 of the Human MOR (hMOR) Gene --- p.43 / Chapter 2.3.2 --- C1031G Polymorphism in Intron 2 of the hMOR Gene --- p.45 / Chapter 2.3.3 --- T921C Polymorphism in Exon 3 of the Human DOR (hDOR) Gene --- p.46 / Chapter 2.3.4 --- 3'VNTR Polymorphism of the DAT Gene --- p.47 / Chapter 2.3.5 --- TaqI A Polymorphism of the DRD2 Gene --- p.48 / Chapter 2.3.6 --- NciI Polymorphism of the GABRG2 Gene --- p.48 / Chapter 2.4 --- DNA Sequencing --- p.49 / Chapter 2.5 --- Statistical Analysis --- p.50 / Chapter CHAPTER THREE --- RESULTS / Chapter 3.1 --- Socio-demographic Data --- p.52 / Chapter 3.1.1 --- Age of the Control and Heroin-dependent Subjects --- p.52 / Chapter 3.1.2 --- Education Standard of the Heroin-dependent Subjects --- p.52 / Chapter 3.1.3 --- Years of Heroin Use --- p.53 / Chapter 3.2 --- Addition Severity Index (ASI) --- p.53 / Chapter 3.2.1 --- ASI-Medical --- p.53 / Chapter 3.2.2 --- ASI-Employment --- p.54 / Chapter 3.2.3 --- ASI-Drug --- p.54 / Chapter 3.2.4 --- ASI-Legal --- p.54 / Chapter 3.2.5 --- ASI-Family/Social Relationships --- p.55 / Chapter 3.2.6 --- ASI-Psychiatry --- p.55 / Chapter 3.2.7 --- Correlation Among the Factors of ASI --- p.55 / Chapter 3.3 --- A118G Polymorphism in Exon 1 of the Human Mu Opioid Receptor (hMOR) Gene --- p.56 / Chapter 3.4 --- C1031G Polymorphism in Intron 2 of the hMOR Gene --- p.58 / Chapter 3.5 --- T921C Polymorphism in Exon 3 of the Human Delta Opioid Receptor (hDOR) Gene --- p.59 / Chapter 3.6 --- Interaction Between Genotypes --- p.60 / Chapter 3.6.1 --- Combined Genotypes of A118G and C1031G Polymorphisms of the hMOR Gene --- p.60 / Chapter 3.6.2 --- Combined Genotypes of A118G Polymorphism of the hMOR Gene and T921C Polymorphism of the hDOR Gene --- p.61 / Chapter 3.6.3 --- Combined Genotypes of C1031G Polymorphism of the hMOR Gene and T921C Polymorphism of the hDOR Gene --- p.61 / Chapter 3.7 --- Correlation Between Allelic Frequencies and Factors of the ASI --- p.62 / Chapter 3.8 --- 3'VNTR Polymorphism of DAT Gene --- p.62 / Chapter 3.9 --- TαqI A Polymorphism of DRD2 Gene --- p.63 / Chapter 3.10 --- NciI Polymorphism of GABRG2 Gene --- p.64 / Chapter CHAPTER FOUR --- DISCUSSION & CONCLUSION --- p.66 / REFERENCES --- p.83 / APPENDIX I The Addiction Severity Index / APPENDIX II Table of Severity Ratings / APPENDIX III Allelic Frequency of A118G Polymorphism in Different Populations / APPENDIX IV Details Information About the Single Nucleotide Polymorphisms In Present Study

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Comorbidity between substance use disorders and post traumatic stress disorder (PTSD) is common. Despite evidence to suggest that people with heroin dependence are at particular risk of PTSD, there is a dearth of research focussing on the interrelationship between these disorders. The present thesis aims to identify the prevalence of PTSD among people with heroin dependence, the correlates of this comorbidity, and its impact on treatment outcomes, the utilisation of treatment services, and treatment costs. Study 1 examines the epidemiology of PTSD and heroin dependence among 10,641 Australian adults who participated in the National Survey of Mental Health and Wellbeing. The prevalence of PTSD was highest among people with heroin or other opioid use disorders compared with any other drug class (33.2%). Comorbid PTSD was associated with poorer occupational functioning, and poorer physical and mental health. While general population studies provide crucial population estimates they do not allow for a detailed examination of the relationship between highly disabling but low prevalence disorders. The remaining studies were undertaken using a sample of 615 treatment seeking and non-treatment seeking dependent heroin users. Study 2 examines the prevalence and correlates of this comorbidity. PTSD was common (lifetime 41%; current 31%) and was associated with a more severe clinical profile. Studies 3 and 4 were based on follow-up data on this large cohort. Study 3 is the first study to examine the impact of PTSD on 2 year treatment outcomes for heroin dependence. Across the 2 year period, those with current PTSD at baseline performed more poorly in terms of their occupational functioning, physical and mental health. Study 4 found that this did not equate to the greater use of treatment services or an increased cost to the health care system among those with PTSD. It is concluded that PTSD and heroin dependence are highly comorbid conditions, and that this comorbidity is associated with poorer functioning and poorer treatment outcomes. Individuals entering treatment for heroin dependence should be assessed for PTSD so that they may receive appropriate treatment and referral. Further research is also needed to determine how best to treat this comorbidity.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1974. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliography.

Heroin dependence, which is escalating within South Africa, has become a symbol of the social disorder of the times - associated with materialism, poverty, crime, the problems of a society in transition, the disadvantaged, and the inner cities. However, that is not to say that all those who misuse heroin develop a problem or become dependent. In reality, only a small minority of heroin users develop a dependence, but for those who do it can result in unpleasant and potentially terrifying experiences/consequences, that can often be extremely difficult to escape from. That is not to say that recovery from dependence to heroin is not possible. Indeed, contrary to the beliefs of many people, the reality is that many people do eventually recover. Despite the vast sums of money devoted to treatment intervention of heroin dependants in the South Africa and worldwide, the processes by which recovery occur remain fairly unclear. Moreover, relatively little is known about the contribution of interventions and processes in facilitating such recovery. The statistical and content analysis of the data revealed that one of the most important factors identified in allowing successful behaviour modification and promoting recovery was psychosocial and pharmacological intervention, which seemed to produce a range of positive effects that facilitated natural healing processes. However, a range of other factors alongside intervention were also important in promoting behaviour modification. This study has provided important information, from forty recovering heroin dependants themselves, on the many factors that are important in achieving abstinence, in allowing recovery to be maintained in the longer term, and in potentially allowing an eventual exit from heroin dependence. A number of difficulties encountered in intervention were also identified. The statistical findings of the study support the `maturing out' hypothesis of heroin dependence (c² = 16.841; r = 0.001; df = 3). Ethnicity, highest level of education, employment status, marital status, biological parents' marital status or whether biological parents were deceased or not did not relate to any of the identified behavioural indices associated with heroin dependence recovery. A framework for the development of a contextual heroin dependence recovery model is also discussed. / Psychology / (M.A.(Psychology))

Heroin dependence, which is escalating within South Africa, has become a symbol of the social disorder of the times - associated with materialism, poverty, crime, the problems of a society in transition, the disadvantaged, and the inner cities. However, that is not to say that all those who misuse heroin develop a problem or become dependent. In reality, only a small minority of heroin users develop a dependence, but for those who do it can result in unpleasant and potentially terrifying experiences/consequences, that can often be extremely difficult to escape from. That is not to say that recovery from dependence to heroin is not possible. Indeed, contrary to the beliefs of many people, the reality is that many people do eventually recover. Despite the vast sums of money devoted to treatment intervention of heroin dependants in the South Africa and worldwide, the processes by which recovery occur remain fairly unclear. Moreover, relatively little is known about the contribution of interventions and processes in facilitating such recovery. The statistical and content analysis of the data revealed that one of the most important factors identified in allowing successful behaviour modification and promoting recovery was psychosocial and pharmacological intervention, which seemed to produce a range of positive effects that facilitated natural healing processes. However, a range of other factors alongside intervention were also important in promoting behaviour modification. This study has provided important information, from forty recovering heroin dependants themselves, on the many factors that are important in achieving abstinence, in allowing recovery to be maintained in the longer term, and in potentially allowing an eventual exit from heroin dependence. A number of difficulties encountered in intervention were also identified. The statistical findings of the study support the `maturing out' hypothesis of heroin dependence (c² = 16.841; r = 0.001; df = 3). Ethnicity, highest level of education, employment status, marital status, biological parents' marital status or whether biological parents were deceased or not did not relate to any of the identified behavioural indices associated with heroin dependence recovery. A framework for the development of a contextual heroin dependence recovery model is also discussed. / Psychology / (M.A.(Psychology))

The history of heroin use disorder intervention has been characterised by fads and fashions. Some of the treatments that have been used have been, at best ineffective, and at worst harmful, and occasionally even dangerous. It is a sad reflection upon the field that practices and procedures for the treatment of heroin use disorders can so easily be introduced and applied without (or even contrary to) evidence. In South Africa, the field of heroin use disorder intervention has been `in transition' since the outbreak of the heroin epidemic. Yet despite growing evidence of an association between heroin dependents use of supplementary intervention services (such as psychosocial and pharmacological/medical care) and intervention outcomes, and the fact that international emerging standards for substance use disorder intervention have called upon treatment intervention providers to enhance traditional substance use disorder services with services that address clients' psychological and social needs, heroin use disorder intervention programmes in South Africa generally fail to meet these research-based intervention standards. Much of what is currently delivered as intervention is based upon current best guesses of how to combine some science-based (for example, cognitive-behavioural therapy and pharmacotherapies) and self-help (12-step programmes) approaches into optimal intervention protocols. As progression is made in the twenty-first century, scientific information is now beginning to be used to guide the evolution and delivery of heroin use disorder care internationally. Regrettably, a scarcity of heroin use disorder intervention research is noted in South Africa. The present study delved into the insights of ten heroin use disorder specialists, and synthesised the findings with the results of a previous study undertaken by the author relating to forty long-term voluntarily abstinent heroin dependents. In terms of theory and practice, findings of the study suggest that the field is less in transition now than it was in 1995. It is an imperative that law-enforcement action be followed by an integrated programme of psychological, social and pharmacological outreach. These programmes will have to be expanded to address new demands and will need to include specialised skills training. Many interventions and procedures have begun to be integrated routinely into clinical practice. / Psychology / (D. Phil. (Psychology))

The history of heroin use disorder intervention has been characterised by fads and fashions. Some of the treatments that have been used have been, at best ineffective, and at worst harmful, and occasionally even dangerous. It is a sad reflection upon the field that practices and procedures for the treatment of heroin use disorders can so easily be introduced and applied without (or even contrary to) evidence. In South Africa, the field of heroin use disorder intervention has been `in transition' since the outbreak of the heroin epidemic. Yet despite growing evidence of an association between heroin dependents use of supplementary intervention services (such as psychosocial and pharmacological/medical care) and intervention outcomes, and the fact that international emerging standards for substance use disorder intervention have called upon treatment intervention providers to enhance traditional substance use disorder services with services that address clients' psychological and social needs, heroin use disorder intervention programmes in South Africa generally fail to meet these research-based intervention standards. Much of what is currently delivered as intervention is based upon current best guesses of how to combine some science-based (for example, cognitive-behavioural therapy and pharmacotherapies) and self-help (12-step programmes) approaches into optimal intervention protocols. As progression is made in the twenty-first century, scientific information is now beginning to be used to guide the evolution and delivery of heroin use disorder care internationally. Regrettably, a scarcity of heroin use disorder intervention research is noted in South Africa. The present study delved into the insights of ten heroin use disorder specialists, and synthesised the findings with the results of a previous study undertaken by the author relating to forty long-term voluntarily abstinent heroin dependents. In terms of theory and practice, findings of the study suggest that the field is less in transition now than it was in 1995. It is an imperative that law-enforcement action be followed by an integrated programme of psychological, social and pharmacological outreach. These programmes will have to be expanded to address new demands and will need to include specialised skills training. Many interventions and procedures have begun to be integrated routinely into clinical practice. / Psychology / (D. Phil. (Psychology))