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Cannabis and its derivatives have been used for both medicinal and recreational purposes. The study of this plant led to the discovery of over 60 cannabinoids, found exclusively in cannabis, that contribute to the behavioral effects of cannabis use, the most common is delta-9-tetrahydrocannabinol. Cannabinoid receptors function to increase activity in the mesolimbic dopamine reward system. Dopamine is a neurotransmitter that plays a major role in addition and its regulation plays a crucial role in mental and physical well-being. There is evidence that CB1 receptors are important to the reinforcing effects and the development of physical dependence on opiate drugs. Studies have shown that increased levels of dopamine are consistent with addiction while reduced levels lead to a decline in recreational use. The goal of this research is to design, synthesize and develop potential CB1 receptors that exhibit a neutral cannabinoid antagonist pharmacological profile.

by Choi, Heung Ling. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves 79-95). / Acknowledgement --- p.iv / Abstract --- p.vi / Chapter CHAPTER 1 --- INTRODUCTION / Chapter 1.1 --- Cocaine --- p.1 / Chapter 1.1.1 --- History --- p.1 / Chapter 1.1.2 --- Epidemiology --- p.2 / Chapter 1.1.3 --- Pharmacology --- p.3 / Chapter 1.2 --- Maternal Cocaine Abuse --- p.5 / Chapter 1.2.1 --- Human Studies --- p.5 / Chapter 1.2.1.1 --- Prevalence --- p.5 / Chapter 1.2.1.2 --- Effects of Cocaine on the Developing Fetus --- p.7 / Chapter 1.2.1.2.1 --- Fetal Mortality --- p.8 / Chapter 1.2.1.2.2 --- Placental Abruption --- p.9 / Chapter 1.2.1.2.3 --- Premature Birth --- p.9 / Chapter 1.2.1.2.4 --- Neonatal Effects --- p.10 / Chapter 1.2.1.3 --- Congenital Abnormalities --- p.11 / Chapter 1.2.1.3.1 --- Cardiovascular Abnormality --- p.11 / Chapter 1.2.1.3.2 --- Genitourinary Tract Malformation --- p.12 / Chapter 1.2.1.3.3 --- Gastrointestinal Abnormality --- p.12 / Chapter 1.2.1.3.4 --- Respiratory Disorders --- p.13 / Chapter 1.2.1.3.5 --- Visual and Hearing Disorders --- p.14 / Chapter 1.2.1.3.6 --- CNS and Behavioural Abnormalities --- p.15 / Chapter 1.2.2 --- Animal Studies --- p.17 / Chapter 1.2.2.1 --- "Routes of Administration, Dosage and Tissue Distribution " --- p.18 / Chapter 1.2.2.2 --- Maternal and Offspring Effects --- p.21 / Chapter 1.2.2.2.1 --- Fetal and Maternal Mortality --- p.22 / Chapter 1.2.2.2.2 --- Gestational Length --- p.22 / Chapter 1.2.2.2.3 --- Maternal Weight Gain and Fetal Weight --- p.23 / Chapter 1.2.2.2.4 --- Little Size --- p.24 / Chapter 1.2.2.3 --- Congenital Abnormalities --- p.24 / Chapter 1.2.2.4 --- Behavioral Changes --- p.26 / Chapter 1.2.2.5 --- Neurochemical Changes --- p.28 / Chapter 1.2.2.5.1 --- Glucose Metabolism --- p.28 / Chapter 1.2.2.5.2 --- Dopamine Transporter --- p.29 / Chapter 1.2.2.5.3 --- Dopamine D1 Receptor --- p.29 / Chapter 1.2.2.5.4 --- Dopamine D2 Receptor --- p.30 / Chapter 1.2.2.5.5 --- Tyrosine Hydroxylase --- p.30 / Chapter 1.2.2.5.6 --- Other Changes --- p.31 / Chapter 1.3 --- The Aim of the Study --- p.31 / Chapter CHAPTER II --- MATERIALS AND METHODS / Chapter 2.1 --- Administration of Cocaine --- p.34 / Chapter 2.2 --- Biochemical Studies --- p.35 / Chapter 2.2.1 --- Receptor Binding Assays --- p.36 / Chapter 2.2.1.1 --- Dopamine Transporter --- p.37 / Chapter 2.2.1.1.1 --- Specific Binding Assay and Scatchard Analysis --- p.37 / Chapter 2.2.1.2 --- Dopamine D1 Receptor --- p.38 / Chapter 2.2.1.2.1 --- Association Curve --- p.38 / Chapter 2.2.1.2.2 --- Competition Assay --- p.39 / Chapter 2.2.1.2.3 --- Specific Binding Assay and Scatchard Analysis --- p.39 / Chapter 2.2.1.3 --- Dopamine D2 Receptor --- p.39 / Chapter 2.2.1.3.1 --- Association Curve --- p.40 / Chapter 2.2.1.3.2 --- Competition Assay --- p.40 / Chapter 2.2.1.3.3 --- Specific Binding Assay and Scatchard Analysis --- p.40 / Chapter 2.2.1.4 --- Assay for Residual Cocaine in Maternal Brain --- p.41 / Chapter 2.3 --- Statistics --- p.42 / Chapter 2.4 --- Morphological Studies --- p.42 / Chapter 2.4.1 --- Tyrosine Hydroxylase (TH) Immunocytochemical Staining --- p.42 / Chapter 2.5 --- Molecular Genetic Studies --- p.44 / Chapter 2.5.1 --- Material for DNA Insert --- p.44 / Chapter 2.5.1.1 --- "Dopamine Transporter, D2 receptor and β-actin cDNA Probe " --- p.44 / Chapter 2.5.2 --- Preparation for DNA Insert --- p.45 / Chapter 2.5.2.1 --- Competent Cells and Transformation of Plasmid --- p.45 / Chapter 2.5.2.2 --- Growth Transformed Bacteria and Isolation of DNA --- p.46 / Chapter 2.5.2.3 --- Purification of cDNA by Geneclean® II Kit --- p.47 / Chapter 2.5.3 --- Isolation of Total mRNA From Tissue --- p.47 / Chapter 2.5.4 --- Northern Blot Analysis --- p.48 / Chapter 2.5.4.1 --- Analysis of Northern Blots --- p.50 / Chapter 2.5.5 --- In Situ Hybridization --- p.50 / Chapter 2.5.5.1 --- Tissue Preparation --- p.50 / Chapter 2.5.5.2 --- Preparation of Dopamine Transporter Ribroprobe …… --- p.50 / Chapter 2.5.5.3 --- In Situ Hybridization Histochemistry --- p.51 / Chapter CHAPTER III --- RESULTS / Chapter 3.1 --- "Litter Size, Birth Weight and Maternal Weight Gain " --- p.53 / Chapter 3.2 --- Biochemical Studies --- p.53 / Chapter 3.2.1 --- Specific Binding --- p.53 / Chapter 3.2.2 --- Dopamine Transporter - Scatchard Analysis --- p.54 / Chapter 3.2.3 --- Dopamine Receptor --- p.55 / Chapter 3.2.3.1 --- Association Curve --- p.56 / Chapter 3.2.3.2 --- Competitive Curve --- p.57 / Chapter 3.2.3.3 --- Scatchard Analysis --- p.57 / Chapter 3.2.4 --- Dopamine D2 Receptor --- p.59 / Chapter 3.2.4.1 --- Association Curve --- p.59 / Chapter 3.2.4.2 --- Competitive Curve --- p.59 / Chapter 3.2.4.3 --- Scatchard Analysis --- p.59 / Chapter 3.2.5 --- Residual Cocaine Assay in Maternal Brain --- p.61 / Chapter 3.2.5.1 --- Specific Binding --- p.61 / Chapter 3.2.5.1.1 --- Dopamine Transporter --- p.61 / Chapter 3.3.5.1.2 --- Dopamine D1 Receptor --- p.62 / Chapter 3.3.5.1.3 --- Dopamine D2 Receptor --- p.62 / Chapter 3.3 --- Morphological Studies --- p.62 / Chapter 3.3.1 --- Tyrosine Hydroxylase (TH) Immunocytochemical Staining --- p.62 / Chapter 3.4 --- Molecular Genetic Studies --- p.63 / Chapter 3.4.1 --- Northern Blot Analysis --- p.63 / Chapter 3.4.1.1 --- Dopamine Transporter --- p.63 / Chapter 3.4.1.2 --- Dopamine D2 Receptor --- p.64 / Chapter 3.4.2 --- In Situ Hybridization --- p.64 / Chapter CHAPTER IV --- DISCUSSION AND CONCLUSION / Chapter 4.1 --- Discussion --- p.65 / Chapter 4.2 --- Conclusion --- p.77 / References --- p.79 / Publications --- p.95

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, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Virginia, 2008. / Includes bibliographical references. Also available via the Internet as viewed 10 July 2008.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 7 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.