Association of polymorphisms in pharmacogenetic candidate genes (OPRD1, GAL, ABCB1, OPRM1) with opioid dependence in European population: a case-control study.

It is becoming increasingly evident that genetic variants contribute to the development of opioid addiction. An elucidation of these genetic factors is crucial for a better understanding of this chronic disease and may help to develop novel therapeutic strategies. In recent years, several candidate genes were implicated in opioid dependence. However, most study findings have not been replicated and additional studies are required before reported associations can be considered robust. Thus, the major objective of this study was to replicate earlier findings and to identify new genetic polymorphisms contributing to the individual susceptibility to opioid addiction, respectively. Therefore, a candidate gene association study was conducted including 142 well-phenotyped long-term opioid addicts undergoing opioid maintenance therapy and 142 well-matched healthy controls. In both study groups, 24 single nucleotide polymorphisms predominantly located in pharmacogenetic candidate genes have been genotyped using an accurate mass spectrometry based method. The most significant associations with opioid addiction (remaining significant after adjustment for multiple testing) were observed for the rs948854 SNP in the galanin gene (GAL, p = 0.001) and the rs2236861 SNP in the delta opioid receptor gene (OPRD1, p = 0.001). Moreover, an association of the ATP binding cassette transporter 1 (ABCB1) variant rs1045642 and the Mu Opioid receptor (OPRM1) variant rs9479757 with opioid addiction was observed. The present study provides further support for a contribution of GAL and OPRD1 variants to the development of opioid addiction. Furthermore, our results indicate a potential contribution of OPRM1 and ABCB1 SNPs to the development of this chronic relapsing disease. Therefore it seems important that these genes are addressed in further addiction related studies.

[Outlines of interdisciplinary addiction research given by the example of medical imaging with PET, SPECT and fMRI regarding effects of psychotropic substances]. / Umrisse interdisziplinärer Suchtforschung am Beispiel medizinischer Bildgebung mittels PET, SPECT und fMRT zur Wirkung psychotroper Substanzen.

The addiction phenomenon provides a fertile ground for the application of the tools of medical imaging which contribute to the development of scientific conceptualization of the effect of psychotropic substances. Medical imaging as for instance PET (Positron Emission Tomography), SPECT (Single Photon Emission Tomography) or functional Magnetic Resonance Imaging (fMRI) are well established for the examination of functional activity in the living brain. Medical imaging permits the development of functional activation maps during perceptual, cognitive or emotional efforts with a high temporal and spatial resolution. Medical imaging devices have therefore also been used to help our understanding of many aspects of the pharmacokinetics and pharmacodynamics of abused drugs. Because Delta-9-Tetrahydrocannabinol and cocaine continue to be the most commonly used illicit drugs, their effects on the brain function are of major interest. The cannabinoid CB(1) receptor agonist Delta(9)-THC as for instance has also been suggested for treatment of Tourette syndrome (TS). This article provides an overview of present applications of medical imaging with PET, SPECT, and fMRI and its results regarding addiction-related research on Delta-9-Tetrahydrocannabinol and cocaine.

[Impact of slow-release oral morphine on drug abusing habits in Austria]. / Der Einfluss von retardiertem Morphin auf die Drogensituation in Osterreich.

A well-established possibility to treat opiate addiction is the participation in opiate maintenance treatment programmes. For this purpose the opioids methadone and buprenorphine have been evaluated and are used nowadays in many countries. However, since 1998 also the use of slow-release oral morphine (SROM) has been legally permitted in Austria. Our data show that these morphine preparations are frequently abused and are dominating the black market in the meantime. Especially the intravenous consumption of SROM goes along with highly dangerous side effects that exceed the risks of needle sharing alone. Special galenics are supposed to ensure a 24 h effect of the otherwise quickly metabolised morphine. If dissolved and injected, insoluble contents such as talcum cause microembolisms, leading to severe damages of the inner organs. Furthermore, SROM, i.e. a drug prescribed by physicians, has been proved to be the main responsible substance in most drug related deaths since its permission and has nearly replaced heroin. Forensic physicians play a major role in the profound examination of these cases, including extensive toxicological analyses and interpretation of results. For instance, a differentiation between a recent morphine and heroin consumption is certainly possible, provided appropriate methods are used. A reliable estimation of the current situation of drug abusing habits is a premise for adequate therapeutic offers and preventive measures. Thus, well-founded and comparable data have to be collected. To facilitate data report a standardized report form has been developed that includes an obligatory statement regarding morphine or heroin consumption. This should help to enlighten the ongoing discussion on the role of SRM in drug abuse cases. Our results indicate that the prescription of SROM in opiate maintenance therapy has to be handled very strictly and should be reserved for special patients only. A slackening of the Austrian law concerning SROM is therefore objected.

[Current consumer conditions among opioid addicts--implications for maintenance-treatment programmes provided by ambulatory drug treatment centers and physicians]. / Aktuelle Konsumformen bei Drogenabhängigkeit--Implikationen für Substitutionsprogramme in ambulanten Einrichtungen und bei behandelnden Arzten.

BACKGROUND: Anonymous evaluation of the current conditions of drug scene and drug consumption, entrance age, personal motives for drug consumption and satisfaction among opioid-dependent clients with treatments available within an ambulant maintenance treatment setting. METHODS: The questionnaire for the study was based on representative studies and covered 112 questions regarding drug consumption. In addition, an instrument of the "Hessische Landesstelle gegen die Suchtgefahren", which measures satisfaction of opioid clients regarding public drug-treatment centers, was used. RESULTS: A total of 158 opioid clients within an ambulant maintenance treatment setting were enrolled in the study. The mean age at first drug consumption was 15.1 (2.4) years for men and 15.2 (3.5) years for women. The Spearman correlation showed a significant positive correlation (r=0.284) between age and time of first drug consumption (p=0.019). Cannabis was the most frequent entrance drug (55.8%), followed by alcohol (33.8%), opioids (17.6%) and nicotine (11.8%). Additional consumption of benzodiazepines was observed in 44.7% of men and 39.7% of women, of cannabis in 74.5% of men and 52.4% of women, and of sustained-release morphine in 41.4% of men and 33.3% of women. Within the previous 6-12 months cocaine was consumed significantly less (p=0.024) by men (63.8%) than by women (90.5%). 93.3% of the drug users rated a follow-up assistance programme after withdrawal and 71.9% special care programmes for designer drugs very important. IMPLICATIONS: The present study supports the assumption of an earlier age of first drug consumption. In view of our findings on entrance age, and on polytoxicomanic consumption patterns and gender-specific differences, we believe that the objectives of substitution programmes can only be reached if programmes are adequately adapted to the actual conditions of the drug scene and are able to cooperate with other public drug-treatment systems.