Genetic Factors Modulating Heroin Tolerance Capacity

By collecting blood samples from volunteers who are receiving methadone replacement therapy, this study aims to determine the role of opioid receptors (i.e. m, k and d ) that contributes to the mechanism of tolerance, drug resistance, and susceptibility to the drug. This study will benefit forensic toxicologists in enabling them to offer a more meaningful interpretation of a blood drug concentration found in heroin abuse cases.

&nbsp.In line with this, the following research objectives will be considered in testing the research hypothesis: (1) determine the extent of variation opioid receptors in heroin-dependent volunteers who are receiving methadone therapy programme (0 – 9 months). (2) identify the functional consequences caused by genetic polymorphism (0 – 24 months). and (3) characterize the effects of methadone replacement therapy based on the levels of methadone replacement tolerance in each volunteer (0 – 36 months).
To determine the extent of phenotypic variation in opioid receptors and identify common genetic polymorphisms, Europeans with a history of heroin-dependent that is currently undergoing methadone replacement therapy programme will be invited to participate in this study. To assess the contribution of methadone replacement in the patterns of opioid receptor expression, the researcher will re-measure the key receptor levels after the 6th week of the methadone replacement period.

Aside from identifying volunteers with a responsive receptor to methadone replacement therapy, this approach will enable the researcher to minimize the potential confounding effect of habitual lifestyle on&nbsp.phenotypically “high” and “low” expressers. Individuals with high or low levels of receptors and those with responsive phenotype will be classified under subgroups. Eventually, lymphocytes taken from the volunteers will be transformed using Epstein Barr Virus (EBV) to produce immortalized cell lines which will be used as a model system in studying the drug-gene interactions that could modulate opiate receptor levels.&nbsp.