Variation in the gene coding for the M5 muscarinic receptor (CHRM5) influences cigarette dose but is not associated with dependence to drugs of addiction : evidence from a prospective population based cohort study of young adults

Background: The mesolimbic structures of the brain are important in the anticipation and perception of reward. Moreover, many drugs of addiction elicit their response in these structures. The M5 muscarinic receptor (M5R) is expressed in dopamine-containing neurones of the substantia nigra pars compacta and ventral tegmental area, and regulates the release of mesolimbic dopamine. Mice lacking M5R show a substantial reduction in both reward and withdrawal responses to morphine and cocaine. The CHRM5, the gene that codes for the M5R, is a strong biological candidate for a role in human addiction. We screened the coding and core promoter sequences of CHRM5 using denaturing high performance liquid chromatography to identify common polymorphisms. Additional polymorphisms within the coding and core promoter regions that were identified through dbSNP were validated in the test population. We investigated whether these polymorphisms influence substance dependence and dose in a cohort of 1947 young Australians.

Results: Analysis was performed on 815 participants of European ancestry who were interviewed at wave 8 of the cohort study and provided DNA. We observed a 26.8% increase in cigarette consumption in carriers of the rs7162140 T-allele, equating to 20.1 cigarettes per week (p=0.01). Carriers of the rs7162140 T-allele were also found to have nearly a 3-fold increased risk of developing cannabis dependence (OR=2.9 (95%CI 1.1-7.4); p=0.03).

Conclusion: Our data suggest that variation within the CHRM5 locus may play an important role in tobacco and cannabis but not alcohol addiction in European ancestry populations. This is the first study to show an association between CHRM5 and substance use in humans. These data support the further investigation of this gene as a risk factor in substance use and dependence.

The devil in high heels : drugs, symbolism and Kate Moss

This paper contributes to critical voices on the issue of organisational responses to employee drug use. It does so by exploring symbolic readings of organisations’ relations with drugs and drug-taking. Our focus is recent coverage of, and organisational responses to, the UK tabloid media’s exposé of fashion supermodel Kate Moss’s alleged cocaine use. We consider that the celebrity endorsement in this particular case highlights the ambiguities created by the symbolic associations between the organisation and the ‘image’ projected by the celebrity. Overall, we use this case to explore symbolic relationships between drugs, sex, femininity and organisation. Through highlighting these connections, we question further the rationality of organisational responses to employee drug use and, utilising Derrida’s (1981) extension of Plato’s notion of the pharmakon, consider whether workforce drug testing might be fruitfully seen as a symbolic mechanism for scapegoating and sacrifice in order to protect the organisation’s (masculine) moral order.

The devil in high heels : drugs, symbolism and Kate Moss

This paper contributes to critical voices on the issue of organisational responses to drugs and employee drug use. It does so by exploring some of the symbolism residing at the heart of organisations’ relations with drugs and drug taking. Our focus is recent media coverage of, and organisational responses to, the UK tabloid media’s exposé of fashion supermodel Kate Moss’s cocaine use. We use this case to explore symbolic relationships between drugs, sex and femininity, and organisation. Through highlighting these symbolic connections we question further the rationality of organisational responses to the ‘spectre’ of drugs and the issue of employee drug use. We conclude by suggesting that workforce drug testing regimes might be fruitfully seen as mechanisms for scapegoating and sacrifice in order to protect the organizational moral order.

Using clinical trial data and linked administrative health data to reduce the risk of adverse events associated with the uptake of newly released drugs by older Australians : a model process

Background
The study was undertaken to evaluate the contribution of a process which uses clinical trial data plus linked de-identified administrative health data to forecast potential risk of adverse events associated with the use of newly released drugs by older Australian patients.

Methods
The study uses publicly available data from the clinical trials of a newly released drug to ascertain which patient age groups, gender, comorbidities and co-medications were excluded in the trials. It then uses linked de-identified hospital morbidity and medications dispensing data to investigate the comorbidities and co-medications of patients who suffer from the target morbidity of the new drug and who are the likely target population for the drug. The clinical trial information and the linked morbidity and medication data are compared to assess which patient groups could potentially be at risk of an adverse event associated with use of the new drug.

Results
Applying the model in a retrospective real-world scenario identified that the majority of the sample group of Australian patients aged 65 years and over with the target morbidity of the newly released COX-2-selective NSAID rofecoxib also suffered from a major morbidity excluded in the trials of that drug, indicating a substantial potential risk of adverse events amongst those patients. This risk was borne out in post-release morbidity and mortality associated with use of that drug.

Conclusions
Clinical trial data and linked administrative health data can together support a prospective assessment of patient groups who could be at risk of an adverse event if they are prescribed a newly released drug in the context of their age, gender, comorbidities and/or co-medications. Communication of this independent risk information to prescribers has the potential to reduce adverse events in the period after the release of the new drug, which is when the risk is greatest.

Note: The terms 'adverse drug reaction' and 'adverse drug event' have come to be used interchangeably in the current literature. For consistency, the authors have chosen to use the wider term 'adverse drug event' (ADE).

Randomised controlled trials and 'unexpected' adverse events associated with newly released drugs : improvements in pharmacovigilance systems are necessary for real-time identification of patient safety risks

Adverse drug events are one of the major causes of morbidity in developed countries, yet the drugs involved in these events have been trialled and approved on the basis of randomised controlled trials (RCTs), regarded as the study design that will produce the best evidence.

Though the focus on adverse drug events has been primarily on processes and outcomes associated with the use of these approved drugs, attention needs to be directed to the way in which the RCT study design is structured. The implementation of controls to achieve internal validity in RCTs may be the very controls that reduce external validity, and contribute to the levels of adverse drug events associated with the release of a new drug to the wider patient population.

An examination of these controls, and the effects they can have on patient safety, underscore the importance of knowing about how the clinical trials of a drug are undertaken, rather than relying only on the recorded outcomes.

As the majority of new drugs are likely to be prescribed to older patients who have one or more comorbidities in addition to that targeted by a new drug, and as the RCTs of those drugs typically under-represent the elderly and exclude patients with multiple comorbidities, timely assessment of drug safety signals is essential.

It is unlikely that regulatory jurisdictions will undertake a reassessment of safety issues for drugs that are already approved. Instead, reliance has been placed on adverse drug event reporting systems. Such systems have a very low reporting rate, and most adverse drug events remain unreported, to the eventual cost to patients and healthcare systems.

This makes it essential for near real-time systems that can pick up safety signals as they occur, so that modifications to the product information (or removal of the drug) can be implemented.

Inhibitory effect of antidepressant drugs on contact hypersensitivity reaction

Background: Contact hypersensitivity (CS) reaction in the skin is T-cell mediated immune reaction which plays a major role in the pathogenesis and chronicity of various inflammatory skin disorders and, like other delayed-type hypersensitivity (DTH) reactions, affords immunity against tumor cells and microbes. CS response is a self-limiting reaction, and interleukin (IL)-10 is considered to be a natural suppressant of cutaneous inflammatory response. Recently, it has been demonstrated that major depression is related to activation of the inflammatory response and elevation of some parameters of cell-mediated immunity. It has been suggested that such activation of the immune system may play a role in etiology of depression. If this immunoactivation is involved in etiology of depression, one would expect that antidepressant agents may have negative immunoregulatory effects. To the best of our knowledge, the effect of antidepressants on contact hypersensitivity has not been studied.

Methods: The aim of the present study was to establish the effect of prolonged desipramine or fluoxetine treatment on CS reaction to picryl chloride.

Results: Antidepressants significantly suppressed CS reaction, fluoxetine by 53% whereas desipramine by 47% compared to positive control. Moreover, desipramine and fluoxetine decreased relative weight of auxillary lymph nodes. Desipramine decreased also relative weight of inguinal lymph nodes and spleens whereas desipramine and fluoxetine increased production of IL-10 in comparison to positive control.

Conclusion: The observed effect of antidepressant drugs on CS reaction is consistent with the hypothesis that T-cell mediated immunity is targeted by antidepressants.

Drugs, ships and containers : how anti-terrorism benefits shipping security

Using ships to transport illicit drugs is not new; nor is the practice of concealing them
in shipping containers decreasing – or is it? This article questions whether recent container security initiatives created to stop terrorism have also achieved a decrease in the use of containers for smuggling illicit drugs. Or, are these maritime security regimes creating a false sense of achievement, being too limited in scope to be truly useful in this secondary role? Logically, improved detection of illicit drugs in containers shipped by sea is more likely when port personnel are better trained, x-ray scanners installed, port fencing improved and official collaboration encouraged. However, since the number of containers being electronically screened and physically searched has only marginally improved, the question is, is it enough?

Disorder and the body of drugs : addiction, consumption, control, and city space

Different cultures and the specific culture manifested within them are intrinsically linked to addiction in a complex fashion which has a long history. For important thinkers, such as Nietzsche, addiction actually embodies human culture, rendering addiction and culture inseparable. This is clearly seen within the Western world’s addiction to the consumption of material goods and the damage that results.

Utopia has often become dystopia. Not only is an understanding of addiction key to understanding culture but to an understanding of the very act thinking itself and the way of being in the world. Addiction raises key philosophical questions, such as: do people really have a choice in their behavior, and what governs them; is it free will or predetermination? Is it biology or environment is it the external world or the internal that drives addiction, or a complex combination of both?

In a contemporary context the media frenzy around celebrity addiction continually fuels public debate in this area, and this book deepens the understanding of addiction within this contentious context. This book addresses a key concern over how addiction became the norm, and it seeks to understand its dominance comprehensively. How did it come to pass that not being an addict was a transgressive act and way of being?

While there has been a great deal of debate about addiction utilizing the discourse of individual and often competing disciplines such as biology and psychology, little attention has been paid to the cultural aspects of addiction. The innovative approach taken by this book is to offer insights into this complex area through a contemporary methodology that covers diverse interrelated areas. Drawing on different disciplines, offering deeper insights, from the analysis of music lyrics to empirical social science and anthropological work in AA groups in Mexico and the portrayal of the “addiction’ to therapy in film and television, amongst other areas, this book addresses the need for a more comprehensive approach.

Academic analysis is also given to the discourse on celebrity culture and addiction. A contemporary fusion of the humanities and the social sciences is the best way forward to tackle this subject and move the debate on. The focus of this study is an innovative interdisciplinary and intercultural approach to addiction, from the social sciences to the humanities, including cultural studies, film and media studies, and literary studies. Areas that have been overlooked, such as lost women’s writings, are examined, in addition to comics, popular film and television, and the work of AA groups.

This edited collection is the first study to provide such a comprehensive analysis of the cultures of addiction. Traversing cultures across the globe, including Asia, Central America, as well as Europe and America, this book opens up the debate in addiction studies and cultural studies. The important insights the book delivers helps to answer questions such as: In what way can Deleuze further the understanding of addiction through the analysis of rock lyrics? How does anthropology improve the understanding of AA groups? How can cultural studies deepen knowledge on the “addiction” to therapy? These are just some of the vast array of areas this book covers. Other areas include the condemnation of “addiction” to comic reading through an historical examination, violence in popular culture, and lost women’s writing on addiction. No other book has such depth and contemporary breadth.

Cultures of Addiction is an important book for those taking cultural studies courses across a range of interrelated disciplines, including English and literary studies, history, American studies, and film and media studies. This will be invaluable to library collections in these fields and beyond in the social sciences, and specifically in addiction studies and psychology.

(Jason Lee, Editor)

Chemiluminescence detection of piperazine designer drugs and related compounds using tris(2,2?-bipyridine)ruthenium(III)

 An exploration of the chemiluminescence from reactions of a large number of benzyl and phenylpiperazine analytes with tris(2,2’-bipyridyl)ruthenium(III) was carried out providing information towards the emission intensity of this chemiluminescent reagent and the structure of analytes it interacts with.