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 treatment of opiate dependency

The portfolio examines use of opiate antagonist medication (naltrexone hydrochloride) as a safe and effective treatment for opiate dependence. The program incorporates evidence-based assessment, treatment planning and after-care counselling. Detoxification using naltrexone is highly effective. Use of naltrexone predicts long-term abstinence and better health and social outcomes. Naltrexone implants improve compliance and outcomes.

Gene-environment interaction in problematic substance use : interaction between DRD4 and insecure attachments

To investigate the combined effect of an exon III variable number tandem repeat in the dopamine receptor gene (DRD4) and insecure attachment style on risk for tobacco, cannabis and alcohol use problems in young adulthood. It was hypothesized that (1) individuals with 5, 6, 7 or 8 repeats (labelled 7R+) would be at increased risk for problematic drug use, and (2) risk for drug use would be further increased in individuals with 7R+ repeats who also have a history of insecure parent–child attachment relations. Data were drawn from the Victorian Adolescent Health Cohort Study, an eight-wave longitudinal study of adolescent and young adult development. DRD4 genotypes were available for 839 participants. Risk attributable to the combined effects of 7R+ genotype and insecure attachments was evaluated within a sufficient causes framework under the assumptions of additive interaction using a two-by-four table format with a common reference group. 7R+ alleles were associated with higher tobacco, cannabis and alcohol use (binging). Insecure attachments were associated with higher tobacco and cannabis use but lower alcohol use. For tobacco, there was evidence of interaction for anxious but not avoidant attachments. For cannabis, there was evidence of interaction for both anxious and avoidant attachments, although the interaction for anxious attachments was more substantial. There is no evidence of interaction for binge drinking. Results are consistent with a generic reward deficit hypothesis of drug addiction for which the 7R+ disposition may play a role. Interaction between 7R+ alleles and attachment insecurity may intensify risk for problematic tobacco and cannabis use.

The self-reported personal wellbeing of a sample of Australian injecting drug users

Aims To examine the self-reported personal wellbeing of a sample of Australian injecting drug users (IDU) using a standardized instrument and determine the key correlates of variations in self-reported personal wellbeing.

Design, setting and participants Cross-sectional survey of 881 Australian IDU.

Measurements Self-reported personal wellbeing collected using the Personal Wellbeing Index (PWI).

Findings IDU scored significantly lower than the general Australian population on the PWI and all subscales. Lower PWI scores were associated with a range of socio-demographic, drug use and other health and social characteristics. Across all PWI subscales, lower personal wellbeing scores were associated with unemployment, past 6-month mental health problems and more frequent injecting (all P < 0.05).

Conclusions The PWI is sufficiently sensitive to distinguish between IDU and the general population, and to identify key correlates of PWI among IDU. Some domains canvassed within the scale, such as health, standard of living and life achievements, are well within the scope of current intervention strategies, such as pharmacotherapy maintenance treatment and housing and employment support services. This suggests that the PWI could be useful in clinical settings by allowing structured identification of the areas of a person's life to be addressed as a part of a treatment regimen. In order to inform targeted prevention and intervention efforts, longitudinal studies of PWI and its correlates among IDU are required.

Quick fixes, drug culture and management culture : excellence and ecstasy, BPR and Brown

This paper critiques the prescriptions of management gurus by charting parallels between management culture and drug culture over the last two decades. I argue that the ‘quick fixes’ peddled by gurus mirror the illicit drug fix of choice popularised in the same era. I suggest that, in terms of the specific nature of their promised highs, Excellence mirrored Ecstasy, and Business Process Reengineering mirrored Heroin. By tracing resonance with drug fixes, I introduce another way to understand why particular corporate fixes are found so attractive, locating this in patterns of addiction and in the gurus’ ability to exploit wider shared cultural contexts. The paper ends by suggesting that the comparison with the world of illicit drugs has lessons not only for our understandings of management and management gurus, but also for critical management academics engagement with both the gurus and our wider audiences.

Harm reduction as anarchist practice : a user’s guide to capitalism and addiction in North America

In spite of its origins as an illegal, clandestine, grassroots activity that took place either outside or in defiant opposition to state and legal authority, there is growing evidence to suggest that harm reduction in North America has become sanitized and depoliticized in its institutionalization as public health policy. Harm reduction remains the most contested and controversial aspect of drug policy on both sides of the Canada–US border, yet the institutionalization of harm reduction in each national context demonstrates a series of stark contrasts. Drawing from regional case study examples in Canada and the US, this article historically traces and politically re-maps the uneasy relationship between the autonomous political origins of harm reduction, contemporary public health policy, and the adoption of the biomedical model for addiction research and treatment in North America. Situated within a broader theoretical interrogation of the etiology of addiction, this study culminates in a politically engaged critique of traditional addiction research and drug/service user autonomy. Arguing that the founding philosophy and spirit of the harm reduction movement represents a fundamentally anarchist-inspired form of practice, this article concludes by considering tactics for reclaiming and re-politicizing the future of harm reduction in North America.

Internet content regulation, public drug websites and the growth in hidden Internet services

Governments have traditionally censored drug-related information, both in traditional media and, in recent years, in online media. We explore Internet content regulation from a drug-policy perspective by describing the likely impacts of censoring drug websites and the parallel growth in hidden Internet services. Australia proposes a compulsory Internet filtering regime that would block websites that ‘depict, express or otherwise deal with matters of… drug misuse or addiction’ and/or ‘promote, incite or instruct in matters of crime’. In this article, we present findings from a mixed-methods study of online drug discussion. Our research found that websites dealing with drugs, that would likely be blocked by the filter, in fact contributed positively to harm reduction. Such sites helped people access more comprehensive and relevant information than was available elsewhere. Blocking these websites would likely drive drug discussion underground at a time when corporate-controlled ‘walled gardens’ (e.g. Facebook) and proprietary operating systems on mobile devices may also limit open drug discussion. At the same time, hidden Internet services, such as Silk Road, have emerged that are not affected by Internet filtering. The inability for any government to regulate Tor websites and the crypto-currency Bitcoin poses a unique challenge to drug prohibition policies.
Read More: http://informahealthcare.com/doi/full/10.3109/09687637.2012.745828

Modifying the risk associated with an impulsive temperament: a prospective study of drug dependence treatment

The evidence linking the personality trait of impulsivity and substance misuse is well established. Importantly, impulsivity not only predicts substance misuse problems but has an association with duration in treatment, likelihood of completing treatment and time to relapse. Treatment that focuses on increasing awareness and acceptance of thoughts and emotions may potentially address impulsive behaviour and in this respect improve treatment outcomes for substance misuse. The current paper investigated the relationship between the facet of impulsivity that taps into poor inhibitory control and treatment outcome. In addition, there was a specific focus on ascertaining the impact of an increase in awareness and attentional control measured in 144 adult substance users receiving treatment in a residential therapeutic community. Impulsivity predicted poorer treatment outcome (measured as drug use severity). Increases in awareness and acceptance of emotions and thoughts during treatment were related to better outcome although this was not associated with baseline levels of impulsivity. Clinical and theoretical implications are discussed.

Offending: drug-related expertise and decision making

Drug use is endemic within offender populations and, as a result, considerable heterogeneity can be found in drug-related crime. Expertise in drug-related offending covers an equally broad base from internal mental processes through skill acquisition to social interactions. This review considers decision making and expertise for crimes in the domains of direct causal effects (e.g., burglary) and non-causal relationships (e.g., apprehension avoidance, detection). Also considered is the notion of expertise as it applies to addiction, in particular the conscious and unconscious goal-directed behaviors articulated in the Selfish Goal model (Huang & Bargh, 2014) and a cool cognition/hot affect dual processing model of criminal decision making (Van Gelder, 2013). The review findings would suggest (a) the need for more focused research into whether expertise differs as a function of drug use and (b) a paradigm shift in terms of treatment for drug-using offenders.

Sober assessment of the link between substance abuse and crime-eliminating drug and alcohol use from the sentencing calculus

The relevance of drug and alcohol involvement to sentencing law and practice is one of the most perplexing and unsettled areas of sentencing law and practice.1 It is also one of the most important issues in the criminal justice system. Most crimes are committed by offenders who are substance involved, and nearly half of all crimes that are committed are done so by offenders who are intoxicated at the time of the offense. Substance involved individuals are grossly over-represented in the criminal courts. Addiction and intoxication impair sound judgment, and hence, it intuitively appears that intoxicated offenders are less culpable for their crimes. Moreover, there is often a sense that addiction and intoxication causes aberrant behavior and that curing the substance involvement will lead to more prudent (law-abiding) conduct.

Cocaine-specific neuroplasticity in the ventral striatum network is linked to delay discounting and drug relapse

AIMS: To contrast functional connectivity on ventral and dorsal striatum networks in cocaine dependence relative to pathological gambling, via a resting-state functional connectivity approach; and to determine the association between cocaine dependence-related neuroadaptations indexed by functional connectivity and impulsivity, compulsivity and drug relapse. DESIGN: Cross-sectional study of 20 individuals with cocaine dependence (CD), 19 individuals with pathological gambling (PG) and 21 healthy controls (HC), and a prospective cohort study of 20 CD followed-up for 12 weeks to measure drug relapse. SETTING AND PARTICIPANTS: CD and PG were recruited through consecutive admissions to a public clinic specialized in substance addiction treatment (Centro Provincial de Drogodependencias) and a public clinic specialized in gambling treatment (AGRAJER), respectively; HC were recruited through community advertisement in the same area in Granada (Spain). MEASUREMENTS: Seed-based functional connectivity in the ventral striatum (ventral caudate and ventral putamen) and dorsal striatum (dorsal caudate and dorsal putamen), the Kirby delay-discounting questionnaire, the reversal-learning task and a dichotomous measure of cocaine relapse indicated with self-report and urine tests. FINDINGS: CD relative to PG exhibit enhanced connectivity between the ventral caudate seed and subgenual anterior cingulate cortex, the ventral putamen seed and dorsomedial pre-frontal cortex and the dorsal putamen seed and insula (P≤0.001, kE=108). Connectivity between the ventral caudate seed and subgenual anterior cingulate cortex is associated with steeper delay discounting (P≤0.001, kE=108) and cocaine relapse (P≤0.005, kE=34). CONCLUSIONS: Cocaine dependence-related neuroadaptations in the ventral striatum of the brain network are associated with increased impulsivity and higher rate of cocaine relapse.

Increased corticolimbic connectivity in cocaine dependence versus pathological gambling is associated with drug severity and emotion-related impulsivity

Neural biomarkers for the active detrimental effects of cocaine dependence (CD) are lacking. Direct comparisons of brain connectivity in cocaine-targeted networks between CD and behavioural addictions (i.e. pathological gambling, PG) may be informative. This study therefore contrasted the resting-state functional connectivity networks of 20 individuals with CD, 19 individuals with PG and 21 healthy individuals (controls). Study groups were assessed to rule out psychiatric co-morbidities (except alcohol abuse and nicotine dependence) and current substance use or gambling (except PG). We first examined global connectivity differences in the corticolimbic reward network and then utilized seed-based analyses to characterize the connectivity of regions displaying between-group differences. We examined the relationships between seed-based connectivity and trait impulsivity and cocaine severity. CD compared with PG displayed increased global functional connectivity in a large-scale ventral corticostriatal network involving the orbitofrontal cortex, caudate, thalamus and amygdala. Seed-based analyses showed that CD compared with PG exhibited enhanced connectivity between the orbitofrontal and subgenual cingulate cortices and between caudate and lateral prefrontal cortex, which are involved in representing the value of decision-making feedback. CD and PG compared with controls showed overlapping connectivity changes between the orbitofrontal and dorsomedial prefrontal cortices and between amygdala and insula, which are involved in stimulus-outcome learning. Orbitofrontal-subgenual cingulate cortical connectivity correlated with impulsivity and caudate/amygdala connectivity correlated with cocaine severity. We conclude that CD is linked to enhanced connectivity in a large-scale ventral corticostriatal-amygdala network that is relevant to decision making and likely to reflect an active cocaine detrimental effect.