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.

Vested interests in addiction research and policy alcohol industry use of social aspect public relations organizations against preventative health measures

Aim It has been proposed that alcohol industry ‘social aspects/public relations’ organizations (SAPROs) serve the agenda of lending credibility to industry claims of corporate responsibility while promoting ineffective industry-friendly interventions (such as school-based education or TV advertising campaigns) and creating doubt about interventions which have a strong evidence base (such as higher taxes on alcoholic beverages). This paper investigated whether submissions to Australia's National Preventative Health Taskforce (NPHT) from alcohol industry bodies regarding the Australian SAPRO, Drinkwise, have used this organization to demonstrate corporate responsibility while promoting industry-friendly interventions.

Method Submissions to the Australian National Preventative Health Taskforce (NPHT) discussion paper Australia, the healthiest country by 2020 (n = 375) were examined to identify those with primary alcohol content. A thematic analysis of the resulting 33 submissions was conducted to determine which organization, institution or individual discussed Drinkwise.

Setting Australia.

Findings Nine of the 33 submissions discussed Drinkwise; all were submitted by the alcohol industry or its affiliates. Every industry submission referred to Drinkwise either as providing evidence of social responsibility or by suggesting the industry-friendly actions of Drinkwise as alternatives to those recommended by the NPHT report.

Conclusions Drinkwise has been used by the alcohol industry to create an impression of social responsibility while promoting interventions that maintain profits and campaigning against effective interventions such as higher taxes on alcohol.