The CB1 receptor of the endocannabinoid system is known to modulate the endocrine hypothalamic-peripheral endocrine axes. Important advances have been made in our understanding of the endocannabinoid signaling system in various aspects of alcoholism and drug consumption. Alcohol increases the synthesis or impairs the degradation of endocannabinoids, leading to a locally elevated endocannabinoid tone within the brain. Elevated endocannabinoid tone might be expected to result in compensatory down-regulation of CB1 receptors or dampened signal transduction. Following release, endocannabinoids diffuse back to the presynaptic neuron where they act as short-range modulators of synaptic activity by altering neurotransmitter release and synaptic plasticity (Basavarajappa, 2007). Several small studies investigated a potential association between variants on the CNR1 gene and alcohol and/or drug consumption yielding inconsistent results (Herman et al. 2006; Racz et al. 2003; Schmidt et al. 2002; Zhang et al. 2004, Zuo et al. 2007).

We used data from the BWHHS study to evaluate whether two different single nucleotide polymorphisms of the CB1 receptor of the endocannabinoid system (CR1=rs1049353; CR2=rs2023239) are associated with obesity (2 variables), blood measures (9 variables), food intake (22 variables), drug consumption (6 variables) or mood (3 variables). There was no evidence that body mass measures, food intake or mood were related to genetic variants. However the results concerning alcohol and tobacco use are intriguing and merits further clarification.

Methods

Data from the ALSPAC study will be used to evaluate a potential association between variants of the CNR1 gene and alcohol consumption. We will genotype the two SNPs from the previous study (rs1049353; rs2023239) as well as to additional SNPs: rs806368 & rs12720071.The following data from the mother's forty seven month post-natal questionnaire will be investigated: alcoholic drinks (B22), own smoking (F4), passive smoking (D2, F5), drug/cannabis consumption (A3), being currently pregnant (A8).

The data will be analyzed using established statistical methods for genetic studies, primarily via regression models adjusted for potential confounding factors. Potential population admixture will be allowed for in the analysis. Genotyping will be done until end of November. Subsequently the analysis will be performed. The results will published in a scientific journal.

Significance

The ALSPAC study has considerable larger sample size than every other previous study on this topic. This candidate gene study will help to understand the role of the endocannabinoid system in the process of addiction. In addition,the study results are relevant regarding the application effects of cannabinoid (CB1) receptor antagonists. For instance a recent Cochrane review found that Rimobanant is helpful for quitting smoking (Cahill & Ussher, 2007).