Any association between availability, initiation and abuse should be modelled as a multistage process where availability or exposure (upstream variable) is followed by initiation, which under certain circumstances, can result in abuse or dependence (downstream variable). Multi-stage modelling or causal-common-contingent (CCC) pathway analyses (17) represent an improvement over the standard independent assessments of drug use and abuse because of the ability to partition genetic and environmental factors into i) those that are common to upstream and downstream variables and ii) those specific to each stage.
