Elsewhere [32] we have suggested levels of analysis for pharmacogenomics and pharmacogenetics: 1) “primary” pharmacogenomics that describes the genetics of individual differences in the adsorption, distribution, metabolism and/or excretion of a drug; 2) “secondary” pharmacogenomics that describes individual differences in drug targets, such as the G-protein coupled receptors, transporters and ligand gated ion channels that are the primary targets of opiates, psychostimulants and barbiturates, respectively and 3) “higher order” pharmacogenomics that provide individual differences in post-receptor drug responses. Such post-receptor drug responses are more likely to be common to actions of abused substances that come from several different chemical classes and act at distinct primary receptor or transporter sites in the brain. Based on the twin data that are currently available, we thus postulate that much, if not most, of the human genetics of addition vulnerability represents “higher order” pharmacogenomics.
