of several pathways from drug experimentation to persistent use and dependence. What is better understood is drug-induced neuronal plasticity - for instance, repeated cocaine administration has been found to relate to modification of neuronal plasticity and increased preference for cocaine in mice104. Studies in humans are largely limited by availability of tissue with gene expression congruent with activity in the central nervous system. Epigenetic modification may be gene and tissue-specific and if so, such effects will be challenging to capture within the human paradigm.