Human studies of gene expression suggest the importance and diversity of epigenetic influences on SUD. In general, these studies indicate drug-specific changes in gene expression as well as differences in gene expression related to the use of multiple substances (Lehrmann & Freed, 2008; Marie-Claire et al., 2007; Zhou, Yuan, Mash, & Goldman, 2011). For example, cocaine users exhibit significant differences in expression of genes involved in neurotransmitter levels in the nucleus accumbens although these results are not consistent across studies (Bannon, Kapatos, & Albertson, 2005). Additionally, these studies suggest that acute early-stage drug use is associated with expression changes in acute early response genes (Vaccarino, Hayward, Nestler, Duman, & Tallman, 1992). In comparison, chronic substance exposure has been associated with widespread changes in expression of genes related to several diverse and fundamental cellular functions, including ion transport, chromosome remodelling, stress and immune response, cell adhesion, cell cycle, apoptosis, protein and lipid metabolism, and mitochondrial functions (Liu, Chen, Lerner, Brackett, & Matsumoto, 2005; Schroeder et al., 2008; Vilar et al., 2006; J. Wang, Kim, Donovan, Becker, & Li, 2009; Zhao et al., 2006).
