Among epigenetic marks, DNA methylation changes are most likely to develop as ideal substance use disorder biomarkers. As reviewed by Ladd-Acosta, there is a broad evidence base supporting DNA methylation signatures as biomarkers of exposure that are likely to translate well to clinical practice [18]. Methylation signatures for different types of environmental exposures (including smoking) have been shown to exhibit temporal stability, specificity with respect to type of exposure, timing of exposure, cumulative dose and cessation time. Equally important, current DNA methylation assays can be used with a variety of accessible tissue types and are becoming more accurate and inexpensive, thus addressing the key core areas of cost, quality, and access. In contrast, assays of histone tail modifications and RNAs are more expensive and technically difficult. Therefore, for reasons of both cost and quality, we will focus this review on DNA methylation biomarkers rather than histone or RNA biomarkers. Additionally, for reasons of specificity, we will focus on methylation patterns at specific CpGs as opposed to measurement of global methylation levels. Changes in in global DNA methylation, often measured via
