AUTHOR=Liu Ya , Wang Xiao-Qian , Zhang Peng , Haghparast Abbas , He Wen-Bin , Zhang Jian-Jun 

TITLE=Research progress of DNA methylation on the regulation of substance use disorders and the mechanisms

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=Volume 19 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2025.1566001

DOI=10.3389/fncel.2025.1566001

ISSN=1662-5102

ABSTRACT=Drug abuse can damage the central nervous system and lead to substance use disorder (SUD). SUD is influenced by both genetic and environmental factors. Genes determine an individual’s susceptibility to drug, while the dysregulation of epigenome drives the abnormal transcription processes, promoting the development of SUD. One of the most widely studied epigenetic mechanisms is DNA methylation, which can be inherited stably. In ontogeny, DNA methylation pattern is dynamic. DNA dysmethylation is prevalent in drug-related psychiatric disorders, resulting in local hypermethylation and transcriptional silencing of related genes. In this review, we summarize the role and regulatory mechanisms of DNA methylation in cocaine, opioids, and methamphetamine in terms of drug exposure, addiction memory, withdrawal relapse, intergenerational inheritance, and focus on cell-specific aspects of the studies with a view to suggesting possible therapeutic regimens for targeting methylation in both human and animal research.