# Drug-Induced Epigenetic Alterations: A Set of Forensic Toxicological Fingerprints?—A Systematic Review

## TL;DR

This review explores whether drug use causes lasting epigenetic changes that could be used as forensic markers in toxicology.

## Contribution

The paper systematically evaluates if drug-induced epigenetic changes can serve as forensic toxicological fingerprints in humans.

## Key findings

- Common drugs like alcohol and cocaine induce specific epigenetic changes in humans.
- Epigenetic alterations persist in tissues like blood and brain even after drug use stops.
- Forensic use is limited due to factors like age and other exposures affecting results.

## Abstract

Background/Objectives: Epigenetics refers to heritable modifications in gene expression that do not involve changes to the DNA sequence. Among these, DNA methylation, histone modifications, and non-coding RNAs play a key role in regulating gene activity and are influenced by environmental factors, including exposure to psychoactive substances. In recent years, it has been hypothesized that such alterations may serve as molecular markers with forensic relevance. This systematic review aims to evaluate whether current evidence supports the use of drug-induced epigenetic changes as potential toxicological fingerprints in human subjects. Methods: A systematic literature search was conducted following PRISMA guidelines, including articles published on PubMed between 1 January, 2010, and 31 December, 2025. Only studies conducted on human samples and published in English were considered; animal studies and articles lacking epigenetic data were excluded. Results: Forty-two studies met the inclusion criteria. The most commonly investigated substances (alcohol, cocaine, methamphetamine, cannabis, and opioids) were found to induce specific and, in some cases, persistent epigenetic changes. These include alterations in CpG methylation in promoter regions, variations in miRNA expression, and modulation of epigenetic enzymes. Such changes were observed in brain tissue, blood cells, and semen, with evidence of persistence even after drug cessation. Conclusions: Current evidence confirms that psychoactive substance use is associated with specific epigenetic modifications. However, forensic application remains limited due to confounding factors such as age, co-exposures, and post-mortem interval. Further standardized research is necessary to validate their use as forensic biomarkers.