Epigenetics of drug abuse: predisposition or response
Open accessAbstract
Drug addiction continues to be a serious medical and social problem. Vulnerability to develop an addiction to drugs is dependent on genetic, environmental, social and biological factors. In particular, the interactions of environmental and genetic factors indicate the significance of epigenetic mechanisms, which have been found to occur in response to illicit drug use or as underlying factors in chronic substance abuse and relapse. Epigenetics is defined as the heritable and possibly reversible modifications in gene expression that do not involve alterations in the DNA sequence. This review discusses the various types of epigenetic modifications and their relevance to drug addiction to elucidate whether epigenetics is a predisposing factor, or a response to, developing an addiction to drugs of abuse.
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In substance use disorders, substance use can alter DRD2 methylation in animal and human models.
“Studies in substance use disorders including cocaine, alcohol, and nicotine show that substance use can alter DRD2 methylation in animal and human models”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [118]
The Cocaine section reports cocaine-induced Pp1 promoter hypermethylation in mice, and the Alcohol section reports methylation differences in people with alcoholism. These passages support the broader point that substance use is associated with methylation changes in animal and human studies, but they do not report altered DRD2 methylation; the nicotine passage discusses histone acetylation rather than DRD2 methylation. No page numbers are available in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredReduced DRD2 expression from DNA hypermethylation is associated with reward deficiency and addiction vulnerability.
“reduced DRD2 expression from DNA hypermethylation is associated with reward deficiency and addiction vulnerability”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [118]
The Alcohol section discusses hypermethylation of genes including SNCA and AVP, while Basic concepts of epigenetics discusses reward-related effects of MeCP2. Searches for DRD2, dopamine D2 receptor hypermethylation, and reward deficiency found no passage linking reduced DRD2 expression to reward deficiency or addiction vulnerability in our copy; page numbers were unavailable. (LLM, conf=0.75)
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- Authors
- Nielsen, D. A., Utrankar, A., Reyes, J. A., Simons, D. D., & Kosten, T. R.
- Affiliations
- Michael E. DeBakey VA Medical Center (US)
- Rice University (US)
- Corresponding author
- Nielsen, David A
- Venue
- Pharmacogenomics
- Publisher
- Informa UK Limited
- Published
- 2012-07
- Volume
- 13
- Issue
- 10
- Pages
- 1149-1160
- ISSN
- 1462-2416 (ISSN-L)
- 1744-8042
- PMC
- PMC3463407
- OpenAlex
- W2023044136
- Cited by
- 125
- References
- 89
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 3 · 2023: 16 · 2022: 8 · 2021: 7 · 2020: 12 · 2019: 14 · 2018: 7 · 2017: 7 · 2016: 8 · 2015: 13 · 2014: 12 · 2013: 6
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Pharmacogenomics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH/NIDA 5 (P50 DA018197-05)
- Veterans Health Administration
- Adrienne Helis Malvin Medical Research Foundation
- Toomim Family Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- epigenetics, drug addiction, substance abuse, epigenetic modifications, gene expression regulation, genetic susceptibility, environmental factors, addiction relapse, illicit drug use
- MeSH terms
- Cocaine, Heroin, Humans, Behavior, Addictive, Receptors, Opioid, mu, DNA Methylation, Substance-Related Disorders, Genetic Predisposition to Disease, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Serotonin Plasma Membrane Transport Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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