{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T16:14:30Z","timestamp":1779898470249,"version":"3.53.1"},"reference-count":136,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R21DA058588"],"award-info":[{"award-number":["R21DA058588"]}]},{"name":"Lieberman Endowment","award":["R21DA058588"],"award-info":[{"award-number":["R21DA058588"]}]},{"name":"Department of Anesthesiology, UNMC","award":["R21DA058588"],"award-info":[{"award-number":["R21DA058588"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Drug abuse is a chronic, relapsing disorder marked by compulsive drug-seeking behavior and profound neurobiological consequences. Each year, millions of individuals face serious social and legal repercussions due to addiction. This review synthesizes findings from both preclinical and clinical studies to examine how chronic exposure to substances such as alcohol, cocaine, methamphetamine, and opioids affects the central nervous system. Specifically, it explores the epigenetic modifications induced by these substances, including DNA methylation, histone modifications, and noncoding RNA regulation. The literature was selected using a thematic approach, emphasizing substance-specific mechanisms and their effects on gene expression, synaptic plasticity, and the brain\u2019s reward circuitry. Emerging evidence links these epigenetic changes to long-term behavioral adaptations and even transgenerational inheritance. This review underscores the complex molecular pathways contributing to addiction, vulnerability, and relapse, offering insights into potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/brainsci15090927","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T09:58:32Z","timestamp":1756288712000},"page":"927","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Decoding Encoded Cravings: Epigenetic Drivers of Addiction"],"prefix":"10.3390","volume":"15","author":[{"given":"Tousif Ahmed","family":"Hediyal","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Shukri","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Stone","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Foroughi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5071-056X","authenticated-orcid":false,"given":"Thangavel","family":"Samikkannu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7226-7367","authenticated-orcid":false,"given":"Gurudutt","family":"Pendyala","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USA"},{"name":"Department of Genetics, Cellular Biology, and Anatomy, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USA"},{"name":"Child\u2019s Health Research Institute, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USA"},{"name":"National Strategic Research Institute, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1002\/jcph.1937","article-title":"The Epidemiology of Drug Abuse","volume":"61","author":"Ignaszewski","year":"2021","journal-title":"J. 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