{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T08:26:06Z","timestamp":1793780766548,"version":"4.6.1"},"reference-count":214,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Drug Policies Department, Presidency of the Council of Ministers, Italy","award":["RBFR12LDOW"],"award-info":[{"award-number":["RBFR12LDOW"]}]},{"name":"Italian Ministry of Education, University and Research","award":["RBFR12LDOW"],"award-info":[{"award-number":["RBFR12LDOW"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>In the recent decade, numerous new psychoactive substances (NPSs) have been added to the illicit drug market. These are synthetized to mimic the effects of classic drugs of abuse (i.e., cannabis, cocaine, etc.), with the purpose of bypassing substance legislations and increasing the pharmacotoxicological effects. To date, research into the acute pharmacological effects of new NPSs is ongoing and necessary in order to provide an appropriate contribution to public health. In fact, multiple examples of NPS-related acute intoxication and mortality have been recorded in the literature. Accordingly, several in vitro and in vivo studies have investigated the pharmacotoxicological profiles of these compounds, revealing that they can cause adverse effects involving various organ systems (i.e., cardiovascular, respiratory effects) and highlighting their potential increased consumption risks. In this sense, NPSs should be regarded as a complex issue that requires continuous monitoring. Moreover, knowledge of long-term NPS effects is lacking. Because genetic and environmental variables may impact NPS responses, epigenetics may aid in understanding the processes behind the harmful events induced by long-term NPS usage. Taken together, \u201cpharmacoepigenomics\u201d may provide a new field of combined study on genetic differences and epigenetic changes in drug reactions that might be predictive in forensic implications.<\/jats:p>","DOI":"10.3390\/biomedicines10061398","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T22:00:38Z","timestamp":1655157638000},"page":"1398","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Epigenetic Studies for Evaluation of NPS Toxicity: Focus on Synthetic Cannabinoids and Cathinones"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5222-5701","authenticated-orcid":false,"given":"Leila","family":"Mazdai","sequence":"first","affiliation":[{"name":"Department of Neurosciences and Rehabilitation, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6343-3944","authenticated-orcid":false,"given":"Matteo","family":"Fabbri","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine, LTTA Center, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9337-9184","authenticated-orcid":false,"given":"Micaela","family":"Tirri","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine, LTTA Center, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2973-2446","authenticated-orcid":false,"given":"Giorgia","family":"Corli","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine, LTTA Center, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Arf\u00e8","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine, LTTA Center, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine, LTTA Center, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrine","family":"Bilel","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine, LTTA Center, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Bergamin","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Department of Health Care Surveillance and Bioethics, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione IRCCS Policlinico Universitario A. Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1003-4007","authenticated-orcid":false,"given":"Rosa Maria","family":"Gaudio","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine, LTTA Center, University of Ferrara, 44121 Ferrara, Italy"},{"name":"University Center for Studies on Gender Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Rubini","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Rehabilitation, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Fondazione IRCCS Policlinico Universitario A. Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"De-Giorgio","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Department of Health Care Surveillance and Bioethics, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione IRCCS Policlinico Universitario A. 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Bmj, 362."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s00204-020-02693-7","article-title":"Designer drugs: Mechanism of action and adverse effects","volume":"94","author":"Luethi","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_3","unstructured":"EMCDDA European Monitoring Centre for Drugs and Drug Addiction (2020). European Drug Report 2020: Trends and Devel-Opments, Publications Office of the European Union."},{"key":"ref_4","unstructured":"United Nations Office on Drugs and Labor (2021). World Drug Report 2020, United Nations."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.bcp.2014.01.024","article-title":"Pharmacological profiles of aminoindanes, piperazines, and pipradrol derivatives","volume":"88","author":"Simmler","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_6","first-page":"458","article-title":"Pharmacological characterization of designer cathinones in vitro Br","volume":"168","author":"Simmler","year":"2013","journal-title":"J. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"109020","DOI":"10.1016\/j.neuropharm.2022.109020","article-title":"In vitro and in vivo pharmaco-dynamic study of the novel fentanyl derivatives: Acrylfentanyl, Ocfentanyl and Furanylfentanyl","volume":"209","author":"Bilel","year":"2022","journal-title":"Neuropharmacology"},{"key":"ref_8","unstructured":"EMCDDA European Monitoring Centre for Drugs and Drug Addiction (2021). European Drug Report 2021: Trends and Devel-Opments, Publications Office of the European Union."},{"key":"ref_9","unstructured":"(2021, November 15). ESPAD Report 2019. Available online: http:\/\/espad.org\/sites\/espad.org\/files\/2020.3878_EN_04.pdf."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1111\/dar.12372","article-title":"Novel psychoactive substance use by US adolescents: Characteristics associated with use of synthetic cannabinoids and synthetic cathinones","volume":"35","author":"Patrick","year":"2015","journal-title":"Drug Alcohol Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1373\/clinchem.2017.275867","article-title":"Human Toxicity Caused by Indole and Indazole Carboxylate Synthetic Cannabinoid Receptor Agonists: From Horizon Scanning to Notification","volume":"64","author":"Hill","year":"2018","journal-title":"Clin. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.forsciint.2016.01.018","article-title":"Suicide attempt with a mix of synthetic cannabinoids and synthetic cathinones: Case report of non-fatal intoxication with AB-CHMINACA, AB-FUBINACA, alpha-PHP, alpha-PVP and 4-CMC","volume":"265","author":"Gorenjak","year":"2016","journal-title":"Forensic Sci. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/jat\/bkx080","article-title":"Toxicokinetics of the Synthetic Cathinone \u03b1-Pyrrolidinohexanophenone","volume":"42","author":"Fujita","year":"2018","journal-title":"J. Anal. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.12688\/f1000research.3-21.v1","article-title":"A case of severe psychosis induced by novel recreational drugs","volume":"3","author":"Dragogna","year":"2014","journal-title":"F1000Research"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.1016\/j.forsciint.2017.10.042","article-title":"Three fatalities associated with the synthetic cannabinoids 5F-ADB, 5F-PB-22, and AB-CHMINACA","volume":"281","author":"Angerer","year":"2017","journal-title":"Forensic Sci. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1177\/0960327114550886","article-title":"Delayed seizure-like activity following analytically confirmed use of previously unreported synthetic cannabinoid analogues","volume":"34","author":"Schep","year":"2015","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.annemergmed.2012.11.021","article-title":"Compartment Syndrome After \u201cBath Salts\u201d Use: A Case Series","volume":"61","author":"Levine","year":"2013","journal-title":"Ann. Emerg. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1080\/15563650.2018.1502443","article-title":"Fetal death associated with the use of 3,4-MDPHP and \u03b1-PHP","volume":"57","author":"Adamowicz","year":"2019","journal-title":"Clin. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1136\/hrt.2010.209338","article-title":"Headshop heartache: Acute mephedrone \u2018meow\u2019 myocarditis","volume":"96","author":"Nicholson","year":"2010","journal-title":"Heart"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1136\/emj.2010.096636","article-title":"Clinical characteristics of mephedrone toxicity reported to the U.K. National Poisons Information Service","volume":"28","author":"James","year":"2011","journal-title":"Emerg. Med. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.drugalcdep.2014.08.005","article-title":"Synthetic cannabinoids: Epidemiology, pharmacodynamics, and clinical implications","volume":"144","author":"Castaneto","year":"2014","journal-title":"Drug Alcohol Depend."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/978-3-319-20825-1_14","article-title":"Endocannabinoids and the Cardiovascular System in Health and Disease","volume":"231","year":"2015","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"79","DOI":"10.4103\/0974-2069.171400","article-title":"Chest pain, troponin rise, and ST-elevation in an adolescent boy following the use of the synthetic cannabis product K2","volume":"9","author":"Kumar","year":"2016","journal-title":"Ann. Pediatr. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1161\/ATVBAHA.108.178129","article-title":"Cannabinoid CB 1 Receptor Antagonists for Atherosclerosis and Cardiometabolic Disorders","volume":"29","author":"Pacher","year":"2009","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/cpt.563","article-title":"Focus on cannabinoids and synthetic cannabinoids","volume":"101","author":"Alexandre","year":"2017","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/nrcardio.2017.130","article-title":"Cardiovascular effects of marijuana and synthetic cannabinoids: The good, the bad, and the ugly","volume":"15","author":"Pacher","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_27","unstructured":"Centers for Disease Control and Prevention (CDC) (2013). Acute kidney injury associated with synthetic cannabinoid use\u2014Multiple states, 2012. MMWR Morb. Mortal. Wkly. Rep., 62, 93\u201398."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/dta.3179","article-title":"In vitro metabolic profile of mexedrone, a mephedrone analog, studied by high- and low-resolution mass spectrometry","volume":"14","author":"Camuto","year":"2022","journal-title":"Drug Test. Anal."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bilel, S., Tirri, M., Arf\u00e8, R., Sturaro, C., Fantinati, A., Cristofori, V., Bernardi, T., Boccuto, F., Cavallo, M., and Cavalli, A. (2021). In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147659"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1007\/s00213-021-05852-5","article-title":"Comparison of N-methyl-2-pyrrolidone (NMP) and the \u201cdate rape\u201d drug GHB: Behavioral toxicology in the mouse model","volume":"238","author":"Bilel","year":"2021","journal-title":"Psychopharmacology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1007\/s00213-021-05813-y","article-title":"Low-normal doses of methiopropamine induce aggressive behaviour in mice","volume":"238","author":"Foti","year":"2021","journal-title":"Psychopharmacology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"879","DOI":"10.3389\/fpsyt.2020.00879","article-title":"Club Drugs: Psychotropic Effects and Psychopathological Characteristics of a Sample of Inpatients","volume":"11","author":"Martinotti","year":"2020","journal-title":"Front. Psychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/dta.2900","article-title":"Urinary excretion profile of methiopropamine in mice following intraperitoneal administration: A liquid chromatography\u2013tandem mass spectrometry investigation","volume":"13","author":"Camuto","year":"2021","journal-title":"Drug Test. Anal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3389\/fpsyt.2020.00275","article-title":"Does DRD2 Taq1A Mediate Aripiprazole-Induced Gambling Disorder? A Pharmacogenetic Hypothesis","volume":"11","author":"Miuli","year":"2020","journal-title":"Front. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"108110","DOI":"10.1016\/j.neuropharm.2020.108110","article-title":"In vitro and in vivo pharmacological characterization of the synthetic opioid MT-45","volume":"171","author":"Bilel","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.neuropharm.2018.08.017","article-title":"Neurological, sensorimotor and cardiorespiratory alterations induced by methoxetamine, ketamine and phencyclidine in mice","volume":"141","author":"Ossato","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"130","DOI":"10.3389\/fpsyt.2017.00130","article-title":"Psychostimulant Effect of the Synthetic Cannabinoid JWH-018 and AKB48: Behavioral, Neurochemical, and Dopamine Transporter Scan Imaging Studies in Mice","volume":"8","author":"Ossato","year":"2017","journal-title":"Front. Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e2560","DOI":"10.1002\/hup.2560","article-title":"1-cyclohexyl-x-methoxybenzene derivatives, novel psychoactive substances seized on the internet market. Synthesis and in vivo pharmacological studies in mice","volume":"32","author":"Fantinati","year":"2017","journal-title":"Hum. Psychopharmacol. Clin. Exp."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Lenzi, M., Cocchi, V., Gasperini, S., Arf\u00e8, R., Marti, M., and Hrelia, P. (2021). Evaluation of Cytotoxic and Mutagenic Effects of the Synthetic Cathinones Mexedrone, \u03b1-PVP and \u03b1-PHP. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126320"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lenzi, M., Cocchi, V., Cavazza, L., Bilel, S., Hrelia, P., and Marti, M. (2020). Genotoxic Properties of Synthetic Cannabinoids on TK6 Human Cells by Flow Cytometry. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031150"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1111\/bcp.14224","article-title":"How preclinical studies have influenced novel psychoactive substance legislation in the UK and Europe","volume":"86","author":"Guirguis","year":"2020","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ejphar.2017.12.012","article-title":"Effects of the new psychoactive substances diclofensine, diphenidine, and methoxphenidine on monoaminergic systems","volume":"819","author":"Luethi","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Belin-Rauscent, A., and Belin, D. (2012). Animal Models of Drug Addiction. Addictions: From Pathophysiology to Treatment, IntechOpen.","DOI":"10.5772\/52079"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.neuro.2012.08.003","article-title":"Effects of synthetic cathinones contained in \u201cbath salts\u201d on motor behavior and a functional observational battery in mice","volume":"33","author":"Marusich","year":"2012","journal-title":"NeuroToxicology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/npp.2012.233","article-title":"In vivo Effects of Abused \u2018Bath Salt\u2019 Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity","volume":"38","author":"Fantegrossi","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.3389\/fnins.2019.01163","article-title":"Pharmacological and Behavioral Effects of the Synthetic Cannabinoid AKB48 in Rats","volume":"13","author":"Bilel","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.neuro.2019.10.002","article-title":"Novel halogenated synthetic cannabinoids impair sensorimotor functions in mice","volume":"76","author":"Bilel","year":"2020","journal-title":"NeuroToxicology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"802","DOI":"10.4103\/1673-5374.268895","article-title":"Neuronal and peripheral damages induced by synthetic psychoactive substances: An update of recent findings from human and animal studies","volume":"15","author":"Simola","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/dta.310","article-title":"Social, policy, and public health perspectives on new psychoactive substances","volume":"3","author":"Sumnall","year":"2011","journal-title":"Drug Test. Anal."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pharmthera.2013.03.001","article-title":"Pharmacogenomics of breast cancer therapy: An update","volume":"139","author":"Westbrook","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1080\/15592294.2019.1640546","article-title":"Epidrugs: Targeting epigenetic marks in cancer treatment","volume":"14","author":"Furtado","year":"2019","journal-title":"Epigenetics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-3-030-24100-1_3","article-title":"Pharmaco-epigenomics: On the Road of Translation Medicine","volume":"1168","author":"Marchat","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ravaei, A., and Rubini, M. (2021). Rescuing effect of folates on methotrexate cytotoxicity in human trophoblast cells. Clin. Exp. Rheumatol.","DOI":"10.55563\/clinexprheumatol\/t1srve"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e1333","DOI":"10.1002\/wsbm.1333","article-title":"Behavioral epigenetics","volume":"9","author":"Moore","year":"2017","journal-title":"WIREs Syst. Biol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.biopsych.2021.08.013","article-title":"Current and Future Perspectives of Noncoding RNAs in Brain Function and Neuropsychiatric Disease","volume":"91","author":"Kyzar","year":"2022","journal-title":"Biol. Psychiatry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3389\/fcell.2014.00049","article-title":"Epigenetics across the human lifespan","volume":"2","author":"Kanherkar","year":"2014","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_57","first-page":"596","article-title":"Epigenetic mechanisms in mammals","volume":"66","author":"Kim","year":"2009","journal-title":"Exp."},{"key":"ref_58","first-page":"4739","article-title":"Epigenome-wide association study reveals differential DNA methylation in individuals with a history of myocardial infarction","volume":"25","author":"Martinsson","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1373\/clinchem.2011.173823","article-title":"Use of Circulating MicroRNAs to Diagnose Acute Myocardial Infarction","volume":"58","author":"Devaux","year":"2012","journal-title":"Clin. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1093\/eurheartj\/ehq221","article-title":"Circulating microRNAs: Novel biomarkers for cardiovascular diseases?","volume":"31","author":"Dimmeler","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1093\/eurheartj\/ehq167","article-title":"Circulating microRNAs are new and sensitive biomarkers of myocardial infarction","volume":"31","author":"Devanna","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/17474124.2017.1374853","article-title":"Pharmacoepigenetics and pharmacoepigenomics of gastrointestinal cancers","volume":"12","author":"Lopomo","year":"2018","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.2217\/14622416.9.12.1903","article-title":"Pharmacoepigenomics in colorectal cancer: A step forward in predicting prognosis and treatment response","volume":"9","author":"Smits","year":"2008","journal-title":"Pharmacogenomics"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Tirri, M., Frisoni, P., Bilel, S., Arf\u00e8, R., Trapella, C., Fantinati, A., Corli, G., Marchetti, B., De-Giorgio, F., and Camuto, C. (2021). Worsening of the Toxic Effects of (\u00b1) Cis-4,4\u2032-DMAR Following Its Co-Administration with (\u00b1) Trans-4,4\u2032-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168771"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Schiavone, S., Neri, M., Maffione, A.B., Frisoni, P., Morgese, M.G., Trabace, L., and Turillazzi, E. (2019). Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051242"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"113778","DOI":"10.1016\/j.expneurol.2021.113778","article-title":"Molecular and clinical aspects of potential neurotoxicity induced by new psychoactive stimulants and psychedelics","volume":"343","author":"Rudin","year":"2021","journal-title":"Exp. Neurol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1007\/s00204-012-0815-5","article-title":"Toxicity of amphetamines: An update","volume":"86","author":"Carvalho","year":"2012","journal-title":"Arch. Toxicol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1126\/science.293.5532.1103","article-title":"Genes, Genetics, and Epigenetics: A Correspondence","volume":"293","author":"Wu","year":"2001","journal-title":"Science"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1055\/s-0029-1237423","article-title":"Epigenetics: Definition, Mechanisms and Clinical Perspective","volume":"27","author":"Dupont","year":"2009","journal-title":"Semin. Reprod. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"76","DOI":"10.4161\/epi.1.2.2762","article-title":"Epigenetics: A Historical Overview","volume":"1","author":"Holliday","year":"2006","journal-title":"Epigenetics"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"20200111","DOI":"10.1098\/rstb.2020.0111","article-title":"How does epigenetics influence the course of evolution?","volume":"376","author":"Ashe","year":"2021","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_72","unstructured":"Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. (2002). Chromosomal DNA and Its Packaging in the Chromatin Fiber. Molecular Biology of the Cell, Garland Science. [4th ed.]."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.conb.2014.11.002","article-title":"Regulation of chromatin states by drugs of abuse","volume":"30","author":"Walker","year":"2015","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_74","unstructured":"Romani, M. (2021). Epigenetica, Zanichelli Publisher. [1st ed.]."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ceb.2016.02.014","article-title":"How to rule the nucleus: Divide et impera","volume":"40","author":"Solovei","year":"2016","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/nyas.14303","article-title":"Establishment and evolution of heterochromatin","volume":"1476","author":"Liu","year":"2020","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/nature01411","article-title":"Controlling the double helix","volume":"421","author":"Felsenfeld","year":"2003","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/cr.2011.22","article-title":"Regulation of chromatin by histone modifications","volume":"21","author":"Bannister","year":"2011","journal-title":"Cell Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e324","DOI":"10.1038\/emm.2017.11","article-title":"Writing, erasing and reading histone lysine methylations","volume":"49","author":"Hyun","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrg3673","article-title":"Every amino acid matters: Essential contributions of histone variants to mammalian development and disease","volume":"15","author":"Maze","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"21","DOI":"10.21767\/2472-1158.100055","article-title":"Recent Advancement in Methodology for Understanding Epigenetic Modifications","volume":"3","author":"Tiwari","year":"2017","journal-title":"J. Clin. Epigenetics"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"a019133","DOI":"10.1101\/cshperspect.a019133","article-title":"DNA Methylation in Mammals","volume":"6","author":"Li","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_83","first-page":"506","article-title":"How epigenomics brings phenotype into being","volume":"9","year":"2011","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1089\/ars.2012.4923","article-title":"Deciphering the Epigenetic Code: An Overview of DNA Methylation Analysis Methods","volume":"18","author":"Umer","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1101\/gad.947102","article-title":"DNA methylation patterns and epigenetic memory. An excellent review of mammalian DNA methylation","volume":"16","author":"Bird","year":"2002","journal-title":"Genes Dev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nrg816","article-title":"The fundamental role of epigenetic events in cancer","volume":"3","author":"Jones","year":"2002","journal-title":"Nat. Rev. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1042\/bj0480581","article-title":"Recognition and estimation of 5-methylcytosine in nucleic acids","volume":"48","author":"Wyatt","year":"1951","journal-title":"Biochem. J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3740","DOI":"10.1073\/pnas.052410099","article-title":"Comprehensive analysis of CpG islands in human chromosomes 21 and 22","volume":"99","author":"Takai","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.chembiol.2015.11.007","article-title":"Nucleic Acid Modifications in Regulation of Gene Expression","volume":"23","author":"Chen","year":"2016","journal-title":"Cell Chem. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/366362a0","article-title":"Role for DNA methylation in genomic imprinting","volume":"366","author":"Li","year":"1993","journal-title":"Nature"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1128\/MCB.22.9.3157-3173.2002","article-title":"Molecular Mechanisms of Gene Silencing Mediated by DNA Methylation","volume":"22","author":"Curradi","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_92","unstructured":"Kundu, T.K. (2013). The Role of DNA Methylation and Histone Modifications in Transcriptional Regulation in Humans. Epigenetics: Development and Disease, Springer."},{"key":"ref_93","first-page":"74","article-title":"DNA Methylation: A Timeline of Methods and Applications","volume":"2","author":"Eharrison","year":"2011","journal-title":"Front. Genet."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/978-1-4939-1804-1_34","article-title":"Global DNA Methylation Profiling Technologies and the Ovarian","volume":"1238","author":"Tang","year":"2015","journal-title":"Cancer Epigenetics"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/wsbm.35","article-title":"Genome-wide DNA methylation profiling","volume":"2","author":"Bibikova","year":"2010","journal-title":"WIREs Syst. Biol. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"R17","DOI":"10.1093\/hmg\/ddl046","article-title":"Non-coding RNA","volume":"15","author":"Mattick","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/nrg1321","article-title":"RNA regulation: A new genetics?","volume":"5","author":"Mattick","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"R121","DOI":"10.1093\/hmg\/ddi101","article-title":"Small regulatory RNAs in mammals","volume":"14","author":"Mattick","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.gpb.2016.03.007","article-title":"Long Non-coding RNAs and Their Roles in Non-small-cell Lung Cancer","volume":"14","author":"Wei","year":"2016","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.gpb.2017.04.002","article-title":"Primate-specific Long Non-coding RNAs and MicroRNAs","volume":"15","author":"Awan","year":"2017","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1016\/j.cell.2013.02.016","article-title":"X-Inactivation, Imprinting, and Long Noncoding RNAs in Health and Disease","volume":"152","author":"Lee","year":"2013","journal-title":"Cell"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.bbagrm.2015.05.006","article-title":"Long noncoding RNAs: Lessons from genomic imprinting","volume":"1859","author":"Kanduri","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA) Bioenerg. Mech."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3390\/biom4010076","article-title":"Long Noncoding RNAs in Imprinting and X Chromosome Inactivation","volume":"4","author":"Autuoro","year":"2014","journal-title":"Biomolecules"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/ncb2140","article-title":"Direct visualization of the co-transcriptional assembly of a nuclear body by noncoding RNAs","volume":"13","author":"Mao","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3892\/or.2016.5236","article-title":"Non-coding RNAs as regulators in epigenetics (Review)","volume":"37","author":"Wei","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/jbt.20325","article-title":"Small noncoding RNAs: Biogenesis, function, and emerging significance in toxicology","volume":"24","author":"Choudhuri","year":"2010","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1007\/s12094-020-02371-1","article-title":"The new function of circRNA: Translation","volume":"22","author":"Shi","year":"2020","journal-title":"Clin. Transl. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"5451","DOI":"10.1002\/jcp.27486","article-title":"An overview of microRNAs: Biology, functions, therapeutics, and analysis methods","volume":"234","author":"Saliminejad","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1146\/annurev.neuro.29.051605.113009","article-title":"Neural mechanisms of addiction: The Role of Reward-Related Learning and Memory","volume":"29","author":"Hyman","year":"2006","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.neuroscience.2013.07.064","article-title":"Mechanisms of transgenerational inheritance of addictive-like behaviors","volume":"264","author":"Vassoler","year":"2014","journal-title":"Neuroscience"},{"key":"ref_111","first-page":"4","article-title":"Addiction and cognition","volume":"5","author":"Gould","year":"2010","journal-title":"Addict. Sci. Clin. Pract."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/bjp.2008.51","article-title":"The neurocircuitry of addiction: An overview","volume":"154","author":"Feltenstein","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1176\/appi.ajp.162.8.1403","article-title":"The Neural Basis of Addiction: A Pathology of Motivation and Choice","volume":"162","author":"Kalivas","year":"2005","journal-title":"Am. J. Psychiatry"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.biopsych.2013.09.034","article-title":"Methamphetamine Downregulates Striatal Glutamate Receptors via Diverse Epigenetic Mechanisms","volume":"76","author":"Jayanthi","year":"2014","journal-title":"Biol. Psychiatry"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Heinbockel, T., and Csoka, A.B. (2018). Epigenetic Effects of Drugs of Abuse. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15102098"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/nrn2763","article-title":"microRNAs at the synapse","volume":"10","author":"Schratt","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/gm213","article-title":"New insights into the roles of microRNAs in drug addiction and neuroplasticity","volume":"2","author":"Dreyer","year":"2010","journal-title":"Genome Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"19186","DOI":"10.1073\/pnas.0509735102","article-title":"CREB-binding protein controls response to cocaine by acetylating histones at the fosB promoter in the mouse striatum","volume":"102","author":"Levine","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.neuron.2005.09.023","article-title":"Chromatin Remodeling Is a Key Mechanism Underlying Cocaine-Induced Plasticity in Striatum","volume":"48","author":"Kumar","year":"2005","journal-title":"Neuron"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.brainres.2015.10.021","article-title":"Chronic methamphetamine treatment reduces the expression of synaptic plasticity genes and changes their DNA methylation status in the mouse brain","volume":"1629","author":"Cheng","year":"2015","journal-title":"Brain Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.neuroscience.2008.09.019","article-title":"Additive effects of histone deacetylase inhibitors and amphetamine on histone H4 acetylation, cAMP responsive element binding protein phosphorylation and Delta FosB expression in the striatum and locomotor sensitization in mice","volume":"157","author":"Shen","year":"2008","journal-title":"Neuroscience"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1126\/science.1149460","article-title":"Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation","volume":"318","author":"Vasudevan","year":"2007","journal-title":"Science"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.neuron.2009.05.029","article-title":"Characterization of Small RNAs in Aplysia Reveals a Role for miR-124 in Constraining Synaptic Plasticity through CREB","volume":"63","author":"Rajasethupathy","year":"2009","journal-title":"Neuron"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nrn2132","article-title":"Epigenetic regulation in psychiatric disorders","volume":"8","author":"Tsankova","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nrn3111","article-title":"Transcriptional and epigenetic mechanisms of addiction","volume":"12","author":"Robison","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1038\/nn.2619","article-title":"Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens","volume":"13","author":"LaPlant","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/bs.irn.2015.02.010","article-title":"Epigenetic Mechanisms of Psychostimulant-Induced Addiction","volume":"120","author":"Kalda","year":"2015","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"15460","DOI":"10.1074\/jbc.M116.719179","article-title":"RNA-seq Analysis of \u03b49-Tetrahydrocannabinol-treated T Cells Reveals Altered Gene Expression Profiles That Regulate Immune Response and Cell Proliferation","volume":"291","author":"Yang","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/nn.3976","article-title":"Role of Tet1 and 5-hydroxymethylcytosine in cocaine action","volume":"18","author":"Feng","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/nrn4004","article-title":"Endocannabinoid signalling in reward and addiction","volume":"16","author":"Parsons","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1146\/annurev-psych-113011-143739","article-title":"The Endocannabinoid System and the Brain","volume":"64","author":"Mechoulam","year":"2013","journal-title":"Annu. Rev. Psychol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/npp.2017.143","article-title":"The Role of the Endocannabinoid System and Genetic Variation in Adolescent Brain Development","volume":"43","author":"Meyer","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1111\/j.1360-0443.2005.01322.x","article-title":"Cannabis use and other illicit drug use: Testing the cannabis gateway hypothesis","volume":"101","author":"Fergusson","year":"2006","journal-title":"Addiction"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"147480","DOI":"10.1016\/j.brainres.2021.147480","article-title":"Cocaine-induced Fos expression in the rat brain: Modulation by prior \u03949-tetrahydrocannabinol exposure during adolescence and sex-specific effects","volume":"1764","author":"Orihuel","year":"2021","journal-title":"Brain Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1111\/adb.12446","article-title":"Chronic exposure to cannabinoids during adolescence causes long-lasting behavioral deficits in adult mice","volume":"22","author":"Benito","year":"2017","journal-title":"Addict. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1007\/s00213-021-05926-4","article-title":"Adolescent cannabinoid exposure modulates the vulnerability to cocaine-induced conditioned place preference and DNMT3a expression in the prefrontal cortex in Swiss mice","volume":"238","author":"Gobira","year":"2021","journal-title":"Psychopharmacology"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"9991","DOI":"10.1073\/pnas.1920866117","article-title":"Cannabinoid exposure in rat adolescence reprograms the initial behavioral, molecular, and epigenetic response to cocaine","volume":"117","author":"Scherma","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.biopsych.2012.04.026","article-title":"Proenkephalin Mediates the Enduring Effects of Adolescent Cannabis Exposure Associated with Adult Opiate Vulnerability","volume":"72","author":"Tomasiewicz","year":"2012","journal-title":"Biol. Psychiatry"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"e1637","DOI":"10.1002\/wrna.1637","article-title":"Role of microRNAs in the pathophysiology of addiction","volume":"12","author":"Gowen","year":"2021","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1038\/npp.2010.128","article-title":"DNA Methylation Regulates Cocaine-Induced Behavioral Sensitization in Mice","volume":"35","author":"Anier","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.nbd.2010.02.014","article-title":"CDKL5 is a brain MeCP2 target gene regulated by DNA methylation","volume":"38","author":"Carouge","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.neuron.2007.09.032","article-title":"Histone Deacetylase 5 Epigenetically Controls Behavioral Adaptations to Chronic Emotional Stimuli","volume":"56","author":"Renthal","year":"2007","journal-title":"Neuron"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.neuron.2009.03.026","article-title":"Genome-wide Analysis of Chromatin Regulation by Cocaine Reveals a Role for Sirtuins","volume":"62","author":"Renthal","year":"2009","journal-title":"Neuron"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1093\/toxsci\/kfv170","article-title":"Ecstasy (MDMA) Alters Cardiac Gene Expression and DNA Methylation: Implications for Circadian Rhythm Dysfunction in the Heart","volume":"148","author":"Koczor","year":"2015","journal-title":"Toxicol. Sci."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Tian, W., Zhao, M., Li, M., Song, T., Zhang, M., Quan, L., Li, S., and Sun, Z. (2012). Reversal of Cocaine-Conditioned Place Preference through Methyl Supplementation in Mice: Altering Global DNA Methylation in the Prefrontal Cortex. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033435"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1017\/S1461145713000394","article-title":"S-adenosylmethionine modifies cocaine-induced DNA methylation and increases locomotor sensitization in mice","volume":"16","author":"Anier","year":"2013","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1124\/mol.106.032011","article-title":"Maternal Cocaine Administration Causes an Epigenetic Modification of Protein Kinase C\u03f5 Gene Expression in Fetal Rat Heart","volume":"71","author":"Zhang","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Prini, P., Penna, F., Sciuccati, E., Alberio, T., and Rubino, T. (2017). Chronic \u03949-THC Exposure Differently Affects Histone Modifications in the Adolescent and Adult Rat Brain. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102094"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1080\/15592294.2018.1554521","article-title":"Cannabinoid exposure and altered DNA methylation in rat and human sperm","volume":"13","author":"Murphy","year":"2018","journal-title":"Epigenetics"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1096\/fj.15-279034","article-title":"Type 2 cannabinoid receptor contributes to the physiological regulation of spermatogenesis","volume":"30","author":"Sette","year":"2016","journal-title":"FASEB J."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.biopsych.2011.06.027","article-title":"Maternal Cannabis Use Alters Ventral Striatal Dopamine D2 Gene Regulation in the Offspring","volume":"70","author":"DiNieri","year":"2011","journal-title":"Biol. Psychiatry"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1038\/npp.2015.155","article-title":"Genome-Wide DNA Methylation Profiling Reveals Epigenetic Changes in the Rat Nucleus Accumbens Associated With Cross-Generational Effects of Adolescent THC Exposure","volume":"40","author":"Watson","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1503\/jpn.170082","article-title":"Adolescent THC exposure in female rats leads to cognitive deficits through a mechanism involving chromatin modifications in the prefrontal cortex","volume":"43","author":"Prini","year":"2018","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e452","DOI":"10.1038\/tp.2014.99","article-title":"Alteration of imprinted Dlk1-Dio3 miRNA cluster expression in the entorhinal cortex induced by maternal immune activation and adolescent cannabinoid exposure","volume":"4","author":"Hollins","year":"2014","journal-title":"Transl. Psychiatry"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"573","DOI":"10.18632\/aging.101414","article-title":"An epigenetic biomarker of aging for lifespan and healthspan","volume":"10","author":"Levine","year":"2018","journal-title":"Aging"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.fsigen.2017.02.009","article-title":"DNA methylation-based forensic age prediction using artificial neural networks and next generation sequencing","volume":"28","author":"Vidaki","year":"2017","journal-title":"Forensic Sci. Int. Genet."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.molcel.2018.08.008","article-title":"DNA Methylation Clocks in Aging: Categories, Causes, and Consequences","volume":"71","author":"Field","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Bocklandt, S., Lin, W., Sehl, M.E., S\u00e1nchez, F.J., Sinsheimer, J.S., Horvath, S., and Vilain, E. (2011). Epigenetic Predictor of Age. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0014821"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-3-030-25650-0_10","article-title":"Epigenetic Clock: Just a Convenient Marker or an Active Driver of Aging?","volume":"1178","author":"Ashapkin","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1186\/s13059-016-1053-6","article-title":"Age-related accrual of methylomic variability is linked to fundamental ageing mechanisms","volume":"17","author":"Slieker","year":"2016","journal-title":"Genome Biol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1186\/s13059-019-1824-y","article-title":"DNA methylation aging clocks: Challenges and recommendations","volume":"20","author":"Bell","year":"2019","journal-title":"Genome Biol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/s41576-018-0004-3","article-title":"DNA methylation-based biomarkers and the epigenetic clock theory of ageing","volume":"19","author":"Horvath","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.18632\/aging.100861","article-title":"Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring","volume":"7","author":"Horvath","year":"2015","journal-title":"Aging"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.neuro.2005.05.006","article-title":"Age-dependent (+)MDMA-mediated Neurotoxicity in Mice","volume":"26","author":"Reveron","year":"2005","journal-title":"Neurotoxicology"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/jnc.13377","article-title":"Influence of caffeine on 3,4-methylenedioxymethamphetamine-induced dopaminergic neuron degeneration and neuroinflammation is age-dependent","volume":"136","author":"Frau","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1007\/s00204-018-2226-8","article-title":"Aged rats are more vulnerable than adolescents to \u201cecstasy\u201d-induced toxicity","volume":"92","author":"Costa","year":"2018","journal-title":"Arch. Toxicol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"24057","DOI":"10.18632\/aging.202251","article-title":"Age-related DNA methylation changes are sex-specific: A comprehensive assessment","volume":"12","author":"Yusipov","year":"2020","journal-title":"Aging"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1111\/acel.12681","article-title":"Sexually divergent DNA methylation patterns with hippocampal aging","volume":"16","author":"Masser","year":"2017","journal-title":"Aging Cell"},{"key":"ref_169","unstructured":"(2021, November 05). Life Expectancy at Birth (Years). Available online: https:\/\/www.who.int\/data\/gho\/data\/indicators\/indicator-details\/GHO\/life-expectancy-at-birth-(years)."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13072-018-0191-3","article-title":"Age-related DNA methylation changes are tissue-specific with ELOVL2 promoter methylation as exception","volume":"11","author":"Slieker","year":"2018","journal-title":"Epigenetics Chromatin"},{"key":"ref_171","first-page":"1254","article-title":"Sex-based differences in drug activity","volume":"80","author":"Whitley","year":"2009","journal-title":"Am. Fam. Physician"},{"key":"ref_172","first-page":"40","article-title":"Gender Differences in Pharmacokinetics","volume":"39","author":"Chu","year":"2014","journal-title":"US Pharm."},{"key":"ref_173","first-page":"391","article-title":"The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects","volume":"76","author":"Lynch","year":"2007","journal-title":"Am. Fam. Physician."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.bbrc.2018.03.028","article-title":"Altered metabolism of synthetic cannabinoid JWH-018 by human cytochrome P450 2C9 and variants","volume":"498","author":"Patton","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.lfs.2013.09.017","article-title":"Distinct pharmacology and metabolism of K2 synthetic cannabinoids compared to Delta(9)-THC: Mechanism underlying greater toxicity?","volume":"97","author":"Fantegrossi","year":"2014","journal-title":"Life Sci."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1124\/dmd.112.050880","article-title":"In Vitro Metabolism and Pharmacokinetic Studies on Methylone","volume":"41","author":"Pedersen","year":"2013","journal-title":"Drug Metab. Dispos."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"222","DOI":"10.2165\/00003495-199550020-00003","article-title":"Gender Effects in Pharmacokinetics and Pharmacodynamics","volume":"50","author":"Harris","year":"1995","journal-title":"Drugs"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.drugalcdep.2018.12.006","article-title":"Cardiovascular effects of 3,4-methylenedioxypyrovalerone (MDPV) in male and female Sprague-Dawley rats","volume":"195","author":"McClenahan","year":"2019","journal-title":"Drug Alcohol Depend."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Fattore, L., Marti, M., Mostallino, R., and Castelli, M.P. (2020). Sex and Gender Differences in the Effects of Novel Psychoactive Substances. Brain Sci., 10.","DOI":"10.3390\/brainsci10090606"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1113\/jphysiol.2005.082701","article-title":"Prenatal cocaine exposure increases heart susceptibility to ischaemia\u2013reperfusion injury in adult male but not female rats","volume":"565","author":"Bae","year":"2005","journal-title":"J. Physiol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.reprotox.2011.10.012","article-title":"Cocaine and its metabolites in the placenta: A systematic review of the literature","volume":"33","author":"Marchetti","year":"2012","journal-title":"Reprod. Toxicol."},{"key":"ref_182","first-page":"900","article-title":"Prenatal cocaine exposure increases apoptosis of neonatal rat heart and heart susceptibility to ischemia-reperfusion injury in 1-month-old rat","volume":"144","author":"Bae","year":"2005","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"H1566","DOI":"10.1152\/ajpheart.00898.2008","article-title":"Prenatal cocaine exposure abolished ischemic preconditioning-induced protection in adult male rat hearts: Role of PKC\u03b5","volume":"296","author":"Meyer","year":"2009","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/syn.20134","article-title":"Neuropathology of the cerebral cortex observed in a range of animal models of prenatal cocaine exposure may reflect alterations in genes involved in the Wnt and cadherin systems","volume":"56","author":"Novikova","year":"2005","journal-title":"Synapse"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1097\/OGX.0000000000000685","article-title":"Marijuana Use in Pregnancy: A Review","volume":"74","author":"Thompson","year":"2019","journal-title":"Obstet. Gynecol. Surv."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"633","DOI":"10.3109\/10408444.2010.493552","article-title":"Alcohol, drugs, caffeine, tobacco, and environmental contaminant exposure: Reproductive health consequences and clinical implications","volume":"40","author":"Sadeu","year":"2010","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_187","first-page":"3476","article-title":"Repeated exposure to JWH-018 induces adaptive changes in the mesolimbic and mesocortical dopaminergic pathways, glial cells alterations, and behavioural correlates","volume":"178","author":"Pintori","year":"2021","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"838","DOI":"10.4161\/epi.6.7.16537","article-title":"Environmental epigenetic transgenerational inheritance and somatic epigenetic mitotic stability","volume":"6","author":"Skinner","year":"2011","journal-title":"Epigenetics"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.reprotox.2007.09.001","article-title":"What is an epigenetic transgenerational phenotype? F3 or F2","volume":"25","author":"Skinner","year":"2008","journal-title":"Reprod. Toxicol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"dvy016","DOI":"10.1093\/eep\/dvy016","article-title":"Environmentally induced epigenetic transgenerational inheritance of disease","volume":"4","author":"Nilsson","year":"2018","journal-title":"Environ. Epigenetics"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/978-1-4939-8766-5_14","article-title":"Experimental Analysis of Imprinted Mouse X-Chromosome Inactivation","volume":"1861","author":"Cloutier","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/em.22288","article-title":"Pregnancy drugs, fetal germline epigenome, and risks for next-generation pathology: A call to action","volume":"60","author":"Escher","year":"2019","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13148-020-00993-4","article-title":"Developmental cannabidiol exposure increases anxiety and modifies genome-wide brain DNA methylation in adult female mice","volume":"13","author":"Wanner","year":"2021","journal-title":"Clin. Epigenetics"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ntt.2011.10.006","article-title":"Prenatal tetrahydrocannabinol (THC) alters cognitive function and amphetamine response from weaning to adulthood in the rat","volume":"34","author":"Silva","year":"2012","journal-title":"Neurotoxicology Teratol."},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Delgado-Morales, R. (2017). Drug Addiction and DNA Modifications. Neuroepigenomics in Aging and Disease, Springer International Publishing.","DOI":"10.1007\/978-3-319-53889-1"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"e12824","DOI":"10.1111\/adb.12824","article-title":"Synthetic cannabinoids and their impact on neurodevelopmental processes","volume":"25","author":"Alexandre","year":"2020","journal-title":"Addict. Biol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.tins.2019.08.010","article-title":"Consequences of Perinatal Cannabis Exposure","volume":"42","author":"Scheyer","year":"2019","journal-title":"Trends Neurosci."},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Alexandre, J., Malheiro, R., Da Silva, D.D., Carmo, H., Carvalho, F., and Silva, J.P. (2020). The Synthetic Cannabinoids THJ-2201 and 5F-PB22 Enhance In Vitro CB1 Receptor-Mediated Neuronal Differentiation at Biologically Relevant Concentrations. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176277"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1007\/s00414-019-02092-3","article-title":"Acute and repeated administration of MDPV increases aggressive behavior in mice: Forensic implications","volume":"133","author":"Bilel","year":"2019","journal-title":"Int. J. Legal. Med."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1016\/S0140-6736(19)32231-7","article-title":"New psychoactive substances: Challenges for drug surveillance, control, and public health responses","volume":"394","author":"Peacock","year":"2019","journal-title":"Lancet"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s00414-018-1891-8","article-title":"Phenotypic effects of chronic and acute use of methiopropamine in a mouse model","volume":"133","author":"Foti","year":"2019","journal-title":"Int. J. Legal Med."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/bcp.14115","article-title":"Clinical value of analytical testing in patients presenting with new psychoactive substances intoxication","volume":"86","author":"Grafinger","year":"2020","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1007\/s00414-020-02302-3","article-title":"Methiopropamine and its acute behavioral effects in mice: Is there a gray zone in new psychoactive substances users?","volume":"134","author":"Bilel","year":"2020","journal-title":"Int. J. Legal Med."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"109125","DOI":"10.1016\/j.drugalcdep.2021.109125","article-title":"Ethanol enhanced MDPV- and cocaine-induced aggressive behavior in mice: Forensic implications","volume":"229","author":"Bergamin","year":"2021","journal-title":"Drug Alcohol Depend."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1186\/s13059-017-1373-1","article-title":"From forensic epigenetics to forensic epigenomics: Broadening DNA investigative intelligence","volume":"18","author":"Vidaki","year":"2017","journal-title":"Genome Biol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1159\/000499496","article-title":"Forensic Epigenetic Analysis: The Path Ahead","volume":"28","author":"Sabeeha","year":"2019","journal-title":"Med. Princ. Pract."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.fsigen.2016.06.007","article-title":"DNA methylation profiling for a confirmatory test for blood, saliva, semen, vaginal fluid and menstrual blood","volume":"24","author":"Lee","year":"2016","journal-title":"Forensic Sci. Int. Genet."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2152\/jmi.62.19","article-title":"Epigenetic regulation of mammalian sex determination","volume":"62","author":"Tachibana","year":"2015","journal-title":"J. Med. Investig."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"R115","DOI":"10.1186\/gb-2013-14-10-r115","article-title":"DNA methylation age of human tissues and cell types","volume":"14","author":"Horvath","year":"2013","journal-title":"Genome Biol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"10604","DOI":"10.1073\/pnas.0500398102","article-title":"From The Cover: Epigenetic differences arise during the lifetime of monozygotic twins","volume":"102","author":"Fraga","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/mp.2016.192","article-title":"A DNA methylation biomarker of alcohol consumption","volume":"23","author":"Liu","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"132","DOI":"10.3389\/fgene.2013.00132","article-title":"Cigarette smoking and DNA methylation","volume":"4","author":"Lee","year":"2013","journal-title":"Front. Genet."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1093\/ilar.53.3-4.370","article-title":"Animal Models in Epigenetic Research: Institutional Animal Care and Use Committee Considerations across the Lifespan","volume":"53","author":"Harris","year":"2012","journal-title":"ILAR J."},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"Phillips, N.L.H., and Roth, T.L. (2019). Animal Models and Their Contribution to Our Understanding of the Relationship Between Environments, Epigenetic Modifications, and Behavior. Genes, 10.","DOI":"10.3390\/genes10010047"}],"container-title":["Biomedicines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9059\/10\/6\/1398\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:30:28Z","timestamp":1760139028000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9059\/10\/6\/1398"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,13]]},"references-count":214,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["biomedicines10061398"],"URL":"https:\/\/doi.org\/10.3390\/biomedicines10061398","relation":{},"ISSN":["2227-9059"],"issn-type":[{"value":"2227-9059","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,13]]}}}