{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T17:10:31Z","timestamp":1778605831634,"version":"3.51.4"},"reference-count":168,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Erasmus+ Programme of the European Union","award":["2020-1-CZ01-KA203-078218"],"award-info":[{"award-number":["2020-1-CZ01-KA203-078218"]}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDP\/04378\/2021"],"award-info":[{"award-number":["UIDP\/04378\/2021"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04378\/2021"],"award-info":[{"award-number":["UIDB\/04378\/2021"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["LA\/P\/0140\/2021"],"award-info":[{"award-number":["LA\/P\/0140\/2021"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["2020.04493.BD"],"award-info":[{"award-number":["2020.04493.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["2021.04999.BD"],"award-info":[{"award-number":["2021.04999.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology","doi-asserted-by":"publisher","award":["EUVEN CA19144"],"award-info":[{"award-number":["EUVEN CA19144"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Cocaine is one of the most consumed stimulants throughout the world, as official sources report. It is a naturally occurring sympathomimetic tropane alkaloid derived from the leaves of Erythroxylon coca, which has been used by South American locals for millennia. Cocaine can usually be found in two forms, cocaine hydrochloride, a white powder, or \u2018crack\u2019 cocaine, the free base. While the first is commonly administered by insufflation (\u2018snorting\u2019) or intravenously, the second is adapted for inhalation (smoking). Cocaine can exert local anaesthetic action by inhibiting voltage-gated sodium channels, thus halting electrical impulse propagation; cocaine also impacts neurotransmission by hindering monoamine reuptake, particularly dopamine, from the synaptic cleft. The excess of available dopamine for postsynaptic activation mediates the pleasurable effects reported by users and contributes to the addictive potential and toxic effects of the drug. Cocaine is metabolised (mostly hepatically) into two main metabolites, ecgonine methyl ester and benzoylecgonine. Other metabolites include, for example, norcocaine and cocaethylene, both displaying pharmacological action, and the last one constituting a biomarker for co-consumption of cocaine with alcohol. This review provides a brief overview of cocaine\u2019s prevalence and patterns of use, its physical-chemical properties and methods for analysis, pharmacokinetics, pharmacodynamics, and multi-level toxicity.<\/jats:p>","DOI":"10.3390\/toxins14040278","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T23:07:16Z","timestamp":1649891236000},"page":"278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":131,"title":["Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern"],"prefix":"10.3390","volume":"14","author":[{"given":"Rita","family":"Roque Bravo","sequence":"first","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Ana Carolina","family":"Faria","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7327-1598","authenticated-orcid":false,"given":"Andreia Machado","family":"Brito-da-Costa","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"TOXRUN\u2014Toxicology Research Unit, University Institute of Health Sciences, IUCS-CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6650-5285","authenticated-orcid":false,"given":"Helena","family":"Carmo","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6076-6900","authenticated-orcid":false,"given":"P\u0159emysl","family":"Mlad\u011bnka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, 500 05 Hradec Kr\u00e1lov\u00e9, Czech Republic"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7331-9157","authenticated-orcid":false,"given":"Diana","family":"Dias da Silva","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"TOXRUN\u2014Toxicology Research Unit, University Institute of Health Sciences, IUCS-CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1382-5119","authenticated-orcid":false,"given":"Fernando","family":"Remi\u00e3o","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"name":"on behalf of The OEMONOM Researchers","sequence":"additional","affiliation":[]}],"member":"1968","published-online":{"date-parts":[[2022,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1021\/acschemneuro.8b00117","article-title":"DARK Classics in Chemical Neuroscience: Cocaine","volume":"9","author":"Drake","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/BF03256574","article-title":"Cocaine cardiotoxicity: A review of the pathophysiology, pathology, and treatment options","volume":"9","author":"Phillips","year":"2009","journal-title":"Am. J. Cardiovasc. Drugs."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"64","DOI":"10.2174\/1874473711205010064","article-title":"Clinical and forensic signs related to cocaine abuse","volume":"5","author":"Carvalho","year":"2012","journal-title":"Curr. Drug. Abuse. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6936","DOI":"10.21037\/apm-21-243","article-title":"Sub-lethal toxicity and elimination of the cocaine metabolite, benzoylecgonine: A narrative review","volume":"10","author":"Wang","year":"2021","journal-title":"Ann. Palliat. Med."},{"key":"ref_5","unstructured":"UNODC (2021). World Drug Report 2021, United Nations."},{"key":"ref_6","unstructured":"EMCDDA (2021). European Drug Report 2021: Trends and Development, European Monitoring Centre for Drugs and Drug Addiction. 1977-9860."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1080\/15563650.2021.1955914","article-title":"Unusual electrocardiographic manifestations of lethal cocaine toxicity","volume":"60","author":"Ali","year":"2021","journal-title":"Clin. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"19795","DOI":"10.1038\/s41598-020-76273-1","article-title":"Cocaine, cardiomyopathy, and heart failure: A systematic review and meta-analysis","volume":"10","author":"Arenas","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"154","DOI":"10.52964\/AMJA.0820","article-title":"Pneumomediastinum, subcutaneous emphysema and pneumorrhachis following cocaine insufflation: A case report","volume":"19","author":"Burns","year":"2020","journal-title":"Acute. Med."},{"key":"ref_10","first-page":"e4405","article-title":"Bilateral Basal Ganglia Infarction After Intranasal Use of Cocaine: A Case Report","volume":"11","author":"Cisneros","year":"2019","journal-title":"Cureus"},{"key":"ref_11","first-page":"4894825","article-title":"Carotid Thrombosis in a Crack Cocaine Smoker Woman","volume":"2020","author":"Cosenza","year":"2020","journal-title":"Case Rep. Vasc. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e239981","DOI":"10.1136\/bcr-2020-239981","article-title":"Rare cause of acute abdomen-cocaine-induced small intestinal perforation with coexisting lower gastrointestinal bleed: An unusual presentation","volume":"14","author":"Deivasigamani","year":"2021","journal-title":"BMJ Case Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.hjc.2017.05.008","article-title":"Case report: Cocaine-induced takotsubo cardiomyopathy","volume":"59","author":"Gill","year":"2018","journal-title":"Hellenic. J. Cardiol."},{"key":"ref_14","first-page":"yty041","article-title":"Sniff of coke breaks the heart: Cocaine-induced coronary vasospasm aggravated by therapeutic hypothermia and vasopressors after aborted sudden cardiac death: A case report","volume":"2","author":"Manninger","year":"2018","journal-title":"Eur. Heart J. Case Rep."},{"key":"ref_15","first-page":"e2576","article-title":"Cocaine Induced Bilateral Posterior Inferior Cerebellar Artery and Hippocampal Infarction","volume":"10","author":"Mullaguri","year":"2018","journal-title":"Cureus"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ortiz-Seller, A., Hernandez-Pons, A., Pascual, E.V., Comin Perez, A., Dolz Gaiton, R., and Albert-Fort, M. (2021). Severe Cocaine-Induced Midline Destructive Lesions (CIMDL) Leading to Orbital Apex Syndrome and Peripheral Ulcerative Keratitis. Ocul. Immunol. Inflamm., 1\u20134.","DOI":"10.1080\/09273948.2021.1906913"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e921565","DOI":"10.12659\/AJCR.921565","article-title":"Cocaine-Induced Renal Artery Dissection as a Cause of Secondary Hypertension: A Rare Presentation","volume":"21","author":"Padilha","year":"2020","journal-title":"Am. J. Case Rep."},{"key":"ref_18","first-page":"e8595","article-title":"Cocaine and Alcohol Co-Ingestion-Induced Severe Rhabdomyolysis With Acute Kidney Injury Culminating in Hemodialysis-Dependent End-Stage Renal Disease: A Case Report and Literature Review","volume":"12","author":"Roy","year":"2020","journal-title":"Cureus"},{"key":"ref_19","first-page":"2324709620924203","article-title":"Reversible Fulminant Hepatitis Secondary to Cocaine in the Setting of beta-Blocker Use","volume":"8","author":"Sharma","year":"2020","journal-title":"J. Investig. Med. High. Impact. Case Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1097\/PAF.0000000000000618","article-title":"Cocaine Consumption and Antineutrophil Cytoplasmic Antibody-associated Glomerulonephritis: A Case Report","volume":"42","author":"Vermeulen","year":"2021","journal-title":"Am. J. Forensic. Med. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4048764","DOI":"10.1155\/2016\/4048764","article-title":"Coca: The History and Medical Significance of an Ancient Andean Tradition","volume":"2016","author":"Biondich","year":"2016","journal-title":"Emerg. Med. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1080\/15332640.2011.573310","article-title":"The use of coca: Prehistory, history, and ethnography","volume":"10","author":"Stolberg","year":"2011","journal-title":"J. Ethn. Subst. Abuse"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/02791072.1979.10472095","article-title":"Botanical perspectives on coca","volume":"11","author":"Plowman","year":"1979","journal-title":"J. Psychedelic. Drugs."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1053\/j.semdp.2008.12.001","article-title":"Cocaine: History, social implications, and toxicity: A review","volume":"26","author":"Goldstein","year":"2009","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1093\/oxfordjournals.aob.a086511","article-title":"Cocaine and Cinnamoylcocaine Content of Erythroxylum Species","volume":"51","author":"Plowman","year":"1983","journal-title":"Ann. Bot"},{"key":"ref_26","unstructured":"National Center for Biotechnology Information (2021, September 13). PubChem Compound Summary for CID 446220, Cocaine, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Cocaine."},{"key":"ref_27","unstructured":"Wexler, P. (2014). Cocaine. Encyclopedia of Toxicology, Academic Press. [3rd ed.]."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/jat\/25.7.621","article-title":"Rapid detection of benzoylecgonine in vitreous humor by enzyme immunoassay","volume":"25","author":"Chronister","year":"2001","journal-title":"J. Anal. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e9784","DOI":"10.1097\/MD.0000000000009784","article-title":"Acute recreational drug toxicity: Comparison of self-reports and results of immunoassay and additional analytical methods in a multicenter European case series","volume":"97","author":"Liakoni","year":"2018","journal-title":"Medicine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1093\/jat\/25.1.62","article-title":"Immunoassay for detection of cocaine\/metabolites in oral fluids","volume":"25","author":"Niedbala","year":"2001","journal-title":"J. Anal. Toxicol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1093\/jat\/27.7.386","article-title":"Urine testing for cocaine abuse: Metabolic and excretion patterns following different routes of administration and methods for detection of false-negative results","volume":"27","author":"Cone","year":"2003","journal-title":"J. Anal. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1097\/00007691-199810000-00019","article-title":"Cocaine metabolism and urinary excretion after different routes of administration","volume":"20","author":"Cone","year":"1998","journal-title":"Ther. Drug. Monit."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1093\/jat\/31.8.462","article-title":"Cocaine and metabolites urinary excretion after controlled smoked administration","volume":"31","author":"Huestis","year":"2007","journal-title":"J. Anal. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1520\/JFS2005118","article-title":"Identification of anhydroecgonine ethyl ester in the urine of a drug overdose victim","volume":"50","author":"Myers","year":"2005","journal-title":"J. Forensic. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/jat\/34.2.57","article-title":"Urinary excretion of ecgonine and five other cocaine metabolites following controlled oral, intravenous, intranasal, and smoked administration of cocaine","volume":"34","author":"Smith","year":"2010","journal-title":"J. Anal. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3320","DOI":"10.1002\/rcm.3738","article-title":"Development and validation of an analytical method for the simultaneous determination of cocaine and its main metabolite, benzoylecgonine, in human hair by gas chromatography\/mass spectrometry","volume":"22","author":"Barroso","year":"2008","journal-title":"Rapid. Commun. Mass. Spectrom."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1177\/096032719701600208","article-title":"Evidence of crack use by anhydroecgonine methylester identification","volume":"16","author":"Kintz","year":"1997","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1002\/dta.2657","article-title":"Detection of cocaine and its metabolites in whole blood and plasma following a single dose, controlled administration of intranasal cocaine","volume":"11","author":"Menzies","year":"2019","journal-title":"Drug. Test. Anal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1093\/jat\/20.5.305","article-title":"Comparison of HPLC and GC-MS for measurement cocaine and metabolites in human urine","volume":"20","author":"Phillips","year":"1996","journal-title":"J. Anal. Toxicol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1002\/dta.2547","article-title":"Optimization and validation of simultaneous analyses of ecgonine, cocaine, and seven metabolites in human urine by gas chromatography-mass spectrometry using a one-step solid-phase extraction","volume":"11","author":"Fernandez","year":"2019","journal-title":"Drug. Test. Anal."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1093\/jalm\/jfaa032","article-title":"Comparison of Oral Fluid and Urine for Detection of Cocaine Abuse Using Liquid Chromatography with Tandem Mass Spectrometry","volume":"5","author":"Melanson","year":"2020","journal-title":"J. Appl. Lab. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.forsciint.2019.03.026","article-title":"Simultaneous determination of cocaine, ecgonine methyl ester, benzoylecgonine, cocaethylene and norcocaine in dried blood spots by ultra-performance liquid chromatography coupled to tandem mass spectrometry","volume":"298","author":"Bastiani","year":"2019","journal-title":"Forensic. Sci. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/S0140-6736(11)61423-2","article-title":"How well do international drug conventions protect public health?","volume":"379","author":"Room","year":"2012","journal-title":"Lancet"},{"key":"ref_44","unstructured":"United States Drug Enforcement Administration (2021, September 17). Drug Scheduling, Available online: https:\/\/www.dea.gov\/drug-information\/drug-scheduling."},{"key":"ref_45","unstructured":"Talking Drugs (2021, September 23). Drug Decriminalization Across the World. Available online: https:\/\/www.talkingdrugs.org\/drug-decriminalisation."},{"key":"ref_46","unstructured":"Misuse of Drugs Act (2021, September 22). Misuse of Drugs Act 1971, Available online: https:\/\/www.legislation.gov.uk\/ukpga\/1971\/38\/section\/5."},{"key":"ref_47","unstructured":"SICAD (2021, September 21). SICAD > Pol\u00edtica Portuguesa. Available online: http:\/\/www.sicad.pt\/PT\/PoliticaPortuguesa\/SitePages\/Home%20Page.aspx."},{"key":"ref_48","unstructured":"Eastwood, N., Fox, E., and Rosmarin, A. (2016). A Quiet Revolution: Drug Decriminalization Across The Globe, Release."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1159\/000079835","article-title":"Cocaine use in Europe-a multi-centre study: Patterns of use in different groups","volume":"10","author":"Prinzleve","year":"2004","journal-title":"Eur Addict. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1111\/j.1360-0443.2006.01497.x","article-title":"Concurrent use and order of use of cocaine and alcohol: Behavioural differences between users of crack cocaine and cocaine powder","volume":"101","author":"Gossop","year":"2006","journal-title":"Addiction"},{"key":"ref_51","unstructured":"SAMHSA (2013). Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits, Substance Abuse and Mental Health Services Administration."},{"key":"ref_52","unstructured":"EMCDDA (2021). Drug-related Deaths and Mortality in Europe: Update from the EMCDDA Expert Network, Publications Office of the European Union."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Cunha-Oliveira, T., Rego, A.C., Carvalho, F., and Oliveira, C.R. (2013). Chapter 17-Medical Toxicology of Drugs of Abuse. Principles of Addiction, Miller, P.M., Ed., Academic Press.","DOI":"10.1016\/B978-0-12-398336-7.00017-6"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5647","DOI":"10.2174\/092986712803988811","article-title":"Data available on the extent of cocaine use and dependence: Biochemistry, pharmacologic effects and global burden of disease of cocaine abusers","volume":"19","author":"Pomara","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1093\/jat\/19.6.459","article-title":"Pharmacokinetics and Pharmacodynamics of Cocaine","volume":"19","author":"Cone","year":"1995","journal-title":"J. Anal. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0378-8741(79)90017-5","article-title":"Cocaine in blood of coca chewers","volume":"1","author":"Homstedt","year":"1979","journal-title":"J. Ethnopharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1097\/00002826-200403000-00010","article-title":"Sublingual cocaine: Novel recurrence of an ancient practice","volume":"27","author":"Clapp","year":"2004","journal-title":"Clin. Neuropharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/0379-0738(95)01860-3","article-title":"Identification and quantitation of alkaloids in coca tea","volume":"77","author":"Jenkins","year":"1996","journal-title":"Forensic. Sci. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1023\/A:1015992502509","article-title":"Protein binding of cocaine in human serum","volume":"5","author":"Edwards","year":"1988","journal-title":"Pharm. Res."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Karch, S.B. (1998). Pharmacokinetics: Drug absorption, distribution, and elimination. Drug Abuse Handbook, CRC Press.","DOI":"10.1201\/9781420048292"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1093\/jat\/30.8.501","article-title":"Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration","volume":"30","author":"Kolbrich","year":"2006","journal-title":"J. Anal. Toxicol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5601","DOI":"10.2174\/092986712803988938","article-title":"Contribution of oxidative metabolism to cocaine-induced liver and kidney damage","volume":"19","author":"Valente","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s002130000568","article-title":"Contribution of the active metabolite, norcocaine, to cocaine\u2019s effects after intravenous and oral administration in rats: Pharmacodynamics","volume":"153","author":"Wang","year":"2001","journal-title":"Psychopharmacology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1093\/jat\/14.4.201","article-title":"Cocaine metabolism in man: Identification of four previously unreported cocaine metabolites in human urine","volume":"14","author":"Zhang","year":"1990","journal-title":"J. Anal. Toxicol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1124\/dmd.31.1.16","article-title":"Cocaethylene metabolism and interaction with cocaine and ethanol: Role of carboxylesterases","volume":"31","author":"Laizure","year":"2003","journal-title":"Drug. Metab. Dispos."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0376-8716(03)00200-X","article-title":"The pharmacology of cocaethylene in humans following cocaine and ethanol administration","volume":"72","author":"Harris","year":"2003","journal-title":"Drug. Alcohol. Depend."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1037\/a0022950","article-title":"Cocaethylene formation following ethanol and cocaine administration by different routes","volume":"19","author":"Herbst","year":"2011","journal-title":"Exp. Clin. Psychopharmacol."},{"key":"ref_68","unstructured":"HIggins, S.T., and Katz, J.L. (1998). Controlled laboratory studies on the effects of cocaine in combination with other commonly abused drugs in humans. Cocaine Abuse: Behavior, Pharmacology and Clinical Applications, Elsevier."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S1570-0232(02)00691-8","article-title":"Chromatographic methods for the determination of markers of chronic and acute alcohol consumption","volume":"781","author":"Musshoff","year":"2002","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.forsciint.2006.11.007","article-title":"Markers of chronic alcohol use in hair: Comparison of ethyl glucuronide and cocaethylene in cocaine users","volume":"172","author":"Politi","year":"2007","journal-title":"Forensic. Sci. Int."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1007\/s12640-017-9813-y","article-title":"Anhydroecgonine Methyl Ester (AEME), a Product of Cocaine Pyrolysis, Impairs Spatial Working Memory and Induces Striatal Oxidative Stress in Rats","volume":"34","author":"Gomes","year":"2018","journal-title":"Neurotox. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1124\/jpet.103.055434","article-title":"Pharmacokinetics and pharmacodynamics of methylecgonidine, a crack cocaine pyrolyzate","volume":"307","author":"Scheidweiler","year":"2003","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/toxsci\/kfs140","article-title":"Neurotoxicity of anhydroecgonine methyl ester, a crack cocaine pyrolysis product","volume":"128","author":"Garcia","year":"2012","journal-title":"Toxicol. Sci."},{"key":"ref_74","first-page":"153","article-title":"Cocaine disposition in humans after intravenous injection, nasal insufflation (snorting), or smoking","volume":"17","author":"Jeffcoat","year":"1989","journal-title":"Drug. Metab. Dispos."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/j.1365-2125.2010.03629.x","article-title":"Role of voltage-gated sodium, potassium and calcium channels in the development of cocaine-associated cardiac arrhythmias","volume":"69","author":"Hancox","year":"2010","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1002\/lary.25836","article-title":"Is cocaine a safe topical agent for use during endoscopic sinus surgery?","volume":"126","author":"Dwyer","year":"2016","journal-title":"Laryngoscope"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.eurpsy.2019.03.003","article-title":"Effects of stimulant drug use on the dopaminergic system: A systematic review and meta-analysis of in vivo neuroimaging studies","volume":"59","author":"Proebstl","year":"2019","journal-title":"Eur. Psychiatry"},{"key":"ref_78","unstructured":"Preedy, V.R. (2017). Chapter 29-Mesolimbic Dopamine Signaling in Cocaine Addiction. The Neuroscience of Cocaine, Academic Press."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"9333","DOI":"10.1073\/pnas.0600905103","article-title":"Abolished cocaine reward in mice with a cocaine-insensitive dopamine transporter","volume":"103","author":"Chen","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","first-page":"685","article-title":"The serotonergic system and its role in cocaine addiction","volume":"57","author":"Filip","year":"2005","journal-title":"Pharmacol. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1097\/01.CCM.0000063258.68159.71","article-title":"Cocaine and the critical care challenge","volume":"31","author":"Shanti","year":"2003","journal-title":"Crit Care Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1177\/1074248416681644","article-title":"beta-Blockers, Cocaine, and the Unopposed alpha-Stimulation Phenomenon","volume":"22","author":"Richards","year":"2017","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5624","DOI":"10.2174\/092986712803988893","article-title":"Side effects of cocaine abuse: Multiorgan toxicity and pathological consequences","volume":"19","author":"Riezzo","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1007\/s12035-014-8636-6","article-title":"Cocaine-induced changes in NMDA receptor signaling","volume":"50","author":"Ortinski","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/syn.21877","article-title":"Cocaine occupancy of sigma1 receptors and dopamine transporters in mice","volume":"70","author":"Lever","year":"2016","journal-title":"Synapse"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.neuropharm.2014.06.012","article-title":"Dopamine reuptake transporter (DAT) \u201cinverse agonism\u201d\u2014A novel hypothesis to explain the enigmatic pharmacology of cocaine","volume":"87","author":"Heal","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.pop.2010.11.004","article-title":"Stimulant abuse: Pharmacology, cocaine, methamphetamine, treatment, attempts at pharmacotherapy","volume":"38","author":"Ciccarone","year":"2011","journal-title":"Prim. Care"},{"key":"ref_88","unstructured":"NIDA (2021). What Are the Short-Term Effects of Cocaine Use?, National Institute on Drug Abuse."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.ccc.2012.07.003","article-title":"Cocaine intoxication","volume":"28","author":"Zimmerman","year":"2012","journal-title":"Crit Care Clin."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3109\/00952998809001555","article-title":"Rapid death during cocaine abuse: A variant of the neuroleptic malignant syndrome?","volume":"14","author":"Kosten","year":"1988","journal-title":"Am. J. Drug Alcohol. Abuse"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1002\/jcph.1918","article-title":"Pharmacology of D.Drugs Used as Stimulants","volume":"61","author":"Docherty","year":"2021","journal-title":"J. Clin. Pharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ajem.2020.12.083","article-title":"Hyperthermia associated with methamphetamine and cocaine use","volume":"42","author":"Marco","year":"2021","journal-title":"Am. J. Emerg. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1093\/ijnp\/pyaa065","article-title":"Risperidone and 5-HT2A Receptor Antagonists Attenuate and Reverse Cocaine-Induced Hyperthermia in Rats","volume":"23","author":"Okada","year":"2020","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"785","DOI":"10.7326\/0003-4819-136-11-200206040-00006","article-title":"Mechanism of cocaine-induced hyperthermia in humans","volume":"136","author":"Crandall","year":"2002","journal-title":"Ann. Intern. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1080\/20009666.2021.1926614","article-title":"Cocaine induced heart failure: Report and literature review","volume":"11","author":"Elkattawy","year":"2021","journal-title":"J. Community Hosp. Intern. Med. Perspect."},{"key":"ref_96","first-page":"e14594","article-title":"Cocaine and Cardiotoxicity: A Literature Review","volume":"13","author":"Pergolizzi","year":"2021","journal-title":"Cureus"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1056\/NEJM200108023450507","article-title":"Cardiovascular complications of cocaine use","volume":"345","author":"Lange","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1161\/CIRCULATIONAHA.107.188950","article-title":"Management of cocaine-associated chest pain and myocardial infarction: A scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology","volume":"117","author":"McCord","year":"2008","journal-title":"Circulation"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.amjcard.2007.04.049","article-title":"Crack whips the heart: A review of the cardiovascular toxicity of cocaine","volume":"100","author":"Afonso","year":"2007","journal-title":"Am. J. Cardiol"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1007\/s00204-018-2227-7","article-title":"Ethanol addictively enhances the in vitro cardiotoxicity of cocaine through oxidative damage, energetic deregulation, and apoptosis","volume":"92","author":"Martins","year":"2018","journal-title":"Arch. Toxicol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.jemermed.2006.05.044","article-title":"An overview of non-cardiac cocaine toxicity","volume":"32","author":"Glauser","year":"2007","journal-title":"J. Emerg Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1177\/0192623308330790","article-title":"Effects of chronic exposure to crack cocaine on the respiratory tract of mice","volume":"37","author":"Herculiani","year":"2009","journal-title":"Toxicol. Pathol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s10140-008-0762-x","article-title":"Cardiovascular complications of cocaine: Imaging findings","volume":"16","author":"Restrepo","year":"2009","journal-title":"Emerg. Radiol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Filho, J., Ogawa, M.Y., de Souza Andrade, T.H., de Andrade Cordeiro Gadelha, S., Fernandes, P., Queiroz, A.L., and Daher, E.F. (2019). Spectrum of acute kidney injury associated with cocaine use: Report of three cases. BMC Nephrol., 20.","DOI":"10.1186\/s12882-019-1279-0"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1093\/ckj\/sfu092","article-title":"Cocaine and kidney injury: A kaleidoscope of pathology","volume":"7","author":"Goel","year":"2014","journal-title":"Clin. Kidney J."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00204-011-0749-3","article-title":"Cocaine-induced kidney toxicity: An in vitro study using primary cultured human proximal tubular epithelial cells","volume":"86","author":"Valente","year":"2012","journal-title":"Arch. Toxicol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/1440-1681.12557","article-title":"Genetic overexpressing of GPx-1 attenuates cocaine-induced renal toxicity via induction of anti-apoptotic factors","volume":"43","author":"Mai","year":"2016","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Kowalczyk-Pachel, D., Iciek, M., Bilska-Wilkosz, A., Gorny, M., Jastrzebska, J., Kaminska, K., Dudzik, P., Filip, M., and Lorenc-Koci, E. (2021). Evaluation of Cysteine Metabolism in the Rat Liver and Kidney Following Intravenous Cocaine Administration and Abstinence. Antioxidants, 10.","DOI":"10.3390\/antiox10010074"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Kowalczyk-Pachel, D., Iciek, M., Wydra, K., Nowak, E., Gorny, M., Filip, M., Wlodek, L., and Lorenc-Koci, E. (2016). Cysteine Metabolism and Oxidative Processes in the Rat Liver and Kidney after Acute and Repeated Cocaine Treatment. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147238"},{"key":"ref_110","first-page":"e10128","article-title":"Cocaine-Induced Headache: A Review of Pathogenesis, Presentation, Diagnosis, and Management","volume":"12","author":"Farooque","year":"2020","journal-title":"Cureus"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.neuint.2018.12.017","article-title":"P53 knockout mice are protected from cocaine-induced kindling behaviors via inhibiting mitochondrial oxidative burdens, mitochondrial dysfunction, and proapoptotic changes","volume":"124","author":"Mai","year":"2019","journal-title":"Neurochem. Int."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.tox.2010.06.009","article-title":"Neurotoxicity of heroin-cocaine combinations in rat cortical neurons","volume":"276","author":"Rego","year":"2010","journal-title":"Toxicology"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1073\/pnas.1524860113","article-title":"Cocaine elicits autophagic cytotoxicity via a nitric oxide-GAPDH signaling cascade","volume":"113","author":"Guha","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1007\/s00204-021-03017-z","article-title":"Anhydroecgonine methyl ester, a cocaine pyrolysis product, contributes to cocaine-induced rat primary hippocampal neuronal death in a synergistic and time-dependent manner","volume":"95","author":"Udo","year":"2021","journal-title":"Arch. Toxicol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/s41398-021-01573-7","article-title":"Ca(2+) channel blockade reduces cocaine\u2019s vasoconstriction and neurotoxicity in the prefrontal cortex","volume":"11","author":"Du","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_116","first-page":"279","article-title":"Cocaine promotes oxidative stress and microglial-macrophage activation in rat cerebellum","volume":"9","author":"Muriach","year":"2015","journal-title":"Front. Cell Neurosci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"111232","DOI":"10.1016\/j.pscychresns.2020.111232","article-title":"Cortical thickness and subcortical volume abnormalities in male crack-cocaine users","volume":"310","author":"Bittencourt","year":"2021","journal-title":"Psychiatry Res. Neuroimaging"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.neulet.2017.02.073","article-title":"Accumbens volumes are reduced among crack-cocaine users","volume":"645","author":"Goi","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/0041-008X(78)90167-9","article-title":"Cocaine-induced hepatotoxicity in mice","volume":"45","author":"Evans","year":"1978","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1177\/019262339101900103","article-title":"Cocaine hepatotoxicity in mice: Histologic and enzymatic studies","volume":"19","author":"Mehanny","year":"1991","journal-title":"Toxicol. Pathol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/0016-5085(87)90331-3","article-title":"Cocaine-induced hepatotoxicity in humans","volume":"93","author":"Perino","year":"1987","journal-title":"Gastroenterology"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"5677","DOI":"10.2174\/092986712803988929","article-title":"Cocaine toxicity and hepatic oxidative stress","volume":"19","author":"Vitcheva","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_123","first-page":"494","article-title":"Metabolomics of cocaine: Implications in toxicity","volume":"25","year":"2015","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1002\/jat.3666","article-title":"Protective potential of glutathione peroxidase-1 gene against cocaine-induced acute hepatotoxic consequences in mice","volume":"38","author":"Mai","year":"2018","journal-title":"J. Appl. Toxicol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.biochi.2018.12.009","article-title":"Genetic depletion of p53 attenuates cocaine-induced hepatotoxicity in mice","volume":"158","author":"Mai","year":"2019","journal-title":"Biochimie"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/S0006-2952(00)00355-5","article-title":"Effects of cocaine and its oxidative metabolites on mitochondrial respiration and generation of reactive oxygen species","volume":"60","author":"Boess","year":"2000","journal-title":"Biochem. Pharmacol."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Krokos, A., Deda, O., Virgiliou, C., Gika, H., Raikos, N., Aggelidou, E., Kritis, A., and Theodoridis, G. (2021). Evaluation of Cocaine Effect on Endogenous Metabolites of HepG2 Cells Using Targeted Metabolomics. Molecules, 26.","DOI":"10.3390\/molecules26154610"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1007\/s00216-013-7234-1","article-title":"Metabolic profiling of urine and blood plasma in rat models of drug addiction on the basis of morphine, methamphetamine, and cocaine-induced conditioned place preference","volume":"406","author":"Zaitsu","year":"2014","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_129","unstructured":"NIDA (2021, September 24). Cocaine DrugFacts, Available online: https:\/\/www.drugabuse.gov\/publications\/drugfacts\/cocaine."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). Stimulant-Related Disorders. Diagnostics and Statistical Manual of Mental health Disorders, American Psychiatric Association. [5th ed.].","DOI":"10.1176\/appi.books.9780890425596"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.jpsychires.2020.09.027","article-title":"Melatonin decreases cocaine-induced locomotor sensitization and cocaine-conditioned place preference in rats","volume":"132","year":"2021","journal-title":"J. Psychiatr. Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e13012","DOI":"10.1111\/adb.13012","article-title":"Repeated exposure to cocaine during adolescence enhances the rewarding threshold for cocaine-conditioned place preference in adulthood","volume":"26","author":"Caffino","year":"2021","journal-title":"Addict. Biol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1093\/ijnp\/pyab067","article-title":"Distinct role of dopamine in the PFC and NAc during exposure to cocaine-associated cues","volume":"24","author":"Kawahara","year":"2021","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Zinani, D.B., Wetzel, H.N., and Norman, A.B. (2021). The compulsion zone explains the self-administration of cocaine, RTI-55 and bupropion in rats. Brain Res., 147707.","DOI":"10.1016\/j.brainres.2021.147707"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1073\/pnas.85.14.5274","article-title":"Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats","volume":"85","author":"Imperato","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"6583","DOI":"10.1523\/JNEUROSCI.1544-06.2006","article-title":"Cocaine cues and dopamine in dorsal striatum: Mechanism of craving in cocaine addiction","volume":"26","author":"Volkow","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1038\/mp.2014.58","article-title":"Stimulant-induced dopamine increases are markedly blunted in active cocaine abusers","volume":"19","author":"Volkow","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"eabg5970","DOI":"10.1126\/sciadv.abg5970","article-title":"Disrupting D1-NMDA or D2-NMDA receptor heteromerization prevents cocaine\u2019s rewarding effects but preserves natural reward processing","volume":"7","author":"Andrianarivelo","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1590\/1516-4446-2015-1708","article-title":"Crack-cocaine dependence and aging: Effects on working memory","volume":"38","author":"Francke","year":"2016","journal-title":"Braz J. Psychiatry"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.pbb.2014.04.006","article-title":"Tolerance to cocaine in brain stimulation reward following continuous cocaine infusions","volume":"122","author":"Pudiak","year":"2014","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.3109\/10826080902961179","article-title":"Tolerance and sensitization to the effects of cocaine use in humans: A retrospective study of long-term cocaine users in Philadelphia","volume":"44","author":"Small","year":"2009","journal-title":"Subst. Use Misuse"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1038\/npp.2012.17","article-title":"Cocaine self-administration produces pharmacodynamic tolerance: Differential effects on the potency.y of dopamine transporter blockers, releasers, and methylphenidate","volume":"37","author":"Ferris","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/jnc.12452","article-title":"Extended access of cocaine self-administration results in tolerance to the dopamine-elevating and locomotor-stimulating effects of cocaine","volume":"128","author":"Calipari","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_144","unstructured":"NIDA (2021). What are the Long-Term Effects of Cocaine Use?, National Institute on Drug Abuse."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1080\/08897077.2017.1389799","article-title":"Mortality risk in a sample of emergency department patients who use cocaine with alcohol and\/or cannabis","volume":"39","author":"Gilmore","year":"2018","journal-title":"Subst. Abus."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1046\/j.1360-0443.2003.00236.x","article-title":"Understanding polydrug use: Review of heroin and cocaine co-use","volume":"98","author":"Leri","year":"2003","journal-title":"Addiction"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.drugpo.2017.07.012","article-title":"I love having benzos after my coke shot: The use of psychotropic medication among cocaine users in downtown Montreal","volume":"49","author":"Bertrand","year":"2017","journal-title":"Int. J. Drug. Policy"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Tassoni, G., Cippitelli, M., Mietti, G., Cerioni, A., Buratti, E., Bury, E., and Cingolani, M. (2021). Hair Analysis to Evaluate Polydrug Use. Healthcare, 9.","DOI":"10.3390\/healthcare9080972"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Obembe, S.B. (2012). Common Psychoactive Drugs. Practical Skills and Clinical Management of Alcoholism & Drug Addiction, Elsevier.","DOI":"10.1016\/B978-0-12-398518-7.00002-X"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0041-008X(92)90210-J","article-title":"Effects of ethanol on cocaine metabolism: Formation of cocaethylene and norcocaethylene","volume":"117","author":"Dean","year":"1992","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/0002-8703(92)90412-O","article-title":"Additive myocardial depressant effects of cocaine and ethanol","volume":"124","author":"Uszenski","year":"1992","journal-title":"Am. Heart J."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s12640-015-9536-x","article-title":"A Comprehensive View of the Neurotoxicity Mechanisms of Cocaine and Ethanol","volume":"28","author":"Pereira","year":"2015","journal-title":"Neurotox. Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.ajem.2021.08.057","article-title":"Relationship between cocaine and cocaethylene blood concentration with the severity of clinical manifestations","volume":"50","author":"Zucoloto","year":"2021","journal-title":"Am. J. Emerg. Med."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"147008","DOI":"10.1016\/j.brainres.2020.147008","article-title":"Cocaine added to heroin fails to affect heroin-induced brain hypoxia","volume":"1746","author":"Thomas","year":"2020","journal-title":"Brain Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1097\/01.smj.0000168701.08879.3f","article-title":"Cocaine cardiovascular toxicity","volume":"98","author":"Karch","year":"2005","journal-title":"South. Med. J."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/0091-3057(91)90222-N","article-title":"Cocaethylene is more potent than cocaine in mediating lethality","volume":"39","author":"Hearn","year":"1991","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1056\/NEJM199604113341507","article-title":"Management of Cocaine Abuse and Dependence","volume":"334","author":"Mendelson","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1056\/NEJMe038195","article-title":"Vasopressin in asystolic cardiac arrest","volume":"350","author":"McIntyre","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1056\/NEJMoa025431","article-title":"A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation","volume":"350","author":"Wenzel","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/clc.20746","article-title":"Cocaine and the heart","volume":"33","author":"Maraj","year":"2010","journal-title":"Clin. Cardiol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ccl.2005.09.003","article-title":"Evaluation and management of the patient who has cocaine-associated chest pain","volume":"24","author":"Hollander","year":"2006","journal-title":"Cardiol. Clin."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1097\/00004714-200302000-00010","article-title":"Psychotropic drugs, cardiac arrhythmia, and sudden death","volume":"23","author":"Witchel","year":"2003","journal-title":"J. Clin. Psychopharmacol"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"DiMaio, T.G., and DiMaio, V.J.M. (2005). Excited Delirium Syndrome: Causes of Death and Prevention, CRC Press.","DOI":"10.1201\/9780203483473"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"eaax1532","DOI":"10.1126\/sciadv.aax1532","article-title":"The treatment of cocaine use disorder","volume":"5","author":"Kampman","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1016\/S0140-6736(16)00205-1","article-title":"Sustained-release dexamfetamine in the treatment of chronic cocaine-dependent patients on heroin-assisted treatment: A randomised, double-blind, placebo-controlled trial","volume":"387","author":"Nuijten","year":"2016","journal-title":"Lancet"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.drugalcdep.2013.05.026","article-title":"A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence","volume":"133","author":"Kampman","year":"2013","journal-title":"Drug. Alcohol. Depend."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.drugalcdep.2014.12.005","article-title":"Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter","volume":"147","author":"Reith","year":"2015","journal-title":"Drug. Alcohol. Depend."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"e218049","DOI":"10.1001\/jamanetworkopen.2021.8049","article-title":"Comparison of Treatments for Cocaine Use Disorder Among Adults: A Systematic Review and Meta-analysis","volume":"4","author":"Bentzley","year":"2021","journal-title":"JAMA Netw. Open"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/4\/278\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:53:01Z","timestamp":1760136781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/4\/278"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,13]]},"references-count":168,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["toxins14040278"],"URL":"https:\/\/doi.org\/10.3390\/toxins14040278","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,13]]}}}