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 'crack' cocaine, the free base. While the first is commonly administered by insufflation ('snorting') 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's prevalence and patterns of use, its physical-chemical properties and methods for analysis, pharmacokinetics, pharmacodynamics, and multi-level toxicity.

Associate Laboratory i4HB Institute for Health and Bioeconomy Faculty of Pharmacy University of Porto 4050 313 Porto Portugal

Department of Pharmacology and Toxicology Faculty of Pharmacy Charles University 500 05 Hradec Králové Czech Republic

TOXRUN Toxicology Research Unit University Institute of Health Sciences IUCS CESPU Rua Central de Gandra 1317 4585 116 Gandra PRD Portugal

UCIBIO Applied Molecular Biosciences Unit Laboratory of Toxicology Department of Biological Sciences Faculty of Pharmacy University of Porto 4050 313 Porto Portugal

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Drake L.R., Scott P.J.H. DARK Classics in Chemical Neuroscience: Cocaine. ACS Chem. Neurosci. 2018;9:2358–2372. doi: 10.1021/acschemneuro.8b00117. PubMed DOI PMC

Phillips K., Luk A., Soor G.S., Abraham J.R., Leong S., Butany J. Cocaine cardiotoxicity: A review of the pathophysiology, pathology, and treatment options. Am. J. Cardiovasc. Drugs. 2009;9:177–196. doi: 10.1007/BF03256574. PubMed DOI

Dinis-Oliveira R.J., Carvalho F., Duarte J.A., Proenca J.B., Santos A., Magalhaes T. Clinical and forensic signs related to cocaine abuse. Curr. Drug. Abuse. Rev. 2012;5:64–83. doi: 10.2174/1874473711205010064. PubMed DOI

Wang J., Deng X., Wu Y., Huang Y., Hou S., Zhang Y., Qiu T., Tong J., Chen X. Sub-lethal toxicity and elimination of the cocaine metabolite, benzoylecgonine: A narrative review. Ann. Palliat. Med. 2021;10:6936–6947. doi: 10.21037/apm-21-243. PubMed DOI

UNODC . World Drug Report 2021. United Nations; Vienna, Austria: 2021.

EMCDDA . European Drug Report 2021: Trends and Development. European Monitoring Centre for Drugs and Drug Addiction; Luxembourg: 2021. 1977-9860.

Ali S.F., Hoglund J.R., Gibbs M.A., Littmann L. Unusual electrocardiographic manifestations of lethal cocaine toxicity. Clin. Toxicol. 2021;60:408–409. doi: 10.1080/15563650.2021.1955914. PubMed DOI

Arenas D.J., Beltran S., Zhou S., Goldberg L.R. Cocaine, cardiomyopathy, and heart failure: A systematic review and meta-analysis. Sci. Rep. 2020;10:19795. doi: 10.1038/s41598-020-76273-1. PubMed DOI PMC

Burns J., Roby A., Jaconelli T. Pneumomediastinum, subcutaneous emphysema and pneumorrhachis following cocaine insufflation: A case report. Acute. Med. 2020;19:154–158. doi: 10.52964/AMJA.0820. PubMed DOI

Cisneros O., Garcia de de Jesus K., Then E.O., Rehmani R. Bilateral Basal Ganglia Infarction After Intranasal Use of Cocaine: A Case Report. Cureus. 2019;11:e4405. doi: 10.7759/cureus.4405. PubMed DOI PMC

Cosenza M., Panza L., Califano A.P., Defendini C., D’Andria M., Romiti R., Vainieri A.F.M., Morelli S. Carotid Thrombosis in a Crack Cocaine Smoker Woman. Case Rep. Vasc. Med. 2020;2020:4894825. doi: 10.1155/2020/4894825. PubMed DOI PMC

Deivasigamani S., Irrinki S., Shah J., Sakaray Y. Rare cause of acute abdomen-cocaine-induced small intestinal perforation with coexisting lower gastrointestinal bleed: An unusual presentation. BMJ Case Rep. 2021;14:e239981. doi: 10.1136/bcr-2020-239981. PubMed DOI PMC

Gill D., Sheikh N., Ruiz V.G., Liu K. Case report: Cocaine-induced takotsubo cardiomyopathy. Hellenic. J. Cardiol. 2018;59:129–132. doi: 10.1016/j.hjc.2017.05.008. PubMed DOI

Manninger M., Perl S., Brussee H., G G.T. Sniff of coke breaks the heart: Cocaine-induced coronary vasospasm aggravated by therapeutic hypothermia and vasopressors after aborted sudden cardiac death: A case report. Eur. Heart J. Case Rep. 2018;2:yty041. doi: 10.1093/ehjcr/yty041. PubMed DOI PMC

Mullaguri N., Battineni A., Narayan A., Guddeti R. Cocaine Induced Bilateral Posterior Inferior Cerebellar Artery and Hippocampal Infarction. Cureus. 2018;10:e2576. doi: 10.7759/cureus.2576. PubMed DOI PMC

Ortiz-Seller A., Hernandez-Pons A., Pascual E.V., Comin Perez A., Dolz Gaiton R., Albert-Fort M. Severe Cocaine-Induced Midline Destructive Lesions (CIMDL) Leading to Orbital Apex Syndrome and Peripheral Ulcerative Keratitis. Ocul. Immunol. Inflamm. 2021:1–4. doi: 10.1080/09273948.2021.1906913. PubMed DOI

Padilha W.S.C., Annes M., Massant C.G., Kaup A.O., Affonso B.B., Batista M.C. Cocaine-Induced Renal Artery Dissection as a Cause of Secondary Hypertension: A Rare Presentation. Am. J. Case Rep. 2020;21:e921565. doi: 10.12659/AJCR.921565. PubMed DOI PMC

Roy S., Konala V.M., Adapa S., Naramala S., Bose S. 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. Cureus. 2020;12:e8595. doi: 10.7759/cureus.8595. PubMed DOI PMC

Sharma R., Kapoor N., Chaudhari K.S., Scofield R.H. Reversible Fulminant Hepatitis Secondary to Cocaine in the Setting of beta-Blocker Use. J. Investig. Med. High. Impact. Case Rep. 2020;8:2324709620924203. doi: 10.1177/2324709620924203. PubMed DOI PMC

Vermeulen L., Dirix M., Dendooven A. Cocaine Consumption and Antineutrophil Cytoplasmic Antibody-associated Glomerulonephritis: A Case Report. Am. J. Forensic. Med. Pathol. 2021;42:198–200. doi: 10.1097/PAF.0000000000000618. PubMed DOI

Biondich A.S., Joslin J.D. Coca: The History and Medical Significance of an Ancient Andean Tradition. Emerg. Med. Int. 2016;2016:4048764. doi: 10.1155/2016/4048764. PubMed DOI PMC

Stolberg V.B. The use of coca: Prehistory, history, and ethnography. J. Ethn. Subst. Abuse. 2011;10:126–146. doi: 10.1080/15332640.2011.573310. PubMed DOI

Plowman T. Botanical perspectives on coca. J. Psychedelic. Drugs. 1979;11:103–117. doi: 10.1080/02791072.1979.10472095. PubMed DOI

Goldstein R.A., DesLauriers C., Burda A., Johnson-Arbor K. Cocaine: History, social implications, and toxicity: A review. Semin. Diagn. Pathol. 2009;26:10–17. doi: 10.1053/j.semdp.2008.12.001. PubMed DOI

Plowman T., Rivier L. Cocaine and Cinnamoylcocaine Content of Erythroxylum Species. Ann. Bot. 1983;51:641–659. doi: 10.1093/oxfordjournals.aob.a086511. DOI

National Center for Biotechnology Information PubChem Compound Summary for CID 446220, Cocaine. [(accessed on 13 September 2021)]; Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Cocaine.

Siegrist M., Wiegand T.J. Cocaine. In: Wexler P., editor. Encyclopedia of Toxicology. 3rd ed. Academic Press; Oxford, UK: 2014. pp. 999–1002.

Chronister C.W., Walrath J.C., Goldberger B.A. Rapid detection of benzoylecgonine in vitreous humor by enzyme immunoassay. J. Anal. Toxicol. 2001;25:621–624. doi: 10.1093/jat/25.7.621. PubMed DOI

Liakoni E., Yates C., Dines A.M., Dargan P.I., Heyerdahl F., Hovda K.E., Wood D.M., Eyer F., Liechti M.E., Euro D.E.N.P.R.G. Acute recreational drug toxicity: Comparison of self-reports and results of immunoassay and additional analytical methods in a multicenter European case series. Medicine. 2018;97:e9784. doi: 10.1097/MD.0000000000009784. PubMed DOI PMC

Niedbala R.S., Kardos K., Fries T., Cannon A., Davis A. Immunoassay for detection of cocaine/metabolites in oral fluids. J. Anal. Toxicol. 2001;25:62–68. doi: 10.1093/jat/25.1.62. PubMed DOI

Cone E.J., Sampson-Cone A.H., Darwin W.D., Huestis M.A., Oyler J.M. Urine testing for cocaine abuse: Metabolic and excretion patterns following different routes of administration and methods for detection of false-negative results. J. Anal. Toxicol. 2003;27:386–401. doi: 10.1093/jat/27.7.386. PubMed DOI

Cone E.J., Tsadik A., Oyler J., Darwin W.D. Cocaine metabolism and urinary excretion after different routes of administration. Ther. Drug. Monit. 1998;20:556–560. doi: 10.1097/00007691-199810000-00019. PubMed DOI

Huestis M.A., Darwin W.D., Shimomura E., Lalani S.A., Trinidad D.V., Jenkins A.J., Cone E.J., Jacobs A.J., Smith M.L., Paul B.D. Cocaine and metabolites urinary excretion after controlled smoked administration. J. Anal. Toxicol. 2007;31:462–468. doi: 10.1093/jat/31.8.462. PubMed DOI PMC

Myers A.L., Williams H.E., Kraner J.C., Callery P.S. Identification of anhydroecgonine ethyl ester in the urine of a drug overdose victim. J. Forensic. Sci. 2005;50:1481–1485. doi: 10.1520/JFS2005118. PubMed DOI

Smith M.L., Shimomura E., Paul B.D., Cone E.J., Darwin W.D., Huestis M.A. Urinary excretion of ecgonine and five other cocaine metabolites following controlled oral, intravenous, intranasal, and smoked administration of cocaine. J. Anal. Toxicol. 2010;34:57–63. doi: 10.1093/jat/34.2.57. PubMed DOI PMC

Barroso M., Dias M., Vieira D.N., Queiroz J.A., Lopez-Rivadulla M. 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. Rapid. Commun. Mass. Spectrom. 2008;22:3320–3326. doi: 10.1002/rcm.3738. PubMed DOI

Kintz P., Sengler C., Cirimele V., Mangin P. Evidence of crack use by anhydroecgonine methylester identification. Hum. Exp. Toxicol. 1997;16:123–127. doi: 10.1177/096032719701600208. PubMed DOI

Menzies E.L., Archer J.R.H., Dargan P.I., Parkin M.C., Yamamoto T., Wood D.M., Braithwaite R.A., Elliott S.P., Kicman A.T. Detection of cocaine and its metabolites in whole blood and plasma following a single dose, controlled administration of intranasal cocaine. Drug. Test. Anal. 2019;11:1419–1430. doi: 10.1002/dta.2657. PubMed DOI

Phillips D.L., Tebbett I.R., Bertholf R.L. Comparison of HPLC and GC-MS for measurement cocaine and metabolites in human urine. J. Anal. Toxicol. 1996;20:305–308. doi: 10.1093/jat/20.5.305. PubMed DOI

Fernandez N., Cabanillas L.M., Olivera N.M., Quiroga P.N. 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. Drug. Test. Anal. 2019;11:361–373. doi: 10.1002/dta.2547. PubMed DOI

Melanson S.E.F., Petrides A.K., Khaliq T., Griggs D.A., Flood J.G. Comparison of Oral Fluid and Urine for Detection of Cocaine Abuse Using Liquid Chromatography with Tandem Mass Spectrometry. J. Appl. Lab. Med. 2020;5:935–942. doi: 10.1093/jalm/jfaa032. PubMed DOI

de Lima Feltraco Lizot L., da Silva A.C.C., Bastiani M.F., Hahn R.Z., Bulcao R., Perassolo M.S., Antunes M.V., Linden R. 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. Forensic. Sci. Int. 2019;298:408–416. doi: 10.1016/j.forsciint.2019.03.026. PubMed DOI

Room R., Reuter P. How well do international drug conventions protect public health? Lancet. 2012;379:84–91. doi: 10.1016/S0140-6736(11)61423-2. PubMed DOI

United States Drug Enforcement Administration Drug Scheduling. [(accessed on 17 September 2021)]; Available online: https://www.dea.gov/drug-information/drug-scheduling.

Talking Drugs Drug Decriminalization Across the World. [(accessed on 23 September 2021)]. Available online: https://www.talkingdrugs.org/drug-decriminalisation.

Misuse of Drugs Act Misuse of Drugs Act 1971. [(accessed on 22 September 2021)]; Available online: https://www.legislation.gov.uk/ukpga/1971/38/section/5.

SICAD SICAD > Política Portuguesa. [(accessed on 21 September 2021)]. Available online: http://www.sicad.pt/PT/PoliticaPortuguesa/SitePages/Home%20Page.aspx.

Eastwood N., Fox E., Rosmarin A. A Quiet Revolution: Drug Decriminalization Across The Globe. Release; London, UK: 2016. p. 51.

Prinzleve M., Haasen C., Zurhold H., Matali J.L., Bruguera E., Gerevich J., Bacskai E., Ryder N., Butler S., Manning V., et al. Cocaine use in Europe-a multi-centre study: Patterns of use in different groups. Eur Addict. Res. 2004;10:147–155. doi: 10.1159/000079835. PubMed DOI

Gossop M., Manning V., Ridge G. Concurrent use and order of use of cocaine and alcohol: Behavioural differences between users of crack cocaine and cocaine powder. Addiction. 2006;101:1292–1298. doi: 10.1111/j.1360-0443.2006.01497.x. PubMed DOI

SAMHSA . Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits. Substance Abuse and Mental Health Services Administration; Rockville, MD, USA: 2013. PubMed

EMCDDA . Drug-related Deaths and Mortality in Europe: Update from the EMCDDA Expert Network. Publications Office of the European Union; Luxembourg: 2021.

Cunha-Oliveira T., Rego A.C., Carvalho F., Oliveira C.R. Principles of Addiction, Miller, P.M., Ed. Academic Press; Cambridge, MA, USA: 2013. Chapter 17-Medical Toxicology of Drugs of Abuse; pp. 159–175.

Pomara C., Cassano T., D’Errico S., Bello S., Romano A.D., Riezzo I., Serviddio G. Data available on the extent of cocaine use and dependence: Biochemistry, pharmacologic effects and global burden of disease of cocaine abusers. Curr. Med. Chem. 2012;19:5647–5657. doi: 10.2174/092986712803988811. PubMed DOI

Cone E.J. Pharmacokinetics and Pharmacodynamics of Cocaine. J. Anal. Toxicol. 1995;19:459–478. doi: 10.1093/jat/19.6.459. PubMed DOI

Homstedt B., Lindgren J.E., Rivier L., Plowman T. Cocaine in blood of coca chewers. J. Ethnopharmacol. 1979;1:69–78. doi: 10.1016/0378-8741(79)90017-5. PubMed DOI

Clapp L., Martin B., Beresford T.P. Sublingual cocaine: Novel recurrence of an ancient practice. Clin. Neuropharmacol. 2004;27:93–94. doi: 10.1097/00002826-200403000-00010. PubMed DOI

Jenkins A.J., Llosa T., Montoya I., Cone E.J. Identification and quantitation of alkaloids in coca tea. Forensic. Sci. Int. 1996;77:179–189. doi: 10.1016/0379-0738(95)01860-3. PubMed DOI PMC

Edwards D.J., Bowles S.K. Protein binding of cocaine in human serum. Pharm. Res. 1988;5:440–442. doi: 10.1023/A:1015992502509. PubMed DOI

Jenkins A.J., Cone E.J. Pharmacokinetics: Drug absorption, distribution, and elimination. In: Karch S.B., editor. Drug Abuse Handbook. CRC Press; New York, NY, USA: 1998. pp. 184–187.

Kolbrich E.A., Barnes A.J., Gorelick D.A., Boyd S.J., Cone E.J., Huestis M.A. Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration. J. Anal. Toxicol. 2006;30:501–510. doi: 10.1093/jat/30.8.501. PubMed DOI

Valente M.J., Carvalho F., Bastos M., de Pinho P.G., Carvalho M. Contribution of oxidative metabolism to cocaine-induced liver and kidney damage. Curr. Med. Chem. 2012;19:5601–5606. doi: 10.2174/092986712803988938. PubMed DOI

Wang Q., Simpao A., Sun L., Falk J.L., Lau C.E. Contribution of the active metabolite, norcocaine, to cocaine’s effects after intravenous and oral administration in rats: Pharmacodynamics. Psychopharmacology. 2001;153:341–352. doi: 10.1007/s002130000568. PubMed DOI

Zhang J.Y., Foltz R.L. Cocaine metabolism in man: Identification of four previously unreported cocaine metabolites in human urine. J. Anal. Toxicol. 1990;14:201–205. doi: 10.1093/jat/14.4.201. PubMed DOI

Laizure S.C., Mandrell T., Gades N.M., Parker R.B. Cocaethylene metabolism and interaction with cocaine and ethanol: Role of carboxylesterases. Drug. Metab. Dispos. 2003;31:16–20. doi: 10.1124/dmd.31.1.16. PubMed DOI

Harris D.S., Everhart E.T., Mendelson J., Jones R.T. The pharmacology of cocaethylene in humans following cocaine and ethanol administration. Drug. Alcohol. Depend. 2003;72:169–182. doi: 10.1016/S0376-8716(03)00200-X. PubMed DOI

Herbst E.D., Harris D.S., Everhart E.T., Mendelson J., Jacob P., Jones R.T. Cocaethylene formation following ethanol and cocaine administration by different routes. Exp. Clin. Psychopharmacol. 2011;19:95–104. doi: 10.1037/a0022950. PubMed DOI

Rush C.R., Roll J.M., Higgins S.T. Controlled laboratory studies on the effects of cocaine in combination with other commonly abused drugs in humans. In: HIggins S.T., Katz J.L., editors. Cocaine Abuse: Behavior, Pharmacology and Clinical Applications. Elsevier; Amsterdam, The Netherlands: 1998. p. 248.

Musshoff F. Chromatographic methods for the determination of markers of chronic and acute alcohol consumption. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2002;781:457–480. doi: 10.1016/S1570-0232(02)00691-8. PubMed DOI

Politi L., Zucchella A., Morini L., Stramesi C., Polettini A. Markers of chronic alcohol use in hair: Comparison of ethyl glucuronide and cocaethylene in cocaine users. Forensic. Sci. Int. 2007;172:23–27. doi: 10.1016/j.forsciint.2006.11.007. PubMed DOI

Gomes E.F., Lipaus I.F.S., Martins C.W., Araujo A.M., Mendonca J.B., Pelicao F.S., Lebarch E.C., de Melo Rodrigues L.C., Nakamura-Palacios E.M. Anhydroecgonine Methyl Ester (AEME), a Product of Cocaine Pyrolysis, Impairs Spatial Working Memory and Induces Striatal Oxidative Stress in Rats. Neurotox. Res. 2018;34:834–847. doi: 10.1007/s12640-017-9813-y. PubMed DOI

Scheidweiler K.B., Plessinger M.A., Shojaie J., Wood R.W., Kwong T.C. Pharmacokinetics and pharmacodynamics of methylecgonidine, a crack cocaine pyrolyzate. J. Pharmacol. Exp. Ther. 2003;307:1179–1187. doi: 10.1124/jpet.103.055434. PubMed DOI

Garcia R.C., Dati L.M., Fukuda S., Torres L.H., Moura S., de Carvalho N.D., Carrettiero D.C., Camarini R., Levada-Pires A.C., Yonamine M., et al. Neurotoxicity of anhydroecgonine methyl ester, a crack cocaine pyrolysis product. Toxicol. Sci. 2012;128:223–234. doi: 10.1093/toxsci/kfs140. PubMed DOI

Jeffcoat A.R., Perez-Reyes M., Hill J.M., Sadler B.M., Cook C.E. Cocaine disposition in humans after intravenous injection, nasal insufflation (snorting), or smoking. Drug. Metab. Dispos. 1989;17:153–159. PubMed

O’Leary M.E., Hancox J.C. Role of voltage-gated sodium, potassium and calcium channels in the development of cocaine-associated cardiac arrhythmias. Br. J. Clin. Pharmacol. 2010;69:427–442. doi: 10.1111/j.1365-2125.2010.03629.x. PubMed DOI PMC

Dwyer C., Sowerby L., Rotenberg B.W. Is cocaine a safe topical agent for use during endoscopic sinus surgery? Laryngoscope. 2016;126:1721–1723. doi: 10.1002/lary.25836. PubMed DOI

Proebstl L., Kamp F., Manz K., Krause D., Adorjan K., Pogarell O., Koller G., Soyka M., Falkai P., Kambeitz J. Effects of stimulant drug use on the dopaminergic system: A systematic review and meta-analysis of in vivo neuroimaging studies. Eur. Psychiatry. 2019;59:15–24. doi: 10.1016/j.eurpsy.2019.03.003. PubMed DOI

Ostlund S.B., Halbout B. Chapter 29-Mesolimbic Dopamine Signaling in Cocaine Addiction. In: Preedy V.R., editor. The Neuroscience of Cocaine. Academic Press; San Diego, CA, USA: 2017. pp. 287–295.

Chen R., Tilley M.R., Wei H., Zhou F., Zhou F.M., Ching S., Quan N., Stephens R.L., Hill E.R., Nottoli T., et al. Abolished cocaine reward in mice with a cocaine-insensitive dopamine transporter. Proc. Natl. Acad. Sci. USA. 2006;103:9333–9338. doi: 10.1073/pnas.0600905103. PubMed DOI PMC

Filip M., Frankowska M., Zaniewska M., Golda A., Przegalinski E. The serotonergic system and its role in cocaine addiction. Pharmacol. Rep. 2005;57:685–700. PubMed

Shanti C.M., Lucas C.E. Cocaine and the critical care challenge. Crit Care Med. 2003;31:1851–1859. doi: 10.1097/01.CCM.0000063258.68159.71. PubMed DOI

Richards J.R., Hollander J.E., Ramoska E.A., Fareed F.N., Sand I.C., Izquierdo Gomez M.M., Lange R.A. beta-Blockers, Cocaine, and the Unopposed alpha-Stimulation Phenomenon. J. Cardiovasc. Pharmacol. Ther. 2017;22:239–249. doi: 10.1177/1074248416681644. PubMed DOI

Riezzo I., Fiore C., De Carlo D., Pascale N., Neri M., Turillazzi E., Fineschi V. Side effects of cocaine abuse: Multiorgan toxicity and pathological consequences. Curr. Med. Chem. 2012;19:5624–5646. doi: 10.2174/092986712803988893. PubMed DOI

Ortinski P.I. Cocaine-induced changes in NMDA receptor signaling. Mol. Neurobiol. 2014;50:494–506. doi: 10.1007/s12035-014-8636-6. PubMed DOI PMC

Lever J.R., Fergason-Cantrell E.A., Watkinson L.D., Carmack T.L., Lord S.A., Xu R., Miller D.K., Lever S.Z. Cocaine occupancy of sigma1 receptors and dopamine transporters in mice. Synapse. 2016;70:98–111. doi: 10.1002/syn.21877. PubMed DOI PMC

Heal D.J., Gosden J., Smith S.L. Dopamine reuptake transporter (DAT) “inverse agonism”—A novel hypothesis to explain the enigmatic pharmacology of cocaine. Neuropharmacology. 2014;87:19–40. doi: 10.1016/j.neuropharm.2014.06.012. PubMed DOI

Ciccarone D. Stimulant abuse: Pharmacology, cocaine, methamphetamine, treatment, attempts at pharmacotherapy. Prim. Care. 2011;38:41–58. doi: 10.1016/j.pop.2010.11.004. PubMed DOI PMC

NIDA . What Are the Short-Term Effects of Cocaine Use? National Institute on Drug Abuse; North Bethesda, ML, USA: 2021.

Zimmerman J.L. Cocaine intoxication. Crit Care Clin. 2012;28:517–526. doi: 10.1016/j.ccc.2012.07.003. PubMed DOI

Kosten T.R., Kleber H.D. Rapid death during cocaine abuse: A variant of the neuroleptic malignant syndrome? Am. J. Drug Alcohol. Abuse. 1988;14:335–346. doi: 10.3109/00952998809001555. PubMed DOI

Docherty J.R., Alsufyani H.A. Pharmacology of D.Drugs Used as Stimulants. J. Clin. Pharmacol. 2021;61((Suppl. 2)):S53–S69. doi: 10.1002/jcph.1918. PubMed DOI

Marco C.A., Gupta K., Lubov J., Jamison A., Murray B.P. Hyperthermia associated with methamphetamine and cocaine use. Am. J. Emerg. Med. 2021;42:20–22. doi: 10.1016/j.ajem.2020.12.083. PubMed DOI

Okada T., Shioda K., Makiguchi A., Suda S. Risperidone and 5-HT2A Receptor Antagonists Attenuate and Reverse Cocaine-Induced Hyperthermia in Rats. Int. J. Neuropsychopharmacol. 2020;23:811–820. doi: 10.1093/ijnp/pyaa065. PubMed DOI PMC

Crandall C.G., Vongpatanasin W., Victor R.G. Mechanism of cocaine-induced hyperthermia in humans. Ann. Intern. Med. 2002;136:785–791. doi: 10.7326/0003-4819-136-11-200206040-00006. PubMed DOI

Elkattawy S., Alyacoub R., Al-Nassarei A., Younes I., Ayad S., Habib M. Cocaine induced heart failure: Report and literature review. J. Community Hosp. Intern. Med. Perspect. 2021;11:547–550. doi: 10.1080/20009666.2021.1926614. PubMed DOI PMC

Pergolizzi J.V., Jr., Magnusson P., LeQuang J.A.K., Breve F., Varrassi G. Cocaine and Cardiotoxicity: A Literature Review. Cureus. 2021;13:e14594. doi: 10.7759/cureus.14594. PubMed DOI PMC

Lange R.A., Hillis L.D. Cardiovascular complications of cocaine use. N. Engl. J. Med. 2001;345:351–358. doi: 10.1056/NEJM200108023450507. PubMed DOI

McCord J., Jneid H., Hollander J.E., de Lemos J.A., Cercek B., Hsue P., Gibler W.B., Ohman E.M., Drew B., Philippides G., et al. 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. Circulation. 2008;117:1897–1907. doi: 10.1161/CIRCULATIONAHA.107.188950. PubMed DOI

Afonso L., Mohammad T., Thatai D. Crack whips the heart: A review of the cardiovascular toxicity of cocaine. Am. J. Cardiol. 2007;100:1040–1043. doi: 10.1016/j.amjcard.2007.04.049. PubMed DOI

Martins M.J., Roque Bravo R., Enea M., Carmo H., Carvalho F., Bastos M.L., Dinis-Oliveira R.J., Dias da Silva D. Ethanol addictively enhances the in vitro cardiotoxicity of cocaine through oxidative damage, energetic deregulation, and apoptosis. Arch. Toxicol. 2018;92:2311–2325. doi: 10.1007/s00204-018-2227-7. PubMed DOI

Glauser J., Queen J.R. An overview of non-cardiac cocaine toxicity. J. Emerg Med. 2007;32:181–186. doi: 10.1016/j.jemermed.2006.05.044. PubMed DOI

Herculiani P.P., Pires-Neto R.C., Bueno H.M., Zorzetto J.C., Silva L.C., Santos A.B., Garcia R.C., Yonamine M., Detregiachi C.R., Saldiva P.H., et al. Effects of chronic exposure to crack cocaine on the respiratory tract of mice. Toxicol. Pathol. 2009;37:324–332. doi: 10.1177/0192623308330790. PubMed DOI

Restrepo C.S., Rojas C.A., Martinez S., Riascos R., Marmol-Velez A., Carrillo J., Vargas D. Cardiovascular complications of cocaine: Imaging findings. Emerg. Radiol. 2009;16:11–19. doi: 10.1007/s10140-008-0762-x. PubMed DOI

Filho J., Ogawa M.Y., de Souza Andrade T.H., de Andrade Cordeiro Gadelha S., Fernandes P., Queiroz A.L., Daher E.F. Spectrum of acute kidney injury associated with cocaine use: Report of three cases. BMC Nephrol. 2019;20:99. doi: 10.1186/s12882-019-1279-0. PubMed DOI PMC

Goel N., Pullman J.M., Coco M. Cocaine and kidney injury: A kaleidoscope of pathology. Clin. Kidney J. 2014;7:513–517. doi: 10.1093/ckj/sfu092. PubMed DOI PMC

Valente M.J., Henrique R., Vilas-Boas V., Silva R., Bastos Mde L., Carvalho F., Guedes de Pinho P., Carvalho M. Cocaine-induced kidney toxicity: An in vitro study using primary cultured human proximal tubular epithelial cells. Arch. Toxicol. 2012;86:249–261. doi: 10.1007/s00204-011-0749-3. PubMed DOI

Mai H.N., Jeong J.H., Kim D.J., Chung Y.H., Shin E.J., Nguyen L.T., Nam Y., Lee Y.J., Cho E.H., Nah S.Y., et al. Genetic overexpressing of GPx-1 attenuates cocaine-induced renal toxicity via induction of anti-apoptotic factors. Clin. Exp. Pharmacol. Physiol. 2016;43:428–437. doi: 10.1111/1440-1681.12557. PubMed DOI

Kowalczyk-Pachel D., Iciek M., Bilska-Wilkosz A., Gorny M., Jastrzebska J., Kaminska K., Dudzik P., Filip M., Lorenc-Koci E. Evaluation of Cysteine Metabolism in the Rat Liver and Kidney Following Intravenous Cocaine Administration and Abstinence. Antioxidants. 2021;10:74. doi: 10.3390/antiox10010074. PubMed DOI PMC

Kowalczyk-Pachel D., Iciek M., Wydra K., Nowak E., Gorny M., Filip M., Wlodek L., Lorenc-Koci E. Cysteine Metabolism and Oxidative Processes in the Rat Liver and Kidney after Acute and Repeated Cocaine Treatment. PLoS ONE. 2016;11:e0147238. doi: 10.1371/journal.pone.0147238. PubMed DOI PMC

Farooque U., Okorie N., Kataria S., Shah S.F., Bollampally V.C. Cocaine-Induced Headache: A Review of Pathogenesis, Presentation, Diagnosis, and Management. Cureus. 2020;12:e10128. doi: 10.7759/cureus.10128. PubMed DOI PMC

Mai H.N., Sharma N., Jeong J.H., Shin E.J., Pham D.T., Trinh Q.D., Lee Y.J., Jang C.G., Nah S.Y., Bing G., et al. P53 knockout mice are protected from cocaine-induced kindling behaviors via inhibiting mitochondrial oxidative burdens, mitochondrial dysfunction, and proapoptotic changes. Neurochem. Int. 2019;124:68–81. doi: 10.1016/j.neuint.2018.12.017. PubMed DOI

Cunha-Oliveira T., Rego A.C., Garrido J., Borges F., Macedo T., Oliveira C.R. Neurotoxicity of heroin-cocaine combinations in rat cortical neurons. Toxicology. 2010;276:11–17. doi: 10.1016/j.tox.2010.06.009. PubMed DOI

Guha P., Harraz M.M., Snyder S.H. Cocaine elicits autophagic cytotoxicity via a nitric oxide-GAPDH signaling cascade. Proc. Natl. Acad. Sci. USA. 2016;113:1417–1422. doi: 10.1073/pnas.1524860113. PubMed DOI PMC

Udo M.S.B., da Silva M.A.A., de Souza Prates S., Dal’Jovem L.F., de Oliveira Duro S., Faiao-Flores F., Garcia R.C.T., Maria-Engler S.S., Marcourakis T. Anhydroecgonine methyl ester, a cocaine pyrolysis product, contributes to cocaine-induced rat primary hippocampal neuronal death in a synergistic and time-dependent manner. Arch. Toxicol. 2021;95:1779–1791. doi: 10.1007/s00204-021-03017-z. PubMed DOI

Du C., Park K., Allen C.P., Hu X.T., Volkow N.D., Pan Y. Ca(2+) channel blockade reduces cocaine’s vasoconstriction and neurotoxicity in the prefrontal cortex. Transl. Psychiatry. 2021;11:459. doi: 10.1038/s41398-021-01573-7. PubMed DOI PMC

Lopez-Pedrajas R., Ramirez-Lamelas D.T., Muriach B., Sanchez-Villarejo M.V., Almansa I., Vidal-Gil L., Romero F.J., Barcia J.M., Muriach M. Cocaine promotes oxidative stress and microglial-macrophage activation in rat cerebellum. Front. Cell Neurosci. 2015;9:279. doi: 10.3389/fncel.2015.00279. PubMed DOI PMC

Bittencourt A.M.L., Bampi V.F., Sommer R.C., Schaker V., Juruena M.F.P., Soder R.B., Franco A.R., Sanvicente-Vieira B., Grassi-Oliveira R., Ferreira P. Cortical thickness and subcortical volume abnormalities in male crack-cocaine users. Psychiatry Res. Neuroimaging. 2021;310:111232. doi: 10.1016/j.pscychresns.2020.111232. PubMed DOI

Schuch-Goi S.B., Goi P.D., Bermudez M., Fara L.S., Kessler F.P., Pechansky F., Gama C.S., Massuda R., von Diemen L. Accumbens volumes are reduced among crack-cocaine users. Neurosci. Lett. 2017;645:86–89. doi: 10.1016/j.neulet.2017.02.073. PubMed DOI

Evans M.A., Harbison R.D. Cocaine-induced hepatotoxicity in mice. Toxicol. Appl. Pharmacol. 1978;45:739–754. doi: 10.1016/0041-008X(78)90167-9. PubMed DOI

Mehanny S.Z., Abdel-Rahman M.S. Cocaine hepatotoxicity in mice: Histologic and enzymatic studies. Toxicol. Pathol. 1991;19:24–29. doi: 10.1177/019262339101900103. PubMed DOI

Perino L.E., Warren G.H., Levine J.S. Cocaine-induced hepatotoxicity in humans. Gastroenterology. 1987;93:176–180. doi: 10.1016/0016-5085(87)90331-3. PubMed DOI

Vitcheva V. Cocaine toxicity and hepatic oxidative stress. Curr. Med. Chem. 2012;19:5677–5682. doi: 10.2174/092986712803988929. PubMed DOI

Dinis-Oliveira R.J. Metabolomics of cocaine: Implications in toxicity. Toxicol. Mech. Methods. 2015;25:494–500. PubMed

Mai H.N., Jung T.W., Kim D.J., Sharma G., Sharma N., Shin E.J., Jang C.G., Nah S.Y., Lee S.H., Chung Y.H., et al. Protective potential of glutathione peroxidase-1 gene against cocaine-induced acute hepatotoxic consequences in mice. J. Appl. Toxicol. 2018;38:1502–1520. doi: 10.1002/jat.3666. PubMed DOI

Mai H.N., Sharma G., Sharma N., Shin E.J., Kim D.J., Pham D.T., Trinh Q.D., Jang C.G., Nah S.Y., Jeong J.H., et al. Genetic depletion of p53 attenuates cocaine-induced hepatotoxicity in mice. Biochimie. 2019;158:53–61. doi: 10.1016/j.biochi.2018.12.009. PubMed DOI

Boess F., Ndikum-Moffor F.M., Boelsterli U.A., Roberts S.M. Effects of cocaine and its oxidative metabolites on mitochondrial respiration and generation of reactive oxygen species. Biochem. Pharmacol. 2000;60:615–623. doi: 10.1016/S0006-2952(00)00355-5. PubMed DOI

Krokos A., Deda O., Virgiliou C., Gika H., Raikos N., Aggelidou E., Kritis A., Theodoridis G. Evaluation of Cocaine Effect on Endogenous Metabolites of HepG2 Cells Using Targeted Metabolomics. Molecules. 2021;26:4610. doi: 10.3390/molecules26154610. PubMed DOI PMC

Zaitsu K., Miyawaki I., Bando K., Horie H., Shima N., Katagi M., Tatsuno M., Bamba T., Sato T., Ishii A., et al. 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. Anal. Bioanal. Chem. 2014;406:1339–1354. doi: 10.1007/s00216-013-7234-1. PubMed DOI

NIDA Cocaine DrugFacts. [(accessed on 24 September 2021)]; Available online: https://www.drugabuse.gov/publications/drugfacts/cocaine.

American Psychiatric Association . Diagnostics and Statistical Manual of Mental health Disorders. 5th ed. American Psychiatric Association; Arlington, VA: 2013. Stimulant-Related Disorders; p. 561.

Barbosa-Mendez S., Perez-Sanchez G., Becerril-Villanueva E., Salazar-Juarez A. Melatonin decreases cocaine-induced locomotor sensitization and cocaine-conditioned place preference in rats. J. Psychiatr. Res. 2021;132:97–110. doi: 10.1016/j.jpsychires.2020.09.027. PubMed DOI

Caffino L., Moro F., Mottarlini F., Targa G., Di Clemente A., Toia M., Orru A., Giannotti G., Fumagalli F., Cervo L. Repeated exposure to cocaine during adolescence enhances the rewarding threshold for cocaine-conditioned place preference in adulthood. Addict. Biol. 2021;26:e13012. doi: 10.1111/adb.13012. PubMed DOI

Kawahara Y., Ohnishi Y.N., Ohnishi Y.H., Kawahara H., Nishi A. Distinct role of dopamine in the PFC and NAc during exposure to cocaine-associated cues. Int. J. Neuropsychopharmacol. 2021;24:988–1001. doi: 10.1093/ijnp/pyab067. PubMed DOI PMC

Zinani D.B., Wetzel H.N., Norman A.B. The compulsion zone explains the self-administration of cocaine, RTI-55 and bupropion in rats. Brain Res. 2021:147707. doi: 10.1016/j.brainres.2021.147707. PubMed DOI

Di Chiara G., Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc. Natl. Acad. Sci. USA. 1988;85:5274–5278. doi: 10.1073/pnas.85.14.5274. PubMed DOI PMC

Volkow N.D., Wang G.J., Telang F., Fowler J.S., Logan J., Childress A.R., Jayne M., Ma Y., Wong C. Cocaine cues and dopamine in dorsal striatum: Mechanism of craving in cocaine addiction. J. Neurosci. 2006;26:6583–6588. doi: 10.1523/JNEUROSCI.1544-06.2006. PubMed DOI PMC

Volkow N.D., Tomasi D., Wang G.J., Logan J., Alexoff D.L., Jayne M., Fowler J.S., Wong C., Yin P., Du C. Stimulant-induced dopamine increases are markedly blunted in active cocaine abusers. Mol. Psychiatry. 2014;19:1037–1043. doi: 10.1038/mp.2014.58. PubMed DOI PMC

Andrianarivelo A., Saint-Jour E., Pousinha P., Fernandez S.P., Petitbon A., De Smedt-Peyrusse V., Heck N., Ortiz V., Allichon M.C., Kappes V., et al. Disrupting D1-NMDA or D2-NMDA receptor heteromerization prevents cocaine’s rewarding effects but preserves natural reward processing. Sci. Adv. 2021;7:eabg5970. doi: 10.1126/sciadv.abg5970. PubMed DOI PMC

Sanvicente-Vieira B., Kommers-Molina J., De Nardi T., Francke I., Grassi-Oliveira R. Crack-cocaine dependence and aging: Effects on working memory. Braz J. Psychiatry. 2016;38:58–60. doi: 10.1590/1516-4446-2015-1708. PubMed DOI PMC

Pudiak C.M., KuoLee R., Bozarth M.A. Tolerance to cocaine in brain stimulation reward following continuous cocaine infusions. Pharmacol. Biochem. Behav. 2014;122:246–252. doi: 10.1016/j.pbb.2014.04.006. PubMed DOI

Small A.C., Kampman K.M., Plebani J., De Jesus Quinn M., Peoples L., Lynch K.G. Tolerance and sensitization to the effects of cocaine use in humans: A retrospective study of long-term cocaine users in Philadelphia. Subst. Use Misuse. 2009;44:1888–1898. doi: 10.3109/10826080902961179. PubMed DOI

Ferris M.J., Calipari E.S., Mateo Y., Melchior J.R., Roberts D.C., Jones S.R. Cocaine self-administration produces pharmacodynamic tolerance: Differential effects on the potency.y of dopamine transporter blockers, releasers, and methylphenidate. Neuropsychopharmacology. 2012;37:1708–1716. doi: 10.1038/npp.2012.17. PubMed DOI PMC

Calipari E.S., Ferris M.J., Jones S.R. Extended access of cocaine self-administration results in tolerance to the dopamine-elevating and locomotor-stimulating effects of cocaine. J. Neurochem. 2014;128:224–232. doi: 10.1111/jnc.12452. PubMed DOI PMC

NIDA . What are the Long-Term Effects of Cocaine Use? National Institute on Drug Abuse; North Bethesda, ML, USA: 2021.

Gilmore D., Zorland J., Akin J., Johnson J.A., Emshoff J.G., Kuperminc G.P. Mortality risk in a sample of emergency department patients who use cocaine with alcohol and/or cannabis. Subst. Abus. 2018;39:266–270. doi: 10.1080/08897077.2017.1389799. PubMed DOI

Leri F., Bruneau J., Stewart J. Understanding polydrug use: Review of heroin and cocaine co-use. Addiction. 2003;98:7–22. doi: 10.1046/j.1360-0443.2003.00236.x. PubMed DOI

Motta-Ochoa R., Bertrand K., Arruda N., Jutras-Aswad D., Roy E. I love having benzos after my coke shot: The use of psychotropic medication among cocaine users in downtown Montreal. Int. J. Drug. Policy. 2017;49:15–23. doi: 10.1016/j.drugpo.2017.07.012. PubMed DOI

Tassoni G., Cippitelli M., Mietti G., Cerioni A., Buratti E., Bury E., Cingolani M. Hair Analysis to Evaluate Polydrug Use. Healthcare. 2021;9:972. doi: 10.3390/healthcare9080972. PubMed DOI PMC

Obembe S.B. Common Psychoactive Drugs. In: Obembe S.B., editor. Practical Skills and Clinical Management of Alcoholism & Drug Addiction. Elsevier; Amsterdam, The Netherlands: 2012. pp. 11–32.

Dean R.A., Harper E.T., Dumaual N., Stoeckel D.A., Bosron W.F. Effects of ethanol on cocaine metabolism: Formation of cocaethylene and norcocaethylene. Toxicol. Appl. Pharmacol. 1992;117:1–8. doi: 10.1016/0041-008X(92)90210-J. PubMed DOI

Uszenski R.T., Gillis R.A., Schaer G.L., Analouei A.R., Kuhn F.E. Additive myocardial depressant effects of cocaine and ethanol. Am. Heart J. 1992;124:1276–1283. doi: 10.1016/0002-8703(92)90412-O. PubMed DOI

Pereira R.B., Andrade P.B., Valentão P. A Comprehensive View of the Neurotoxicity Mechanisms of Cocaine and Ethanol. Neurotox. Res. 2015;28:253–267. doi: 10.1007/s12640-015-9536-x. PubMed DOI

Zucoloto A.D., Eller S., de Oliveira T.F., Wagner G.A., Fruchtengarten L.V.G., de Oliveira C.D.R., Yonamine M. Relationship between cocaine and cocaethylene blood concentration with the severity of clinical manifestations. Am. J. Emerg. Med. 2021;50:404–408. doi: 10.1016/j.ajem.2021.08.057. PubMed DOI

Thomas S.A., Perekopskiy D., Kiyatkin E.A. Cocaine added to heroin fails to affect heroin-induced brain hypoxia. Brain Res. 2020;1746:147008. doi: 10.1016/j.brainres.2020.147008. PubMed DOI PMC

Karch S.B. Cocaine cardiovascular toxicity. South. Med. J. 2005;98:794–799. doi: 10.1097/01.smj.0000168701.08879.3f. PubMed DOI

Hearn W.L., Rose S., Wagner J., Ciarleglio A., Mash D.C. Cocaethylene is more potent than cocaine in mediating lethality. Pharmacol. Biochem. Behav. 1991;39:531–533. doi: 10.1016/0091-3057(91)90222-N. PubMed DOI

Mendelson J.H., Mello N.K. Management of Cocaine Abuse and Dependence. N. Engl. J. Med. 1996;334:965–972. doi: 10.1056/NEJM199604113341507. PubMed DOI

McIntyre K.M. Vasopressin in asystolic cardiac arrest. N. Engl. J. Med. 2004;350:179–181. doi: 10.1056/NEJMe038195. PubMed DOI

Wenzel V., Krismer A.C., Arntz H.R., Sitter H., Stadlbauer K.H., Lindner K.H., European Resuscitation Council Vasopressor during Cardiopulmonary Resuscitation Study Group A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N. Engl. J. Med. 2004;350:105–113. doi: 10.1056/NEJMoa025431. PubMed DOI

Maraj S., Figueredo V.M., Lynn Morris D. Cocaine and the heart. Clin. Cardiol. 2010;33:264–269. doi: 10.1002/clc.20746. PubMed DOI PMC

Hollander J.E., Henry T.D. Evaluation and management of the patient who has cocaine-associated chest pain. Cardiol. Clin. 2006;24:103–114. doi: 10.1016/j.ccl.2005.09.003. PubMed DOI

Witchel H.J., Hancox J.C., Nutt D.J. Psychotropic drugs, cardiac arrhythmia, and sudden death. J. Clin. Psychopharmacol. 2003;23:58–77. doi: 10.1097/00004714-200302000-00010. PubMed DOI

DiMaio T.G., DiMaio V.J.M. Excited Delirium Syndrome: Causes of Death and Prevention. CRC Press; Boca Raton: 2005.

Kampman K.M. The treatment of cocaine use disorder. Sci. Adv. 2019;5:eaax1532. doi: 10.1126/sciadv.aax1532. PubMed DOI PMC

Nuijten M., Blanken P., van de Wetering B., Nuijten B., van den Brink W., Henrdriks V. Sustained-release dexamfetamine in the treatment of chronic cocaine-dependent patients on heroin-assisted treatment: A randomised, double-blind, placebo-controlled trial. Lancet. 2016;387:2226–2234. doi: 10.1016/S0140-6736(16)00205-1. PubMed DOI

Kampman K.M., Pettinati H.M., Lynch K.G., Spratt K., Wierzbicki M.R., O’Brien C.P. A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence. Drug. Alcohol. Depend. 2013;133:94–99. doi: 10.1016/j.drugalcdep.2013.05.026. PubMed DOI PMC

Reith M.E., Blough B.E., Hong W.C., Jones K.T., Schmitt K.C., Baumann M.H., Partilla J.S., Rothman R.B., Katz J.L. Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter. Drug. Alcohol. Depend. 2015;147:1–19. doi: 10.1016/j.drugalcdep.2014.12.005. PubMed DOI PMC

Bentzley B.S., Han S.S., Neuner S., Humphreys K., Kampman K.M., Halpern C.H. Comparison of Treatments for Cocaine Use Disorder Among Adults: A Systematic Review and Meta-analysis. JAMA Netw. Open. 2021;4:e218049. doi: 10.1001/jamanetworkopen.2021.8049. PubMed DOI PMC

Natural Sympathomimetic Drugs: From Pharmacology to Toxicology