View source for Cocaine

{{Short description|Tropane alkaloid and stimulant drug}}
{{About|the purified salt form of cocaine|the vaporized freebase|Crack cocaine|the crude coca leaf extract|Cocaine paste|the disguised smuggled form|Black cocaine}}
{{Distinguish|text="Pink cocaine", which typically does not contain cocaine; see [[Tusi (drug)]]}}
{{Other uses}}
{{Pp-semi-indef}}
{{pp-move}}
{{Use American English|date=December 2017}}
{{Use dmy dates|date=October 2025}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| image = Kokain - Cocaine.svg
| image_class = skin-invert-image
| width =
| alt =
| caption =
| image2 = Cocaine-from-xtal-1983-3D-balls.png
| width2 =
| alt2 = 

<!-- Clinical data -->
| pronounce = kə(ʊ)ˈkeɪn
| tradename = Neurocaine,<ref>{{Cite book |vauthors=Nordegren T |title=The A-Z Encyclopedia of Alcohol and Drug Abuse |date=2002 |publisher=Universal-Publishers |isbn=978-1-58112-404-0 |page=461 |url=https://books.google.com/books?id=4yaGePenGKgC&pg=PA461 |access-date=3 September 2020 |archive-date=8 July 2024 |archive-url=https://web.archive.org/web/20240708191823/https://books.google.com/books?id=4yaGePenGKgC&pg=PA461#v=onepage&q&f=false |url-status=live }}</ref> Goprelto,<ref name="Goprelto FDA label" /> Numbrino,<ref name="Numbrino FDA label" /> others
| Drugs.com = {{drugs.com|CONS|cocaine}}
| MedlinePlus =
| DailyMedID = Cocaine
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU_comment =
| pregnancy_category =
| dependency_liability = [[Physical dependence|Physical]]: Low [[Psychological dependence|Psychological]]: High<ref name="Gho_2010">{{Cite book | vauthors = Ghodse H | title = Ghodse's Drugs and Addictive Behaviour: A Guide to Treatment|date=2010|publisher=Cambridge University Press|isbn=978-1-139-48567-8|page=91|edition=4|url=https://books.google.com/books?id=WYQ23OMjWbcC&pg=PA91|url-status=live|archive-url=https://web.archive.org/web/20170910234911/https://books.google.com/books?id=WYQ23OMjWbcC&pg=PA91|archive-date=10 September 2017}}</ref>
| addiction_liability = High<ref>{{Cite book|title=Introduction to Pharmacology|edition=3 |date=2007|publisher=CRC Press|location=Abingdon|isbn=978-1-4200-4742-4|pages=222–223|url=https://books.google.com/books?id=qfrLBQAAQBAJ&pg=PA222|url-status=live|archive-url=https://web.archive.org/web/20170910234921/https://books.google.com/books?id=qfrLBQAAQBAJ&pg=PA222|archive-date=10 September 2017}}</ref>
| routes_of_administration = [[Topical]], [[Oral administration|by mouth]], [[insufflation (medicine)|insufflation]], [[intravenous]], [[smoking|inhalation]]
| class = {{plainlist|
* [[Local anesthetic]];
* [[SNDRI]];<ref name="Sora_2001">{{cite journal | vauthors = Sora I, Hall FS, Andrews AM, Itokawa M, Li XF, Wei HB, Wichems C, Lesch KP, Murphy DL, Uhl GR | title = Molecular mechanisms of cocaine reward: combined dopamine and serotonin transporter knockouts eliminate cocaine place preference | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 9 | pages = 5300–5305 | date = April 2001 | pmid = 11320258 | pmc = 33204 | doi = 10.1073/pnas.091039298 | doi-access = free | bibcode = 2001PNAS...98.5300S }}</ref><ref name="Azizi_2022">{{cite journal | vauthors = Azizi SA | title = Monoamines: Dopamine, Norepinephrine, and Serotonin, Beyond Modulation, "Switches" That Alter the State of Target Networks | journal = The Neuroscientist | volume = 28 | issue = 2 | pages = 121–143 | date = April 2022 | pmid = 33292070 | doi = 10.1177/1073858420974336 | s2cid = 228080727 }}</ref>
* [[Stimulant]]
}}
| ATC_prefix = N01
| ATC_suffix = BC01
| ATC_supplemental = {{ATC|R02|AD03}}, {{ATC|S01|HA01}}, {{ATC|S02|DA02}}

<!-- Legal status -->
| legal_AU = Schedule 8
| legal_AU_comment =
| legal_BR = F1
| legal_BR_comment =
| legal_CA = Schedule I
| legal_CA_comment =
| legal_DE = Anlage III
| legal_DE_comment =
| legal_NZ = Class A
| legal_NZ_comment =
| legal_UK = Class A
| legal_UK_comment =
| legal_US = Schedule II
| legal_US_comment = <ref name=DEA2017Sched>{{Cite web|title=DEA / Drug Scheduling|url=https://www.dea.gov/druginfo/ds.shtml|website=www.dea.gov|access-date=7 August 2017|archive-url=https://web.archive.org/web/20170809044016/https://www.dea.gov/druginfo/ds.shtml|archive-date=9 August 2017}}</ref>
| legal_EU = 
| legal_EU_comment = 
| legal_UN = N I III
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability = {{plainlist|
* [[Oral administration|By mouth]]: 33%<ref name="Fattinger_2000">{{Cite journal | vauthors = Fattinger K, Benowitz NL, Jones RT, Verotta D | title = Nasal mucosal versus gastrointestinal absorption of nasally administered cocaine | journal = European Journal of Clinical Pharmacology | volume = 56 | issue = 4 | pages = 305–10 | date = July 2000 | pmid = 10954344 | doi = 10.1007/s002280000147 | s2cid = 20708443 }}</ref>
* [[Insufflation (medicine)|Insufflation]]: 60<ref>{{Cite journal | vauthors = Barnett G, Hawks R, Resnick R | title = Cocaine pharmacokinetics in humans | journal = Journal of Ethnopharmacology | volume = 3 | issue = 2–3 | pages = 353–66 | year = 1981 | pmid = 7242115 | doi = 10.1016/0378-8741(81)90063-5 }}</ref>–80%<ref>{{Cite journal | vauthors = Jeffcoat AR, Perez-Reyes M, Hill JM, Sadler BM, Cook CE | title = Cocaine disposition in humans after intravenous injection, nasal insufflation (snorting), or smoking | journal = Drug Metabolism and Disposition | volume = 17 | issue = 2 | pages = 153–9 | year = 1989 | doi = 10.1016/S0090-9556(25)08737-9 | pmid = 2565204 }}</ref>
* [[Nasal spray]]: 25<ref name="Wilkinson_1980">{{Cite journal | vauthors = Wilkinson P, Van Dyke C, Jatlow P, Barash P, Byck R | title = Intranasal and oral cocaine kinetics | journal = Clinical Pharmacology and Therapeutics | volume = 27 | issue = 3 | pages = 386–94 | date = March 1980 | pmid = 7357795 | doi = 10.1038/clpt.1980.52 | s2cid = 29851205 }}</ref>–43%<ref name="Fattinger_2000" />}}
| protein_bound =
| metabolism = [[Liver]], [[CYP3A4]]
| metabolites = [[Norcocaine]], [[benzoylecgonine]], [[cocaethylene]] (when consumed with [[alcohol (drug)|alcohol]])
| onset = Seconds to minutes<ref name="Zimmerman_2012">{{Cite journal | vauthors = Zimmerman JL | title = Cocaine intoxication | journal = Critical Care Clinics | volume = 28 | issue = 4 | pages = 517–26 | date = October 2012 | pmid = 22998988 | doi = 10.1016/j.ccc.2012.07.003 }}</ref>
| elimination_half-life = 
| duration_of_action = 20 to 90 minutes<ref name="Zimmerman_2012" />
| excretion = [[Kidney]]

<!-- Identifiers -->
| index_label =
| index2_label =
| CAS_number = 50-36-2
| CAS_supplemental =
| PubChem = 446220
| IUPHAR_ligand = 2286
| DrugBank = DB00907
| ChemSpiderID = 10194104
| UNII = I5Y540LHVR
| KEGG = D00110
| ChEBI = 27958
| ChEMBL = 370805
| NIAID_ChemDB =
| PDB_ligand = COC
| synonyms = Benzoylmethylecgonine

<!-- Chemical and physical data -->
| IUPAC_name = Methyl (1''R'',2''R'',3''S'',5''S'')-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
| C = 17
| H = 21
| N = 1
| O = 4
| SMILES = CN1[C@H]2CC[C@@H]1[C@@H](C(OC)=O)[C@@H](OC(C3=CC=CC=C3)=O)C2
| StdInChI = 1S/C17H21NO4/c1-18-12-8-9-13(18)15(17(20)21-2)14(10-12)22-16(19)11-6-4-3-5-7-11/h3-7,12-15H,8-10H2,1-2H3/t12-,13+,14-,15+/m0/s1
| StdInChI_comment =
| StdInChIKey = ZPUCINDJVBIVPJ-LJISPDSOSA-N
| density =
| density_notes =
| melting_point = 98<!--Pubchem-->
| melting_high =
| melting_notes =
| boiling_point = 187
| boiling_notes =
| solubility = 1.8
| sol_units = g/L (22 °C)<!--YALKOWSKY,SH & DANNENFELSER,RM (1992) via Pubchem-->
| specific_rotation =
}}
<!-- Definition and effects -->
'''Cocaine''' is a central nervous system [[stimulant]] and [[tropane alkaloid]] derived primarily from the leaves of two [[coca]] species native to South America: ''[[Erythroxylum coca]]'' and ''[[Erythroxylum novogranatense|E. novogranatense]]''.<ref name="EUDA">{{cite web |title=Cocaine and crack drug profile {{!}} www.euda.europa.eu |url=https://www.euda.europa.eu/publications/drug-profiles/cocaine_en |website=www.euda.europa.eu}}</ref><ref>{{cite web |title=Cocaine - Alcohol and Drug Foundation |url=https://adf.org.au/drug-facts/cocaine/ |website=adf.org.au }}</ref><ref>{{Cite journal | title=The identification of coca (Erythroxylum species) | journal=Botanical Journal of the Linnean Society | doi=10.1111/j.1095-8339.1982.tb00368.x}}</ref><ref name="Pom_2012">{{Cite journal | vauthors = Pomara C, Cassano T, D'Errico S, Bello S, Romano AD, Riezzo I, Serviddio G | title = Data available on the extent of cocaine use and dependence: biochemistry, pharmacologic effects and global burden of disease of cocaine abusers | journal = Current Medicinal Chemistry | volume = 19 | issue = 33 | pages = 5647–57 | date = 2012 | pmid = 22856655 | doi = 10.2174/092986712803988811 }}</ref><ref name="Andean_full_report.pdf">{{cite web | title = Coca Cultivation in the Andean Region | publisher = UNODC | date = June 2006 |url=https://www.unodc.org/pdf/andean/Andean_full_report.pdf}}</ref> Coca leaves are processed into [[cocaine paste]], a crude mix of [[coca alkaloids]] from which cocaine base is isolated and converted to '''cocaine hydrochloride'''.<ref name="Andean_full_report.pdf" /> Cocaine was once a standard [[topical medication]] as a [[local anesthetic]] with intrinsic [[vasoconstriction|vasoconstrictor]] activity, but its high abuse potential, adverse effects, and cost have limited its use and led to its replacement by other medicines.<ref name="Latorre_1999" /><ref name="Bremner_2019" /><ref name="Armbuster_2021">{{cite journal | vauthors = Armbuster YC, Banas BN, Feickert KD, England SE, Moyer EJ, Christie EL, Chughtai S, Giuliani TJ, Halden RU, Graham JH, McCall KL, Piper BJ | title = Decline and Pronounced Regional Disparities in Medical Cocaine Usage in the United States | journal = The Journal of Pharmacy Technology | volume = 37 | issue = 6 | pages = 278–285 | date = December 2021 | pmid = 34790964 | pmc = 8592245 | doi = 10.1177/87551225211035563 }}</ref>

<!-- Pharmacokinetics/Pharmacodynamics -->
Street cocaine is commonly [[Nasal administration|snorted]], [[injection (medicine)|injected]], or smoked as [[crack cocaine]], with effects lasting up to 90 minutes depending on the route.<ref name="Zimmerman_2012" /><ref name="smokablecocaine_eng_web-def.pdf">{{cite book | vauthors = Cortés E, Metaal P | title = Smokable cocaine markets in Latin America and the Caribbean |url=https://www.tni.org/files/publication-downloads/tni-smokablecocaine_eng_web-def.pdf}}</ref> Cocaine acts pharmacologically as a [[serotonin–norepinephrine–dopamine reuptake inhibitor]] (SNDRI),<ref name="Azizi_2022" /><ref name="Cheng_2015">{{Cite journal | vauthors = Cheng MH, Block E, Hu F, Cobanoglu MC, Sorkin A, Bahar I | title = Insights into the Modulation of Dopamine Transporter Function by Amphetamine, Orphenadrine, and Cocaine Binding | journal = Frontiers in Neurology | volume = 6 | page = 134 | date = 2015 | pmid = 26106364 | pmc = 4460958 | doi = 10.3389/fneur.2015.00134 | doi-access = free }}</ref><ref name="Pom_2012" /> producing reinforcing effects such as [[euphoria]], increased [[alertness]], [[Attentional control|concentration]], [[aphrodisiac|libido]], and reduced fatigue and [[Anorectic|appetite]].<ref name="Roque_2022">{{cite journal | vauthors = Roque Bravo R, Faria AC, Brito-da-Costa AM, Carmo H, Mladěnka P, Dias da Silva D, Remião F | title = Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern | journal = Toxins | volume = 14 | issue = 4 | page = 278 | date = April 2022 | pmid = 35448887 | pmc = 9032145 | doi = 10.3390/toxins14040278 | doi-access = free }}</ref>

<!-- Side effects -->
Cocaine has numerous [[adverse effect]]s. Acute use can cause [[vasoconstriction]], [[tachycardia]], [[hypertension]], [[hyperthermia]], or seizures, while overdose may lead to [[stroke]], [[myocardial infarction|heart attack]], or [[sudden cardiac death]].<ref name="Pom_2012" /><ref name="Zimmerman_2012" /><ref name="Sordo_2014">{{Cite journal |vauthors=Sordo L, Indave BI, Barrio G, Degenhardt L, de la Fuente L, Bravo MJ |title=Cocaine use and risk of stroke: a systematic review |journal=Drug and Alcohol Dependence |volume=142 |pages=1–13 |date=September 2014 |pmid=25066468 |doi=10.1016/j.drugalcdep.2014.06.041 |type=Systematic Review |doi-access=free}}</ref> Cocaine also produces a spectrum of [[psychiatric symptoms]] including agitation, [[paranoia]], anxiety, irritability, [[stimulant psychosis|psychosis]], hallucinations, delusions, violence, as well as [[suicidal ideation|suicidal]] and homicidal thinking.<ref name="Morton_1999" /><ref name="Pom_2012" /> [[Prenatal cocaine exposure|Prenatal exposure]] poses risks to fetal development.<ref name="Buckingham-Howes_2013" /><ref name="Lambert_2012" /><ref name="McCarthy_2014" /><ref name="Eiden_2009" /> Chronic use may result in [[cocaine dependence]], withdrawal symptoms, [[neurotoxicity]], and [[#Cocaine nose|nasal damage]], including [[cocaine-induced midline destructive lesions]].<ref name="Gawin_1989" /><ref name="Sofuoglu_2005" /><ref name="Clare_2024" /><ref name="Berberi_2024" /><ref name="Nitro_2022" /><ref name="Di_Cosola_2021" />

<!-- Sources -->
Coca cultivation and its subsequent processes occur primarily in [[Latin America]], especially in the [[Andes]] of Bolivia, Peru, and Colombia, though cultivation is expanding into [[Central America]], including Honduras, Guatemala, and Belize.<ref name="Andean_full_report.pdf" /><ref name="Murillo-Sandoval_2024">{{cite journal | vauthors = Murillo-Sandoval PJ, Sesnie SE, Ordoñez Armas ME, Magliocca N, Tellman B, Devine JA, Nielsen E, McSweeney K | title = Central America's agro-ecological suitability for cultivating coca, Erythroxylum spp | journal = Environmental Research Letters | volume = 19 | issue = 10 | page = 104068 | date = 1 October 2024 | doi = 10.1088/1748-9326/ad7276 | bibcode = 2024ERL....19j4068M | doi-access = free }}</ref><ref name="plantaciones-laboratorios-y-narcorutas-de-coca-en-honduras-LJ17693091">{{cite news |title=Plantaciones, laboratorios y narcorutas de coca en Honduras |url=https://www.elheraldo.hn/elheraldoplus/interactivos/plantaciones-laboratorios-y-narcorutas-de-coca-en-honduras-LJ17693091 |work=www.elheraldo.hn |language=es-HN}}</ref><ref name="uatemala-registra-record-produccion-coca-no-cocaina">{{cite news | vauthors = Papadovassilakis A, Voss G |title=Guatemala registra récord en producción de coca, pero no de cocaína |url=https://insightcrime.org/es/noticias/guatemala-registra-record-produccion-coca-no-cocaina/ |work=InSight Crime |date=10 February 2023 |language=es-ES}}</ref><ref name="police-find-half-a-million-coca-plants-in-southern-belize">{{cite news |title=Police find half a million coca plants in Southern Belize |url=https://www.breakingbelizenews.com/2023/08/31/police-find-half-a-million-coca-plants-in-southern-belize/ |work=Belize News and Opinion on www.breakingbelizenews.com |date=31 August 2023}}</ref> Violence linked to the cocaine trade continues to affect [[Latin America and the Caribbean]] and is expanding into [[Western Europe]], [[Asia]], and [[Africa]] as [[transnational organized crime]] groups compete globally.<ref name="WDR25_Special_points_of_interest.pdf" /><ref name="ow-the-drug-wars-impact-latin-america-and-the-caribbean-development" /> Cocaine remains the world's fastest-growing [[illegal drug trade|illicit drug market]].<ref name="Press_release_WDR_2025_English.pdf" /><ref>{{cite news |title=Cocaine Market Booming as Meth Trafficking Spreads, UN Report Says |url=https://www.voanews.com/a/cocaine-market-booming-as-meth-trafficking-spreads-un-report-says/7152417.html |work=Voice of America |date=25 June 2023 }}</ref> Coca chewing dates back at least 8,000 years in South America.<ref>{{cite journal| vauthors = Dillehay TD, Rossen J, Ugent D, Karathanasis A, Vásquez V, Netherly PJ |year=2010|title=Early Holocene coca chewing in northern Peru|journal=[[Antiquity (journal)|Antiquity]]|volume=84|issue=326|pages=939–953|doi=10.1017/S0003598X00067004|s2cid=162889680}}</ref> Large-scale cultivation occurred in Taiwan and [[Java]] prior to [[World War II]].<ref name="Lu_2024" /><ref name="Musto_1998" /> Decades later, the [[cocaine boom]] marked a sharp rise in illegal cocaine production and trade, beginning in the late 1970s and peaking in the 1980s.<ref>{{cite web |url=https://www.pbs.org/newshour/arts/what-it-was-really-like-to-be-in-miami-in-the-crazy-cocaine-years |title=What it was really like to be in Miami during the crazy cocaine boom | vauthors = Flock E |date= 21 January 2017 |website=pbs.org}}</ref> Cocaine is regulated under [[international drug control conventions]], though [[legal status of cocaine|national laws vary]]: several countries have decriminalized small quantities.<ref name="Housego_2004">{{cite news | vauthors = Housego K | title= As addiction rises, Colombia weighs rolling back decade-old drug legalization | date=5 April 2004 | work=[[The San Diego Union-Tribune]] | url =http://www.signonsandiego.com/news/world/20040405-0915-legalizeddrugs.html | agency =Associated Press | access-date = 9 August 2009 }}</ref><ref name="Murphy_2004">{{cite news | vauthors = Murphy J | title=Colombia sinks in sea of legal cocaine, heroin | date=5 April 2004 | work=[[CBS News]] | url =http://www.cbsnews.com/stories/2004/04/05/world/main610293.shtml | archive-url =https://web.archive.org/web/20040405221943/http://www.cbsnews.com/stories/2004/04/05/world/main610293.shtml | archive-date =5 April 2004 | access-date = 9 August 2009 }}</ref><ref name="independent">{{cite web|url=https://www.independent.co.uk/news/world/americas/heroin-and-cocaine-now-legal-in-mexico-ndash-in-small-doses-1776792.html|title=Heroin and cocaine now legal in Mexico – in small doses &#124; Americas &#124; News &#124; The Independent|date=23 October 2011|work=The Independent|access-date=15 May 2016}}</ref><ref name="Greenwald_2009">{{Cite book| vauthors = Greenwald G, Reuter P, Lynch T |author-link=Glenn Greenwald | contribution=Lessons for Creating Fair and Successful Drug Policies| title=Drug Decriminalization in Portugal| publisher=Cato Institute| date=3 April 2009| contribution-url=http://www.cato.org/pubs/wtpapers/greenwald_whitepaper.pdf}}</ref>

{{TOC limit}}

== Uses ==
Coca leaves have been used by [[Andean civilizations]] since [[Andean civilizations|ancient times]].<ref name="Goldstein_2009">{{Cite journal | vauthors = Goldstein RA, DesLauriers C, Burda AM | title = Cocaine: history, social implications, and toxicity--a review | journal = Disease-a-Month | volume = 55 | issue = 1 | pages = 6–38 | date = January 2009 | pmid = 19081448 | doi = 10.1016/j.disamonth.2008.10.002 }}</ref> In ancient [[Wari culture]],<ref name="Valdez_2015">{{Cite journal | vauthors = Valdez LM, Taboada J, Valdez JE |title=Ancient Use of Coca Leaves in the Peruvian Central Highlands |journal=Journal of Anthropological Research |date=June 2015 |volume=71 |issue=2 |pages=231–258 |doi=10.3998/jar.0521004.0071.204|s2cid=163842955 |hdl=2027/spo.0521004.0071.204 |hdl-access=free }}</ref> [[Quechua people|Inca]] culture, and through modern successor [[Indigenous peoples|indigenous]] cultures of the [[Andes Mountains]], coca leaves are chewed, taken orally in the form of a [[Coca tea|tea]], or alternatively, prepared in a sachet wrapped around alkaline burnt ashes, and held in the [[buccal pouch|mouth against the inner cheek]]; it has traditionally been used as an [[anorectic]] and to combat the effects of cold and [[altitude sickness]],<ref name="Martin_1970">{{Cite journal | vauthors = Martin RT |title=The role of coca in the history, religion, and medicine of South American Indians |journal=Economic Botany |date=October 1970 |volume=24 |issue=4 |pages=422–438 |doi=10.1007/BF02860746|bibcode=1970EcBot..24..422M |s2cid=34523519 }}</ref><ref name="Plant_2008">{{Cite journal | vauthors = Plant T, Aref-Adib G | title = Travelling to new heights: practical high altitude medicine | journal = British Journal of Hospital Medicine | volume = 69 | issue = 6 | pages = 348–352 | date = June 2008 | pmid = 18646420 | doi = 10.12968/hmed.2008.69.6.29626 }}</ref> although its actual effectiveness has never been systematically studied.<ref name="Luks_2014">{{cite journal | vauthors = Luks AM, McIntosh SE, Grissom CK, Auerbach PS, Rodway GW, Schoene RB, Zafren K, Hackett PH | title = Wilderness Medical Society practice guidelines for the prevention and treatment of acute altitude illness: 2014 update | journal = Wilderness & Environmental Medicine | volume = 25 | issue = 4 Suppl | pages = S4–14 | date = December 2014 | pmid = 25498261 | doi = 10.1016/j.wem.2014.06.017 }}</ref>

Globally, in 2019, cocaine was used by an estimated 20 million people (0.4% of adults aged 15 to 64 years). The highest prevalence of cocaine use was in [[Australia]] and [[New Zealand]] (2.1%), followed by [[North America]] (2.1%), [[Western Europe|Western]] and [[Central Europe]] (1.4%), and [[South America|South]] and [[Central America]] (1.0%).<ref name="WDR2021">{{Cite book |title=World Drug Report 2021: Booklet 4 |date= 2021 |publisher=United Nations Office on Drugs and Crime |location=[S.l.]| page = 35|isbn=978-92-1-148361-1 |url=https://www.unodc.org/res/wdr2021/field/WDR21_Booklet_4.pdf |archive-url=https://web.archive.org/web/20210624081524/https://www.unodc.org/res/wdr2021/field/WDR21_Booklet_4.pdf |archive-date=24 June 2021 |url-status=live}}</ref> Since 1961, the [[Single Convention on Narcotic Drugs]] has required countries to make recreational use of cocaine a [[crime]].<ref>{{Cite journal | vauthors = Room R, Reuter P | title = How well do international drug conventions protect public health? | journal = Lancet | volume = 379 | issue = 9810 | pages = 84–91 | date = January 2012 | pmid = 22225673 | doi = 10.1016/s0140-6736(11)61423-2 | quote = The international treaties have also constrained national policy experimentation because they require nation states to criminalise drug use | s2cid = 23386203 }}</ref> In the United States, cocaine is regulated as a [[Schedule II Controlled Substance|Schedule II]] drug under the [[Controlled Substances Act]], meaning that it has a high potential for abuse but has an accepted medical use.<ref>{{Cite web |title=Drug Fact Sheet: Cocaine |url=https://www.dea.gov/sites/default/files/2020-06/Cocaine-2020_1.pdf |archive-url=https://web.archive.org/web/20200621183713/https://www.dea.gov/sites/default/files/2020-06/Cocaine-2020_1.pdf |archive-date=21 June 2020 |url-status=live |publisher=[[Drug Enforcement Administration]] (DEA) |access-date=17 June 2022}}</ref> While rarely used medically today, its accepted uses include serving as a topical local anesthetic for the upper [[respiratory tract]] and as an [[antihemorrhagic]] agent to stop bleeding in the mouth, throat, and nasal cavities.<ref>{{cite web |url=https://www.dea.gov/sites/default/files/2020-06/Cocaine-2020_1.pdf |title=Drug Fact Sheet: Cocaine |publisher=[[Drug Enforcement Administration]] (DEA) |access-date=29 June 2024 |archive-date=21 June 2020 |archive-url=https://web.archive.org/web/20200621183713/https://www.dea.gov/sites/default/files/2020-06/Cocaine-2020_1.pdf |url-status=live }}</ref>

=== Traditional medicine ===

==== Coca leaves ====
{{Main|Coca}}

[[File:Llipta on coca leaf.jpeg|thumb|''Llipta'' is used to improve extraction when chewing coca (Museo de la Coca, [[Cusco]], Peru).]]

It is legal for people to use [[coca]] leaves in the [[Andean Community]], such as [[Peru]] and [[Bolivia]], and Argentina, where they are chewed, consumed in the form of tea, or are sometimes incorporated into food products.<ref>{{Cite web|url=https://www.pri.org/stories/2011-04-01/tradition-chewing-coca|title=The tradition of chewing coca|date=15 August 2013 |access-date=6 May 2021|archive-date=6 May 2021|archive-url=https://web.archive.org/web/20210506205057/https://www.pri.org/stories/2011-04-01/tradition-chewing-coca|url-status=live}}</ref> Coca leaves are typically mixed with an alkaline substance (such as [[calcium hydroxide|slaked lime]]) and chewed into a wad that is retained in the [[buccal pouch]] (mouth between gum and cheek, much the same as [[chewing tobacco]] is chewed) and sucked of its juices. The juices are absorbed slowly by the [[mucous membrane]] of the inner cheek and by the [[gastrointestinal tract]] when swallowed.

===== Coca tea =====
{{Main|Coca tea}}

[[File:Mate de coca Peru.jpg|right|thumb|Two cups of coca tea]]

Coca herbal [[infusion]] (also referred to as [[coca tea]]) is used in coca-leaf producing countries much as any herbal medicinal infusion would elsewhere in the world. The free and legal commercialization of dried coca leaves under the form of filtration bags to be used as "coca tea" has been actively promoted by the governments of [[Peru]] and [[Bolivia]] for many years as a drink having [[alternative medicine|medicinal powers]]. In Peru, the [[National Coca Company]], a state-run corporation, sells cocaine-infused teas and other medicinal products and also exports leaves to the U.S. for medicinal use.<ref>{{Cite web|url=https://www.businessinsider.com/britain-is-the-worlds-biggest-exporter-of-legal-cocaine-and-heroin-2018-4|title=It's legal to manufacture cocaine and heroin for medical use — and Britain is the world's biggest exporter|vauthors=Embury-Dennis T|website=Business Insider|access-date=17 March 2019|archive-date=28 July 2020|archive-url=https://web.archive.org/web/20200728165239/https://www.businessinsider.com/britain-is-the-worlds-biggest-exporter-of-legal-cocaine-and-heroin-2018-4|url-status=live}}</ref> The effects of drinking coca tea are mild stimulation and mood lift.<ref>{{Cite web|url=https://www.drugs.com/illicit/cocaine.html|title=Cocaine: Effects, Hazards & Warnings|website=Drugs.com|access-date=17 March 2019|archive-date=28 July 2020|archive-url=https://web.archive.org/web/20200728162727/https://www.drugs.com/illicit/cocaine.html|url-status=live}}</ref>

In 1986 an article in the ''[[Journal of the American Medical Association]]'' revealed that U.S. [[health food store]]s were selling dried coca leaves to be prepared as an infusion as "Health Inca Tea". While the packaging claimed it had been "decocainized", no such process had actually taken place. The article stated that drinking two cups of the tea per day gave a mild [[stimulation]], increased [[heart rate]], and [[emotional mood|mood]] elevation, and the tea was essentially harmless.<ref name="Siegel_1986">{{Cite journal | vauthors = Siegel RK, Elsohly MA, Plowman T, Rury PM, Jones RT | title = Cocaine in herbal tea | journal = JAMA | volume = 255 | issue = 1 | page = 40 | date = January 1986 | pmid = 3940302 | doi = 10.1001/jama.1986.03370010042021 }}</ref>

===== Ypadu =====
{{Main|Ypadu}}

[[File:Mambe indigena coca colombia crista castellanos.jpg|thumb|Mambe or ypadu is made from toasted and ground coca leaves with ashes]]

[[Ypadu|Ypadú]] or ypadu (also known as mambé) is an unrefined, unconcentrated [[Powder (substance)|powder]] made from toasted [[coca]] leaves and the ash of various other plants. It is traditionally prepared and consumed by indigenous tribes in the Northwest Amazon.<ref>{{Cite journal | vauthors = Schultes RE |title=A New Method of Coca Preparation in the Colombian Amazon |date=1957 |journal=Botanical Museum Leaflets, Harvard University |volume=17 |issue=9 |pages=241–246 |doi=10.5962/p.168505 |jstor=41762172 |issn=0006-8098|doi-access=free }}</ref> Like coca teas consumed in [[Peru]] to adapt to sickness induced by high elevation, it has a long [[ethnobotanical]] history and cultural associations.

=== Medical ===
[[Karl Koller (ophthalmologist)|Karl Koller]]'s groundbreaking discovery of cocaine as a local anesthetic is regarded as the second most significant advance in the history of anesthesia. Although cocaine was once widely preferred for topical anesthesia, the search for replacement agents intensified due to rising costs, strict regulations, and its habit-forming potential.<ref name="Armbuster_2021" /> Cocaine is not included on the [[WHO Model List of Essential Medicines]]; the list formally excludes "cocaine and its combinations" as therapeutic alternatives to [[WHO Model List of Essential Medicines#Ophthalmological preparations|ophthalmological preparations]].<ref name="WHO-MHP-HPS-EML-2023.02">{{cite web |title=WHO Model List of Essential Medicines - 23rd list, 2023 |url=https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2023.02 |website=[[World Health Organization]] (WHO) }}</ref>

Today, the US [[Drug Enforcement Administration]] (DEA) classifies cocaine as a [[Schedule II drug]], recognizing its high potential for abuse but still permitting its limited use for medical purposes. However, current [[Pharmacoepidemiology|pharmacoepidemiological]] trends suggest that cocaine may soon reach the point where, in practical terms, it is no longer used medically in health care as a Schedule II substance. This report may prompt some states (such as North Dakota) and institutions to reconsider whether further efforts to identify alternative agents are needed. As physician boards—but not pharmacy boards—continue to assess knowledge of licit cocaine, attention may shift toward drugs with more contemporary medical use.<ref name="Armbuster_2021" />

Cocaine is rarely prescribed in modern medicine due to its high potential for abuse and significant risk of adverse effects; its use is now almost exclusively limited to [[health facility|health facilities]] for specific diagnostic procedures or surgeries.

====Topical====
Cocaine is used in medical practice as a [[topical medication]].<ref name="Armbuster_2021" /> Because it is not absorbed into the bloodstream in significant amounts when used this way, topical application does not produce the psychoactive effects associated with recreational cocaine use.

=====Topical anesthetic=====
{{See also|Moffett's solution}}
[[File:Cocaine hydrochloride CII for medicinal use.jpg|thumb|upright|Cocaine [[hydrochloride]]]]

Cocaine is sometimes used in [[otorhinolaryngology]] as a [[topical anesthetic]] and [[vasoconstrictor]] to help control pain and bleeding during surgery of the nose, mouth, throat, or [[lacrimal duct]]. It is also used for topical airway anaesthesia for procedures such as awake fibreoptic [[bronchoscopy]] or [[intubation]]. Although some absorption and systemic effects may occur, the use of cocaine as a topical anesthetic and vasoconstrictor is generally safe, rarely causing [[cardiovascular]] toxicity, [[glaucoma]], and [[mydriasis|pupil dilation]].<ref name="Dwyer_2016">{{Cite journal | vauthors = Dwyer C, Sowerby L, Rotenberg BW | title = Is cocaine a safe topical agent for use during endoscopic sinus surgery? | journal = The Laryngoscope | volume = 126 | issue = 8 | pages = 1721–1723 | date = August 2016 | pmid = 27075241 | doi = 10.1002/lary.25836 | type = Review | doi-access = free }}</ref><ref name="Latorre_1999">{{Cite journal | vauthors = Latorre F, Klimek L | title = Does cocaine still have a role in nasal surgery? | journal = Drug Safety | volume = 20 | issue = 1 | pages = 9–13 | date = January 1999 | pmid = 9935273 | doi = 10.2165/00002018-199920010-00002 | s2cid = 40598106 }}</ref> Occasionally, cocaine is mixed with [[adrenaline]] and [[sodium bicarbonate]] and used topically for surgery, a formulation called [[Moffett's solution]].<ref>{{Cite journal | vauthors = Benjamin E, Wong DK, Choa D | title = 'Moffett's' solution: a review of the evidence and scientific basis for the topical preparation of the nose | journal = Clinical Otolaryngology and Allied Sciences | volume = 29 | issue = 6 | pages = 582–587 | date = December 2004 | pmid = 15533141 | doi = 10.1111/j.1365-2273.2004.00894.x | doi-access = free }}</ref> It is occasionally used in surgeries involving the [[pharynx]] or [[nasopharynx]] to reduce pain, bleeding, and [[laryngospasm|vocal cord spasm]].<ref>{{Cite book |vauthors=Hamdan AL, Sataloff RT, Hawkshaw MJ |title=Office-Based Laryngeal Surgery |chapter=Topical Anesthesia in Office-Based Laryngeal Surgery |chapter-url=https://link.springer.com/chapter/10.1007/978-3-030-91936-8_6 |date=2022 |pages=123–137 |publisher=Springer |location=USA |doi=10.1007/978-3-030-91936-8_6 |isbn=978-3-030-91935-1 |access-date=18 July 2022 |archive-date=18 July 2022 |archive-url=https://web.archive.org/web/20220718085028/https://link.springer.com/chapter/10.1007/978-3-030-91936-8_6 |url-status=live }}</ref>

Nasal solution cocaine hydrochloride ('''Goprelto'''), an ester used for intranasal application, was approved for medical use in the United States in December 2017, and is indicated for the introduction of topical anesthesia of the mucous membranes for diagnostic procedures and surgeries on or through the nasal cavities of adults.<ref>{{Cite web | title=Drug Approval Package: Goprelto (cocaine hydrochloride) | website=U.S. [[Food and Drug Administration]] (FDA) | date=30 April 2018 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209963Orig1s000TOC.cfm | access-date=30 April 2020 | archive-date=28 July 2020 | archive-url=https://web.archive.org/web/20200728161852/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209963Orig1s000TOC.cfm }}</ref><ref name="Goprelto FDA label">{{Cite web | title=Goprelto – cocaine hydrochloride solution | website=DailyMed | date=3 January 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=689750b7-8e51-47d9-a428-078f3f6c9dec | access-date=30 April 2020 | archive-date=30 July 2020 | archive-url=https://web.archive.org/web/20200730202926/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=689750b7-8e51-47d9-a428-078f3f6c9dec | url-status=live }}</ref> Cocaine hydrochloride ('''Numbrino''') was approved for medical use in the United States in January 2020.<ref>{{Citation-attribution|1={{Cite web | title=Numbrino: FDA-Approved Drugs | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=209575 | access-date=30 April 2020 | archive-date=28 July 2020 | archive-url=https://web.archive.org/web/20200728172108/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=209575 | url-status=live }} }}</ref><ref name="Numbrino FDA label">{{Cite web | title=Numbrino – cocaine hydrochloride nasal solution | website=DailyMed | date=28 February 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=94f9b3f8-bce5-41ed-9453-c54ed1d6c269 | access-date=30 April 2020 | archive-date=30 July 2020 | archive-url=https://web.archive.org/web/20200730063812/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=94f9b3f8-bce5-41ed-9453-c54ed1d6c269 | url-status=live }}</ref> Headache and [[epistaxis]] are the most frequently reported adverse reactions with Goprelto,<ref name="Goprelto FDA label" /> while hypertension and tachycardia-including [[sinus tachycardia]]-are most common with Numbrino.<ref name="Numbrino FDA label" />

=====Ophthalmological use=====
Cocaine [[eye drop]]s have traditionally been used by [[Neurology|neurologists]] when examining people suspected of having [[Horner's syndrome|Horner syndrome]]. In Horner syndrome, [[sympathetic innervation]] to the eye is blocked. In a healthy eye, cocaine stimulates the [[sympathetic nervous system]] (SNS) by inhibiting norepinephrine reuptake, causing the [[pupil]] to dilate. In patients with Horner syndrome, sympathetic innervation to the eye is disrupted, so the affected pupil does not dilate in response to cocaine and remains constricted, or dilates to a lesser extent than the unaffected eye, which also receives the eye drop test. If both eyes dilate equally, the patient does not have Horner syndrome.<ref>{{Cite book | vauthors = Berkowitz AL |title=Clinical Neurology & Neuroanatomy: A Localization-Based Approach |publisher=McGraw Hill |year=2022 |isbn=978-1-260-45336-2 |edition=2nd |chapter=Chapter 10: Pupillary Control & Approach to Anisocoria: Cranial Nerves 2 & 3 |type=Digital}}</ref>

However, [[apraclonidine]] has largely replaced cocaine as the first-line pharmacologic agent for the diagnosis of Horner syndrome in routine clinical practice.<ref>{{cite journal | vauthors = Smit D | title = Pharmacologic testing in Horner's syndrome - a new paradigm. | journal = South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde | volume = 100 | issue = 11 | pages = 738–740 | date = 9 November 2010 | pmid = 21081027 | doi = 10.7196/samj.3773 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Freedman K, Brown S | title = Topical apraclonidine in the diagnosis of suspected Horner syndrome. | journal = Journal of Neuro-Ophthalmology | volume = 25 | issue = 2 | pages = 83–85 | date = June 2005 | pmid = 15937427 | doi = 10.1097/01.wno.0000165108.31731.36 }}</ref><ref name="Bremner_2019">{{cite journal | vauthors = Bremner F | title = Apraclonidine Is Better Than Cocaine for Detection of Horner Syndrome. | journal = Frontiers in Neurology | volume = 10 | article-number = 55 | date = 2019 | pmid = 30804875 | pmc = 6371044 | doi = 10.3389/fneur.2019.00055 | doi-access = free }}</ref>

=== Recreational ===
{{For|Cocaine or crack cocaine combined with other drugs|List of polysubstance combinations}}
[[File:Peruvian Flake Cocaine.jpg|thumb|Peruvian flake cocaine on a metal milligram [[weighing scale|scale]] tray]]

Recreational cocaine is typically not taken by mouth due to its poor bioavailability, instead it is usually [[Nasal administration|snorted]] or [[injection (medicine)|injected]]. Cocaine hydrochloride can also be chemically converted into its [[free base]] form, [[crack cocaine]], which can be vaporized.{{Citation needed|date=November 2025}}

Cocaine is a [[central nervous system]] [[stimulant]].<ref name="WHO2004">{{Cite book|author=World Health Organization|year=2004|url=https://books.google.com/books?id=G9OhG-dZdAwC&pg=PA89|title=Neuroscience of psychoactive substance use and dependence|page=89|publisher=World Health Organization |isbn=978-92-4-156235-5|url-status=live|archive-url=https://web.archive.org/web/20160430122452/https://books.google.com/books?id=G9OhG-dZdAwC&pg=PA89|archive-date=30 April 2016}}</ref> Its effects can last from 15 minutes to an hour. The duration of cocaine's effects depends on the amount taken and the route of administration.<ref name="WHO2007">{{Cite book|author=World Health Organization|year=2007|url=https://books.google.com/books?id=ptVjyRs7AdsC&pg=PA242|title=International medical guide for ships|page=242|publisher=World Health Organization |isbn=978-92-4-154720-8|url-status=live|archive-url=https://web.archive.org/web/20160430152905/https://books.google.com/books?id=ptVjyRs7AdsC&pg=PA242|archive-date=30 April 2016}}</ref> Cocaine can be in the form of fine white powder and has a bitter taste. [[Crack cocaine]] is a smokeable form of cocaine made into small "rocks" by processing cocaine with [[sodium bicarbonate]] (baking soda) and water.<ref name="Zimmerman_2012" /><ref name="Sordo_2014"/>

Cocaine use leads to increases in alertness, feelings of well-being and [[euphoria]], increased energy and [[motor control|motor]] activity, and increased feelings of competence and [[Human sexuality|sexuality]].<ref name="Donroe_2017">{{Cite journal | vauthors = Donroe JH, Tetrault JM | title = Substance Use, Intoxication, and Withdrawal in the Critical Care Setting | journal = Critical Care Clinics | volume = 33 | issue = 3 | pages = 543–558 | date = July 2017 | pmid = 28601134 | doi = 10.1016/j.ccc.2017.03.003 | type = Review }}</ref>

Analysis of the [[correlation]] between the use of 18 various [[psychoactive substance]]s shows that cocaine use correlates with the use of other "[[Club drug|party drugs]]" (e.g., [[MDMA]], [[amphetamine]]), as well as with [[heroin]] and [[benzodiazepine]]s use, and can be considered as a bridge between the use of different groups of drugs.<ref>{{Cite book | vauthors = Fehrman E, Egan V, Gorban AN, Levesley J, Mirkes EM, Muhammad AK |date= 2019|title= Personality Traits and Drug Consumption. A Story Told by Data|doi= 10.1007/978-3-030-10442-9|publisher= Springer, Cham|isbn=978-3-030-10441-2 |arxiv= 2001.06520  |s2cid= 151160405}}</ref>

==== Insufflation ====
[[File:Cocaine lines 2.jpg|thumb|left|Lines of cocaine prepared for snorting. [[Contaminated currency]] such as banknotes might serve as a [[fomite]] of diseases like hepatitis C<ref name="LV">{{cite web |url=http://cocaine.org/cokemoney/banknotes.html |title='Shared banknote' health warning to cocaine users |access-date=26 July 2008 | vauthors = Veevers L |date=1 October 2006 |work=The Observer }}</ref>]]

Nasal [[insufflation (medicine)|insufflation]] (known colloquially as "snorting", "sniffing", or "blowing") is a common method of ingestion of recreational powdered cocaine.<ref>{{Cite web|title=DrugFacts: Cocaine|url=https://www.drugabuse.gov/publications/drugfacts/cocaine|publisher=National Institute on Drug Abuse|access-date=11 July 2015|date=April 2013|url-status=live|archive-url=https://web.archive.org/web/20150711234545/https://www.drugabuse.gov/publications/drugfacts/cocaine|archive-date=11 July 2015}}</ref> The drug coats and is absorbed through the mucous membranes lining the [[nasal passages]]. Cocaine's desired euphoric effects are delayed when snorted through the nose by about five minutes. This occurs because cocaine's absorption is slowed by its constricting effect on the blood vessels of the nose.<ref name="Zimmerman_2012" /> Insufflation of cocaine also leads to the longest duration of its effects (60–90 minutes).<ref name="Zimmerman_2012" /> When insufflating cocaine, absorption through the nasal membranes is approximately 30–60%<ref>{{Cite web|title=The Dangers Of Snorting Cocaine (Insufflation)|url=https://vertavahealth.com/cocaine/insufflation/|access-date=25 February 2022|website=Vertava Health|archive-date=8 April 2022|archive-url=https://web.archive.org/web/20220408044303/https://vertavahealth.com/cocaine/insufflation/|url-status=live}}</ref>

Most [[Contaminated currency|banknotes have traces of cocaine]] on them; this has been confirmed by studies done in several countries.<ref>{{cite web | vauthors = Mikkelson B |url= http://www.snopes.com/business/money/cocaine.asp|title=Drug Money |date=9 July 2002 |access-date=23 July 2008 |publisher=Snopes}}</ref> In 1994, the [[United States Court of Appeals for the Ninth Circuit|US 9th Circuit Court of Appeals]] cited findings that in Los Angeles, three out of four banknotes were tainted by cocaine or another illicit drug.<ref>{{cite news | vauthors = Abrahamson A |title=Prevalence of Drug-Tainted Money Voids Case Law: Court cites findings that more than 75% of currency in L.A. bears traces of cocaine or other illegal substances |url=https://pqasb.pqarchiver.com/latimes/access/59564073.html?dids=59564073:59564073&FMT=ABS&FMTS=ABS:FT&type=current&date=Nov+13%2C+1994&author=ALAN+ABRAHAMSON&pub=Los+Angeles+Times+(pre-1997+Fulltext)&edition=&startpage=1&desc=Prevalence+of+Drug-Tainted+Money+Voids+Case+Law%3A+Court+cites+findings+that+more+than+75%25+of+currency+in+L.A.+bears+traces+of+cocaine+or+other+illegal+substances. |work=Los Angeles Times |date=13 November 1994 |access-date=23 July 2008 |archive-date=4 June 2011 |archive-url=https://web.archive.org/web/20110604092358/http://pqasb.pqarchiver.com/latimes/access/59564073.html?dids=59564073:59564073&FMT=ABS&FMTS=ABS:FT&type=current&date=Nov+13,+1994&author=ALAN+ABRAHAMSON&pub=Los+Angeles+Times+(pre-1997+Fulltext)&edition=&startpage=1&desc=Prevalence+of+Drug-Tainted+Money+Voids+Case+Law:+Court+cites+findings+that+more+than+75%+of+currency+in+L.A.+bears+traces+of+cocaine+or+other+illegal+substances. }}</ref><ref>{{cite news | vauthors = Price DM |title=Use of Drug-Sniffing Dogs Challenged;ACLU Backs Complaint by Men Whose Pocket Cash Was Seized |url=https://pqasb.pqarchiver.com/washingtonpost/access/72586089.html?dids=72586089:72586089&FMT=ABS&FMTS=ABS:FT&date=May+6%2C+1990&author=Debbie+M.+Price&pub=The+Washington+Post+(pre-1997+Fulltext)&edition=&startpage=d.01&desc=Use+of+Drug-Sniffing+Dogs+Challenged%3BACLU+Backs+Complaint+by+Men+Whose+Pocket+Cash+Was+Seized |archive-url=https://web.archive.org/web/20110604092431/http://pqasb.pqarchiver.com/washingtonpost/access/72586089.html?dids=72586089:72586089&FMT=ABS&FMTS=ABS:FT&date=May+6,+1990&author=Debbie+M.+Price&pub=The+Washington+Post+(pre-1997+Fulltext)&edition=&startpage=d.01&desc=Use+of+Drug-Sniffing+Dogs+Challenged%3BACLU+Backs+Complaint+by+Men+Whose+Pocket+Cash+Was+Seized |archive-date=4 June 2011 |newspaper=The Washington Post |date=6 May 1990 |access-date=23 July 2008 }}</ref>

[[Snuff spoon]]s, hollowed-out [[pen]]s, cut [[drinking straw|straws]], pointed ends of keys,<ref>{{Cite web | vauthors = Rossen J |date=19 March 2021|title=Sniffing Around the History of the McDonald's 'Cocaine Spoon'|url=https://www.mentalfloss.com/article/642413/mcdonalds-cocaine-spoon-controversy|access-date=14 June 2021|website=www.mentalfloss.com|archive-date=8 July 2024|archive-url=https://web.archive.org/web/20240708191807/https://www.mentalfloss.com/article/642413/mcdonalds-cocaine-spoon-controversy|url-status=live}}</ref> long [[fingernails]] or [[artificial nails]], and (clean) [[tampon]] applicators are also used to insufflate cocaine. The cocaine typically is poured onto a flat, hard surface and divided into "bumps", "lines", or "rails", and then insufflated.<ref>{{Cite web |url=https://www.cesar.umd.edu/cesar/drugs/cocaine.asp#Terminology |title=Cocaine terminology | work = Center for Substance use and Addiction Research – CESAR | publisher = University of Maryland |url-status=live |archive-url=https://web.archive.org/web/20070709115212/https://www.cesar.umd.edu/cesar/drugs/cocaine.asp#Terminology |archive-date=9 July 2007 }}</ref> A 2001 study reported that the sharing of straws used to "snort" cocaine can spread blood diseases such as [[hepatitis C]].<ref>{{Cite journal | vauthors = Bonkovsky HL, Mehta S | title = Hepatitis C: a review and update | journal = Journal of the American Academy of Dermatology | volume = 44 | issue = 2 | pages = 159–182 | date = February 2001 | pmid = 11174373 | doi = 10.1067/mjd.2001.109311 }}</ref>

===== Cocaine spoon =====
[[File:Stopper, snuff bottle (AM 687402-2).jpg|thumb|Chinese snuff bottle stopper with a spoon]]

Historically, [[snuff spoon]]s were used for cocaine in the 20th century, hence the names "cocaine spoon" and "coke spoon". Some local statutes in the US treat spoons that are too small and thus "unsuited for the typical, lawful uses of a spoon" as [[drug paraphernalia]].<ref>{{cite web |title=Code of ordinances village of Dundee, Michigan. Chapter 51. |url=https://library.municode.com/mi/dundee/codes/code_of_ordinances?nodeId=PTIICOOR_CH51DRARNUPR_ARTIDRPA_S51-1DE |publisher=[[Dundee, Michigan|Village of Dundee]]}}</ref><ref>{{Cite web |title=Code of Ordinances{{snd}}Clark County, NV |url=https://library.municode.com/nv/clark_county/codes/code_of_ordinances?nodeId=TIT12PUPESAMO_CH12.06DRPA |archive-url=https://web.archive.org/web/20240913094223/https://library.municode.com/nv/clark_county/codes/code_of_ordinances?nodeId=TIT12PUPESAMO_CH12.06DRPA |archive-date=13 September 2024 |access-date=13 September 2024 |website=Municode Library}}</ref><ref>{{Cite web |title=Township of Middlesex, PA Drugs and Drug Paraphernalia |url=https://ecode360.com/11231035#11231037 |archive-url=https://web.archive.org/web/20240913094426/https://ecode360.com/11231035#11231037 |archive-date=13 September 2024 |access-date=13 September 2024 |website=eCode360}}</ref>

==== Injection ====
Subjective effects not commonly shared with other methods of administration include a ringing in the ears moments after injection (usually when over 120&nbsp;milligrams) lasting 2 to 5&nbsp;minutes including [[tinnitus]] and audio distortion. This is colloquially referred to as a "bell ringer". In a study of cocaine users, the average time taken to reach peak subjective effects was 3.1&nbsp;minutes.<ref name="Volkow_2000">{{Cite journal |vauthors=Volkow ND, Wang GJ, Fischman MW, Foltin R, Fowler JS, Franceschi D, Franceschi M, Logan J, Gatley SJ, Wong C, Ding YS, Hitzemann R, Pappas N |date=August 2000 |title=Effects of route of administration on cocaine-induced dopamine transporter blockade in the human brain |journal=Life Sciences |volume=67 |issue=12 |pages=1507–1515 |doi=10.1016/S0024-3205(00)00731-1 |pmid=10983846}}</ref> The euphoria passes quickly. Aside from the toxic effects of cocaine, there is also the danger of circulatory [[embolism|emboli]] from the insoluble substances that may be used to cut the drug. As with all injected [[illicit substances]], there is a risk of the user contracting [[Blood-borne disease|blood-borne infections]] if sterile injecting equipment is not available or used.

==== Inhalation ====

===== Cocaine paste =====
{{Main|Cocaine paste}}

[[Coca paste]] (paco, basuco, oxi, pasta) is a crude [[extract]] of the [[coca leaf]] which contains 40% to 91% [[cocaine freebase]] along with companion coca alkaloids and varying quantities of [[benzoic acid]], [[methanol]], and [[kerosene]]. The caustic reactions associated with the local application of coca paste prevents its use by oral, intranasal, mucosal, intramuscular, intravenous or subcutaneous routes. Coca paste can only be smoked when combined with a combustible material such as tobacco or cannabis.<ref name="Arif_1987">{{cite book | veditors = Arif A | title=Adverse health consequences of cocaine abuse | location = Geneva | publisher=[[World Health Organization]] (WHO) | year=1987 | url=https://iris.who.int/bitstreams/de99504b-4a88-4b77-b4ae-35c68bec4c5e/download | hdl=10665/37270 }}</ref>

Crude cocaine preparation intermediates are marketed as cheaper alternatives to pure cocaine to local markets while the more expensive end product is exported to United States and European markets. [[Freebase cocaine]] paste preparations can be smoked. The psychological and physiological effects of the ''paco'' are quite severe.<ref name="Jeri_1984">{{cite journal | vauthors = Jeri F | title = Coca-paste smoking in some Latin American countries: a severe and unabated form of addiction | journal = Bulletin on Narcotics | volume = 36 | issue = 2 | year = 1984 }}</ref><ref name="Phillips_2009">{{cite journal | vauthors = Phillips K, Luk A, Soor GS, Abraham JR, Leong S, Butany DJ | title = Cocaine Cardiotoxicity | journal = American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions | volume = 9 | issue = 3 | pages = 177–196 | date = June 2009 | pmid = 19463023 | doi = 10.1007/bf03256574 | s2cid = 70385136 }}</ref> Media usually report that it is extremely toxic and addictive.<ref name="Mcdonnell_2007">{{cite web | vauthors = Mcdonnell PJ | title = Argentina confronts plague named Paco | date = 25 May 2007 | url = https://www.latimes.com/archives/la-xpm-2007-may-25-fg-paco25-story.html | work = Los Angeles Times | access-date = 5 April 2009 }}</ref><ref name="Legrand_2009">{{cite news | vauthors = Legrand C | title = En Argentine, des mères se mobilisent contre le "paco", la drogue des pauvres – Amériques | date = 26 March 2009 | url = http://www.lemonde.fr/ameriques/article/2009/03/26/en-argentine-des-meres-se-mobilisent-contre-le-paco-la-drogue-des-pauvres_1172844_3222.html#ens_id=1170226 | newspaper = Le Monde.fr | access-date = 5 April 2009 }}</ref><ref name="Navai_2008">{{cite news | vauthors = Navai R | title = Cocaine's lethal leftovers take violent grip on slum children | location = London | date = 28 April 2008 | url = http://www.timesonline.co.uk/tol/news/world/us_and_americas/article3828309.ece | archive-url = https://web.archive.org/web/20080726120712/http://www.timesonline.co.uk/tol/news/world/us_and_americas/article3828309.ece | archive-date = 26 July 2008 | work = The Times | access-date = 5 April 2009 }} {{Registration required}}</ref> According to a study by Intercambios, media appear to exaggerate the effects of ''paco''. These stereotypes create a sense that nothing can be done to help a ''paco'' addict and thus stand in the way of rehabilitation programs.<ref>{{cite web | vauthors = Valente M | title = DRUGS-ARGENTINA: 'Pasta Base' Destructive but Not Invincible | date = 12 September 2006 | url = http://ipsnews.net/news.asp?idnews=34692 | publisher = Ipsnews.net | access-date = 5 April 2009 | archive-url = https://web.archive.org/web/20090213162639/http://www.ipsnews.net/news.asp?idnews=34692 | archive-date = 13 February 2009 }}</ref>

===== Crack cocaine =====
{{Further|Crack cocaine}}

[[File:Man smoking crack cocaine in Bogotá, Colombia..jpg|thumb|Man smoking crack cocaine in Bogotá, Colombia]]

Powder cocaine (cocaine hydrochloride) must be heated to a high temperature to be smoked (about 197&nbsp;°C), and considerable decomposition/burning occurs at these high temperatures. This effectively destroys some of the cocaine and yields a sharp, acrid, and foul-tasting smoke. Cocaine base/crack can be smoked because it vaporizes with little or no decomposition at {{convert|98|°C|0|abbr=on}},<ref>{{Cite book | vauthors = Ries RK, Miller SC, Fiellin DA |title=Principles of addiction medicine |url=https://books.google.com/books?id=j6GGBud8DXcC&pg=PT166 |access-date=5 January 2014 |year=2009 |publisher=[[Lippincott Williams & Wilkins]] |isbn=978-0-7817-7477-2 |page=137 |url-status=live |archive-url=https://web.archive.org/web/20140404151454/https://books.google.com/books?id=j6GGBud8DXcC&pg=PT166 |archive-date=4 April 2014 }}</ref> which is below the boiling point of water.

==Contraindications==
{{For|harm caused by the freebase form|Crack cocaine#Contraindications}}

Cocaine should not be used in individuals with a known allergy or [[hypersensitivity]] to the drug or any components of its topical formulation. It is also contraindicated in [[Geriatrics|elderly patients]] and those with a history of hypertension or [[cardiovascular disease]].<ref name="Richards_2023">{{cite book | vauthors = Richards JR, Laurin EG | chapter = Cocaine | date = June 2023 | title = StatPearls [Internet]. | location = Treasure Island (FL) | publisher = StatPearls Publishing | pmid=28613520}}</ref>

===Pregnancy===
{{Main|Prenatal cocaine exposure|Teratology#Cocaine}}

[[Prenatal cocaine exposure]] (PCE) may occur when a pregnant woman uses cocaine.<ref name="Buckingham-Howes_2013">{{cite journal | vauthors = Buckingham-Howes S, Berger SS, Scaletti LA, Black MM | title = Systematic Review of Prenatal Cocaine Exposure and Adolescent Development | journal = Pediatrics | volume = 131 | issue = 6 | pages = e1917–e1936 | date = 2013 | pmid = 23713107 | pmc = 3666107 | doi = 10.1542/peds.2012-0945 }}</ref><ref name="Lambert_2012">{{cite journal | vauthors = Lambert B, Bauer C | title = Developmental and behavioral consequences of prenatal cocaine exposure: a review | journal = Journal of Perinatology | volume = 32 | issue = 11 | pages = 819–828 | date = November 2012 | pmid = 22791278 | pmc = 4143247 | doi = 10.1038/jp.2012.90 }}</ref><ref name="McCarthy_2014">{{cite book | vauthors = McCarthy DM, Kabir ZD, Bhide PG, Kosofsky BE | chapter = Effects of prenatal exposure to cocaine on brain structure and function | title = Progress in Brain Research | volume = 211 | pages = 277–289 | year = 2014 | pmid = 24968785 | doi = 10.1016/B978-0-444-63425-2.00012-X | isbn = 978-0-444-63425-2 }}</ref><ref name="Eiden_2009">{{cite journal | vauthors = Eiden RD, McAuliffe S, Kachadourian L, Coles C, Colder C, Schuetze P | title = Effects of prenatal cocaine exposure on infant reactivity and regulation | journal = Neurotoxicology and Teratology | volume = 31 | issue = 1 | pages = 60–68 | date = January 2009 | pmid = 18822371 | pmc = 2631277 | doi = 10.1016/j.ntt.2008.08.005 | bibcode = 2009NTxT...31...60E }}</ref>

Under the former FDA [[pregnancy category]] system, cocaine was classified as a Category C drug. Its potential to cause harm to the fetus is not fully known, so it should only be administered to pregnant women if clearly necessary.<ref name="Richards_2023" />

Cocaine can act as a [[teratogen]], having various effects on the developing fetus.<ref name="ASU">{{Cite encyclopedia |title=Cocaine as a Teratogen | encyclopedia = Embryo Project Encyclopedia |url=https://embryo.asu.edu/pages/cocaine-teratogen |access-date=7 April 2025 | publisher = Arizona State University }}</ref> Some common teratogenic defects caused by cocaine include [[hydronephrosis]], [[Cleft lip and cleft palate|cleft palate]], [[polydactyly]], and [[down syndrome]].<ref name="ASU" /> Cocaine as a drug has a low molecular weight and high water and lipid solubility which enables it to cross the [[placenta]] and fetal blood-brain barrier.<ref>{{cite journal | vauthors = Singer L, Arendt R, Minnes S | title = Neurodevelopmental effects of cocaine | journal = Clinics in Perinatology | volume = 20 | issue = 1 | pages = 245–262 | date = March 1993 | pmid = 8458168 | pmc = 4181371 | doi = 10.1016/S0095-5108(18)30422-6 }}</ref> Because cocaine is able to pass through the placenta and enter the fetus, the fetus' circulation can be negatively affected. With restriction of fetal circulation, the development of organs in the fetus can be impacted, even resulting in [[Gastroschisis|intestines developing outside]] of the fetus' body.<ref name="ASU" /> Cocaine use during pregnancy can also result in [[obstetric labor complication]]s such as, [[placental abruption]],<ref>{{cite journal | vauthors = Flowers D, Clark JF, Westney LS | title = Cocaine intoxication associated with abruptio placentae | journal = Journal of the National Medical Association | volume = 83 | issue = 3 | pages = 230–232 | date = March 1991 | pmid = 2038082 | pmc = 2627035 }}</ref> [[preterm birth]] or delivery, [[uterine rupture]], [[miscarriage]], and [[stillbirth]].<ref name="ASU" /><ref>{{cite journal | vauthors = Cain MA, Bornick P, Whiteman V | title = The maternal, fetal, and neonatal effects of cocaine exposure in pregnancy | journal = Clinical Obstetrics and Gynecology | volume = 56 | issue = 1 | pages = 124–132 | date = March 2013 | pmid = 23314714 | doi = 10.1097/GRF.0b013e31827ae167 }}</ref> Prenatal cocaine exposure may cause subtle cognitive deficits and lower the chance of above-average IQ by age 4, but supportive caregiving can significantly improve outcomes.<ref>{{cite journal | vauthors = Singer LT, Minnes S, Short E, Arendt R, Farkas K, Lewis B, Klein N, Russ S, Min MO, Kirchner HL | title = Cognitive outcomes of preschool children with prenatal cocaine exposure | journal = JAMA | volume = 291 | issue = 20 | pages = 2448–2456 | date = May 2004 | pmid = 15161895 | pmc = 1901972 | doi = 10.1001/jama.291.20.2448 }}</ref>

===Breastfeeding===
Mothers utilizing recreational drugs, such as cocaine, methamphetamines, PCP, and heroin, should not [[Breastfeeding|breastfeed]].<ref name="CDC-2021e">{{cite web |date=10 August 2021|title=When breastfeeding or feeding expressed milk is not recommended.|url=https://www.cdc.gov/breastfeeding/breastfeeding-special-circumstances/contraindications-to-breastfeeding.html|access-date=14 November 2021|website=U.S. [[Centers for Disease Control and Prevention]] (CDC) }}</ref><ref name="Eglash_2020">{{cite book| title=The Little Green Book of Breastfeeding Management for Physicians & Other Healthcare Providers| vauthors= Eglash A, Leeper K| publisher=The Institute for the Advancement of Breastfeeding and Lactation Education| year=2020|isbn=978-0-9987789-0-7|edition=7|location=Madison, WI}}</ref>{{rp|13}}

The [[March of Dimes]] said "it is likely that cocaine will reach the baby through breast milk," and advises the following regarding cocaine use during pregnancy:
{{Blockquote|Cocaine use during pregnancy can affect a pregnant woman and her unborn baby in many ways. During the early months of pregnancy, it may increase the risk of [[miscarriage]]. Later in pregnancy, it can trigger [[Preterm birth|preterm labor]] (labor that occurs before 37 weeks of pregnancy) or cause the baby to grow poorly. As a result, cocaine-exposed babies are more likely than unexposed babies to be born with [[low birth weight]] (less than {{convert|5.5|lb|kg|disp=or|abbr=on}}). Low-birthweight babies are 20 times more likely to die in their first month of life than normal-weight babies, and face an increased risk of [[developmental disability|lifelong disabilities]] such as mental retardation and [[cerebral palsy]]. Cocaine-exposed babies also tend to have smaller heads, which generally reflect smaller brains. Some studies suggest that cocaine-exposed babies are at increased risk of birth defects, including urinary tract defects and, possibly, heart defects. Cocaine also may cause an unborn baby to have a [[stroke]], irreversible [[brain injury]], or a [[myocardial infarction]].<ref name="mod">{{Cite web |url=http://www.marchofdimes.org/pregnancy/illicit-drug-use-during-pregnancy.aspx |title=Street Drugs and pregnancy |work=March of Dimes |access-date=26 May 2009 |archive-date=5 September 2015 |archive-url=https://web.archive.org/web/20150905080845/http://www.marchofdimes.org/pregnancy/illicit-drug-use-during-pregnancy.aspx }}</ref>}}

== Adverse effects ==
{{For|harm caused by the freebase form|Crack cocaine#Adverse effects}}
{{See also|Cocaine#Lacing}}

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| HarmCausedByDrugsTable.svg
 | A 2010 study ranking various illegal and legal drugs based on statements by drug-harm experts in the UK. Crack cocaine and cocaine were found to be the third and fifth overall most dangerous drugs respectively.<ref>{{Cite journal | vauthors = Nutt DJ, King LA, Phillips LD | title = Drug harms in the UK: a multicriteria decision analysis | journal = Lancet | volume = 376 | issue = 9752 | pages = 1558–65 | date = November 2010 | pmid = 21036393 | doi = 10.1016/S0140-6736(10)61462-6 | s2cid = 5667719 | citeseerx = 10.1.1.690.1283 }}</ref>
| Rational harm assessment of drugs bar plot.svg
 | 2007 [[Delphi method|delphic analysis]] regarding 20 popular recreational drugs based on expert opinion in the UK. Cocaine was ranked the 2nd in dependence and physical harm and 3rd in social harm.<ref name="Nutt_2007">{{Cite journal|vauthors = Nutt D, King LA, Saulsbury W, Blakemore C|title = Development of a rational scale to assess the harm of drugs of potential misuse|journal = Lancet|volume = 369|issue = 9566|pages = 1047–53|date = March 2007|pmid = 17382831|doi = 10.1016/S0140-6736(07)60464-4|s2cid = 5903121|author-link4 = Colin Blakemore|author-link1 = David Nutt }}</ref>
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=== Cardiac complications ===
Cocaine use can cause serious heart problems like sudden death, heart inflammation, [[arrhythmia]]s, and heart attacks. It triggers coronary artery spasms, increases blood clot risk, and accelerates [[atherosclerosis]], especially with long-term use. The severity of heart disease often relates to how long and how often cocaine is used.<ref>{{cite journal | vauthors = Talarico GP, Crosta ML, Giannico MB, Summaria F, Calò L, Patrizi R | title = Cocaine and coronary artery diseases: a systematic review of the literature | journal = Journal of Cardiovascular Medicine | volume = 18 | issue = 5 | pages = 291–294 | date = May 2017 | pmid = 28306693 | doi = 10.2459/JCM.0000000000000511 }}</ref> It can also become a serious risk at high doses due to cocaine's blocking effect on cardiac sodium channels.<ref name="O'Leary_2010" />

===Levamisole syndromes===
[[Levamisole]] is one of the most common adulterants found in illicit cocaine, with studies showing that between 2009 and 2016, 50–70% of all cocaine specimens worldwide contained levamisole, reflecting similar high rates of contamination across North America and Europe.<ref name="Vonmoos_2018">{{cite journal | vauthors = Vonmoos M, Hirsiger S, Preller KH, Hulka LM, Allemann D, Herdener M, Baumgartner MR, Quednow BB | title = Cognitive and neuroanatomical impairments associated with chronic exposure to levamisole-contaminated cocaine | journal = Translational Psychiatry | volume = 8 | issue = 1 | article-number = 235 | date = October 2018 | pmid = 30368522 | pmc = 6204136 | doi = 10.1038/s41398-018-0279-3 }}</ref> Before trafficking to the United States, the cocaine is frequently adulterated with levamisole.<ref name="Buchanan_2010">{{cite journal |vauthors=Buchanan JA, Oyer RJ, Patel NR, Jacquet GA, Bornikova L, Thienelt C, Shriver DA, Shockley LW, Wilson ML, Hurlbut KM, Lavonas EJ |date=June 2010 |title=A confirmed case of agranulocytosis after use of cocaine contaminated with levamisole |journal=Journal of Medical Toxicology |volume=6 |issue=2 |pages=160–164 |doi=10.1007/s13181-010-0060-3 |pmc=3550277 |pmid=20358411}}</ref> By October 2017, this figure had risen further, with the US [[Drug Enforcement Administration]] (DEA) reporting that 87% of seized and analyzed cocaine bricks in the United States contained levamisole, making it the most common adulterant in cocaine at that time.<ref name="DIR-040-17_2017-NDTA.pdf">{{cite web |title=2017 National Drug Threat Assessment |url=https://www.dea.gov/sites/default/files/2018-07/DIR-040-17_2017-NDTA.pdf |publisher=[[Drug Enforcement Administration]] (DEA) |date=1 October 2017 |access-date= 17 June 2025}}</ref>

In the body, levamisole is converted into [[aminorex]], a substance with [[amphetamine]]-like stimulant effects and a long duration of action.<ref>{{cite journal | vauthors = Solomon N, Hayes J | title = Levamisole: A High Performance Cutting Agent | journal = Academic Forensic Pathology | volume = 7 | issue = 3 | pages = 469–476 | date = September 2017 | pmid = 31239995 | pmc = 6474566 | doi = 10.23907/2017.039 }}</ref> Levamisole-adulterated cocaine is associated with cocaine- and levamisole-induced [[vasculitis]] (CLIV) and cocaine/levamisole-associated [[autoimmune disease|autoimmune syndrome]] (CLAAS).<ref name="Gill_2021" /><ref name="Cascio_2018" /> [[List of reagent testing color charts|Reagent testing kits]] can be used to detect the presence of cocaine and levamisole.<ref name="DS_Instructions_Reagents_v17Spring24.pdf">{{cite web | title = How to Test Your Drugs With Reagents| work = DanceSafe  |url=https://dancesafe.org/wp-content/uploads/2024/05/DS_Instructions_Reagents_v17Spring24.pdf}}</ref>

====Levamisole-induced necrosis syndrome====
{{Main|Levamisole-induced necrosis syndrome}}

[[Levamisole-induced necrosis syndrome]] (LINES) is a complication characterized by [[necrosis]] resulting from exposure to [[levamisole]], a medication with immunomodulatory properties. While LINES can occur with levamisole use alone, most reported cases are associated with the use of cocaine adulterated with levamisole as a cutting agent. This syndrome is marked by skin necrosis, often affecting areas such as the ears, face, and extremities, and is thought to result from levamisole's effects on blood vessels and the immune system.<ref>{{cite journal | vauthors = Fredericks C, Yon JR, Alex G, Morton M, Messer T, Bokhari F, Poulakidas S | title = Levamisole-induced Necrosis Syndrome: Presentation and Management | journal = Wounds | volume = 29 | issue = 3 | pages = 71–76 | date = March 2017 | pmid = 28355139 }}</ref>

====Cocaine/levamisole-associated syndromes====
The skin necrosis associated with levamisole toxicity ranges from [[leukocytoclastic vasculitis]] to occlusive [[vasculopathy]]. Several cases of severe agranulocytosis associated with cocaine use have been reported since 2006. With the recently recognized dermal disease, the face and ears are commonly affected, especially the bilateral [[helix (ear)|helices]] and cheeks. However, there have also been case reports of involvement of the abdomen, chest, lower buttocks and legs.<ref name="Morris_2012">{{cite journal | vauthors = Morris GW, Mason BC, Harris Sprunger R, Hake Harris H, White LA, Patterson DA | title = Levamisole-adulterated cocaine: a case series | journal = Journal of the American Board of Family Medicine | volume = 25 | issue = 4 | pages = 531–535 | year = 2012 | pmid = 22773722 | doi = 10.3122/jabfm.2012.04.110287 | doi-access = free }}</ref><ref name="lee2012">{{cite journal | vauthors = Lee KC, Ladizinski B, Federman DG | title = Complications associated with use of levamisole-contaminated cocaine: an emerging public health challenge | journal = Mayo Clinic Proceedings | volume = 87 | issue = 6 | pages = 581–586 | date = June 2012 | pmid = 22677078 | pmc = 3498128 | doi = 10.1016/j.mayocp.2012.03.010 }}</ref>

During the mid-2010s, levamisole was found in most cocaine products available in both the United States and Europe.<ref>{{cite web |title=Cocaine retail markets: multiple indicators suggest continued growth and diversification {{!}} www.euda.europa.eu |url=https://www.euda.europa.eu/publications/eu-drug-markets/cocaine/retail-markets_en |website=www.euda.europa.eu}}</ref> Levamisole is known to cause an acute condition involving a severe and dangerous lowered white blood cell count, known as [[agranulocytosis]], in cocaine users, and may also accentuate cocaine's effects.<ref name="chang2010">{{cite journal | vauthors = Chang A, Osterloh J, Thomas J | title = Levamisole: a dangerous new cocaine adulterant | journal = Clinical Pharmacology and Therapeutics | volume = 88 | issue = 3 | pages = 408–411 | date = September 2010 | pmid = 20668440 | doi = 10.1038/clpt.2010.156 | s2cid = 31414939 }}</ref><ref>{{cite journal | vauthors = Tallarida CS, Egan E, Alejo GD, Raffa R, Tallarida RJ, Rawls SM | title = Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo | journal = Neuropharmacology | volume = 79 | pages = 590–595 | date = April 2014 | pmid = 24440755 | pmc = 3989204 | doi = 10.1016/j.neuropharm.2014.01.002 }}</ref>

Clinical studies have shown that taking levamisole at doses of 50–200&nbsp;mg per day can lead to agranulocytosis in approximately 0.08–5% of patients.<ref>{{cite web |title=697. Levamisole | work = WHO Food Additives Series 27 | publisher = INCHEM; International Programme on Chemical Safety (IPCS); World Health Organization |url=https://www.inchem.org/documents/jecfa/jecmono/v27je04.htm }}</ref>

=====Cocaine- and levamisole-induced vasculitis=====
{{See also|Desomorphine#Toxicity of krokodil}}

Cocaine- and levamisole-induced vasculitis (CLIV) is often used as an umbrella term for the vasculitic and necrotic complications seen with levamisole-adulterated cocaine, including both LINES and CLAAS.<ref name="Gill_2021">{{cite journal | vauthors = Gill H, Trinh D, Anderson DJ, Li N, Madenberg D | title = Cocaine and Levamisole Induced Vasculitis | journal = Cureus | volume = 13 | issue = 8 | article-number = e17192 | date = August 2021 | pmid = 34548986 | pmc = 8439268 | doi = 10.7759/cureus.17192 | doi-access = free }}</ref>

Cocaine and levamisole-adulterated cocaine (LAC) can cause cocaine-induced [[vasculitis]] (CIV) that mimics primary [[anti-neutrophil cytoplasmic antibody|anti-neutrophil cytoplasmic antibody (ANCA)]]-associated vasculitis (AAV), presenting as [[cocaine-induced midline destructive lesions]], LAC vasculopathy, or CIV. These conditions involve immune activation through [[neutrophil extracellular traps#NETosis|NETosis]] and ANCA formation, leading to [[injury|tissue damage]]. Diagnosis is challenging due to symptom overlap and undisclosed drug use, making clinical suspicion and drug history essential for proper management.<ref>{{cite journal | vauthors = Iorio L, Davanzo F, Cazzador D, Codirenzi M, Fiorin E, Zanatta E, Nicolai P, Doria A, Padoan R | title = Cocaine- and Levamisole-Induced Vasculitis: Defining the Spectrum of Autoimmune Manifestations | journal = Journal of Clinical Medicine | volume = 13 | issue = 17 | page = 5116 | date = August 2024 | pmid = 39274328 | pmc = 11396482 | doi = 10.3390/jcm13175116 | doi-access = free }}</ref>

======Cocaine/levamisole-associated autoimmune syndrome======
The broader cocaine/levamisole-associated autoimmune syndrome (CLAAS) includes LINES as a subset and is also common, but LINES is more specifically and frequently cited in the context of street cocaine adulteration.<ref name="Cascio_2018">{{cite journal | vauthors = Cascio MJ, Jen KY | title = Cocaine/levamisole-associated autoimmune syndrome: a disease of neutrophil-mediated autoimmunity | journal = Current Opinion in Hematology | volume = 25 | issue = 1 | pages = 29–36 | date = January 2018 | pmid = 29211697 | doi = 10.1097/MOH.0000000000000393 }}</ref>

Levamisole has become a common additive to illicit cocaine. It is thought to intensify the "high" by releasing [[dopamine]] in the brain, acts as a bulking agent, and is a difficult adulterant to recognize. Potential risks of levamisole-laced cocaine include [[autoimmune disease]], [[neutropenia]], [[arthralgias]], [[retiform purpura]], skin [[necrosis]], and [[fever]].<ref>{{Cite journal | vauthors = Cascio MJ, Jen KY | title = Cocaine/levamisole-associated autoimmune syndrome: a disease of neutrophil-mediated autoimmunity | journal = Current Opinion in Hematology | volume = 25 | issue = 1 | pages = 29–36 | date = January 2018 | pmid = 29211697 | doi = 10.1097/MOH.0000000000000393 | s2cid = 23795272 }}</ref>

=== Mortality ===
Persons with regular or problematic use of cocaine have a significantly higher [[mortality rate]], and are specifically at higher risk of traumatic deaths and deaths attributable to infectious disease.<ref>{{Cite journal | vauthors = Peacock A, Tran LT, Larney S, Stockings E, Santo T, Jones H, Santomauro D, Degenhardt L | title = All-cause and cause-specific mortality among people with regular or problematic cocaine use: a systematic review and meta-analysis | journal = Addiction | volume = 116 | issue = 4 | pages = 725–742 | date = April 2021 | pmid = 32857457 | pmc = 7914269 | doi = 10.1111/add.15239 }}</ref> In 2025, the Liberty House Clinic in the United Kingdom noted that chronic cocaine usage in fact had a higher risk of death than [[alcoholism]].<ref>{{cite web|url=https://www.libertyhouseclinic.co.uk/blog/substance-abuse/cocaine-or-alcohol-whats-worse/|title=Cocaine or alcohol, what's worse?|publisher=Liberty House Clinic|date=17 February 2025|access-date=19 April 2025}}</ref>

=== Neurotoxicity ===
Cocaine is considered [[neurotoxic]] due to its damaging effects on the brain and nervous system.<ref>{{cite journal | vauthors = Sharma HS, Muresanu D, Sharma A, Patnaik R | title = Cocaine-induced breakdown of the blood-brain barrier and neurotoxicity | journal = International Review of Neurobiology | volume = 88 | pages = 297–334 | date = 2009 | pmid = 19897082 | doi = 10.1016/S0074-7742(09)88011-2 | isbn = 978-0-12-374504-0 }}</ref><ref>{{cite journal | vauthors = Pereira RB, Andrade PB, Valentão P | title = A Comprehensive View of the Neurotoxicity Mechanisms of Cocaine and Ethanol | journal = Neurotoxicity Research | volume = 28 | issue = 3 | pages = 253–267 | date = October 2015 | pmid = 26105693 | doi = 10.1007/s12640-015-9536-x }}</ref><ref name="Clare_2024" /><ref name="Nicolucci_2020">{{cite journal | vauthors = Nicolucci C, Pais ML, Santos AC, Ribeiro FM, Encarnação PM, Silva AL, Castro IF, Correia PM, Veloso JF, Reis J, Lopes MZ, Botelho MF, Pereira FC, Priolli DG | title = Single Low Dose of Cocaine-Structural Brain Injury Without Metabolic and Behavioral Changes | journal = Frontiers in Neuroscience | volume = 14 | article-number = 589897 | date = 2020 | pmid = 33584173 | pmc = 7874143 | doi = 10.3389/fnins.2020.589897 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hofmaier T, Luf A, Seddik A, Stockner T, Holy M, Freissmuth M, Ecker GF, Schmid R, Sitte HH, Kudlacek O | title = Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters | journal = Neurochemistry International | volume = 73 | issue = 100 | pages = 32–41 | date = July 2014 | pmid = 24296074 | pmc = 4077236 | doi = 10.1016/j.neuint.2013.11.010 }}</ref><ref name="Little_2009">{{Cite journal | vauthors = Little KY, Ramssen E, Welchko R, Volberg V, Roland CJ, Cassin B | title = Decreased brain dopamine cell numbers in human cocaine users | journal = Psychiatry Research | volume = 168 | issue = 3 | pages = 173–80 | date = August 2009 | pmid = 19233481 | doi = 10.1016/j.psychres.2008.10.034 | s2cid = 27618292 }}</ref> Research has shown that both acute and chronic cocaine use can lead to significant reductions in cerebral blood flow, disrupt neurovascular interactions, and impair brain function. These changes are associated with [[nerve injury]], cognitive deficits, and an increased risk of cerebrovascular accidents such as strokes. Brain imaging studies consistently report that individuals who misuse cocaine exhibit structural and functional abnormalities compared to non-users, supporting the classification of cocaine as a neurotoxic substance.<ref name="Clare_2024">{{cite journal | vauthors = Clare K, Park K, Pan Y, Lejuez CW, Volkow ND, Du C | title = Neurovascular effects of cocaine: relevance to addiction | journal = Frontiers in Pharmacology | volume = 15 | article-number = 1357422 | date = 2024 | pmid = 38455961 | pmc = 10917943 | doi = 10.3389/fphar.2024.1357422 | doi-access = free }}</ref>

Cocaine use damages [[gray matter]] in brain regions critical for memory, attention, and emotion, leading to cognitive and behavioral impairments. It also disrupts dopamine levels and blood flow, accelerating [[aging brain|brain aging]] and causing long-term neurological harm.<ref>{{cite journal | vauthors = Beheshti I | title = Cocaine Destroys Gray Matter Brain Cells and Accelerates Brain Aging | journal = Biology | volume = 12 | issue = 5 | page = 752 | date = May 2023 | pmid = 37237564 | pmc = 10215125 | doi = 10.3390/biology12050752 | doi-access = free }}</ref>

===Psychiatric symptoms===
Cocaine produces a spectrum of [[psychiatric symptoms]] including agitation, paranoia, anxiety, irritability, [[psychosis]], hallucinations, delusions, violence, as well as suicidal and homicidal thinking.<ref name="Morton_1999">{{cite journal | vauthors = Morton WA | title = Cocaine and Psychiatric Symptoms | journal = Primary Care Companion to the Journal of Clinical Psychiatry | volume = 1 | issue = 4 | pages = 109–113 | date = August 1999 | pmid = 15014683 | pmc = 181074 | doi = 10.4088/pcc.v01n0403 }}</ref><ref name="Pom_2012" />

A considerable proportion of cocaine addicts exhibit [[hypomanic]] personality traits that are [[ego-syntonic]] with their pattern of cocaine abuse.<ref>{{cite journal | vauthors = Lemere F, Smith JW | title = Hypomanic personality trait in cocaine addiction | journal = British Journal of Addiction | volume = 85 | issue = 4 | pages = 575–576 | date = April 1990 | pmid = 2346798 | doi = 10.1111/j.1360-0443.1990.tb01679.x }}</ref>

[[Cocaine intoxication]] mirrors core traits of [[narcissism]]—both involve a dopamine-driven, compulsive drive for reward. Just as cocaine produces a brief high that temporarily enhances the sense of worth, narcissists rely on external [[admiration]] to feed an addiction to their [[self-esteem]], resulting in a [[positive feedback|self-reinforcing feedback]] cycle.<ref>{{cite journal | vauthors = Kastner-Bosek A, Dajic I, Mikus N, Weidenauer A, Willeit M | title = Addicted to Self-esteem: Understanding the neurochemistry of narcissism by using cocaine as a pharmacological model | journal = Journal of Experimental Psychopathology | volume = 12 | issue = 3 | date = July 2021 | article-number = 20438087211044362 | doi = 10.1177/20438087211044362 | doi-access = free }}</ref>

The misuse of cocaine has a high correlation with [[suicide]].<ref name="Vijayakumar_2011">{{cite journal | vauthors = Vijayakumar L, Kumar MS, Vijayakumar V | title = Substance use and suicide | journal = Current Opinion in Psychiatry | volume = 24 | issue = 3 | pages = 197–202 | date = May 2011 | pmid = 21430536 | doi = 10.1097/YCO.0b013e3283459242 | s2cid = 206143129 }}</ref><ref>{{cite journal | vauthors = Moçambique M, Hoffmann A, Roglio V, Kessler F, Dalbosco C, Schuch J, Pechansky F | title = Prevalence of suicide in cocaine users accessing health services: a systematic review and meta-analysis. | journal = Revista Brasileira de Psiquiatria | location = Sao Paulo, Brazil | volume = 44 | issue = 4 | pages = 441–448 | date = 24 June 2022 | pmid = 35751594 | pmc = 9375660 | doi = 10.47626/1516-4446-2021-2207 }}</ref> In those who use cocaine, the risk is greatest during the [[Cocaine withdrawal|withdrawal phase]].<ref>{{cite book | vauthors = Ayd FJ | title = Lexicon of psychiatry, neurology, and the neurosciences | location = Philadelphia [u.a.] | page = 256 | year = 2000 | url = https://books.google.com/books?id=ea_QVG2BFy8C&q=256 | publisher = Lippincott Williams & Wilkins | isbn = 978-0-7817-2468-5 | edition = 2nd }}</ref> Cocaine use has been linked to homicide, with up to 31% of homicide victims testing positive for the drug.<ref name="Morton_1999" /> In 1989 Fulton County, 40% of [[homicide]] victims had cocaine metabolites, especially Black and firearm victims.<ref>{{cite journal | vauthors = Hanzlick R, Gowitt GT | title = Cocaine metabolite detection in homicide victims | journal = JAMA | volume = 265 | issue = 6 | pages = 760–761 | date = February 1991 | pmid = 1990194 | doi = 10.1001/jama.1991.03460060092031 }}</ref>

A 2020 study found that men with cocaine use disorder have greater difficulty identifying [[emotional expression]] in female faces, affecting relationships and suggesting a target for intervention.<ref>{{cite journal | vauthors = Bland AR, Ersche KD | title = Deficits in recognizing female facial expressions related to social network in cocaine-addicted men | journal = Drug and Alcohol Dependence | volume = 216 | article-number = 108247 | date = November 2020 | pmid = 32896724 | pmc = 7616971 | doi = 10.1016/j.drugalcdep.2020.108247 }}</ref> A 2021 study found that cocaine use disorder impairs emotion recognition, especially for happiness and fear, with improvement after long-term abstinence.<ref>{{cite journal | vauthors = Rabin RA, Parvaz MA, Alia-Klein N, Goldstein RZ | title = Emotion recognition in individuals with cocaine use disorder: the role of abstinence length and the social brain network | journal = Psychopharmacology | volume = 239 | issue = 4 | pages = 1019–1033 | date = April 2022 | pmid = 34089343 | pmc = 8689230 | doi = 10.1007/s00213-021-05868-x }}</ref>

[[Depression (mood)|Depression]] is modestly linked to current drug use in cocaine users but does not clearly predict treatment participation or future use.<ref>{{cite journal | vauthors = Conner KR, Pinquart M, Holbrook AP | title = Meta-analysis of depression and substance use and impairment among cocaine users | journal = Drug and Alcohol Dependence | volume = 98 | issue = 1–2 | pages = 13–23 | date = November 2008 | pmid = 18585871 | pmc = 2570759 | doi = 10.1016/j.drugalcdep.2008.05.005 }}</ref> For people who use cocaine, stress and craving can make each other worse. This may help explain why stress can lead to [[relapse]] in people trying to stop using cocaine.<ref>{{cite journal | vauthors = Kexel AK, Kluwe-Schiavon B, Baumgartner MR, Engeli EJ, Visentini M, Kirschbaum C, Seifritz E, Ditzen B, Soravia LM, Quednow BB | title = Cue-induced cocaine craving enhances psychosocial stress and vice versa in chronic cocaine users | journal = Translational Psychiatry | volume = 12 | issue = 1 | article-number = 443 | date = October 2022 | pmid = 36220809 | pmc = 9554190 | doi = 10.1038/s41398-022-02204-5 }}</ref>

====Psychosis====
Cocaine has a similar potential to induce temporary psychosis<ref name="Brady_1991">{{cite journal | vauthors = Brady KT, Lydiard RB, Malcolm R, Ballenger JC | title = Cocaine-induced psychosis | journal = The Journal of Clinical Psychiatry | volume = 52 | issue = 12 | pages = 509–512 | date = December 1991 | pmid = 1752853 }}</ref> with more than half of cocaine abusers reporting at least some psychotic symptoms at some point.<ref name="Thirthalli_2006">{{cite journal | vauthors = Thirthalli J, Benegal V | title = Psychosis among substance users | journal = Current Opinion in Psychiatry | volume = 19 | issue = 3 | pages = 239–245 | date = May 2006 | pmid = 16612208 | doi = 10.1097/01.yco.0000218593.08313.fd | s2cid = 13350537 }}</ref> Typical symptoms include paranoid delusions that they are being followed and that their drug use is being watched, accompanied by hallucinations that support the delusional beliefs.<ref name="Thirthalli_2006" /> [[Delusional parasitosis]] with [[formication]] ('cocaine bugs') is also a fairly common symptom.<ref name="Elliott_2012">{{cite journal | vauthors = Elliott A, Mahmood T, Smalligan RD | title = Cocaine bugs: a case report of cocaine-induced delusions of parasitosis | journal = The American Journal on Addictions | volume = 21 | issue = 2 | pages = 180–181 | year = 2012 | pmid = 22332864 | doi = 10.1111/j.1521-0391.2011.00208.x }}</ref>

Cocaine-induced psychosis shows [[drug sensitization|sensitization]] toward the psychotic effects of the drug. This means that psychosis becomes more severe with repeated intermittent use.<ref name="Thirthalli_2006" /><ref>{{cite journal | vauthors = DiSclafani II A, Hall RC, Gardner ER | title = Drug-induced psychosis: emergency diagnosis and management | journal = Psychosomatics | volume = 22 | issue = 10 | pages = 845–50, 855 | date = October 1981 | pmid = 7313045 | doi = 10.1016/s0033-3182(81)73092-5 | doi-access =  }}</ref>

=== Short-term effects ===
Insufflating (snorting) cocaine commonly causes increased [[mucus]] production due to irritation and inflammation of the nasal passages. This irritation leads to symptoms such as a [[Rhinorrhea|runny nose]], [[nasal congestion]], and excessive or thickened mucus.

Acute exposure to cocaine has many effects on humans, including euphoria, increases in heart rate and blood pressure, and increases in cortisol secretion from the adrenal gland.<ref>{{Cite journal | vauthors = Heesch CM, Negus BH, Keffer JH, Snyder RW, Risser RC, Eichhorn EJ | title = Effects of cocaine on cortisol secretion in humans | journal = The American Journal of the Medical Sciences | volume = 310 | issue = 2 | pages = 61–4 | date = August 1995 | pmid = 7631644 | doi = 10.1097/00000441-199508000-00004 | s2cid = 11042810 }}</ref> In humans with acute exposure followed by continuous exposure to cocaine at a constant blood concentration, the acute tolerance to the [[chronotropic]] cardiac effects of cocaine begins after about 10 minutes, while acute tolerance to the euphoric effects of cocaine begins after about one hour.<ref name="Ambre_1988">{{Cite journal | vauthors = Ambre JJ, Belknap SM, Nelson J, Ruo TI, Shin SG, Atkinson AJ | title = Acute tolerance to cocaine in humans | journal = Clinical Pharmacology and Therapeutics | volume = 44 | issue = 1 | pages = 1–8 | date = July 1988 | pmid = 3390996 | doi = 10.1038/clpt.1988.104 | s2cid = 44253676 }}</ref><ref>{{Cite journal | vauthors = Pudiak CM, KuoLee R, Bozarth MA | title = Tolerance to cocaine in brain stimulation reward following continuous cocaine infusions | journal = Pharmacology, Biochemistry, and Behavior | volume = 122 | pages = 246–52 | date = July 2014 | pmid = 24768900 | doi = 10.1016/j.pbb.2014.04.006 | s2cid = 207332822 }}</ref><ref>{{Cite journal | vauthors = Gullapalli BT, Natarajan A, Angarita GA, Malison RT, Ganesan D, Rahman T |title=On-body Sensing of Cocaine Craving, Euphoria and Drug-Seeking Behavior Using Cardiac and Respiratory Signals |journal=Proceedings of the ACM on Interactive, Mobile, Wearable and Ubiquitous Technologies |date=21 June 2019 |volume=3 |issue=2 |pages=1–31 |doi=10.1145/3328917|s2cid=195357215 }}</ref><ref>{{Cite journal | vauthors = Calipari ES, Ferris MJ, Jones SR | title = Extended access of cocaine self-administration results in tolerance to the dopamine-elevating and locomotor-stimulating effects of cocaine | journal = Journal of Neurochemistry | volume = 128 | issue = 2 | pages = 224–32 | date = January 2014 | pmid = 24102293 | pmc = 3947316 | doi = 10.1111/jnc.12452 }}</ref> With excessive or prolonged use, the drug can cause [[itch]]ing, [[tachycardia|fast heart rate]], and [[formication|paranoid delusions or sensations of insects crawling on the skin]].<ref name="Weizhao_2008">{{Cite book |title=Mechanisms Mediating Sex Differences in the Effects of Cocaine | vauthors = Zhao W |year=2008 |isbn=978-0-549-99458-9 |page=3 | publisher = University of Michigan |access-date=25 September 2012 |url=https://books.google.com/books?id=AF8zjRBtSuIC&pg=PA3 |url-status=live |archive-url=https://web.archive.org/web/20140404151302/https://books.google.com/books?id=AF8zjRBtSuIC&pg=PA3 |archive-date=4 April 2014 }}</ref> Cocaine can induce [[psychosis]] characterized by [[paranoia]], impaired [[reality testing]], [[hallucinations]], irritability, and physical aggression. [[Cocaine intoxication]] can cause hyperawareness, [[hypervigilance]], [[psychomotor agitation]], and [[delirium]]. Consumption of large doses of cocaine can cause violent outbursts, especially by those with preexisting psychosis.<ref>{{Cite journal | vauthors = Boles SM, Miotto K |title=Substance abuse and violence: A review of the literature |journal=Aggression and Violent Behavior |date=March–April 2003 |volume=8 |issue=2 |pages=155–174 |doi=10.1016/S1359-1789(01)00057-X }}</ref> Acute exposure may induce [[arrhythmia]], including [[atrial fibrillation]], [[supraventricular tachycardia]], [[ventricular tachycardia]], and [[ventricular fibrillation]]. Acute exposure may also lead to [[angina]], [[myocardial infarction|heart attack]], and [[congestive heart failure]].<ref>{{Cite journal | vauthors = Pergolizzi JV, Magnusson P, LeQuang JA, Breve F, Varrassi G | title = Cocaine and Cardiotoxicity: A Literature Review | journal = Cureus | volume = 13 | issue = 4 | article-number = e14594 | date = April 2021 | pmid = 34036012 | pmc = 8136464 | doi = 10.7759/cureus.14594 | issn=2168-8184  | doi-access = free }}</ref> Cocaine overdose may cause [[seizures]], [[hyperthermia|abnormally high body temperature]] and a marked elevation of blood pressure, which can be life-threatening,<ref name="Weizhao_2008" /> [[Heart arrhythmia|abnormal heart rhythms]],<ref name="O'Leary_2010">{{Cite journal | vauthors = O'Leary ME, Hancox JC | title = Role of voltage-gated sodium, potassium and calcium channels in the development of cocaine-associated cardiac arrhythmias | journal = British Journal of Clinical Pharmacology | volume = 69 | issue = 5 | pages = 427–42 | date = May 2010 | pmid = 20573078 | pmc = 2856043 | doi = 10.1111/j.1365-2125.2010.03629.x }}</ref> and death.<ref name="O'Leary_2010" /> Anxiety, paranoia, and restlessness can also occur, especially during the [[Comedown (drugs)|comedown]]. With excessive dosage, [[tremor]]s, [[convulsion]]s, and [[Hypothermia|increased body temperature]] are observed.<ref name="WHO2004" />

=== Long-term effects ===
[[File:Side effects of chronic use of Cocaine.png|class=skin-invert-image|thumb|upright=1.4|Side effects of chronic cocaine use]]

Cocaine is highly addictive and has poor bioavailability when taken orally. Individuals often engage in repeated use by either insufflating it [[intranasally]] or converting it to [[crack cocaine]] for vaporization. Cocaine's effects last longest when insufflated (60–90 minutes),<ref name="Zimmerman_2012" /> but the drug itself has a short [[biological half-life]] of about 0.7–1.5 hours.<ref name="Treadwell_2007">{{cite journal | vauthors = Treadwell SD, Robinson TG | title = Cocaine use and stroke | journal = Postgraduate Medical Journal | volume = 83 | issue = 980 | pages = 389–394 | date = June 2007 | pmid = 17551070 | pmc = 2600058 | doi = 10.1136/pgmj.2006.055970 }}</ref> Repeated use raises the risk of developing "[[#Cocaine nose|cocaine nose]]," referring to severe nasal tissue damage from intranasal use, as well as "[[#Crack lung|crack lung]]," a condition involving lung tissue damage caused by inhaling crack cocaine.

Cocaine use leads to an increased risk of hemorrhagic and ischemic [[stroke]]s.<ref name="Sordo_2014"/> Cocaine use also increases the risk of having a [[myocardial infarction|heart attack]].<ref name="Havakuk_2017">{{Cite journal | vauthors = Havakuk O, Rezkalla SH, Kloner RA | title = The Cardiovascular Effects of Cocaine | journal = Journal of the American College of Cardiology | volume = 70 | issue = 1 | pages = 101–113 | date = July 2017 | pmid = 28662796 | doi = 10.1016/j.jacc.2017.05.014 | type = Review | doi-access = free}}</ref>

Cocaine use also promotes the [[thrombosis|formation of blood clots]].<ref name="Zimmerman_2012" /> This increase in blood clot formation is attributed to cocaine-associated increases in the activity of [[Plasminogen activator inhibitor-1|plasminogen activator inhibitor]], and an increase in the number, activation, and aggregation of [[platelet]]s.<ref name="Zimmerman_2012" />

Cocaine [[Vasoconstriction|constricts blood vessels]], [[Mydriasis|dilates pupils]], and increases body temperature, heart rate, and blood pressure. It can also cause headaches and gastrointestinal complications such as abdominal pain and nausea. Chronic users may lose their [[appetite]] and experience severe [[malnutrition]], leading to being [[underweight]].

A 2014 study found that increased cocaine use is linked to greater [[cognitive impairment]], particularly in working memory, while reduced or ceased use can lead to partial or full recovery of cognitive function. These findings suggest that some cocaine-related cognitive deficits are reversible, especially if use begins later in life.<ref>{{cite journal | vauthors = Vonmoos M, Hulka LM, Preller KH, Minder F, Baumgartner MR, Quednow BB | title = Cognitive impairment in cocaine users is drug-induced but partially reversible: evidence from a longitudinal study | journal = Neuropsychopharmacology | volume = 39 | issue = 9 | pages = 2200–2210 | date = August 2014 | pmid = 24651468 | pmc = 4104339 | doi = 10.1038/npp.2014.71 }}</ref> A 2018 review found little evidence that chronic cocaine use causes widespread cognitive impairment.<ref>{{cite journal | vauthors = Frazer KM, Richards Q, Keith DR | title = The long-term effects of cocaine use on cognitive functioning: A systematic critical review | journal = Behavioural Brain Research | volume = 348 | pages = 241–262 | date = August 2018 | pmid = 29673580 | doi = 10.1016/j.bbr.2018.04.005 }}</ref> Exposure to cocaine may lead to the breakdown of the [[blood–brain barrier]].<ref>{{cite journal | vauthors = Sharma HS, Muresanu D, Sharma A, Patnaik R | title = Cocaine-induced breakdown of the blood-brain barrier and neurotoxicity | journal = International Review of Neurobiology | volume = 88 | pages = 297–334 | year = 2009 | pmid = 19897082 | doi = 10.1016/S0074-7742(09)88011-2 | isbn = 978-0-12-374504-0 }}</ref><ref>{{Cite book| vauthors = Karch SB |title=Karch's pathology of drug abuse|date=2009|publisher=CRC Press|location=Boca Raton|isbn=978-0-8493-7881-2|page=70|edition=4th |url= https://books.google.com/books?id=G9E7gfJq0KkC&pg=PA70 |url-status=live|archive-url=https://web.archive.org/web/20170910234911/https://books.google.com/books?id=G9E7gfJq0KkC&pg=PA70 |archive-date=10 September 2017 }}</ref>

Cocaine use is frequently associated with involuntary tooth grinding, known as [[bruxism]], which can cause [[dental attrition]] and [[gingivitis]].<ref>{{cite journal | vauthors = Shekarchizadeh H, Khami MR, Mohebbi SZ, Ekhtiari H, Virtanen JI | title = Oral Health of Drug Abusers: A Review of Health Effects and Care | journal = Iranian Journal of Public Health | volume = 42 | issue = 9 | pages = 929–940 | date = September 2013 | pmid = 26060654 | pmc = 4453891 }}</ref><ref>{{Cite journal | vauthors = Baigent M | title = Physical complications of substance abuse: what the psychiatrist needs to know | journal = Curr Opin Psychiatry | volume = 16 | issue = 3 | pages = 291–296 | year = 2003 | doi = 10.1097/00001504-200305000-00004 }}</ref> Additionally, stimulants like cocaine, [[methamphetamine]], and even [[caffeine]] cause dehydration and [[Xerostomia|dry mouth]].

==== Addiction ====
{{See also|Epigenetics of cocaine addiction}}
{{For|harm caused by the freebase form|Crack cocaine#Addiction}}

Cocaine can induce [[Drug tolerance|tolerance]] after a single dose, and repeated use frequently leads to the development of [[addiction]] and prolonged [[Cocaine dependence|craving]].<ref name="Ambre_1988" /><ref>{{cite web |title=Cocaine |work= National Institute on Drug Abuse (NIDA) | publisher = U.S. Department of Health and Human Services |url=https://nida.nih.gov/research-topics/cocaine|archive-url= https://web.archive.org/web/20220606183508/https://nida.nih.gov/research-topics/cocaine|archive-date=6 June 2022}}</ref><ref>{{cite journal | vauthors = Paludetto LS, Florence LL, Torales J, Ventriglio A, Castaldelli-Maia JM | title = Mapping the Neural Substrates of Cocaine Craving: A Systematic Review | journal = Brain Sciences | volume = 14 | issue = 4 | page = 329 | date = March 2024 | pmid = 38671981 | pmc = 11048489 | doi = 10.3390/brainsci14040329 | doi-access = free }}</ref> Assessment tools like the Obsessive Compulsive Cocaine Use Scale (OCCUS) may be employed to quantify obsessive and compulsive thoughts related to cocaine consumption.<ref>{{cite journal | vauthors = Hormes JM, Coffey SF, Drobes DJ, Saladin ME | title = The Obsessive Compulsive Cocaine Use Scale: development and initial validation of a self-rated instrument for the quantification of thoughts about cocaine use | journal = Drug and Alcohol Dependence | volume = 120 | issue = 1–3 | pages = 250–254 | date = January 2012 | pmid = 21890282 | pmc = 3245789 | doi = 10.1016/j.drugalcdep.2011.07.024 }}</ref><ref>{{cite journal | vauthors = Kirschner M, Sladky R, Haugg A, Stämpfli P, Jehli E, Hodel M, Engeli E, Hösli S, Baumgartner MR, Sulzer J, Huys QJ, Seifritz E, Quednow BB, Scharnowski F, Herdener M | title = Self-regulation of the dopaminergic reward circuit in cocaine users with mental imagery and neurofeedback | journal = eBioMedicine | volume = 37 | pages = 489–498 | date = November 2018 | pmid = 30377073 | pmc = 6286189 | doi = 10.1016/j.ebiom.2018.10.052 }}</ref>

Withdrawal symptoms include disrupted sleep, [[irritability]], [[Depression (mood)|depression]], and reduced ability to experience pleasure ([[anhedonia]]).<ref>{{cite journal | vauthors = Walsh SL, Stoops WW, Moody DE, Lin SN, Bigelow GE | title = Repeated dosing with oral cocaine in humans: assessment of direct effects, withdrawal, and pharmacokinetics | journal = Experimental and Clinical Psychopharmacology | volume = 17 | issue = 4 | pages = 205–216 | date = August 2009 | pmid = 19653786 | pmc = 2811070 | doi = 10.1037/a0016469 }}</ref><ref name="Pom_2012" /> Chronic nasal use may cause destructive damage to the nasal septum, including [[cocaine-induced midline destructive lesions]] (CIMDL). Illicit cocaine is frequently adulterated with substances such as [[fentanyl]], [[levamisole]], or [[local anesthetics]], increasing its toxicity.<ref name="Goldstein_2009" /><ref>{{Cite web | vauthors = Gold M | date = 16 October 2022 | work = Addiction Policy Forum |url=https://www.addictionpolicy.org/post/fentanyl-adulterated-cocaine-strategies-to-address-the-new-normal|title=Fentanyl-Adulterated Cocaine: Strategies To Address The New Normal|access-date=17 December 2022|archive-date=17 December 2022|archive-url=https://web.archive.org/web/20221217214902/https://www.addictionpolicy.org/post/fentanyl-adulterated-cocaine-strategies-to-address-the-new-normal|url-status=live}}</ref> Concurrent use with [[alcohol (drug)|alcohol]] produces [[cocaethylene]], a metabolite that significantly increases the risk of sudden death. According to the [[Global Burden of Disease Study]], cocaine use is responsible for approximately 7,300 deaths annually.<ref>{{Cite journal | vauthors = Roth GA, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, Abbastabar H, Abd-Allah F, Abdela J, Abdelalim A, Abdollahpour I, etal | collaboration = GBD 2017 Causes of Death Collaborators | title = Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017 | journal = Lancet | volume = 392 | issue = 10159 | pages = 1736–1788 | date = November 2018 | pmid = 30496103 | pmc = 6227606 | doi = 10.1016/S0140-6736(18)32203-7 | doi-access = free }}</ref>

Cocaine abuse can trigger [[addiction-related structural neuroplasticity]] in the human brain, although the permanence of such changes remains uncertain.<ref name="Hamp_2019">{{cite journal | vauthors = Hampton WH, Hanik I, Olson IR | title = [Substance Abuse and White Matter: Findings, Limitations, and Future of Diffusion Tensor Imaging Research] | journal = Drug and Alcohol Dependence | volume = 197 | issue = 4 | pages = 288–298 | year = 2019 | pmid = 30875650 | pmc = 6440853 | doi = 10.1016/j.drugalcdep.2019.02.005}}</ref> [[Genealogy|Family history]] is a known risk factor, as relatives of cocaine users have an increased likelihood of developing [[cocaine addiction]].<ref>{{Cite journal | vauthors = Fernàndez-Castillo N, Cabana-Domínguez J, Corominas R, Cormand B | title = Molecular genetics of cocaine use disorders in humans | journal = Molecular Psychiatry | volume = 27 | issue = 1 | pages = 624–639 | date = January 2022 | pmid = 34453125 | doi = 10.1038/s41380-021-01256-1 | pmc = 8960411 }}</ref>

A key mechanism involves the overexpression of [[ΔFosB]] in the [[nucleus accumbens]], altering [[transcriptional regulation]] and reinforcing drug-seeking behavior.<ref name="Hope_1998">{{Cite journal | vauthors = Hope BT | title = Cocaine and the AP-1 transcription factor complex | journal = Annals of the New York Academy of Sciences | volume = 844 | issue = 1 | pages = 1–6 | date = May 1998 | pmid = 9668659 | doi = 10.1111/j.1749-6632.1998.tb08216.x | s2cid = 11683570 | bibcode = 1998NYASA.844....1H | url = https://zenodo.org/record/1230756 | access-date = 30 June 2019 | archive-date = 28 July 2020 | archive-url = https://web.archive.org/web/20200728160757/https://zenodo.org/record/1230756 | url-status = live }}</ref> Each dose of cocaine raises ΔFosB levels without a known saturation point. This elevation leads to increased [[brain-derived neurotrophic factor]] ([[BDNF]]) levels, which in turn enhance [[dendrite|dendritic]] branching and [[dendritic spine|spine]] density in neurons of the nucleus accumbens and [[prefrontal cortex]], potentially persisting for weeks after drug cessation.{{Citation needed|date=June 2025}} In [[genetically modified mouse|transgenic mice]] engineered to express ΔFosB in the nucleus accumbens and [[dorsal striatum]], heightened behavioral sensitization to cocaine has been observed.<ref name="Kelz_1999">{{Cite journal |author-link13=D. James Surmeier | vauthors = Kelz MB, Chen J, Carlezon WA, Whisler K, Gilden L, Beckmann AM, Steffen C, Zhang YJ, Marotti L, Self DW, Tkatch T, Baranauskas G, Surmeier DJ, Neve RL, Duman RS, Picciotto MR, Nestler EJ | title = Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine | journal = Nature | volume = 401 | issue = 6750 | pages = 272–6 | date = September 1999 | pmid = 10499584 | doi = 10.1038/45790 | bibcode = 1999Natur.401..272K | s2cid = 4390717 }}</ref> These mice self-administer cocaine at lower doses and display a greater propensity for [[relapse]] after withdrawal<ref name="Colby_2003">{{Cite journal | vauthors = Colby CR, Whisler K, Steffen C, Nestler EJ, Self DW | title = Striatal cell type-specific overexpression of DeltaFosB enhances incentive for cocaine | journal = The Journal of Neuroscience | volume = 23 | issue = 6 | pages = 2488–93 | date = March 2003 | pmid = 12657709 | doi =  10.1523/JNEUROSCI.23-06-02488.2003| pmc = 6742034 }}</ref><ref name="Nestler_2011">{{Cite journal | vauthors = Nestler EJ, Barrot M, Self DW | title = DeltaFosB: a sustained molecular switch for addiction | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 20 | pages = 11042–6 | date = September 2001 | pmid = 11572966 | pmc = 58680 | doi = 10.1073/pnas.191352698 | quote = <!-- Although the ΔFosB signal is relatively long-lived, it is not permanent. ΔFosB degrades gradually and can no longer be detected in brain after 1–2 months of drug withdrawal&nbsp;... Indeed, ΔFosB is the longest-lived adaptation known to occur in adult brain, not only in response to drugs of abuse, but to any other perturbation (that doesn't involve lesions) as well. --> | bibcode = 2001PNAS...9811042N | doi-access = free }}</ref> ΔFosB also enhances sensitivity to reward by upregulating the [[AMPA receptor]] subunit GluR2<ref name="Kelz_1999" /> and downregulating the expression of [[dynorphin]].<ref name="Nestler_2011"/>

Cocaine use has also been shown to increase [[DNA damage (naturally occurring)|DNA damage]] in the brains of rodents.<ref name="de_Souza_2014">{{Cite journal | vauthors = de Souza MF, Gonçales TA, Steinmetz A, Moura DJ, Saffi J, Gomez R, Barros HM | title = Cocaine induces DNA damage in distinct brain areas of female rats under different hormonal conditions | journal = Clinical and Experimental Pharmacology & Physiology | volume = 41 | issue = 4 | pages = 265–9 | date = April 2014 | pmid = 24552452 | doi = 10.1111/1440-1681.12218 | s2cid = 20849951 }}</ref><ref name="Alvarenga_2010">{{Cite journal | vauthors = Alvarenga TA, Andersen ML, Ribeiro DA, Araujo P, Hirotsu C, Costa JL, Battisti MC, Tufik S | title = Single exposure to cocaine or ecstasy induces DNA damage in brain and other organs of mice | journal = Addiction Biology | volume = 15 | issue = 1 | pages = 96–9 | date = January 2010 | pmid = 19878142 | doi = 10.1111/j.1369-1600.2009.00179.x | s2cid = 21347765 }}</ref> During subsequent [[DNA repair]], enduring alterations in [[chromatin]] structure may arise, such as [[DNA methylation]] and [[histone methylation|methylation or acetylation of histones]] at the repair loci.<ref name="Dabin_2016">{{Cite journal | vauthors = Dabin J, Fortuny A, Polo SE | title = Epigenome Maintenance in Response to DNA Damage | journal = Molecular Cell | volume = 62 | issue = 5 | pages = 712–27 | date = June 2016 | pmid = 27259203 | pmc = 5476208 | doi = 10.1016/j.molcel.2016.04.006 }}</ref> These modifications may result in lasting [[epigenetics|epigenetic "scars"]], which are believed to contribute to the persistent [[Epigenetics of cocaine addiction|epigenetic changes]] observed in cocaine addiction.

==== Dependence and withdrawal ====
{{Further information|Cocaine dependence}}

[[Cocaine dependence]] develops after even brief periods of regular cocaine use.<ref name="Gawin_1989">{{Cite journal |vauthors=Gawin FH, Ellinwood EH |title=Cocaine dependence |journal=Annual Review of Medicine |volume=40 |pages=149–61 |date=1989 |pmid=2658744 |doi=10.1146/annurev.me.40.020189.001053}}</ref>

About 25% of adults with [[attention deficit hyperactivity disorder]] (ADHD) use cocaine, and 10% develop a cocaine use disorder during their lifetime. Because cocaine use can worsen health outcomes, adults with ADHD should be screened for cocaine use disorder and referred for treatment if needed.<ref>{{cite journal | vauthors = Oliva F, Mangiapane C, Nibbio G, Berchialla P, Colombi N, Vigna-Taglianti FD | title = Prevalence of cocaine use and cocaine use disorder among adult patients with attention-deficit/hyperactivity disorder: A systematic review and meta-analysis | journal = Journal of Psychiatric Research | volume = 143 | pages = 587–598 | date = November 2021 | pmid = 33199055 | doi = 10.1016/j.jpsychires.2020.11.021 | hdl-access = free | hdl = 2318/1768539 }}</ref>

Cocaine-dependent patients with high [[neuroticism]] scores are more likely to experience cocaine-induced psychotic symptoms, regardless of other drug use factors, making [[Personality test|personality assessment]] important for risk identification and patient warning.<ref>{{cite journal | vauthors = Roncero C, Daigre C, Barral C, Ros-Cucurull E, Grau-López L, Rodríguez-Cintas L, Tarifa N, Casas M, Valero S | title = Neuroticism associated with cocaine-induced psychosis in cocaine-dependent patients: a cross-sectional observational study | journal = PLOS ONE | volume = 9 | issue = 9 | article-number = e106111 | date = 2014 | pmid = 25254365 | pmc = 4177812 | doi = 10.1371/journal.pone.0106111 | doi-access = free | bibcode = 2014PLoSO...9j6111R }}</ref>

Cocaine [[drug withdrawal|withdrawal]] symptoms group into two types: depressive (e.g., [[Depression (mood)|depression]], craving, insomnia) and somatic (e.g., increased appetite, fatigue). Depressive symptoms are linked to worse outcomes like longer depression, treatment, and risky behaviors.<ref name="Sofuoglu_2005">{{cite journal | vauthors = Sofuoglu M, Dudish-Poulsen S, Poling J, Mooney M, Hatsukami DK | title = The effect of individual cocaine withdrawal symptoms on outcomes in cocaine users | journal = Addictive Behaviors | volume = 30 | issue = 6 | pages = 1125–1134 | date = July 2005 | pmid = 15925122 | doi = 10.1016/j.addbeh.2004.10.010 }}</ref>

===== Treatment =====
Because there are no medications with an approved [[Indication (medicine)|indication]] for cocaine use disorder, psychosocial treatments are the current standard. Effective approaches include group and individual counseling, [[cognitive behavioral therapy]] (CBT), and [[motivational interviewing]] (MI). [[Contingency management]] (CM)—which rewards patients with vouchers for meeting treatment goals—has proven especially effective, particularly for helping patients achieve initial [[abstinence]] from cocaine.<ref name="Kampman_2019">{{cite journal | vauthors = Kampman KM | title = The treatment of cocaine use disorder | journal = Science Advances | volume = 5 | issue = 10 | article-number = eaax1532 | date = October 2019 | pmid = 31663022 | pmc = 6795516 | doi = 10.1126/sciadv.aax1532 | bibcode = 2019SciA....5.1532K }}</ref>

[[File:Cocaine Anonymous Chips.jpg|thumb|Cocaine Anonymous [[sobriety coin]]s]]
[[Cocaine Anonymous]] (CA) is a [[twelve-step program]] formed in 18 November 1982 for people who seek recovery from drug [[Substance dependence|addiction]]. It is patterned very closely after [[Alcoholics Anonymous]] (AA), although the two groups are unaffiliated.  While many CA members have been addicted to cocaine, crack, speed or similar substances, CA accepts all who desire freedom from "cocaine and all other mind-altering substances" as members.<ref name="CAMIND2007">{{cite web |author=Cocaine Anonymous |title=And All Other Mind-Altering Substances |access-date=15 November 2007 |date=13 November 2007 |url=http://www.ca.org/literature/allothermas.htm |archive-url=https://web.archive.org/web/20090304202508/http://www.ca.org/literature/allothermas.htm |archive-date=4 March 2009 }}</ref>

Numerous medications have been investigated for use in cocaine dependence, but {{as of|2015|lc=y}}, none of them were considered to be effective.<ref name="Minozzi2015">{{cite journal | vauthors = Minozzi S, Cinquini M, Amato L, Davoli M, Farrell MF, Pani PP, Vecchi S | veditors = Minozzi S | title = Anticonvulsants for cocaine dependence | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 4 | article-number = CD006754 | date = April 2015 | pmid = 25882271 | pmc = 8812341 | doi = 10.1002/14651858.CD006754.pub4 | type = Systematic Review & Meta-Analysis }}</ref> Drugs which help to re-stabilize the glutamate system such as [[N-acetylcysteine|''N''-acetylcysteine]] have been proposed for the treatment of addiction to cocaine, [[nicotine]], and [[Alcohol (drug)|alcohol]].<ref name="McClure_2014">{{cite journal | vauthors = McClure EA, Gipson CD, Malcolm RJ, Kalivas PW, Gray KM | title = Potential role of N-acetylcysteine in the management of substance use disorders | journal = CNS Drugs | volume = 28 | issue = 2 | pages = 95–106 | year = 2014 | pmid = 24442756 | pmc = 4009342 | doi = 10.1007/s40263-014-0142-x }}</ref> However, none have sufficient evidence or regulatory approval for routine clinical use, so psychosocial interventions remain the mainstay of treatment.<ref name="Kampman_2019" />

==== Cocaine nose ====
{{Redirect|Cocaine nose|the Playboi Carti song|Cocaine Nose (song)}}
[[File:Cocaine nose.jpg|thumb|200px|[[Nasal septum perforation]] caused by cocaine insufflation (pictured) can progress to [[cocaine-induced midline destructive lesions]]]]

"Cocaine nose" or "coke nose" are informal terms that refer to nose disorders resulting from repeated or chronic cocaine use.<ref name="Berberi_2024">{{cite journal | vauthors = Berberi A, Azar E | title = Oral Rehabilitation for a Patient with Cocaine-Induced Midline Destructive Lesions | journal = Case Reports in Otolaryngology | volume = 2024 | article-number = 7109261 | date = 2024 | pmid = 38939732 | pmc = 11208820 | doi = 10.1155/2024/7109261 | doi-access = free }}</ref><ref name="Jalali_2023">{{cite journal | vauthors = Jalali A | title = Cocaine Nose Correction: A Nonsurgical Approach Using a Novel Hyaluronic Acid Filler | journal = Plastic and Reconstructive Surgery. Global Open | volume = 11 | issue = 10 | article-number = e5329 | date = October 2023 | pmid = 37817926 | pmc = 10561808 | doi = 10.1097/GOX.0000000000005329 }}</ref><ref name="Taams_2022">{{cite journal | vauthors = Taams KO, Taams SJ | title = The Bilateral Trans Alar Forehead Flap to Reconstruct the Cocaine Nose: A Case Report | journal = Plastic and Reconstructive Surgery. Global Open | volume = 10 | issue = 1 | article-number = e4044 | date = January 2022 | pmid = 35083102 | pmc = 8785930 | doi = 10.1097/GOX.0000000000004044 }}</ref><ref name="Chatzaraki_2019">{{cite journal | vauthors = Chatzaraki V, Schweitzer W, Thali MJ, Ampanozi G | title = Nasal Septum Defects Detected on Postmortem Computed Tomography | journal = The American Journal of Forensic Medicine and Pathology | volume = 40 | issue = 3 | pages = 279–284 | date = September 2019 | pmid = 30985333 | doi = 10.1097/PAF.0000000000000482 | url = https://www.zora.uzh.ch/id/eprint/171280/1/thali_nasalseptum_verlag.pdf }}</ref>

About 30% of people who had snorted cocaine at least 25 times but less than daily, and 47% of daily users, reported experiencing nasal irritation, crusting or scabbing, and frequent nosebleeds. Cocaine use should be considered as a potential cause of persistent or unexplained [[rhinitis]], including in adolescent patients.<ref>{{cite journal | vauthors = Schwartz R, Estroff T, Fairbanks D, Hoffmann N | title = Nasal symptoms associated with cocaine abuse during adolescence. | journal = Archives of Otolaryngology–Head & Neck Surgery | volume = 115 | issue = 1 | pages = 63–64 | date = January 1989 | pmid = 2909232 | doi = 10.1001/archotol.1989.01860250065028 }}</ref>

Because the nose is a prominent facial feature, such visible damage often leads to embarrassment, stigma, and negative reactions from others. As a result, individuals with cocaine-induced nasal damage frequently withdraw from social activities and relationships, leading to [[social isolation]]. In many cases, this isolation is not just likely but almost inevitable, as affected individuals may feel unable to face the outside world due to the noticeable and sometimes severe changes to their appearance.<ref name="fraser-nose-the-irreparable-damage-cocaine-use-can-do">{{cite web |title=Fraser 'Nose' The Irreparable Damage Cocaine Use Can Do | work = National Health Service (NHS) Lanarkshire |url=https://www.nhslanarkshire.scot.nhs.uk/fraser-nose-the-irreparable-damage-cocaine-use-can-do/ }}</ref><ref name="BBC_2023">{{cite news |title=Patients face losing noses due to cocaine use, medics warn |url=https://www.bbc.com/news/uk-scotland-glasgow-west-64901125 |date=9 March 2023 | work = [[BBC]] }}</ref>

Nose disorders associated with cocaine nose include:
* [[Cocaine-induced midline destructive lesions]] (CIMDL)<ref name="Di_Cosola_2021" />
* [[Nasal septum perforation]]<ref name="Di_Cosola_2021" />
* [[Palate]] perforation<ref>{{cite journal | vauthors = Maloney B, Hinchion K, Conlon N, Omer O, Pierse D | title = Cocaine-induced destruction of the palate: a diagnostic and management challenge | journal = British Dental Journal | volume = 237 | issue = 6 | pages = 465–471 | date = September 2024 | pmid = 39333814 | pmc = 11436349 | doi = 10.1038/s41415-024-7834-5 }}</ref><ref>{{cite journal | vauthors = Trimarchi M, Bondi S, Della Torre E, Terreni MR, Bussi M | title = Palate perforation differentiates cocaine-induced midline destructive lesions from granulomatosis with polyangiitis | journal = Acta Otorhinolaryngologica Italica | volume = 37 | issue = 4 | pages = 281–285 | date = August 2017 | pmid = 28663599 | pmc = 5584099 | doi = 10.14639/0392-100X-1586 }}</ref>
* [[Saddle nose]]<ref name="Schreiber_2014">{{cite journal | vauthors = Schreiber BE, Twigg S, Marais J, Keat AC | title = Saddle-nose deformities in the rheumatology clinic | journal = Ear, Nose, & Throat Journal | volume = 93 | issue = 4–5 | pages = E45–E47 | date = April–May 2014 | pmid = 24817241 | type = Review }}</ref>

===== Cocaine-induced midline destructive lesions =====
[[Cocaine-induced midline destructive lesions]] (CIMDL)<ref name="Nitro_2022">{{cite journal | vauthors = Nitro L, Pipolo C, Fadda GL, Allevi F, Borgione M, Cavallo G, Felisati G, Saibene AM | title = Distribution of cocaine-induced midline destructive lesions: systematic review and classification | journal = European Archives of Oto-Rhino-Laryngology | volume = 279 | issue = 7 | pages = 3257–3267 | date = July 2022 | pmid = 35138441 | pmc = 9130192 | doi = 10.1007/s00405-022-07290-1 }}</ref> is the progressive destruction of nasal architecture with the erosion of the [[palate]], [[Nasal Concha|nasal conchae]], and [[ethmoid sinus]]es associated with prolonged [[Insufflation (medicine)|insufflation]], colloquially 'snorting', of cocaine.<ref name="Di_Cosola_2021">{{cite journal | vauthors = Di Cosola M, Ambrosino M, Limongelli L, Favia G, Santarelli A, Cortelazzi R, Lo Muzio L | title = Cocaine-Induced Midline Destructive Lesions (CIMDL): A Real Challenge in Diagnosis | journal = International Journal of Environmental Research and Public Health | volume = 18 | issue = 15 | page = 7831 | date = July 2021 | pmid = 34360121 | pmc = 8345435 | doi = 10.3390/ijerph18157831 | doi-access = free }}</ref>

Chronic intranasal usage can degrade the [[cartilage]] separating the [[nostrils]] (the [[septum nasi]]), leading eventually to its complete disappearance.<ref name="Pagliaro_2004">{{Cite book| vauthors = Pagliaro L, Pagliaro AM |title=Pagliaros' Comprehensive Guide to Drugs and Substances of Abuse|publisher=[[American Pharmacists Association]]|location=Washington, D.C.|year=2004|isbn=978-1-58212-066-9|url=https://archive.org/details/pagliaroscompreh0000pagl}}</ref>

===== Causes =====
The cause of "cocaine nose" can be traced to the chemical process that occurs when cocaine hydrochloride is insufflated (snorted). As cocaine is absorbed through the [[nasal mucosa]], the remaining hydrochloride component forms a dilute [[hydrochloric acid]].<ref name="Pagliaro_2004" /> The short half-life of cocaine,<ref name="Treadwell_2007" /> combined with binge use, may expose the nasal tissues to this acidic environment more frequently, increasing the risk of irritation and damage.

===== Treatment =====
For people with cocaine abuse, mild symptoms may resolve completely with total abstinence from cocaine, making early involvement of addiction services essential.<ref>{{cite journal | vauthors = Hansen FV, Kiehn OT, Lomholt AF, Ringdom H, Aanæs K | title = [Not Available] | journal = Ugeskrift for Laeger | volume = 185 | issue = 40 | date = October 2023 | pmid = 37874002 }}</ref>

Repair may involve [[rhinoplasty]], which includes creating a new internal lining with nasolabial flaps and restoring support with costal cartilage grafts.<ref>{{cite journal | vauthors = Millard DR, Mejia FA | title = Reconstruction of the nose damaged by cocaine | journal = Plastic and Reconstructive Surgery | volume = 107 | issue = 2 | pages = 419–424 | date = February 2001 | pmid = 11214057 | doi = 10.1097/00006534-200102000-00018 }}</ref>

In 2024, Belgian doctors report a rise in patients needing nose reconstruction due to cocaine use, which damages nasal tissue and cartilage; however, few undergo surgery because it requires at least six months of abstinence from cocaine for proper healing.<ref>{{cite news | vauthors = Min R |title=Doctors in Belgium see serious nose lesions amid rising cocaine use |url=https://www.euronews.com/health/2024/03/28/more-people-in-belgium-need-nose-reconstruction-due-to-cocaine-use-doctors-say |work=euronews |date=28 March 2024 }}</ref>

Some individuals seek [[plastic surgery]] to repair or reconstruct nasal damage caused by cocaine use, although surgical outcomes can be complicated by ongoing tissue loss and poor healing. When nasal damage is too severe for reconstruction, a [[nose prosthesis]] may be used to restore appearance and [[quality of life]].<ref name="fraser-nose-the-irreparable-damage-cocaine-use-can-do" /><ref name="BBC_2023" />

== Overdose ==
{{Main|Cocaine intoxication}}

[[File:Death rates from cocaine overdoses, OWID.svg|thumb|Death rates from cocaine overdoses]]
[[File:US timeline. Cocaine deaths.svg|thumb|upright=1.3|US yearly overdose deaths involving cocaine.<ref name="NIDA-deaths">{{cite web | url = http://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates | title = Overdose Death Rates | work = [[National Institute on Drug Abuse]] (NIDA) | date = 21 August 2024 }}</ref>]]

According to the [[European Union Drugs Agency]], the estimated minimum lethal dose is 1.2 grams. However, sensitive individuals have died from as little as 30 milligrams applied to mucous membranes-an amount that is 40 times less than the minimum lethal dose. In contrast, addicts may tolerate doses as high as 5 grams per day.<ref name="EUDA" />

Use of cocaine causes [[cardiac arrhythmia|abnormally fast heart rhythms]] and a marked elevation of blood pressure ([[hypertension]]), which can be life-threatening. This can lead to death from acute [[myocardial infarction]], acute [[respiratory failure]] (i.e., [[hypoxemia]], with or without [[hypercapnia]]), [[stroke]], [[cerebral hemorrhage]], and [[Cardiac arrest|sudden cardiac arrest]].<ref>{{cite journal | vauthors = O'Leary ME, Hancox JC | title = Role of voltage-gated sodium, potassium and calcium channels in the development of cocaine-associated cardiac arrhythmias | journal = British Journal of Clinical Pharmacology | volume = 69 | issue = 5 | pages = 427–442 | date = May 2010 | pmid = 20573078 | pmc = 2856043 | doi = 10.1111/j.1365-2125.2010.03629.x }}</ref> Overdose can also cause acute [[hepatotoxicity]]—typically due to toxic metabolites—though most cases resolve quickly; however, fatal outcomes from [[multiple organ dysfunction syndrome]] are possible, and there is no specific antidote.<ref>{{cite journal | vauthors =  | title = Cocaine | journal = LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. | location = Bethesda (MD) | publisher = National Institute of Diabetes and Digestive and Kidney Diseases | date = 2017 | pmid = 31643773 | url = https://www.ncbi.nlm.nih.gov/books/NBK548454/ }}</ref> Cocaine overdose may result in [[hyperthermia]] as stimulation and increased muscular activity cause greater heat production. Heat loss is also inhibited by the cocaine-induced [[vasoconstriction]].{{Citation needed|date=November 2025}}

In 2024, drug-related deaths in England and Wales reached their highest level in three decades, with a notable increase in fatalities involving cocaine and experts urging urgent government intervention to address the crisis. Martin Powell, from the charity Transform, which campaigns for the [[drug liberalization|legal regulation of drugs]], suggested that the recent rise in cocaine-related deaths in the UK may be due to the increased purity of cocaine, leading users to consume it more frequently and alongside other substances.<ref>{{cite news | vauthors = Lawrie E |title=Cocaine use fuels record high in drug deaths |url=https://www.bbc.com/news/articles/cy5l4nknew0o |work=www.bbc.com |date=23 October 2024}}</ref>

== Interactions ==
{{See also|Combined drug intoxication}}

=== Alcohol ===
{{Main|Cocaethylene}}

{{See also|Coca wine}}

[[Alcohol (drug)|Alcohol]] interacts with cocaine ''in vivo'' to produce [[cocaethylene]], another psychoactive substance which may be substantially more [[cardiotoxic]] than either cocaine or alcohol by themselves.<ref>{{cite journal |vauthors=Laizure SC, Mandrell T, Gades NM, Parker RB |title=Cocaethylene metabolism and interaction with cocaine and ethanol: role of carboxylesterases |journal=Drug Metabolism and Disposition |volume=31 |issue=1 |pages=16–20 |date=January 2003 |pmid=12485948 |doi=10.1124/dmd.31.1.16}}</ref><ref>{{cite journal |vauthors=Pergolizzi J, Breve F, Magnusson P, LeQuang JA, Varrassi G |title=Cocaethylene: When Cocaine and Alcohol Are Taken Together |journal=Cureus |volume=14 |issue=2 |date=February 2022 |article-number=e22498 |pmid=35345678 |pmc=8956485 |doi=10.7759/cureus.22498 |doi-access=free}}</ref> In 2024, a systematic review of human studies concluded that, despite some inconsistencies in the findings, the co-use of cocaine and alcohol poses a significantly greater risk of cardiovascular fatalities compared to cocaine use alone. This elevated risk is largely attributed to the formation of cocaethylene, a unique and toxic metabolite produced only when both substances are consumed together. Cocaethylene is associated with an 18- to 25-fold increased risk of sudden death, as well as a higher incidence of myocardial injury and cardiac arrest, underscoring the serious health risks of simultaneous cocaine and alcohol use.<ref>{{cite journal | vauthors = van Amsterdam J, Gresnigt F, van den Brink W | title = Cardiovascular Risks of Simultaneous Use of Alcohol and Cocaine-A Systematic Review | journal = Journal of Clinical Medicine | volume = 13 | issue = 5 | page = 1475 | date = March 2024 | pmid = 38592322 | pmc = 10935323 | doi = 10.3390/jcm13051475 | doi-access = free }}</ref>

=== MAOIs ===
[[Monoamine oxidase inhibitor]]s (MAOIs) should not be combined with other psychoactive substances (antidepressants, painkillers, stimulants, including prescribed, OTC and illegally acquired drugs, etc.) except under expert care.{{citation needed|date=June 2025}}

=== Opioids ===
{{See also|Speedball (drug)|Opioid epidemic in the United States}}
The [[opioid epidemic]] now involves more overdose deaths with both opioids and cocaine, especially among non-Hispanic Blacks who are twice as likely to die from combined opioid-stimulant overdoses compared to non-Hispanic whites. Cocaine-related deaths in Blacks are similar to opioid deaths in whites. Risk factors include young age, education, urban living, mental disorders, and stress. It remains unclear if co-use is intentional. Recent studies expand focus beyond heroin to all opioids, reflecting changing overdose patterns.<ref>{{cite journal | vauthors = Liu X, Singer ME | title = Intentional use of both opioids and cocaine in the United States | journal = Preventive Medicine Reports | volume = 33 | article-number = 102227 | date = June 2023 | pmid = 37223567 | pmc = 10201855 | doi = 10.1016/j.pmedr.2023.102227 }}</ref>

== Pharmacology ==

=== Pharmacokinetics ===
The extent of absorption of cocaine into the [[circulatory system]] after nasal insufflation is similar to that after oral ingestion. The rate of absorption after nasal insufflation is limited by cocaine-induced vasoconstriction of capillaries in the nasal mucosa. Onset of absorption after oral ingestion is delayed because cocaine is a weak base with a [[pKa]] of 8.6, and is thus in an ionized form that is poorly absorbed from the [[gastric acid]] and easily absorbed from the alkaline [[duodenum]].<ref name="Wilkinson_1980" /> The rate and extent of absorption from inhalation of cocaine is similar or greater than with intravenous injection, as inhalation provides access directly to the [[capillary]] bed. The delay in absorption after oral ingestion may account for the popular belief that cocaine bioavailability from the stomach is lower than after insufflation. Compared with ingestion, the faster absorption of insufflated cocaine results in quicker attainment of maximum drug effects. Snorting cocaine produces maximum physiological effects within 40&nbsp;minutes and maximum psychotropic effects within 20&nbsp;minutes. Physiological and psychotropic effects from nasally insufflated cocaine are sustained for approximately 40–60&nbsp;minutes after the peak effects are attained.<ref>{{Cite journal | vauthors = Barnett G, Hawks R, Resnick R | title = Cocaine pharmacokinetics in humans | journal = Journal of Ethnopharmacology | volume = 3 | issue = 2–3 | pages = 353–66 | year = 1981 | pmid = 7242115 | doi = 10.1016/0378-8741(81)90063-5 }}; Jones, supra note 19; Wilkinson ''et al.'', Van Dyke ''et al.''</ref>

Cocaine crosses the [[blood–brain barrier]] via both a proton-coupled [[Organic cation transport protein|organic cation antiporter]]<ref name="How do psychostimulants enter the h">{{Cite journal | vauthors = Sachkova A, Doetsch DA, Jensen O, Brockmöller J, Ansari S | title = How do psychostimulants enter the human brain? Analysis of the role of the proton-organic cation antiporter | journal = Biochemical Pharmacology | volume = 192 | article-number = 114751 | date = October 2021 | pmid = 34464621 | doi = 10.1016/j.bcp.2021.114751 }}</ref><ref name="Structural Requirements for Uptake">{{Cite journal | vauthors = Tega Y, Tabata H, Kurosawa T, Kitamura A, Itagaki F, Oshitari T, Deguchi Y | title = Structural Requirements for Uptake of Diphenhydramine Analogs into hCMEC/D3 Cells Via the Proton-Coupled Organic Cation Antiporter | journal = Journal of Pharmaceutical Sciences | volume = 110 | issue = 1 | pages = 397–403 | date = January 2021 | pmid = 32898521 | doi = 10.1016/j.xphs.2020.09.001 | doi-access = free | bibcode = 2021JPhmS.110..397T }}</ref> and (to a lesser extent) via [[Passive transport|passive diffusion across cell membranes]].<ref name="Chapy_2014">{{Cite journal | vauthors = Chapy H, Smirnova M, André P, Schlatter J, Chiadmi F, Couraud PO, Scherrmann JM, Declèves X, Cisternino S | title = Carrier-mediated cocaine transport at the blood–brain barrier as a putative mechanism in addiction liability | journal = The International Journal of Neuropsychopharmacology | volume = 18 | issue = 1 | article-number = pyu001 | date = October 2014 | pmid = 25539501 | pmc = 4368859 | doi = 10.1093/ijnp/pyu001 }}</ref> As of September 2022, the gene or genes encoding the human proton-organic cation antiporter had not been identified.<ref>{{Cite journal | vauthors = Sachkova A, Jensen O, Dücker C, Ansari S, Brockmöller J | title = The mystery of the human proton-organic cation antiporter: One transport protein or many? | journal = Pharmacology & Therapeutics | article-number = 108283 | date = September 2022 | volume = 239 | pmid = 36162727 | doi = 10.1016/j.pharmthera.2022.108283 | s2cid = 252527522 | url = https://resolver.sub.uni-goettingen.de/purl?gro-2/117956 }}</ref>

Cocaine has a short elimination half-life of 0.7–1.5 hours and is extensively [[metabolism|metabolized]] by [[Blood plasma|plasma]] esterases and also by liver [[cholinesterase]]s, with only about 1% excreted unchanged in the urine.<ref name="Zimmerman_2012" /> The metabolism is dominated by [[hydrolysis|hydrolytic]] [[ester]] cleavage, so the eliminated metabolites consist mostly of [[benzoylecgonine]] (BE), the major [[metabolite]], and other metabolites in lesser amounts such as ecgonine methyl ester (EME) and [[ecgonine]].<ref>{{Cite journal | vauthors = Ambre J, Ruo TI, Nelson J, Belknap S | title = Urinary excretion of cocaine, benzoylecgonine, and ecgonine methyl ester in humans | journal = Journal of Analytical Toxicology | volume = 12 | issue = 6 | pages = 301–6 | date = November 1988 | pmid = 3244269 | doi = 10.1093/jat/12.6.301 }}</ref><ref name="Zimmerman_2012" /> Further minor metabolites of cocaine include [[norcocaine]], p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine ({{chem name|pOHBE}}), and m-hydroxybenzoylecgonine.<ref>{{Cite journal | vauthors = Kolbrich EA, Barnes AJ, Gorelick DA, Boyd SJ, Cone EJ, Huestis MA | title = Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration | journal = Journal of Analytical Toxicology | volume = 30 | issue = 8 | pages = 501–10 | date = October 2006 | pmid = 17132243 | doi = 10.1093/jat/30.8.501 | url = https://openurl.ingenta.com/content/nlm?genre=article&issn=0146-4760&volume=30&issue=8&spage=501&aulast=Kolbrich | doi-access = free | archive-url = https://archive.today/20120718083717/http://openurl.ingenta.com/content/nlm?genre=article&issn=0146-4760&volume=30&issue=8&spage=501&aulast=Kolbrich | archive-date = 18 July 2012 }}</ref>

Depending on [[liver]] and [[kidney]] functions, cocaine metabolites are detectable in urine between three and eight days. Generally speaking [[benzoylecgonine]] is eliminated from someone's urine between three and five days. In urine from heavy cocaine users, benzoylecgonine can be detected within four hours after intake and in concentrations greater than 150&nbsp;ng/mL for up to eight days later.<ref>{{cite web|title=Schaffer Library of Drug Policy: Urine Testing for Cocaine|access-date=3 April 2025|url=https://www.druglibrary.drugsense.org/schaffer/cocaine/clearurine.htm}}</ref>

=== Detection in the body ===

==== Body fluids ====
Cocaine and its major metabolites may be quantified in blood, plasma, or urine to monitor for use, confirm a diagnosis of poisoning, or assist in the forensic investigation of a traffic or other criminal violation or sudden death. Most commercial cocaine [[immunoassay]] screening tests cross-react appreciably with the major cocaine metabolites, but [[chromatography|chromatographic]] techniques can easily distinguish and separately measure each of these substances. When interpreting the results of a test, it is important to consider the cocaine usage history of the individual, since a chronic user can develop tolerance to doses that would incapacitate a cocaine-naive individual, and the chronic user often has high baseline values of the metabolites in his system. Cautious interpretation of testing results may allow a distinction between passive or active usage, and between smoking versus other routes of administration.<ref>{{cite book | vauthors = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 9th | publisher = Biomedical Publications | location = Seal Beach, California |year = 2011 |pages = 390–394 }}</ref>

==== Hair ====
[[Hair analysis]] can detect cocaine [[metabolite]]s in regular users until after the sections of hair grown during the period of cocaine use are cut or fall out.<ref>{{Cite web|url=https://www.chemistryviews.org/details/news/8693061/Cocaine_Metabolites_in_Hair.html|title=Cocaine Metabolites in Hair|vauthors=Czykanski M|date=30 December 2015|website=Chemistry Views|access-date=22 July 2019|archive-date=22 July 2019|archive-url=https://web.archive.org/web/20190722212558/https://www.chemistryviews.org/details/news/8693061/Cocaine_Metabolites_in_Hair.html|url-status=live}}</ref>

=== Pharmacodynamics ===
Cocaine acts as a [[serotonin–norepinephrine–dopamine reuptake inhibitor]] (SNDRI).<ref name="Azizi_2022" /><ref name="Cheng_2015" /> Cocaine increases levels of [[serotonin]], [[norepinephrine]], and [[dopamine]] in the synaptic cleft, leading to heightened post-synaptic activation, with dopamine contributing to euphoria and arousal, and the other monoamines enhancing additional effects.<ref name="Azizi_2022" /><ref>{{Cite journal | vauthors = Proebstl L, Kamp F, Manz K, Krause D, Adorjan K, Pogarell O, Koller G, Soyka M, Falkai P, Kambeitz J | title = Effects of stimulant drug use on the dopaminergic system: A systematic review and meta-analysis of in vivo neuroimaging studies | journal = European Psychiatry | volume = 59 | pages = 15–24 | date = June 2019 | pmid = 30981746 | doi = 10.1016/j.eurpsy.2019.03.003 | doi-access = free }}</ref><ref>{{Cite web|url=https://www.drugabuse.gov/publications/research-reports/cocaine/how-does-cocaine-produce-its-effects|title=How does cocaine produce its effects?|access-date=12 May 2021|archive-date=18 January 2022|archive-url=https://web.archive.org/web/20220118113925/https://www.drugabuse.gov/publications/research-reports/cocaine/how-does-cocaine-produce-its-effects}}</ref><ref>{{Cite journal | vauthors = Wise RA, Robble MA | title = Dopamine and Addiction | journal = Annual Review of Psychology | volume = 71 | issue = 1 | pages = 79–106 | date = January 2020 | pmid = 31905114 | doi = 10.1146/annurev-psych-010418-103337 | doi-access = free }}</ref>

The [[pharmacodynamics]] of cocaine involve the complex relationships of neurotransmitters (inhibiting [[monoamine]] uptake in rats with ratios of about: [[5HT|serotonin]]:dopamine = 2:3, serotonin:[[norepinephrine]] = 2:5).<ref>{{Cite journal | vauthors = Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS | title = Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | journal = Synapse | volume = 39 | issue = 1 | pages = 32–41 | date = January 2001 | pmid = 11071707 | doi = 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 | s2cid = 15573624 }} (Table V. on page 37)</ref><ref name="Pom_2012" /> The most extensively studied effect of cocaine on the [[central nervous system]] is the blockade of the [[dopamine transporter]] protein. Dopamine [[neurotransmitter]] released during neural signaling is normally recycled via the transporter; i.e., the transporter binds the transmitter and pumps it out of the synaptic cleft back into the [[presynaptic]] [[neuron]], where it is taken up into storage [[vesicle (biology)|vesicles]]. Cocaine binds tightly at the dopamine transporter forming a complex that blocks the transporter's function. The dopamine transporter can no longer perform its reuptake function, and thus [[dopamine]] accumulates in the [[synaptic cleft]]. The increased concentration of dopamine in the synapse activates post-synaptic dopamine receptors, which makes the drug [[Reward system|rewarding]] and promotes the compulsive use of cocaine.<ref>{{Cite journal | vauthors = Hummel M, Unterwald EM | title = D1 dopamine receptor: a putative neurochemical and behavioral link to cocaine action | journal = Journal of Cellular Physiology | volume = 191 | issue = 1 | pages = 17–27 | date = April 2002 | pmid = 11920678 | doi = 10.1002/jcp.10078 | s2cid = 40444893 | doi-access = free }}</ref>

Cocaine affects certain serotonin (5-HT) receptors; in particular, it has been shown to [[receptor antagonist|antagonize]] the [[5-HT3 receptor|5-HT<sub>3</sub> receptor]], which is a [[ligand-gated ion channel]]. An overabundance of 5-HT<sub>3</sub> receptors is reported in cocaine-conditioned rats, though 5-HT<sub>3</sub>'s role is unclear.<ref>{{Cite journal | vauthors = Carta M, Allan AM, Partridge LD, Valenzuela CF | title = Cocaine inhibits 5-HT3 receptor function in neurons from transgenic mice overexpressing the receptor | journal = European Journal of Pharmacology | volume = 459 | issue = 2–3 | pages = 167–9 | date = January 2003 | pmid = 12524142 | doi = 10.1016/S0014-2999(02)02867-4 }}</ref> The [[5-HT2 receptor|5-HT<sub>2</sub> receptor]] (particularly the subtypes [[5-HT2A receptor|5-HT<sub>2A</sub>]], [[5-HT2B receptor|5-HT<sub>2B</sub>]] and [[5-HT2C receptor|5-HT<sub>2C</sub>]]) are involved in the [[Locomotor activity|locomotor-activating]] effects of cocaine.<ref>{{Cite journal | vauthors = Filip M, Bubar MJ, Cunningham KA | title = Contribution of serotonin (5-hydroxytryptamine; 5-HT) 5-HT2 receptor subtypes to the hyperlocomotor effects of cocaine: acute and chronic pharmacological analyses | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 310 | issue = 3 | pages = 1246–54 | date = September 2004 | pmid = 15131246 | doi = 10.1124/jpet.104.068841 | s2cid = 25809734 }}</ref>

Cocaine has been demonstrated to bind as to directly stabilize the [[Dopamine transporter|DAT]] transporter on the open outward-facing conformation. Further, cocaine binds in such a way as to inhibit a [[hydrogen bond]] innate to DAT. Cocaine's binding properties are such that it attaches so this hydrogen bond will not form and is blocked from formation due to the tightly locked orientation of the cocaine molecule. Research studies have suggested that the affinity for the transporter is not what is involved in the habituation of the substance so much as the conformation and binding properties to where and how on the transporter the molecule binds.<ref>{{Cite journal | vauthors = Beuming T, Kniazeff J, Bergmann ML, Shi L, Gracia L, Raniszewska K, Newman AH, Javitch JA, Weinstein H, Gether U, Loland CJ | title = The binding sites for cocaine and dopamine in the dopamine transporter overlap | journal = Nature Neuroscience | volume = 11 | issue = 7 | pages = 780–9 | date = July 2008 | pmid = 18568020 | pmc = 2692229 | doi = 10.1038/nn.2146 }}</ref>

Conflicting findings have challenged the widely accepted view that cocaine functions solely as a reuptake inhibitor. To induce euphoria an intravenous dose of 0.3-0.6&nbsp;mg/kg of cocaine is required, which blocks 66-70% of DAT in the brain.<ref>{{cite journal | vauthors = Volkow ND, Wang GJ, Fischman MW, Foltin RW, Fowler JS, Abumrad NN, Vitkun S, Logan J, Gatley SJ, Pappas N, Hitzemann R, Shea CE | title = Relationship between subjective effects of cocaine and dopamine transporter occupancy | journal = Nature | volume = 386 | issue = 6627 | pages = 827–830 | date = April 1997 | pmid = 9126740 | doi = 10.1038/386827a0 | bibcode = 1997Natur.386..827V }}</ref> Re-administering cocaine beyond this threshold does not significantly increase DAT occupancy but still results in an increase of euphoria which cannot be explained by reuptake inhibition alone. This discrepancy is not shared with other dopamine reuptake inhibitors like [[bupropion]], [[sibutramine]], [[mazindol]] or [[tesofensine]], which have similar or higher potencies than cocaine as dopamine reuptake inhibitors. Furthermore, a similar response-occupancy discrepancy has been observed with [[methylphenidate]], which also stabilizes the dopamine transporter in an open outward-facing conformation.<ref name="Heal_2014">{{cite journal | vauthors = Heal DJ, Gosden J, Smith SL | title = Dopamine reuptake transporter (DAT) "inverse agonism"--a novel hypothesis to explain the enigmatic pharmacology of cocaine | journal = Neuropharmacology | volume = 87 | pages = 19–40 | date = December 2014 | pmid = 24953830 | doi = 10.1016/j.neuropharm.2014.06.012 | series = CNS Stimulants }}</ref><ref>{{cite journal | vauthors = Volkow ND, Wang GJ, Fowler JS, Gatley SJ, Ding YS, Logan J, Dewey SL, Hitzemann R, Lieberman J | title = Relationship between psychostimulant-induced "high" and dopamine transporter occupancy | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 19 | pages = 10388–10392 | date = September 1996 | pmid = 8816810 | pmc = 38394 | doi = 10.1073/pnas.93.19.10388 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Schmitt KC, Reith ME | title = The atypical stimulant and nootropic modafinil interacts with the dopamine transporter in a different manner than classical cocaine-like inhibitors | journal = PLOS ONE | volume = 6 | issue = 10 | article-number = e25790 | date = 2011 | pmid = 22043293 | pmc = 3197159 | doi = 10.1371/journal.pone.0025790 | doi-access = free | bibcode = 2011PLoSO...625790S }}</ref> These findings have evoked a hypothesis that cocaine may also function as a so-called "DAT inverse agonist" or "negative allosteric modifier of DAT" resulting in dopamine [[Reverse transport|transporter reversal]], and subsequent dopamine release into the synaptic cleft from the axon terminal in a manner similar to but distinct from [[amphetamine]]s.<ref name="Heal_2014" />

[[Sigma receptor]]s are affected by cocaine, as cocaine functions as a sigma ligand agonist.<ref>{{cite journal | vauthors = Zhu LX, Sharma S, Gardner B, Escuadro B, Atianzar K, Tashkin DP, Dubinett SM | title = IL-10 mediates sigma 1 receptor-dependent suppression of antitumor immunity | journal = Journal of Immunology | location = Baltimore, Md. | volume = 170 | issue = 7 | pages = 3585–91 | date = April 2003 | pmid = 12646621 | doi = 10.4049/jimmunol.170.7.3585 }} {{lay source |template=cite news |url=https://www.sciencedaily.com/releases/2003/05/030506073758.htm |title=Sigma Receptors Play Role in Cocaine-induced Suppression of Immune System |date= 6 May 2003 |work=ScienceDaily }}</ref> Further specific receptors it has been demonstrated to function on are [[NMDA]] and the D<sub>1</sub> dopamine receptor.<ref>{{Cite journal | vauthors = Lluch J, Rodríguez-Arias M, Aguilar MA, Miñarro J | title = Role of dopamine and glutamate receptors in cocaine-induced social effects in isolated and grouped male OF1 mice | journal = Pharmacology Biochemistry and Behavior | volume = 82 | issue = 3 | pages = 478–87 | date = November 2005 | pmid = 16313950 | doi = 10.1016/j.pbb.2005.10.003 | s2cid = 13307446 }}</ref>

Cocaine also blocks [[ion channel|sodium channels]], thereby interfering with the propagation of [[action potential]]s;<ref>{{Cite journal | vauthors = Knuepfer MM | title = Cardiovascular disorders associated with cocaine use: myths and truths | journal = Pharmacology & Therapeutics | volume = 97 | issue = 3 | pages = 181–222 | date = March 2003 | pmid = 12576134 | doi = 10.1016/S0163-7258(02)00329-7 }}</ref><ref name="O'Leary_2010" /> thus, like [[lignocaine]] and [[novocaine]], it acts as a local anesthetic. It also functions on the binding sites to the dopamine and serotonin [[sodium]] dependent transport area as targets as separate mechanisms from its reuptake of those transporters; unique to its local anesthetic value which makes it in a class of functionality different from both its own derived [[phenyltropane]]s analogues which have that removed. In addition to this, cocaine has some target binding to the site of the [[κ-opioid receptor]].<ref>{{Cite web |url=https://www.drugbank.ca/drugs/DB00907 |title=Drugbank website "drug card", "(DB00907)" for Cocaine: Giving ten targets of the molecule in vivo, including dopamine/serotonin sodium channel affinity & K-opioid affinity |publisher=Drugbank.ca |access-date=9 March 2010 |url-status=live |archive-url=https://web.archive.org/web/20100220190540/https://www.drugbank.ca/drugs/DB00907 |archive-date=20 February 2010 }}</ref>{{Unreliable medical source|date=May 2025}} Cocaine also causes [[vasoconstriction]], thus reducing bleeding during minor surgical procedures. Recent research points to an important role of circadian mechanisms<ref>{{Cite journal | vauthors = Uz T, Akhisaroglu M, Ahmed R, Manev H | title = The pineal gland is critical for circadian Period1 expression in the striatum and for circadian cocaine sensitization in mice | journal = Neuropsychopharmacology | volume = 28 | issue = 12 | pages = 2117–23 | date = December 2003 | pmid = 12865893 | doi = 10.1038/sj.npp.1300254 | doi-access = free }}</ref> and [[clock genes]]<ref>{{Cite journal | vauthors = McClung CA, Sidiropoulou K, Vitaterna M, Takahashi JS, White FJ, Cooper DC, Nestler EJ | title = Regulation of dopaminergic transmission and cocaine reward by the Clock gene | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 26 | pages = 9377–81 | date = June 2005 | pmid = 15967985 | pmc = 1166621 | doi = 10.1073/pnas.0503584102 | bibcode = 2005PNAS..102.9377M | doi-access = free }}</ref> in behavioral actions of cocaine.

Cocaine is known to suppress hunger and appetite by increasing co-localization of sigma σ<sub>1</sub>R receptors and [[ghrelin]] GHS-R1a [[cell surface receptor]]s, thereby increasing ghrelin-mediated signaling of satiety<ref>{{Cite journal | vauthors = Aguinaga D, Medrano M, Cordomí A, Jiménez-Rosés M, Angelats E, Casanovas M, Vega-Quiroga I, Canela EI, Petrovic M, Gysling K, Pardo L, Franco R, Navarro G | title = Cocaine Blocks Effects of Hunger Hormone, Ghrelin, Via Interaction with Neuronal Sigma-1 Receptors | journal = Molecular Neurobiology | volume = 56 | issue = 2 | pages = 1196–1210 | date = February 2019 | pmid = 29876881 | doi = 10.1007/s12035-018-1140-7 | hdl-access = free | s2cid = 46964405 | hdl = 2445/127306 }}</ref> and possibly via other effects on appetitive hormones.<ref>{{Cite journal | vauthors = Bouhlal S, Ellefsen KN, Sheskier MB, Singley E, Pirard S, Gorelick DA, Huestis MA, Leggio L | title = Acute effects of intravenous cocaine administration on serum concentrations of ghrelin, amylin, glucagon-like peptide-1, insulin, leptin and peptide YY and relationships with cardiorespiratory and subjective responses | journal = Drug and Alcohol Dependence | volume = 180 | pages = 68–75 | date = November 2017 | pmid = 28881319 | pmc = 5654385 | doi = 10.1016/j.drugalcdep.2017.07.033 }}</ref>

Cocaine effects, further, are shown to be potentiated for the user when used in conjunction with new surroundings and stimuli, and otherwise novel environs.<ref>{{Cite journal | vauthors = Carey RJ, Damianopoulos EN, Shanahan AB | title = Cocaine effects on behavioral responding to a novel object placed in a familiar environment | journal = Pharmacology Biochemistry and Behavior | volume = 88 | issue = 3 | pages = 265–71 | date = January 2008 | pmid = 17897705 | doi = 10.1016/j.pbb.2007.08.010 | s2cid = 22711773 }}</ref>

== Chemistry ==
{{see also|coca alkaloid|list of cocaine analogues}}

=== Forms ===
{{See also|Cocaine paste|Crack cocaine#Chemistry}}
[[File:CocaineHydrochloridePowder cropped.jpg|right|thumb|A pile of [[micronization|micronized]] cocaine hydrochloride]]
[[File:CocaineHCl.jpg|right|thumb|A piece of compressed cocaine hydrochloride, commonly used for smuggling]]

In its purest form, cocaine is a white, pearly powder. As a [[tropane alkaloid]], cocaine is a weak base and readily forms salts when combined with acids. The most commonly encountered form is the hydrochloride (HCl) salt, although other salts such as the sulfate (SO<sub>4</sub><sup>2−</sup>) and nitrate (NO<sub>3</sub><sup>−</sup>) are occasionally observed. The solubility of these salts varies depending on their polarity; the hydrochloride salt is polar and highly soluble in water.<ref>{{Cite web | vauthors = Cotton S | date = February 2016 | work = Molecule of the Month | publisher = University of Bristol |url= https://www.chm.bris.ac.uk/motm/cocaine/cocaineh.htm |title=Cocaine: The notorious recreational drug |access-date=4 May 2020|archive-date=8 July 2024|archive-url=https://web.archive.org/web/20240708191819/https://www.chm.bris.ac.uk/motm/cocaine/cocaineh.htm|url-status=live}}</ref>

=== Synthesis ===

==== Total synthesis ====
The first [[Chemical structure#Structural elucidation|structure elucidation]] and [[total synthesis]] of the cocaine molecule was accomplished by [[Richard Willstätter]] in 1898.<ref name="Humphrey_2001">{{Cite journal | vauthors = Humphrey AJ, O'Hagan D | title = Tropane alkaloid biosynthesis. A century-old problem unresolved | journal = Natural Product Reports | volume = 18 | issue = 5 | pages = 494–502 | date = October 2001 | pmid = 11699882 | doi = 10.1039/b001713m }}</ref> Willstätter's synthesis involved constructing the cocaine structure from simpler precursors, notably via the intermediate [[tropinone]]. Subsequent significant contributions to understanding the synthetic pathway and stereochemistry were made by [[Robert Robinson (organic chemist)|Robert Robinson]] and Edward Leete.

Cocaine contains four [[chiral]] centers (1''R'', 2''R'', 3''S'', and 5''S''), two of which are [[Molecular configuration|configuration]]ally dependent, resulting in eight possible [[stereoisomer]]s. The formation of inactive stereoisomers, along with various synthetic by-products, limits both the yield and purity of the final product.<ref name="Amara_2021">{{cite journal | vauthors = Amara SB, Koslowski T, Zaidi A | title=Quantum Chemistry of Cocaine and its Isomers I: Energetics, Reactivity and Solvation | journal=South African Journal of Chemistry | volume=75 | date=2021 | doi=10.17159/0379-4350/2021/v75a3| doi-access=free }}</ref><ref name="Drake_2018">{{cite journal | vauthors = Drake LR, Scott PJ | title = DARK Classics in Chemical Neuroscience: Cocaine | journal = ACS Chemical Neuroscience | volume = 9 | issue = 10 | pages = 2358–2372 | date = October 2018 | pmid = 29630337 | pmc = 6197930 | doi = 10.1021/acschemneuro.8b00117 }}</ref>

Although the chemical synthesis of cocaine is technically feasible, it is generally considered impractical due to its high cost, low efficiency, and challenges in stereoselective synthesis compared to extraction from natural plant sources. While domestic clandestine laboratories could theoretically reduce reliance on offshore production and international smuggling—as seen with illicit [[methamphetamine]]—manufacture and synthetic production of cocaine remains rare. Large-scale commercial synthesis has not been explored.<ref name="Kohnen-Johannsen_2019">{{cite journal | vauthors = Kohnen-Johannsen KL, Kayser O | title = Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production | journal = Molecules | volume = 24 | issue = 4 | page = 796 | date = February 2019 | pmid = 30813289 | pmc = 6412926 | doi = 10.3390/molecules24040796 | doi-access = free }}</ref>

==== Biosynthesis ====
{{Main|Biosynthesis of cocaine}}

The [[biosynthesis of cocaine]] is the natural metabolic process by which the [[coca plant]] (''Erythroxylum'' species) produces cocaine, a [[tropane alkaloid]], through a multi-step enzymatically catalyzed pathway beginning with [[ornithine]] or [[arginine]] and culminating in the formation of the cocaine metabolite [[benzoylecgonine]].

Large-scale biosynthesis of cocaine is unexplored.<ref name="Kohnen-Johannsen_2019" />

The biosynthesis of cocaine has long attracted the attention of biochemists and organic chemists.  This interest is partly motivated by the strong physiological effects of cocaine, but a further incentive was the unusual [[Bicyclic molecule|bicyclic]] structure of the molecule.  The biosynthesis can be viewed as occurring in two phases, one phase leading to the N-methylpyrrolinium ring, which is preserved in the final product.  The second phase incorporates a C4 unit with formation of the bicyclic [[tropane]] core.<ref name="Leete_1990">{{cite journal | vauthors = Leete E | title = Recent Developments in the Biosynthesis of the Tropane Alkaloids1 | journal = Planta Medica | volume = 56 | issue = 4 | pages = 339–352 | date = Aug 1990 | pmid = 2236285 | doi = 10.1055/s-2006-960979 | doi-access = free | bibcode = 1990PlMed..56..339L }}</ref>

==== GMO synthesis ====

In 2022, a [[GMO]] produced ''[[N. benthamiana]]'' were discovered that were able to produce 25% of the amount of cocaine found in a coca plant.<ref>{{Cite web | vauthors = Wilkins A | date = 25 November 2022 |title=Genetically modified tobacco plant produces cocaine in its leaves |url=https://www.newscientist.com/article/2348568-genetically-modified-tobacco-plant-produces-cocaine-in-its-leaves/ |website=New Scientist |access-date=27 November 2022 |archive-date=27 November 2022 |archive-url=https://web.archive.org/web/20221127225822/https://www.newscientist.com/article/2348568-genetically-modified-tobacco-plant-produces-cocaine-in-its-leaves/ |url-status=live }}</ref>

However, since ''N. benthamiana'' also naturally contains [[nicotine]], separating the cocaine from nicotine and related alkaloids would be challenging.

=== Field analysis ===
[[File:Drugwipe Kokain.jpg|thumb|[[Drugwipe test]] can detect traces of illicit substances, including cocaine, on surfaces such as driver's licenses at [[random checkpoint]]s.]]
[[File:Cocaine under UV light 03.jpg|thumb|Cocaine under [[UV light]]]]

[[Personal data|Personal]] cards-including ID cards and driver's licenses-are frequently swabbed by inspectors to detect drug residue, as these items are commonly used to prepare lines of cocaine. Swabbing can reveal traces of cocaine or other illicit substances, providing evidence of recent drug handling or use. This practice may be employed during security checks at border crossings.

A ''[[Newsbeat]]'' investigation found that "cocaine torches" used by UK police to detect cocaine use are ineffective on typical street cocaine, as independent lab tests showed they fail to make the drug [[fluoresce]]. Experts and drug charities criticized the devices, warning they can give false positives and waste resources, while police forces defended their use as a deterrent. The manufacturer says the torches only work on much purer forms of cocaine than are found on the street.<ref>{{cite news | vauthors = Crawford D |title=Drug torches 'don't always work' |url=https://www.bbc.com/news/newsbeat-10000473 |work=BBC News |date=22 July 2009}}</ref><ref>{{cite news | vauthors = Taylor J |title=Drug torches for bouncers 'don't always spot cocaine' |url=https://www.bbc.com/news/newsbeat-22774362 |work=BBC News |date=14 June 2013}}</ref>

Cocaine may be detected by law enforcement using the [[Scott reagent]]. The test can easily generate [[False positives and false negatives|false positives]] for common substances and must be confirmed with a laboratory test.<ref>{{Cite news |url=https://psmag.com/news/meet-the-chemist-behind-many-popular-and-faulty-police-drug-kits | vauthors = Gabrielson R |title=Meet the Chemist Behind Many Popular—and Faulty—Police Drug Kits |date=22 June 2016 |work=Pacific Standard |access-date=21 April 2020 |archive-date=8 August 2020 |archive-url=https://web.archive.org/web/20200808062758/https://psmag.com/news/meet-the-chemist-behind-many-popular-and-faulty-police-drug-kits |url-status=live }}</ref><ref>{{Cite news | vauthors = Gabrielson R, Sanders T |url= https://www.nytimes.com/2016/07/10/magazine/how-a-2-roadside-drug-test-sends-innocent-people-to-jail.html |archive-url=https://ghostarchive.org/archive/20220101/https://www.nytimes.com/2016/07/10/magazine/how-a-2-roadside-drug-test-sends-innocent-people-to-jail.html |archive-date=1 January 2022 |url-access=limited |title=How a $2 Roadside Drug Test Sends Innocent People to Jail |date=7 July 2016 |work=The New York Times |access-date=21 April 2020 | url-status=live }}</ref>

Approximate cocaine purity can be determined using 1&nbsp;mL 2% cupric sulfate pentahydrate in dilute HCl, 1&nbsp;mL 2% potassium thiocyanate and 2&nbsp;mL of [[chloroform]]. The shade of brown shown by the chloroform is proportional to the cocaine content. This test is not cross sensitive to heroin, methamphetamine, [[benzocaine]], procaine and a number of other drugs but other chemicals could cause false positives.<ref>{{Cite journal | vauthors = Travnikoff B |title=Semiquantitative screening test for cocaine |date=1 April 1983 |journal=Analytical Chemistry |issue=4 |volume=55 |pages=795–796 |doi=10.1021/ac00255a048 |bibcode=1983AnaCh..55..795T |issn=0003-2700}}</ref>

== Society and culture ==
{{main|Cocaine and society}}

Both the [[Cocaine and society#Pharmaceutical supply chain|pharmaceutical supply chain]] and the [[Cocaine and society#Illicit supply chain|illicit supply chain]] obtain cocaine from coca cultivated in Latin America, but they operate under very different controls and oversight. In Peru, for example, legal coca cultivation is monopolized by the state company [[National Coca Company]] (ENACO), yet approximately 90% of coca leaves produced in the country are diverted to illegal actors for cocaine manufacturing.<ref>{{cite journal | vauthors = Busnel R, Manrique López H | title = The political economy of a failed drug reform: Insights from Peru's main legal coca valley | journal = The International Journal on Drug Policy | volume = 117 | article-number = 104050 | date = July 2023 | pmid = 37267739 | doi = 10.1016/j.drugpo.2023.104050 }}</ref> As a result, these illicit coca crops are a primary target of ongoing government-led [[coca eradication]] efforts.<ref name="Grisaffi_2016">{{cite journal | vauthors = Grisaffi T, Ledebur K | title = Citizenship or Repression? Coca, Eradication and Development in the Andes | journal = Stability: International Journal of Security and Development | volume = 5 | issue = 1 | date = 31 March 2016 | article-number = 3 | doi = 10.5334/sta.440 | doi-access = free | issn = 2165-2627 }}</ref>

Cocaine is prohibited in competition for athletes by the [[World Anti-Doping Agency]] (WADA), which lists it as a stimulant on its [[List of drugs banned by the World Anti-Doping Agency|International Standard for the Prohibited List]].<ref name=WADA17>{{cite web | url = https://www.wada-ama.org/sites/default/files/resources/files/2016-09-29_-_wada_prohibited_list_2017_eng_final.pdf | title = World Anti-Doping Code: International Standard Prohibited List 2017 | date = January 2017}}</ref>{{rp|6}}

===Street names===
Cocaine is sometimes referred to on the street as blow, coca, coke, crank, flake, snow, or soda cot. Slang terms for free base cocaine include crack or rock.<ref name="DEA">{{cite web |title=Cocaine |url=https://www.dea.gov/factsheets/cocaine |website=DEA }}</ref>

[https://en.wiktionary.org/wiki/fishscale#Noun Fishscale cocaine], from ''fish'' + ''scale'', is named for its shiny, yellowish flakes that resemble fish scales—distinct from the dull white appearance of standard cocaine powder.

=== Legal status ===
{{Main|Legal status of cocaine}}

[[File:Legal status of cocaine possession.png|thumb|Legal status of cocaine possession]]

The production, distribution, and sale of cocaine products is restricted (and illegal in most contexts) in most countries as regulated by the [[Single Convention on Narcotic Drugs]], and the [[United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances]]. In the United States the manufacture, importation, possession, and distribution of cocaine are additionally regulated by the 1970 [[Controlled Substances Act]].

Some countries, such as Bolivia, Colombia, and Peru, permit the cultivation of coca leaf for traditional consumption by the local [[indigenous peoples of the Americas|indigenous population]], but nevertheless, prohibit the production, sale, and consumption of cocaine.<ref name="bolivia-cocaine-bar-route-36">{{Cite news|url=https://www.theguardian.com/world/2009/aug/19/bolivia-cocaine-bar-route-36|title=The world's first cocaine bar| vauthors = Franklin J |date=18 August 2009|newspaper=The Guardian|issn=0261-3077|access-date=23 December 2016|url-status=live|archive-url=https://web.archive.org/web/20170112142609/https://www.theguardian.com/world/2009/aug/19/bolivia-cocaine-bar-route-36|archive-date=12 January 2017}}</ref> The provisions as to how much a coca farmer can yield annually is protected by laws such as the Bolivian Cato accord.<ref>{{Cite web | vauthors = Grisaffi T |title=The Cato Accord: Bolivia's Humane and Effective Approach to Controlling Coca Cultivation|url=https://ain-bolivia.org/wp-content/uploads/The-Cato-Accord-Bolivias-Humane-and-Effective-Approach-to-Controlling-Coca-Cultivation.pdf|website=ain-bolivia.org|access-date=12 January 2017|url-status=live|archive-url=https://web.archive.org/web/20160503160349/https://ain-bolivia.org/wp-content/uploads/The-Cato-Accord-Bolivias-Humane-and-Effective-Approach-to-Controlling-Coca-Cultivation.pdf|archive-date=3 May 2016}}</ref> In addition, some parts of Europe, the United States, and Australia allow processed cocaine for medicinal uses only.

==== Australia ====
Cocaine is a Schedule 8 controlled drug in Australia under the [[Standard for the Uniform Scheduling of Medicines and Poisons|Poisons Standard]].<ref>{{Cite web|url=https://www.legislation.gov.au/F2023L01294/asmade/text|title=Therapeutic Goods (Poisons Standard—October 2023) Instrument 2023|website=Federal Register of Legislation|date=26 September 2023 |publisher=Australian Government|access-date=22 January 2024}}</ref> It is the second most popular illicit recreational drug in Australia [[Cannabis in Australia|behind cannabis]].<ref>{{Cite web|url=https://www.aihw.gov.au/reports/illicit-use-of-drugs/illicit-drug-use|title=Illicit drug use|date=13 December 2023|website=Australian Institute of Health and Welfare|access-date=22 January 2024|archive-date=20 January 2024|archive-url=https://web.archive.org/web/20240120123407/https://www.aihw.gov.au/reports/illicit-use-of-drugs/illicit-drug-use|url-status=live}}</ref>

In [[Western Australia]] under the Misuse of Drugs Act 1981, 4.0g of cocaine is the amount of prohibited drugs determining a court of trial, 2.0g is the amount of cocaine required for the presumption of intention to sell or supply, and 28.0g is the amount of cocaine required for purposes of drug trafficking.<ref>{{Cite web|url=https://www.legislation.wa.gov.au/legislation/prod/filestore.nsf/FileURL/mrdoc_46172.pdf/$FILE/Misuse%20Of%20Drugs%20Act%201981%20-%20%5B08-f0-00%5D.pdf?OpenElement|title=Misuse of Drugs Act 1981|website=Western Australian Legislation|publisher=Government of Western Australia Department of Justice Parliamentary Counsel's Office|access-date=22 January 2024|archive-date=17 February 2024|archive-url=https://web.archive.org/web/20240217143325/https://www.legislation.wa.gov.au/legislation/prod/filestore.nsf/FileURL/mrdoc_46172.pdf/$FILE/Misuse%20Of%20Drugs%20Act%201981%20-%20%5B08-f0-00%5D.pdf?OpenElement|url-status=live}}</ref>

==== United States ====
{{See also|Cocaine in the United States}}
[[File:George_H._W._Bush_holds_up_a_bag_of_crack_cocaine_during_his_Address_to_the_Nation_on_National_Drug_Control_Strategy.jpg|thumb|upright |President [[George H. W. Bush]] holds up a bag of [[crack cocaine]] during his Address to the Nation on National Drug Control Strategy on 5 September 1989.]]

The US federal government instituted a national [[prescribing information|drug labelling]] requirement for cocaine and cocaine-containing products through the [[Pure Food and Drug Act]] of 1906.<ref name="Gootenberg_1999">{{Cite book | veditors = Gootenberg P |title=Cocaine: Global Histories |url= https://archive.org/details/cocaineglobalhist00goot |url-access=registration |year=1999 |publisher=Routledge |location=London |isbn=978-0-203-02646-5}}</ref>{{rp|37}} The next important federal regulation was the [[Harrison Narcotics Tax Act]] of 1914. While this act is often seen as the start of prohibition, the act itself was not actually a prohibition on cocaine, but instead it set up a regulatory and licensing regime.<ref name="Madge_2001">{{Cite book | vauthors = Madge T |title=White Mischief: A Cultural History of Cocaine |year=2001 |publisher=Mainstream Publishing Company |location=Edinburgh |isbn=978-1-84018-405-1|page = 106}}</ref> The Harrison Act did not recognize addiction as a treatable condition and therefore the therapeutic use of cocaine, heroin, or morphine to such individuals was outlawed{{Spaced ndash}} leading a 1915 editorial in the journal ''American Medicine'' to remark that the addict "is denied the medical care he urgently needs, open, above-board sources from which he formerly obtained his drug supply are closed to him, and he is driven to the underworld where he can get his drug, but of course, surreptitiously and in violation of the law."<ref>{{Cite journal|title=Narcotic drug addiction|journal=American Medicine|date=November 1915|page=799|url=https://books.google.com/books?id=tvAAAAAAYAAJ&pg=PA799|access-date=29 April 2018|publisher=American-Medicine Publishing Company|url-status=live|archive-url=https://web.archive.org/web/20180509174117/https://books.google.com/books?id=tvAAAAAAYAAJ&pg=PA799|archive-date=9 May 2018}}</ref> The Harrison Act left manufacturers of cocaine untouched so long as they met certain purity and labeling standards.<ref name="Gootenberg_1999" />{{rp|40}} Despite that cocaine was typically illegal to sell and legal outlets were rarer, the quantities of legal cocaine produced declined very little.<ref name="Gootenberg_1999" />{{rp|40}} Legal cocaine quantities did not decrease until the [[Narcotic Drugs Import and Export Act|Jones–Miller Act]] of 1922 put serious restrictions on cocaine manufactures.<ref name="Gootenberg_1999" />{{rp|40}}

Before the early 1900s, newspapers primarily portrayed addiction (rather than violence or crime) as the main problem caused by cocaine use, and depicted cocaine users as upper or middle class [[White people]]. In 1914, The New York Times published an article titled "Negro Cocaine 'Fiends' Are a New Southern Menace," portraying [[Black people]] who used cocaine as dangerous and able to withstand wounds that would normally be fatal.<ref>{{Cite book |vauthors=Brown E, Barganier G |title=Race and Crime: Geographies of Injustice |date=2018 |publisher=University of California Press |location=Oakland, California |isbn=978-0-520-29418-9 |pages=207–209 |url=https://books.google.com/books?id=2ChtDwAAQBAJ |access-date=21 November 2021 |archive-date=12 April 2023 |archive-url=https://web.archive.org/web/20230412145040/https://books.google.com/books?id=2ChtDwAAQBAJ |url-status=live }}</ref> The [[Anti-Drug Abuse Act of 1986]] mandated the same prison sentences for distributing 500 grams of powdered cocaine and just 5 grams of crack cocaine.<ref>{{Cite book |vauthors=Moore NM |title=The Political Roots of Racial Tracking in American Criminal Justice |date=2015 |publisher=Cambridge University Press |location=New York, NY |isbn=978-1-107-02297-3 |page=270 |url=https://books.google.com/books?id=QKwPBgAAQBAJ&pg=PA270 |access-date=21 November 2021 |archive-date=6 April 2023 |archive-url=https://web.archive.org/web/20230406100009/https://books.google.com/books?id=QKwPBgAAQBAJ&pg=PA270 |url-status=live }}</ref> In the [[National Survey on Drug Use and Health]], white respondents reported a higher rate of powdered cocaine use, and Black respondents reported a higher rate of crack cocaine use.<ref>{{Cite book |vauthors=Glaser J |title=Suspect Race: Causes and Consequences of Racial Profiling |date=2015 |publisher=Oxford University Press |location=New York, NY |isbn=978-0-19-537040-9 |page=7 |url=https://books.google.com/books?id=3GjDBAAAQBAJ&pg=PA7 |access-date=21 November 2021 |archive-date=12 April 2023 |archive-url=https://web.archive.org/web/20230412145042/https://books.google.com/books?id=3GjDBAAAQBAJ&pg=PA7 |url-status=live }}</ref>

===Prevalence and trends===
Cocaine production, seizures, and use all reached record levels in 2023, making it the world's fastest-growing illicit drug market. Seizures rose by 68% from 2019 to 2023, while the number of users increased from 17 million in 2013 to 25 million in 2023, according to the UNODC [[World Drug Report]] 2025.<ref name="Press_release_WDR_2025_English.pdf">{{cite web | title = UNODC World Drug Report 2025: Global instability compounding social, economic and security costs of the world drug problem |url=https://www.unodc.org/documents/data-and-analysis/WDR_2025/Press_release_WDR_2025_English.pdf | publisher = United Nations Office on Drugs and Crime }}</ref>

The report further states that Western Europe's cocaine market is rapidly expanding, resulting in increased violence driven by traffickers, including organized criminal groups from the Western Balkans. Concurrently, record levels of cocaine production have enabled traffickers to enter new markets across Asia and Africa, reflecting the expanding global reach of cocaine trafficking.<ref name="WDR25_Special_points_of_interest.pdf">{{cite report |title=World Drug Report 2025: Special points of interest |url=https://www.unodc.org/documents/data-and-analysis/WDR_2025/WDR25_Special_points_of_interest.pdf |publisher=United Nations Office on Drugs and Crime |date=2025 |access-date=29 June 2025 |type=PDF}}</ref>

The U.S. is the world's largest consumer of cocaine,<ref name="WFK Illicit drugs">{{Cite web |url=https://www.cia.gov/library/publications/the-world-factbook/fields/2086.html |title=Field Listing – Illicit drugs (by country) |publisher=Cia.gov |access-date=15 January 2011 |archive-url=https://web.archive.org/web/20101229044611/https://www.cia.gov/library/publications/the-world-factbook/fields/2086.html |archive-date=29 December 2010 }}</ref> while South America, as a continent, ranks third in terms of consumer market size.<ref name="Andean_full_report.pdf" /> Europe ranks cocaine as the second most commonly used illicit drug.<ref>{{cite web |title=Cocaine – the current situation in Europe (European Drug Report 2024) {{!}} www.euda.europa.eu |url=https://www.euda.europa.eu/publications/european-drug-report/2024/cocaine_en |website=www.euda.europa.eu}}</ref>

Cocaine is among the most widely consumed [[Recreational drug use|recreational]] stimulants worldwide.<ref name="Roque_2022"/>

=== Impact ===

==== Impact of illicit cocaine ====

===== Impact on impoverished communities =====
In countries where cocaine is illicitly produced, an intermediate product known as cocaine paste—often referred to as "poor man's cocaine"—is frequently smoked in impoverished communities. This substance is favored in these areas primarily because it is inexpensive and more accessible than refined cocaine. However, the use of cocaine paste poses severe health risks. During its production, various toxic chemicals are used to extract coca alkaloids from the coca leaves. Many of these hazardous substances, such as solvents and acids, remain in the paste after processing. When the paste is smoked, individuals are exposed not only to the addictive effects of the drug itself but also to the dangerous residual chemicals, which can cause significant harm to the lungs, nervous system, and overall health. This combination of affordability, accessibility, and toxicity makes cocaine paste particularly damaging to vulnerable populations in cocaine-producing regions.<ref name="smokablecocaine_eng_web-def.pdf" /><ref name="Arif_1987" /><ref name="Jeri_1984" /><ref name="Phillips_2009" />

===== Environmental impact =====
{{See also|Environmental impact of illicit drug production}}

Most of the world's cocaine is produced in South America, particularly in the [[Andes|Andean region]].<ref name="UNODC_2019">{{cite report | author = UNODC | date = 2006 | url = https://www.unodc.org/pdf/andean/Andean_report_Part2.pdf | title = Part 2. Environmental Effects of Illicit Drug Cultivation and Processing | access-date = 6 May 2019 }}</ref> The environmental destruction caused by the production of cocaine has been well documented, with reports made the UN and other government bodies.<ref name="McSweeney_2015">{{cite web | vauthors = McSweeney K | title = The Impact of Drug Policy on the Environment | url = https://www.opensocietyfoundations.org/sites/default/files/impact-drug-policy-environment-20151208.pdf | date = 2015 | access-date = 7 May 2019 }}</ref> Due to the illegal nature of [[Coca production in Colombia|coca production]], farmers make little effort in soil conservation and sustainability practices as seen in the high mobility and short life of coca plots in Colombia.<ref name="UNODC_2019" />

One of the major implications of cocaine production is [[deforestation]] as large areas of forest are cleared for coca cultivation. The UNODC approximated that 97,622 hectares of [[Old-growth forest|primary forest]] were cleared for coca cultivation during 2001–2004 in the Andean region.<ref name="UNODC_2019" /> This further causes [[habitat destruction]], especially in [[biodiversity hotspot]]s, areas rich in a variety of species. Such areas are chosen for coca cultivation due to their remote locations, minimising chances of detection.<ref name="Burns-Edel_2016">{{cite journal | vauthors = Burns-Edel T | title = Environmental Impacts of Illicit Drug Production. Issue | journal = Global Societies Journal | volume = 4 | year = 2016 | url = https://gsj.global.ucsb.edu/sites/secure.lsit.ucsb.edu.gisp.d7_gs-2/files/sitefiles/Burns-Edel.pdf }}</ref> Deforestation impacts [[soil erosion]] which further inhibits the survival of native species.<ref name="UNODC_2019" />

The use of [[pesticide]]s can also severely affect the environment. Farmers are able to use unregulated and highly toxic pesticides due to the clandestine nature of drug production.<ref name="Burns-Edel_2016" /> The use of such pesticides can have both direct and indirect effects on the ecosystem. Where lethal levels of exposure directly cause the death of fauna, which is further carried up the [[food chain]] where secondary feeders who consume the poisoned animals are also impacted. Furthermore, non-lethal levels of exposure can also cause weaker immune system development and neurological issues, further increasing mortality rates.<ref name="Burns-Edel_2016" />

===== Impact of illicit cocaine trade =====
Cocaine is extremely expensive on the black market, with prices rising sharply at each distribution level—often more than its weight in gold.<ref>{{cite journal | vauthors = Hulme S, Hughes CE, Nielsen S | title = The price and mark up of pharmaceutical drugs supplied on the black market | journal = The International Journal on Drug Policy | volume = 76 | article-number = 102626 | date = February 2020 | pmid = 31841773 | doi = 10.1016/j.drugpo.2019.102626 }}</ref>

====== Latin America ======
Drug war policies in Latin America and the Caribbean have led to more violence, higher incarceration rates, health crises, and deeper poverty, while undermining trust in institutions and worsening inequality. There is increasing support for shifting toward drug policies that focus on sustainable development and human rights instead of punitive measures.<ref name="ow-the-drug-wars-impact-latin-america-and-the-caribbean-development">{{cite web | vauthors = Zepeda R | date = 16 August 2023 |title=How the drug wars impact Latin America and the Caribbean development? | publisher = King's College London |url=https://www.kcl.ac.uk/how-the-drug-wars-impact-latin-america-and-the-caribbean-development }}</ref>

====== West Africa ======
Cocaine trafficking in West Africa has become closely linked with the activities of several [[List of designated terrorist groups|terrorist organizations]].<ref>{{cite web |title=Organized Crime Module 16 Key Issues: Terrorism and drug trafficking |url=https://www.unodc.org/e4j/fr/organized-crime/module-16/key-issues/terrorism-and-drug-trafficking.html |website=www.unodc.org }}</ref><ref>{{cite report | title =  Transnational Organized Crime in West Africa: A Threat Assessment | date = 2013 | publisher = United Nations Office on Drugs and Crime (UNODC) | url = https://www.unodc.org/documents/data-and-analysis/tocta/West_Africa_TOCTA_2013_EN.pdf }}</ref><ref>{{cite web | title = Linkages Between Organized Crime and Terrorism | publisher = United Nations Office on Drugs and Crime (UNODC) | date = 2019 |url= https://www.unodc.org/documents/e4j/FINAL_Module_16_Linkages_between_Organized_Crime_andTerrorism_14_Mar_2019.pdf }}</ref>

==== Impact of enforcement ====

===== Impact of coca eradication =====
{{See also|Coca eradication}}

In December 2000, Dutch journalist [[Marjon van Royen]] found that "because the chemical is sprayed in Colombia from planes on inhabited areas, there have been consistent health complaints [in humans]. Burning eyes, dizziness and respiratory problems being most frequently reported." In some areas, 80 percent of the children of the indigenous community fell sick with skin rashes, fever, diarrhoea and eye infections.<ref>{{cite web | vauthors = van Royen M | url = http://marjonvanroyen.nl/index.php?option=com_content&view=article&id=525&Itemid=46 | title = Driven Mad by Itch | work = [[NRC Handelsblad]] | date = 28 December 2000 }}</ref> Because the glyphosate is sprayed from the air, there is a much higher chance of human error when spraying suspected illegal coca plantations. In many cases the wrong fields are sprayed, resulting in not only a total loss of the farmer's crop- but the loss of that field altogether as nothing will grow where the herbicide has been sprayed.<ref name="Sue Branford 2005">{{cite book | vauthors = O'Shaughnessy H, Branford S | title = Chemical Warfare in Colombia: The Costs of Coca Fumigation | location = London | date = 2005 | publisher = Latin America Bureau | isbn = 978-1-899365-68-5 | url = https://books.google.com/books?id=6E5_tAEACAAJ }}</ref> Though official documentation of the health effects of glyphosate spraying in Colombia are virtually non-existent, neighbouring Ecuador has conducted studies to determine the cause of mysterious illnesses amongst people living along the border of Colombia and has since demanded that no aerial sprayings occur within 10&nbsp;km of the border because of the damages caused to the people, animals and environment in that area.<ref name="Sue Branford 2005"/> In 2015, Colombia announced a ban on using glyphosate in these programs due to concerns about human toxicity of the chemical.<ref name = BBCColumbia>{{cite web | work = [[BBC]] | date = 10 May 2015 | url = https://www.bbc.com/news/world-latin-america-32677411 | title = Colombia to ban coca spraying herbicide glyphosate }}</ref>

=====Impact of interdiction=====
The Consolidated Counterdrug Database (CCDB) is a U.S. government dataset created in the 1990s that compiles vetted data on cocaine trafficking and seizures in the [[Western Hemisphere]] "transit zone," involving 26 U.S. agencies and 20 foreign partners. It provides a highly reliable, conservative record of cocaine movements and interdiction efforts, revealing that despite large seizures, interdiction captures only a small fraction of trafficking events and has minimal impact on U.S. cocaine prices. The CCDB challenges optimistic views of drug interdiction effectiveness and underscores the need for new policy approaches, yet remains underutilized in research despite being unclassified.<ref>{{cite journal | vauthors = McSweeney K | title = Reliable drug war data: The Consolidated Counterdrug Database and cocaine interdiction in the "Transit Zone" | journal = The International Journal on Drug Policy | volume = 80 | article-number = 102719 | date = June 2020 | pmid = 32416537 | doi = 10.1016/j.drugpo.2020.102719 }}</ref>

== Research ==
Cocaine [[hapten]]s are chemically modified derivatives of cocaine that retain key immunogenic features, allowing them to be attached to carrier proteins such as [[keyhole limpet hemocyanin]] or [[bovine serum albumin]]. This enables the immune system to recognize cocaine and produce anti-cocaine antibodies, which can bind cocaine in the bloodstream and prevent it from reaching the brain, thereby blocking its psychoactive effects.<ref name="Janda_2011">{{cite journal | vauthors = Janda KD, Treweek JB | title = Vaccines targeting drugs of abuse: is the glass half-empty or half-full? | journal = Nature Reviews. Immunology | volume = 12 | issue = 1 | pages = 67–72 | date = December 2011 | pmid = 22173478 | doi = 10.1038/nri3130 }}</ref><ref>{{cite journal | vauthors = Anthenelli RM, Somoza E | title = Vaccine for cocaine addiction: A promising new immunotherapy | journal = Current Psychiatry | volume = 9 | issue = 9 | pages = 16–20 | date = September 2010 | url = https://cdn.mdedge.com/files/s3fs-public/Document/September-2017/0909CP_Article1.pdf }}</ref><ref name="Bremer_2017">{{cite journal | vauthors = Bremer PT, Schlosburg JE, Banks ML, Steele FF, Zhou B, Poklis JL, Janda KD | title = Development of a Clinically Viable Heroin Vaccine | journal = Journal of the American Chemical Society | volume = 139 | issue = 25 | pages = 8601–8611 | date = June 2017 | pmid = 28574716 | pmc = 5612493 | doi = 10.1021/jacs.7b03334 | bibcode = 2017JAChS.139.8601B | url = }}</ref>

The [[cocaine esterase]] enzyme and redesigned versions of it have been studied as a potential treatment for [[cocaine dependence|cocaine addiction]] in humans.<ref>{{cite journal | vauthors = Narasimhan D, Woods JH, Sunahara RK | title = Bacterial cocaine esterase: a protein-based therapy for cocaine overdose and addiction | journal = [[Future Medicinal Chemistry]] | volume = 4 | issue = 2 | pages = 137–50 | date = February 2012 | pmid = 22300094 | doi = 10.4155/fmc.11.194 | pmc = 3290992 }}</ref>

[[Coca tea]] has been explored as a supportive treatment for cocaine dependence. A study in [[Lima]], Peru, found that using coca leaf infusion along with counseling reduced relapse rates and significantly increased the duration of abstinence among addicted individuals, suggesting that this approach may help prevent relapse during treatment.<ref name="Teobaldo_2014">{{Cite journal | vauthors = Teobaldo L |title=The Standard Low Dose of Oral Cocaine: Used for Treatment of Cocaine Dependence. |journal=Substance Abuse |date=1994 |volume=15 |issue=4 |pages=215–220 |url=http://www.dronet.org/sostanze/sos_pdf/cocaine21.pdf |archive-url=https://web.archive.org/web/20140602154528/http://www.dronet.org/sostanze/sos_pdf/cocaine21.pdf |archive-date=2 June 2014 |url-status=live}}</ref>

Recent research has also examined the use of prescription psychostimulants for cocaine dependence, following the [[Self-medication#Self-medication hypothesis|Self-Medication Hypothesis]]. This hypothesis suggests that some individuals use cocaine to address underlying neurochemical or psychological issues. While some studies indicate that psychostimulant therapy may reduce cocaine use and cravings, the evidence is mixed and further research is needed.<ref>{{cite journal | vauthors = Mariani JJ, Khantzian EJ, Levin FR | title = The self-medication hypothesis and psychostimulant treatment of cocaine dependence: an update | journal = The American Journal on Addictions | volume = 23 | issue = 2 | pages = 189–193 | date = March 2014 | pmid = 25187055 | pmc = 4227391 | doi = 10.1111/j.1521-0391.2013.12086.x }}</ref>

In animal studies, nicotine exposure in [[Laboratory mouse|mice]] increases the likelihood of later cocaine use, with clear molecular changes in the brain.<ref name="Kandel_2014">{{cite journal | vauthors = Kandel ER, Kandel DB | title = Shattuck Lecture. A molecular basis for nicotine as a gateway drug | journal = The New England Journal of Medicine | volume = 371 | issue = 10 | pages = 932–943 | date = September 2014 | pmid = 25184865 | pmc = 4353486 | doi = 10.1056/NEJMsa1405092 | author2-link = Denise Kandel | author1-link = Eric Kandel }}</ref> These findings mirror human [[Epidemiology|epidemiological]] data showing a link between nicotine use and increased risk of later cannabis and cocaine use, as well as other substances.<ref name="Keyes_2016">{{cite journal | vauthors = Keyes KM, Hamilton A, Kandel DB | title = Birth Cohorts Analysis of Adolescent Cigarette Smoking and Subsequent Marijuana and Cocaine Use | journal = American Journal of Public Health | volume = 106 | issue = 6 | pages = 1143–1149 | date = June 2016 | pmid = 27077359 | pmc = 4880234 | doi = 10.2105/AJPH.2016.303128 }}</ref><ref name="Ren_2019">{{cite journal | vauthors = Ren M, Lotfipour S | title = Nicotine Gateway Effects on Adolescent Substance Use | journal = The Western Journal of Emergency Medicine | volume = 20 | issue = 5 | pages = 696–709 | date = August 2019 | pmid = 31539325 | pmc = 6754186 | doi = 10.5811/westjem.2019.7.41661 }}</ref> Similarly, in rats, alcohol consumption raises the probability of later cocaine addiction and is associated with changes in the brain's reward system.<ref name="Griffin_2017">{{cite journal | vauthors = Griffin EA, Melas PA, Zhou R, Li Y, Mercado P, Kempadoo KA, Stephenson S, Colnaghi L, Taylor K, Hu MC, Kandel ER, Kandel DB | title = Prior alcohol use enhances vulnerability to compulsive cocaine self-administration by promoting degradation of HDAC4 and HDAC5 | journal = Science Advances | volume = 3 | issue = 11 | article-number = e1701682 | date = November 2017 | pmid = 29109977 | pmc = 5665598 | doi = 10.1126/sciadv.1701682 | bibcode = 2017SciA....3E1682G }}</ref><ref name="Anderson_2019">{{cite journal | vauthors = Anderson EM, Penrod RD, Barry SM, Hughes BW, Taniguchi M, Cowan CW | title = It is a complex issue: emerging connections between epigenetic regulators in drug addiction | journal = The European Journal of Neuroscience | volume = 50 | issue = 3 | pages = 2477–2491 | date = August 2019 | pmid = 30251397 | doi = 10.1111/ejn.14170 | s2cid = 52816486 }}</ref> Human studies also show that alcohol use increases the risk of transitioning from cocaine use to addiction.<ref name="Lopez-Quintero_2011">{{cite journal | vauthors = Lopez-Quintero C, Pérez de los Cobos J, Hasin DS, Okuda M, Wang S, Grant BF, Blanco C | title = Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) | journal = Drug and Alcohol Dependence | volume = 115 | issue = 1–2 | pages = 120–130 | date = May 2011 | pmid = 21145178 | pmc = 3069146 | doi = 10.1016/j.drugalcdep.2010.11.004 }}</ref><ref name="Bickel_2016">{{cite book | vauthors = Bickel WK, Snider SE, Quisenberry AJ, Stein JS, Hanlon CA | title = Competing neurobehavioral decision systems theory of cocaine addiction: From mechanisms to therapeutic opportunities | chapter = Competing neurobehavioral decision systems theory of cocaine addiction | series = Progress in Brain Research | volume = 223 | pages = 269–293 | year = 2016 | pmid = 26806781 | pmc = 5495192 | doi = 10.1016/bs.pbr.2015.07.009 | isbn = 978-0-444-63545-7 }}</ref>

Experimentally, cocaine injections can be delivered to animals such as [[Drosophila melanogaster|fruit flies]] to study the mechanisms of cocaine addiction.<ref>{{Cite journal | vauthors = Dimitrijevic N, Dzitoyeva S, Manev H | title = An automated assay of the behavioral effects of cocaine injections in adult Drosophila | journal = Journal of Neuroscience Methods | volume = 137 | issue = 2 | pages = 181–184 | date = August 2004 | pmid = 15262059 | doi = 10.1016/j.jneumeth.2004.02.023 | s2cid = 19882594 }}</ref>

===Cocaine vaccines===

====Calixcoca====
{{Main|Calixcoca}}

[[Calixcoca]] is an experimental [[vaccine]] to treat cocaine and crack cocaine addiction. It has been in development since 2015 by the [[Federal University of Minas Gerais]] (UFMG) in Brazil.<ref name="Corrêa_2023">{{Cite web | vauthors = Corrêa F |date=30 May 2023 |title=Brasileiros desenvolvem vacina contra crack e cocaína |url=https://www1.folha.uol.com.br/equilibrioesaude/2023/05/brasileiros-desenvolvem-vacina-contra-crack-e-cocaina.shtml |archive-url=https://web.archive.org/web/20230614024354/https://www1.folha.uol.com.br/equilibrioesaude/2023/05/brasileiros-desenvolvem-vacina-contra-crack-e-cocaina.shtml |archive-date=14 June 2023 |access-date=14 June 2023 |website=Folha de S.Paulo |language=pt-BR}}</ref>

====TA-CD====
{{Main|TA-CD}}

[[TA-CD]] is a [[vaccine]] developed by the Xenova Group and designed to negate the effects of cocaine, making it suitable for use in treatment of addiction. It is created by combining [[norcocaine]] with inactivated [[cholera]] toxin.<ref name="Martell_2005">{{cite journal |vauthors=Martell BA, Mitchell E, Poling J, Gonsai K, Kosten TR |title=Vaccine pharmacotherapy for the treatment of cocaine dependence |journal=Biol. Psychiatry |volume=58 |issue=2 |pages=158–64 |date=July 2005 |pmid=16038686 |doi=10.1016/j.biopsych.2005.04.032 |s2cid=22415520 }}</ref>

== History ==
{{Main|History of cocaine}}

Coca leaves have been used by indigenous South Americans for thousands of years, both as a stimulant and for medicinal purposes.<ref name="Hesse_2002">{{Cite book| vauthors = Hesse M |title=Alkaloids: Nature's Curse or Blessing?|page=304|publisher=Wiley-VCH|location=Weinheim|year=2002|isbn=978-3-906390-24-6}}</ref>

When the [[Spanish colonization of the Americas|Spanish arrived in South America]], they initially banned coca but soon legalized and taxed it after seeing its importance to local labor.<ref>{{Cite news|date=2006 <!--2006-03-02--> |title=Drug that spans the ages: The history of cocaine |url=https://www.independent.co.uk/news/uk/this-britain/drug-that-spans-the-ages-the-history-of-cocaine-468286.html |publisher=The Independent (UK) |location=London |access-date=30 April 2010 |archive-url=https://web.archive.org/web/20100228194626/https://www.independent.co.uk/news/uk/this-britain/drug-that-spans-the-ages-the-history-of-cocaine-468286.html |archive-date=28 February 2010 }}</ref> The active ingredient, cocaine, was first isolated in 1855 by [[Friedrich Gaedcke]] and later refined by [[Albert Niemann (chemist)|Albert Niemann]], who named it "cocaine."<ref name="Luch_2009">{{cite book | vauthors = Luch A | title=Molecular, Clinical and Environmental Toxicology | publisher=Springer Science & Business Media | publication-place=Basel Boston | date=3 April 2009 | isbn=978-3-7643-8336-7 | page=20 }}</ref><ref name="Niemann_1860">{{Cite journal|volume = 153|issue = 2 and 3|pages = 129–155; 291–308|year = 1860|title = Ueber eine neue organische Base in den Cocablättern|vauthors = Niemann A|doi = 10.1002/ardp.18601530202|journal = Archiv der Pharmazie|s2cid = 98195820|url = https://zenodo.org/record/1424541|access-date = 30 June 2019|archive-date = 28 July 2020|archive-url = https://web.archive.org/web/20200728162205/https://zenodo.org/record/1424541|url-status = live}}</ref><ref>{{OEtymD|Cocaine}}</ref> In the late 1800s, cocaine became popular in Western medicine as a local anesthetic and was widely used in various products, including drinks and remedies.<ref>{{Cite journal|title=Practical comments on the use and abuse of cocaine| vauthors = Halsted W |journal=New York Medical Journal|year=1885|pages=294–295|volume=42}}</ref> and [[James Leonard Corning]] demonstrated [[peridural]] anesthesia.<ref>{{Cite journal| vauthors = Corning JL |year=1885|journal=New York Medical Journal|title=An experimental study|volume=42|page=483}}</ref> However, due to its toxic effects and potential for abuse, safer alternatives eventually replaced it in medical practice.<ref name="Latorre_1999" />

Large-scale coca cultivation and cocaine production occurred in Taiwan Asia, in [[Geography of Taiwan|Taiwan]] (then known as Formosa) and [[Java]] (today part of Indonesia) before [[World War II]].<ref name="Lu_2024">{{cite journal | vauthors = Lu SL | title = A Promising Tropical Medicinal Plant: Taiwan as the Production Hub of Japan's Coca Empire | journal = Berichte zur Wissenschaftsgeschichte | volume = 47 | issue = 4 | pages = 352–381 | date = December 2024 | pmid = 39570053 | doi = 10.1002/bewi.202400005 }}</ref><ref name="Musto_1998">{{cite journal | vauthors = Musto DF | title = International traffic in coca through the early 20th century | journal = Drug and Alcohol Dependence | volume = 49 | issue = 2 | pages = 145–156 | date = January 1998 | pmid = 9543651 | doi = 10.1016/s0376-8716(97)00157-9 | doi-access = free }}</ref>

Since the 1980s, the cocaine trade was dominated by centralized, hierarchical [[drug cartel]]s such as [[Medellín Cartel|Medellín]] and [[Cali Cartel|Cali]], along with their successors and early [[Revolutionary Armed Forces of Colombia|FARC]] factions. By the early 2000s, this model fragmented into a diverse network of global trafficking links, allowing South American cocaine production to easily supply markets in Europe, Africa, Asia, and Oceania through various routes.<ref name="Lien_2025">{{cite journal | vauthors = Lien N, Feltran G | title = (I)llicit Chains: Some New Hypotheses Regarding a Changing Global Cocaine Market | journal = Journal of Illicit Economies and Development | volume = 7 | issue = 1 | date = 11 March 2025 | pages = 20–34 | doi = 10.31389/jied.274 | issn = 2516-7227 | doi-access = free }}</ref>

== Etymology ==
The word cocaine derives {{ety|fr|Cocaïne}}, {{ety|es|[[coca]]}}, ultimately {{ety|que|kúka}}.<ref>{{Cite web |title=Cocaine |url=https://ahdictionary.com/word/search.html?q=+COCAINE |url-status=live |archive-url=https://web.archive.org/web/20230103150607/https://ahdictionary.com/word/search.html?q=+COCAINE |archive-date=3 January 2023 |access-date=3 January 2023 |website=American Heritage Dictionary}}</ref>

== See also ==
{{Portal|Medicine}}
* [[Cocaine reverse ester]]
* [[Cocaine and amphetamine regulated transcript]]
{{clear}}

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{Cite book | veditors = Spillane JF |title=Cocaine: From Medical Marvel to Modern Menace in the United States, 1884–1920 |year=2000 |publisher=The Johns Hopkins University Press |location=Baltimore and London |isbn=978-0-8018-6230-4 |url=https://archive.org/details/cocainefrommedic00spil }}
* {{Cite book | vauthors = Feiling T |title=The Candy Machine: How Cocaine Took Over the World |location=London |publisher=Penguin |year=2009 |isbn=978-0-14-103446-1}}
*  {{cite journal | vauthors = Gewin V | url =  http://www.nature.com/news/2011/111102/full/news.2011.627.html | title = Smoking stokes cocaine cravings: Molecular mechanism found for controversial 'gateway drug' hypothesis | journal = Nature News | date = 2 November 2011 | doi = 10.1038/news.2011.627 | url-access = subscription }}
* {{cite web |title=Global Report on Cocaine 2023 | work = United Nations Office on Drugs and Crime (UNODC) |url=https://www.unodc.org/documents/data-and-analysis/cocaine/Global_cocaine_report_2023.pdf}}
{{refend}}

== External links ==
{{sister project links|d=Q41576|c=Category:Cocaine|n=no|b=no|v=no|voy=no|m=no|mw=no|s=no|wikt=cocaine|species=no}}

{{Drug use}}
{{Euphoriants}}
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{{Local anesthetics}}
{{Ancient anaesthesia-footer}}
{{Ion channel modulators}}
{{Monoamine reuptake inhibitors}}
{{Sigma receptor modulators}}
{{Chemical classes of psychoactive drugs}}
{{Psychoactive substance use}}
{{Addiction}}
{{Authority control}}

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