Просмотр кода страницы Английская Википедия:Cocaine

{{Английская Википедия/Панель перехода}}
{{Short description|Tropane alkaloid and stimulant drug}}
{{Other uses}}
{{Pp-semi-indef}}
{{pp-move-indef}}
{{Use dmy dates|date=January 2022}}
{{Use American English|date=December 2017}}

{{Infobox drug
| Verifiedfields     = changed
| Watchedfields      = changed
| verifiedrevid      = 477165921
| drug_name          = 
| INN                = 
| type               = <!-- empty -->
| image              = Kokain - Cocaine.svg
| 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 }}</ref> Goprelto,<ref name="Goprelto FDA label" /> Numbrino,<ref name="Numbrino FDA label" /> others
| Drugs.com          = {{drugs.com|CONS|cocaine}}
| MedlinePlus        = 
| licence_CA         = <!-- Health Canada may use generic or brand name (generic name preferred) -->
| licence_EU         = 
| DailyMedID         = Cocaine
| licence_US         = 
| pregnancy_AU       = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU_comment = 
| pregnancy_US       = C
| pregnancy_US_comment = <ref name="Drugs.com pregnancy">{{Cite web | title=Cocaine topical (C-Topical Solution) Use During Pregnancy | website=Drugs.com | date=10 April 2020 | url=https://www.drugs.com/pregnancy/cocaine-topical.html | access-date=30 April 2020}}</ref>
| pregnancy_category = 
| dependency_liability = [[Physical dependence|Physical]]: Low [[Psychological dependence|Psychological]]: High<ref name=Gho2010>{{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|
*[[SNDRI]]<ref name="Monoamines: Dopamine, Norepinephrin">{{Cite journal | vauthors = Azizi SA | title = Monoamines: Dopamine, Norepinephrine, and Serotonin, Beyond Modulation, "Switches" That Alter the State of Target Networks | journal = The Neuroscientist | pages = 121–143 | date = December 2020 | volume = 28 | issue = 2 | pmid = 33292070 | doi = 10.1177/1073858420974336 | s2cid = 228080727 }}</ref>
*[[Central nervous system|CNS]] [[stimulant]]
*[[Local anesthetic]]}}
| 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<!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->
| 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|url-status=dead|archive-url=https://web.archive.org/web/20170809044016/https://www.dea.gov/druginfo/ds.shtml|archive-date=9 August 2017}}</ref>
| 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="fattinger2000">{{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)|Insufflated]]: 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 | pmid = 2565204 }}</ref>
*[[Nasal spray]]: 25<ref name="Intranasal and oral cocaine kinetic">{{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="fattinger2000" />}}
| protein_bound      = 
| metabolism         = [[Liver]], [[CYP3A4]]
| metabolites        = [[Norcocaine]], [[benzoylecgonine]], [[cocaethylene]]
| onset              = Seconds to minutes<ref name="Zimmerman2012" />
| duration_of_action = 20 to 90 minutes<ref name="Zimmerman2012" />
| excretion          = Kidney

<!-- Identifiers -->| index_label        = 
| index2_label       = 
| CAS_number_Ref     = {{cascite|correct|CAS}}
| CAS_number         = 50-36-2
| CAS_supplemental   = 
| PubChem            = 446220
| IUPHAR_ligand      = 2286
| DrugBank_Ref       = {{drugbankcite|correct|drugbank}}
| DrugBank           = DB00907
| ChemSpiderID_Ref   = {{chemspidercite|correct|chemspider}}
| ChemSpiderID       = 10194104
| UNII_Ref           = {{fdacite|correct|FDA}}
| UNII               = I5Y540LHVR
| KEGG_Ref           = {{keggcite|correct|kegg}}
| KEGG               = D00110
| ChEBI_Ref          = {{ebicite|correct|EBI}}
| ChEBI              = 27958
| ChEMBL_Ref         = {{ebicite|correct|EBI}}
| ChEMBL             = 370805
| NIAID_ChemDB       = 
| PDB_ligand         = COC
| synonyms           = Coke, blow, snow, [[crack cocaine|crack]] (in free base form)

<!-- 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
| Jmol               = 
| StdInChI_Ref       = {{stdinchicite|correct|chemspider}}
| 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_Ref    = {{stdinchicite|correct|chemspider}}
| 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''' (from {{Lang-fr|cocaïne}}, from {{Lang-es|[[coca]]}}, ultimately from [[Quechuan languages|Quechua]]: ''kúka'')<ref>{{Cite web|url=https://ahdictionary.com/word/search.html?q=+COCAINE|title=Cocaine|website=American Heritage Dictionary}}</ref> is a [[tropane alkaloid]] that acts as a [[central nervous system]] (CNS) [[stimulant]]. As an extract, it is mainly [[recreational drug use|used recreationally]], and often [[prohibition of drugs|illegally]] for its [[euphoria|euphoric]] and [[Reward system|rewarding]] effects. It is also used in [[medicine]] by [[Indigenous South Americans]] for various purposes and rarely, but more formally, as a [[local anaesthetic]] or diagnostic tool by medical practitioners in more developed countries. It is primarily obtained from the leaves of two [[Coca]] species native to South America: ''[[Erythroxylum coca]]'' and ''[[Erythroxylum novogranatense|E. novogranatense]]''.<ref>{{Cite journal | vauthors = Plowman T |title=The identification of coca (Erythroxylum species): 1860–1910 |journal=Botanical Journal of the Linnean Society |date=June 1982 |volume=84 |issue=4 |pages=329–353 |doi=10.1111/j.1095-8339.1982.tb00368.x}}</ref><ref name=Pom2012>{{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> After extraction from the plant, and further processing into cocaine [[hydrochloride]] (powdered cocaine), the drug is [[Route of administration|administered]] by being either [[Nasal administration|snorted]], applied [[topical administration|topically]] to the [[mouth]], or dissolved and [[injection (medicine)|injected]] into a [[vein]]. It can also then be turned into [[free base]] form (typically [[crack cocaine]]), in which it can be heated until [[Sublimation (phase transition)|sublimated]] and then the vapours can be [[smoking|inhaled]].<ref name="Zimmerman2012" /> 

Cocaine stimulates the [[mesolimbic pathway|reward pathway]] in the brain.<ref name=Pom2012 /> Mental effects may include an [[euphoria|intense feeling of happiness]], [[sexual arousal]], [[psychosis|loss of contact with reality]], or [[psychomotor agitation|agitation]].<ref name="Zimmerman2012" /> Physical effects may include a [[tachycardia|fast heart rate]], sweating, and [[mydriasis|dilated pupils]].<ref name="Zimmerman2012">{{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> High doses can result in [[hypertension|high blood pressure]] or [[hyperthermia|high body temperature]].<ref>{{Cite journal | vauthors = Connors NJ, Hoffman RS | title = Experimental treatments for cocaine toxicity: a difficult transition to the bedside | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 347 | issue = 2 | pages = 251–7 | date = November 2013 | pmid = 23978563 | doi = 10.1124/jpet.113.206383 | s2cid = 6767268 }}</ref> Onset of effects can begin within seconds to minutes of use, depending on method of delivery, and can last between five and ninety minutes.<ref name="Zimmerman2012" /> As cocaine also has [[topical anesthetic|numbing]] and [[vasoconstrictor|blood vessel constriction]] properties, it is occasionally used during surgery on the [[pharynx|throat]] or [[nasopharynx|inside of the nose]] to control 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 }}</ref>

<!-- Pharmacokinetics/Pharmacodynamics -->
Cocaine crosses the [[blood–brain barrier]] via 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 | pages = 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 }}</ref> and (to a lesser extent) via [[Passive transport|passive diffusion across cell membranes]].<ref name="ReferenceA">{{Cite journal | vauthors = Chapy H, Smirnova M, André P, Schlatter J, Chiadmi F, Couraud PO, Scherrmann JM, Declèves X, Cisternino S | display-authors = 6 | 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 | pages = pyu001 | date = October 2014 | pmid = 25539501 | pmc = 4368859 | doi = 10.1093/ijnp/pyu001 }}</ref> Cocaine blocks the [[dopamine transporter]],<ref>{{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 | pages = 134 | date = 2015 | pmid = 26106364 | pmc = 4460958 | doi = 10.3389/fneur.2015.00134 | doi-access = free }}</ref> inhibiting [[reuptake]] of [[dopamine]] from the [[synaptic cleft]] into the pre-synaptic [[axon terminal]]; the higher dopamine levels in the synaptic cleft increase [[dopamine receptor]] activation in the post-synaptic neuron,<ref>{{Cite journal | vauthors = Proebstl L, Kamp F, Manz K, Krause D, Adorjan K, Pogarell O, Koller G, Soyka M, Falkai P, Kambeitz J | display-authors = 6 | 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?}}</ref> causing euphoria and arousal.<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> Cocaine also blocks the [[serotonin transporter]] and [[norepinephrine transporter]], inhibiting reuptake of [[serotonin]] and [[norepinephrine]] from the synaptic cleft into the pre-synaptic [[axon terminal]] and increasing activation of [[serotonin receptor]]s and [[norepinephrine receptor]]s in the post-synaptic neuron, contributing to the mental and physical effects of cocaine exposure.<ref name="Monoamines: Dopamine, Norepinephrin" />

<!-- Risks -->
A single dose of cocaine induces [[Drug tolerance|tolerance]] to the drug's effects.<ref name=Ambre1988>{{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> Repeated use is likely to result in [[substance use disorder|addiction]]. Addicts who abstain from cocaine may experience [[Cocaine dependence|craving]] and [[drug withdrawal]] symptoms, with [[Depression (mood)|depression]], [[decreased libido]], [[anhedonia|decreased ability to feel pleasure]], and fatigue being most common.<ref name=Pom2012 /> Use of cocaine increases the overall risk of death, and intravenous use potentially increases the risk of trauma and infectious diseases such as [[sepsis|blood infections]] and [[HIV]] through the use of shared [[drug paraphernalia|paraphernalia]]. It also increases risk of [[stroke]], [[myocardial infarction|heart attack]], cardiac arrhythmia, lung injury (when smoked), and [[sudden cardiac death]].<ref name=Pom2012 /><ref name=Sor2014>{{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 | doi-access = free }}</ref> Illicitly sold cocaine can be adulterated with [[fentanyl]], [[local anesthetics]], [[levamisole]], cornstarch, [[quinine]], or sugar, which can result in additional toxicity.<ref name=Gold2009>{{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><ref>{{Cite web|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| date=25 April 2019 }}</ref> In 2017, the Global Burden of Disease study found that cocaine use caused around 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>

{{TOC limit}}

== Uses ==
Coca leaves have been used by [[Andean civilizations]] since [[Andean civilizations|ancient times]].<ref name=Gold2009 /> In ancient [[Wari culture]],<ref name="Valdez">{{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 }}</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 to combat the effects of cold, hunger, and [[altitude sickness]].<ref name="Martin">{{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|s2cid=34523519 }}</ref><ref name="Plant">{{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> Cocaine was first isolated from the leaves in 1860.<ref name=Pom2012 />

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 and Central Europe (1.4%), and 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=2021-06-24 |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 drug under the [[Controlled Substances Act]], meaning that it has a high potential for abuse but has an accepted medical use.<ref name="DEA">{{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=2020-06-21 |url-status=live |publisher=Drug Enforcement Agency |access-date=17 June 2022}}</ref> While rarely used medically today, its accepted uses are as a topical local anesthetic for the upper respiratory tract as well as to reduce bleeding in the mouth, throat and nasal cavities.{{cn|date=May 2023}}

=== Medical ===
Cocaine [[Eye drop|eye drops]] are frequently used by [[Neurology|neurologists]] when examining patients suspected of having [[Horner's syndrome|Horner syndrome]]. In Horner syndrome, [[sympathetic innervation]] to the eye is blocked. In a healthy eye, cocaine will stimulate the sympathetic nerves by inhibiting norepinephrine reuptake, and the [[pupil]] will dilate; if the patient has Horner syndrome, the sympathetic nerves are blocked, and the affected eye will remain constricted or dilate to a lesser extent than the opposing (unaffected) eye which also receives the eye drop test. If both eyes dilate equally, the patient does not have Horner syndrome.<ref>{{Cite book |last=Berkowitz |first=Aaron L. |title=Clinical Neurology & Neuroanatomy: A Localization-Based Approach |publisher=McGraw Hill |year=2022 |isbn=978-1260453362 |edition=2nd |language=English |chapter=Chapter 10: Pupillary Control & Approach to Anisocoria: Cranial Nerves 2 & 3 |type=Digital}}</ref>[[File:Cocaine hydrochloride CII for medicinal use.jpg|thumb|upright|Cocaine [[hydrochloride]]]]
Topical cocaine is sometimes used as a local [[anesthetic|numbing agent]] and [[vasoconstrictor]] to help control pain and bleeding with surgery of the nose, mouth, throat or [[lacrimal duct]]. 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="Dwyer2016">{{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>{{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>

Cocaine [[hydrochloride]] ('''Goprelto'''), an ester local anesthetic, was approved for medical use in the United States in December 2017, and is indicated for the introduction of local 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}}</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}}</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}} }}</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}}</ref>

The most common adverse reactions in people treated with Goprelto are headache and [[epistaxis]].<ref name="Goprelto FDA label" /> The most common adverse reactions in people treated with Numbrino are hypertension, tachycardia, and sinus tachycardia.<ref name="Numbrino FDA label" />

=== Recreational ===
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=978-9241562355|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=978-9241547208|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="Zimmerman2012" /><ref name="Sordo2014">{{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> Crack cocaine is referred to as "crack" because of the crackling sounds it makes when heated.<ref name="Zimmerman2012" />

Cocaine use leads to increases in alertness, feelings of well-being and [[euphoria]], increased energy and motor activity, and increased feelings of competence and sexuality.<ref name="Donroe2017">{{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 and dependence|correlation]] between the use of 18 various [[psychoactive substance]]s shows that cocaine use correlates with other "[[Club drug|party drugs]]" (such as [[Ecstasy (drug)|ecstasy]] or [[amphetamines]]), 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>

==== Coca leaves ====

It is legal for people to use [[coca]] leaves in some Andean nations, such as Peru and Bolivia, 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}}</ref> Coca leaves are typically mixed with an alkaline substance (such as [[calcium hydroxide|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. Alternatively, coca leaves can be infused in liquid and consumed like tea. [[Coca tea]], an infusion of coca leaves, is also a traditional method of consumption. The tea has often been recommended for travelers in the Andes to prevent [[altitude sickness]].<ref name=luks>{{Cite journal | vauthors = Luks AM, McIntosh SE, Grissom CK, Auerbach PS, Rodway GW, Schoene RB, Zafren K, Hackett PH | title = Wilderness Medical Society consensus guidelines for the prevention and treatment of acute altitude illness | journal = Wilderness & Environmental Medicine | volume = 21 | issue = 2 | pages = 146–155 | date = June 2010 | pmid = 20591379 | doi = 10.1016/j.wem.2010.03.002 | s2cid = 30571498 | url = https://oyyum.net/Wilderness/pdf/wilderness-medical.pdf | df = dmy-all | url-status=dead | archive-url = https://web.archive.org/web/20121015131014/https://oyyum.net/Wilderness/pdf/wilderness-medical.pdf | archive-date = 15 October 2012 }} {{link note|note=mirror: [https://brad-jackson.info/wp-content/uploads/2012/03/Wilderness-Medicine-Guidelines-for-Treatment-of-Acute-Altitude-Illness-2010.pdf]}}</ref> Its actual effectiveness has never been systematically studied.<ref name=luks />

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">{{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>

==== Insufflation ====
[[File:Cocaine lines 2.jpg|thumb|Lines of cocaine prepared for [[Insufflation (medicine)|snorting]]]]
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 membrane]]s 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="Zimmerman2012" /> Insufflation of cocaine also leads to the longest duration of its effects (60–90 minutes).<ref name="Zimmerman2012" /> 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=2022-02-25|website=Vertava Health|language=en-US}}</ref>

In a study of cocaine users, the average time taken to reach peak subjective effects was 14.6&nbsp;minutes.<ref name="Volkow">{{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 | 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 | date = August 2000 | pmid = 10983846 | doi = 10.1016/S0024-3205(00)00731-1 }}</ref> Any damage to the inside of the nose is due to cocaine constricting blood vessels — and therefore restricting blood and oxygen/nutrient flow — to that area.

Rolled up [[currency|banknotes]], hollowed-out [[pen]]s, cut [[drinking straw|straws]], pointed ends of keys, [[cocaine spoon|specialized spoons]],<ref>{{Cite web|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|language=en}}</ref> long [[fingernails]], and (clean) tampon applicators are often used to insufflate cocaine. The cocaine typically is poured onto a flat, hard surface (such as a mobile phone screen, mirror, CD case or book) 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 |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>

==== 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 two 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" /> 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 infections if sterile injecting equipment is not available or used.

An injected mixture of cocaine and [[heroin]], known as "[[speedball (drug)|speedball]]", is a particularly dangerous combination, as the converse effects of the drugs actually complement each other, but may also mask the symptoms of an overdose. It has been responsible for numerous deaths, including celebrities such as comedians/actors [[John Belushi]] and [[Chris Farley]], [[Mitch Hedberg]], [[River Phoenix]], grunge singer [[Layne Staley]] and actor [[Philip Seymour Hoffman]]. 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>

==== Inhalation ====
{{See also|Crack cocaine}}
The onset of cocaine's euphoric effects is fastest with inhalation, beginning after 3–5 seconds.<ref name="Zimmerman2012" /> However, inhalation gives the shortest duration of euphoria (5–15 minutes).<ref name="Zimmerman2012" /> Cocaine is smoked by inhaling the vapor produced when [[crack cocaine|free base cocaine]] is heated to the point of sublimation.<ref>{{Cite web |url=https://www.justice.gov/oig/special/9712/appb.htm |title=Appendix B: Production of Cocaine Hydrochloride and Cocaine Base |publisher=US Justice Dep |url-status=live |archive-url=https://web.archive.org/web/20091130195140/https://www.justice.gov/oig/special/9712/appb.htm |archive-date=30 November 2009 }}</ref> In a 2000 Brookhaven National Laboratory medical department study, based on self-reports of 32 people who used cocaine who participated in the study, "peak high" was found at a mean of 1.4&nbsp;±&nbsp;0.5&nbsp;minutes.<ref name="Volkow" /> [[Pyrolysis]] products of cocaine that occur only when heated/smoked have been shown to change the effect profile, ''i.e.'' [[Methylecgonidine|anhydroecgonine methyl ester]], when co-administered with cocaine, increases the dopamine in CPu and NAc brain regions, and has M<sub>1</sub> — and M<sub>3</sub> — receptor affinity.<ref name="GarciaTorres2016">{{Cite journal | vauthors = Garcia RC, Torres LH, Balestrin NT, Andrioli TC, Flório JC, de Oliveira CD, da Costa JL, Yonamine M, Sandoval MR, Camarini R, Marcourakis T | title = Anhydroecgonine methyl ester, a cocaine pyrolysis product, may contribute to cocaine behavioral sensitization | journal = Toxicology | volume = 376 | pages = 44–50 | date = February 2017 | pmid = 27129946 | doi = 10.1016/j.tox.2016.04.009 }}</ref>

Smoking freebase cocaine is often accomplished using a pipe made from a small glass tube, often taken from "[[love rose]]s", small glass tubes with a paper rose that are promoted as romantic gifts.<ref>{{Cite news|url=https://www.journalstar.com/news/local/article_28e66c86-1ef8-52dc-ac0a-f3933ed6ec5a.html|title=A rose by another name: crack pipe|newspaper=[[Lincoln Journal Star]] | vauthors = Reist M | date=16 January 2005|access-date=21 August 2009|url-status=live|archive-url=https://web.archive.org/web/20100726074900/https://journalstar.com/news/local/article_28e66c86-1ef8-52dc-ac0a-f3933ed6ec5a.html|archive-date=26 July 2010}}</ref> These are sometimes called "stems", "horns", "blasters" and "straight shooters". A small piece of clean heavy copper or occasionally stainless steel scouring pad{{spaced ndash}}often called a "brillo" (actual [[Brillo Pad]]s contain soap, and are not used) or "chore" (named for [[Chore Boy]] brand copper scouring pads){{spaced ndash}}serves as a reduction base and flow modulator in which the "rock" can be melted and boiled to vapor. Crack is smoked by placing it at the end of the pipe; a flame held close to it produces vapor, which is then inhaled by the smoker. The effects felt almost immediately after smoking, are very intense and do not last long — usually 2 to 10 minutes.<ref>{{Cite web|url=https://www.talktofrank.com/drug/cocaine|title=Cocaine|website=www.talktofrank.com|access-date=23 January 2017|url-status=live|archive-url=https://web.archive.org/web/20170202020535/https://www.talktofrank.com/drug/cocaine|archive-date=2 February 2017}}</ref> When smoked, cocaine is sometimes combined with other drugs, such as [[cannabis (drug)|cannabis]], often rolled into a joint or [[blunt (drug culture)|blunt]].

== Effects ==
{{Main|Cocaine intoxication}}
[[File:HarmCausedByDrugsTable.svg|thumb|left|upright=1.4|A 2010 study ranking various illegal and legal drugs based on statements by drug-harm experts in the UK. Crack cocaine and cocaine was 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>]]
<gallery mode="packed" style="text-align:left" heights="210px">
File:US timeline. Opioid involvement in cocaine overdose.jpg|alt=Opioid involvement in cocaine overdose deaths in the US. The green line is cocaine and any opioid (top line in 2017). The gray line is cocaine without any opioids (bottom line in 2017). The yellow line is cocaine and other synthetic opioids (middle line in 2017).|Opioid involvement in cocaine overdose deaths in the US. The pale green line is cocaine without any opioid (bottom line in 2017). The yellow line is cocaine and [[:Category:Synthetic opioids|synthetic opioids]] other than methadone (top line in 2017).<ref name=NIDA-deaths>{{Cite web | url = https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates | title = Overdose Death Rates | archive-url = https://web.archive.org/web/20151128091723/https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates| archive-date=28 November 2015 | work =  By [[National Institute on Drug Abuse]] (NIDA) }}</ref>
File:Rational harm assessment of drugs bar plot.svg|[[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="Lancet">{{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>
</gallery>

=== Acute ===
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=Ambre1988 /><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="weizhao2008">{{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> Intranasal cocaine and crack use are both associated with pharmacological violence. Aggressive behavior may be displayed by both addicts and casual users. Cocaine can induce [[psychosis]] characterized by paranoia, impaired [[reality testing]], [[hallucinations]], irritability, and physical aggression. [[Cocaine intoxication]] can cause hyperawareness, [[hypervigilance]], and psychomotor agitation and [[delirium]]. Consumption of large doses of cocaine can cause violent outbursts, especially by those with preexisting psychosis. Crack-related violence is also systemic, relating to disputes between crack dealers and users.<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 cardiac arrhythmias, 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 | pages = 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="weizhao2008" /> [[Heart arrhythmia|abnormal heart rhythms]],<ref name="Nav">{{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="Nav" /> Anxiety, [[paranoia]], and restlessness can also occur, especially during the comedown. With excessive dosage, tremors, convulsions and increased body temperature are observed.<ref name=WHO2004 /> Severe cardiac adverse events, particularly [[sudden cardiac death]], become a serious risk at high doses due to cocaine's blocking effect on cardiac sodium channels.<ref name="Nav" /> Incidental exposure of the eye to sublimated cocaine while smoking crack cocaine can cause serious injury to the [[cornea]] and long-term loss of visual acuity.<ref>{{Cite journal | vauthors = Gohil H, Miskovic M, Buxton JA, Holland SP, Strike C | title = Smoke Gets in the Eye: A systematic review of case reports of ocular complications of crack cocaine use | journal = Drug and Alcohol Review | pages = 347–355 | date = August 2021 | volume = 41 | issue = 2 | pmid = 34337815 | doi = 10.1111/dar.13366 | s2cid = 236775586 }}</ref>

=== Chronic ===
[[File:Side effects of chronic use of Cocaine.png|thumb|upright=1.4|Side effects of chronic cocaine use]]Although it has been commonly asserted, the available evidence does not show that chronic use of cocaine is associated with broad cognitive deficits.<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 | s2cid = 4992738 }}</ref> Research is inconclusive on age-related loss of [[striatum|striatal]] [[dopamine transporter]] (DAT) sites, suggesting cocaine has neuroprotective or neurodegenerative properties for dopamine neurons.<ref>{{Cite book|title=Biological Psychiatry | veditors = D'haenen H, den Boer JA, Willner P | publisher = Wiley | volume = 2 | edition = 2 | isbn=978-0-471-49198-9|year=2002 |page=528}}</ref><ref>{{Cite journal | vauthors = Wang GJ, Volkow ND, Fowler JS, Fischman M, Foltin R, Abumrad NN, Logan J, Pappas NR | display-authors = 6 | title = Cocaine abusers do not show loss of dopamine transporters with age | journal = Life Sciences | volume = 61 | issue = 11 | pages = 1059–65 | date = 8 August 1997 | pmid = 9307051 | doi = 10.1016/s0024-3205(97)00614-0 | doi-access = free }}</ref><ref>{{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> 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=4|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>

Physical side effects from chronic smoking of cocaine include [[hemoptysis|coughing up blood]], [[bronchospasm]], [[pruritus|itching]], [[fever]], diffuse alveolar infiltrates without effusions, pulmonary and systemic [[eosinophilia]], chest pain, lung trauma, sore throat, [[asthma]], hoarse voice, [[dyspnea]] (shortness of breath), and an aching, [[flu]]-like syndrome. 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. A common but untrue belief is that the smoking of cocaine chemically breaks down [[tooth enamel]] and causes [[tooth decay]]. Cocaine can cause involuntary tooth grinding, known as [[bruxism]], which can deteriorate tooth enamel and lead to [[gingivitis]].<ref>{{Cite journal | vauthors = Baigent M |year=2003|title=Physical complications of substance abuse: what the psychiatrist needs to know |journal=Curr Opin Psychiatry |volume=16 |issue=3 |pages=291–296|doi=10.1097/00001504-200305000-00004}}</ref> Additionally, stimulants like cocaine, methamphetamine, and even caffeine cause dehydration and [[Xerostomia|dry mouth]]. Since saliva is an important mechanism in maintaining one's oral pH level, people who use cocaine over a long period of time who do not hydrate sufficiently may experience demineralization of their teeth due to the pH of the tooth surface dropping too low (below 5.5). Cocaine use also promotes the [[thrombosis|formation of blood clots]].<ref name="Zimmerman2012" /> 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="Zimmerman2012" />

Chronic intranasal usage can degrade the [[cartilage]] separating the [[nostrils]] (the [[septum nasi]]), leading eventually to its complete disappearance. Due to the absorption of the cocaine from cocaine hydrochloride, the remaining hydrochloride forms a dilute hydrochloric acid.<ref name="pagliaros">{{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>

Illicitly-sold cocaine may be contaminated with levamisole.<ref>{{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 = 408–11 | date = September 2010 | pmid = 20668440 | doi = 10.1038/clpt.2010.156 | s2cid = 31414939 }}</ref> Levamisole may accentuate cocaine's effects.<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 = 590–5 | date = April 2014 | pmid = 24440755 | pmc = 3989204 | doi = 10.1016/j.neuropharm.2014.01.002 }}</ref> Levamisole-adulterated cocaine has been associated with autoimmune disease.<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>

Cocaine use leads to an increased risk of hemorrhagic and ischemic [[stroke]]s.<ref name="Sordo2014" /> Cocaine use also increases the risk of having a [[myocardial infarction|heart attack]].<ref name="Havakuk2017">{{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>

=== Addiction ===
{{See also|Epigenetics of cocaine addiction}}

Relatives of persons with cocaine addiction have an increased risk of 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> [[Cocaine addiction]] occurs through [[ΔFosB]] overexpression in the [[nucleus accumbens]], which results in altered [[transcriptional regulation]] in neurons within the [[nucleus accumbens]]. ΔFosB levels have been found to increase upon the use of cocaine.<ref name="pmid9668659">{{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 }}</ref> Each subsequent dose of cocaine continues to increase ΔFosB levels with no ceiling of tolerance. Elevated levels of ΔFosB leads to increases in brain-derived neurotrophic factor ([[BDNF]]) levels, which in turn increases the number of [[dendrite|dendritic]] branches and [[dendritic spine|spines]] present on neurons involved with the nucleus accumbens and [[prefrontal cortex]] areas of the brain. This change can be identified rather quickly, and may be sustained weeks after the last dose of the drug.

Transgenic mice exhibiting inducible expression of ΔFosB primarily in the nucleus accumbens and [[dorsal striatum]] exhibit [[drug sensitization|sensitized]] behavioural responses to cocaine.<ref name="pmid10499584">{{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> They self-administer cocaine at lower doses than control,<ref name="pmid12657709">{{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> but have a greater likelihood of [[relapse]] when the drug is withheld.<ref name="pmid12657709" /><ref name="pmid11572966">{{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 increases the expression of [[AMPA receptor]] subunit GluR2<ref name="pmid10499584" /> and also decreases expression of [[dynorphin]], thereby enhancing sensitivity to reward.<ref name="pmid11572966" />

[[DNA damage (naturally occurring)|DNA damage]] is increased in the brain of rodents by administration of cocaine.<ref name="pmid24552452">{{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="pmid19878142">{{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 [[DNA repair]] of such damages, persistent chromatin alterations may occur such as [[DNA methylation|methylation of DNA]] or the acetylation or [[histone methylation|methylation of histones]] at the sites of repair.<ref name="pmid27259203">{{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 alterations can be [[epigenetics|epigenetic scars]] in the [[chromatin]] that contribute to the persistent epigenetic changes found in [[Epigenetics of cocaine addiction|cocaine addiction]].

In humans, cocaine abuse may cause structural changes in brain connectivity, though it is unclear to what extent these changes are permanent.<ref name=Hamp2019>{{cite journal | vauthors = Hampton WH, Hanik I, Olson IR | title = [Substance Abuse and White Matter: Findings, Limitations, and Future of Diffusion Tensor Imaging Research] | language = en | 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>

=== Dependence and withdrawal ===
[[Cocaine dependence]] develops after even brief periods of regular cocaine use<ref>{{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> and produces a [[drug withdrawal|withdrawal]] state with emotional-motivational deficits upon cessation of cocaine use.

=== During pregnancy ===
{{Main|Prenatal cocaine exposure}}
''Crack baby'' is a term for a child born to a mother who used crack cocaine during her pregnancy. The threat that cocaine use during [[pregnancy]] poses to the [[fetus]] is now considered exaggerated.<ref>{{Cite news| url=https://www.nytimes.com/2009/01/27/health/27coca.html | work=The New York Times | vauthors = Okie S | title=The Epidemic That Wasn't | date=2009-01-27}}</ref> Studies show that prenatal cocaine exposure (independent of other effects such as, for example, alcohol, tobacco, or physical environment) has no appreciable effect on childhood growth and development.<ref>{{Cite journal | vauthors = Frank DA, Augustyn M, Knight WG, Pell T, Zuckerman B | title = Growth, development, and behavior in early childhood following prenatal cocaine exposure: a systematic review | journal = JAMA | volume = 285 | issue = 12 | pages = 1613–1625 | date = March 2001 | pmid = 11268270 | pmc = 2504866 | doi = 10.1001/jama.285.12.1613 | publisher = Jama.ama-assn.org }}</ref>
However, the official opinion of the [[National Institute on Drug Abuse]] of the United States warns about health risks while cautioning against stereotyping:
{{Blockquote|Many recall that "crack babies", or babies born to mothers who used crack cocaine while pregnant, were at one time written off by many as a lost generation. They were predicted to suffer from severe, irreversible damage, including reduced intelligence and social skills. It was later found that this was a gross exaggeration. However, the fact that most of these children appear normal should not be over-interpreted as indicating that there is no cause for concern. Using sophisticated technologies, scientists are now finding that exposure to cocaine during fetal development may lead to subtle, yet significant, later deficits in some children, including deficits in some aspects of cognitive performance, information-processing, and attention to tasks—abilities that are important for success in school.<ref>[http://www.drugabuse.gov/ResearchReports/Cocaine/cocaine4.html#maternal NIDA – Research Report Series – Cocaine Abuse and Addiction] {{webarchive |url=https://web.archive.org/web/20070926234838/http://www.drugabuse.gov/ResearchReports/Cocaine/cocaine4.html#maternal |date=September 26, 2007 }}</ref>}}

There are also warnings about the threat of [[breastfeeding]]: 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 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 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 damage, or a heart attack.<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=2009-05-26}}</ref>}}

=== Mortality ===
Persons with regular or problematic use of cocaine have a significantly higher rate of death, 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 | display-authors = 6 | 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>

== Pharmacology ==

=== Pharmacokinetics ===
The extent of absorption of cocaine into the systemic circulation 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 acidic stomach and easily absorbed from the alkaline duodenum.<ref name="Intranasal and oral cocaine kinetic" /> 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 pulmonary 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" /><ref name="Structural Requirements for Uptake" /> and (to a lesser extent) via [[Passive transport|passive diffusion across cell membranes]].<ref name="ReferenceA" /> 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 | pages = 108283 | date = September 2022 | volume = 239 | pmid = 36162727 | doi = 10.1016/j.pharmthera.2022.108283 | s2cid = 252527522 }}</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="Zimmerman2012" /> 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="Zimmerman2012" /> 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 | url-status = dead | 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> If consumed with [[ethanol|alcohol]], cocaine combines with [[Alcohol (drug)|alcohol]] in the [[liver]] to form [[cocaethylene]].<ref name="Zimmerman2012" /> Studies have suggested cocaethylene is more [[Euphoria|euphoric]], and has a higher [[cardiovascular]] toxicity than cocaine by itself.<ref name="Zimmerman2012" />

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. However, for high users of cocaine, benzoylecgonine can be detected in their urine within four hours after cocaine intake and remains detectable in concentrations greater than 150&nbsp;ng/mL typically for up to eight days after cocaine was used.<ref>{{cite web|title=Schaffer Library of Drug Polocy|url=https://www.druglibrary.drugsense.org/schaffer/cocaine/clearurine.htm}}</ref>

Detection of cocaine [[metabolite]]s in hair is possible 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}}</ref>

=== Pharmacodynamics ===

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=Pom2012 /> 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 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-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>

[[Sigma receptor]]s are affected by cocaine, as cocaine functions as a sigma ligand agonist.<ref>{{Cite web |url=https://www.sciencedaily.com/releases/2003/05/030506073758.htm |title=Sigma Receptors Play Role in Cocaine-induced Suppression of Immune System |publisher=Sciencedaily.com |date=6 May 2003 |access-date=9 March 2010 |url-status=live |archive-url=https://web.archive.org/web/20110112031919/https://www.sciencedaily.com/releases/2003/05/030506073758.htm |archive-date=12 January 2011 }}</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="Nav" /> 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|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> 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 receptors at the neuronal cell surface, 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 | display-authors = 6 | 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 | display-authors = 6 | 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> Chronic users may lose their [[appetite]] and can experience severe [[malnutrition]] and significant weight loss.

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 ==

=== Appearance ===
[[File:CocaineHydrochloridePowder cropped.jpg|right|thumb|A pile of cocaine hydrochloride]]
[[File:CocaineHCl.jpg|right|thumb|A piece of compressed cocaine powder]]

Cocaine in its purest form is a white, pearly product. Cocaine appearing in powder form is a [[salt (chemistry)|salt]], typically cocaine [[hydrochloride]]. Street cocaine is often adulterated or "cut" with [[talc]], [[lactose]], [[sucrose]], [[glucose]], [[mannitol]], [[inositol]], [[caffeine]], [[procaine]], [[phencyclidine]], [[phenytoin]], [[lignocaine]], [[strychnine]], [[levamisole]], [[amphetamine]], or [[heroin]].<ref>{{Citation | vauthors = Pillay VV | title=Modern Medical Toxicology | edition=4th | year=2013 | publisher=Jaypee | isbn=978-93-5025-965-8 | pages=553–554}}</ref>{{Dubious|date=March 2019}}

Crack cocaine looks like irregular shaped white rocks.<ref>{{Cite web |title=DEA fact sheet |url=https://www.dea.gov/factsheets/cocaine}}</ref>

=== Forms ===

==== Salts ====
Cocaine — a [[tropane alkaloid]] — is a weakly alkaline compound, and can therefore combine with acidic compounds to form salts. The [[hydrochloride]] (HCl) salt of cocaine is by far the most commonly encountered, although the [[sulfate]] (SO<sub>4</sub><sup>2−</sup>) and the [[nitrate]] (NO<sub>3</sub><sup>−</sup>) salts are occasionally seen. Different salts dissolve to a greater or lesser extent in various solvents — the hydrochloride salt is polar in character and is quite soluble in water.<ref>{{Cite web|url=https://www.chm.bris.ac.uk/motm/cocaine/cocaineh.htm|website=duke.edu|title=Content Background: Chemical Characteristics of Cocaine|access-date=4 May 2020}}</ref>

==== Base ====
{{Main|Freebase (chemistry)}}
As the name implies, "freebase" is the [[base (chemistry)|base]] form of cocaine, as opposed to the [[salt (chemistry)|salt]] form. It is practically insoluble in water whereas hydrochloride salt is water-soluble.

Smoking freebase cocaine has the additional effect of releasing [[methylecgonidine]] into the user's system due to the [[pyrolysis]] of the substance (a side effect which [[insufflating]] or injecting powder cocaine does not create). Some research suggests that smoking freebase cocaine can be even more cardiotoxic than other [[routes of administration]]<ref>{{Cite journal | vauthors = Scheidweiler KB, Plessinger MA, Shojaie J, Wood RW, Kwong TC | title = Pharmacokinetics and pharmacodynamics of methylecgonidine, a crack cocaine pyrolyzate | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 307 | issue = 3 | pages = 1179–87 | date = December 2003 | pmid = 14561847 | doi = 10.1124/jpet.103.055434 | s2cid = 15619796 }}</ref> because of methylecgonidine's effects on lung tissue<ref>{{Cite journal | vauthors = Yang Y, Ke Q, Cai J, Xiao YF, Morgan JP | title = Evidence for cocaine and methylecgonidine stimulation of M(2) muscarinic receptors in cultured human embryonic lung cells | journal = British Journal of Pharmacology | volume = 132 | issue = 2 | pages = 451–60 | date = January 2001 | pmid = 11159694 | pmc = 1572570 | doi = 10.1038/sj.bjp.0703819 }}</ref> and liver tissue.<ref>{{Cite journal | vauthors = Fandiño AS, Toennes SW, Kauert GF | title = Studies on hydrolytic and oxidative metabolic pathways of anhydroecgonine methyl ester (methylecgonidine) using microsomal preparations from rat organs | journal = Chemical Research in Toxicology | volume = 15 | issue = 12 | pages = 1543–8 | date = December 2002 | pmid = 12482236 | doi = 10.1021/tx0255828 }}</ref>

Pure cocaine is prepared by neutralizing its compounding salt with an alkaline solution, which will precipitate non-polar basic cocaine. It is further refined through aqueous-solvent [[liquid–liquid extraction]].

==== Crack cocaine ====
{{Main|Crack cocaine}}

[[File:Smoking Crack.jpg|thumb|A woman smoking crack cocaine]]
[[File:Rocks of crack cocaine.jpg|thumb|right|upright=0.9|"Rocks" of crack cocaine]]
Crack is usually smoked in a glass pipe, and once inhaled, it passes from the lungs directly to the [[central nervous system]], producing an almost immediate "high" that can be very powerful – this initial crescendo of stimulation is known as a "rush". This is followed by an equally intense low, leaving the user craving more drug. Addiction to crack usually occurs with four to six weeks; much more rapidly than with regular cocaine.<ref name="Lamar">{{Cite news | vauthors = Lamar JV |title=Crack – A Cheap and Deadly Cocaine Is a Spreading Menace. |url= https://www.ojp.gov/ncjrs/virtual-library/abstracts/crack-cheap-and-deadly-cocaine-spreading-menace |access-date=17 June 2022 |publisher=Time |date=2 June 1986 |pages=16–18}}</ref>

Powder cocaine (cocaine hydrochloride) must be heated to a high temperature (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.

Crack is a lower purity form of free-base cocaine that is usually produced by neutralization of cocaine hydrochloride with a solution of baking soda (sodium bicarbonate, NaHCO<sub>3</sub>) and water, producing a very hard/brittle, off-white-to-brown colored, amorphous material that contains sodium carbonate, entrapped water, and other by-products as the main impurities. The origin of the name "crack" comes from the "crackling" sound (and hence the [[onomatopoeic]] moniker "crack") that is produced when the cocaine and its impurities (i.e. water, sodium bicarbonate) are heated past the point of vaporization.<ref name=Nelson98>{{Cite book | vauthors = Nelson G |title=Hip Hop America |year=1998 |publisher=Viking Penguin |url={{Google books |8nw6VlsqOUsC|Hip Hop America |page=40 |plainurl=yes}} |page=40 }}</ref>

==== Coca leaf infusions ====
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 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}}</ref>

Visitors to the city of [[Cuzco]] in Peru, and [[La Paz]] in Bolivia are greeted with the offering of coca leaf infusions (prepared in teapots with whole coca leaves) purportedly to help the newly arrived traveler overcome the malaise of high altitude sickness.<ref name="Vera">{{Cite news | vauthors = Vera N |title=The Coca Story Goes Way Beyond Cola. |url=https://tastecooking.com/the-coca-story-goes-way-beyond-the-cola/ |access-date=15 June 2022 |publisher=Taste |date=26 October 2021}}</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}}</ref> It has also been promoted as an adjuvant for the treatment of cocaine dependence. One study on coca leaf infusion used with counseling in the treatment of 23 addicted coca-paste smokers in [[Lima]], Peru found that the relapses rate fell from 4.35 times per month on average before coca tea treatment to one during treatment. The duration of abstinence increased from an average of 32&nbsp;days before treatment to 217.2&nbsp;days during treatment. This suggests that coca leaf infusion plus counseling may be effective at preventing relapse during cocaine addiction treatment.<ref name="Teobaldo">{{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=2014-06-02 |url-status=live}}</ref>

There is little information on the pharmacological and toxicological effects of consuming coca tea. A chemical analysis by [[solid-phase extraction]] and [[gas chromatography–mass spectrometry]] (SPE-GC/MS) of Peruvian and Bolivian tea bags indicated the presence of significant amounts of cocaine, the metabolite [[benzoylecgonine]], ecgonine methyl ester and trans-cinnamoylcocaine in coca tea bags and coca tea. [[Urine]] specimens were also analyzed from an individual who consumed one cup of coca tea and it was determined that enough cocaine and cocaine-related metabolites were present to produce a positive drug test.<ref name="Jenkins">{{Cite journal | vauthors = Jenkins AJ, Llosa T, Montoya I, Cone EJ | title = Identification and quantitation of alkaloids in coca tea | journal = Forensic Science International | volume = 77 | issue = 3 | pages = 179–189 | date = February 1996 | pmid = 8819993 | pmc = 2705900 | doi = 10.1016/0379-0738(95)01860-3 }}</ref>

=== Synthesis ===

==== Biosynthesis ====
{{Main|Biosynthesis of cocaine}}
[[File:Tropane alkaloids biochemistry.png|right|thumb|Biological source of cocaine molecule in the context of the tropane class of molecules. The biological source of each tropane alkaloid is indicated by species, and below that a phylogenetic map is provided.]]
The first synthesis and elucidation of the cocaine molecule was by [[Richard Willstätter]] in 1898.<ref name="Humphrey2001">{{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 derived cocaine from [[tropinone]]. Since then, [[Robert Robinson (organic chemist)|Robert Robinson]] and Edward Leete have made significant contributions to the mechanism of the synthesis. (-NO<sub>3</sub>)

The additional carbon atoms required for the synthesis of cocaine are derived from acetyl-CoA, by addition of two acetyl-CoA units to the ''N''-methyl-Δ<sup>1</sup>-pyrrolinium cation.<ref>{{Cite book | vauthors = Dewick PM |title=Medicinal Natural Products |publisher=Wiley-Blackwell |location=Chichester|year=2009 |isbn=978-0-470-74276-1}}</ref> The first addition is a [[Mannich reaction|Mannich]]-like reaction with the enolate anion from acetyl-CoA acting as a [[nucleophile]] towards the pyrrolinium cation. The second addition occurs through a Claisen condensation. This produces a racemic mixture of the 2-substituted pyrrolidine, with the retention of the thioester from the Claisen condensation. In formation of [[tropinone]] from [[racemic]] ethyl [2,3-13C<sub>2</sub>]<sub>4</sub>(Nmethyl-2-pyrrolidinyl)-3-oxobutanoate there is no preference for either stereoisomer.<ref>{{Cite journal|doi = 10.1021/ja964461p|title = The Biosynthesis of Tropane Alkaloids in Datura stramonium: The Identity of the Intermediates between ''N''-Methylpyrrolinium Salt and Tropinone|year = 1997 | vauthors = Robins RJ, Abraham TE, Parr AJ, Eagles J, Walton NJ |journal = J. Am. Chem. Soc.|volume = 119|pages = 10929–10934|issue = 45}}</ref> In cocaine biosynthesis, only the (S)-enantiomer can cyclize to form the tropane ring system of cocaine. The stereoselectivity of this reaction was further investigated through study of prochiral methylene hydrogen discrimination.<ref>{{Cite journal | vauthors = Hoye TR, Bjorklund JA, Koltun DO, Renner MK | title = N-methylputrescine oxidation during cocaine biosynthesis: study of prochiral methylene hydrogen discrimination using the remote isotope method | journal = Organic Letters | volume = 2 | issue = 1 | pages = 3–5 | date = January 2000 | pmid = 10814231 | doi = 10.1021/ol990940s }}</ref> This is due to the extra chiral center at C-2.<ref>{{Cite journal|doi = 10.1021/ja00024a039|title = Late intermediates in the biosynthesis of cocaine: 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoate and methyl ecgonine|year = 1991| vauthors = Leete E, Bjorklund JA, Couladis MM, Kim SH |journal = J. Am. Chem. Soc.|volume = 113|pages = 9286–9292|issue = 24}}</ref> This process occurs through an oxidation, which regenerates the pyrrolinium cation and formation of an enolate anion, and an intramolecular Mannich reaction. The tropane ring system undergoes [[hydrolysis]], SAM-dependent methylation, and reduction via [[NADPH]] for the formation of [[methylecgonine]]. The [[benzoyl]] moiety required for the formation of the cocaine diester is synthesized from phenylalanine via cinnamic acid.<ref>{{Cite journal|doi = 10.1016/0031-9422(88)87026-2|title = The biosynthesis of the benzoyl moiety of cocaine|year = 1988 | vauthors = Leete E, Bjorklund JA, Kim SH |journal = Phytochemistry|volume = 27|pages = 2553–2556|issue = 8| bibcode=1988PChem..27.2553L }}</ref> Benzoyl-CoA then combines the two units to form cocaine.

[[File:Biosynthesis of cocaine.png|thumb|400px|center|Biosynthesis of cocaine]]

===== ''N''-methyl-pyrrolinium cation =====

The [[biosynthesis]] begins with L-[[Glutamine]], which is derived to L-[[ornithine]] in plants. The major contribution of L-ornithine and L-[[arginine]] as a precursor to the [[tropane]] ring was confirmed by Edward Leete.<ref>{{Cite journal | vauthors = Leete E, Marion L, Spenser ID | title = Biogenesis of hyoscyamine | journal = Nature | volume = 174 | issue = 4431 | pages = 650–1 | date = October 1954 | pmid = 13203600 | doi = 10.1038/174650a0 | bibcode = 1954Natur.174..650L | s2cid = 4264282 }}</ref> Ornithine then undergoes a [[pyridoxal phosphate]]-dependent decarboxylation to form putrescine. In some animals, the urea cycle derives putrescine from ornithine. L-ornithine is converted to L-arginine,<ref>{{Cite journal | vauthors = Robins RJ, Waltons NJ, Hamill JD, Parr AJ, Rhodes MJ | title = Strategies for the genetic manipulation of alkaloid-producing pathways in plants | journal = Planta Medica | volume = 57 | issue = 7 Suppl | pages = S27-35 | date = October 1991 | pmid = 17226220 | doi = 10.1055/s-2006-960226 | s2cid = 45912704 }}</ref> which is then decarboxylated via PLP to form agmatine. Hydrolysis of the imine derives ''N''-carbamoylputrescine followed with hydrolysis of the urea to form putrescine. The separate pathways of converting ornithine to putrescine in plants and animals have converged. A SAM-dependent ''N''-methylation of putrescine gives the ''N''-methylputrescine product, which then undergoes oxidative deamination by the action of diamine oxidase to yield the aminoaldehyde. Schiff base formation confirms the biosynthesis of the ''N''-methyl-Δ<sup>1</sup>-pyrrolinium cation.

[[File:Biosynthesis of N-methyl-pyrrolinium cation.png|center|thumb|500px|Biosynthesis of ''N''-methyl-pyrrolinium cation]]

===== Robert Robinson's acetonedicarboxylate =====
The biosynthesis of the [[tropane alkaloid]] is still not understood. Hemscheidt proposes that Robinson's acetonedicarboxylate emerges as a potential intermediate for this reaction.<ref>{{Cite journal|doi = 10.1007/3-540-48146-X|title = Tropane and Related Alkaloids|year = 2000| vauthors = Hemscheidt T, Vederas JC | journal = Top. Curr. Chem.|volume = 209|page = 175|series = Topics in Current Chemistry | veditors = Leeper FJ, Vederas JC | isbn = 978-3-540-66573-1}}</ref> Condensation of ''N''-methylpyrrolinium and acetonedicarboxylate would generate the oxobutyrate. Decarboxylation leads to tropane alkaloid formation.

[[File:Robinson biosynthesis of tropane.png|center|thumb|500px|Robinson biosynthesis of tropane]]

===== Reduction of tropinone =====
The reduction of tropinone is mediated by [[NADPH]]-dependent reductase enzymes, which have been characterized in multiple plant species.<ref>{{Cite journal|doi = 10.1016/0031-9422(92)80247-C|title = Two tropinone reducing enzymes from Datura stramonium transformed root cultures|year = 1992 | vauthors =  Portsteffen A, Draeger B, Nahrstedt A |journal = Phytochemistry|volume = 31|pages = 1135–1138|issue = 4| bibcode=1992PChem..31.1135P }}</ref> These plant species all contain two types of the reductase enzymes, tropinone reductase I and tropinone reductase II. TRI produces tropine and TRII produces pseudotropine. Due to differing kinetic and pH/activity characteristics of the enzymes and by the 25-fold higher activity of TRI over TRII, the majority of the tropinone reduction is from TRI to form tropine.<ref>{{Cite journal | vauthors = Boswell HD, Dräger B, McLauchlan WR, Portsteffen A, Robins DJ, Robins RJ, Walton NJ | title = Specificities of the enzymes of N-alkyltropane biosynthesis in Brugmansia and Datura | journal = Phytochemistry | volume = 52 | issue = 5 | pages = 871–8 | date = November 1999 | pmid = 10626376 | doi = 10.1016/S0031-9422(99)00293-9 | bibcode = 1999PChem..52..871B }}</ref>

[[File:Reduction of tropinone.png|thumb|center|500px|Reduction of tropinone]]

==== GMO synthesis ====

===== Research =====
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 |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}}</ref>

=== Detection in 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 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>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 9th edition, Biomedical Publications, Seal Beach, California, 2011, pp. 390–394.</ref>

=== Field analysis ===

Cocaine may be detected by law enforcement using the [[Scott reagent]]. The test can easily generate 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 |title=Meet the Chemist Behind Many Popular—and Faulty—Police Drug Kits |date=22 June 2016 |work=Pacific Standard |access-date=21 April 2020 }}</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 |issn=0003-2700}}</ref>

== Usage ==
{{Main|List of countries by prevalence of cocaine use}}
{{Global estimates of illicit drug users}}
According to a 2016 United Nations report, [[England and Wales]] are the countries with the highest rate of cocaine usage (2.4% of adults in the previous year).<ref name="unodc">{{Cite web | title = World Drug Report 2016 (interactive map) | url = https://www.unodc.org/wdr2016/interactive-map.html | year = 2016 | publisher = United Nations Office on Drugs and Crime | url-status=live | archive-url = https://web.archive.org/web/20180309120506/https://www.unodc.org/wdr2016/interactive-map.html | archive-date = 9 March 2018 | df = dmy-all }}</ref> Other countries where the usage rate meets or exceeds 1.5% are Spain and Scotland (2.2%), the United States (2.1%), Australia (2.1%), Uruguay (1.8%), Brazil (1.75%), Chile (1.73%), the Netherlands (1.5%) and Ireland (1.5%).<ref name="unodc" />

=== Europe ===
Cocaine is the second most popular illegal recreational drug in Europe (behind [[cannabis (drug)|cannabis]]). Since the mid-1990s, overall cocaine usage in Europe has been on the rise, but usage rates and attitudes tend to vary between countries. European countries with the highest usage rates are the United Kingdom, Spain, Italy, and the Republic of Ireland.

Approximately 17 million Europeans (5.1%) have used cocaine at least once and 3.5 million (1.1%) in the last year. About 1.9% (2.3 million) of young adults (15–34 years old) have used cocaine in the last year (latest data available as of 2018).<ref>{{Cite web|url=https://www.emcdda.europa.eu/data/stats2018/gps_en|title=Statistical Bulletin 2018 —&nbsp;prevalence of drug use |website=www.emcdda.europa.eu|access-date=5 February 2019}}</ref>

Usage is particularly prevalent among this demographic: 4% to 7% of males have used cocaine in the last year in Spain, Denmark, the Republic of Ireland, Italy, and the United Kingdom. The ratio of male to female users is approximately 3.8:1, but this statistic varies from 1:1 to 13:1 depending on country.<ref name="European Monitoring Centre for Drugs and Drug Addiction">{{Cite book | url = https://www.emcdda.europa.eu/attachements.cfm/att_64227_EN_EMCDDA_AR08_en.pdf |publisher=European Monitoring Centre for Drugs and Drug Addiction|title=The State of the Drugs Problem in Europe 2008|location=Luxembourg|year=2008|pages=58–62|access-date=31 December 2013|url-status=live|archive-url=https://web.archive.org/web/20130425191815/https://www.emcdda.europa.eu/attachements.cfm/att_64227_EN_EMCDDA_AR08_en.pdf|archive-date=25 April 2013}}</ref>

In 2014 London had the highest amount of cocaine in its sewage out of 50 European cities.<ref>{{Cite web|url=https://www.bbc.co.uk/news/uk-33009682|title=Cocaine in sewage: London tops league table|work=BBC News | vauthors = Casciani D |date=4 June 2015|access-date=4 June 2015|url-status=live|archive-url=https://web.archive.org/web/20150604232505/https://www.bbc.co.uk/news/uk-33009682|archive-date=4 June 2015}}</ref>

=== United States ===
{{Main|Cocaine in the United States}}
Cocaine is the second most popular illegal recreational drug in the United States (behind [[cannabis (drug)|cannabis]])<ref>{{Cite web|url=https://www.erowid.org/chemicals/cocaine/cocaine.shtml|title=Cocaine & Crack|publisher=Erowid.org|access-date=10 July 2007|archive-url = https://web.archive.org/web/20071006230957/https://www.erowid.org/chemicals/cocaine/cocaine.shtml |archive-date = 6 October 2007|url-status=dead}}</ref> and the U.S. is the world's largest consumer of cocaine.<ref name="WFK Illicit drugs" /> Its users span over different ages, races, and professions. In the 1970s and 1980s, the drug became particularly popular in the [[disco]] culture as cocaine usage was very common and popular in many discos such as [[Studio 54]].

== Dependence treatment ==
{{main|Cocaine dependence#Treatment}}

== History ==

=== Discovery ===
[[File:Folha de coca.jpg|thumb|[[Coca leaf]] in [[Bolivia]]]]
[[Indigenous peoples of South America]] have chewed the leaves of ''[[coca|Erythroxylon coca]]''—a plant that contains vital nutrients as well as numerous [[alkaloids]], including cocaine—for over a thousand years.<ref>{{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> The coca leaf was, and still is, chewed almost universally by some indigenous communities. The remains of coca leaves have been found with ancient Peruvian mummies, and pottery from the time period depicts humans with bulged cheeks, indicating the presence of something on which they are chewing.<ref name="mummies">{{Cite journal | vauthors = Altman AJ, Albert DM, Fournier GA | title = Cocaine's use in ophthalmology: our 100-year heritage | journal = Survey of Ophthalmology | volume = 29 | issue = 4 | pages = 300–6 | year = 1985 | pmid = 3885453 | doi = 10.1016/0039-6257(85)90153-5 }}</ref> There is also evidence that these cultures used a mixture of coca leaves and saliva as an anesthetic for the performance of [[Trepanning|trepanation]].<ref name="trepanning">{{Cite journal | vauthors = Gay GR, Inaba DS, Sheppard CW, Newmeyer JA | title = Cocaine: history, epidemiology, human pharmacology, and treatment. a perspective on a new debut for an old girl | journal = Clinical Toxicology | volume = 8 | issue = 2 | pages = 149–78 | year = 1975 | pmid = 1097168 | doi = 10.3109/15563657508988061 }}</ref>

When the [[Spanish colonization of the Americas|Spanish arrived in South America]], the conquistadors at first banned coca as an "evil agent of devil". But after discovering that without the coca the locals were barely able to work, the conquistadors legalized and taxed the leaf, taking 10% off the value of each crop.<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 |url-status=dead |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> In 1569, Spanish botanist [[Nicolás Monardes]] described the indigenous peoples' practice of chewing a mixture of tobacco and coca leaves to induce "great contentment":
{{Blockquote|When they wished to make themselves drunk and out of judgment they chewed a mixture of tobacco and coca leaves which make them go as they were out of their wittes.<ref name="monardes">{{Cite book|title=Joyfull Newes out of the Newe Founde Worlde | vauthors = Monardes N, Frampton J |publisher=Alfred Knopf|year=1925|location=New York}}</ref>}}

In 1609, [[Military chaplain|Padre]] [[Blas Valera]] wrote:
{{Blockquote|Coca protects the body from many ailments, and our doctors use it in powdered form to reduce the swelling of wounds, to strengthen broken bones, to expel cold from the body or prevent it from entering, and to cure rotten wounds or sores that are full of maggots. And if it does so much for outward ailments, will not its singular virtue have even greater effect in the entrails of those who eat it?<ref>{{Cite web|title=InterAndean Institute of Coca Sciences|url=https://www.cienciadelacoca.org/CocaVega.html|website=www.cienciadelacoca.org|url-status=live|archive-url=https://web.archive.org/web/20161230070400/https://cienciadelacoca.org/CocaVega.html|archive-date=30 December 2016|df=dmy-all}}</ref>}}

=== Isolation and naming ===
Although the stimulant and hunger-suppressant properties of coca had been known for many centuries, the isolation of the cocaine [[alkaloid]] was not achieved until 1855. Various European scientists had attempted to isolate cocaine, but none had been successful for two reasons: the knowledge of chemistry required was insufficient at the time, and contemporary conditions of sea-shipping from South America could degrade the cocaine in the plant samples available to European chemists.{{Citation needed|date=July 2022}}

The cocaine alkaloid was first isolated by the German chemist [[Friedrich Gaedcke]] in 1855. Gaedcke named the alkaloid "erythroxyline", and published a description in the journal ''[[Archiv der Pharmazie]].''<ref>{{Cite journal|title = Ueber das Erythroxylin, dargestellt aus den Blättern des in Südamerika cultivirten Strauches Erythroxylon Coca| vauthors = Gaedcke F |journal = Archiv der Pharmazie|volume = 132|issue = 2|pages = 141–150|year = 1855|doi = 10.1002/ardp.18551320208| s2cid = 86030231 | url = https://zenodo.org/record/1424529 }}</ref>

In 1856, [[Friedrich Wöhler]] asked Dr. [[Carl Scherzer]], a scientist aboard the ''[[SMS Novara (1850)|Novara]]'' (an Austrian [[frigate]] sent by Emperor [[Franz Joseph of Austria|Franz Joseph]] to circle the globe), to bring him a large amount of coca leaves from South America. In 1859, the ship finished its travels and Wöhler received a trunk full of coca. Wöhler passed on the leaves to [[Albert Niemann (chemist)|Albert Niemann]], a [[Doctor of Philosophy|PhD]] student at the [[University of Göttingen]] in Germany, who then developed an improved purification process.<ref name=nie1860>{{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}}</ref>

Niemann described every step he took to isolate cocaine in his [[dissertation]] titled ''[[On a New Organic Base in the Coca Leaves|Über eine neue organische Base in den Cocablättern]]'' (''On a New Organic Base in the Coca Leaves''), which was published in 1860 and earned him his Ph.D. He wrote of the alkaloid's "colourless transparent prisms" and said that "Its solutions have an alkaline reaction, a bitter taste, promote the flow of saliva and leave a peculiar numbness, followed by a sense of cold when applied to the tongue." Niemann named the alkaloid "cocaine" from "coca" (from [[Quechua languages|Quechua]] "kúka") + [[affix|suffix]] "ine".<ref name=nie1860 /><ref>{{OEtymD|Cocaine}}</ref>

The first synthesis and elucidation of the structure of the cocaine molecule was by [[Richard Willstätter]] in 1898.<ref name="Humphrey2001" /> It was the first [[biomimetics|biomimetic]] synthesis of an organic structure recorded in academic chemical literature.<ref name="Singh2">{{Cite journal | vauthors = Singh S | title = Chemistry, design, and structure-activity relationship of cocaine antagonists | journal = Chemical Reviews | volume = 100 | issue = 3 | pages = 925–1024 | date = March 2000 | pmid = 11749256 | doi = 10.1021/cr9700538 | url = https://www.erowid.org/archive/rhodium/pdf/cocaineanalogs.pdf | archive-url = https://web.archive.org/web/20160304193726/https://www.erowid.org/archive/rhodium/pdf/cocaineanalogs.pdf |archive-date = 4 March 2016 | url-status=live | quote = Page 970 (46th page of article) first, ninth, and tenth lines }}</ref><ref>(a) {{Cite journal | vauthors = Willstatter R | title = Synthese der Ecgoninsäure | trans-title = Synthesis of Tropine | language = de | journal = Liebigs Ann. | year = 1903 | volume = 326 | issue = 1–2 | page = 23 | doi = 10.1002/jlac.19033260105 }} (b) {{Cite journal | vauthors = Robinson RJ | title = LXIII. A synthesis of tropinone | journal = J. Chem. Soc., Trans. | year = 1917 | volume = 111 | pages = 762–768 | doi = 10.1039/CT9171100762 | url = https://zenodo.org/record/1429739 }} (c) {{Cite journal | title = Die Synthese des Tropinons, Pseudopelletierins, Lobelanins und verwandter Alkaloide unter physiologischen Bedingungen | trans-title = The synthesis of tropinone, pseudopelletierin, lobelanin and related alkaloids under physiological conditions | language = de | vauthors = Schopf C, Lehman G | journal = Liebigs Ann. | year = 1935 | volume = 518 | pages = 1–37 | doi = 10.1002/jlac.19355180102 }}</ref> The synthesis started from [[tropinone]], a related natural product and took five steps.

Because of the former use of cocaine as a [[local anesthetic]], a suffix "-caine" was later extracted and used to form names of synthetic [[local anesthetic]]s.

=== Medicalization ===
<!--yes, this is a word, go look it up in the OED ;)-->
[[File:Cocaine for kids.png|thumb|"Cocaine toothache drops", 1885 advertisement of cocaine for [[toothache|dental pain]] in children]]
[[File:Burnett's Cocaine for the hair (advertisement, McClure's 1896).jpg|thumb|Advertisement in the January 1896 issue of ''[[McClure's]] Magazine'' for Burnett's Cocaine "for the hair"]]
[[File:Bottle for cocaine solution 2.jpg|thumb|Bottle of cocaine solution, Germany, circa 1915]]
With the discovery of this new alkaloid, Western medicine was quick to exploit the possible uses of this plant.

In 1879, Vassili von Anrep, of the [[University of Würzburg]], devised an experiment to demonstrate the analgesic properties of the newly discovered alkaloid. He prepared two separate jars, one containing a cocaine-salt solution, with the other containing merely saltwater. He then submerged a frog's legs into the two jars, one leg in the treatment and one in the control solution, and proceeded to stimulate the legs in several different ways. The leg that had been immersed in the cocaine solution reacted very differently from the leg that had been immersed in saltwater.<ref name="anrep_frog">{{Cite journal | vauthors = Yentis SM, Vlassakov KV | title = Vassily von Anrep, forgotten pioneer of regional anesthesia | journal = Anesthesiology | volume = 90 | issue = 3 | pages = 890–5 | date = March 1999 | pmid = 10078692 | doi = 10.1097/00000542-199903000-00033 }}</ref>

[[Karl Koller (ophthalmologist)|Karl Koller]] (a close associate of [[Sigmund Freud]], who would write about cocaine later) experimented with cocaine for [[ophthalmology|ophthalmic]] usage. In an infamous experiment in 1884, he experimented upon himself by applying a cocaine solution to his own eye and then pricking it with pins. His findings were presented to the Heidelberg Ophthalmological Society. Also in 1884, Jellinek demonstrated the effects of cocaine as a [[respiratory system]] anesthetic. In 1885, [[William Halsted]] demonstrated nerve-block anesthesia,<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> 1898 saw [[Heinrich Quincke]] use cocaine for [[spinal anesthesia]].

=== Popularization ===
[[File:Mariani pope.jpg|thumb|[[Pope Leo XIII]] purportedly carried a hip flask of the coca-treated Vin Mariani with him, and awarded a [[Vatican City|Vatican]] [[gold medal]] to [[Angelo Mariani (chemist)|Angelo Mariani]].<ref>{{Cite web |url=https://www.cocanaturally.com/ |title=Experience Vin Mariani today &#124; Grupo Mariani S.A |publisher=Cocanaturally.com |access-date=15 January 2011 |url-status=dead |archive-url=https://web.archive.org/web/20110208034115/https://cocanaturally.com/ |archive-date=8 February 2011 }}</ref>]]
In 1859, an Italian [[physician|doctor]], [[Paolo Mantegazza]], returned from [[Peru]], where he had witnessed first-hand the use of coca by the local indigenous peoples. He proceeded to experiment on himself and upon his return to [[Milan]], he wrote a paper in which he described the effects. In this paper, he declared coca and cocaine (at the time they were assumed to be the same) as being useful medicinally, in the treatment of "a furred tongue in the morning, [[flatulence]], and whitening of the teeth."

A chemist named [[Angelo Mariani (chemist)|Angelo Mariani]] who read Mantegazza's paper became immediately intrigued with coca and its economic potential. In 1863, Mariani started marketing a [[wine]] called [[Vin Mariani]], which had been treated with coca leaves, to become [[coca wine]]. The [[ethanol]] in wine acted as a solvent and extracted the cocaine from the coca leaves, altering the drink's effect. It contained 6&nbsp;mg cocaine per ounce of wine, but Vin Mariani which was to be exported contained 7.2&nbsp;mg per ounce, to compete with the higher cocaine content of similar drinks in the United States. A "pinch of coca leaves" was included in [[John Pemberton|John Styth Pemberton]]'s original 1886 recipe for [[Coca-Cola]], though the company began using decocainized leaves in 1906 when the [[Pure Food and Drug Act]] was passed.

In 1879 cocaine began to be used to treat [[morphine]] addiction. Cocaine was introduced into clinical use as a [[local anesthetic]] in Germany in 1884, about the same time as [[Sigmund Freud]] published his work ''Über Coca'',<ref>{{Cite book | vauthors = Freud S | veditors = Byck R | title=Cocaine Papers | publisher=Stonehill | location= | year=1975 | isbn=0-88373-010-3 }}</ref> in which he wrote that cocaine causes:<ref>{{Cite web|title=How a Young Sigmund Freud Researched & Got Addicted to Cocaine, the New "Miracle Drug," in 1894|url=https://www.openculture.com/2014/04/igmund-freud-researched-got-addicted-to-cocaine.html|website=Open Culture|url-status=live|archive-url=https://web.archive.org/web/20170307204530/https://www.openculture.com/2014/04/igmund-freud-researched-got-addicted-to-cocaine.html|archive-date=7 March 2017}}</ref>

{{Blockquote|Exhilaration and lasting euphoria, which in no way differs from the normal euphoria of the healthy person. You perceive an increase of self-control and possess more vitality and capacity for work. In other words, you are simply normal, and it is soon hard to believe you are under the influence of any drug. Long intensive physical work is performed without any fatigue. This result is enjoyed without any of the unpleasant after-effects that follow exhilaration brought about by [[alcoholic beverage]]s. No craving for the further use of cocaine appears after the first, or even after repeated taking of the drug.<ref>{{Cite web|title=Sigmund Freud and Cocaine|url=https://cocaine.org/cokespoon.htm|website=cocaine.org|url-status=live|archive-url=https://web.archive.org/web/20170119115241/https://cocaine.org/cokespoon.htm|archive-date=19 January 2017|df=dmy-all}}</ref>}}

By 1885 the U.S. manufacturer [[Parke-Davis]] sold coca-leaf cigarettes and cheroots, a cocaine inhalant, a Coca Cordial, cocaine crystals, and cocaine solution for intravenous injection.<ref>{{Cite journal | vauthors = Musto DF |title=America's First Cocaine Epidemic |url=https://www.jstor.org/stable/40257908 |journal=The Wilson Quarterly |pages=59–64 |date=1989|volume=13 |issue=3 | pmid = 11619697| jstor=40257908 }}</ref> The company promised that its cocaine products would "supply the place of food, make the coward brave, the silent eloquent and render the sufferer insensitive to pain."

[[File:BEAUTY-COMFORT By Madame Falloppe (1904).jpg|left|thumb|In this 1904 [[advice column]] from ''[[the Tacoma Times]]'', "Madame [[Fallopian tube|Falloppe]]" recommended that [[cold sores]] be treated with a solution of [[borax]], cocaine, and [[morphine]].]]

By the late [[Victorian era]], cocaine use had appeared as a vice in [[literature]]. For example, it was injected by [[Arthur Conan Doyle]]'s fictional [[Sherlock Holmes]], generally to offset the boredom he felt when he was not working on a case.

In early 20th-century [[Memphis, Tennessee]], cocaine was sold in neighborhood drugstores on [[Beale Street]], costing five or ten cents for a small boxful. Stevedores along the Mississippi River used the drug as a stimulant, and white employers encouraged its use by black laborers.<ref name= barlow>{{Cite book | vauthors = Barlow W | title = Looking Up At Down: The Emergence of Blues Culture | url = https://archive.org/details/lookingupatdowne0000barl | url-access = registration | date = 1989 | publisher = Temple University Press | location = Philadelphia | isbn = 0-87722-583-4 | page = [https://archive.org/details/lookingupatdowne0000barl/page/207 207] }}</ref>

In 1909, [[Ernest Shackleton]] took "Forced March" brand cocaine tablets to [[Antarctica]], as did [[Captain Scott]] a year later on his ill-fated journey to the [[South Pole]].<ref name="dominic_streatfeild">{{Cite book | vauthors = Streatfeild D |title=Cocaine: An Unauthorized Biography|publisher=Picador|year=2003|isbn=978-0-312-42226-4}}</ref>

In the 1931 song "[[Minnie the Moocher]]", [[Cab Calloway]] heavily references cocaine use. He uses the phrase "kicking the gong around", slang for cocaine use; describes titular character Minnie as "tall and skinny;" and describes Smokey Joe as "cokey".<ref>{{Cite magazine| vauthors = White T |date=August 14, 1993|title=Catchin' Cab: The Magic of Calloway|url=https://books.google.com/books?id=6BEEAAAAMBAJ&q=billboard+minnie+the+moocher+1931&pg=PA3 |magazine=Billboard|pages=3}}</ref> In the 1932 comedy musical film ''[[The Big Broadcast]]'', Cab Calloway performs the song with his orchestra and mimes snorting cocaine in between verses.<ref>{{Citation|title=The Big Broadcast (1932) (Full Movie)|url=https://www.youtube.com/watch?v=nCC4zlrC5rQ&t=1h20m30s|pages=at 1:20:29|language=en|access-date=2022-01-13}}</ref>

During the mid-1940s, amidst World War II, cocaine was considered for inclusion as an ingredient of a future generation of 'pep pills' for the German military, code named [[D-IX]].<ref>{{Cite web |url=https://amphetamines.com/nazidrug.html |title=Jeevan Vasagar: cocaine-based "wonder drug" tested on concentration camp inmates |publisher=Amphetamines.com |date=19 November 2002 |access-date=15 January 2011 |url-status=live |archive-url=https://web.archive.org/web/20110227003229/https://www.amphetamines.com/nazidrug.html |archive-date=27 February 2011 }}</ref>

In modern popular culture, references to cocaine are common. The drug has a glamorous image associated with the wealthy, famous and powerful, and is said to make users "feel rich and beautiful".<ref name=nyt1>{{Cite news | vauthors = Ryzik M |title=Cocaine: Hidden in Plain Sight |url= https://www.nytimes.com/2007/06/10/fashion/10cocaine.html |newspaper=The New York Times |access-date=18 May 2017 |date=10 June 2007 |url-status=live|archive-url=https://web.archive.org/web/20170811060445/https://www.nytimes.com/2007/06/10/fashion/10cocaine.html |archive-date=11 August 2017 }}</ref><ref>{{Cite web|title=The Buyers – A Social History of America's Most Popular Drugs | work = FRONTLINE |url= https://www.pbs.org/wgbh/pages/frontline/shows/drugs/buyers/socialhistory.html |publisher=PBS |access-date=18 May 2017 |url-status=live |archive-url= https://web.archive.org/web/20170514022136/https://www.pbs.org/wgbh/pages/frontline/shows/drugs/buyers/socialhistory.html |archive-date=14 May 2017 }}</ref><ref>{{Cite book | vauthors = Brisbane FL, Womble M | title = Treatment of Black Alcoholics|publisher=Psychology Press | isbn = 978-0-86656-403-8 | url = https://books.google.com/books?id=DA7SmDh-X5cC&pg=PA167 | access-date = 18 May 2017 | url-status=live | archive-url = https://web.archive.org/web/20170910234911/https://books.google.com/books?id=DA7SmDh-X5cC&pg=PA167 | archive-date=10 September 2017| year = 1985 }}</ref><ref>{{Cite book| vauthors = Waldorf D, Reinarman C, Murphy S |title=Cocaine Changes: The Experience of Using and Quitting|publisher=Temple University Press|isbn=978-1-56639-013-2|url=https://archive.org/details/cocainechangesex00wald|url-access=registration|page=[https://archive.org/details/cocainechangesex00wald/page/95 95]|access-date=18 May 2017|date=June 1992}}</ref> In addition the pace of modern society − such as in finance − gives many the incentive to make use of the drug.<ref name=nyt1 />

[[File:Bundesarchiv Bild 102-07741, Berlin, "Koks Emil" der Kokain-Verkäufer.jpg|thumb|Women purchase cocaine capsules in Berlin, 1929]]

=== Modern usage ===
[[File:Marion Barry smoking crack.gif|thumb|right|D.C. Mayor [[Marion Barry]] captured on a surveillance camera smoking crack cocaine during a sting operation by the [[FBI]] and [[D.C. Police]]]]
In many countries, cocaine is a popular [[recreational drug]]. In the United States, the development of [[crack cocaine|"crack" cocaine]] introduced the substance to a generally poorer inner-city market. The use of the powder form has stayed relatively constant, experiencing a new height of use during the late 1990s and early 2000s in the U.S., and has become much more popular in the last few years in the UK. {{Citation needed|date=November 2010}}{{When|date=March 2013}}

Cocaine use is prevalent across all socioeconomic strata, including age, demographics, economic, social, political, religious, and livelihood.<ref name="Current">{{Cite book |vauthors = Current JD | chapter = Cocaine |title=Pharmacology for Anesthetists | chapter-url=https://books.google.com/books?id=_Du2bfrO9FwC&pg=PA27 | page = 27 }}</ref>

The estimated U.S. cocaine market exceeded US$70 billion in street value for the year 2005, exceeding revenues by corporations such as [[Starbucks]].<ref>{{Cite web|url=https://www.applesanity.com/fetish/blow/ |archive-url=https://web.archive.org/web/20080617113902/https://www.applesanity.com/fetish/blow/ |archive-date=17 June 2008 |title=Apple Sanity – Fetish – Blow: War on Drugs VS. Cocaine |publisher=Applesanity.com |date=17 June 2008 |access-date=13 November 2011}}</ref><ref>{{Cite web|url=https://www.havocscope.com/tag/cocaine/ |archive-url=https://web.archive.org/web/20121111114403/https://www.havocscope.com/tag/cocaine/ |archive-date=11 November 2012 |title=Cocaine Market |date=28 April 2008 |publisher=Havocscope.com |access-date=9 March 2010}}</ref> Cocaine's status as a [[club drug]] shows its immense popularity among the "party crowd".<ref name="Current" />

In 1995 the [[World Health Organization]] (WHO) and the [[United Nations Interregional Crime and Justice Research Institute]] (UNICRI) announced in a press release the publication of the results of the largest global study on cocaine use ever undertaken. An American representative in the [[World Health Assembly]] banned the publication of the study, because it seemed to make a case for the positive uses of cocaine. An excerpt of the report strongly conflicted with accepted paradigms, for example, "that occasional cocaine use does not typically lead to severe or even minor physical or social problems." In the sixth meeting of the B committee, the US representative threatened that "If World Health Organization activities relating to drugs failed to reinforce proven drug control approaches, funds for the relevant programs should be curtailed". This led to the decision to discontinue publication. A part of the study was recuperated and published in 2010, including profiles of cocaine use in 20 countries, but are unavailable {{As of|2015|lc=y}}.<ref name=TNI>{{Cite web|title=The WHO Cocaine Project|author=WHO/UNICRI|url=https://www.tni.org/article/who-cocaine-project|publisher=Transnational Institute|date=4 February 2010|access-date=8 June 2012|url-status=live|archive-url=https://web.archive.org/web/20120809073614/https://www.tni.org/article/who-cocaine-project|archive-date=9 August 2012}}</ref>

In October 2010 it was reported that the use of cocaine in Australia has doubled since monitoring began in 2003.<ref>{{Cite news |title=Cocaine use doubles in a decade |url=https://www.smh.com.au/lifestyle/wellbeing/cocaine-use-doubles-in-a-decade-20101015-16mli.html |work=Sydney Morning Herald |date=15 October 2010 |access-date=19 October 2010 |url-status=live |archive-url=https://web.archive.org/web/20101018051009/https://www.smh.com.au/lifestyle/wellbeing/cocaine-use-doubles-in-a-decade-20101015-16mli.html |archive-date=18 October 2010 }}</ref>

A problem with illegal cocaine use, especially in the higher volumes used to combat fatigue (rather than increase euphoria) by long-term users, is the risk of ill effects or damage caused by the compounds used in adulteration. Cutting or "stepping on" the drug is commonplace, using compounds which simulate ingestion effects, such as [[Novocain]] (procaine) producing temporary anesthesia, as many users believe a strong numbing effect is the result of strong and/or pure cocaine, ephedrine or similar stimulants that are to produce an increased heart rate. The normal adulterants for profit are inactive sugars, usually mannitol, creatine, or glucose, so introducing active adulterants gives the illusion of purity and to 'stretch' or make it so a dealer can sell more product than without the adulterants.{{Citation needed|date=May 2009}} The adulterant of sugars allows the dealer to sell the product for a higher price because of the illusion of purity and allows the sale of more of the product at that higher price, enabling dealers to significantly increase revenue with little additional cost for the adulterants. A 2007 study by the [[European Monitoring Centre for Drugs and Drug Addiction]] showed that the purity levels for street purchased cocaine was often under 5% and on average under 50% pure.<ref>{{Cite web|title=EMCDDA Retail Cocaine Purity Study|year=2007|author=EMCDDA|url=https://www.emcdda.europa.eu/stats09/ppptab7a|access-date=31 December 2013|url-status=live|archive-url=https://web.archive.org/web/20140101041854/https://www.emcdda.europa.eu/stats09/ppptab7a|archive-date=1 January 2014}}</ref>

== Society and culture ==

=== Legal status ===
{{Main|Legal status of cocaine}}
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 Peru and Bolivia, 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>{{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|language=en-GB|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}}</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}}</ref>

==== United States ====
{{See also|Cocaine in the United States}}
[[File:US timeline. Drugs involved in overdose deaths.jpg|thumb|230px|[[Drug overdose]]s killed more than 70,200 Americans in 2017, with [[Cocaine intoxication|cocaine overdoses]] making up 13,942 of those deaths.<ref name=NIDA-deaths />]]

The US federal government instituted a national labeling requirement for cocaine and cocaine-containing products through the Pure Food and Drug Act of 1906.{{sfn|Gootenberg|1999|p=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 set up a regulatory and licensing regime.{{sfn|Madge|2001|p=106}} 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|language=en|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.{{sfn|Gootenberg|1999|p=40}} Despite that cocaine was typically illegal to sell and legal outlets were rarer, the quantities of legal cocaine produced declined very little.{{sfn|Gootenberg|1999|p=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.{{sfn|Gootenberg|1999|p=40}}

Before the early 1900s, the primary problem caused by cocaine use was portrayed by newspapers to be addiction, not violence or crime, and the cocaine user was represented as an upper- or middle-class White person. In 1914, ''The New York Times'' published an article titled "Negro Cocaine 'Fiends' Are a New Southern Menace", portraying Black cocaine users 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}}</ref> The [[Anti-Drug Abuse Act of 1986]] mandated prison sentences for 500 grams of powdered cocaine and 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}}</ref> In the [[National Survey on Drug Use and Health]], Whites reported a higher rate of powdered cocaine use, and Blacks 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}}</ref>

=== Interdiction ===
[[File:PHL Cocaine596H 061719 (48099711998).jpg|thumb|United States [[U.S. Customs and Border Protection|CBP]] police inspect a seized shipment of cocaine.]]
[[File:U.S. Coast Guard Cutter Tahoma Cocaine Offload DVIDS311738.jpg|thumb|The U.S. Coast Guard in [[Miami]] offloading confiscated cocaine]]
In 2004, according to the [[United Nations]], 589 [[tonne]]s of cocaine were seized globally by law enforcement authorities. [[Colombia]] seized 188&nbsp;t, the United States 166&nbsp;t, Europe 79&nbsp;t, Peru 14&nbsp;t, Bolivia 9&nbsp;t, and the rest of the world 133 t.<ref name="un-wdr2006">{{Cite book|title=World Drug Report 2006|publisher=[[United Nations]]|location=New York|chapter-url=https://www.unodc.org/pdf/WDR_2006/wdr2006_chap4_cocaine.pdf|year=2006|chapter=Cocaine: Seizures, 1998–2003|volume=2|url-status=live|archive-url=https://web.archive.org/web/20070614092314/https://www.unodc.org/pdf/WDR_2006/wdr2006_chap4_cocaine.pdf|archive-date=14 June 2007}}</ref>

==== Production ====
Colombia is as of 2019 the world's largest cocaine producer, with production more than tripling since 2013.<ref name="CIA World Factbook">[https://www.cia.gov/the-world-factbook/countries/colombia/ Colombia] . CIA World Factbook</ref><ref name="NBC Worldnews">{{Cite web | url = https://worldnews.nbcnews.com/_news/2012/07/31/13045253-us-peru-overtakes-colombia-as-top-cocaine-producer | title = Peru Overtakes Colombia as Top Cocaine Producer | work = NBC News | date = 31 July 2012 | archive-url = https://web.archive.org/web/20160304055344/https://worldnews.nbcnews.com/_news/2012/07/31/13045253-us-peru-overtakes-colombia-as-top-cocaine-producer | archive-date=4 March 2016 }}</ref> Three-quarters of the world's annual yield of cocaine has been produced in Colombia, both from cocaine base imported from Peru (primarily the [[Huallaga Valley]]) and Bolivia and from locally grown coca. There was a 28% increase in the amount of potentially harvestable coca plants which were grown in Colombia in 1998. This, combined with crop reductions in Bolivia and Peru, made Colombia the nation with the largest area of [[cocaine production in Colombia|coca under cultivation]] after the mid-1990s. Coca grown for traditional purposes by indigenous communities, a use which is still present and is permitted by Colombian laws, only makes up a small fragment of total coca production, most of which is used for the illegal drug trade.{{Citation needed|date=September 2015}}

An interview with a coca farmer published in 2003 described a mode of production by [[acid-base extraction]] that has changed little since 1905. Roughly {{convert|625|lb|kg}} of leaves were harvested per [[hectare]], six times per year. The leaves were dried for half a day, then chopped into small pieces with a string trimmer and sprinkled with a small amount of powdered cement (replacing [[sodium carbonate]] from former times). Several hundred pounds of this mixture were soaked in {{convert|50|USgal|L}} of gasoline for a day, then the gasoline was removed and the leaves were pressed for the remaining liquid, after which they could be discarded. Then [[battery acid]] (weak [[sulfuric acid]]) was used, one bucket per {{convert|25|kg|0|abbr=on|order=flip}} of leaves, to create a [[phase (matter)|phase]] separation in which the cocaine [[free base]] in the gasoline was acidified and extracted into a few buckets of "murky-looking smelly liquid". Once powdered [[caustic soda]] was added to this, the cocaine precipitated and could be removed by filtration through a cloth. The resulting material, when dried, was termed ''[[cocaine paste|pasta]]'' and sold by the farmer. The {{convert|3,750|lb}} yearly harvest of leaves from a hectare produced {{convert|2.5|kg|0|abbr=on|order=flip}} of ''pasta''<!--- note that this figure is only about ⅓ of the figure inferred from the numbers below --->, approximately 40–60% cocaine. Repeated recrystallization from solvents, producing ''pasta lavada'' and eventually crystalline cocaine were performed at specialized laboratories after the sale.<ref>{{Cite book|url=https://books.google.com/books?id=9ceLzaeHsZAC&pg=PA462|title=Cocaine: An Unauthorized Biography | vauthors = Streatfeild D |publisher=Macmillan|year=2003|isbn=978-0-312-42226-4|access-date=5 January 2014|url-status=live|archive-url=https://web.archive.org/web/20140115082648/https://books.google.com/books?id=9ceLzaeHsZAC&pg=PA462|archive-date=15 January 2014}}</ref>

Attempts to eradicate coca fields through the use of [[defoliants]] have devastated part of the farming economy in some coca-growing regions of Colombia, and strains appear to have been developed that are more resistant or immune to their use. Whether these strains are natural mutations or the product of human tampering is unclear. These strains have also shown to be more potent than those previously grown, increasing profits for the drug cartels responsible for the exporting of cocaine. Although production fell temporarily, coca crops rebounded in numerous smaller fields in Colombia, rather than the larger plantations.{{Citation needed|date=September 2015}}

The cultivation of coca has become an attractive economic decision for many growers due to the combination of several factors, including the lack of other employment alternatives, the lower profitability of alternative crops in official crop substitution programs, the eradication-related damages to non-drug farms, the spread of new strains of the coca plant due to persistent worldwide demand.{{Citation needed|date=September 2015}}

{| class="wikitable" style="margin: 1em auto 1em auto"
|+ Estimated Andean region coca cultivation and potential pure cocaine production<ref>{{Cite web |title=National Drug Threat Assessment 2006 |year=2006 |url=https://www.justice.gov/ndic/pubs11/18862/index.htm |archive-url=https://web.archive.org/web/20101111172335/https://www.justice.gov/ndic/pubs11/18862/index.htm |archive-date=11 November 2010 |website=[[National Drug Intelligence Center]]}}</ref>
|-
! !!2000!!2001!!2002!!2003!!2004
|-
| Net cultivation km<sup>2</sup> (sq mi)||{{Convert|1875|km2|mi2|abbr = values}}||{{Convert|2218|km2|mi2|abbr = values}}||{{convert|2007.5|km2|mi2|abbr = values}}||{{Convert|1663|km2|mi2|abbr = values}}||{{Convert|1662|km2|mi2|abbr = values}}
|-
| Potential pure cocaine production ([[tonne]]s)||770||925||830||680||645
|}

The latest estimate provided by the U.S. authorities on the annual production of cocaine in Colombia refers to 290 metric tons.
As of the end of 2011, the seizure operations of [[Colombian cocaine]] carried out in different countries have totaled 351.8 metric tons of cocaine, i.e. 121.3% of Colombia's annual production according to the U.S. Department of State's estimates.<ref>{{Cite news |url=https://www.flarenetwork.org/report/top_news_100615/article/cocaine_seized_worldwide_highest_ever_in_2011.htm |title=Cocaine Seized Worldwide Highest Ever in 2011 |date=18 January 2012 |publisher=Flare Network (Flarenetwork.org) |access-date=5 January 2014 |url-status=dead |archive-url=https://web.archive.org/web/20140106033115/https://www.flarenetwork.org/report/top_news_100615/article/cocaine_seized_worldwide_highest_ever_in_2011.htm |archive-date=6 January 2014 }}</ref><!--OLD URL:https://dl.dropbox.com/u/13210473/NARCOLEAKS%20ENG.pdf Narcoleaks--><ref>{{Cite web |url=https://2009-2017.state.gov/r/pa/ei/bgn/35754.htm |title=Colombia |newspaper=U.S. Department of State |publisher=State.gov |access-date=26 March 2013 }}</ref>

==== Synthesis ====
Synthesizing cocaine could eliminate the high visibility and low reliability of offshore sources and international smuggling, replacing them with clandestine domestic laboratories, as are common for illicit [[methamphetamine]], but is rarely done. Natural cocaine remains the lowest cost and highest quality supply of cocaine. Formation of inactive [[stereoisomers]] (cocaine has four chiral centres – 1''R'' 2''R'', 3''S'', and 5''S'', two of them dependent, hence eight possible stereoisomers) plus synthetic by-products limits the yield and purity.{{Citation needed|date=September 2015}}

==== Trafficking and distribution ====
[[File:CocaineCharango-Opened.jpg|thumb|Cocaine smuggled in a [[charango]], 2008]]
[[Organized crime|Organized criminal]] gangs operating on a large scale dominate the cocaine trade. Most cocaine is grown and processed in South America, particularly in Colombia, [[Bolivia]], Peru, and smuggled into the United States and Europe, the United States being 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 |url-status=dead |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> where it is sold at huge markups; usually in the US at $80–120 for 1&nbsp;gram, and $250–300 for 3.5&nbsp;grams ({{sfrac|1|8}} of an ounce, or an "eight ball").<ref>{{Cite web|title=How Much Is a Gram of Coke?|url=https://www.newhealthadvisor.com/How-Much-Is-a-Gram-of-Coke.html|website=New Health Advisor|date=3 September 2015|url-status=live|archive-url=https://web.archive.org/web/20170307123722/https://www.newhealthadvisor.com/How-Much-Is-a-Gram-of-Coke.html|archive-date=7 March 2017}}</ref>

===== Caribbean and Mexican routes =====
The primary cocaine importation points in the United States have been in [[Arizona]], southern [[California]], southern [[Florida]], and [[Texas]]. Typically, land vehicles are driven across the U.S.–Mexico border. Sixty-five percent of cocaine enters the United States through Mexico, and the vast majority of the rest enters through Florida.<ref>{{Cite book | vauthors = Jacobson R | title = Illegal drugs: America's anguish | date = 2006 | publisher = Thomson Gale | location = Farmington Hills, Michigan | isbn = 978-1-4144-0419-6 | edition = 2005 | url = https://archive.org/details/illegaldrugsamer00jaco }}</ref>{{page needed|date=December 2015}} {{As of|2015}}, the [[Sinaloa Cartel]] is the most active [[drug cartel]] involved in smuggling illicit drugs like cocaine into the United States and trafficking them throughout the United States.<ref name="DEA 2015 assessment">{{Cite web|title=2015 National Drug Threat Assessment Summary|url=https://www.dea.gov/docs/2015%20NDTA%20Report.pdf|website=Drug Enforcement Administration|publisher=United States Department of Justice: Drug Enforcement Administration|access-date=10 April 2016|pages=1–2|date=October 2015|quote=Mexican TCOs pose the greatest criminal drug threat to the United States; no other group is currently positioned to challenge them. These Mexican poly-drug organizations traffic heroin, methamphetamine, cocaine, and marijuana throughout the United States, using established transportation routes and distribution networks. ... While all of these Mexican TCOs transport wholesale quantities of illicit drugs into the United States, the Sinaloa Cartel appears to be the most active supplier. The Sinaloa Cartel leverages its expansive resources and dominance in Mexico to facilitate the smuggling and transportation of drugs throughout the United States.|url-status=dead|archive-url=https://web.archive.org/web/20160410100038/https://www.dea.gov/docs/2015%20NDTA%20Report.pdf|archive-date=10 April 2016}}</ref>

Cocaine traffickers from Colombia and Mexico have established a labyrinth of [[smuggling]] routes throughout the Caribbean, the Bahama Island chain, and South Florida. They often hire traffickers from Mexico or the [[Dominican Republic]] to transport the drug using a variety of smuggling techniques to U.S. markets. These include airdrops of {{convert|500|to|700|kg|-2|abbr=on}} in the [[Bahama Islands]] or off the coast of [[Puerto Rico]], mid-ocean boat-to-boat transfers of {{convert|500|to|2000|kg|-2|abbr=on}}, and the commercial shipment of tonnes of cocaine through the port of [[Miami]].{{Citation needed|date=September 2015}}

===== Chilean route =====
Another route of cocaine traffic goes through Chile, which is primarily used for cocaine produced in Bolivia since the nearest seaports lie in northern Chile. The arid Bolivia–Chile border is easily crossed by 4×4 vehicles that then head to the seaports of [[Iquique]] and [[Antofagasta]]. While the price of cocaine is higher in Chile than in Peru and Bolivia, the final destination is usually Europe, especially Spain where drug dealing networks exist among South American immigrants.{{Citation needed|date=March 2017}}

===== Techniques =====
Cocaine is also carried in small, concealed, kilogram quantities across the border by couriers known as "[[mule (smuggling)|mules]]" (or "mulas"), who cross a border either legally, for example, through a port or airport, or illegally elsewhere. The drugs may be strapped to the waist or legs or hidden in bags, or hidden in the body. If the mule gets through without being caught, the gangs will reap most of the profits. If caught, gangs will sever all links and the mule will usually stand trial for trafficking alone.{{Citation needed|date=September 2015}}

Bulk cargo ships are also used to smuggle cocaine to staging sites in the western Caribbean–[[Gulf of Mexico]] area. These vessels are typically 150–250-foot (50–80&nbsp;m) coastal freighters that carry an average cocaine load of approximately 2.5 tonnes. Commercial fishing vessels are also used for smuggling operations. In areas with a high volume of recreational traffic, smugglers use the same types of vessels, such as [[go-fast boat]]s, like those used by the local populations.{{Citation needed|date=September 2015}}

Sophisticated [[narco-submarine|drug subs]] are the latest tool drug runners are using to bring cocaine north from Colombia, it was reported on 20 March 2008. Although the vessels were once viewed as a quirky sideshow in the drug war, they are becoming faster, more seaworthy, and capable of carrying bigger loads of drugs than earlier models, according to those charged with catching them.<ref>{{Cite news|url=https://edition.cnn.com/2008/CRIME/03/20/drug.subs/index.html|title=Coast Guard hunts drug-running semi-subs|access-date=20 March 2008|publisher=CNN|date=20 March 2008|url-status=live|archive-url=https://web.archive.org/web/20080321111250/https://edition.cnn.com/2008/CRIME/03/20/drug.subs/index.html|archive-date=21 March 2008}}</ref>

==== Sales to consumers ====
[[File:Flavcocaine.jpg|thumb|Cocaine adulterated with fruit flavoring]]

Cocaine is readily available in all major countries' metropolitan areas. According to the ''Summer 1998 Pulse Check'', published by the U.S. [[Office of National Drug Control Policy]], cocaine use had stabilized across the country, with a few increases reported in [[San Diego]], [[Bridgeport, Connecticut|Bridgeport]], Miami, and [[Boston]]. In the West, cocaine usage was lower, which was thought to be due to a switch to [[methamphetamine]] among some users; methamphetamine is cheaper, three and a half times more powerful, and lasts 12–24&nbsp;times longer with each dose.<ref>{{Cite web|url=https://methproject.org/Meth_Info/education.php|archive-url=https://web.archive.org/web/20100327140334/https://methproject.org/Meth_Info/education.php |archive-date=27 March 2010|title=Meth Info |publisher=Methproject.org}}</ref><ref>{{Cite web|url=https://www.denisonia.com/policeDept/amphetamines.asp|title=Drugs of Abuse|work=City of Denison Iowa|access-date=13 November 2011|url-status=live|archive-url=https://web.archive.org/web/20111106092215/https://www.denisonia.com/policeDept/amphetamines.asp|archive-date=6 November 2011}}</ref> Nevertheless, the number of cocaine users remain high, with a large concentration among urban youth.

In addition to the amounts previously mentioned, cocaine can be sold in "bill sizes": {{As of|2007}} for example, $10 might purchase a "dime bag", a very small amount (0.1–0.15&nbsp;g) of cocaine. These amounts and prices are very popular among young people because they are inexpensive and easily concealed on one's body. Quality and price can vary dramatically depending on supply and demand, and on geographic region.<ref>{{Cite news |url=https://www.economist.com/node/9414607 |title=Drugs: Pricing Power |newspaper=[[The Economist]] |date=28 June 2007 |quote=Prices: USA around $110/g, Israel/Germany/Britain around $46/g, Colombia $2/g, New Zealand recordbreaking $714.30/g. |url-status=live |archive-url=https://web.archive.org/web/20140106040602/https://www.economist.com/node/9414607 |archive-date=6 January 2014 }}</ref><!--OLD URL:https://www.economist.com/daily/chartgallery/displaystory.cfm?story_id=9414607-->

In 2008, the [[European Monitoring Centre for Drugs and Drug Addiction]] reports that the typical retail price of cocaine varied between €50 and €75 per gram in most European countries, although Cyprus, Romania, Sweden, and Turkey reported much higher values.<ref>{{Cite book |author=European Monitoring Centre for Drugs and Drug Addiction |title=Annual report: the state of the drugs problem in Europe |year=2008 |publisher=Office for Official Publications of the European Communities |location=Luxembourg |isbn=978-92-9168-324-6 |page=59 |url=https://www.emcdda.europa.eu/attachements.cfm/att_64227_EN_EMCDDA_AR08_en.pdf |access-date=31 December 2013 |url-status=live |archive-url=https://web.archive.org/web/20130425191815/https://www.emcdda.europa.eu/attachements.cfm/att_64227_EN_EMCDDA_AR08_en.pdf |archive-date=25 April 2013 |author-link=European Monitoring Centre for Drugs and Drug Addiction }}</ref>

==== Consumption ====
World annual cocaine consumption, as of 2000, stood at around 600 tonnes, with the United States consuming around 300&nbsp;t, 50% of the total, Europe about 150&nbsp;t, 25% of the total, and the rest of the world the remaining 150&nbsp;t or 25%.<ref>{{Cite book|url=https://www.defenselink.mil/policy/sections/policy_offices/solic/cn/cocaine2.pdf|archive-url=https://web.archive.org/web/20080911061809/https://www.defenselink.mil/policy/sections/policy_offices/solic/cn/cocaine2.pdf|archive-date=11 September 2008|title=The Cocaine Threat: A Hemispheric Perspective|publisher=[[United States Department of Defense]]}}</ref> It is estimated that 1.5 million people in the United States used cocaine in 2010, down from 2.4 million in 2006.<ref name="Zimmerman2012" /> Conversely, cocaine use appears to be increasing{{When|date=January 2023}} in Europe with the highest prevalences in [[Spain]], the [[United Kingdom]], [[Italy]], and [[Republic of Ireland|Ireland]].<ref name="Zimmerman2012" />

The 2010 UN [[World Drug Report]] concluded that "it appears that the North American cocaine market has declined in value from US$47 billion in 1998 to US$38 billion in 2008. Between 2006 and 2008, the value of the market remained basically stable".<ref name="Nations2010">{{Cite book|author=United Nations|title=World Drug Report 2010|url=https://books.google.com/books?id=HB9PuEhHahQC&pg=PA77|date=June 2010|publisher=United Nations Publications|isbn=978-92-1-148256-0|page=77|url-status=live|archive-url=https://web.archive.org/web/20160426034255/https://books.google.com/books?id=HB9PuEhHahQC&pg=PA77 |archive-date=26 April 2016}}</ref>

== See also ==
{{Portal|Medicine}}
{{Div col|colwidth=22em}}
* [[Black cocaine]]
* [[Coca alkaloid]]s
* [[Coca eradication]]
* [[Cocaine and amphetamine regulated transcript]]
* [[Cocaine Anonymous]]
* ''[[Cocaine Cowboys (2006 film)|Cocaine Cowboys]]''
* [[Cocaine paste]]
* {{section link|Crack cocaine|Crack lung}}
* [[Crack epidemic]]
* [[Illegal drug trade in Latin America]]
* [[Coca production in Colombia]]
* [[Clan del Golfo]]
* [[Legal status of cocaine]]
* [[List of cocaine analogues]]
* [[List of countries by prevalence of cocaine use]]
* [[Methylphenidate]]
* [[Modafinil]]
* [[Pre-Columbian trans-oceanic contact theories#Claims of Egyptian coca and tobacco|Pre-Columbian trans-oceanic evidence for cocaine in ancient Egypt]]
* [[Prenatal cocaine exposure]]
* [[Route 36 (bar)|Route 36, cocaine bar in Bolivia]]
* [[Tranquilandia]]
* [[Ypadu]]
{{Div col end}}

== References ==
{{Reflist}}

== General bibliography ==
{{refbegin}}
* {{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}}
* {{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}}
* {{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 }}
{{refend}}

== Further reading ==
{{refbegin}}
* {{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}}
{{refend}}

== External links ==
{{Wikiquote}}
{{Commons category|Cocaine}}
{{Wiktionary|cocaine}}
* {{Cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/cocaine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Cocaine }}
* {{Cite web | url = https://www.emcdda.europa.eu/publications/drug-profiles/cannabis | publisher = European Monitoring Centre for Drugs | title = Cocaine }}

{{Drug use}}
{{Euphoriants}}
{{Stimulants}}
{{Local anesthetics}}
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{{Ion channel modulators}}
{{Monoamine reuptake inhibitors}}
{{Sigma receptor modulators}}
{{Authority control}}

[[Category:Cocaine| ]]
[[Category:Alkaloids found in Erythroxylum]]
[[Category:Anorectics]]
[[Category:Benzoate esters]]
[[Category:Carboxylate esters]]
[[Category:Cardiac stimulants]]
[[Category:CYP2D6 inhibitors]]
[[Category:Euphoriants]]
[[Category:German inventions]]
[[Category:Glycine receptor agonists]]
[[Category:Local anesthetics]]
[[Category:Methyl esters]]
[[Category:Otologicals]]
[[Category:Powders]]
[[Category:Secondary metabolites]]
[[Category:Serotonin–norepinephrine–dopamine reuptake inhibitors]]
[[Category:Sigma agonists]]
[[Category:Stimulants]]
[[Category:Sympathomimetic amines]]
[[Category:Teratogens]]
[[Category:Tropane alkaloids found in Erythroxylum coca]]
[[Category:Vasoconstrictors]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Obsolete medications]]
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[[Категория:Английская Википедия]]
[[Категория:Википедия]]
[[Категория:Статья из Википедии]]
[[Категория:Статья из Английской Википедии]]