cocaine#Freebase

Coca leaves have been used by Andean civilizations since ancient times.{{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 }} In ancient Wari culture,{{Cite journal | vauthors = Valdez LM, Taboada J, Valdez JE |title=Ancient Use of Coca Leaves in the Peruvian Central Highlands |journal=Journal of Anthropological Research |date=June 2015 |volume=71 |issue=2 |pages=231–258 |doi=10.3998/jar.0521004.0071.204|s2cid=163842955 |hdl=2027/spo.0521004.0071.204 |hdl-access=free }} Inca culture, and through modern successor indigenous cultures of the Andes mountains, coca leaves are chewed, taken orally in the form of a tea, or alternatively, prepared in a sachet wrapped around alkaline burnt ashes, and held in the mouth against the inner cheek; it has traditionally been used as an anorectic and to combat the effects of cold and altitude sickness,{{Cite journal | vauthors = Martin RT |title=The role of coca in the history, religion, and medicine of South American Indians |journal=Economic Botany |date=October 1970 |volume=24 |issue=4 |pages=422–438 |doi=10.1007/BF02860746|bibcode=1970EcBot..24..422M |s2cid=34523519 }}{{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 }} although its actual effectiveness has never been systematically studied.{{cite journal | vauthors = Luks AM, McIntosh SE, Grissom CK, Auerbach PS, Rodway GW, Schoene RB, Zafren K, Hackett PH | title = Wilderness Medical Society practice guidelines for the prevention and treatment of acute altitude illness: 2014 update | journal = Wilderness & Environmental Medicine | volume = 25 | issue = 4 Suppl | pages = S4–14 | date = December 2014 | pmid = 25498261 | doi = 10.1016/j.wem.2014.06.017 }}

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%).{{Cite book |title=World Drug Report 2021: Booklet 4 |date= 2021 |publisher=United Nations Office on Drugs and Crime |location=[S.l.]| page = 35|isbn=978-92-1-148361-1 |url=https://www.unodc.org/res/wdr2021/field/WDR21_Booklet_4.pdf |archive-url=https://web.archive.org/web/20210624081524/https://www.unodc.org/res/wdr2021/field/WDR21_Booklet_4.pdf |archive-date=24 June 2021 |url-status=live}} Since 1961, the Single Convention on Narcotic Drugs has required countries to make recreational use of cocaine a crime.{{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 }} 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.{{Cite web |title=Drug Fact Sheet: Cocaine |url=https://www.dea.gov/sites/default/files/2020-06/Cocaine-2020_1.pdf |archive-url=https://web.archive.org/web/20200621183713/https://www.dea.gov/sites/default/files/2020-06/Cocaine-2020_1.pdf |archive-date=21 June 2020 |url-status=live |publisher=Drug Enforcement Agency |access-date=17 June 2022}} While rarely used medically today, its accepted uses include serving as a topical local anesthetic for the upper respiratory tract and as an antihemorrhagic agent to stop bleeding in the mouth, throat, and nasal cavities.{{cite web |url=https://www.dea.gov/sites/default/files/2020-06/Cocaine-2020_1.pdf |title=Drug Fact Sheet: Cocaine |publisher=US Department for Justice and Drug Enforcement Administration |access-date=29 June 2024 |archive-date=21 June 2020 |archive-url=https://web.archive.org/web/20200621183713/https://www.dea.gov/sites/default/files/2020-06/Cocaine-2020_1.pdf |url-status=live }}

{{Main|Coca}}

File:Llipta on coca leaf.jpeg, Peru).]]

It is legal for people to use coca leaves in the Andean Community, such as Peru and Bolivia, where they are chewed, consumed in the form of tea, or are sometimes incorporated into food products.{{Cite web|url=https://www.pri.org/stories/2011-04-01/tradition-chewing-coca|title=The tradition of chewing coca|date=15 August 2013 |access-date=6 May 2021|archive-date=6 May 2021|archive-url=https://web.archive.org/web/20210506205057/https://www.pri.org/stories/2011-04-01/tradition-chewing-coca|url-status=live}} Coca leaves are typically mixed with an alkaline substance (such as 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.

{{Main|Coca tea}}

File:Mate de coca Peru.jpg

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.{{Cite web|url=https://www.businessinsider.com/britain-is-the-worlds-biggest-exporter-of-legal-cocaine-and-heroin-2018-4|title=It's legal to manufacture cocaine and heroin for medical use — and Britain is the world's biggest exporter|vauthors=Embury-Dennis T|website=Business Insider|access-date=17 March 2019|archive-date=28 July 2020|archive-url=https://web.archive.org/web/20200728165239/https://www.businessinsider.com/britain-is-the-worlds-biggest-exporter-of-legal-cocaine-and-heroin-2018-4|url-status=live}} The effects of drinking coca tea are mild stimulation and mood lift.{{Cite web|url=https://www.drugs.com/illicit/cocaine.html|title=Cocaine: Effects, Hazards & Warnings|website=Drugs.com|access-date=17 March 2019|archive-date=28 July 2020|archive-url=https://web.archive.org/web/20200728162727/https://www.drugs.com/illicit/cocaine.html|url-status=live}}

In 1986 an article in the Journal of the American Medical Association revealed that U.S. health food stores 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 mood elevation, and the tea was essentially harmless.{{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 }}

{{Main|Ypadu}}

File:Mambe indigena coca colombia crista castellanos.jpg

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

Karl Koller’s groundbreaking discovery of cocaine as a local anesthetic is regarded as the second most significant advance in the history of anesthesia. Although cocaine was once widely preferred for topical anesthesia, the search for replacement agents intensified due to rising costs, strict regulations, and its habit-forming potential. Today, the US Drug Enforcement Administration (DEA) classifies cocaine as a Schedule II drug, recognizing its high potential for abuse but still permitting its limited use for medical purposes.

However, current pharmacoepidemiological trends suggest that cocaine may soon reach the point where, in practical terms, it is no longer used medically in health care as a Schedule II substance. This report may prompt some states (such as North Dakota) and institutions to reconsider whether further efforts to identify alternative agents are needed. As physician boards—but not pharmacy boards—continue to assess knowledge of licit cocaine, attention may shift toward drugs with more contemporary medical use.

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

Cocaine is used in medical practice as a topical medication. Because it is not absorbed into the bloodstream in significant amounts when used this way, topical application does not produce the psychoactive effects associated with recreational cocaine use.

{{See also|Moffett's solution}}

File:Cocaine hydrochloride CII for medicinal use.jpg]]

Cocaine is sometimes used in otorhinolaryngology as a topical anesthetic and vasoconstrictor to help control pain and bleeding during surgery of the nose, mouth, throat, or lacrimal duct. It is also used for topical airway anaesthesia for procedures such as awake fibreoptic bronchoscopy or intubation. Although some absorption and systemic effects may occur, the use of cocaine as a topical anesthetic and vasoconstrictor is generally safe, rarely causing cardiovascular toxicity, glaucoma, and pupil dilation.{{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 }}{{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 }} Occasionally, cocaine is mixed with adrenaline and sodium bicarbonate and used topically for surgery, a formulation called Moffett's solution.{{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 }} It is occasionally used in surgeries involving the pharynx or nasopharynx to reduce pain, bleeding, and vocal cord spasm.{{Cite book |vauthors=Hamdan AL, Sataloff RT, Hawkshaw MJ |title=Office-Based Laryngeal Surgery |chapter=Topical Anesthesia in Office-Based Laryngeal Surgery |chapter-url=https://link.springer.com/chapter/10.1007/978-3-030-91936-8_6 |date=2022 |pages=123–137 |publisher=Springer |location=USA |doi=10.1007/978-3-030-91936-8_6 |isbn=978-3-030-91935-1 |access-date=18 July 2022 |archive-date=18 July 2022 |archive-url=https://web.archive.org/web/20220718085028/https://link.springer.com/chapter/10.1007/978-3-030-91936-8_6 |url-status=live }}

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

Cocaine is an ophthalmological agent classified under ATC code S01HA Local anesthetics.

Cocaine eye drops are frequently used by neurologists when examining people suspected of having Horner syndrome. In Horner syndrome, sympathetic innervation to the eye is blocked. In a healthy eye, cocaine stimulates the sympathetic nervous system (SNS) by inhibiting norepinephrine reuptake, causing the pupil to dilate. In patients with Horner syndrome, sympathetic innervation to the eye is disrupted, so the affected pupil does not dilate in response to cocaine and remains constricted, or dilates to a lesser extent than the unaffected eye, which also receives the eye drop test. If both eyes dilate equally, the patient does not have Horner syndrome.{{Cite book | vauthors = Berkowitz AL |title=Clinical Neurology & Neuroanatomy: A Localization-Based Approach |publisher=McGraw Hill |year=2022 |isbn=978-1260453362 |edition=2nd |chapter=Chapter 10: Pupillary Control & Approach to Anisocoria: Cranial Nerves 2 & 3 |type=Digital}}

{{For|Cocaine or crack cocaine combined with other drugs|List of polysubstance combinations}}

File:Peruvian Flake Cocaine.jpg tray]]

Recreational cocaine is typically not taken by mouth due to its poor bioavailability, instead it is usually snorted, injected.

Cocaine hydrochloride can also be chemically converted into its free base form, crack cocaine, which can be vaporized.

Cocaine is a central nervous system stimulant.{{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}} 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.{{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}} 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.{{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 }}

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.{{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 }}

Analysis of the correlation between the use of 18 various psychoactive substances shows that cocaine use correlates with other "party drugs" (such as ecstasy or amphetamines), as well as with heroin and benzodiazepines use, and can be considered as a bridge between the use of different groups of drugs.{{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}}

In 2023, David Liddell of the Scottish Drugs Forum reported a rise in cocaine use, particularly among people with long-term drug problems, and noted that stigma often delays users from seeking help until their issues become severe.{{cite news |title=Patients face losing noses due to cocaine use, medics warn |url=https://www.bbc.com/news/uk-scotland-glasgow-west-64901125 |date=9 March 2023}}

File:Cocaine lines 2.jpg such as banknotes might serve as a fomite of diseases like hepatitis C{{cite web |url=http://cocaine.org/cokemoney/banknotes.html |title='Shared banknote' health warning to cocaine users |access-date=26 July 2008 | vauthors = Veevers L |date=1 October 2006 |work=The Observer }}]]

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

In a study of cocaine users, the average time taken to reach peak subjective effects was 14.6 minutes.{{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 }} 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, which, after chronic use, may cause "cocaine nose."

Most banknotes have traces of cocaine on them; this has been confirmed by studies done in several countries.{{cite web |url= http://www.snopes.com/business/money/cocaine.asp|title=Drug Money |date=9 July 2002 |accessdate=2008-07-23 |publisher=Snopes}}

In 1994, the U.S. 9th Circuit Court of Appeals cited findings that in Los Angeles, three out of four banknotes were tainted by cocaine or another illicit drug.{{cite news | vauthors = Abrahamson A |title=Prevalence of Drug-Tainted Money Voids Case Law: Court cites findings that more than 75% of currency in L.A. bears traces of cocaine or other illegal substances |url=https://pqasb.pqarchiver.com/latimes/access/59564073.html?dids=59564073:59564073&FMT=ABS&FMTS=ABS:FT&type=current&date=Nov+13%2C+1994&author=ALAN+ABRAHAMSON&pub=Los+Angeles+Times+(pre-1997+Fulltext)&edition=&startpage=1&desc=Prevalence+of+Drug-Tainted+Money+Voids+Case+Law%3A+Court+cites+findings+that+more+than+75%25+of+currency+in+L.A.+bears+traces+of+cocaine+or+other+illegal+substances. |work=Los Angeles Times |date=13 November 1994 |accessdate=2008-07-23 |archive-date=2011-06-04 |archive-url=https://web.archive.org/web/20110604092358/http://pqasb.pqarchiver.com/latimes/access/59564073.html?dids=59564073:59564073&FMT=ABS&FMTS=ABS:FT&type=current&date=Nov+13,+1994&author=ALAN+ABRAHAMSON&pub=Los+Angeles+Times+(pre-1997+Fulltext)&edition=&startpage=1&desc=Prevalence+of+Drug-Tainted+Money+Voids+Case+Law:+Court+cites+findings+that+more+than+75%+of+currency+in+L.A.+bears+traces+of+cocaine+or+other+illegal+substances. |url-status=dead }}{{cite news | vauthors = Price DM |title=Use of Drug-Sniffing Dogs Challenged;ACLU Backs Complaint by Men Whose Pocket Cash Was Seized |url=https://pqasb.pqarchiver.com/washingtonpost/access/72586089.html?dids=72586089:72586089&FMT=ABS&FMTS=ABS:FT&date=May+6%2C+1990&author=Debbie+M.+Price&pub=The+Washington+Post+(pre-1997+Fulltext)&edition=&startpage=d.01&desc=Use+of+Drug-Sniffing+Dogs+Challenged%3BACLU+Backs+Complaint+by+Men+Whose+Pocket+Cash+Was+Seized |archive-url=https://web.archive.org/web/20110604092431/http://pqasb.pqarchiver.com/washingtonpost/access/72586089.html?dids=72586089:72586089&FMT=ABS&FMTS=ABS:FT&date=May+6,+1990&author=Debbie+M.+Price&pub=The+Washington+Post+(pre-1997+Fulltext)&edition=&startpage=d.01&desc=Use+of+Drug-Sniffing+Dogs+Challenged%3BACLU+Backs+Complaint+by+Men+Whose+Pocket+Cash+Was+Seized |url-status=dead |archive-date=June 4, 2011 |newspaper=The Washington Post |date=6 May 1990 |accessdate=2008-07-23 }}

Snuff spoons, hollowed-out pens, cut straws, pointed ends of keys,{{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|archive-date=8 July 2024|archive-url=https://web.archive.org/web/20240708191807/https://www.mentalfloss.com/article/642413/mcdonalds-cocaine-spoon-controversy|url-status=live}} long fingernails or artificial nails, and (clean) tampon applicators are also used to insufflate cocaine. The cocaine typically is poured onto a flat, hard surface (such as a mobile phone screen, plate, mirror, CD case or book) and divided into "bumps", "lines" or "rails", and then insufflated.{{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 }} A 2001 study reported that the sharing of straws used to "snort" cocaine can spread blood diseases such as hepatitis C.{{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 }}

File:Stopper, snuff bottle (AM 687402-2).jpg

Historically, snuff spoons were used for cocaine in the 20th century, hence the names "cocaine spoon" and "coke spoon". Some local statutes in the US treat spoons that are too small and thus "unsuited for the typical, lawful uses of a spoon" as drug paraphernalia.{{cite web |title=Code of ordinances village of Dundee, Michigan. Chapter 51. |url=https://library.municode.com/mi/dundee/codes/code_of_ordinances?nodeId=PTIICOOR_CH51DRARNUPR_ARTIDRPA_S51-1DE |publisher=Village of Dundee}}{{Cite web |title=Code of Ordinances{{snd}}Clark County, NV |url=https://library.municode.com/nv/clark_county/codes/code_of_ordinances?nodeId=TIT12PUPESAMO_CH12.06DRPA |archive-url=https://web.archive.org/web/20240913094223/https://library.municode.com/nv/clark_county/codes/code_of_ordinances?nodeId=TIT12PUPESAMO_CH12.06DRPA |archive-date=2024-09-13 |access-date=2024-09-13 |website=Municode Library}}{{Cite web |title=Township of Middlesex, PA Drugs and Drug Paraphernalia |url=https://ecode360.com/11231035#11231037 |archive-url=https://web.archive.org/web/20240913094426/https://ecode360.com/11231035#11231037 |archive-date=2024-09-13 |access-date=2024-09-13 |website=eCode360}}

In the US, McDonald's provides straight swizzle sticks to stir the coffee, while in the rest of the world a small plastic stirring spoon is used. According to Anthony J. Graybosch, this is due to the 1960s rumor that the spoons can be used to snort cocaine.{{cite book | vauthors = Graybosch AJ | chapter = American Beauty | title = Deconstruction and Reconstruction | pages = 96 | date = 1 January 2004 | doi = 10.1163/9789004495876_013 | publisher = Brill | isbn = 978-90-420-1681-1 }}

Subjective effects not commonly shared with other methods of administration include a ringing in the ears moments after injection (usually when over 120 milligrams) lasting 2 to 5 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 minutes. The euphoria passes quickly. Aside from the toxic effects of cocaine, there is also the danger of circulatory 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.

{{Further|Crack cocaine}}

File:Man smoking crack cocaine in Bogotá, Colombia..jpg

Powder cocaine (cocaine hydrochloride) must be heated to a high temperature (about 197 °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}},{{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 }} which is below the boiling point of water.

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

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

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

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

Under the former FDA pregnancy category system, cocaine was classified as a Category C drug. Its potential to cause harm to the fetus is not fully known, so it should only be administered to pregnant women if clearly necessary.

Cocaine can act as a teratogen, having various effects on the developing fetus.{{Cite encyclopedia |title=Cocaine as a Teratogen | encyclopedia = Embryo Project Encyclopedia |url=https://embryo.asu.edu/pages/cocaine-teratogen |access-date=2025-04-07 | publisher = Arizona State University |language=en}} Some common teratogenic defects caused by cocaine include hydronephrosis, cleft palate, polydactyly, and down syndrome. Cocaine as a drug has a low molecular weight and high water and lipid solubility which enables it to cross the placenta and fetal blood-brain barrier.{{cite journal | vauthors = Singer L, Arendt R, Minnes S | title = Neurodevelopmental effects of cocaine | journal = Clinics in Perinatology | volume = 20 | issue = 1 | pages = 245–262 | date = March 1993 | pmid = 8458168 | pmc = 4181371 | doi = 10.1016/S0095-5108(18)30422-6 }} Because cocaine is able to pass through the placenta and enter the fetus, the fetus' circulation can be negatively affected. With restriction of fetal circulation, the development of organs in the fetus can be impacted, even resulting in intestines developing outside of the fetus' body. Cocaine use during pregnancy can also result in obstetric labor complications such as premature labor,{{cite journal | vauthors = Cain MA, Bornick P, Whiteman V | title = The maternal, fetal, and neonatal effects of cocaine exposure in pregnancy | journal = Clinical Obstetrics and Gynecology | volume = 56 | issue = 1 | pages = 124–132 | date = March 2013 | pmid = 23314714 | doi = 10.1097/GRF.0b013e31827ae167 }} placental abruption,{{cite journal | vauthors = Flowers D, Clark JF, Westney LS | title = Cocaine intoxication associated with abruptio placentae | journal = Journal of the National Medical Association | volume = 83 | issue = 3 | pages = 230–232 | date = March 1991 | pmid = 2038082 | pmc = 2627035 }} preterm birth or delivery, uterine rupture, miscarriage, and stillbirth.

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

The March of Dimes said "it is likely that cocaine will reach the baby through breast milk," and advises the following regarding cocaine use during pregnancy:

{{Blockquote|Cocaine use during pregnancy can affect a pregnant woman and her unborn baby in many ways. During the early months of pregnancy, it may increase the risk of miscarriage. Later in pregnancy, it can trigger preterm 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 injury, or a myocardial infarction.{{Cite web |url=http://www.marchofdimes.org/pregnancy/illicit-drug-use-during-pregnancy.aspx |title=Street Drugs and pregnancy |work=March of Dimes |access-date=26 May 2009 |archive-date=5 September 2015 |archive-url=https://web.archive.org/web/20150905080845/http://www.marchofdimes.org/pregnancy/illicit-drug-use-during-pregnancy.aspx |url-status=dead }}}}

{{For|harm caused by the freebase form|Crack cocaine#Adverse effects}}

{{See also|Cocaine#Lacing}}

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| A 2010 study ranking various illegal and legal drugs based on statements by drug-harm experts in the UK. Crack cocaine and cocaine were found to be the third and fifth overall most dangerous drugs respectively.{{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 }}

| Rational harm assessment of drugs bar plot.svg

| 2007 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.{{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 }}

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Cocaine use can cause serious heart problems like sudden death, heart inflammation, arrhythmias, and heart attacks. It triggers coronary artery spasms, increases blood clot risk, and accelerates atherosclerosis, especially with long-term use. The severity of heart disease often relates to how long and how often cocaine is used.{{cite journal | vauthors = Talarico GP, Crosta ML, Giannico MB, Summaria F, Calò L, Patrizi R | title = Cocaine and coronary artery diseases: a systematic review of the literature | journal = Journal of Cardiovascular Medicine | volume = 18 | issue = 5 | pages = 291–294 | date = May 2017 | pmid = 28306693 | doi = 10.2459/JCM.0000000000000511 }} It can also become a serious risk at high doses due to cocaine's blocking effect on cardiac sodium channels.

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

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

{{Main|Levamisole induced necrosis syndrome}}

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

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

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

Clinical studies have shown that taking levamisole at doses of 50–200 mg per day can lead to agranulocytosis in approximately 0.08–5% of patients.{{cite web |title=697. Levamisole (WHO Food Additives Series 27) |url=https://www.inchem.org/documents/jecfa/jecmono/v27je04.htm |website=www.inchem.org}}

{{Also|Desomorphine#Toxicity of krokodil}}

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

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

The broader cocaine/levamisole-associated autoimmune syndrome (CLAAS) includes LINES as a subset and is also common, but LINES is more specifically and frequently cited in the context of street cocaine adulteration.{{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 }}

Levamisole has become a common additive to illicit cocaine. It is thought to intensify the "high" by releasing dopamine in the brain, acts as a bulking agent, and is a difficult adulterant to recognize. Potential risks of levamisole-laced cocaine include autoimmune disease, neutropenia, arthralgias, retiform purpura, skin necrosis, and fever.{{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 }}

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

Cocaine is considered neurotoxic due to its damaging effects on the brain and nervous system.{{cite journal | vauthors = Nicolucci C, Pais ML, Santos AC, Ribeiro FM, Encarnação PM, Silva AL, Castro IF, Correia PM, Veloso JF, Reis J, Lopes MZ, Botelho MF, Pereira FC, Priolli DG | title = Single Low Dose of Cocaine-Structural Brain Injury Without Metabolic and Behavioral Changes | journal = Frontiers in Neuroscience | volume = 14 | pages = 589897 | date = 2020 | pmid = 33584173 | pmc = 7874143 | doi = 10.3389/fnins.2020.589897 | doi-access = free }}{{cite journal | vauthors = Hofmaier T, Luf A, Seddik A, Stockner T, Holy M, Freissmuth M, Ecker GF, Schmid R, Sitte HH, Kudlacek O | title = Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters | journal = Neurochemistry International | volume = 73 | issue = 100 | pages = 32–41 | date = July 2014 | pmid = 24296074 | pmc = 4077236 | doi = 10.1016/j.neuint.2013.11.010 }} Research has shown that both acute and chronic cocaine use can lead to significant reductions in cerebral blood flow, disrupt neurovascular interactions, and impair brain function. These changes are associated with nerve injury, cognitive deficits, and an increased risk of cerebrovascular accidents such as strokes. Brain imaging studies consistently report that individuals who misuse cocaine exhibit structural and functional abnormalities compared to non-users, supporting the classification of cocaine as a neurotoxic substance.{{cite journal | vauthors = Clare K, Park K, Pan Y, Lejuez CW, Volkow ND, Du C | title = Neurovascular effects of cocaine: relevance to addiction | journal = Frontiers in Pharmacology | volume = 15 | pages = 1357422 | date = 2024 | pmid = 38455961 | pmc = 10917943 | doi = 10.3389/fphar.2024.1357422 | doi-access = free }}

Cocaine has a similar potential to induce temporary psychosis{{cite journal | vauthors = Brady KT, Lydiard RB, Malcolm R, Ballenger JC | title = Cocaine-induced psychosis | journal = The Journal of Clinical Psychiatry | volume = 52 | issue = 12 | pages = 509–512 | date = December 1991 | pmid = 1752853 }} with more than half of cocaine abusers reporting at least some psychotic symptoms at some point.{{cite journal | vauthors = Thirthalli J, Benegal V | title = Psychosis among substance users | journal = Current Opinion in Psychiatry | volume = 19 | issue = 3 | pages = 239–245 | date = May 2006 | pmid = 16612208 | doi = 10.1097/01.yco.0000218593.08313.fd | s2cid = 13350537 }} Typical symptoms include paranoid delusions that they are being followed and that their drug use is being watched, accompanied by hallucinations that support the delusional beliefs. Delusional parasitosis with formication ("cocaine bugs") is also a fairly common symptom.{{cite journal | vauthors = Elliott A, Mahmood T, Smalligan RD | title = Cocaine bugs: a case report of cocaine-induced delusions of parasitosis | journal = The American Journal on Addictions | volume = 21 | issue = 2 | pages = 180–181 | year = 2012 | pmid = 22332864 | doi = 10.1111/j.1521-0391.2011.00208.x }}

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

Insufflating (snorting) cocaine commonly causes increased mucus production due to irritation and inflammation of the nasal passages. This irritation leads to symptoms such as a runny nose, nasal congestion, and excessive or thickened mucus.

Acute exposure to cocaine has many effects on humans, including euphoria, increases in heart rate and blood pressure, and increases in cortisol secretion from the adrenal gland.{{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 }} 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.{{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 }}{{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 }}{{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 }}{{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 }} With excessive or prolonged use, the drug can cause itching, fast heart rate, and paranoid delusions or sensations of insects crawling on the skin.{{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 }} 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, psychomotor agitation, and delirium. Consumption of large doses of cocaine can cause violent outbursts, especially by those with preexisting psychosis.{{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 }} Acute exposure may induce arrhythmia, including atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, and ventricular fibrillation. Acute exposure may also lead to angina, heart attack, and congestive heart failure.{{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 }} Cocaine overdose may cause seizures, abnormally high body temperature and a marked elevation of blood pressure, which can be life-threatening, abnormal heart rhythms,{{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 }} and death. Anxiety, paranoia, and restlessness can also occur, especially during the comedown. With excessive dosage, tremors, convulsions, and increased body temperature are observed.

File:Side effects of chronic use of Cocaine.png

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

Cocaine use leads to an increased risk of hemorrhagic and ischemic strokes. Cocaine use also increases the risk of having a heart attack.{{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 }}

Cocaine use also promotes the formation of blood clots. This increase in blood clot formation is attributed to cocaine-associated increases in the activity of plasminogen activator inhibitor, and an increase in the number, activation, and aggregation of platelets.

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

Although it has been commonly asserted, the available evidence does not show that chronic use of cocaine is associated with broad cognitive impairment.{{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 }} Research is inconclusive on age-related loss of striatal dopamine transporter (DAT) sites, suggesting cocaine has neuroprotective or neurodegenerative properties for dopamine neurons.{{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}}{{Cite journal | vauthors = Wang GJ, Volkow ND, Fowler JS, Fischman M, Foltin R, Abumrad NN, Logan J, Pappas NR |author6-link=Naji Abumrad | 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 }}{{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 }} Exposure to cocaine may lead to the breakdown of the blood–brain barrier.{{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 }}{{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}}

The misuse of cocaine has a high correlation with suicide.{{cite journal | vauthors = Vijayakumar L, Kumar MS, Vijayakumar V | title = Substance use and suicide | journal = Current Opinion in Psychiatry | volume = 24 | issue = 3 | pages = 197–202 | date = May 2011 | pmid = 21430536 | doi = 10.1097/YCO.0b013e3283459242 | s2cid = 206143129 }}{{cite journal | vauthors = Moçambique M, Hoffmann A, Roglio V, Kessler F, Dalbosco C, Schuch J, Pechansky F | title = Prevalence of suicide in cocaine users accessing health services: a systematic review and meta-analysis. | journal = Revista Brasileira de Psiquiatria | location = Sao Paulo, Brazil | volume = 44 | issue = 4 | pages = 441–448 | date = 24 June 2022 | pmid = 35751594 | pmc = 9375660 | doi = 10.47626/1516-4446-2021-2207 }} In those who use cocaine, the risk is greatest during the withdrawal phase.{{cite book | vauthors = Ayd FJ | title = Lexicon of psychiatry, neurology, and the neurosciences | location = Philadelphia [u.a.] | pages = 256 | year = 2000 | url = https://books.google.com/books?id=ea_QVG2BFy8C&q=256 | publisher = Lippincott Williams & Wilkins | isbn = 978-0-7817-2468-5 | edition = 2nd }}

Chronic cocaine use, but not cocaine itself, can contribute to tooth wear and the development of tooth decay through indirect mechanisms.{{Clarify|reason=What about cocaine administration causes these complications?|date=June 2025}} Cocaine use is frequently associated with involuntary tooth grinding, known as bruxism, which can cause dental attrition and gingivitis.{{cite journal | vauthors = Shekarchizadeh H, Khami MR, Mohebbi SZ, Ekhtiari H, Virtanen JI | title = Oral Health of Drug Abusers: A Review of Health Effects and Care | journal = Iranian Journal of Public Health | volume = 42 | issue = 9 | pages = 929–940 | date = September 2013 | pmid = 26060654 | pmc = 4453891 }}{{Cite journal | vauthors = Baigent M | title = Physical complications of substance abuse: what the psychiatrist needs to know | journal = Curr Opin Psychiatry | volume = 16 | issue = 3 | pages = 291–296 | year = 2003 | doi = 10.1097/00001504-200305000-00004 }} Additionally, stimulants like cocaine, methamphetamine, and even caffeine cause dehydration and 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). Poor oral hygiene, which is common among individuals with substance use disorders, may contribute significantly to tooth decay in cocaine users.{{Citation needed|date=June 2025}}

{{See also|Epigenetics of cocaine addiction}}

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

Cocaine can induce tolerance after a single dose, and repeated use frequently leads to the development of addiction and prolonged craving.{{cite web |title=Cocaine |work=NIDA |url=https://nida.nih.gov/research-topics/cocaine}}{{cite journal | vauthors = Paludetto LS, Florence LL, Torales J, Ventriglio A, Castaldelli-Maia JM |title=Mapping the Neural Substrates of Cocaine Craving: A Systematic Review |journal=Brain Sciences |date=29 March 2024 |volume=14 |issue=4 |pages=329 |doi=10.3390/brainsci14040329|doi-access=free |pmid=38671981 |pmc=11048489 }} Withdrawal symptoms include disrupted sleep, irritability, depression, and reduced ability to experience pleasure (anhedonia).{{cite journal | vauthors = Walsh SL, Stoops WW, Moody DE, Lin SN, Bigelow GE | title = Repeated dosing with oral cocaine in humans: assessment of direct effects, withdrawal, and pharmacokinetics | journal = Experimental and Clinical Psychopharmacology | volume = 17 | issue = 4 | pages = 205–216 | date = August 2009 | pmid = 19653786 | pmc = 2811070 | doi = 10.1037/a0016469 }} Chronic nasal use may cause destructive damage to the nasal septum, including cocaine-induced midline destructive lesions (CIMDL). Illicit cocaine is frequently adulterated with substances such as fentanyl, levamisole, or local anesthetics, increasing its toxicity.{{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|access-date=17 December 2022|archive-date=17 December 2022|archive-url=https://web.archive.org/web/20221217214902/https://www.addictionpolicy.org/post/fentanyl-adulterated-cocaine-strategies-to-address-the-new-normal|url-status=live}} Concurrent use with alcohol produces cocaethylene, a metabolite that significantly increases the risk of sudden death. According to the Global Burden of Disease Study, cocaine use is responsible for approximately 7,300 deaths annually.{{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 }}

Cocaine abuse can trigger addiction-related structural neuroplasticity in the human brain, although the permanence of such changes remains uncertain.{{cite journal | vauthors = Hampton WH, Hanik I, Olson IR | title = [Substance Abuse and White Matter: Findings, Limitations, and Future of Diffusion Tensor Imaging Research] | journal = Drug and Alcohol Dependence | volume = 197 | issue = 4 | pages = 288–298 | year = 2019 | pmid = 30875650 | pmc = 6440853 | doi = 10.1016/j.drugalcdep.2019.02.005}} Family history is a known risk factor, as relatives of cocaine users have an increased likelihood of developing cocaine addiction.{{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 }} A key mechanism involves the overexpression of ΔFosB in the nucleus accumbens, altering transcriptional regulation and reinforcing drug-seeking behavior.{{Cite journal | vauthors = Hope BT | title = Cocaine and the AP-1 transcription factor complex | journal = Annals of the New York Academy of Sciences | volume = 844 | issue = 1 | pages = 1–6 | date = May 1998 | pmid = 9668659 | doi = 10.1111/j.1749-6632.1998.tb08216.x | s2cid = 11683570 | bibcode = 1998NYASA.844....1H | url = https://zenodo.org/record/1230756 | access-date = 30 June 2019 | archive-date = 28 July 2020 | archive-url = https://web.archive.org/web/20200728160757/https://zenodo.org/record/1230756 | url-status = live }} Each dose of cocaine raises ΔFosB levels without a known saturation point. This elevation leads to increased brain-derived neurotrophic factor (BDNF) levels, which in turn enhance dendritic branching and spine density in neurons of the nucleus accumbens and prefrontal cortex, potentially persisting for weeks after drug cessation.{{Citation needed|date=June 2025}}

In transgenic mice engineered to express ΔFosB in the nucleus accumbens and dorsal striatum, heightened behavioral sensitization to cocaine has been observed.{{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 }} These mice self-administer cocaine at lower doses and display a greater propensity for relapse after withdrawal{{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 }}{{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 = | bibcode = 2001PNAS...9811042N | doi-access = free }} ΔFosB also enhances sensitivity to reward by upregulating the AMPA receptor subunit GluR2 and downregulating the expression of dynorphin.{{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 = | bibcode = 2001PNAS...9811042N | doi-access = free }}

Cocaine use has also been shown to increase DNA damage in the brains of rodents.{{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 }}{{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 }} During subsequent DNA repair, enduring alterations in chromatin structure may arise, such as DNA methylation and methylation or acetylation of histones at the repair loci.{{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 }} These modifications may result in lasting epigenetic "scars", which are believed to contribute to the persistent epigenetic changes observed in cocaine addiction.

{{Further information|Cocaine dependence}}

Cocaine dependence develops after even brief periods of regular cocaine use.{{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}}

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

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

File:Cocaine Anonymous Chips.jpgs]]

Cocaine Anonymous (CA) is a twelve-step program formed in 18 November 1982 for people who seek recovery from drug addiction. It is patterned very closely after Alcoholics Anonymous (AA), although the two groups are unaffiliated. While many CA members have been addicted to cocaine, crack, speed or similar substances, CA accepts all who desire freedom from "cocaine and all other mind-altering substances" as members.{{cite web |author=Cocaine Anonymous |title=And All Other Mind-Altering Substances |accessdate=2007-11-15 |date=2007-11-13 |url=http://www.ca.org/literature/allothermas.htm |url-status=dead |archiveurl=https://web.archive.org/web/20090304202508/http://www.ca.org/literature/allothermas.htm |archivedate=2009-03-04 }}

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

File:Cocaine nose.jpg caused by cocaine insufflation (pictured) can progress to cocaine-induced midline destructive lesions]]

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

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

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

Nose disorders associated with cocaine nose include:

• Cocaine-induced midline destructive lesions (CIMDL)
• Nasal septum perforation
• Saddle nose{{cite journal | vauthors = Schreiber BE, Twigg S, Marais J, Keat AC | title = Saddle-nose deformities in the rheumatology clinic | journal = Ear, Nose, & Throat Journal | volume = 93 | issue = 4–5 | pages = E45–E47 | date = April–May 2014 | pmid = 24817241 | type = Review }}

{{main|Cocaine-induced midline destructive lesions}}

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

Chronic intranasal usage can degrade the cartilage separating the nostrils (the septum nasi), leading eventually to its complete disappearance.{{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}}

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

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

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

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

Some individuals seek plastic surgery to repair or reconstruct nasal damage caused by cocaine use, although surgical outcomes can be complicated by ongoing tissue loss and poor healing. When nasal damage is too severe for reconstruction, a nose prosthesis may be used to restore appearance and quality of life.

{{Main|Cocaine intoxication}}

File:Death rates from cocaine overdoses, OWID.svg

File:US timeline. Cocaine deaths.svg (NIDA).]]

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

Cocaine can be snorted, swallowed, injected, or smoked. Most deaths due to cocaine are accidental but may also be the result of body packing or stuffing with rupture in the gastrointestinal tract. Alcohol impairment increases the likelihood of risk-taking behaviors and susceptibility to peer pressure, and also raises the risk of overdose due to the formation of cocaethylene (see the alcohol section).

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

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

{{See also|Combined drug intoxication}}

{{Main|Cocaethylene}}

{{See also|Coca wine}}

Alcohol interacts with cocaine in vivo to produce cocaethylene, another psychoactive substance which may be substantially more cardiotoxic than either cocaine or alcohol by themselves.{{cite journal |vauthors=Laizure SC, Mandrell T, Gades NM, Parker RB |title=Cocaethylene metabolism and interaction with cocaine and ethanol: role of carboxylesterases |journal=Drug Metabolism and Disposition |volume=31 |issue=1 |pages=16–20 |date=January 2003 |pmid=12485948 |doi=10.1124/dmd.31.1.16}}{{cite journal |vauthors=Pergolizzi J, Breve F, Magnusson P, LeQuang JA, Varrassi G |title=Cocaethylene: When Cocaine and Alcohol Are Taken Together |journal=Cureus |volume=14 |issue=2 |date=February 2022 |pages=e22498 |pmid=35345678 |pmc=8956485 |doi=10.7759/cureus.22498 |doi-access=free}}

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

{{See also|Speedball (drug)}}

{{See also|Opioid epidemic in the United States}}

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

The extent of absorption of cocaine into the circulatory system after nasal insufflation is similar to that after oral ingestion. The rate of absorption after nasal insufflation is limited by cocaine-induced vasoconstriction of capillaries in the nasal mucosa. Onset of absorption after oral ingestion is delayed because cocaine is a weak base with a pKa of 8.6, and is thus in an ionized form that is poorly absorbed from the gastric acid and easily absorbed from the alkaline duodenum. The rate and extent of absorption from inhalation of cocaine is similar or greater than with intravenous injection, as inhalation provides access directly to the capillary bed. The delay in absorption after oral ingestion may account for the popular belief that cocaine bioavailability from the stomach is lower than after insufflation. Compared with ingestion, the faster absorption of insufflated cocaine results in quicker attainment of maximum drug effects. Snorting cocaine produces maximum physiological effects within 40 minutes and maximum psychotropic effects within 20 minutes. Physiological and psychotropic effects from nasally insufflated cocaine are sustained for approximately 40–60 minutes after the peak effects are attained.{{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.

Cocaine crosses the blood–brain barrier via both a proton-coupled organic cation antiporter{{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 }}{{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 }} and (to a lesser extent) via passive diffusion across cell membranes.{{Cite journal | vauthors = Chapy H, Smirnova M, André P, Schlatter J, Chiadmi F, Couraud PO, Scherrmann JM, Declèves X, Cisternino S | title = Carrier-mediated cocaine transport at the blood–brain barrier as a putative mechanism in addiction liability | journal = The International Journal of Neuropsychopharmacology | volume = 18 | issue = 1 | pages = pyu001 | date = October 2014 | pmid = 25539501 | pmc = 4368859 | doi = 10.1093/ijnp/pyu001 }} As of September 2022, the gene or genes encoding the human proton-organic cation antiporter had not been identified.{{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 | url = https://resolver.sub.uni-goettingen.de/purl?gro-2/117956 }}

Cocaine has a short elimination half life of 0.7–1.5 hours and is extensively metabolized by plasma esterases and also by liver cholinesterases, with only about 1% excreted unchanged in the urine. The metabolism is dominated by 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.{{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 }} Further minor metabolites of cocaine include norcocaine, p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine ({{chem name|pOHBE}}), and m-hydroxybenzoylecgonine.{{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 }}

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

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.R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 9th edition, Biomedical Publications, Seal Beach, California, 2011, pp. 390–394.

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

Cocaine acts as a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI). Cocaine increases levels of serotonin, norepinephrine, and dopamine in the synaptic cleft, leading to heightened post-synaptic activation, with dopamine contributing to euphoria and arousal, and the other monoamines enhancing additional effects.{{Cite journal | vauthors = Proebstl L, Kamp F, Manz K, Krause D, Adorjan K, Pogarell O, Koller G, Soyka M, Falkai P, Kambeitz J | title = Effects of stimulant drug use on the dopaminergic system: A systematic review and meta-analysis of in vivo neuroimaging studies | journal = European Psychiatry | volume = 59 | pages = 15–24 | date = June 2019 | pmid = 30981746 | doi = 10.1016/j.eurpsy.2019.03.003 | doi-access = free }}{{Cite web|url=https://www.drugabuse.gov/publications/research-reports/cocaine/how-does-cocaine-produce-its-effects|title=How does cocaine produce its effects?|access-date=12 May 2021|archive-date=18 January 2022|archive-url=https://web.archive.org/web/20220118113925/https://www.drugabuse.gov/publications/research-reports/cocaine/how-does-cocaine-produce-its-effects|url-status=dead}}{{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 }}

The pharmacodynamics of cocaine involve the complex relationships of neurotransmitters (inhibiting monoamine uptake in rats with ratios of about: serotonin:dopamine = 2:3, serotonin:norepinephrine = 2:5).{{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) 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 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 rewarding and promotes the compulsive use of cocaine.{{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 }}

Cocaine affects certain serotonin (5-HT) receptors; in particular, it has been shown to antagonize the 5-HT₃ receptor, which is a ligand-gated ion channel. An overabundance of 5-HT₃ receptors is reported in cocaine-conditioned rats, though 5-HT₃'s role is unclear.{{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 }} The 5-HT₂ receptor (particularly the subtypes 5-HT_2A, 5-HT_2B and 5-HT_2C) are involved in the locomotor-activating effects of cocaine.{{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 }}

Cocaine has been demonstrated to bind as to directly stabilize the 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.{{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 }}

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

Sigma receptors are affected by cocaine, as cocaine functions as a sigma ligand agonist.{{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 }} Further specific receptors it has been demonstrated to function on are NMDA and the D₁ dopamine receptor.{{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 }}

Cocaine also blocks sodium channels, thereby interfering with the propagation of action potentials;{{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 }} 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 phenyltropanes analogues which have that removed. In addition to this, cocaine has some target binding to the site of the κ-opioid receptor.{{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 }}{{Unreliable medical source|date=May 2025}} Cocaine also causes vasoconstriction, thus reducing bleeding during minor surgical procedures. Recent research points to an important role of circadian mechanisms{{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 }} and clock genes{{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 }} in behavioral actions of cocaine.

Cocaine is known to suppress hunger and appetite by increasing co-localization of sigma σ₁R receptors and ghrelin GHS-R1a cell surface receptors, thereby increasing ghrelin-mediated signaling of satiety{{Cite journal | vauthors = Aguinaga D, Medrano M, Cordomí A, Jiménez-Rosés M, Angelats E, Casanovas M, Vega-Quiroga I, Canela EI, Petrovic M, Gysling K, Pardo L, Franco R, Navarro G | title = Cocaine Blocks Effects of Hunger Hormone, Ghrelin, Via Interaction with Neuronal Sigma-1 Receptors | journal = Molecular Neurobiology | volume = 56 | issue = 2 | pages = 1196–1210 | date = February 2019 | pmid = 29876881 | doi = 10.1007/s12035-018-1140-7 | hdl-access = free | s2cid = 46964405 | hdl = 2445/127306 }} and possibly via other effects on appetitive hormones.{{Cite journal | vauthors = Bouhlal S, Ellefsen KN, Sheskier MB, Singley E, Pirard S, Gorelick DA, Huestis MA, Leggio L | title = Acute effects of intravenous cocaine administration on serum concentrations of ghrelin, amylin, glucagon-like peptide-1, insulin, leptin and peptide YY and relationships with cardiorespiratory and subjective responses | journal = Drug and Alcohol Dependence | volume = 180 | pages = 68–75 | date = November 2017 | pmid = 28881319 | pmc = 5654385 | doi = 10.1016/j.drugalcdep.2017.07.033 }}

Cocaine effects, further, are shown to be potentiated for the user when used in conjunction with new surroundings and stimuli, and otherwise novel environs.{{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 }}

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

{{For|the freebase form|Crack cocaine#Chemistry}}

File:CocaineHydrochloridePowder cropped.jpg cocaine hydrochloride]]

File:CocaineHCl.jpg

In its purest form, cocaine is a white, pearly powder. As a tropane alkaloid, cocaine is a weak base and readily forms salts when combined with acids. The most commonly encountered form is the hydrochloride (HCl) salt, although other salts such as the sulfate (SO₄²⁻) and nitrate (NO₃⁻) are occasionally observed. The solubility of these salts varies depending on their polarity; the hydrochloride salt is polar and highly soluble in water.{{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|archive-date=8 July 2024|archive-url=https://web.archive.org/web/20240708191819/https://www.chm.bris.ac.uk/motm/cocaine/cocaineh.htm|url-status=live}}

The first structure elucidation and total synthesis of the cocaine molecule was accomplished by Richard Willstätter in 1898.{{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 }} Willstätter’s synthesis involved constructing the cocaine structure from simpler precursors, notably via the intermediate tropinone. Subsequent significant contributions to understanding the synthetic pathway and stereochemistry were made by Robert Robinson and Edward Leete.

Cocaine contains four chiral centers (1R, 2R, 3S, and 5S), two of which are configurationally dependent, resulting in eight possible stereoisomers. The formation of inactive stereoisomers, along with various synthetic by-products, limits both the yield and purity of the final product.{{cite journal | vauthors = Amara SB, Koslowski T, Zaidi A | title=Quantum Chemistry of Cocaine and its Isomers I: Energetics, Reactivity and Solvation | journal=South African Journal of Chemistry | volume=75 | date=2021 | doi=10.17159/0379-4350/2021/v75a3| doi-access=free }}{{cite journal | vauthors = Drake LR, Scott PJ | title = DARK Classics in Chemical Neuroscience: Cocaine | journal = ACS Chemical Neuroscience | volume = 9 | issue = 10 | pages = 2358–2372 | date = October 2018 | pmid = 29630337 | pmc = 6197930 | doi = 10.1021/acschemneuro.8b00117 }}

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

{{Main|Biosynthesis of cocaine}}

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

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

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.{{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 |access-date=27 November 2022 |archive-date=27 November 2022 |archive-url=https://web.archive.org/web/20221127225822/https://www.newscientist.com/article/2348568-genetically-modified-tobacco-plant-produces-cocaine-in-its-leaves/ |url-status=live }}

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

File:Drugwipe Kokain.jpg can detect traces of illicit substances, including cocaine, on surfaces such as driver's licenses at random checkpoints.]]

File:Cocaine under UV light 03.jpg]]

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

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

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.{{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 |archive-date=8 August 2020 |archive-url=https://web.archive.org/web/20200808062758/https://psmag.com/news/meet-the-chemist-behind-many-popular-and-faulty-police-drug-kits |url-status=live }}{{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 }}

Approximate cocaine purity can be determined using 1 mL 2% cupric sulfate pentahydrate in dilute HCl, 1 mL 2% potassium thiocyanate and 2 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.{{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}}

{{main|Cocaine and society}}

Large-scale chemical synthesis of cocaine is unexplored; Both the pharmaceutical supply chain and the illicit supply chain obtain cocaine from coca cultivated almost exclusively in the Andean regions of Colombia, Peru, and Bolivia, which together account for nearly all global coca production, but they operate under very different controls and oversight. In Peru, for example, legal coca cultivation is monopolized by the state company National Coca Company (ENACO), yet approximately 90% of coca leaves produced in the country are diverted to illegal actors for cocaine manufacturing.{{cite journal | vauthors = Busnel R, Manrique López H | title = The political economy of a failed drug reform: Insights from Peru's main legal coca valley | journal = The International Journal on Drug Policy | volume = 117 | pages = 104050 | date = July 2023 | pmid = 37267739 | doi = 10.1016/j.drugpo.2023.104050 }} As a result, these illicit coca crops are a primary target of ongoing government-led coca eradication efforts.{{cite journal | vauthors = Grisaffi T, Ledebur K | title = Citizenship or Repression? Coca, Eradication and Development in the Andes | journal = Stability: International Journal of Security and Development | volume = 5 | issue = 1 | date = 31 March 2016 | doi = 10.5334/sta.440 | doi-access = free | issn = 2165-2627 }}

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

{{Main|Legal status of cocaine}}

File:Legal_status_of_cocaine_possession.png

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

Some countries, such as Bolivia, Colombia, and Peru, permit the cultivation of coca leaf for traditional consumption by the local indigenous population, but nevertheless, prohibit the production, sale, and consumption of cocaine.{{Cite news|url=https://www.theguardian.com/world/2009/aug/19/bolivia-cocaine-bar-route-36|title=The world's first cocaine bar| vauthors = Franklin J |date=18 August 2009|newspaper=The Guardian|issn=0261-3077|access-date=23 December 2016|url-status=live|archive-url=https://web.archive.org/web/20170112142609/https://www.theguardian.com/world/2009/aug/19/bolivia-cocaine-bar-route-36|archive-date=12 January 2017}} The provisions as to how much a coca farmer can yield annually is protected by laws such as the Bolivian Cato accord.{{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}} In addition, some parts of Europe, the United States, and Australia allow processed cocaine for medicinal uses only.

Cocaine is a Schedule 8 controlled drug in Australia under the Poisons Standard.{{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}} It is the second most popular illicit recreational drug in Australia behind cannabis.{{Cite web|url=https://www.aihw.gov.au/reports/illicit-use-of-drugs/illicit-drug-use|title=Illicit drug use|date=13 December 2023|website=Australian Institute of Health and Welfare|access-date=22 January 2024|archive-date=20 January 2024|archive-url=https://web.archive.org/web/20240120123407/https://www.aihw.gov.au/reports/illicit-use-of-drugs/illicit-drug-use|url-status=live}}

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.{{Cite web|url=https://www.legislation.wa.gov.au/legislation/prod/filestore.nsf/FileURL/mrdoc_46172.pdf/$FILE/Misuse%20Of%20Drugs%20Act%201981%20-%20%5B08-f0-00%5D.pdf?OpenElement|title=Misuse of Drugs Act 1981|website=Western Australian Legislation|publisher=Government of Western Australia Department of Justice Parliamentary Counsel's Office|access-date=22 January 2024|archive-date=17 February 2024|archive-url=https://web.archive.org/web/20240217143325/https://www.legislation.wa.gov.au/legislation/prod/filestore.nsf/FileURL/mrdoc_46172.pdf/$FILE/Misuse%20Of%20Drugs%20Act%201981%20-%20%5B08-f0-00%5D.pdf?OpenElement|url-status=live}}

{{See also|Cocaine in the United States}}

File:George_H._W._Bush_holds_up_a_bag_of_crack_cocaine_during_his_Address_to_the_Nation_on_National_Drug_Control_Strategy.jpg holds up a bag of crack cocaine during his Address to the Nation on National Drug Control Strategy on September 5, 1989.]]

The US federal government instituted a national drug labelling requirement for cocaine and cocaine-containing products through the Pure Food and Drug Act of 1906.{{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}}{{rp|37}} The next important federal regulation was the Harrison Narcotics Tax Act of 1914. While this act is often seen as the start of prohibition, the act itself was not actually a prohibition on cocaine, but instead set up a regulatory and licensing regime.{{Cite book | vauthors = Madge T |title=White Mischief: A Cultural History of Cocaine |year=2001 |publisher=Mainstream Publishing Company |location=Edinburgh |isbn=978-1-84018-405-1|page = 106}} 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."{{Cite journal|title=Narcotic drug addiction|journal=American Medicine|date=November 1915|page=799|url=https://books.google.com/books?id=tvAAAAAAYAAJ&pg=PA799|access-date=29 April 2018|publisher=American-Medicine Publishing Company|url-status=live|archive-url=https://web.archive.org/web/20180509174117/https://books.google.com/books?id=tvAAAAAAYAAJ&pg=PA799|archive-date=9 May 2018}} The Harrison Act left manufacturers of cocaine untouched so long as they met certain purity and labeling standards.{{rp|40}} Despite that cocaine was typically illegal to sell and legal outlets were rarer, the quantities of legal cocaine produced declined very little.{{rp|40}} Legal cocaine quantities did not decrease until the Jones–Miller Act of 1922 put serious restrictions on cocaine manufactures.{{rp|40}}

Before the early 1900s, newspapers primarily portrayed addiction-not violence or crime-as the main problem caused by cocaine use, and depicted cocaine users as upper or middle class White people. In 1914, The New York Times published an article titled "Negro Cocaine 'Fiends' Are a New Southern Menace," portraying Black people who used cocaine as dangerous and able to withstand wounds that would normally be fatal.{{Cite book |vauthors=Brown E, Barganier G |title=Race and Crime: Geographies of Injustice |date=2018 |publisher=University of California Press |location=Oakland, California |isbn=978-0-520-29418-9 |pages=207–209 |url=https://books.google.com/books?id=2ChtDwAAQBAJ |access-date=21 November 2021 |archive-date=12 April 2023 |archive-url=https://web.archive.org/web/20230412145040/https://books.google.com/books?id=2ChtDwAAQBAJ |url-status=live }} The Anti-Drug Abuse Act of 1986 mandated the same prison sentences for distributing 500 grams of powdered cocaine and just 5 grams of crack cocaine.{{Cite book |vauthors=Moore NM |title=The Political Roots of Racial Tracking in American Criminal Justice |date=2015 |publisher=Cambridge University Press |location=New York, NY |isbn=978-1-107-02297-3 |page=270 |url=https://books.google.com/books?id=QKwPBgAAQBAJ&pg=PA270 |access-date=21 November 2021 |archive-date=6 April 2023 |archive-url=https://web.archive.org/web/20230406100009/https://books.google.com/books?id=QKwPBgAAQBAJ&pg=PA270 |url-status=live }} In the National Survey on Drug Use and Health, white respondents reported a higher rate of powdered cocaine use, and Black respondents reported a higher rate of crack cocaine use.{{Cite book |vauthors=Glaser J |title=Suspect Race: Causes and Consequences of Racial Profiling |date=2015 |publisher=Oxford University Press |location=New York, NY |isbn=978-0-19-537040-9 |page=7 |url=https://books.google.com/books?id=3GjDBAAAQBAJ&pg=PA7 |access-date=21 November 2021 |archive-date=12 April 2023 |archive-url=https://web.archive.org/web/20230412145042/https://books.google.com/books?id=3GjDBAAAQBAJ&pg=PA7 |url-status=live }}

Cocaine production, seizures, and use all reached record levels in 2023, making it the world’s fastest-growing illicit drug market. Seizures rose by 68% from 2019 to 2023, while the number of users increased from 17 million in 2013 to 25 million in 2023, according to the UNODC World Drug Report 2025.{{cite web |url=https://www.unodc.org/documents/data-and-analysis/WDR_2025/Press_release_WDR_2025_English.pdf}}

The report further states that Western Europe’s cocaine market is rapidly expanding, resulting in increased violence driven by traffickers, including organized criminal groups from the Western Balkans. Concurrently, record levels of cocaine production have enabled traffickers to enter new markets across Asia and Africa, reflecting the expanding global reach of cocaine trafficking.{{cite web |url=https://www.unodc.org/documents/data-and-analysis/WDR_2025/WDR25_Special_points_of_interest.pdf}}

The U.S. is the world's largest consumer of cocaine,{{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 }} while South America ranks third. Europe ranks cocaine as the second most commonly used illicit drug.{{cite web |title=Cocaine – the current situation in Europe (European Drug Report 2024) {{!}} www.euda.europa.eu |url=https://www.euda.europa.eu/publications/european-drug-report/2024/cocaine_en |website=www.euda.europa.eu}}

Cocaine is among the most widely consumed recreational stimulants worldwide.{{cite journal | vauthors = Roque Bravo R, Faria AC, Brito-da-Costa AM, Carmo H, Mladěnka P, Dias da Silva D, Remião F | title = Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern | journal = Toxins | volume = 14 | issue = 4 | page = 278 | date = April 2022 | pmid = 35448887 | pmc = 9032145 | doi = 10.3390/toxins14040278 | doi-access = free }}

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

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

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

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

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

Experimentally, cocaine injections can be delivered to animals such as fruit flies to study the mechanisms of cocaine addiction.{{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 }}

{{Main|TA-CD}}

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

{{Main|History of cocaine}}

Coca leaves have been used by indigenous South Americans for thousands of years, both as a stimulant and for medicinal purposes.{{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}} When the Spanish arrived in South America, they initially banned coca but soon legalized and taxed it after seeing its importance to local labor.{{Cite news|date=2006 |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 }} The active ingredient, cocaine, was first isolated in 1855 by Friedrich Gaedcke and later refined by Albert Niemann, who named it “cocaine.”{{cite book | vauthors = Luch A | title=Molecular, Clinical and Environmental Toxicology | publisher=Springer Science & Business Media | publication-place=Basel Boston | date=3 April 2009 | isbn=978-3-7643-8336-7 | page=20 }}{{Cite journal|volume = 153|issue = 2 and 3|pages = 129–155; 291–308|year = 1860|title = Ueber eine neue organische Base in den Cocablättern|vauthors = Niemann A|doi = 10.1002/ardp.18601530202|journal = Archiv der Pharmazie|s2cid = 98195820|url = https://zenodo.org/record/1424541|access-date = 30 June 2019|archive-date = 28 July 2020|archive-url = https://web.archive.org/web/20200728162205/https://zenodo.org/record/1424541|url-status = live}}{{OEtymD|Cocaine}} In the late 1800s, cocaine became popular in Western medicine as a local anesthetic and was widely used in various products, including drinks and remedies.{{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}} and James Leonard Corning demonstrated peridural anesthesia.{{Cite journal| vauthors = Corning JL |year=1885|journal=New York Medical Journal|title=An experimental study|volume=42|page=483}} However, due to its toxic effects and potential for abuse, safer alternatives eventually replaced it in medical practice.

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

{{Portal|Medicine}}

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• Cocaine reverse ester
• Cocaine and amphetamine regulated transcript
• MDMA – also acts, to a lesser extent, as an SNDRI like cocaine

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{{Reflist}}

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• {{Cite book | veditors = Spillane JF |title=Cocaine: From Medical Marvel to Modern Menace in the United States, 1884–1920 |year=2000 |publisher=The Johns Hopkins University Press |location=Baltimore and London |isbn=978-0-8018-6230-4 |url=https://archive.org/details/cocainefrommedic00spil }}
• {{Cite book | vauthors = Feiling T |title=The Candy Machine: How Cocaine Took Over the World |location=London |publisher=Penguin |year=2009 |isbn=978-0-14-103446-1}}

{{refend}}

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

• Virginia Gewin: [http://www.nature.com/news/2011/111102/full/news.2011.627.html Smoking stokes cocaine cravings: Molecular mechanism found for controversial 'gateway drug' hypothesis], Nature News, November 2, 2011.

{{Drug use}}

{{Euphoriants}}

{{Stimulants}}

{{Local anesthetics}}

{{Ancient anaesthesia-footer}}

{{Ion channel modulators}}

{{Monoamine reuptake inhibitors}}

{{Sigma receptor modulators}}

{{Chemical classes of psychoactive drugs}}

{{Authority control}}

Category:1855 introductions

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Category:Adulteration

Category:Alkaloids found in Erythroxylum

Category:Anorectics

Category:Benzoate esters

Category:Carboxylate esters

Category:Cardiac stimulants

Cocaine in the United States

Category:Counterculture of the 1980s

Category:CYP2D6 inhibitors

Category:Euphoriants

Category:German inventions

Category:Local anesthetics

Category:Methyl esters

Category:Neurotoxins

Category:Otologicals

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

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