Cocaine#Basic

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

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.Andrew M. Luks, et al. [http://www.wemjournal.org/article/S1080-6032(14)00257-9/fulltext "Wilderness Medical Society Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2014 Update"]. Wilderness & Environmental Medicine, 25, S4–S14 (2014).

Cocaine was first isolated from the leaves in 1860.

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 }} However, chronic recreational use may lead to severe nasal and sinus damage known as "cocaine nose," which can result in frequent nosebleeds, septal perforation, and even deformities of the nasal structure.

{{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.

{{Unreferenced section|date=June 2025}}

Topical medication is the only form in which cocaine is used in medical practice. 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 }} Crack cocaine is referred to as "crack" because of the crackling sounds it makes when heated.

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}}

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."

Snuff spoons, rolled up banknotes, 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 often 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}}

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 is considered neurotoxic due to its damaging effects on the brain and nervous system. 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 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 |last1=Talarico |first1=GP |last2=Crosta |first2=ML |last3=Giannico |first3=MB |last4=Summaria |first4=F |last5=Calò |first5=L |last6=Patrizi |first6=R |title=Cocaine and coronary artery diseases: a systematic review of the literature. |journal=Journal of Cardiovascular Medicine (Hagerstown, Md.) |date=May 2017 |volume=18 |issue=5 |pages=291–294 |doi=10.2459/JCM.0000000000000511 |pmid=28306693}} It can also become a serious risk at high doses due to cocaine's blocking effect on cardiac sodium channels.

{{Main|Levamisole induced necrosis syndrome}}

File:Levamisole.svg

Levamisole induced necrosis syndrome (LINES){{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 : A Compendium of Clinical Research and Practice | volume = 29 | issue = 3 | pages = 71–76 | date = Mar 2017 | pmid = 28355139 }} is a complication of adulterated cocaine recognized in 2011, caused by the use of levamisole as a cutting agent for cocaine. Spontaneous bruising of the earlobes is considered characteristic of this condition, but lesions can present anywhere on the body.

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 neutropenia, agranulocytosis, arthralgias, retiform purpura, skin necrosis, and fever.{{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 = Sep 2010 | pmid = 20668440 | doi = 10.1038/clpt.2010.156 | s2cid = 31414939 }} 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 : JABFM | 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 = Jun 2012 | pmid = 22677078 | pmc = 3498128 | doi = 10.1016/j.mayocp.2012.03.010 }}

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 | doi = 10.23907/2017.039 | pmid = 31239995 | pmc = 6474566 }}

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 = 408–11 | 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 = 590–5 | date = April 2014 | pmid = 24440755 | pmc = 3989204 | doi = 10.1016/j.neuropharm.2014.01.002 }} Levamisole-adulterated cocaine has been associated with autoimmune disease.{{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 }}

Levamisole test kits can be utilized to detect the presence of levamisole in cocaine.

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 has a similar potential to induce temporary psychosis{{cite journal |vauthors=Brady KT, Lydiard RB, Malcolm R, Ballenger JC | year = 1991 | title = Cocaine-induced psychosis | journal = J Clin Psychiatry | volume = 52 | issue = 12| pages = 509–512 | pmid = 1752853 }} with more than half of cocaine abusers reporting at least some psychotic symptoms at some point.{{cite journal |author1=Thirthalli J. |author2=Vivek B. |title=Psychosis Among Substance Users |journal= Curr Opin Psychiatry|volume= 19|issue= 3|pages= 239–245|year=2006 | url= http://www.medscape.com/viewarticle/528487_5 |doi=10.1097/01.yco.0000218593.08313.fd|pmid=16612208 |s2cid=13350537 |url-access=subscription }} 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 |author1=Elliott A. |author2=Mahmood T. |author3=Smalligan R. D. | year = 2012 | 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 | doi=10.1111/j.1521-0391.2011.00208.x|pmid=22332864 }}

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 | author = DiSCLAFANI| year = 1981 | title = Drug-induced psychosis: Emergency diagnosis and management | journal = Psychosomatics | volume = 22 | issue = 10| pages = 845–855 | doi=10.1016/s0033-3182(81)73092-5| pmid = 7313045 |display-authors=etal| doi-access =}}

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 |last1=Iorio |first1=L |last2=Davanzo |first2=F |last3=Cazzador |first3=D |last4=Codirenzi |first4=M |last5=Fiorin |first5=E |last6=Zanatta |first6=E |last7=Nicolai |first7=P |last8=Doria |first8=A |last9=Padoan |first9=R |title=Cocaine- and Levamisole-Induced Vasculitis: Defining the Spectrum of Autoimmune Manifestations. |journal=Journal of Clinical Medicine |date=28 August 2024 |volume=13 |issue=17 |page=5116 |doi=10.3390/jcm13175116 |doi-access=free |pmid=39274328 |pmc=11396482}}

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

Because 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 cocaine has a shorter half-life than most drugs, which further encourages frequent redosing over extended periods. This cycle of repeated use can lead to "cocaine nose," referring to severe nasal tissue damage from intranasal use, and "crack lung," which describes respiratory complications from vaporizing cocaine. Both cocaine nose and crack lung can also affect the throat, leading to additional complications.

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 and methamphetamine 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 = Darke S, Kaye S, McKetin R, Duflou J | title = Major physical and psychological harms of methamphetamine use | journal = Drug and Alcohol Review | volume = 27 | issue = 3 | pages = 253–262 | date = May 2008 | pmid = 18368606 | doi = 10.1080/09595230801923702 | s2cid = 39592475 }}{{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. 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.

{{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. The 2014 Amsterdam drug deaths underscore the dangers of misidentified drugs, as two tourists died after using heroin sold as cocaine. 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.

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.

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 }} and produces a withdrawal state with emotional-motivational deficits upon cessation of cocaine use.

File:Cocaine nose.jpg caused by cocaine use (pictured)-sometimes referred to as a "cocaine nose hole"-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.

Cocaine nose can develop even in individuals who use the drug recreationally or only on weekends, not just in chronic or daily users.

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 ("cocaine nose hole")
• 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. This acid, combined with the powerful vasoconstrictive effects of cocaine (which restricts blood flow and oxygen to the tissues), leads to irritation, necrosis, and ultimately the breakdown of the nasal septum and surrounding structures.

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}}

{{main|Cocaine dependence#Treatment}}

{{See also|Cocaine Anonymous}}

File:Cocaine Anonymous Chips.jpgs]]

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 }}

{{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}}

{{main|Speedball (drug)}}

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

{{Unreferenced section|date=June 2025}}

File:US timeline. Opioid involvement in cocaine overdose.jpg.]]

A mixture of cocaine and opioids, known as "speedball", is a particularly dangerous combination, as the converse effects of the drugs actually complement each other, but may also mask the symptoms of an overdose.

Common prescription opioids include codeine, fentanyl, methadone, morphine, oxycodone, and tramadol. These substances, as well as heroin, are frequently found on the illicit drug market.

Speedball has been responsible for numerous deaths, including celebrities such as comedians/actors John Belushi and Chris Farley, Mitch Hedberg, River Phoenix, grunge singer Layne Staley and actor Philip Seymour Hoffman.

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

Cocaine in its purest form is a white, pearly product. Cocaine — a tropane alkaloid — is a weakly alkaline compound, and can therefore combine with acidic compounds to form salts. The hydrochloride (HCl) salt of cocaine is by far the most commonly encountered, although the sulfate (SO₄²⁻) and the nitrate (NO₃⁻) salts are occasionally seen. Different salts dissolve to a greater or lesser extent in various solvents — the hydrochloride salt is polar in character and is quite soluble in water.{{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}}

Synthesizing (i.e., not extracting) cocaine is possible but impractical because natural sources provide a lower-cost and higher-quality supply. While domestic clandestine laboratories could, in theory, replace the reliance on offshore sources and international smuggling—as is common with illicit methamphetamine production—this approach is rarely used.

Formation of inactive stereoisomers (cocaine has four chiral centres – 1R 2R, 3S, and 5S, two of them dependent, hence eight possible stereoisomers) plus synthetic by-products limits the yield and purity.{{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 }}

{{Main|Biosynthesis of cocaine}}

File:Biosynthesis of cocaine.png

The first synthesis and elucidation of the cocaine molecule was 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 derived cocaine from tropinone. Since then, Robert Robinson and Edward Leete have made significant contributions to the mechanism of the synthesis. (-NO₃)

The additional carbon atoms required for the synthesis of cocaine are derived from acetyl-CoA, by addition of two acetyl-CoA units to the N-methyl-Δ¹-pyrrolinium cation.{{Cite book | vauthors = Dewick PM |title=Medicinal Natural Products |publisher=Wiley-Blackwell |location=Chichester|year=2009 |isbn=978-0-470-74276-1}} The first addition is a Mannich-like reaction with the enolate anion from acetyl-CoA acting as a nucleophile toward the pyrrolinium cation. The second addition occurs through a Claisen condensation. This produces a racemic mixture of the 2-substituted pyrrolidine, with the retention of the thioester from the Claisen condensation. In formation of tropinone from racemic ethyl [2,3-13C₂]₄(Nmethyl-2-pyrrolidinyl)-3-oxobutanoate there is no preference for either stereoisomer.{{Cite journal|doi = 10.1021/ja964461p|title = The Biosynthesis of Tropane Alkaloids in Datura stramonium: The Identity of the Intermediates between N-Methylpyrrolinium Salt and Tropinone|year = 1997 | vauthors = Robins RJ, Abraham TE, Parr AJ, Eagles J, Walton NJ |journal = J. Am. Chem. Soc.|volume = 119|pages = 10929–10934|issue = 45| bibcode=1997JAChS.11910929R }}

File:Tropane alkaloids biochemistry.png

In cocaine biosynthesis, only the (S)-enantiomer can cyclize to form the tropane ring system of cocaine. The stereoselectivity of this reaction was further investigated through study of prochiral methylene hydrogen discrimination.{{Cite journal | vauthors = Hoye TR, Bjorklund JA, Koltun DO, Renner MK | title = N-methylputrescine oxidation during cocaine biosynthesis: study of prochiral methylene hydrogen discrimination using the remote isotope method | journal = Organic Letters | volume = 2 | issue = 1 | pages = 3–5 | date = January 2000 | pmid = 10814231 | doi = 10.1021/ol990940s }} This is due to the extra chiral center at C-2.{{Cite journal|doi = 10.1021/ja00024a039|title = Late intermediates in the biosynthesis of cocaine: 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoate and methyl ecgonine|year = 1991| vauthors = Leete E, Bjorklund JA, Couladis MM, Kim SH |journal = J. Am. Chem. Soc.|volume = 113|pages = 9286–9292|issue = 24| bibcode=1991JAChS.113.9286L }} This process occurs through an oxidation, which regenerates the pyrrolinium cation and formation of an enolate anion, and an intramolecular Mannich reaction. The tropane ring system undergoes hydrolysis, SAM-dependent methylation, and reduction via NADPH for the formation of methylecgonine. The benzoyl moiety required for the formation of the cocaine diester is synthesized from phenylalanine via cinnamic acid.{{Cite journal|doi = 10.1016/0031-9422(88)87026-2|title = The biosynthesis of the benzoyl moiety of cocaine|year = 1988 | vauthors = Leete E, Bjorklund JA, Kim SH |journal = Phytochemistry|volume = 27|pages = 2553–2556|issue = 8| bibcode=1988PChem..27.2553L }} Benzoyl-CoA then combines the two units to form cocaine.

Large-scale commercial biosynthesis remains unexplored.{{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 }}

The biosynthesis begins with L-Glutamine, which is derived to L-ornithine in plants. The major contribution of L-ornithine and L-arginine as a precursor to the tropane ring was confirmed by Edward Leete.{{Cite journal | vauthors = Leete E, Marion L, Spenser ID | title = Biogenesis of hyoscyamine | journal = Nature | volume = 174 | issue = 4431 | pages = 650–1 | date = October 1954 | pmid = 13203600 | doi = 10.1038/174650a0 | bibcode = 1954Natur.174..650L | s2cid = 4264282 }} Ornithine then undergoes a pyridoxal phosphate (PLP)-dependent decarboxylation to form putrescine. In some animals, the urea cycle derives putrescine from ornithine. L-ornithine is converted to L-arginine,{{Cite journal | vauthors = Robins RJ, Waltons NJ, Hamill JD, Parr AJ, Rhodes MJ | title = Strategies for the genetic manipulation of alkaloid-producing pathways in plants | journal = Planta Medica | volume = 57 | issue = 7 Suppl | pages = S27-35 | date = October 1991 | pmid = 17226220 | doi = 10.1055/s-2006-960226 | bibcode = 1991PlMed..57S..27R | s2cid = 45912704 }} which is then decarboxylated via PLP to form agmatine. Hydrolysis of the imine derives N-carbamoylputrescine followed with hydrolysis of the urea to form putrescine. The separate pathways of converting ornithine to putrescine in plants and animals have converged. A SAM-dependent N-methylation of putrescine gives the N-methylputrescine product, which then undergoes oxidative deamination by the action of diamine oxidase to yield the aminoaldehyde. Schiff base formation confirms the biosynthesis of the N-methyl-Δ¹-pyrrolinium cation.

File:Biosynthesis of N-methyl-pyrrolinium cation.png

The biosynthesis of the tropane alkaloid is still not understood. Hemscheidt proposes that Robinson's acetonedicarboxylate emerges as a potential intermediate for this reaction.{{Cite journal|doi = 10.1007/3-540-48146-X|title = Tropane and Related Alkaloids|year = 2000| vauthors = Hemscheidt T, Vederas JC | journal = Top. Curr. Chem.|volume = 209|page = 175|series = Topics in Current Chemistry | veditors = Leeper FJ, Vederas JC | url=https://link.springer.com/chapter/10.1007/3-540-48146-X_4|url-access=subscription| isbn = 978-3-540-66573-1}} Condensation of N-methylpyrrolinium and acetonedicarboxylate would generate the oxobutyrate.{{which|date=May 2025}} Decarboxylation leads to tropane alkaloid formation.

File:Robinson biosynthesis of tropane.png

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

File:Reduction of tropinone.png

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|List of countries by prevalence of cocaine use}}

File:List of countries by prevalence of cocaine use.jpg

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

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

{{Global estimates of illicit drug users}}

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

Cocaine is the second most popular illegal recreational drug in Europe (behind cannabis). Since the mid-1990s, overall cocaine usage in Europe has been on the rise, but usage rates and attitudes tend to vary between countries.

Prevalence estimates for the general population: age ranges are 18-64 and 18-34 for Germany, Greece, France, Italy and Hungary; 16-64 and 16-34 for Denmark, Estonia and Norway; 18-65 for Malta; 17-34 for Sweden. Cocaine use in the general population is highest-ranging from 4.2% to 5.5%-in Denmark, Norway, Ireland, the Netherlands, in that order.{{cite web |title=Dashboard. Prevalence of cocaine use in Europe (updated June 2024) {{!}} www.euda.europa.eu |url=https://www.euda.europa.eu/media-library/edr24/dashboard-prevalence-cocaine-use-europe_en |website=www.euda.europa.eu}}

{{Main|Cocaine in the United States}}

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

{{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 }}

{{Unreferenced section|date=June 2025}}

File:Needle Exchange deposit bin.jpg

Harm reduction efforts for cocaine use focus on reducing health risks associated with methods like cocaine injection and smoking crack cocaine. These include providing clean needles and crack cocaine paraphernalia, promoting safer consumption practices, and offering drug-checking services to detect dangerous contaminants such as fentanyl. Such strategies aim to minimize overdose risk and disease transmission while supporting users’ health and access to treatment, forming an essential part of modern drug policy.

{{Main|Coca eradication}}

File:Figure 6 Colombian Manual Eradicators Destroying Coca Fields (31352594937).jpg

Coca eradication is a strategy promoted by the United States government starting in 1961 as part of its "war on drugs" to eliminate the cultivation of coca, a plant whose leaves are not only traditionally used by indigenous cultures but also, in modern society, in the manufacture of cocaine. The strategy was adopted in place of running educational campaigns against drug usage.{{cite book| vauthors = Webb G |year=1999|pages=35|title=Dark Alliance|publisher=Seven Stories Press|isbn=978-1-888363-93-7}}{{Unreliable source?|date=July 2024}} The prohibitionist strategy is being pursued in the coca-growing regions of Colombia (Plan Colombia), Peru, and formerly Bolivia, where it is highly controversial because of its environmental, health and socioeconomic impact. Furthermore, indigenous cultures living in the Altiplano, such as the Aymaras, use the coca leaf (which they dub the "millenary leaf") in many of their cultural traditions, notably for its medicinal qualities in alleviating the feeling of hunger, fatigue and headaches symptomatic of altitude sicknesses.{{Citation needed|date=July 2024}} The growers of coca are named Cocaleros and part of the coca production for traditional use is legal in Peru, Bolivia and Chile.{{Citation needed|date=July 2024}}

{{More citations needed|section|date=June 2025}}

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| U.S. Coast Guard Cutter Bertholf crewmembers offload approximately 14 tons of cocaine

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| United States CBP police inspect a seized shipment of cocaine.

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| 1 kilo of cocaine seized from forwarded luggage at Innsbruck Airport

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In 2004, according to the United Nations, 589 tonnes of cocaine were seized globally by law enforcement authorities. Colombia seized 188 t, the United States 166 t, Europe 79 t, Peru 14 t, Bolivia 9 t, and the rest of the world 133 t.{{Cite book|title=World Drug Report 2006|publisher=United Nations|location=New York|chapter-url=https://www.unodc.org/pdf/WDR_2006/wdr2006_chap4_cocaine.pdf|year=2006|chapter=Cocaine: Seizures, 1998–2003|volume=2|url-status=live|archive-url=https://web.archive.org/web/20070614092314/https://www.unodc.org/pdf/WDR_2006/wdr2006_chap4_cocaine.pdf|archive-date=14 June 2007}}

In Bolivia, legal coca cultivation is regulated by the Coca and Integral Development agency, which operates under the Ministry of Rural Development.

In Colombia, the regulation of legal coca cultivation for traditional and scientific uses falls under the responsibility of government agencies, primarily the Ministry of Justice and Law (Ministerio de Justicia y del Derecho).

In Peru, The National Company of the Coca (Spanish: Empresa Nacional de la Coca, ENACO) is a state company dedicated to the commercialization of the coca leaf and derivatives. It is the only state company that has a monopoly on the commercialization and derivatives of the coca leaf. It was created in 1949.{{cite journal | vauthors = Engelke BF, Gentner WA | title = Determination of cocaine in "Mate de Coca" herbal tea | journal = Journal of Pharmaceutical Sciences | volume = 80 | issue = 1 | pages = 96 | date = January 1991 | pmid = 2013859 | doi = 10.1002/jps.2600800123 }} In 1982, it became a state company under private law. Nonetheless, much of this cocaine enters the black market.{{Cite web|url=https://larepublica.pe/politica/576620-al-campesino-no-le-queda-otra-alternativa-que-vender-su-coca-al-narcotrafico-enaco-paga-un-bajo-precio|title="Al campesino no le queda otra alternativa que vender su coca al narcotráfico... Enaco paga un bajo precio"|date=11 August 2015}} In 2004, one estimate was 83%.{{Citation needed|date=April 2024}} The operation of the company is specified in Law 22095.

The Stepan Company operates a unique facility in Maywood, New Jersey,Benson, Drew. [http://www.washingtontimes.com/world/20040419-093635-4754r.htm "Coca kick in drinks spurs export fears"], The Washington Times, April 20, 2004. Accessed June 14, 2007. "Coke dropped cocaine from its recipe around 1900, but the secret formula still calls for a cocaine-free coca extract produced at a Stepan Co. factory in Maywood, N.J. Stepan buys about 100 metric tons of dried Peruvian coca leaves each year, said Marco Castillo, spokesman for Peru's state-owned National Coca Co." which is the only commercial plant in the United States authorized by the Drug Enforcement Administration to import and process coca leaves, primarily sourced from Peru via the National Coca Company. The Stepan Company extracts cocaine from the leaves, producing a cocaine-free coca extract that is supplied to The Coca-Cola Company for use as a flavoring ingredient in its beverages. The separated pharmaceutical-grade cocaine is sold to Mallinckrodt, a pharmaceutical company, for use in medical applications such as local anesthesia.May, Clifford D. [https://www.nytimes.com/1988/07/01/business/how-coca-cola-obtains-its-coca.html "How Coca-Cola Obtains Its Coca"], The New York Times, July 1, 1988. Accessed April 11, 2008. "A Stepan laboratory in Maywood, N.J., is the nation's only legal commercial importer of coca leaves, which it obtains mainly from Peru and, to a lesser extent, Bolivia. Besides producing the coca flavoring agent sold to The Coca-Cola Company, Stepan extracts cocaine from the coca leaves, which it sells to Mallinckrodt Inc., a St. Louis pharmaceutical manufacturer that is the only company in the United States licensed to purify the product for medicinal use." See links for more information

{{as of|1988}}, Mallinckrodt is the only company in the U.S. that is allowed to receive cocaine, which is sold as a prescription drug for use in hospitals as a local anesthetic by eye and ear, nose and throat (ENT) doctors.{{Cite web |title=Mallinckrodt Pharmaceuticals – Compounding Powders – Cocaine Hydrochloride USP CII |url=https://www.mallinckrodt.com/products/generics/compounding-powders/cocaine-hydrochloride-usp-cii/ |website=Mallinckrodt Pharmaceuticals}}

{{Unreferenced section|date=June 2025}}

Cocaine is rarely produced entirely through chemical synthesis because the process is prohibitively expensive and complex (see synthesis for more information.) Instead, it is far more economical to extract cocaine from the leaves of the coca plant, which grows abundantly in the tropical regions of South America. The natural habitat of coca is concentrated in countries such as Colombia, Peru, and Bolivia, making South America the primary source of the world's illicit cocaine supply.

As a result, the global cocaine trade follows a characteristic illicit supply chain. Production begins in South America, where coca is cultivated and processed into cocaine. The drug is then trafficked-often across international borders-using a variety of smuggling routes and methods. After reaching consumer countries, cocaine enters distribution networks, where it is broken down into smaller quantities for local markets. Before reaching end users, the product is frequently adulterated, or “laced,” with various substances to increase profits. Finally, the cocaine is sold at the retail level to consumers. This supply chain-production in South America, trafficking, distribution, lacing, and sales-reflects both the geographic and economic realities of the illicit cocaine market.

{{See also|Coca production in Colombia}}

File:Drugpackscorpion.png

Colombia is as of 2019 the world's largest cocaine producer, with production more than tripling since 2013.{{cite web | url = https://www.cia.gov/the-world-factbook/countries/colombia/ | title = Colombia | work = CIA World Factbook | access-date = 24 January 2021 | archive-date = 18 June 2021 | archive-url = https://web.archive.org/web/20210618105825/https://www.cia.gov/the-world-factbook/countries/colombia/ | url-status = live }}{{Cite web | url = https://worldnews.nbcnews.com/_news/2012/07/31/13045253-us-peru-overtakes-colombia-as-top-cocaine-producer | title = Peru Overtakes Colombia as Top Cocaine Producer | work = NBC News | date = 31 July 2012 | archive-url = https://web.archive.org/web/20160304055344/https://worldnews.nbcnews.com/_news/2012/07/31/13045253-us-peru-overtakes-colombia-as-top-cocaine-producer | archive-date=4 March 2016 }} Three-quarters of the world's annual yield of cocaine has been produced in Colombia, both from cocaine base imported from Peru (primarily the Huallaga Valley) and Bolivia and from locally grown coca. There was a 28% increase in the amount of potentially harvestable coca plants which were grown in Colombia in 1998. This, combined with crop reductions in Bolivia and Peru, made Colombia the nation with the largest area of coca under cultivation after the mid-1990s. Coca grown for traditional purposes by indigenous communities, a use which is still present and is permitted by Colombian laws, only makes up a small fragment of total coca production, most of which is used for the illegal drug trade.{{cite journal | vauthors = Ciro E, Ryder M, Sánchez S | title=Peace and reparations in legal drug markets in Colombia | journal=Futures | volume=157 | date=2024 | doi=10.1016/j.futures.2024.103336 | page=103336| doi-access=free }}

The latest estimate provided by the U.S. authorities on the annual production of cocaine in Colombia refers to 290 metric tons.

As of the end of 2011, the seizure operations of Colombian cocaine carried out in different countries have totaled 351.8 metric tons of cocaine, i.e. 121.3% of Colombia's annual production according to the U.S. Department of State's estimates.{{Cite news |url=https://www.flarenetwork.org/report/top_news_100615/article/cocaine_seized_worldwide_highest_ever_in_2011.htm |title=Cocaine Seized Worldwide Highest Ever in 2011 |date=18 January 2012 |publisher=Flare Network (Flarenetwork.org) |access-date=5 January 2014 |url-status=dead |archive-url=https://web.archive.org/web/20140106033115/https://www.flarenetwork.org/report/top_news_100615/article/cocaine_seized_worldwide_highest_ever_in_2011.htm |archive-date=6 January 2014 }}{{Cite web |url=https://2009-2017.state.gov/r/pa/ei/bgn/35754.htm |title=Colombia |newspaper=U.S. Department of State |publisher=State.gov |access-date=26 March 2013 |archive-date=22 January 2017 |archive-url=https://web.archive.org/web/20170122194352/https://2009-2017.state.gov/r/pa/ei/bgn/35754.htm |url-status=live }}

File:Women gathering leaves of the coca plant (Erythroxylum coca) Wellcome V0043210.jpg

Attempts to eradicate coca fields through the use of defoliants have devastated part of the farming economy in some coca-growing regions of Colombia, and strains appear to have been developed that are more resistant or immune to their use. Whether these strains are natural mutations or the product of human tampering is unclear. These strains have also shown to be more potent than those previously grown, increasing profits for the drug cartels responsible for the exporting of cocaine. Although production fell temporarily, coca crops rebounded in numerous smaller fields in Colombia, rather than the larger plantations.{{cite journal | vauthors = Messina JP, Delamater PL | title=Defoliation and the war on drugs in Putumayo, Colombia | journal=International Journal of Remote Sensing | volume=27 | issue=1 | date=10 January 2006 | issn=0143-1161 | doi=10.1080/01431160500293708 | pages=121–128| bibcode=2006IJRS...27..121M }}{{cite journal | vauthors = Ferreira JF, Smeda RJ, Duke SO | title=Control of coca plants ( Erythroxylum coca and E. novogranatense ) with glyphosate | journal=Weed Science | volume=45 | issue=4 | date=1997 | issn=0043-1745 | doi=10.1017/S0043174500088809 | pages=551–556| bibcode=1997WeedS..45..551F }}

The cultivation of coca has become an attractive economic decision for many growers due to the combination of several factors, including the lack of other employment alternatives, the lower profitability of alternative crops in official crop substitution programs, the eradication-related damages to non-drug farms, the spread of new strains of the coca plant due to persistent worldwide demand.{{Cite journal |vauthors=Marcela I |date=August 2010 |title=Who crops coca and why? The case of Colombian farmers |url=https://www.econstor.eu/bitstream/10419/90527/1/CRC-PEG_DP_40.pdf |journal=Econstor |access-date=28 April 2024 |archive-date=28 April 2024 |archive-url=https://web.archive.org/web/20240428033001/https://www.econstor.eu/bitstream/10419/90527/1/CRC-PEG_DP_40.pdf |url-status=live }}{{Cite web |title=Colombia: 'I'm not proud cultivating coca, but we have no choice' |url=https://www.aljazeera.com/gallery/2018/9/2/colombia-im-not-proud-cultivating-coca-but-we-have-no-choice |access-date=28 April 2024 |website=Al Jazeera |archive-date=8 July 2024 |archive-url=https://web.archive.org/web/20240708192313/https://www.aljazeera.com/gallery/2018/9/2/colombia-im-not-proud-cultivating-coca-but-we-have-no-choice |url-status=live }}

In 1991, the United States Department of Justice released a report detailing the typical process in which leaves from coca plants were ultimately converted into cocaine hydrochloride by Latin American drug cartels:{{Cite report |date=1991 |title=Coca Cultivation and Cocaine Processing:An Overview|publisher=U.S. Department of Justice, Drug Enforcement Administration |author=Drug Enforcement Administration Office of Intelligence Strategic Intelligence Section Latin America Unit |place=Washington, D.C. |url=https://www.ojp.gov/pdffiles1/Digitization/132907NCJRS.pdf}}

{{Unreferenced section|date=June 2025}}

• the exact species of coca to be planted was determined by the location of its cultivation, with Erythroxylum coca being grown in tropical high altitude climates of the eastern Andes in Peru and Bolivia, while Erythroxylum novogranatense was favoured in drier lowland areas of Colombia
• the average cocaine alkaloid content of a sample of coca leaf varied between 0.1 and 0.8 percent, with coca from higher altitudes containing the largest percentages of cocaine alkaloids
• the typical farmer will plant coca on a sloping hill so rainfall will not drown the plants as they reach full maturity over 12 to 24 months after being planted
• the main harvest of coca leaves takes place after the traditional wet season in March, with additional harvesting also taking place in July and November
• the leaves are then taken to a flat area and spread out on tarpaulins to dry in the hot sun for approximately 6 hours, and afterwards placed in {{cvt|25|lb}} sacks to be transported to market or to a cocaine processing facility depending on location
• in the early 1990s, Peru and Bolivia were the main locations for converting coca leaf to coca paste and cocaine base, while Colombia was the primary location for the final conversion for these products into cocaine hydrochloride
• the conversion of coca leaf into coca paste was typically done very close to the coca fields to minimize the need to transport the coca leaves, with a plastic lined pit in the ground used as a "pozo"
• the leaves are added to the pozo along with fresh water from a nearby river, along with kerosene and sodium carbonate, then a team of several people will repeatedly stomp on the mixture in their bare feet for several hours to help turn the leaves into paste
• the cocaine alkaloids and kerosene eventually separate from the water and coca leaves, which are then drained off / scooped out of the mixture
• the cocaine alkaloids are then extracted from the kerosene and added into a dilute acidic solution, to which more sodium carbonate is added to cause a precipitate to form
• the acid and water are afterwards drained off and the precipitate is filtered and dried to produce an off-white putty-like substance, which is coca paste ready for transportation to cocaine base processing facility
• at the processing facility, coca paste is dissolved in a mixture of sulfuric acid and water, to which potassium permanganate is then added and the solution is left to stand for 6 hours to allow the unwanted alkaloids to break down
• the solution is then filtered and the precipitate is discarded, after which ammonia water is added and another precipitate is formed
• when the solution has finished reacting the liquid is drained, then the remaining precipitate is dried under heating lamps, and resulting powder is cocaine base ready for transfer to a cocaine hydrochloride laboratory
• at the laboratory, acetone is added to the cocaine base and after it has dissolved the solution is filtered to remove undesired material
• hydrochloric acid diluted in ether is added to the solution, which causes the cocaine to precipitate out of the solution as cocaine hydrochloride crystals
• the cocaine hydrochloride crystals are finally dried under lamps or in microwave ovens, then pressed into {{cvt|1|kg}} blocks and wrapped in plastic ready for export

{{Main|Cocaine paste}}

File:Precursor chemicals.gif

In traditional cocaine production, solvents are key precursor chemicals used to extract and process cocaine from coca plant leaves. The process typically involves:

• Kerosene: Used to extract the cocaine alkaloid from the alkaline mixture of coca leaves and water.
• Acetone, diethyl ether, ethyl acetate, chloroform: Used in later purification steps to dissolve or precipitate cocaine base or hydrochloride.

Cocaine paste (paco, basuco, oxi, pasta) is a crude extract of the coca leaf which contains 40% to 91% cocaine freebase along with companion coca alkaloids and varying quantities of benzoic acid, methanol, and kerosene. In South America, coca paste—also known as cocaine base and often confused with cocaine sulfate in North America—is relatively inexpensive and widely used by working class consumers. The coca paste is smoked in tobacco or cannabis cigarettes and use has become widespread in several Latin American countries. Traditionally, coca paste has been relatively abundant in South American countries such as Colombia where it is processed into cocaine hydrochloride ("street cocaine") for distribution to the rest of the world.{{cite book | veditors = Kozel NJ, Adams EH | vauthors = Siegel RK | author-link=Ronald K. Siegel | contribution=New Patterns of Cocaine Use: Changing Doses and Routes | title=Cocaine Use in America: Epidemiologic and Clinical Perspectives | series=NIDA Research Monograph | volume=61 | year=1985 | publisher=U.S. Dept. of Health and Human Services | pages=204–222 | url=http://archives.drugabuse.gov/pdf/monographs/61.pdf | access-date=9 April 2016 | archive-url=https://web.archive.org/web/20161009021412/http://archives.drugabuse.gov/pdf/monographs/61.pdf | archive-date=9 October 2016 | url-status=dead }} The caustic reactions associated with the local application of coca paste prevents its use by oral, intranasal, mucosal, or injection routes. Coca paste can only be smoked when combined with a combustible material such as tobacco or cannabis.{{citation | editor=A. Arif | title=Adverse health consequences of cocaine abuse | publisher=World Health Organization | year=1987 | url=http://apps.who.int/iris/bitstream/10665/37270/1/9241561076.pdf}}

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

{{See also|CIA involvement in Contra cocaine trafficking|Illegal drug trade in Latin America}}

File:Global-cocaine-flows-WDR2010.jpg

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

File:Destroyed Drugs Vessel MOD 45150489.jpg seized £33 million of cocaine and destroyed a smuggling speedboat off the coast of South America]]

Cocaine traffickers from Colombia and Mexico have established a labyrinth of smuggling routes throughout the Caribbean, the Bahama Islands chain, and South Florida. They often hire traffickers from Mexico or the Dominican Republic to transport the drug using a variety of smuggling techniques to U.S. markets. These include airdrops of {{convert|500|to|700|kg|-2|abbr=on}} in the Bahama Islands or off the coast of Puerto Rico, mid-ocean boat-to-boat transfers of {{convert|500|to|2000|kg|-2|abbr=on}}, and the commercial shipment of tonnes of cocaine through the port of Miami.{{cite web |url=https://www.justice.gov/archive/ndic/pubs3/3950/cocaine.htm |title=Cocaine. Puerto Rico and the U.S. Virgin Islands Drug Threat Assessment |date=2003 |publisher=National Drug Intelligence Center |access-date=29 June 2024 |archive-date=29 June 2024 |archive-url=https://web.archive.org/web/20240629201032/https://www.justice.gov/archive/ndic/pubs3/3950/cocaine.htm |url-status=live }}{{cite book | vauthors = Zimmerman S | title=A History of Smuggling in Florida | publisher=Arcadia Publishing | date=23 October 2012 | isbn=978-1-61423-356-5}}{{cite book | vauthors = Corben B, Spellman A | title=Cocaine Cowboys | publisher=powerHouse Books | date= May 2009 | isbn=978-1-57687-503-2 | page=}}

Another route of cocaine traffic goes through Chile, which is primarily used for cocaine produced in Bolivia since the nearest seaports lie in northern Chile. The arid Bolivia–Chile border is easily crossed by 4×4 vehicles that then head to the seaports of Iquique and Antofagasta. While the price of cocaine is higher in Chile than in Peru and Bolivia, the final destination is usually Europe, especially Spain where drug dealing networks exist among South American immigrants.{{cite web |url=https://globalinitiative.net/wp-content/uploads/2021/02/The-cocaine-pipeline-to-Europe-GI-TOCInsightCrime.pdf |title=The Cocaine Pipeline to Europe |date=Feb 2021 |publisher=Global Initiative |access-date=29 June 2024}}{{cite book | vauthors = ((United Nations Office on Drugs and Crime)) | title=World Drug Report 2015 | publisher=United Nations | date=16 December 2015 | isbn=978-92-1-057300-9 | page=XV}}

The primary cocaine importation points in the United States have been in Arizona, Southern California, South Florida, and Texas. Typically, land vehicles are driven across the Mexico–United States border. {{As of|2006}}, sixty-five percent of cocaine enters the United States through Mexico, where the drug is first transported from South American countries.{{Cite book | vauthors = Jacobson R | title = Illegal drugs: America's anguish | date = 2006 | publisher = Thomson Gale | location = Farmington Hills, Michigan | isbn = 978-1-4144-0419-6 | edition = 2005 | url = https://archive.org/details/illegaldrugsamer00jaco|page=82 }} {{As of|2015}}, the Sinaloa Cartel is the most active drug cartel involved in smuggling illicit drugs like cocaine into the United States and trafficking them throughout the United States.{{Cite web|title=2015 National Drug Threat Assessment Summary|url=https://www.dea.gov/docs/2015%20NDTA%20Report.pdf|website=Drug Enforcement Administration|publisher=United States Department of Justice: Drug Enforcement Administration|access-date=10 April 2016|pages=1–2|date=October 2015|quote=Mexican TCOs pose the greatest criminal drug threat to the United States; no other group is currently positioned to challenge them. These Mexican poly-drug organizations traffic heroin, methamphetamine, cocaine, and marijuana throughout the United States, using established transportation routes and distribution networks. ... While all of these Mexican TCOs transport wholesale quantities of illicit drugs into the United States, the Sinaloa Cartel appears to be the most active supplier. The Sinaloa Cartel leverages its expansive resources and dominance in Mexico to facilitate the smuggling and transportation of drugs throughout the United States.|url-status=dead|archive-url=https://web.archive.org/web/20160410100038/https://www.dea.gov/docs/2015%20NDTA%20Report.pdf|archive-date=10 April 2016}}

{{See also|Smuggling tunnel}}

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| File:CBP Port of Savannah Cocaine Seizure.jpg

| A 2,133-pound seizure of cocaine in a shipping container shipped from South America to Europe.

| File:CBP Seizes Concealed Drugs at Calexico Port of Entry (9471929203).jpg

| CBP seized 77 packages of cocaine and 34 packages of methamphetamine hidden in a hidden compartment in a cargo truck floor.

| File:Can(Easy_Open_Can).JPG

| Vacuum-sealed food cans containing cocaine-stuffed food products have been used to smuggle the drug

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Cocaine is frequently smuggled within shipping containers, mixed with legitimate cargo such as fruit, clothing, or canned goods. It is also commonly concealed in hidden compartments of vehicles and other objects, and criminal organizations have even created operational businesses to disguise drug shipments.

Additionally, cocaine is often concealed in a variety of everyday items and commercial goods to evade detection by authorities. Smugglers have hidden cocaine inside chocolate candies and other sweets, sometimes disguising the drug to look like ordinary candy bars or lollipops, which can be especially dangerous if accidentally consumed by children. Traffickers also use machinery and equipment-such as cotton-candy machines, construction equipment, and even heavy machinery parts-to hide cocaine, sometimes by impregnating the drug into materials like rubber or plastic components.

Black cocaine (Spanish: coca negra) is a form of cocaine in which the drug is mixed with various substances to disguise its appearance, interfere with color-based drug tests, and evade detection by drug-sniffing dogs; these additives may include pigments like charcoal, chemicals such as thiocyanates and iron or cobalt salts, and activated carbon to mask odors.

Another commonality is creating an operational business to disguise the mass shipments.{{Cite book| vauthors = McNicholas MA |title=Maritime Security, 2nd Edition|publisher=Butterworth-Heinemann|year=2016|pages=222}} Notorious drug lord Joaquin 'El Chapo' Guzman is one of many who have mixed legitimate business with their drug activities to conceal their illicit trading. El Chapo opened a cannery in Mexico and began producing canned jalapeños and peppers, and stuffed them with cocaine.{{Cite news| vauthors = Woody C |date=5 April 2017|title=Fake vegetables, bananas, drones and pastries – here are some of drug smuggler's most bizarre methods|work=Business Insider|url=https://www.businessinsider.com/drug-smugglers-methods-hiding-places-2017-4?r=US&IR=T#/|access-date=22 May 2020}}

At Miami International Airport in 1993, authorities discovered that some of the 312 boa constrictors in a shipment from Colombia had been surgically filled with condoms containing a total of 80 pounds (36 kg) of cocaine, resulting in the death of all the snakes.{{cite news |title=Writhing shipment yeilds smuggled cocaine - UPI Archives |url=https://www.upi.com/Archives/1993/07/02/Writhing-shipment-yeilds-smuggled-cocaine/2132741585600/ |work=UPI |language=en}}{{cite web |url=https://www.reuters.com/article/lifestyle/exotic-animals-trapped-in-net-of-drug-trade-idUSTRE5154PM/ |title=Exotic animals trapped in net of drug trade | vauthors = Esposito R | work = Reuters |date=February 2, 2009 |access-date=2025-06-10}}

{{Main|Mochilero (drug courier)|mule (smuggling)}}

Mochileros ({{literal translation|backpackers}}) are drug couriers in the Latin American drug trade. They move drugs on foot from areas where it is produced, such as cocaine from the Valle de los Ríos Apurímac, Ene y Mantaro in Peru, to pick-up points from which it can be collected by the next link in the transport chain.{{cite web|title = The Mochileros|url = https://www.bbc.co.uk/news/resources/idt-07eeeebb-d450-4e4b-98d4-755369be7855|accessdate = 2015-11-24|publisher = BBC News| vauthors = Pressly L |date = 24 November 2015}} The work is highly dangerous.

In Mexico, the people who engage in this type of activity are called "Burreros" (Spanish wordplay that refers to the person as a donkey, a pack animal), these people cross the border between Mexico and United States through the Sonoran Desert into Arizona. They usually trek through the desert in small groups, the journey taking more than a week to complete, each with a square-shaped package on their backs, containing around 55 pounds of illegal substances.{{cite web | url=https://archivo.eluniversal.com.mx/nacion/199721.html | title=Cruzan desierto con pacas de droga en la espalda }}

File:Bolletjes.jpg showing swallowed packages of cocaine.]]

File:CBP Officers Arrest Man at Port Everglades with Cocaine Wrapped Around Ankles (20901225020).jpg with cocaine wrapped around ankles]]

Internationally, cocaine is also carried in small, concealed, kilogram quantities across the border by couriers known as "mules" (or "mulas"), who cross a border either legally, for example, through a port or airport, or illegally elsewhere. If the mule gets through without being caught, the gangs will receive most of the profits. If the mule is caught, gangs may sever all links and the mule will usually stand trial for trafficking alone.{{cite book | vauthors = Fleetwood J | title=Drug Mules | publisher=Springer | date=18 June 2014 | isbn=978-1-137-27190-7 | page=}} In many cases, mules are often forced into the role, as result of coercion, violence, threats or extreme poverty.{{cite web |url=https://www.unodc.org/southasia/frontpage/2012/october/drug-mules_-swallowed-by-the-illicit-drug-trade.html |title=Drug mules: Swallowed by the illicit drug trade |publisher=UN Office of Drugs and Crime |access-date=29 June 2024 |archive-date=8 July 2024 |archive-url=https://web.archive.org/web/20240708192316/https://www.unodc.org/southasia/frontpage/2012/october/drug-mules_-swallowed-by-the-illicit-drug-trade.html |url-status=live }}

General smuggling techniques, which also have been used for cocaine, include:

• Concealment: Methods of smuggling include hiding the goods in a large vehicle in secret compartments,{{cite news | title = 75-year-old man arrested after $930K in cocaine found hidden in vehicle seats | date = 13 May 2025 |url= https://cbsaustin.com/news/local/75-year-old-man-arrested-after-930k-of-cocaine-found-in-seats-of-vehicle-texas-border-secondary-inspection-driver-narcotics-discovered | work = CBS Austin }} luggage,{{cite news | vauthors = Zamora K | date = 16 May 2025 | title = Court documents: Nearly $500K worth of cocaine found at Amarillo bus station | url = https://www.newschannel10.com/2025/05/16/court-documents-nearly-500k-worth-cocaine-found-amarillo-bus-station/ | work = newschannel10 }} or clothes.{{cite news | work = The Brussels Times |title=Man caught smuggling cocaine in his clothes at Brussels Airport |url=https://www.brusselstimes.com/1401920/man-caught-smuggling-cocaine-in-his-clothes-at-brussels-airport |language=en}}
• Body packing: The practice of transporting goods outside or inside of the body is called body packing.{{cite web | vauthors = Abuja NK |title=NDLEA arrests businessman at Kano airport for body packing large consignment of cocaine |url=https://thenationonlineng.net/ndlea-arrests-businessman-at-kano-airport-for-body-packing-large-consignment-of-cocaine/ |website=The Nation Newspaper |date=22 December 2024}} This is done by a person usually called a mule or bait. The contraband is attached to the outside of the body using adhesive tape, glue, or straps, often in such places as between the cheeks of the buttocks or between rolls of fat.
• Swallowing: This is often done using a mule's gastrointestinal tract or other body cavities as containers.{{cite web | work = The National |title=Drug smuggler who swallowed kilo of cocaine worth Dh5 million arrested at Abu Dhabi airport |url=https://www.thenationalnews.com/news/uae/2025/05/18/man-arrested-over-bid-to-smuggle-dh5m-of-drugs-in-his-intestines-at-abu-dhabi-airport/ |language=en}} In some cases, this has resulted in cardiac arrest.{{cite journal | vauthors = Resiere D, Mehdaoui H, Megarbane B | title = Cardiac Arrest in the Airport Revealing Cocaine Body Packing: A Case Report | journal = Case Reports in Medicine | volume = 2019 | pages = 6183154 | date = 6 January 2019 | pmid = 30723506 | pmc = 6339722 | doi = 10.1155/2019/6183154 | doi-access = free }}

{{Main|Maritime cocaine smuggling}}

{{See also|2019 Philadelphia Packer Marine Terminal cocaine seizure}}

Bulk cargo ships are also used to smuggle cocaine to staging sites in the Western Caribbean zone–Gulf of Mexico area. These vessels are typically 150–250-foot (50–80 m) coastal freighters that carry an average cocaine load of approximately 2.5 tonnes. Commercial fishing vessels are also used for smuggling operations. In areas with a high volume of recreational traffic, smugglers use the same types of vessels, such as go-fast boats, like those used by the local populations.{{cite book | vauthors = Klein A, Day M, Harriott A | title=Caribbean Drugs | publisher=Zed Books Ltd. | date=18 July 2013 | isbn=978-1-84813-622-9}}{{cite web |url=https://www.forbes.com/sites/hisutton/2020/08/21/3-types-of-high-speed-smuggling-boats-facing-the-coast-guard/ |title=3 Types Of Go-Fast Narco Boats The Coast Guard Faces |vauthors=Sutton H |date=August 2020 |work=Forbes |access-date=29 June 2024 |archive-date=6 February 2024 |archive-url=https://web.archive.org/web/20240206095729/https://www.forbes.com/sites/hisutton/2020/08/21/3-types-of-high-speed-smuggling-boats-facing-the-coast-guard/ |url-status=live }}

File:US Navy 070819-O-0000X-001 U.S. Navy helps seize $352 million in cocaine from semi-submersible in the Eastern Pacific.jpg]]

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

{{Unreferenced section|date=June 2025}}

After large-scale trafficking, cocaine is distributed within countries or regions by mid-level networks. These distributors break down bulk shipments into smaller quantities and supply local dealers or retail sellers. Distribution often involves organized groups that manage storage, transportation, and logistics to ensure the drug reaches various markets, preparing it for final sale to consumers.

{{see also|Gray death|Tusi (drug)}}

{{For|adverse effects of levamisole laced cocaine|Cocaine#Levamisole induced necrosis syndrome}}

File:Flavcocaine.jpg

Street cocaine is often laced or "cut" with cheaper substances to increase bulk, including talc, lactose, sucrose, glucose, mannitol, inositol, caffeine, procaine, phencyclidine, phenytoin, lidocaine, strychnine, levamisole, fentanyl, and amphetamine.{{Citation | vauthors = Pillay VV | title=Modern Medical Toxicology | edition=4th | year=2013 | publisher=Jaypee | isbn=978-93-5025-965-8 | pages=553–554}}

Cocaine is rarely prescribed for medical use, so nearly all recreational cocaine is sourced illegally. As it moves through a long chain of traffickers—often a dozen or more—each looking to maximize profit, the drug is commonly mixed with various adulterants. This widespread adulteration significantly raises the risk of poisoning or overdose. For users, this means it is extremely difficult to know what substances have been added to the cocaine they purchase. Even when purity tests or reagent kits are used, these methods may not detect all possible contaminants or dangerous additives, making it nearly impossible to guarantee the drug's safety or purity.

The extent of cutting can vary significantly over time but for the last 15 years drugs such as cocaine ranged in Europe on average from 32% to 65% in purity.{{cite web |url=https://www.euda.europa.eu/data/stats2024/ppp_en#displayTable:PPP-01-1-1-1-5-3 |website=European Union Drugs Agency |access-date=25 February 2025 |title=Statistical Bulletin 2024 — price, purity and potency | www.euda.europa.eu }}

A problem with illegal cocaine use, especially in the higher volumes used to combat fatigue (rather than increase euphoria) by long-term users, is the risk of ill effects or damage caused by the compounds used in adulteration. Cutting or "stepping on" the drug is commonplace, using compounds which simulate ingestion effects, such as Novocain (procaine) producing temporary anesthesia, as many users believe a strong numbing effect is the result of strong and/or pure cocaine, ephedrine or similar stimulants that are to produce an increased heart rate. The normal adulterants for profit are inactive sugars, usually mannitol, creatine, or glucose, so introducing active adulterants gives the illusion of purity and to 'stretch' or make it so a dealer can sell more product than without the adulterants, however the purity of the cocaine is subsequently lowered.{{cite journal | vauthors = Ribeiro M, Trevizol AP, Frajzinger R, Ribeiro A, Speierl H, Pires L, Andraus M, Tsanaclis L, Alonso AL, Cordeiro Q, Laranjeira R | title = Adulterants in crack cocaine in Brazil | journal = Trends in Psychiatry and Psychotherapy | volume = 41 | issue = 2 | pages = 186–190 | date = July 2019 | pmid = 31314858 | doi = 10.1590/2237-6089-2017-0143 | doi-access = free }}{{cite book | vauthors = ((United Nations Office on Drugs and Crime. Laboratory and Scientific Section)) | title=Methods for Impurity Profiling of Heroin and Cocaine | publisher=United Nations Publications | date=2005 | isbn=978-92-1-148206-5}} The adulterant of sugars allows the dealer to sell the product for a higher price because of the illusion of purity and allows the sale of more of the product at that higher price, enabling dealers to significantly increase revenue with little additional cost for the adulterants. A 2007 study by the European Monitoring Centre for Drugs and Drug Addiction showed that the purity levels for street purchased cocaine was often under 5% and on average under 50% pure.{{Cite web|title=EMCDDA Retail Cocaine Purity Study|year=2007|author=EMCDDA|url=https://www.emcdda.europa.eu/stats09/ppptab7a|access-date=31 December 2013|url-status=live|archive-url=https://web.archive.org/web/20140101041854/https://www.emcdda.europa.eu/stats09/ppptab7a|archive-date=1 January 2014}}

Cocaine is sometimes cut with lidocaine,{{cite journal | vauthors = Bernardo NP, Siqueira ME, De Paiva MJ, Maia PP | title = Caffeine and other adulterants in seizures of street cocaine in Brazil |year=2003 | journal = International Journal of Drug Policy | volume = 14 | issue = 4 | pages = 331–4 | doi = 10.1016/S0955-3959(03)00083-5 }}{{cite web | url = https://bulk.resource.org/courts.gov/c/F2/599/599.F2d.635.78-5314.html | title = UNITED STATES of America, Plaintiff-Appellee, v. Luis A. CUELLO, Alvaro Bastides-Benitez, John Doe, a/k/a Hugo Hurtado, and Alvaro Carvajal, Defendants-Appellants | date = 25 July 1979 | work = Docket No. 78-5314 | publisher = United States Court of Appeals, Fifth Circuit | url-status = dead | archive-url = https://web.archive.org/web/20120524141840/http://bulk.resource.org/courts.gov/c/F2/599/599.F2d.635.78-5314.html | archive-date = 24 May 2012 }} and procaine.{{cite web | title = Procaine | url = http://www.ecstasydata.org/search.php?substance1=2023 | work = ecstasydata.org }}

{{Main|Speedball (drug)}}

{{For|Cocaine interactions with opioids|Cocaine#Interactions}}

Fentanyl has been increasingly found in cocaine samples.{{cite journal | vauthors = Wagner KD, Fiuty P, Page K, Tracy EC, Nocera M, Miller CW, Tarhuni LJ, Dasgupta N | title = Prevalence of fentanyl in methamphetamine and cocaine samples collected by community-based drug checking services | journal = Drug and Alcohol Dependence | volume = 252 | pages = 110985 | date = November 2023 | pmid = 37826988 | doi = 10.1016/j.drugalcdep.2023.110985 | pmc = 10688611 }} In February 2022, 24 people in Argentina died after using cocaine laced with the fentanyl-analogue carfentanil.{{cite news |title=Cocaína 'envenenada' que causou mortes na Argentina tinha anestésico para elefantes |url=https://g1.globo.com/mundo/noticia/2022/02/10/cocaina-envenenada-que-causou-mortes-na-argentina-tinha-anestesico-para-elefantes.ghtml |work=G1 |language=pt-br}}

Nitazenes, a family of potent synthetic opioids, have also been detected.{{cite news | vauthors = Barratt M, Lee N |title=Cocaine is being contaminated with powerful opioids called nitazenes. Here's why it's a dangerous mix |url=https://theconversation.com/cocaine-is-being-contaminated-with-powerful-opioids-called-nitazenes-heres-why-its-a-dangerous-mix-234476 |work=The Conversation |date=15 July 2024}}

{{See also|2014 Amsterdam drug deaths}}

File:Bag of cocaine.jpg]]

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

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

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

Cocaine haptens are chemically modified derivatives of cocaine designed to retain the molecule’s immunogenic determinants while allowing for conjugation to carrier proteins. This enables the immune system to recognize and mount a response against cocaine.{{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 }} By coupling cocaine haptens to carrier proteins (such as keyhole limpet hemocyanin or bovine serum albumin), researchers have developed vaccines that elicit the production of anti-cocaine antibodies. These antibodies can bind cocaine in the bloodstream, preventing it from reaching the brain and producing psychoactive effects.{{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 promoted as an adjuvant for the treatment of cocaine dependence. One study on coca leaf infusion used with counseling in the treatment of 23 addicted coca-paste smokers in Lima, Peru found that the relapses rate fell from 4.35 times per month on average before coca tea treatment to one during treatment. The duration of abstinence increased from an average of 32 days before treatment to 217.2 days during treatment. This suggests that coca leaf infusion plus counseling may be effective at preventing relapse during cocaine addiction 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}}

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 }}

File:Coquero (Figure Chewing Coca), 850-1500 C.E..jpg]]

Indigenous peoples of South America have chewed the leaves of Erythroxylon coca—a plant that contains vital nutrients as well as numerous alkaloids, including cocaine—for over a thousand years.{{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}} The oldest evidence for cocaine used dates back to c. 8000 B.C.E in Peru.{{Cite journal | vauthors = Dillehay TD, Rossen J, Ugent D, Karathanasis A, Vásquez V, Netherly PJ |date=2010 |title=Early Holocene coca chewing in northern Peru |url=https://www.cambridge.org/core/journals/antiquity/article/abs/early-holocene-coca-chewing-in-northern-peru/6452FDEFF4B27959A376256AFCFAEECE |journal=Antiquity |language=en |volume=84 |issue=326 |pages=939–953 |doi=10.1017/S0003598X00067004 |issn=0003-598X}} The coca leaf was, and still is, chewed almost universally by some indigenous communities. The remains of coca leaves have been found with ancient Peruvian mummies, and pottery from the time period depicts humans with bulged cheeks, indicating the presence of something on which they are chewing.{{Cite journal | vauthors = Altman AJ, Albert DM, Fournier GA | title = Cocaine's use in ophthalmology: our 100-year heritage | journal = Survey of Ophthalmology | volume = 29 | issue = 4 | pages = 300–6 | year = 1985 | pmid = 3885453 | doi = 10.1016/0039-6257(85)90153-5 }} There is also evidence that these cultures used a mixture of coca leaves and saliva as an anesthetic for the performance of trepanation.{{Cite journal | vauthors = Gay GR, Inaba DS, Sheppard CW, Newmeyer JA | title = Cocaine: history, epidemiology, human pharmacology, and treatment. a perspective on a new debut for an old girl | journal = Clinical Toxicology | volume = 8 | issue = 2 | pages = 149–78 | year = 1975 | pmid = 1097168 | doi = 10.3109/15563657508988061 }}

When the Spanish arrived in South America, the conquistadors at first banned coca as an "evil agent of devil". But after discovering that without the coca the locals were barely able to work, the conquistadors legalized and taxed the leaf, taking 10% off the value of each crop.{{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 }} In 1569, Spanish botanist Nicolás Monardes described the indigenous peoples' practice of chewing a mixture of tobacco and coca leaves to induce "great contentment":

{{Blockquote|When they wished to make themselves drunk and out of judgment they chewed a mixture of tobacco and coca leaves which make them go as they were out of their wittes.{{Cite book|title=Joyfull Newes out of the Newe Founde Worlde | vauthors = Monardes N, Frampton J |publisher=Alfred Knopf|year=1925|location=New York}}}}

In 1609, Padre Blas Valera wrote:

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

Although the stimulant and hunger-suppressant properties of coca leaves had been known for many centuries, the isolation of the cocaine alkaloid was not achieved until 1855. Various European scientists had attempted to isolate cocaine, but none had been successful for two reasons: the knowledge of chemistry required was insufficient, and conditions of sea-shipping from South America at the time would often degrade the quality of the cocaine in the plant samples available to European chemists by the time they arrived.{{cite book | vauthors = Karch SB | title=A Brief History of Cocaine | publisher=CRC Press | publication-place=Boca Raton, Fla | date=May 1998 | isbn=978-0-8493-4019-2}} However, by 1855, the German chemist Friedrich Gaedcke successfully isolated the cocaine alkaloid for the first time.{{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 }} Gaedcke named the alkaloid "erythroxyline", and published a description in the journal Archiv der Pharmazie.{{Cite journal|title = Ueber das Erythroxylin, dargestellt aus den Blättern des in Südamerika cultivirten Strauches Erythroxylon Coca|vauthors = Gaedcke F|journal = Archiv der Pharmazie|volume = 132|issue = 2|pages = 141–150|year = 1855|doi = 10.1002/ardp.18551320208|s2cid = 86030231|url = https://zenodo.org/record/1424529|access-date = 3 September 2020|archive-date = 14 April 2021|archive-url = https://web.archive.org/web/20210414225914/https://zenodo.org/record/1424529|url-status = live}}

In 1856, Friedrich Wöhler asked Dr. Carl Scherzer, a scientist aboard the Novara (an Austrian frigate sent by Emperor Franz Joseph to circle the globe), to bring him a large amount of coca leaves from South America. In 1859, the ship finished its travels and Wöhler received a trunk full of coca. Wöhler passed on the leaves to Albert Niemann, a PhD student at the University of Göttingen in Germany, who then developed an improved purification process.{{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}}

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

The first synthesis and elucidation of the structure of the cocaine molecule was by Richard Willstätter in 1898. It was the first biomimetic synthesis of an organic structure recorded in academic chemical literature.{{Cite journal | vauthors = Singh S | title = Chemistry, design, and structure-activity relationship of cocaine antagonists | journal = Chemical Reviews | volume = 100 | issue = 3 | pages = 925–1024 | date = March 2000 | pmid = 11749256 | doi = 10.1021/cr9700538 | url = https://www.erowid.org/archive/rhodium/pdf/cocaineanalogs.pdf | archive-url = https://web.archive.org/web/20160304193726/https://www.erowid.org/archive/rhodium/pdf/cocaineanalogs.pdf |archive-date = 4 March 2016 | url-status=live | quote = Page 970 (46th page of article) first, ninth, and tenth lines }}(a) {{Cite journal | vauthors = Willstatter R | title = Synthese der Ecgoninsäure | trans-title = Synthesis of Tropine | language = de | journal = Liebigs Ann. | year = 1903 | volume = 326 | issue = 1–2 | page = 23 | doi = 10.1002/jlac.19033260105 }} (b) {{Cite journal | vauthors = Robinson RJ | title = LXIII. A synthesis of tropinone | journal = J. Chem. Soc., Trans. | year = 1917 | volume = 111 | pages = 762–768 | doi = 10.1039/CT9171100762 | url = https://zenodo.org/record/1429739 | access-date = 30 June 2019 | archive-date = 30 September 2020 | archive-url = https://web.archive.org/web/20200930155710/https://zenodo.org/record/1429739 | url-status = live }} (c) {{Cite journal | title = Die Synthese des Tropinons, Pseudopelletierins, Lobelanins und verwandter Alkaloide unter physiologischen Bedingungen | trans-title = The synthesis of tropinone, pseudopelletierin, lobelanin and related alkaloids under physiological conditions | language = de | vauthors = Schopf C, Lehman G | journal = Liebigs Ann. | year = 1935 | volume = 518 | pages = 1–37 | doi = 10.1002/jlac.19355180102 }} The synthesis started from tropinone, a related natural product and took five steps.

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

{{See also|Brompton cocktail}}

File:BEAUTY-COMFORT By Madame Falloppe (1904).jpg from the Tacoma Times, "Madame Falloppe" recommended that cold sores be treated with a solution of borax, cocaine, and morphine.]]

File:Cocaine for kids.png in children]]

File:Bottle for cocaine solution 2.jpg

With the discovery of this new alkaloid, Western medicine was quick to exploit the possible uses of this plant.

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

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

In 1859, an Italian doctor, Paolo Mantegazza, returned from Peru, where he had witnessed first-hand the use of coca by the local indigenous peoples. He proceeded to experiment on himself and upon his return to Milan, he wrote a paper in which he described the effects. In this paper, he declared coca and cocaine (at the time they were assumed to be the same) as being useful medicinally, in the treatment of "a furred tongue in the morning, flatulence, and whitening of the teeth."

A chemist named Angelo Mariani who read Mantegazza's paper became immediately intrigued with coca and its economic potential. In 1863, Mariani started marketing a wine called Vin Mariani, which had been treated with coca leaves, to become coca wine. The ethanol in wine acted as a solvent and extracted the cocaine from the coca leaves, altering the drink's effect. It contained 6 mg cocaine per ounce of wine, but Vin Mariani which was to be exported contained 7.2 mg per ounce, to compete with the higher cocaine content of similar drinks in the United States.

File:Mariani pope.jpg purportedly carried a hip flask of the coca-treated Vin Mariani with him, and awarded a Vatican gold medal to Angelo Mariani.{{Cite web |url=https://www.cocanaturally.com/ |title=Experience Vin Mariani today | Grupo Mariani S.A |publisher=Cocanaturally.com |access-date=15 January 2011 |url-status=dead |archive-url=https://web.archive.org/web/20110208034115/https://cocanaturally.com/ |archive-date=8 February 2011 }}]]

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

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

By 1885 the U.S. manufacturer Parke-Davis sold coca-leaf cigarettes and cheroots, a cocaine inhalant, a Coca Cordial, cocaine crystals, and cocaine solution for intravenous injection.{{Cite journal |vauthors=Musto DF |title=America's First Cocaine Epidemic |url=https://www.jstor.org/stable/40257908 |journal=The Wilson Quarterly |pages=59–64 |date=1989 |volume=13 |issue=3 |pmid=11619697 |jstor=40257908 |access-date=12 July 2022 |archive-date=12 July 2022 |archive-url=https://web.archive.org/web/20220712020654/https://www.jstor.org/stable/40257908 |url-status=live }} The company promised that its cocaine products would "supply the place of food, make the coward brave, the silent eloquent and render the sufferer insensitive to pain."

File:Tri-state Drug sign, Route 80, Shreveport, Louisiana LCCN2017703923.tif

A "pinch of coca leaves" was included in John Styth Pemberton's original 1886 recipe for Coca-Cola, though the company began using decocainized leaves in 1906 when the Pure Food and Drug Act was passed. Today, Coca-Cola continues to use decocainized coca leaf extract for flavoring, which is processed by the Stepan Company in New Jersey; the leftover cocaine byproduct is sold for medical use.{{cite news | title = Coca-Cola's cocaine connection is worth billions |url=https://nationalpost.com/news/coca-colas-cocaine-connection-is-worth-over-billions | date= 12 April 2023 | work = National Post }}

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

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

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

File:Bundesarchiv Bild 102-07741, Berlin, "Koks Emil" der Kokain-Verkäufer.jpg

In the 1931 song "Minnie the Moocher", Cab Calloway heavily references cocaine use. He uses the phrase "kicking the gong around", slang for cocaine use; describes titular character Minnie as "tall and skinny;" and describes Smokey Joe as "cokey".{{Cite magazine|vauthors=White T|date=14 August 1993|title=Catchin' Cab: The Magic of Calloway|url=https://books.google.com/books?id=6BEEAAAAMBAJ&q=billboard+minnie+the+moocher+1931&pg=PA3|magazine=Billboard|pages=3|access-date=13 January 2022|archive-date=8 July 2024|archive-url=https://web.archive.org/web/20240708191810/https://books.google.com/books?id=6BEEAAAAMBAJ&q=billboard+minnie+the+moocher+1931&pg=PA3#v=snippet&q=billboard%20minnie%20the%20moocher%201931&f=false|url-status=live}} In the 1932 comedy musical film The Big Broadcast, Cab Calloway performs the song with his orchestra and mimes snorting cocaine in between verses.{{Cite AV media|title=The Big Broadcast (1932)|type=Full Movie|date=8 January 2021|url=https://www.youtube.com/watch?v=nCC4zlrC5rQ&t=1h20m30s|time=1:20:29|via=YouTube|access-date=13 January 2022|archive-date=13 January 2022|archive-url=https://web.archive.org/web/20220113093159/https://www.youtube.com/watch?v=nCC4zlrC5rQ&t=1h20m30s|url-status=live}}

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

File:Cocaine_Energy_Drink_(7983571911).jpg

Cocaine Energy Supplement, also known as "Cocaine Energy Drink", is a highly caffeinated energy drink distributed by Hype Beverages.{{Cite web|url=http://www.drinkcocaine.com/|title=The Cocaine Energy Drink|date=2006-10-03|website=www.drinkcocaine.com|archive-url=https://web.archive.org/web/20061004200026/http://www.drinkcocaine.com/|archive-date=2006-10-04|url-status=live|access-date=2019-07-05}} Although the beverage contained no actual cocaine, the product launch attracted criticism from lawmakers and anti-drug organizations, who felt that Cocaine glamorized drug usage to children.{{Cite news|url=https://www.nytimes.com/2006/10/03/nyregion/03cocaine.html|title=Lawmakers Scold Maker of 'Cocaine' Drink| vauthors = Chan S |date=2006-10-03|work=The New York Times|access-date=2019-07-05|language=en-US|issn=0362-4331}}{{Cite web|url=https://www.seattletimes.com/nation-world/latest-energy-drink-gets-some-bad-buzz/|title=Latest energy drink gets some bad buzz| vauthors = Campbell CA |date=2006-09-22|website=The Seattle Times|language=en-US|access-date=2019-07-05}}

Coca Colla is an energy drink produced in Bolivia with the use of coca extract as its base. It was launched on the Bolivian market in La Paz, Santa Cruz and Cochabamba in April 2010.{{cite news|url=https://www.telegraph.co.uk/news/worldnews/southamerica/bolivia/6962746/Evo-Morales-launches-Coca-Colla.html|title=Evo Morales launches 'Coca Colla'|date=10 Jan 2010|publisher=Telegraph|access-date=22 January 2010 | location=London}}{{cite web|url=https://www.google.com/hostednews/afp/article/ALeqM5jFUaMjoArM16Nqy4rY--1-Z2lPpg|archive-url=https://web.archive.org/web/20100115055623/http://www.google.com/hostednews/afp/article/ALeqM5jFUaMjoArM16Nqy4rY--1-Z2lPpg|url-status=dead|archive-date=January 15, 2010|title=Bolivia banks on 'Coca Colla,' fizzy coca-leaf drink|date=10 Jan 2010|publisher=AFP|access-date=22 January 2010}}

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

{{see also|Cocaine boom|2023 White House cocaine incident}}

File:Cocainaestudiante.jpg

In many countries, cocaine is a popular recreational drug. Cocaine use is prevalent across all socioeconomic strata, including age, demographics, economic, social, political, religious, and livelihood.{{Cite book |vauthors = Current JD | chapter = Cocaine |title=Pharmacology for Anesthetists | chapter-url=https://books.google.com/books?id=_Du2bfrO9FwC&pg=PA27 | page = 27 }}

In the United States, the development of "crack" cocaine introduced the substance to a generally poorer inner-city market. The use of the powder form has stayed relatively constant, experiencing a new height of use across the 1980s and 1990s in the U.S.{{cite book | vauthors = Kozel NJ, Adams EH | title=Cocaine Use in America | publisher=DIANE Publishing | date=July 1996 | isbn=978-0-7881-2968-1}}{{cite book | vauthors = Spillane JF | title=Cocaine | publisher=JHU Press | publication-place=Baltimore, MD | date=11 January 2000 | isbn=978-0-8018-6230-4}} However, from 2006 to 2010 cocaine use in the US declined by roughly half before again rising once again from 2017 onwards.{{cite web |url=https://www.brookings.edu/articles/mixed-messages-is-cocaine-consumption-in-the-u-s-going-up-or-down/ |title=Mixed messages: Is cocaine consumption in the U.S. going up or down? |vauthors=Kilmer B |date=2017 |publisher=Brookings |access-date=29 June 2024 |archive-date=29 June 2024 |archive-url=https://web.archive.org/web/20240629195048/https://www.brookings.edu/articles/mixed-messages-is-cocaine-consumption-in-the-u-s-going-up-or-down/ |url-status=live }} In the UK, cocaine use increased significantly between the 1990s and late 2000s, with a similar high consumption in some other European countries, including Spain.{{cite book | author = Great Britain: Parliament: House of Commons: Home Affairs Committee | title=The cocaine trade | publisher=The Stationery Office | date=3 March 2010 | isbn=978-0-215-54425-4 | page=22}}

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

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

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

{{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}}

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