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For other uses, see Cocaine (disambiguation).

Template:Infobox drug Cocaine, also known as coke, is a strong stimulant mostly used as a recreational drug.<ref name=Pom2012>Pomara, C; Cassano, T; D'Errico, S; Bello, S; Romano, AD; Riezzo, I; Serviddio, G (2012). "Data available on the extent of cocaine use and dependence: biochemistry, pharmacologic effects and global burden of disease of cocaine abusers.". Current medicinal chemistry. 19 (33): 5647–57. PMID 22856655. doi:10.2174/092986712803988811. </ref> It is commonly snorted, inhaled as smoke, or as a solution injected into a vein.<ref name=Zim2012/> Mental effects may include loss of contact with reality, an intense feeling of happiness, or agitation.<ref name=Zim2012/> Physical symptoms may include a fast heart rate, sweating, and large pupils.<ref name=Zim2012>Zimmerman, JL (October 2012). "Cocaine intoxication.". Critical care clinics. 28 (4): 517–26. PMID 22998988. doi:10.1016/j.ccc.2012.07.003. </ref> High doses can result in very high blood pressure or body temperature.<ref>Connors, NJ; Hoffman, RS (November 2013). "Experimental treatments for cocaine toxicity: a difficult transition to the bedside.". The Journal of Pharmacology and Experimental Therapeutics. 347 (2): 251–7. PMID 23978563. doi:10.1124/jpet.113.206383. </ref> Effects begin within seconds to minutes of use and last between five and ninety minutes.<ref name=Zim2012/> Cocaine has a small number of accepted medical uses such as numbing and decreasing bleeding during nasal surgery.<ref>Harper, SJ; Jones, NS (October 2006). "Cocaine: what role does it have in current ENT practice? A review of the current literature.". The Journal of laryngology and otology. 120 (10): 808–11. PMID 16848922. doi:10.1017/s0022215106001459. </ref>

Cocaine is addictive due to its effect on the reward pathway in the brain.<ref name=Pom2012/> After a short period of use, there is a high risk that dependence will occur.<ref name=Pom2012/> Its use also increases the risk of stroke, myocardial infarction, lung problems in those who smoke it, blood infections, and sudden cardiac death.<ref name=Pom2012/><ref name=Sor2014>Sordo, L; Indave, BI; Barrio, G; Degenhardt, L; de la Fuente, L; Bravo, MJ (1 September 2014). "Cocaine use and risk of stroke: a systematic review.". Drug and Alcohol Dependence. 142: 1–13. PMID 25066468. doi:10.1016/j.drugalcdep.2014.06.041. </ref> Cocaine sold on the street is commonly mixed with local anesthetics, cornstarch, quinine, or sugar, which can result in additional toxicity.<ref name=Gold2009>Goldstein, RA; DesLauriers, C; Burda, AM (January 2009). "Cocaine: history, social implications, and toxicity—a review.". Disease-a-month : DM. 55 (1): 6–38. PMID 19081448. doi:10.1016/j.disamonth.2008.10.002. </ref> Following repeated doses a person may have decreased ability to feel pleasure and be very physically tired.<ref name=Pom2012/>

Cocaine acts by inhibiting the reuptake of serotonin, norepinephrine, and dopamine.<ref name=Pom2012/> This results in greater concentrations of these three neurotransmitters in the brain.<ref name=Pom2012/> It can easily cross the blood–brain barrier and may lead to the breakdown of the barrier.<ref>Sharma, HS; Muresanu, D; Sharma, A; Patnaik, R (2009). "Cocaine-induced breakdown of the blood–brain barrier and neurotoxicity". International Review of Neurobiology. International Review of Neurobiology. 88: 297–334. ISBN 978-0-12-374504-0. PMID 19897082. doi:10.1016/S0074-7742(09)88011-2. </ref><ref>Karch, Steven B. (2009). Karch's pathology of drug abuse (4 ed.). Boca Raton: CRC Press. p. 70. ISBN 9780849378812. Archived from the original on 10 September 2017. </ref> Cocaine is a naturally occurring substance found in the coca plant which is mostly grown in South America.<ref name=Zim2012/> In 2013, 419 kilograms were produced legally.<ref name=UN2015>Narcotic Drugs 2014 (pdf). INTERNATIONAL NARCOTICS CONTROL BOARD. 2015. p. 21. ISBN 9789210481571. Archived (PDF) from the original on 2 June 2015. </ref> It is estimated that the illegal market for cocaine is 100 to 500 billion USD each year.<ref name=Pom2012/> With further processing crack cocaine can be produced from cocaine.<ref name=Pom2012/>

After cannabis, cocaine is the most frequently used illegal drug globally.<ref>Karila, L; Zarmdini, R; Petit, A; Lafaye, G; Lowenstein, W; Reynaud, M (January 2014). "[Cocaine addiction: current data for the clinician].". Presse Médicale. 43 (1): 9–17. PMID 23727012. doi:10.1016/j.lpm.2013.01.069. </ref> Between 14 and 21 million people use the drug each year.<ref name="Pom2012"/> Use is highest in North America followed by Europe and South America.<ref name=Pom2012/> Between one and three percent of people in the developed world have used cocaine at some point in their life.<ref name=Pom2012/> In 2013 cocaine use directly resulted in 4,300 deaths, up from 2,400 in 1990.<ref name=GDB2013>GBD 2013 Mortality and Causes of Death, Collaborators (17 December 2014). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013.". Lancet. 385: 117–71. PMC 4340604Freely accessible. PMID 25530442. doi:10.1016/S0140-6736(14)61682-2. </ref> The leaves of the coca plant have been used by Peruvians since ancient times.<ref name=Gold2009/> Cocaine was first isolated from the leaves in 1860.<ref name=Pom2012/> Since 1961 the international Single Convention on Narcotic Drugs has required countries to make recreational use of cocaine a crime.<ref>Room, R; Reuter, P (7 January 2012). "How well do international drug conventions protect public health?". Lancet. 379 (9810): 84–91. PMID 22225673. doi:10.1016/s0140-6736(11)61423-2. </ref>

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Cocaine hydrochloride

Topical cocaine can be used as a local numbing agent to help with painful procedures in the mouth or nose.<ref name="Dwyer2016">Dwyer, C; Sowerby, L; Rotenberg, BW (August 2016). "Is cocaine a safe topical agent for use during endoscopic sinus surgery?". Laryngoscope (Review). 126 (8): 1721–3. PMID 27075241. doi:10.1002/lary.25836. </ref> TAC is one such formulation used for pediatrics.

Cocaine is now predominantly used for nasal and lacrimal duct surgery. The major disadvantages of this use are cocaine's potential for cardiovascular toxicity, glaucoma, and pupil dilation.<ref name="Dwyer2016"/> Medicinal use of cocaine has decreased as other synthetic local anesthetics such as benzocaine, proparacaine, lidocaine, and tetracaine are now used more often.<ref name="Dwyer2016"/> If vasoconstriction is desired for a procedure (as it reduces bleeding), the anesthetic is combined with a vasoconstrictor such as phenylephrine or epinephrine. Some ENT specialists occasionally use cocaine within the practice when performing procedures such as nasal cauterization. In this scenario dissolved cocaine is soaked into a ball of cotton wool, which is placed in the nostril for the 10–15 minutes immediately before the procedure, thus performing the dual role of both numbing the area to be cauterized, and vasoconstriction. Even when used this way, some of the used cocaine may be absorbed through oral or nasal mucosa and give systemic effects.[citation needed] An alternative method of administration for ENT surgery is mixed with adrenaline and sodium bicarbonate, as Moffett's solution.


Cocaine is a powerful nervous system stimulant.<ref name=WHO2004>World Health Organization (2004). Neuroscience of psychoactive substance use and dependence. p. 89. ISBN 9789241562355. Archived from the original on 30 April 2016. </ref> Its effects can last from fifteen or thirty minutes to an hour. The duration of cocaine's effects depends on the amount taken and the route of administration.<ref name=WHO2007>World Health Organization (2007). International medical guide for ships. p. 242. ISBN 9789241547208. Archived from the original on 30 April 2016. </ref> Cocaine can be in the form of fine white powder, bitter to the taste. When inhaled or injected, it causes a numbing effect. Crack cocaine is a smokeable form of cocaine made into small "rocks" by processing cocaine with sodium bicarbonate (baking soda) and water.<ref name="Sordo2014">Sordo, L; Indave, BI; Barrio, G; Degenhardt, L; de la Fuente, L; Bravo, MJ (September 2014). "Cocaine use and risk of stroke: a systematic review". Drug and Alcohol Dependence (Systematic Review). 142: 1–13. PMID 25066468. doi:10.1016/j.drugalcdep.2014.06.041. </ref><ref name="Zimmerman2012"/> Crack cocaine is referred to as "crack" because of the crackling sounds it makes when heated.<ref name="Zimmerman2012"/>

Cocaine use leads to increases in alertness, feelings of well-being and euphoria, increased energy and motor activity, and increased feelings of competence and sexuality.<ref name="Donroe2017">Donroe, JH; Tetrault, JM (July 2017). "Substance Use, Intoxication, and Withdrawal in the Critical Care Setting". Critical Care Clinics (Review). 33 (3): 543–58. PMID 28601134. doi:10.1016/j.ccc.2017.03.003. </ref>




Coca leaves




Contrary to popular belief, both ingestion and insufflation result in approximately the same proportion of the drug being absorbed: 30 to 60%. Compared to 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, however, a more realistic activation period is closer to 5 to 10 minutes. Physiological and psychotropic effects from nasally insufflated cocaine are sustained for approximately 40–60 minutes after the peak effects are attained.<ref>Barnett, G; Hawks, R; Resnick, R (1981). "Cocaine pharmacokinetics in humans". Journal of Ethnopharmacology. 3 (2–3): 353–66. PMID 7242115. doi:10.1016/0378-8741(81)90063-5. ; Jones, supra note 19; Wilkinson et al., Van Dyke et al.</ref>

Coca tea, an infusion of coca leaves, is also a traditional method of consumption. The tea has often been recommended for travelers in the Andes to prevent altitude sickness.<ref name=luks>Luks, Andrew M. (2010). "Wilderness Medical Society Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness" (PDF). Wilderness. Wilderness & Environmental Medicine. 21 (2): 146–155. doi:10.1016/j.wem.2010.03.002. Archived (PDF) from the original on 15 October 2012.  (mirror: [1])</ref> However, its actual effectiveness has never been systematically studied.<ref name=luks /> This method of consumption has been practised for many centuries by the indigenous tribes of South America. One specific purpose of ancient coca leaf consumption was to increase energy and reduce fatigue in messengers who made multi-day quests to other settlements.[citation needed]

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."<ref>Siegel RK, Elsohly MA, Plowman T, Rury PM, Jones RT (3 January 1986). "Cocaine in herbal tea". Journal of the American Medical Association. 255 (1): 40. PMID 3940302. doi:10.1001/jama.255.1.40. </ref> 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. Despite this, the DEA seized several shipments in Hawaii, Chicago, Georgia, and several locations on the East Coast of the United States, and the product was removed from the shelves.


Lines of cocaine prepared for insufflation

Nasal insufflation (known colloquially as "snorting", "sniffing", or "blowing") is a common method of ingestion of recreational powdered cocaine.<ref>"DrugFacts: Cocaine". National Institute on Drug Abuse. April 2013. Archived from the original on 11 July 2015. Retrieved 11 July 2015. </ref> The drug coats and is absorbed through the mucous membranes lining the nasal passages. Cocaine's desired euphoric effects are delayed when snorted through the nose by about five minutes. This occurs because cocaine's absorption is slowed by its constricting effect on the blood vessels of the nose.<ref name="Zimmerman2012"/> Insufflation of cocaine also leads to the longest duration of its effects (60–90 minutes).<ref name="Zimmerman2012"/> When insufflating cocaine, absorption through the nasal membranes is approximately 30–60%, with higher doses leading to increased absorption efficiency. Any material not directly absorbed through the mucous membranes is collected in mucus and swallowed (this "drip" is considered pleasant by some and unpleasant by others).

In a study of cocaine users, the average time taken to reach peak subjective effects was 14.6 minutes.<ref name="Volkow">Nora D. Volkow; et al. (2000). "Effects of route of administration on cocaine induced dopamine transporter blockade in the human brain". Life Sciences. 67 (12): 1507–1515. PMID 10983846. doi:10.1016/S0024-3205(00)00731-1. </ref> Any damage to the inside of the nose is because cocaine highly constricts blood vessels – and therefore blood and oxygen/nutrient flow – to that area. Nosebleeds after cocaine insufflation are due to irritation and damage of mucus membranes by foreign particles and adulterants and not the cocaine itself;[citation needed] as a vasoconstrictor, cocaine acts to reduce bleeding.

Rolled up banknotes, hollowed-out pens, cut straws, pointed ends of keys, specialized spoons, long fingernails, and (clean) tampon applicators are often used to insufflate cocaine. Such devices are often called "tooters" by users. The cocaine typically is poured onto a flat, hard surface (such as a mirror, CD case or book) and divided into "bumps", "lines" or "rails", and then insufflated.<ref>"Cocaine terminology". Archived from the original on 9 July 2007. </ref> The amount of cocaine in a line varies widely from person to person and occasion to occasion (the purity of the cocaine is also a factor), but one line is generally considered to be a single dose and is typically 35 mg (a "bump") to 100 mg (a "rail").[dubious ] As tolerance builds rapidly in the short-term (hours), many lines are often snorted to produce greater effects.[citation needed] A 2001 study reported that the sharing of straws used to "snort" cocaine can spread blood diseases such as hepatitis C.<ref>Bonkovsky HL, Mehta S (2001). "Hepatitis C: a review and update". J. Am. Acad. Dermatol. 44 (2): 159–182. PMID 11174373. doi:10.1067/mjd.2001.109311. </ref>



An injected mixture of cocaine and heroin, 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. It has been responsible for numerous deaths, including celebrities such as comedians/actors John Belushi and Chris Farley, Mitch Hedberg, River Phoenix, grunge singer Layne Staley and actor Philip Seymour Hoffman. Experimentally, cocaine injections can be delivered to animals such as fruit flies to study the mechanisms of cocaine addiction.<ref>Dimitrijevic N, Dzitoyeva S, Manev H (2004). "An automated assay of the behavioral effects of cocaine injections in adult Drosophila". J Neurosci Methods. 137 (2): 181–184. PMID 15262059. doi:10.1016/j.jneumeth.2004.02.023. </ref>


See also: Crack cocaine

Inhalation by smoking cocaine is one of the several ways the drug is consumed. The onset of cocaine's desired euphoric effects is fastest with inhaling cocaine and begins after 3–5 seconds.<ref name="Zimmerman2012"/> In contrast, inhalation of cocaine leads to the shortest duration of its effects (5–15 minutes).<ref name="Zimmerman2012"/> The two main ways cocaine is smoked are freebasing and by using cocaine which has been converted to smokable "crack cocaine". Cocaine is smoked by inhaling the vapor produced when solid cocaine is heated to the point that it sublimates.<ref>"Appendix B: Production of Cocaine Hydrochloride and Cocaine Base". US Justice Dep. Archived from the original on 30 November 2009. </ref> In a 2000 Brookhaven National Laboratory medical department study, based on self reports of 32 abusers who participated in the study,"peak high" was found at mean of 1.4min +/- 0.5 minutes.<ref name="Volkow" /> Pyrolysis products of cocaine that occur only when heated/smoked have been shown to change the effect profile, i.e. anhydroecgonine methyl ester when co-administered with cocaine increases the dopamine in CPu and NAc brain regions, and has M1- and M3- receptor affinity.<ref name="GarciaTorres2016">Garcia, Raphael Caio Tamborelli; Torres, Larissa Helena; Balestrin, Natália Trigo; Andrioli, Tatiana Costa; Flório, Jorge Camilo; de Oliveira, Carolina Dizioli Rodrigues; da Costa, José Luiz; Yonamine, Mauricio; Sandoval, Maria Regina Lopes; Camarini, Rosana; Marcourakis, Tania (2016). "Anhydroecgonine methyl ester, a cocaine pyrolysis product, may contribute to cocaine behavioral sensitization". Toxicology. ISSN 0300-483X. PMID 27129946. doi:10.1016/j.tox.2016.04.009. </ref>




Adverse effects


Main article: Cocaine intoxication

With excessive or prolonged use, the drug can cause itching, fast heart rate, hallucinations, and paranoid delusions.<ref name="weizhao2008">Zhao, Wei (2008). Mechanisms Mediating Sex Differences in the Effects of Cocaine. ProQuest. p. 3. ISBN 0-549-99458-0. Archived from the original on 4 April 2014. Retrieved 25 September 2012. </ref> Overdoses cause hyperthermia and a marked elevation of blood pressure, which can be life-threatening,<ref name="weizhao2008" /> arrhythmias,<ref name="Nav">O'Leary, ME; Hancox, JC (May 2010). "Role of voltage-gated sodium, potassium and calcium channels in the development of cocaine-associated cardiac arrhythmias". British Journal of Clinical Pharmacology. 69 (5): 427–42. PMC 2856043Freely accessible. PMID 20573078. doi:10.1111/j.1365-2125.2010.03629.x. </ref> and death.<ref name="Nav" />

Anxiety, paranoia, and restlessness can also occur, especially during the comedown. With excessive dosage, tremors, convulsions and increased body temperature are observed.<ref name=WHO2004 /> Severe cardiac adverse events, particularly sudden cardiac death, become a serious risk at high doses due to cocaine's blocking effect on cardiac sodium channels.<ref name="Nav" />


Side effects of chronic cocaine use

Chronic cocaine intake causes strong imbalances of transmitter levels in order to compensate extremes. Thus, receptors disappear from the cell surface or reappear on it, resulting more or less in an "off" or "working mode" respectively, or they change their susceptibility for binding partners (ligands) – mechanisms called downregulation and upregulation. However, studies suggest cocaine abusers do not show normal age-related loss of striatal dopamine transporter (DAT) sites, suggesting cocaine has neuroprotective properties for dopamine neurons.<ref>Hugo D'haenen; Johan A. den Boer; P. Willner, eds. (2002). Biological Psychiatry. 2 (2 ed.). Wiley. p. 528. ISBN 978-0-471-49198-9. </ref> Possible side effects include insatiable hunger, aches, insomnia/oversleeping, lethargy, and persistent runny nose. Depression with suicidal ideation may develop in very heavy users. Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes appear to indicate a long term damage of dopamine neurons. All these effects contribute a rise in tolerance thus requiring a larger dosage to achieve the same effect.<ref name="Substance Abuse Textbook">Lowinson, Joyce, H; Ruiz, Pedro; Millman, Robert B. (2004). Substance abuse: a comprehensive textbook (4th ed.). Lippincott Williams & Wilkins. p. 204. ISBN 978-0-7817-3474-5. Archived from the original on 4 April 2014. Retrieved 5 January 2014. </ref> The lack of normal amounts of serotonin and dopamine in the brain is the cause of the dysphoria and depression felt after the initial high. Physical withdrawal is not dangerous. Physiological changes caused by cocaine withdrawal include vivid and unpleasant dreams, insomnia or hypersomnia, increased appetite and psychomotor retardation or agitation.<ref name="Substance Abuse Textbook" />

Physical side effects from chronic smoking of cocaine include coughing up blood, bronchospasm, itching, fever, diffuse alveolar infiltrates without effusions, pulmonary and systemic eosinophilia, chest pain, lung trauma, sore throat, asthma, hoarse voice, dyspnea (shortness of breath), and an aching, flu-like syndrome. Cocaine 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. A common but untrue belief is that the smoking of cocaine chemically breaks down tooth enamel and causes tooth decay. However, cocaine does often cause involuntary tooth grinding, known as bruxism, which can deteriorate tooth enamel and lead to gingivitis.<ref>Baigent, Michael (2003). "Physical complications of substance abuse: what the psychiatrist needs to know". Curr Opin Psychiatry. 16 (3): 291–296. doi:10.1097/00001504-200305000-00004. </ref> 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, chronic stimulant abusers who do not hydrate sufficiently may experience demineralization of their teeth due to the pH of the tooth surface dropping too low (below 5.5). Cocaine use also promotes the formation of blood clots.<ref name="Zimmerman2012"/> This increase in blood clot formation is attributed to cocaine-associated increases in the activity of plasminogen activator inhibitor, and an increase in the number, activation, and aggregation of platelets.<ref name="Zimmerman2012"/>

Chronic intranasal usage can degrade the cartilage separating the nostrils (the septum nasi), leading eventually to its complete disappearance. Due to the absorption of the cocaine from cocaine hydrochloride, the remaining hydrochloride forms a dilute hydrochloric acid.<ref name="pagliaros">Pagliaro, Louis; Ann Marie Pagliaro (2004). Pagliaros’ Comprehensive Guide to Drugs and Substances of Abuse. Washington, D.C.: American Pharmacists Association. ISBN 978-1-58212-066-9. </ref>

Cocaine may also greatly increase this risk of developing rare autoimmune or connective tissue diseases such as lupus, Goodpasture syndrome, vasculitis, glomerulonephritis, Stevens–Johnson syndrome, and other diseases.<ref>"More bad news for cocaine users: Drug can triple risk of aneurysm". 1999. Archived from the original on 11 October 2007. Retrieved 10 July 2007. </ref><ref>Trozak D, Gould W (1984). "Cocaine abuse and connective tissue disease". J Am Acad Dermatol. 10 (3): 525. PMID 6725666. doi:10.1016/S0190-9622(84)80112-7. </ref><ref>Ramón Peces; Navascués, RA; Baltar, J; Seco, M; Alvarez, J (1999). "Antiglomerular Basement Membrane Antibody-Mediated Glomerulonephritis after Intranasal Cocaine Use". Nephron. 81 (4): 434–438. PMID 10095180. doi:10.1159/000045328. </ref><ref>Moore PM, Richardson B (1998). "Neurology of the vasculitides and connective tissue diseases". J. Neurol. Neurosurg. Psychiatry. 65 (1): 10–22. PMC 2170162Freely accessible. PMID 9667555. doi:10.1136/jnnp.65.1.10. </ref> It can also cause a wide array of kidney diseases and kidney failure.<ref>Jared A. Jaffe; Kimmel, PL (2006). "Chronic Nephropathies of Cocaine and Heroin Abuse: A Critical Review". Clinical Journal of the American Society of Nephrology. American Society of Nephrology. 1 (4): 655–67. PMID 17699270. doi:10.2215/CJN.00300106. </ref><ref>Fokko J. van der Woude (2000). "Cocaine use and kidney damage". Nephrology Dialysis Transplantation. Oxford University Press. 15 (3): 299–301. PMID 10692510. doi:10.1093/ndt/15.3.299. Archived from the original on 20 April 2011. </ref>

Cocaine use leads to an increased risk of hemorrhagic and ischemic strokes.<ref name="Sordo2014"/> Cocaine use also increases the risk of having a heart attack.<ref name="Havakuk2017">Havakuk, O; Rezkalla, SH; Kloner, RA (July 2017). "The Cardiovascular Effects of Cocaine". Journal of the American College of Cardiology (Review). 70 (1): 101–13. PMID 28662796. doi:10.1016/j.jacc.2017.05.014. </ref>



ΔFosB levels have been found to increase upon the use of cocaine.<ref name="pmid9668659">Hope BT (May 1998). "Cocaine and the AP-1 transcription factor complex". Annals of the New York Academy of Sciences. 844: 1–6. PMID 9668659. doi:10.1111/j.1749-6632.1998.tb08216.x. </ref> Each subsequent dose of cocaine continues to increase ΔFosB levels with no ceiling of tolerance. Elevated levels of ΔFosB leads to increases in brain-derived neurotrophic factor (BDNF) levels, which in turn increases the number of dendritic branches and spines present on neurons involved with the nucleus accumbens and prefrontal cortex areas of the brain. This change can be identified rather quickly, and may be sustained weeks after the last dose of the drug.

Transgenic mice exhibiting inducible expression of ΔFosB primarily in the nucleus accumbens and dorsal striatum exhibit sensitized behavioural responses to cocaine.<ref name="pmid10499584">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 (Sep 1999). "Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine". Nature. 401 (6750): 272–6. PMID 10499584. doi:10.1038/45790. </ref> They self-administer cocaine at lower doses than control,<ref name="pmid12657709">Colby CR, Whisler K, Steffen C, Nestler EJ, Self DW (Mar 2003). "Striatal cell type-specific overexpression of DeltaFosB enhances incentive for cocaine". The Journal of Neuroscience. 23 (6): 2488–93. PMID 12657709. </ref> but have a greater likelihood of relapse when the drug is withheld.<ref name="pmid12657709">Colby CR, Whisler K, Steffen C, Nestler EJ, Self DW (Mar 2003). "Striatal cell type-specific overexpression of DeltaFosB enhances incentive for cocaine". The Journal of Neuroscience. 23 (6): 2488–93. PMID 12657709. </ref><ref name="pmid11572966">Nestler EJ, Barrot M, Self DW (Sep 2001). "DeltaFosB: a sustained molecular switch for addiction". Proceedings of the National Academy of Sciences of the United States of America. 98 (20): 11042–6. PMC 58680Freely accessible. PMID 11572966. doi:10.1073/pnas.191352698. </ref> ΔFosB increases the expression of AMPA receptor subunit GluR2<ref name="pmid10499584">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 (Sep 1999). "Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine". Nature. 401 (6750): 272–6. PMID 10499584. doi:10.1038/45790. </ref> and also decreases expression of dynorphin, thereby enhancing sensitivity to reward.<ref name="pmid11572966">Nestler EJ, Barrot M, Self DW (Sep 2001). "DeltaFosB: a sustained molecular switch for addiction". Proceedings of the National Academy of Sciences of the United States of America. 98 (20): 11042–6. PMC 58680Freely accessible. PMID 11572966. doi:10.1073/pnas.191352698. </ref>

Dependence and withdrawal


During pregnancy

According to a 2005 review, "it is unclear whether prenatal cocaine exposure is associated with SIDS."<ref>Schiller, Cassandra; Allen, Pat Jackson (September 2005). "Follow-up of Infants Prenatally Exposed to Cocaine". Pediatric Nursing. 31 (5): 429. </ref>



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).<ref>Rothman, Richard B.; et al. (2001). "Amphetamine-Type Central Nervous System Stimulants Release Norepinepehrine more Potently than they Release Dopamine and Serotonin". Synapse. 39 (1): 32–41. PMID 11071707. doi:10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3.  (Table V. on page 37)</ref><ref name=Pom2012/> The most extensively studied effect of cocaine on the central nervous system is the blockade of the dopamine transporter protein. Dopamine transmitter 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.

Cocaine's 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. The overabundance of 5-HT3 receptors in cocaine conditioned rats display this trait, however the exact effect of 5-HT3 in this process is unclear.<ref>Carta M, Allan AM, Partridge LD, Valenzuela CF (2003). "Cocaine inhibits 5-HT3 receptor function in neurons from transgenic mice overexpressing the receptor". Eur. J. Pharmacol. 459 (2–3): 167–9. PMID 12524142. doi:10.1016/S0014-2999(02)02867-4. </ref> The 5-HT2 receptor (particularly the subtypes 5-HT2AR, 5-HT2BR and 5-HT2CR) are involved in the locomotor-activating effects of cocaine.<ref>Filip M, Bubar MJ, Cunningham KA (2004). "Contribution of serotonin (5-hydroxytryptamine; 5-HT) 5-HT2 receptor subtypes to the hyperlocomotor effects of cocaine: acute and chronic pharmacological analyses". J. Pharmacol. Exp. Ther. 310 (3): 1246–54. PMID 15131246. doi:10.1124/jpet.104.068841. </ref>

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 habituation of the substance so much as the conformation and binding properties to where and how on the transporter the molecule binds.<ref>Beuming, Thijs; et al. (2008). "The binding sites for cocaine and dopamine in the dopamine transporter overlap". Nature Neuroscience. 11 (7): 780–9. PMC 2692229Freely accessible. PMID 18568020. doi:10.1038/nn.2146. </ref>

Sigma receptors are affected by cocaine, as cocaine functions as a sigma ligand agonist.<ref>"Sigma Receptors Play Role In Cocaine-induced Suppression Of Immune System". 6 May 2003. Archived from the original on 12 January 2011. Retrieved 9 March 2010. </ref> Further specific receptors it has been demonstrated to function on are NMDA and the D1 dopamine receptor.<ref>Lluch J, Rodríguez-Arias M, Aguilar MA, Miñarro J (2005). "Role of dopamine and glutamate receptors in cocaine-induced social effects in isolated and grouped male OF1 mice". Pharmacol. Biochem. Behav. 82 (3): 478–87. PMID 16313950. doi:10.1016/j.pbb.2005.10.003. </ref>

Cocaine also blocks sodium channels, thereby interfering with the propagation of action potentials;<ref name="Nav">O'Leary, ME; Hancox, JC (May 2010). "Role of voltage-gated sodium, potassium and calcium channels in the development of cocaine-associated cardiac arrhythmias". British Journal of Clinical Pharmacology. 69 (5): 427–42. PMC 2856043Freely accessible. PMID 20573078. doi:10.1111/j.1365-2125.2010.03629.x. </ref> 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 Kappa-opioid receptor as well.<ref>"Drugbank website "drug card", "(DB00907)" for Cocaine: Giving ten targets of the molecule in vivo, including dopamine/serotonin sodium channel affinity & K-opioid affinity". Archived from the original on 20 February 2010. Retrieved 9 March 2010. </ref> Cocaine also causes vasoconstriction, thus reducing bleeding during minor surgical procedures. The locomotor enhancing properties of cocaine may be attributable to its enhancement of dopaminergic transmission from the substantia nigra. Recent research points to an important role of circadian mechanisms<ref>Uz T, Akhisaroglu M, Ahmed R, Manev H (2003). "The pineal gland is critical for circadian Period 1 expression in the striatum and for circadian cocaine sensitization in mice". Neuropsychopharmacology. 28 (12): 2117–2123. PMID 12865893. doi:10.1038/sj.npp.1300254. </ref> and clock genes<ref>McClung C, Sidiropoulou K, Vitaterna M, Takahashi J, White F, Cooper D, Nestler E (2005). "Regulation of dopaminergic transmission and cocaine reward by the Clock gene". Proc Natl Acad Sci USA. 102 (26): 9377–81. PMC 1166621Freely accessible. PMID 15967985. doi:10.1073/pnas.0503584102. </ref> in behavioral actions of cocaine.

Cocaine can often cause reduced food intake, many chronic users lose their appetite and can experience severe malnutrition and significant weight loss. Cocaine effects, further, are shown to be potentiated for the user when used in conjunction with new surroundings and stimuli, and otherwise novel environs.<ref>Carey RJ, Damianopoulos EN, Shanahan AB (2008). "Cocaine effects on behavioral responding to a novel object placed in a familiar environment". Pharmacol. Biochem. Behav. 88 (3): 265–71. PMID 17897705. doi:10.1016/j.pbb.2007.08.010. </ref>


Cocaine has a short half life of 0.7-1.5 hours and is extensively metabolized by cholinesterase enzymes (primarily in the liver and plasma), with only about 1% excreted unchanged in the urine.<ref name="Zimmerman2012"/> The metabolism is dominated by hydrolytic ester cleavage, so the eliminated metabolites consist mostly of benzoylecgonine (BE), the major metabolite, and other significant metabolites in lesser amounts such as ecgonine methyl ester (EME) and ecgonine.<ref name="Zimmerman2012"/> Further minor metabolites of cocaine include norcocaine, p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine (pOHBE), and m-hydroxybenzoylecgonine.<ref>Kolbrich EA, Barnes AJ, Gorelick DA, Boyd SJ, Cone EJ, Huestis MA (2006). "Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration". J Anal Toxicol. 30 (8): 501–10. PMID 17132243. doi:10.1093/jat/30.8.501. [permanent dead link]</ref> If consumed with alcohol, cocaine combines with alcohol in the liver to form cocaethylene.<ref name="Zimmerman2012"/> Studies have suggested cocaethylene is both more euphoric, and has a higher cardiovascular toxicity than cocaine by itself.<ref name="Zimmerman2012"/>




A pile of cocaine hydrochloride
A piece of compressed cocaine powder

Cocaine in its purest form is a white, pearly product. Cocaine appearing in powder form is a salt, typically cocaine hydrochloride. Street cocaine is often adulterated or "cut" with talc, lactose, sucrose, glucose, mannitol, inositol, caffeine, procaine, phencyclidine, phenytoin, lignocaine, strychnine, amphetamine, or heroin.<ref>VV Pillay (2013), Modern Medical Toxicology (4th ed.), Jaypee, pp. 553–554, ISBN 978-93-5025-965-8 </ref>






Main article: Freebase (chemistry)


Smoking freebase cocaine has the additional effect of releasing methylecgonidine into the user's system due to the pyrolysis of the substance (a side effect which insufflating or injecting powder cocaine does not create). Some research suggests that smoking freebase cocaine can be even more cardiotoxic than other routes of administration<ref>Scheidweiler, K. B.; Plessinger, MA; Shojaie, J; Wood, RW; Kwong, TC (15 October 2003). "Pharmacokinetics and Pharmacodynamics of Methylecgonidine, a Crack Cocaine Pyrolyzate". Journal of Pharmacology and Experimental Therapeutics. 307 (3): 1179–87. PMID 14561847. doi:10.1124/jpet.103.055434. </ref> because of methylecgonidine's effects on lung tissue<ref>Yang Y, Ke Q, Cai J, Xiao YF, Morgan JP (2001). "Evidence for cocaine and methylecgonidine stimulation of M2 muscarinic receptors in cultured human embryonic lung cells". Br. J. Pharmacol. 132 (2): 451–60. PMC 1572570Freely accessible. PMID 11159694. doi:10.1038/sj.bjp.0703819. </ref> and liver tissue.<ref>Fandiño AS, Toennes SW, Kauert GF (2002). "Studies on hydrolytic and oxidative metabolic pathways of anhydroecgonine methyl ester (methylecgonidine) using microsomal preparations from rat organs". Chem. Res. Toxicol. 15 (12): 1543–8. PMID 12482236. doi:10.1021/tx0255828. </ref>


Crack cocaine

Main article: Crack cocaine
A woman smoking crack cocaine
"Rocks" of crack cocaine


The "freebase" and "crack" forms of cocaine are usually administered by vaporization of the powdered substance into smoke, which is then inhaled.<ref>"Substances – Cocaine". The Steinhardt School of Culture, Education, and Human Development. Archived from the original on 2 May 2009. Retrieved 1 August 2009. </ref>

The origin of the name "crack" comes from the "crackling" sound (and hence the onomatopoeic moniker "crack") that is produced when the cocaine and its impurities (i.e. water, sodium bicarbonate) are heated past the point of vaporization.<ref name=Nelson98>George, Nelson (1998). [[[:Template:Google books]] Hip Hop America] Check |url= value (help). Viking Penguin. p. 40. </ref>

Pure cocaine base/crack can be smoked because it vaporizes smoothly, with little or no decomposition at 98 °C (208 °F),<ref>Ries, Richard K.; Miller, Sharon C.; Fiellin, David A. (2009). Principles of addiction medicine. Lippincott Williams & Wilkins. p. 137. ISBN 0-7817-7477-2. Archived from the original on 4 April 2014. Retrieved 5 January 2014. </ref> which is below the boiling point of water.



Coca leaf infusions



The cocaine metabolite benzoylecgonine can be detected in the urine of people a few hours after drinking one cup of coca leaf infusion.<ref>"Coca tea or mate de coca – the holy coca leaf infusion". Archived from the original on 20 December 2015. Retrieved 17 December 2015. </ref>


Biosynthesis of N-methyl-pyrrolinium cation
Biosynthesis of cocaine
Robinson biosynthesis of tropane
Reduction of tropinone

The first synthesis and elucidation of the cocaine molecule was by Richard Willstätter in 1898.<ref name="Humphrey2001">Humphrey AJ, O'Hagan D (2001). "Tropane alkaloid biosynthesis. A century old problem unresolved". Nat Prod Rep. 18 (5): 494–502. PMID 11699882. doi:10.1039/b001713m. </ref> 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.<ref>Dewick, P. M. (2009). Medicinal Natural Products. Chicester: Wiley-Blackwell. ISBN 978-0-470-74276-1. </ref> The first addition is a Mannich-like reaction with the enolate anion from acetyl-CoA acting as a nucleophile towards the pyrrolinium cation. The second addition occurs through a Claisen condensation. This produces a racemic mixture of the 2-substituted pyrrolidine, with the retention of the thioester from the Claisen condensation. In formation of tropinone from racemic ethyl [2,3-13C2]4(Nmethyl-2-pyrrolidinyl)-3-oxobutanoate there is no preference for either stereoisomer.<ref>R. J. Robins; T. W. Abraham; A. J. Parr; J. Eagles; N. J. Walton (1997). "The Biosynthesis of Tropane Alkaloids in Datura stramonium: The Identity of the Intermediates between N-Methylpyrrolinium Salt and Tropinone". J. Am. Chem. Soc. 119 (45): 10929–10934. doi:10.1021/ja964461p. </ref> In the biosynthesis of cocaine, however, only the (S)-enantiomer can cyclize to form the tropane ring system of cocaine. The stereoselectivity of this reaction was further investigated through study of prochiral methylene hydrogen discrimination.<ref>Hoye TR, Bjorklund JA, Koltun DO, Renner MK (2000). "N-methylputrescine oxidation during cocaine biosynthesis: study of prochiral methylene hydrogen discrimination using the remote isotope method". Org. Lett. 2 (1): 3–5. PMID 10814231. doi:10.1021/ol990940s. </ref> This is due to the extra chiral center at C-2.<ref>E. Leete; J. A. Bjorklund; M. M. Couladis; S. H. Kim (1991). "Late intermediates in the biosynthesis of cocaine: 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoate and methyl ecgonine". J. Am. Chem. Soc. 113 (24): 9286–9292. doi:10.1021/ja00024a039. </ref> This process occurs through an oxidation, which regenerates the pyrrolinium cation and formation of an enolate anion, and an intramolecular Mannich reaction. The tropane ring system undergoes hydrolysis, SAM-dependent methylation, and reduction via NADPH for the formation of methylecgonine. The benzoyl moiety required for the formation of the cocaine diester is synthesized from phenylalanine via cinnamic acid.<ref>E. Leete; J. A. Bjorklund; S. H. Kim (1988). "The biosynthesis of the benzoyl moiety of cocaine". Phytochemistry. 27 (8): 2553–2556. doi:10.1016/0031-9422(88)87026-2. </ref> Benzoyl-CoA then combines the two units to form cocaine.

N-methyl-pyrrolinium cation

The biosynthesis begins with L-Glutamine, which is derived to L-ornithine in plants. The major contribution of L-ornithine and L-arginine as a precursor to the tropane ring was confirmed by Edward Leete.<ref>Leete E, Marion L, Sspenser ID (1954). "Biogenesis of hyoscyamine". Nature. 174 (4431): 650–1. PMID 13203600. doi:10.1038/174650a0. </ref> Ornithine then undergoes a pyridoxal phosphate-dependent decarboxylation to form putrescine. In animals, however, the urea cycle derives putrescine from ornithine. L-ornithine is converted to L-arginine,<ref>Robins RJ, Waltons NJ, Hamill JD, Parr AJ, Rhodes MJ (1991). "Strategies for the genetic manipulation of alkaloid-producing pathways in plants". Planta Med. 57 (7 Suppl): S27–35. PMID 17226220. doi:10.1055/s-2006-960226. </ref> which is then decarboxylated via PLP to form agmatine. Hydrolysis of the imine derives N-carbamoylputrescine followed with hydrolysis of the urea to form putrescine. The separate pathways of converting ornithine to putrescine in plants and animals have converged. A SAM-dependent N-methylation of putrescine gives the N-methylputrescine product, which then undergoes oxidative deamination by the action of diamine oxidase to yield the aminoaldehyde. Schiff base formation confirms the biosynthesis of the N-methyl-Δ1-pyrrolinium cation.

Robert Robinson's acetonedicarboxylate

The biosynthesis of the tropane alkaloid, however, is still uncertain. Hemscheidt proposes that Robinson's acetonedicarboxylate emerges as a potential intermediate for this reaction.<ref>T. Hemscheidt; Vederas, John C. (2000). Leeper, Finian J.; Vederas, John C., eds. "Tropane and Related Alkaloids". Top. Curr. Chem. Topics in Current Chemistry. 209: 175. ISBN 978-3-540-66573-1. doi:10.1007/3-540-48146-X. </ref> Condensation of N-methylpyrrolinium and acetonedicarboxylate would generate the oxobutyrate. Decarboxylation leads to tropane alkaloid formation.

Reduction of tropinone

The reduction of tropinone is mediated by NADPH-dependent reductase enzymes, which have been characterized in multiple plant species.<ref>A. Portsteffen; B. Draeger; A. Nahrstedt (1992). "Two tropinone reducing enzymes from Datura stramonium transformed root cultures". Phytochemistry. 31 (4): 1135–1138. doi:10.1016/0031-9422(92)80247-C. </ref> These plant species all contain two types of the reductase enzymes, tropinone reductase I and tropinone reductase II. TRI produces tropine and TRII produces pseudotropine. Due to differing kinetic and pH/activity characteristics of the enzymes and by the 25-fold higher activity of TRI over TRII, the majority of the tropinone reduction is from TRI to form tropine.<ref>Boswell HD, Dräger B, McLauchlan WR (1999). "Specificities of the enzymes of N-alkyltropane biosynthesis in Brugmansia and Datura". Phytochemistry. 52 (5): 871–8. PMID 10626376. doi:10.1016/S0031-9422(99)00293-9. </ref>

Detection in body fluids

Cocaine and its major metabolites may be quantified in blood, plasma, or urine to monitor for abuse, confirm a diagnosis of poisoning, or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. Most commercial cocaine immunoassay screening tests cross-react appreciably with the major cocaine metabolites, but chromatographic techniques can easily distinguish and separately measure each of these substances. When interpreting the results of a test, it is important to consider the cocaine usage history of the individual, since a chronic user can develop tolerance to doses that would incapacitate a cocaine-naive individual, and the chronic user often has high baseline values of the metabolites in his system. Cautious interpretation of testing results may allow a distinction between passive or active usage, and between smoking versus other routes of administration.<ref>R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 9th edition, Biomedical Publications, Seal Beach, California, 2011, pp. 390–394.</ref> In 2011, researchers at John Jay College of Criminal Justice reported that dietary zinc supplements can mask the presence of cocaine and other drugs in urine. Similar claims have been made in web forums on that topic.<ref>Venkatratnam, Abhishek; Nathan H. Lents (July 2011). "Zinc Reduces the Detection of Cocaine, Methamphetamine, and THC by ELISA Urine Testing". Journal of Analytical Toxicology. 35 (6): 333–340. PMID 21740689. doi:10.1093/anatox/35.6.333. Archived from the original on 18 May 2012. </ref>


Template:Global estimates of illicit drug users According to a 2007 United Nations report, Spain is the country with the highest rate of cocaine usage (3.0% of adults in the previous year).<ref name="unodc">World Drug Report 2007 (PDF). New York: United Nations. 2007. p. 243. Archived (PDF) from the original on 12 September 2012. Retrieved 31 December 2013. </ref> Other countries where the usage rate meets or exceeds 1.5% are the United States (2.8%), England and Wales (2.4%), Canada (2.3%), Italy (2.1%), Bolivia (1.9%), Chile (1.8%), and Scotland (1.5%).<ref name="unodc" />




About 3.5 million or 87.5% of those who have used the drug in the last yearTemplate:When are young adults (15–34 years old). Usage is particularly prevalent among this demographic: 4% to 7% of males have used cocaine in the last year in Spain, Denmark, Republic of Ireland, Italy, and the United Kingdom. The ratio of male to female users is approximately 3.8:1, but this statistic varies from 1:1 to 13:1 depending on country.<ref name="European Monitoring Centre for Drugs and Drug Addiction">The State of the Drugs Problem in Europe 2008 (PDF). Luxembourg: European Monitoring Centre for Drugs and Drug Addiction. 2008. pp. 58–62. Archived (PDF) from the original on 25 April 2013. Retrieved 31 December 2013. </ref>

In 2014 London had the highest amount of cocaine in its sewage out of 50 European cities.<ref>Dominic Casciani ( 4 June 2015). "Cocaine in sewage: London tops league table". BBC news. Archived from the original on 4 June 2015. Retrieved 4 June 2015. </ref>

United States

Cocaine is the second most popular illegal recreational drug in the United States (behind cannabis)<ref>"Cocaine & Crack". Archived from the original on 6 October 2007. Retrieved 10 July 2007. </ref> and the U.S. is the world's largest consumer of cocaine.<ref name="WFK Illicit drugs" /> Cocaine is commonly used in middle to upper-class communities and is known as a "rich man's drug". It is also popular amongst college students, as a party drug. A study throughout the entire United States has reported that around 48 percent of people who graduated high school in 1979 have used cocaine recreationally during some point in their lifetime, compared to approximately 20 percent of students who graduated between the years of 1980 and 1995.<ref>"McGraw-Hill Connect". </ref> 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.



For over a thousand years South American indigenous peoples have chewed the leaves of Erythroxylon coca, a plant that contains vital nutrients as well as numerous alkaloids, including cocaine. The coca leaf was, and still is, chewed almost universally by some indigenous communities. The remains of coca leaves have been found with ancient Peruvian mummies, and pottery from the time period depicts humans with bulged cheeks, indicating the presence of something on which they are chewing.<ref name="mummies">Altman AJ, Albert DM, Fournier GA (1985). "Cocaine's use in ophthalmology: our 100-year heritage". Surv Ophthalmol. 29 (4): 300–6. PMID 3885453. doi:10.1016/0039-6257(85)90153-5. </ref> There is also evidence that these cultures used a mixture of coca leaves and saliva as an anesthetic for the performance of trepanation.<ref name="trepanning">Gay GR, Inaba DS, Sheppard CW, Newmeyer JA (1975). "Cocaine: history, epidemiology, human pharmacology, and treatment. a perspective on a new debut for an old girl". Clin. Toxicol. 8 (2): 149–78. PMID 1097168. doi:10.3109/15563657508988061. </ref>

When the Spanish arrived in South America, most at first ignored aboriginal claims that the leaf gave them strength and energy, and declared the practice of chewing it the work of the Devil.<ref>Baselmans, John. Drugs. p. 55. ISBN 9781326843250. Archived from the original on 10 September 2017. </ref> But after discovering that these claims were true, they legalized and taxed the leaf, taking 10% off the value of each crop.<ref>"Drug that spans the ages: The history of cocaine". London: The Independent (UK). 2006. Archived from the original on 28 February 2010. Retrieved 30 April 2010. </ref> In 1569, Nicolás Monardes described the indigenous peoples' practice of chewing a mixture of tobacco and coca leaves to induce "great contentment":


In 1609, Padre Blas Valera wrote:

Coca protects the body from many ailments, and our doctors use it in powdered form to reduce the swelling of wounds, to strengthen broken bones, to expel cold from the body or prevent it from entering, and to cure rotten wounds or sores that are full of maggots. And if it does so much for outward ailments, will not its singular virtue have even greater effect in the entrails of those who eat it?<ref>"InterAndean Institute of Coca Sciences". Archived from the original on 30 December 2016. </ref>

Isolation and naming


The cocaine alkaloid was first isolated by the German chemist Friedrich Gaedcke in 1855. Gaedcke named the alkaloid "erythroxyline", and published a description in the journal Archiv der Pharmazie.<ref>Gaedcke, F. (1855). "Ueber das Erythroxylin, dargestellt aus den Blättern des in Südamerika cultivirten Strauches Erythroxylon Coca". Archiv der Pharmazie. 132 (2): 141–150. doi:10.1002/ardp.18551320208. </ref>



The first synthesis and elucidation of the structure of the cocaine molecule was by Richard Willstätter in 1898.<ref name="Humphrey2001" /> It was the first biomimetic synthesis of an organic structure recorded in academic chemical literature.<ref name="Singh2">Satendra Singh et al. Chemistry, Design, and Structure-Activity Relationship of Cocaine Antagonists." Chem. Rev 2000; 100. 925–1024. PubMed; Chemical Reviews (Impact Factor: 45.66). 04/2000; 100(3):925–1024 American Chemical Society; 2000 Archived 4 March 2016 at the Wayback Machine. Template:ISSN ChemInform; May, 16th 2000, Volume 31, Issue 20, Template:DOI. Mirror hotlink. Archived 3 July 2015 at the Wayback Machine. ←Page #970 (46th page of article) 1st ¶. ninth & tenth lines.</ref><ref>Willstatter, R. Leibigs Am. Chem. 1903, 326, 23. (b) Robinson, R. J. Chem. Soc. 1917, 111, 762. (c) Schopf, C.; Lehman, G. Liebigs Am. 1935, 518, 1.</ref> The synthesis started from tropinone, a related natural product and took five steps.




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 salt water. 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 salt water.<ref name="anrep_frog">Yentis SM, Vlassakov KV (1999). "Vassily von Anrep, forgotten pioneer of regional anesthesia". Anesthesiology. 90 (3): 890–5. PMID 10078692. doi:10.1097/00000542-199903000-00033. </ref>

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,<ref>Halsted W (1885). "Practical comments on the use and abuse of cocaine". New York Medical Journal. 42: 294–295. </ref> and James Leonard Corning demonstrated peridural anesthesia.<ref>Corning JL (1885). "An experimental study". New York Medical Journal. 42: 483. </ref> 1898 saw Heinrich Quincke use cocaine for spinal anesthesia.



Pope Leo XIII purportedly carried a hip flask of the coca-treated Vin Mariani with him, and awarded a Vatican gold medal to Angelo Mariani.<ref>"Experience Vin Mariani today | Grupo Mariani S.A". Archived from the original on 8 February 2011. Retrieved 15 January 2011. </ref>



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, in which he wrote that cocaine causes:<ref>"How a Young Sigmund Freud Researched & Got Addicted to Cocaine, the New “Miracle Drug,” in 1894". Open Culture. Archived from the original on 7 March 2017. </ref>

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.<ref>"Sigmund Freud and Cocaine". Archived from the original on 19 January 2017. </ref>




In early 20th-century Memphis, Tennessee, cocaine was sold in neighborhood drugstores on Beale Street, costing five or ten cents for a small boxful. Stevedores along the Mississippi River used the drug as a stimulant, and white employers encouraged its use by black laborers.<ref name= barlow>Barlow, William. "Looking Up At Down": The Emergence of Blues Culture. Temple University Press (1989), p. 207. Template:Catalog lookup linkScript error: No such module "check isxn"..</ref>

In 1909, Ernest Shackleton took "Forced March" brand cocaine tablets to Antarctica, as did Captain Scott a year later on his ill-fated journey to the South Pole.<ref name="dominic_streatfeild">Streatfeild, Dominic (2003). Cocaine: An Unauthorized Biography. Picador. ISBN 978-0-312-42226-4. </ref>

During the mid-1940s, amidst World War II, cocaine was considered for inclusion as an ingredient of a future generation of 'pep pills' for the German military, code named D-IX.<ref>"Jeevan Vasagar: cocaine-based "wonder drug" tested on concentration camp inmates". 19 November 2002. Archived from the original on 27 February 2011. Retrieved 15 January 2011. </ref>

In modern popular culture references to the drug are prevalent, in it the drug has a glamorous image associated with the rich, famous and powerful with it also making users to "feel rich and beautiful".<ref name=nyt1>Ryzik, Melena (10 June 2007). "Cocaine: Hidden in Plain Sight". The New York Times. Archived from the original on 11 August 2017. Retrieved 18 May 2017. </ref><ref>"The Buyers – A Social History Of America's Most Popular Drugs | Drug Wars | FRONTLINE | PBS". PBS. Archived from the original on 14 May 2017. Retrieved 18 May 2017. </ref><ref>Brisbane, Frances Larry; Womble, Maxine. Treatment of Black Alcoholics. Psychology Press. ISBN 9780866564038. Archived from the original on 10 September 2017. Retrieved 18 May 2017. </ref><ref>Waldorf, Dan; Reinarman, Craig; Murphy, Sheigla. Cocaine Changes: The Experience of Using and Quitting. Temple University Press. ISBN 9781566390132. Archived from the original on 10 September 2017. Retrieved 18 May 2017. </ref> In addition the pace of modern society − such as in finance − gives many the incentive to make use of the drug.<ref name=nyt1/>

Women purchase cocaine capsules in Berlin, 1924

Modern usage




The estimated U.S. cocaine market exceeded US$70 billion in street value for the year 2005, exceeding revenues by corporations such as Starbucks.<ref>"Apple Sanity – Fetish – Blow: War on Drugs VS. Cocaine". 17 June 2008. Archived from the original on 17 June 2008. Retrieved 13 November 2011. </ref><ref>"Cocaine Market". Archived from the original on 11 November 2012. Retrieved 9 March 2010. </ref> There is a tremendous demand for cocaine in the U.S. market, particularly among those who are making incomes affording luxury spending, such as single adults and professionals with discretionary income. Cocaine's status as a club drug shows its immense popularity among the "party crowd".


In October 2010 it was reported that the use of cocaine in Australia has doubled since monitoring began in 2003.<ref>"Cocaine use doubles in a decade". Sydney Morning Herald. 15 October 2010. Archived from the original on 18 October 2010. Retrieved 19 October 2010. </ref>


Society and culture

Legal status


Some countries, such as Peru and Bolivia permit the cultivation of coca leaf for traditional consumption by the local indigenous population, but nevertheless, prohibit the production, sale, and consumption of cocaine.<ref>Franklin, Jonathan (18 August 2009). "The world's first cocaine bar". The Guardian. ISSN 0261-3077. Archived from the original on 12 January 2017. Retrieved 23 December 2016. </ref> The provisions as to how much a coca farmer can yield annually is protected by laws such as the Bolivian Cato accord.<ref>Grisaffi, Thomas. "The Cato Accord: Bolivia's Humane and Effective Approach to Controlling Coca Cultivation" (PDF). Archived (PDF) from the original on 3 May 2016. Retrieved 12 January 2017. </ref> In addition, some parts of Europe and Australia allow processed cocaine for medicinal uses only.


Cocaine is a Schedule 8 prohibited substance in Australia under the Poisons Standard (July 2016).<ref name="Poisons Standard">Poisons Standard July 2016 Archived 19 January 2016 at the Wayback Machine.</ref> A schedule 8 substance is a controlled Drug – Substances which should be available for use but require restriction of manufacture, supply, distribution, possession and use to reduce abuse, misuse and physical or psychological dependence.<ref name="Poisons Standard" />

In Western Australia under the Misuse of Drugs Act 1981 4.0g of cocaine is the amount of prohibited drugs determining a court of trial, 2.0g is the amount of cocaine required for the presumption of intention to sell or supply and 28.0g is the amount of cocaine required for purposes of drug trafficking.<ref>Misuse of Drugs Act 1981 (2015) Archived 22 December 2015 at the Wayback Machine.</ref>

United States

The US federal government instituted a national labeling requirement for cocaine and cocaine-containing products through the Food and Drug Act of 1906.<ref name="Gootenberg 1999 37">Template:Harv</ref> 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.<ref name="Madge 2001 106">Template:Harv</ref> The Harrison Act did not recognize addiction as a treatable condition and therefore the therapeutic use of cocaine, heroin or morphine to such individuals was outlawed – leading the Journal of American Medicine to remark, "[the addict] is denied the medical care he urgently needs, open, above-board sources from which he formerly obtained his drug supply are closed to him, and he is driven to the underworld where he can get his drug, but of course, surreptitiously and in violation of the law."<ref>Template:Harv</ref> The Harrison Act left manufacturers of cocaine untouched so long as they met certain purity and labeling standards.<ref name="Gootenberg 1999 40">Template:Harv</ref> Despite that cocaine was typically illegal to sell and legal outlets were rarer, the quantities of legal cocaine produced declined very little.<ref name="Gootenberg 1999 40" /> Legal cocaine quantities did not decrease until the Jones–Miller Act of 1922 put serious restrictions on cocaine manufactures.<ref name="Gootenberg 1999 40" />


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.<ref name="un-wdr2006">"Cocaine: Seizures, 1998–2003". World Drug Report 2006 (PDF). 2. New York: United Nations. 2006. Archived (PDF) from the original on 14 June 2007. </ref>




Until 2012, Colombia was the world's leading producer of cocaine.<ref name="CIA World Factbook">Colombia Archived 13 May 2009 at the Wayback Machine.. CIA World Factbook</ref><ref name="NBC Worldnews">Peru Overtakes Colombia as Top Cocaine Producer. NBC News (31 July 2012) Archived 4 March 2016 at the Wayback Machine.</ref> Three-quarters of the world's annual yield of cocaine has been produced in Colombia, both from cocaine base imported from Peru (primarily the Huallaga Valley) and Bolivia, and from locally grown coca. There was a 28% increase from 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 is grown for traditional purposes by indigenous communities, a use which is still present and is permitted by Colombian laws only makes up a small fragment of total coca production, most of which is used for the illegal drug trade.[citation needed]




Estimated Andean region coca cultivation and potential pure cocaine production<ref>NDIC (2006). "National Drug Threat Assessment 2006". Archived from the original on 11 November 2010. </ref>
2000 2001 2002 2003 2004
Potential pure cocaine production (tonnes) 770 925 830 680 645

The latest estimate provided by the U.S. authorities on the annual production of cocaine in Colombia refers to 290 metric tons. As of the end of 2011, the seizure operations of Colombian cocaine carried out in different countries have totaled 351.8 metric tons of cocaine, i.e. 121.3% of Colombia's annual production according to the U.S. Department of State's estimates. <ref>"Cocaine Seized Worldwide Highest Ever in 2011". Flare Network ( 18 January 2012. Archived from the original on 6 January 2014. Retrieved 5 January 2014. </ref><ref>"Colombia". Archived from the original on 2 April 2013. Retrieved 26 March 2013. </ref>



Trafficking and distribution

Cocaine smuggled in a charango, 2008

Organized criminal gangs operating on a large scale dominate the cocaine trade. Most cocaine is grown and processed in South America, particularly in Colombia, Bolivia, Peru, and smuggled into the United States and Europe, the United States being the world's largest consumer of cocaine,<ref name="WFK Illicit drugs">"Field Listing – Illicit drugs (by country)". Archived from the original on 29 December 2010. Retrieved 15 January 2011. </ref> where it is sold at huge markups; usually in the US at $80–120 for 1 gram, and $250–300 for 3.5 grams (⅛ of an ounce, or an "eight ball").<ref>"How Much Is a Gram of Coke?". New Health Advisor. 3 September 2015. Archived from the original on 7 March 2017. </ref>

Caribbean and Mexican routes

As of 2005, cocaine shipments from South America transported through Mexico or Central America were generally moved over land or by air to staging sites in northern Mexico. The cocaine is then broken down into smaller loads for smuggling across the U.S.–Mexico border. The primary cocaine importation points in the United States have been in Arizona, southern California, southern Florida, and Texas. Typically, land vehicles are driven across the U.S.–Mexico border. Sixty-five percent of cocaine enters the United States through Mexico, and the vast majority of the rest enters through Florida.<ref>Jacobson, Robert (2005). Illegal Drugs: America's Anguish. Farmington Hills, Michigan: Thomson Gale. Template:Catalog lookup linkScript error: No such module "check isxn"..</ref>[page needed] As of 2015, the Sinaloa Cartel is the most active drug cartel involved in smuggling illicit drugs like cocaine into the United States and trafficking them throughout the United States.<ref name="DEA 2015 assessment">"2015 National Drug Threat Assessment Summary" (PDF). Drug Enforcement Administration. United States Department of Justice: Drug Enforcement Administration. October 2015. pp. 1–2. Archived (PDF) from the original on 10 April 2016. Retrieved 10 April 2016. 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. </ref>


Chilean route






Sales to consumers

Cocaine adulterated with fruit flavoring

Cocaine is readily available in all major countries' metropolitan areas. According to the Summer 1998 Pulse Check, published by the U.S. Office of National Drug Control Policy, cocaine use had stabilized across the country, with a few increases reported in San Diego, Bridgeport, Miami, and Boston. In the West, cocaine usage was lower, which was thought to be due to a switch to methamphetamine among some users; methamphetamine is cheaper, three and a half times more powerful, and lasts 12–24 times longer with each dose.<ref>"Meth Info". Archived from the original on 27 March 2010. </ref><ref>"Drugs of Abuse". City of Denison Iowa. Archived from the original on 6 November 2011. Retrieved 13 November 2011. </ref> Nevertheless, the number of cocaine users remain high, with a large concentration among urban youth.




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%.<ref>The Cocaine Threat: A Hemispheric Perspective (PDF). United States Department of Defense. Archived from the original (PDF) on 11 September 2008. </ref> It is estimated that 1.5 million people in the United States used cocaine in 2010 down from 2.4 million in 2006.<ref name="Zimmerman2012"/> Conversely, cocaine use appears to be increasing in Europe with the highest prevalences in Spain, the United Kingdom, Italy, and Ireland.<ref name="Zimmerman2012">Zimmerman, JL (October 2012). "Cocaine intoxication". Critical Care Clinics. 28 (4): 517–26. PMID 22998988. doi:10.1016/j.ccc.2012.07.003. </ref>

The 2010 UN World Drug Report concluded that "it appears that the North American cocaine market has declined in value from US$47 billion in 1998 to US$38 billion in 2008. Between 2006 and 2008, the value of the market remained basically stable".<ref name="Nations2010">United Nations (June 2010). World Drug Report 2010. United Nations Publications. p. 77. ISBN 978-92-1-148256-0. Archived from the original on 26 April 2016. </ref>


In 2005, researchers proposed the use of cocaine in conjunction with phenylephrine administered in the form of an eye drop as a diagnostic test for Parkinson's disease.<ref name="Sawada, H. 932–4">Sawada, H.; et al. (23 February 2005). "Cocaine and Phenylephrine Eye Drop Test for Parkinson Disease". JAMA: The Journal of the American Medical Association. Journal of the American Medical Association. 293 (8): 932–4. PMID 15728162. doi:10.1001/jama.293.8.932-c. </ref>

See also

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  • Gootenberg, Paul, ed. (1999). Cocaine: Global Histories. London: Routledge. ISBN 0-203-02646-2. 

Further reading


External links

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