a b Azizi SA (December 2020). "Monoamines: Dopamine, Norepinephrine, and Serotonin, Beyond Modulation, "Switches" That Alter the State of Target Networks". The Neuroscientist. 28 (2): 121–143. doi: 10.1177/1073858420974336. PMID 33292070. S2CID 228080727. Leete E, Bjorklund JA, Kim SH (1988). "The biosynthesis of the benzoyl moiety of cocaine". Phytochemistry. 27 (8): 2553–2556. Bibcode: 1988PChem..27.2553L. doi: 10.1016/0031-9422(88)87026-2. Jacobson R (2006). Illegal drugs: America's anguish (2005ed.). Farmingto

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". Clinical Toxicology. 8 (2): 149–78. doi: 10.3109/15563657508988061. PMID 1097168. a b Fattinger K, Benowitz NL, Jones RT, Verotta D (July 2000). "Nasal mucosal versus gastrointestinal absorption of nasally administered cocaine". European Journal of Clinical Pharmacology. 56 (4): 305–10. doi: 10.1007/s002280000147. PMID 10954344. S2CID 20708443.

Jeevan Vasagar: cocaine-based "wonder drug" tested on concentration camp inmates". Amphetamines.com. 19 November 2002. Archived from the original on 27 February 2011 . Retrieved 15 January 2011. Annual prevalence of use of drugs, by region and globally, 2016". World Drug Report 2018. United Nations Office on Drugs and Crime. 2018 . Retrieved 7 July 2018. 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. [139] Ornithine then undergoes a pyridoxal phosphate-dependent decarboxylation to form putrescine. In some animals, the urea cycle derives putrescine from ornithine. L-ornithine is converted to L-arginine, [140] which is then decarboxylated via PLP to form agmatine. Hydrolysis of the imine derives N-carbamoylputrescine followed with hydrolysis of the urea to form putrescine. The separate pathways of converting ornithine to putrescine in plants and animals have converged. A SAM-dependent N-methylation of putrescine gives the N-methylputrescine product, which then undergoes oxidative deamination by the action of diamine oxidase to yield the aminoaldehyde. Schiff base formation confirms the biosynthesis of the N-methyl-Δ 1-pyrrolinium cation. a b c d 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. doi: 10.1111/j.1365-2125.2010.03629.x. PMC 2856043. PMID 20573078. Omar Little: Well, you see, Mike-Mike thought he should keep that cocaine he was slingin’ and the money he was makin’ from slingin’ it. I thought otherwise.

Musto DF (1989). "America's First Cocaine Epidemic". The Wilson Quarterly. 13 (3): 59–64. JSTOR 40257908. PMID 11619697. a b Zhao W (2008). Mechanisms Mediating Sex Differences in the Effects of Cocaine. University of Michigan. p.3. ISBN 978-0-549-99458-9. Archived from the original on 4 April 2014 . Retrieved 25 September 2012. World Drug Report 2021: Booklet 4 (PDF). [S.l.]: United Nations Office on Drugs and Crime. 2021. p.35. ISBN 978-92-1-148361-1. Archived (PDF) from the original on 24 June 2021. World annual cocaine consumption, as of 2000, stood at around 600 tonnes, with the United States consuming around 300t, 50% of the total, Europe about 150t, 25% of the total, and the rest of the world the remaining 150t or 25%. [218] It is estimated that 1.5 million people in the United States used cocaine in 2010, down from 2.4 million in 2006. [12] Conversely, cocaine use appears to be increasing [ when?] in Europe with the highest prevalences in Spain, the United Kingdom, Italy, and Ireland. [12] The most popular form of taking powdered cocaine is “insufflation” — using rolled-up banknotes, straws, hollowed-out pens, long fingernails, specially designed spoons, and even tampon applicators. The drug is poured onto a flat surface and divided into “bumps“, “lines” or “rails” and snorted.

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Despite the legislation authorities remained relaxed about its use and prosecutions were rare. It was recognised for its ability to stave off fatigue and became increasingly popular among students and the music industry. WHO/UNICRI (4 February 2010). "The WHO Cocaine Project". Transnational Institute. Archived from the original on 9 August 2012 . Retrieved 8 June 2012.

Yentis SM, Vlassakov KV (March 1999). "Vassily von Anrep, forgotten pioneer of regional anesthesia". Anesthesiology. 90 (3): 890–5. doi: 10.1097/00000542-199903000-00033. PMID 10078692. Rolled up banknotes, hollowed-out pens, cut straws, pointed ends of keys, specialized spoons, [53] long fingernails, and (clean) tampon applicators are often used to insufflate cocaine. The cocaine typically is poured onto a flat, hard surface (such as a mobile phone screen, mirror, CD case or book) and divided into "bumps", "lines" or "rails", and then insufflated. [54] A 2001 study reported that the sharing of straws used to "snort" cocaine can spread blood diseases such as hepatitis C. [55] Injection Hesse M (2002). Alkaloids: Nature's Curse or Blessing?. Weinheim: Wiley-VCH. p.304. ISBN 978-3-906390-24-6. Illicitly-sold cocaine may be contaminated with levamisole. [81] Levamisole may accentuate cocaine's effects. [82] Levamisole-adulterated cocaine has been associated with autoimmune disease. [83]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. [192] The provisions as to how much a coca farmer can yield annually is protected by laws such as the Bolivian Cato accord. [193] In addition, some parts of Europe, the United States, and Australia allow processed cocaine for medicinal uses only. Misuse of Drugs Act 1981" (PDF). Slp.wa.gov.au. 2015. Archived from the original (PDF) on 22 December 2015. 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). [150] 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%). [150] Europe 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.

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. [161] In 1569, Spanish botanist Nicolás Monardes described the indigenous peoples' practice of chewing a mixture of tobacco and coca leaves to induce "great contentment": 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. [145] Field analysis 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. [169] Medicalization "Cocaine toothache drops", 1885 advertisement of cocaine for dental pain in children Advertisement in the January 1896 issue of McClure's Magazine for Burnett's Cocaine "for the hair" Bottle of cocaine solution, Germany, circa 1915EMCDDA (2007). "EMCDDA Retail Cocaine Purity Study". Archived from the original on 1 January 2014 . Retrieved 31 December 2013. Ambre J, Ruo TI, Nelson J, Belknap S (November 1988). "Urinary excretion of cocaine, benzoylecgonine, and ecgonine methyl ester in humans". Journal of Analytical Toxicology. 12 (6): 301–6. doi: 10.1093/jat/12.6.301. PMID 3244269. Valdez LM, Taboada J, Valdez JE (June 2015). "Ancient Use of Coca Leaves in the Peruvian Central Highlands". Journal of Anthropological Research. 71 (2): 231–258. doi: 10.3998/jar.0521004.0071.204. S2CID 163842955. There are also warnings about the threat of breastfeeding: The March of Dimes said "it is likely that cocaine will reach the baby through breast milk," and advises the following regarding cocaine use during pregnancy: The onset of cocaine's euphoric effects is fastest with inhalation, beginning after 3–5 seconds. [12] However, inhalation gives the shortest duration of euphoria (5–15 minutes). [12] Cocaine is smoked by inhaling the vapor produced when free base cocaine is heated to the point of sublimation. [57] In a 2000 Brookhaven National Laboratory medical department study, based on self-reports of 32 people who used cocaine who participated in the study, "peak high" was found at a mean of 1.4±0.5minutes. [52] 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 M 1 — and M 3 — receptor affinity. [58]