Cocaine is a stimulant derived from the coca plant. It acts as a serotonin-norepinephrine-dopamine reuptake inhibitor. Acute effects include increased alertness and euphoria, while chronic use can cause depression, addiction, and various physical harms. Cocaine is internationally controlled and highly addictive due to its effects on the brain's reward pathway. The biosynthesis of cocaine begins with amino acids and involves an acetyl-CoA dependent condensation and cyclization reaction to form the tropane ring system found in cocaine.
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Cocaine is a stimulant derived from the coca plant. It acts as a serotonin-norepinephrine-dopamine reuptake inhibitor. Acute effects include increased alertness and euphoria, while chronic use can cause depression, addiction, and various physical harms. Cocaine is internationally controlled and highly addictive due to its effects on the brain's reward pathway. The biosynthesis of cocaine begins with amino acids and involves an acetyl-CoA dependent condensation and cyclization reaction to form the tropane ring system found in cocaine.
Cocaine is a stimulant derived from the coca plant. It acts as a serotonin-norepinephrine-dopamine reuptake inhibitor. Acute effects include increased alertness and euphoria, while chronic use can cause depression, addiction, and various physical harms. Cocaine is internationally controlled and highly addictive due to its effects on the brain's reward pathway. The biosynthesis of cocaine begins with amino acids and involves an acetyl-CoA dependent condensation and cyclization reaction to form the tropane ring system found in cocaine.
Copyright:
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Cocaine is a stimulant derived from the coca plant. It acts as a serotonin-norepinephrine-dopamine reuptake inhibitor. Acute effects include increased alertness and euphoria, while chronic use can cause depression, addiction, and various physical harms. Cocaine is internationally controlled and highly addictive due to its effects on the brain's reward pathway. The biosynthesis of cocaine begins with amino acids and involves an acetyl-CoA dependent condensation and cyclization reaction to form the tropane ring system found in cocaine.
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carboxyate Cnca data AHFS/Drugs.com Mcromedex Detaed Consumer Informaton Pregnancy cat. C Lega status Controed (S8) (AU) Schedue I (CA) A (UK) Schedue II (US) Narcotc Schedues I and III (UN) Dependence abty Hgh Routes Topca, Ora, Insuffaton, IV, PO Pharmacoknetc data Boavaabty Ora: 33%|1| Insuffated: 60|2|-80%|3| Nasa Spray: 25|4|-43%|1| Metabosm Hepatc CYP3A4 Haf-fe 1 hour Excreton Rena (benzoyecgonne and ecgonne methy ester) Synonyms methybenzoyecgonne, benzoymethyecgonne, ecgonne methy ester benzoate, 2b-Carbomethoxy -3b-benzoyoxy tropane Chemca data Formua C17H21NO4 Mo. mass 303.353 g/mo Cocane (INN) (benzoymethyecgonne, an ecgonne dervatve) s a crystane tropane akaod that s obtaned from the eaves of the coca pant. |5| The name comes from "coca" and the akaod suffx "-ne", formng "cocane". It s a stmuant, an appette suppressant, and a nonspecfc votage gated sodum channe bocker, whch n turn causes t to produce anaesthesa at ow doses. Boogcay, cocane acts as a serotonn- norepnephrne-dopamne reuptake nhbtor, aso known as a trpe reuptake nhbtor (TRI). It s addctve because of ts effect on the mesombc reward pathway.|6| It s markedy more dangerous than other CNS stmuants, ncudng the amphetamne cass, at hgh doses due to ts effect on sodum channes, as bockade of Nav1.5 can cause sudden cardac death.|7| Unke most moecues, cocane has pockets|carfcaton needed| wth both hgh hydrophc and pophc effcency, voatng the rue of hydrophc- pophc baance. Ths causes t to cross the bood-bran barrer far better than other psychoactve chemcas|ctaton needed| and may even nduce bood-bran barrer breakdown.|8||9| It s controed nternatonay by Snge Conventon on Narcotc Drugs (Schedue I, preparaton n Schedue III). Medca effects Data from The Lancet suggests cocane s ranked both the 2nd most addctve and the 2nd most harmfu of 20 popuar recreatona drugs.|10| Cocane s a powerfu nervous system stmuant.|11| Its effects can ast from 15-30 mnutes to an hour, dependng on dosage and the route of admnstraton.|12| Cocane ncreases aertness, feengs of we-beng and euphora, energy and motor actvty, feengs of competence and sexuaty. Anxety, paranoa and restessness can aso occur, especay durng the comedown. Wth excessve dosage, tremors, convusons and ncreased body temperature are observed. |11| Severe cardac adverse events, partcuary sudden cardac death, become a serous rsk at hgh doses due to cocane's bockng effect on cardac sodum channes.|7| Occasona cocane use does not typcay ead to severe or even mnor physca or soca probems.|13||14| Acute Man artce: Cocane ntoxcaton Wth excessve or proonged use, the drug can cause tchng, tachycarda, haucnatons, and paranod deusons.|15| Overdoses cause hypertherma and a marked eevaton of bood pressure, whch can be fe-threatenng,|15| arrhythmas,|7| and death.|7| Chronc Sde effects of chronc cocane use Cocane hydrochorde Chronc cocane ntake causes bran ces to adapt functonay to strong mbaances of transmtter eves n order to compensate extremes. Thus, receptors dsappear from the ce surface or reappear on t, resutng more or ess n an "off" or "workng mode" respectvey, or they change ther susceptbty for bndng partners (gands) - mechansms caed down-/upreguaton. However, studes suggest cocane abusers do not show norma age-reated oss of strata dopamne transporter (DAT) stes, suggestng cocane has neuroprotectve propertes for dopamne neurons.|16| Possbe sde effects ncude nsatabe hunger, aches, nsomna/overseepng, ethargy, and persstent runny nose. Depresson wth sucda deaton may deveop n very heavy users. Fnay, a oss of vescuar monoamne transporters, neurofament protens, and other morphoogca changes appear to ndcate a ong term damage of dopamne neurons. A these effects contrbute a rse n toerance thus requrng a arger dosage to acheve the same effect.|17| The ack of norma amounts of serotonn and dopamne n the bran s the cause of the dysphora and depresson fet after the nta hgh. Physca wthdrawa s not dangerous. Physoogca changes caused by cocane wthdrawa ncude vvd and unpeasant dreams, nsomna or hypersomna, ncreased appette and psychomotor retardaton or agtaton.|18| Physca sde effects from chronc smokng of cocane ncude hemoptyss, bronchospasm, prurtus, fever, dffuse aveoar nftrates wthout effusons, pumonary and systemc eosnopha, chest pan, ung trauma, sore throat, asthma, hoarse voce, dyspnea (shortness of breath), and an achng, fu-ke syndrome. Cocane constrcts bood vesses, dates pups, and ncreases body temperature, heart rate, and bood pressure. It can aso cause headaches and gastrontestna compcatons such as abdomna pan and nausea. A common but untrue beef s that the smokng of cocane chemcay breaks down tooth ename and causes tooth decay. However, cocane does often cause nvountary tooth grndng, known as bruxsm, whch can deterorate tooth ename and ead to gngvts.|19| Addtonay, stmuants ke cocane, methamphetamne, and even caffene cause dehydraton and dry mouth. Snce sava s an mportant mechansm n mantanng one's ora pH eve, chronc stmuant abusers who do not hydrate suffcenty may experence demnerazaton of ther teeth due to the pH of the tooth surface droppng too ow (beow 5.5). Chronc ntranasa usage can degrade the cartage separatng the nostrs (the septum nas), eadng eventuay to ts compete dsappearance. Due to the absorpton of the cocane from cocane hydrochorde, the remanng hydrochorde forms a dute hydrochorc acd.|20| Cocane may aso greaty ncrease ths rsk of deveopng rare autommune or connectve tssue dseases such as upus, Goodpasture's dsease, vascuts, gomeruonephrts, Stevens-|ohnson syndrome and other dseases.|21||22| |23||24| It can aso cause a wde array of kdney dseases and rena faure. |25||26| Cocane msuse doubes both the rsks of hemorrhagc and schemc strokes, |27| as we as ncreases the rsk of other nfarctons, such as myocarda nfarcton.|28| Addcton Man artce: Cocane dependence Cocane dependence (or addcton) s psychoogca dependency on the reguar use of cocane. Cocane dependency may resut n physoogca damage, ethargy, psychoss, depresson, akathsa, and fata overdose. Bosynthess Man artce: Bosynthess of cocane The frst synthess and eucdaton of the cocane moecue was by Rchard Wsttter n 1898.|29| Wsttter's synthess derved cocane from tropnone. Snce then, Robert Robnson and Edward Leete have made sgnfcant contrbutons to the mechansm of the synthess. (-NO3) The addtona carbon atoms requred for the synthess of cocane are derved from acety-CoA, by addton of two acety-CoA unts to the N-methy-A1- pyrronum caton.|30| The frst addton s a Mannch-ke reacton wth the enoate anon from acety-CoA actng as a nuceophe towards the pyrronum caton. The second addton occurs through a Casen condensaton. Ths produces a racemc mxture of the 2-substtuted pyrrodne, wth the retenton of the thoester from the Casen condensaton. In formaton of tropnone from racemc ethy |2,3-13C2|4(Nmethy-2- pyrrodny)-3-oxobutanoate there s no preference for ether stereosomer. |31| In the bosynthess of cocane, however, ony the (S)-enantomer can cycze to form the tropane rng system of cocane. The stereoseectvty of ths reacton was further nvestgated through study of prochra methyene hydrogen dscrmnaton.|32| Ths s due to the extra chra center at C-2.|33| Ths process occurs through an oxdaton, whch regenerates the pyrronum caton and formaton of an enoate anon, and an ntramoecuar Mannch reacton. The tropane rng system undergoes hydroyss, SAM-dependent methyaton, and reducton va NADPH for the formaton of methyecgonne. The benzoy moety requred for the formaton of the cocane dester s syntheszed from phenyaanne va cnnamc acd.|34| Benzoy-CoA then combnes the two unts to form cocane. N-methy-pyrronum caton Bosynthess of N-methy-pyrronum caton Bosynthess of cocane Robnson bosynthess of tropane Reducton of tropnone The bosynthess begns wth L-Gutamne, whch s derved to L-ornthne n pants. The ma|or contrbuton of L-ornthne and L-argnne as a precursor to the tropane rng was confrmed by Edward Leete.|35| Ornthne then undergoes a Pyrdoxa phosphate-dependent decarboxyaton to form putrescne. In anmas, however, the urea cyce derves putrescne from ornthne. L-ornthne s converted to L-argnne,|36| whch s then decarboxyated va PLP to form agmatne. Hydroyss of the mne derves N- carbamoyputrescne foowed wth hydroyss of the urea to form putrescne. The separate pathways of convertng ornthne to putrescne n pants and anmas have converged. A SAM-dependent N-methyaton of putrescne gves the N-methyputrescne product, whch then undergoes oxdatve deamnaton by the acton of damne oxdase to yed the amnoadehyde. Schff base formaton confrms the bosynthess of the N-methy-A1-pyrronum caton. Robert Robnson's acetonedcarboxyate The bosynthess of the tropane akaod, however, s st uncertan. Hemschedt proposes that Robnson's acetonedcarboxyate emerges as a potenta ntermedate for ths reacton.|37| Condensaton of N- methypyrronum and acetonedcarboxyate woud generate the oxobutyrate. Decarboxyaton eads to tropane akaod formaton. Reducton of tropnone The reducton of tropnone s medated by NADPH-dependent reductase enzymes, whch have been characterzed n mutpe pant speces.|38| These pant speces a contan two types of the reductase enzymes, tropnone reductase I and tropnone reductase II. TRI produces tropne and TRII produces pseudotropne. Due to dfferng knetc and pH/actvty characterstcs of the enzymes and by the 25-fod hgher actvty of TRI over TRII, the ma|orty of the tropnone reducton s from TRI to form tropne.|39| Pharmacoogy Appearance A pe of cocane hydrochorde A pece of compressed cocane powder Cocane n ts purest form s a whte, peary product. Cocane appearng n powder form s a sat, typcay cocane hydrochorde (CAS 53-21-4). Street market cocane s frequenty aduterated or "cut" wth varous powdery fers to ncrease ts weght; the substances most commony used n ths process are bakng soda; sugars, such as actose, dextrose, nosto, and mannto; and oca anesthetcs, such as docane or benzocane, whch mmc or add to cocane's numbng effect on mucous membranes. Cocane may aso be "cut" wth other stmuants such as methamphetamne.|40| Aduterated cocane s often a whte, off-whte or pnksh powder. The coor of "crack" cocane depends upon severa factors ncudng the orgn of the cocane used, the method of preparaton - wth ammona or bakng soda - and the presence of mpurtes, but w generay range from whte to a yeowsh cream to a ght brown. Its texture w aso depend on the aduterants, orgn and processng of the powdered cocane, and the method of convertng the base. It ranges from a crumby texture, sometmes extremey oy, to a hard, amost crystane nature. Forms Sats Cocane s a weaky akane compound (an "akaod"), and can therefore combne wth acdc compounds to form varous sats. The hydrochorde (HC) sat of cocane s by far the most commony encountered, athough the sufate (-SO4) and the ntrate (-NO3) are occasonay seen. Dfferent sats dssove to a greater or esser extent n varous sovents - the hydrochorde sat s poar n character and s qute soube n water. Basc Man artce: Freebase (chemstry) As the name mpes, "freebase" s the base form of cocane, as opposed to the sat form. It s practcay nsoube n water whereas hydrochorde sat s water soube. Smokng freebase cocane has the addtona effect of reeasng methyecgondne nto the user's system due to the pyroyss of the substance (a sde effect whch nsuffatng or n|ectng powder cocane does not create). Some research suggests that smokng freebase cocane can be even more cardotoxc than other routes of admnstraton|41| because of methyecgondne's effects on ung tssue|42| and ver tssue.|43| Pure cocane s prepared by neutrazng ts compoundng sat wth an akane souton whch w precptate to non-poar basc cocane. It s further refned through aqueous-sovent Lqud-qud extracton. Crack cocane Man artce: Crack cocane A woman smokng crack cocane Crack s a ower purty form of free-base cocane that s usuay produced by neutrazaton of cocane hydrochorde wth a souton of bakng soda (sodum bcarbonate, NaHCO3) and water, producng a very hard/brtte, off-whte-to- brown coored, amorphous matera that contans sodum carbonate, entrapped water, and other by-products as the man mpurtes. The "freebase" and "crack" forms of cocane are usuay admnstered by vaporzaton of the powdered substance nto smoke, whch s then nhaed. |44| The orgn of the name "crack" comes from the "crackng" sound (and hence the onomatopoec monker "crack") that s produced when the cocane and ts mpurtes (.e. water, sodum bcarbonate) are heated past the pont of vaporzaton.|45| Pure cocane base/crack can be smoked because t vaporzes smoothy, wth tte or no decomposton at 98 C (208 F),|46| whch s beow the bong pont of water. The smoke produced from cocane base s usuay descrbed as havng a very dstnctve, peasant taste. In contrast, cocane hydrochorde does not vaporze unt heated to a much hgher temperature (about 197C), and consderabe decomposton/burnng occurs at these hgh temperatures. Ths effectvey destroys some of the cocane, and yeds a sharp, acrd, and fou-tastng smoke. Smokng or vaporzng cocane and nhang t nto the ungs produces an amost mmedate "hgh" that can be very powerfu (and addctng) qute rapdy - ths nta crescendo of stmuaton s known as a "rush". Whe the stmuatng effects may ast for hours, the euphorc sensaton s very bref, promptng the user to smoke more mmedatey. Coca eaf nfusons Oueston book-new.svg Ths secton does not cte any references or sources. Pease hep mprove ths secton by addng ctatons to reabe sources. Unsourced matera may be chaenged and removed. (December 2012) Coca herba nfuson (aso referred to as coca tea) s used n coca-eaf producng countres much as any herba medcna nfuson woud esewhere n the word. The free and ega commercazaton of dred coca eaves under the form of ftraton bags to be used as "coca tea" has been actvey promoted by the governments of Peru and Bova for many years as a drnk havng medcna powers. Vstors to the cty of Cuzco n Peru, and La Paz n Bova are greeted wth the offerng of coca eaf nfusons (prepared n tea pots wth whoe coca eaves) purportedy to hep the newy arrved traveer overcome the maase of hgh attude sckness. The effects of drnkng coca tea are a md stmuaton and mood ft. It does not produce any sgnfcant numbng of the mouth nor does t gve a rush ke snortng cocane. In order to prevent the demonzaton of ths product, ts promoters pubcze the unproven concept that much of the effect of the ngeston of coca eaf nfuson woud come from the secondary akaods, as beng not ony quanttatvey dfferent from pure cocane but aso quatatvey dfferent. It has been promoted as an ad|uvant for the treatment of cocane dependence. In one controversa study, coca eaf nfuson was used -n addton to counseng- to treat 23 addcted coca-paste smokers n Lma, Peru. Reapses fe from an average of four tmes per month before treatment wth coca tea to one durng the treatment. The duraton of abstnence ncreased from an average of 32 days pror to treatment to 217 days durng treatment. These resuts suggest that the admnstraton of coca eaf nfuson pus counseng woud be an effectve method for preventng reapse durng treatment for cocane addcton. Importanty, these resuts aso suggest strongy that the prmary pharmacoogcay actve metabote n coca eaf nfusons s actuay cocane and not the secondary akaods. The cocane metabote benzoyecgonne can be detected n the urne of peope a few hours after drnkng one cup of coca eaf nfuson. Routes of admnstraton Ora A spoon contanng bakng soda, cocane, and a sma amount of water. Used n a "poor-man's" crack-cocane producton Many users rub the powder aong the gum ne, or onto a cgarette fter whch s then smoked, whch numbs the gums and teeth - hence the cooqua names of "numbes", "gummers" or "cocoa puffs" for ths type of admnstraton. Ths s mosty done wth the sma amounts of cocane remanng on a surface after nsuffaton. Another ora method s to wrap up some cocane n rong paper and swaow (parachute) t. Ths s sometmes caed a "snow bomb." Coca eaf Coca eaves are typcay mxed wth an akane substance (such as me) and chewed nto a wad that s retaned n the mouth between gum and cheek (much n the same as chewng tobacco s chewed) and sucked of ts |uces. The |uces are absorbed sowy by the mucous membrane of the nner cheek and by the gastrontestna tract when swaowed. Aternatvey, coca eaves can be nfused n qud and consumed ke tea. Ingestng coca eaves generay s an neffcent means of admnsterng cocane. Advocates of the consumpton of the coca eaf state that coca eaf consumpton shoud not be crmnazed as t s not actua cocane, and consequenty t s not propery the ct drug. Because cocane s hydroyzed and rendered nactve n the acdc stomach, t s not ready absorbed when ngested aone. Ony when mxed wth a hghy akane substance (such as me) can t be absorbed nto the boodstream through the stomach. The effcency of absorpton of oray admnstered cocane s mted by two addtona factors. Frst, the drug s party catabozed by the ver. Second, capares n the mouth and esophagus constrct after contact wth the drug, reducng the surface area over whch the drug can be absorbed. Nevertheess, cocane metabotes can be detected n the urne of sub|ects that have spped even one cup of coca eaf nfuson. Therefore, ths s an actua addtona form of admnstraton of cocane, abet an neffcent one. Oray admnstered cocane takes approxmatey 30 mnutes to enter the boodstream. Typcay, ony a thrd of an ora dose s absorbed, athough absorpton has been shown to reach 60% n controed settngs. Gven the sow rate of absorpton, maxmum physoogca and psychotropc effects are attaned approxmatey 60 mnutes after cocane s admnstered by ngeston. Whe the onset of these effects s sow, the effects are sustaned for approxmatey 60 mnutes after ther peak s attaned. Contrary to popuar beef, both ngeston and nsuffaton resut n approxmatey the same proporton of the drug beng absorbed: 30 to 60%. Compared to ngeston, the faster absorpton of nsuffated cocane resuts n qucker attanment of maxmum drug effects. Snortng cocane produces maxmum physoogca effects wthn 40 mnutes and maxmum psychotropc effects wthn 20 mnutes, however, a more reastc actvaton perod s coser to 5 to 10 mnutes, whch s smar to ngeston of cocane. Physoogca and psychotropc effects from nasay nsuffated cocane are sustaned for approxmatey 40-60 mnutes after the peak effects are attaned.|47| Coca tea, an nfuson of coca eaves, s aso a tradtona method of consumpton. The tea has often been recommended for traveers n the Andes to prevent attude sckness.|48| However, ts actua effectveness has never been systematcay studed.|48| Ths method of consumpton has been practced for many centures by the natve trbes of South Amerca. One specfc purpose of ancent coca eaf consumpton was to ncrease energy and reduce fatgue n messengers who made mut-day quests to other settements. In 1986 an artce n the |ourna of the Amercan Medca Assocaton reveaed that U.S. heath food stores were seng dred coca eaves to be prepared as an nfuson as "Heath Inca Tea."|49| Whe the packagng camed t had been "decocanzed," no such process had actuay taken pace. The artce stated that drnkng two cups of the tea per day gave a md stmuaton, ncreased heart rate, and mood eevaton, and the tea was essentay harmess. Despte ths, the DEA sezed severa shpments n Hawa, Chcago, Inos, Georga, and severa ocatons on the East Coast of the Unted States, and the product was removed from the sheves. Insuffaton A man snffng cocane Nasa nsuffaton (known cooquay as "snortng," "snffng," or "bowng") s the most common method of ngeston of recreatona powdered cocane n the Western word. The drug coats and s absorbed through the mucous membranes nng the snuses. When nsuffatng cocane, absorpton through the nasa membranes s approxmatey 30-60%, wth hgher doses eadng to ncreased absorpton effcency. Any matera not drecty absorbed through the mucous membranes s coected n mucus and swaowed (ths "drp" s consdered peasant by some and unpeasant by others). In a study|50| of cocane users, the average tme taken to reach peak sub|ectve effects was 14.6 mnutes. Any damage to the nsde of the nose s because cocane hghy constrcts bood vesses - and therefore bood and oxygen/nutrent fow - to that area. Nosebeeds after cocane nsuffaton are due to rrtaton and damage of mucus membranes by foregn partces and aduterants and not the cocane tsef; as a vasoconstrctor, cocane acts to reduce beedng. Pror to nsuffaton, cocane powder must be dvded nto very fne partces. Cocane of hgh purty breaks nto fne dust very easy, except when t s most (not we stored) and forms "chunks," whch reduces the effcency of nasa absorpton. Roed up banknotes, hoowed-out pens, cut straws, ponted ends of keys, specazed spoons, ong fngernas, and (cean) tampon appcators are often used to nsuffate cocane. Such devces are often caed "tooters" by users. The cocane typcay s poured onto a fat, hard surface (such as a mrror, CD case or book) and dvded nto "bumps", "nes" or "ras", and then nsuffated.|51| The amount of cocane n a ne vares wdey from person to person and occason to occason (the purty of the cocane s aso a factor), but one ne s generay consdered to be a snge dose and s typcay 35 mg (a "bump") to 100 mg (a "ra")|dubous - dscuss|. As toerance buds rapdy n the short-term (hours), many nes are often snorted to produce greater effects. A study by Bonkovsky and Mehta|52| reported that, |ust ke shared needes, the sharng of straws used to "snort" cocane can spread bood dseases such as Hepatts C. In|ecton Drug n|ecton provdes the hghest bood eves of drug n the shortest amount of tme. Sub|ectve effects not commony shared wth other methods of admnstraton ncude a rngng n the ears moments after n|ecton (usuay when n excess of 120 mgrams) astng 2 to 5 mnutes ncudng tnntus & audo dstorton. Ths s cooquay referred to as a "be rnger". |53| In a study|50| of cocane users, the average tme taken to reach peak sub|ectve effects was 3.1 mnutes. The euphora passes qucky. Asde from the toxc effects of cocane, there s aso danger of crcuatory embo from the nsoube substances that may be used to cut the drug. As wth a n|ected ct substances, there s a rsk of the user contractng bood-borne nfectons f stere n|ectng equpment s not avaabe or used. Addtonay, because cocane s a vasoconstrctor, and usage often entas mutpe n|ectons wthn severa hours or ess, subsequent n|ectons are progressvey more dffcut to admnster, whch n turn may ead to more n|ecton attempts and more sequeae from mpropery performed n|ecton. An n|ected mxture of cocane and heron, known as "speedba" s a partcuary dangerous combnaton, as the converse effects of the drugs actuay compement each other, but may aso mask the symptoms of an overdose. It has been responsbe for numerous deaths, ncudng ceebrtes such as |ohn Beush, Chrs Farey, Mtch Hedberg, Rver Phoenx and Layne Staey. Expermentay, cocane n|ectons can be devered to anmas such as frut fes to study the mechansms of cocane addcton.|54| Inhaaton See aso: Crack cocane Inhaaton or smokng s one of the severa means cocane s admnstered. Cocane s smoked by nhang the vapor by submatng sod cocane by heatng.|55| In a 2000 Brookhaven Natona Laboratory medca department study, based on sef reports of 32 abusers who partcpated n the study,"peak hgh" was found at mean of 1.4mn +/- 0.5 mnutes.|50| Smokng freebase or crack cocane s most often accompshed usng a ppe made from a sma gass tube, often taken from "Love roses," sma gass tubes wth a paper rose that are promoted as romantc gfts.|56| These are sometmes caed "stems", "horns", "basters" and "straght shooters". A sma pece of cean heavy copper or occasonay staness stee scourng pad - often caed a "bro" (actua Bro pads contan soap, and are not used), or "chore", named for Chore Boy brand copper scourng pads, - serves as a reducton base and fow moduator n whch the "rock" can be meted and boed to vapor. Crack smokers aso sometmes smoke through a soda can wth sma hoes n the bottom. Crack s smoked by pacng t at the end of the ppe; a fame hed cose to t produces vapor, whch s then nhaed by the smoker. The effects, fet amost mmedatey after smokng, are very ntense and do not ast ong - usuay 5 to 15 mnutes. When smoked, cocane s sometmes combned wth other drugs, such as cannabs, often roed nto a |ont or bunt. Powdered cocane s aso sometmes smoked, though heat destroys much of the chemca; smokers often sprnke t on cannabs. The anguage referrng to paraphernaa and practces of smokng cocane vary, as do the packagng methods n the street eve sae. Suppostory Ltte research has been focused on the suppostory (ana or vagna nserton) method of admnstraton, aso known as "puggng". Ths method of admnstraton s commony admnstered usng an ora syrnge. Cocane can be dssoved n water and wthdrawn nto an ora syrnge whch may then be ubrcated and nserted nto the anus or vagna before the punger s pushed. Anecdota evdence of ts effects are nfrequenty dscussed, possby due to soca taboos n many cutures. The rectum and the vagna cana s where the ma|orty of the drug woud key be taken up, through the membranes nng ts was.|ctaton needed| Mechansm of acton Cocane bnds drecty to the DAT1 transporter, nhbtng reuptake wth more effcacy than amphetamnes whch phosphoryate t causng nternazaton; nstead prmary reeasng DAT (whch cocane does not do) and ony nhbtng ts reuptake as a secondary, and much more mnor, mode of acton than cocane and n another manner: from the opposte conformaton/orentaton to DAT. The pharmacodynamcs of cocane nvove the compex reatonshps of neurotransmtters (nhbtng monoamne uptake n rats wth ratos of about: serotonn:dopamne = 2:3, serotonn:norepnephrne = 2:5|57|) The most extensvey studed effect of cocane on the centra nervous system s the bockade of the dopamne transporter proten. Dopamne transmtter reeased durng neura sgnang s normay recyced va the transporter; .e., the transporter bnds the transmtter and pumps t out of the synaptc ceft back nto the presynaptc neuron, where t s taken up nto storage vesces. Cocane bnds tghty at the dopamne transporter formng a compex that bocks the transporter's functon. The dopamne transporter can no onger perform ts reuptake functon, and thus dopamne accumuates n the synaptc ceft. Ths resuts n an enhanced and proonged postsynaptc effect of dopamnergc sgnang at dopamne receptors on the recevng neuron. Proonged exposure to cocane, as occurs wth habtua use, eads to homeostatc dysreguaton of norma (.e. wthout cocane) dopamnergc sgnang va down-reguaton of dopamne receptors and enhanced sgna transducton. The decreased dopamnergc sgnang after chronc cocane use may contrbute to depressve mood dsorders and senstze ths mportant bran reward crcut to the renforcng effects of cocane (for exampe, enhanced dopamnergc sgnang ony when cocane s sef-admnstered). Ths senstzaton contrbutes to the ntractabe nature of addcton and reapse. Dopamne-rch bran regons such as the ventra tegmenta area, nuceus accumbens, and prefronta cortex are frequent targets of cocane addcton research. Of partcuar nterest s the pathway consstng of dopamnergc neurons orgnatng n the ventra tegmenta area that termnate n the nuceus accumbens. Ths pro|ecton may functon as a "reward center", n that t seems to show actvaton n response to drugs of abuse ke cocane n addton to natura rewards ke food or sex.|58| Whe the precse roe of dopamne n the sub|ectve experence of reward s hghy controversa among neuroscentsts, the reease of dopamne n the nuceus accumbens s wdey consdered to be at east partay responsbe for cocane's rewardng effects. Ths hypothess s argey based on aboratory data nvovng rats that are traned to sef-admnster cocane. If dopamne antagonsts are nfused drecty nto the nuceus accumbens, we-traned rats sef-admnsterng cocane w undergo extncton (.e. ntay ncrease respondng ony to stop competey) thereby ndcatng that cocane s no onger renforcng (.e. rewardng) the drug-seekng behavor. Cocane's effects on serotonn (5-hydroxytryptamne, 5-HT) show across mutpe serotonn receptors, and s shown to nhbt the re-uptake of 5-HT3 specfcay as an mportant contrbutor to the effects of cocane. The overabundance of 5-HT3 receptors n cocane condtoned rats dspay ths trat, however the exact effect of 5-HT3 n ths process s uncear.|59| The 5- HT2 receptor (partcuary the subtypes 5-HT2AR, 5-HT2BR and 5-HT2CR) show nfuence n the evocaton of hyperactvty dspayed n cocane use.|60| In addton to the mechansm shown on the above chart, cocane has been demonstrated to bnd as to drecty stabze the DAT transporter on the open outward-facng conformaton whereas other stmuants (namey phenethyamnes) stabze the cosed conformaton. Further, cocane bnds n such a way as to nhbt a hydrogen bond nnate to DAT that otherwse st forms when amphetamne and smar moecues are bound. Cocane's bndng propertes are such that t attaches so ths hydrogen bond w not form and s bocked from formaton due to the tghty ocked orentaton of the cocane moecue. Research studes have suggested that the affnty for the transporter s not what s nvoved n habtuaton of the substance so much as the conformaton and bndng propertes to where & how on the transporter the moecue bnds.|61| Sgma receptors are affected by cocane, as cocane functons as a sgma gand agonst.|62| Further specfc receptors t has been demonstrated to functon on are NMDA and the D1 dopamne receptor.|63| Cocane aso bocks sodum channes, thereby nterferng wth the propagaton of acton potentas;|7| thus, ke gnocane and novocane, t acts as a oca anesthetc. It aso functons on the bndng stes to the dopamne and serotonn sodum dependent transport area as targets as separate mechansms from ts reuptake of those transporters; unque to ts oca anesthetc vaue whch makes t n a cass of functonaty dfferent from both ts own derved phenytropanes anaogues whch have that removed and the amphetamne cass of stmuants whch as we atogether ack that. In addton to ths cocane has some target bndng to the ste of the Kappa- opod receptor as we.|64| Cocane aso causes vasoconstrcton, thus reducng beedng durng mnor surgca procedures. The ocomotor enhancng propertes of cocane may be attrbutabe to ts enhancement of dopamnergc transmsson from the substanta ngra. Recent research ponts to an mportant roe of crcadan mechansms|65| and cock genes|66| n behavora actons of cocane. Because ncotne ncreases the eves of dopamne n the bran, many cocane users fnd that consumpton of tobacco products durng cocane use enhances the euphora. Ths, however, may have undesrabe consequences, such as uncontroabe chan smokng durng cocane use (even users who do not normay smoke cgarettes have been known to chan smoke when usng cocane), n addton to the detrmenta heath effects and the addtona stran on the cardovascuar system caused by tobacco. Cocane can often cause reduced food ntake, many chronc users ose ther appette and can experence severe manutrton and sgnfcant weght oss. Cocane effects, further, are shown to be potentated for the user when used n con|uncton wth new surroundngs and stmu, and otherwse nove envrons.|67| Metabosm and excreton Cocane s extensvey metabozed, prmary n the ver, wth ony about 1% excreted unchanged n the urne. The metabosm s domnated by hydroytc ester ceavage, so the emnated metabotes consst mosty of benzoyecgonne (BE), the ma|or metabote, and other sgnfcant metabotes n esser amounts such as ecgonne methy ester (EME) and ecgonne. Further mnor metabotes of cocane ncude norcocane, p- hydroxycocane, m-hydroxycocane, p-hydroxybenzoyecgonne (pOHBE), and m-hydroxybenzoyecgonne.|68| Dependng on ver and kdney functon, cocane metabotes are detectabe n urne. Benzoyecgonne can be detected n urne wthn four hours after cocane ntake and remans detectabe n concentratons greater than 150 ng/mL typcay for up to eght days after cocane s used. Detecton of accumuaton of cocane metabotes n har s possbe n reguar users unt the sectons of har grown durng use are cut or fa out. If consumed wth acoho, cocane combnes wth acoho n the ver to form cocaethyene. Studes have suggested cocaethyene s both more euphorgenc, and has a hgher cardovascuar toxcty than cocane by tsef. |69||70||71| A study n mce has suggested that capsacn found n pepper spray may nteract wth cocane wth potentay fata consequences. The method through whch they woud nteract however, s not known.|72||73| Detecton n boogca fuds Cocane and ts ma|or metabotes may be quanttated n bood, pasma or urne to montor for abuse, confrm a dagnoss of posonng or assst n the forensc nvestgaton of a traffc or other crmna voaton or a sudden death. Most commerca cocane mmunoassay screenng tests cross-react apprecaby wth the ma|or cocane metabotes, but chromatographc technques can easy dstngush and separatey measure each of these substances. When nterpretng the resuts of a test, t s mportant to consder the cocane usage hstory of the ndvdua, snce a chronc user can deveop toerance to doses that woud ncapactate a cocane-nave ndvdua, and the chronc user often has hgh basene vaues of the metabotes n hs system. Cautous nterpretaton of testng resuts may aow a dstncton between passve or actve usage, and between smokng versus other routes of admnstraton.|74| In 2011, researchers at |ohn |ay Coege of Crmna |ustce reported that detary znc suppements can mask the presence of cocane and other drugs n urne. Smar cams have been made n web forums on that topc.|75| Loca anesthetc Cocane was hstorcay usefu as a topca anesthetc n eye and nasa surgery, athough t s now predomnanty used for nasa and acrma duct surgery. The ma|or dsadvantages of ths use are cocane's ntense vasoconstrctor actvty and potenta for cardovascuar toxcty. Cocane has snce been argey repaced n Western medcne by synthetc oca anesthetcs such as benzocane, proparacane, gnocane/xyocane/docane, and tetracane though t remans avaabe for use f specfed. If vasoconstrcton s desred for a procedure (as t reduces beedng), the anesthetc s combned wth a vasoconstrctor such as phenyephrne or epnephrne. In Austraa t s currenty prescrbed for use as a oca anesthetc for condtons such as mouth and ung ucers. Some ENT specasts occasonay use cocane wthn the practce when performng procedures such as nasa cauterzaton. In ths scenaro dssoved cocane s soaked nto a ba of cotton woo, whch s paced n the nostr for the 10-15 mnutes mmedatey before the procedure, thus performng the dua roe of both numbng the area to be cauterzed, and vasoconstrcton. Even when used ths way, some of the used cocane may be absorbed through ora or nasa mucosa and gve systemc effects. In 2005, researchers from Kyoto Unversty Hospta proposed the use of cocane n con|uncton wth phenyephrne admnstered n the form of an eye drop as a dagnostc test for Parknson's dsease.|76| Hstory Dscovery Coca eaf n Bova For over a thousand years South Amercan ndgenous peopes have chewed the eaves of Erythroxyon coca, a pant that contans vta nutrents as we as numerous akaods, ncudng cocane. The coca eaf was, and st s, chewed amost unversay by some ndgenous communtes. The remans of coca eaves have been found wth ancent Peruvan mummes, and pottery from the tme perod depcts humans wth buged cheeks, ndcatng the presence of somethng on whch they are chewng.|77| There s aso evdence that these cutures used a mxture of coca eaves and sava as an anesthetc for the performance of trepanaton.|78| When the Spansh arrved n South Amerca, most at frst gnored aborgna cams that the eaf gave them strength and energy, and decared the practce of chewng t the work of the Dev.|ctaton needed| But after dscoverng that these cams were true, they egazed and taxed the eaf, takng 10% off the vaue of each crop.|79| In 1569, Ncos Monardes descrbed the practce of the natves of chewng a mxture of tobacco and coca eaves to nduce "great contentment": When they wshed to make themseves drunk and out of |udgment they chewed a mxture of tobacco and coca eaves whch make them go as they were out of ther wttes. -|80| In 1609, Padre Bas Vaera wrote: Coca protects the body from many aments, and our doctors use t n powdered form to reduce the sweng of wounds, to strengthen broken bones, to expe cod from the body or prevent t from enterng, and to cure rotten wounds or sores that are fu of maggots. And f t does so much for outward aments, w not ts snguar vrtue have even greater effect n the entras of those who eat t?|ctaton needed| Isoaton and namng Athough the stmuant and hunger-suppressant propertes of coca had been known for many centures, the soaton of the cocane akaod was not acheved unt 1855. Varous European scentsts had attempted to soate cocane, but none had been successfu for two reasons: the knowedge of chemstry requred was nsuffcent at the tme.|ctaton needed| Addtonay contemporary condtons of sea-shppng from South Amerca coud degrade the cocane n the pant sampes avaabe to Europeans.|ctaton needed| The cocane akaod was frst soated by the German chemst Fredrch Gaedcke n 1855. Gaedcke named the akaod "erythroxyne", and pubshed a descrpton n the |ourna Archv der Pharmaze.|81| In 1856, Fredrch Wher asked Dr. Car Scherzer, a scentst aboard the Novara (an Austran frgate sent by Emperor Franz |oseph to crce the gobe), to brng hm a arge amount of coca eaves from South Amerca. In 1859, the shp fnshed ts traves and Wher receved a trunk fu of coca. Wher passed on the eaves to Abert Nemann, a Ph.D. student at the Unversty of Gttngen n Germany, who then deveoped an mproved purfcaton process. |82| Nemann descrbed every step he took to soate cocane n hs dssertaton tted ber ene neue organsche Base n den Cocabttern (On a New Organc Base n the Coca Leaves), whch was pubshed n 1860-t earned hm hs Ph.D. and s now n the Brtsh Lbrary. He wrote of the akaod's "coouress transparent prsms" and sad that, "Its soutons have an akane reacton, a btter taste, promote the fow of sava and eave a pecuar numbness, foowed by a sense of cod when apped to the tongue." Nemann named the akaod "cocane" from "coca" (from Ouechua "cuca") + suffx "ne".|82||83| Because of ts use as a oca anesthetc, a suffx "-cane" was ater extracted and used to form names of synthetc oca anesthetcs. The frst synthess and eucdaton of the structure of the cocane moecue was by Rchard Wsttter n 1898.|29| The synthess started from tropnone, a reated natura product and took fve steps. Medcazaton "Cocane toothache drops", 1885 advertsement of cocane for denta pan n chdren Advertsement n the |anuary 1896 ssue of McCure's Magazne for Burnett's Cocane "for the har". Wth the dscovery of ths new akaod, Western medcne was quck to expot the possbe uses of ths pant. In 1879, Vass von Anrep, of the Unversty of Wrzburg, devsed an experment to demonstrate the anagesc propertes of the newy dscovered akaod. He prepared two separate |ars, one contanng a cocane-sat souton, wth the other contanng merey sat water. He then submerged a frog's egs nto the two |ars, one eg n the treatment and one n the contro souton, and proceeded to stmuate the egs n severa dfferent ways. The eg that had been mmersed n the cocane souton reacted very dfferenty from the eg that had been mmersed n sat water.|84| Kar Koer (a cose assocate of Sgmund Freud, who woud wrte about cocane ater) expermented wth cocane for ophthamc usage. In an nfamous experment n 1884, he expermented upon hmsef by appyng a cocane souton to hs own eye and then prckng t wth pns. Hs fndngs were presented to the Hedeberg Ophthamoogca Socety. Aso n 1884, |enek demonstrated the effects of cocane as a respratory system anesthetc. In 1885, Wam Hasted demonstrated nerve-bock anesthesa, |85| and |ames Leonard Cornng demonstrated perdura anesthesa.|86| 1898 saw Henrch Ouncke use cocane for spna anesthesa. Today, cocane has very mted medca use. See the secton Cocane as a oca anesthetc Popuarzaton Pope Leo XIII purportedy carred a hpfask of the coca-treated Vn Maran wth hm, and awarded a Vatcan god meda to Angeo Maran.|87| In 1859, an Itaan doctor, Paoo Mantegazza, returned from Peru, where he had wtnessed frst-hand the use of coca by the natves. He proceeded to experment on hmsef and upon hs return to Man he wrote a paper n whch he descrbed the effects. In ths paper he decared coca and cocane (at the tme they were assumed to be the same) as beng usefu medcnay, n the treatment of "a furred tongue n the mornng, fatuence, and whtenng of the teeth." A chemst named Angeo Maran who read Mantegazza's paper became mmedatey ntrgued wth coca and ts economc potenta. In 1863, Maran started marketng a wne caed Vn Maran, whch had been treated wth coca eaves, to become cocawne. The ethano n wne acted as a sovent and extracted the cocane from the coca eaves, aterng the drnk's effect. It contaned 6 mg cocane per ounce of wne, but Vn Maran whch was to be exported contaned 7.2 mg per ounce, to compete wth the hgher cocane content of smar drnks n the Unted States. A "pnch of coca eaves" was ncuded n |ohn Styth Pemberton's orgna 1886 recpe for Coca-Coa, though the company began usng decocanzed eaves n 1906 when the Pure Food and Drug Act was passed. The actua amount of cocane that Coca-Coa contaned durng the frst 20 years of ts producton s practcay mpossbe to determne.|ctaton needed| In 1879 cocane began to be used to treat morphne addcton. Cocane was ntroduced nto cnca use as a oca anesthetc n Germany n 1884, about the same tme as Sgmund Freud pubshed hs work ber Coca, n whch he wrote that cocane causes: Exharaton and astng euphora, whch n no way dffers from the norma euphora of the heathy person. You perceve an ncrease of sef-contro and possess more vtaty and capacty for work. In other words, you are smpy norma, and t s soon hard to beeve you are under the nfuence of any drug. Long ntensve physca work s performed wthout any fatgue. Ths resut s en|oyed wthout any of the unpeasant after-effects that foow exharaton brought about by acoho. Absoutey no cravng for the further use of cocane appears after the frst, or even after repeated takng of the drug. In 1885 the U.S. manufacturer Parke-Davs sod cocane n varous forms, ncudng cgarettes, powder, and even a cocane mxture that coud be n|ected drecty nto the user's vens wth the ncuded neede. The company promsed that ts cocane products woud "suppy the pace of food, make the coward brave, the sent eoquent and render the sufferer nsenstve to pan." By the ate Vctoran era cocane use had appeared as a vce n terature. For exampe, t was n|ected by Arthur Conan Doye's fctona Sherock Homes, generay to offset the boredom he fet when he was not workng on a case. In eary 20th-century Memphs, Tennessee, cocane was sod n neghborhood drugstores on Beae Street, costng fve or ten cents for a sma boxfu. Stevedores aong the Msssspp Rver used the drug as a stmuant, and whte empoyers encouraged ts use by back aborers.|88| In 1909, Ernest Shacketon took "Forced March" brand cocane tabets to Antarctca, as dd Captan Scott a year ater on hs -fated |ourney to the South Poe.|89| Durng the md-1940s, amdst WWII, cocane was consdered for ncuson as an ngredent of a future generaton of 'pep ps' for the German mtary code named D-IX.|90| Prohbton See aso: Lega status of cocane Gobe con. The exampes and perspectve n ths secton dea prmary wth the Unted States and do not represent a wordwde vew of the sub|ect. Pease mprove ths artce and dscuss the ssue on the tak page. (August 2012) Prosttutes buy cocane capsues from a drug deaer n Bern, 1924 Prohbton of cocane n the Unted States See aso: Cocane n the Unted States Cas for prohbton began ong before the Harrson Act was passed by Congress n 1914 - a aw requrng cocane and narcotcs to be dspensed ony wth a doctor's order.|91| Before ths, varous factors and groups acted on prmary a state eve nfuencng a move towards prohbton and away from a assez-fare atttude.|92| By 1903 cocane consumpton had grown to about fve tmes that of 1890. Non-medca users accounted for amost the entre ncrease as cocane-users extended outsde the mdde-aged, whte, professona cass. Cocane became assocated wth aborers, youths, backs and the urban underword.|93| The popuarzaton of cocane frst began wth aborers who used cocane as a stmuant to ncrease productvty.|93| Cocane was often supped by empoyers.|94| Cocane was often supped to Afrcan Amercan workers, who many empoyers beeved were better physca workers; cocane was thought to provde added strength and consttuton and accordng to the Medca News, made backs "mpervous to the extremes of heat and cod."|93| However, users of cocane qucky acqured a reputaton as dangerous and n 1897, the frst state b of contro for cocane saes came from a mnng county n Coorado.|95| The popuarzaton of cocane use was not confned to Afrcan Amercans or smpe aborers. In Northern ctes, cocane use ncreased amongst poorer peope - n fact, cocane was often cheaper than acoho.|94| In the Northeast n partcuar, cocane became popuar amongst workers n factores, texte ms and on ra roads.|96| In some nstances, cocane use suppemented or repaced caffene as the drug-of-choce to keep workers awake and workng overtme.|96| Ths perod of ncreasng cocane use foowed wth ncreasng fears that young chdren were beng preyed upon and forced nto cocane addcton. |97| Indeed, t was even thought that cocane was used to seduce young grs away from ther homes and cause them to be addcted and dependent upon the substance and therefore fa prey to an nescapabe cyce of prosttuton. |98| Fears of the corrupton of the youth by cocane were popuar and wdespread but there s tte evdence to support ther veracty.|97| Manstream meda reported cocane epdemcs as eary as 1894 n Daas, Texas. Reports of the cocane epdemc woud foreshadow a famar theme n ater so-caed epdemcs, namey that cocane presented a soca threat more dangerous than smpe heath effects and had nsdous resuts when used by backs and members of the ower cass. Smar anxety-rdden reports appeared throughout ctes n the South eadng some to decare that "the cocane habt has assumed the proportons of an epdemc among the coored peope." In 1900, state egsatures n Aabama, Georga and Tennessee consdered ant-cocane bs for the frst tme.|99| Hyperboc reports of the effect of cocane on Afrcan Amercans went hand- n-hand wth ths hystera. In 1901, the Atanta Consttuton reported that "Use of the drug |cocane| among negroes s growng to an aarmng extent."|100| The New York Tmes reported that under the nfuence of cocane, "sexua desres are ncreased and perverted . peacefu negroes become quarresome, and tmd negroes deveop a degree of 'Dutch courage' that s sometmes amost ncredbe."|101| A medca doctor even wrote "cocane s often the drect ncentve to the crme of rape by the negroes."|101| To compete the characterzaton, a |udge n Msssspp decared that suppyng a "negro" wth cocane was more dangerous than n|ectng a dog wth rabes.|102| These atttudes not ony nfuenced drug aw and pocy but aso ed to ncreased voence aganst Afrcan Amercans. In 1906, a ma|or race rot ed by whtes erupted; t was sparked by reports of crmes commtted by back cocane fends.|100| Indeed, whte-ed, race rots spawnng from reports of backs under the nfuence of cocane were not uncommon.|103| Poce n the South wdey adopted the use of a heaver caber handguns so as to better stop a cocane-crazed back person - beeved to be empowered wth super- human strength.|104| Another dangerous myth perpetuated amongst poce was that cocane mbued Afrcan Amercans wth tremendous accuracy wth frearms and therefore poce were better advsed to shoot frst n questonabe crcumstances.|105| Utmatey pubc opnon rested aganst the cocane user. Crmnaty was commony beeved to be a natura resut of cocane use.|106| Much of the nfuence for these knd of perceptons came from the wdespread pubcty gven to notorous cases.|92| Whe the hstorca reaty of cocanes effect on voence and crme s dffcut to dsentange from nfamed perceptons, t does appear that pubc opnon was swayed by the mage of the voent, cocane-crazed fend and pushed over the edge by a few voent epsodes. |106| It was an mage of the cocane-user that carred acute raca overtones. |92| Before any substantve federa reguaton of cocane, state and oca muncpates evoked ther own means to reguate cocane. Because of the nta ack of targeted egsaton, on both federa and state eve, the most typca strategy by aw enforcement was the appcaton of nusance aws pertanng to vagrancy and dsturbng the peace.|107| Subsequent egsatve actons amed at controng the dstrbuton of cocane rather than ts manufacture.|108| Reformers took ths approach n part because of ega precedents whch made t easer to contro dstrbutors such as pharmaces; state and oca boards of hearth or boards of pharmacy often took the pace of reguatory bodes for controng the dstrbuton of cocane.|108| Some states took the poston of outrght bannng of a forms of cocane sae; Georga was the frst to do ths n 1902.|109| A New Oreans ordnance banned cocane saes as we but eft an -defned excepton for therapeutc uses.|108| A more common requrement was to restrct the sae of cocane or mpose abeng requrements. A 1907 Caforna aw mtng sae of cocane to ony those wth a physcans prescrpton resuted n the arrest of over 50 store owners and cerks n the frst year.|108| A 1913 New York state aw mted druggsts cocane stocks to under 5 ounces. Labeng requrements ntay operated on a state eve wth some states even gong so far as to requre that cocane and cocane-contanng products be abeed as poson. |110| Eventuay the federa government stepped n and nsttuted a natona abeng requrement for cocane and cocane-contanng products through the Food and Drug Act of 1906.|110| The next mpactfu federa reguaton was the Harrson Narcotcs Tax Act of 1914. Whe ths act s often seen as the start of prohbton, the act tsef was not actuay a prohbton on cocane, but nstead setup a reguatory and censng regme.|91| The Harrson Act dd not recognze addcton as a treatabe condton and therefore the therapeutc use of cocane, heron or morphne to such ndvduas was outawed - eadng the |ourna of Amercan Medcne to remark, "|the addct| s dened the medca care he urgenty needs, open, above-board sources from whch he formery obtaned hs drug suppy are cosed to hm, and he s drven to the underword where he can get hs drug, but of course, surrepttousy and n voaton of the aw."|111| The Harrson Act eft manufacturers of cocane untouched so ong as they met certan purty and abeng standards.|112| Despte that cocane was typcay ega to se and ega outets were more rare, the quanttes of ega cocane produced decned very tte.|112| Lega cocane quanttes dd not decrease unt the |ones-Mer Act of 1922 put serous restrctons on cocane manufactures.|112| Modern usage D.C. Mayor Maron Barry captured on a surveance camera smokng crack cocane durng a stng operaton by the FBI and D.C. Poce. In many countres, cocane s a popuar recreatona drug. In the Unted States, the deveopment of "crack" cocane ntroduced the substance to a generay poorer nner-cty market. Use of the powder form has stayed reatvey constant, experencng a new heght of use durng the ate 1990s and eary 2000s n the U.S., and has become much more popuar n the ast few years n the UK.|ctaton needed||when?| Cocane use s prevaent across a socoeconomc strata, ncudng age, demographcs, economc, soca, potca, regous, and vehood.|ctaton needed| The estmated U.S. cocane market exceeded $70 bon n street vaue for the year 2005, exceedng revenues by corporatons such as Starbucks.|113| |114| There s a tremendous demand for cocane n the U.S. market, partcuary among those who are makng ncomes affordng uxury spendng, such as snge aduts and professonas wth dscretonary ncome. Cocanes status as a cub drug shows ts mmense popuarty among the "party crowd". In 1995 the Word Heath Organzaton (WHO) and the Unted Natons Interregona Crme and |ustce Research Insttute (UNICRI) announced n a press reease the pubcaton of the resuts of the argest goba study on cocane use ever undertaken. However, a decson by an Amercan representatve n the Word Heath Assemby banned the pubcaton of the study, because t seemed to make a case for the postve uses of cocane. An excerpt of the report strongy confcted wth accepted paradgms, for exampe "that occasona cocane use does not typcay ead to severe or even mnor physca or soca probems."|115| In the sxth meetng of the B commttee the US representatve threatened that "If WHO actvtes reatng to drugs faed to renforce proven drug contro approaches, funds for the reevant programs shoud be curtaed". Ths ed to the decson to dscontnue pubcaton. A part of the study has been recuperated. Avaabe are profes of cocane use n 20 countres. It was reported n October 2010 that the use of cocane n Austraa has doubed snce montorng began n 2003.|116| A probem wth ega cocane use, especay n the hgher voumes used to combat fatgue (rather than ncrease euphora) by ong-term users, s the rsk of effects or damage caused by the compounds used n aduteraton. Cuttng or "steppng on" the drug s commonpace, usng compounds whch smuate ngeston effects, such as Novocan (procane) producng temporary anesthaesa as many users beeve a strong numbng effect s the resut of strong and/or pure cocane, ephedrne or smar stmuants that are to produce an ncreased heart rate. The norma aduterants for proft are nactve sugars, usuay mannto, creatne or gucose, so ntroducng actve aduterants gves the uson of purty and to 'stretch' or make t so a deaer can se more product than wthout the aduterants.|ctaton needed| The aduterant of sugars therefore aows the deaer to se the product for a hgher prce because of the uson of purty and aows to se more of the product at that hgher prce, enabng deaers to make a ot of revenue wth tte cost of the aduterants. Cocane tradng carres arge penates n most |ursdctons, so user decepton about purty and consequent hgh profts for deaers are the norm.|orgna research?| A study by the European Montorng Centre for Drugs and Drug Addcton n 2007 showed that the purty eves for street purchased cocane was often under 5% and on average under 50% pure.|117| Socety and cuture Lega status Man artce: Lega status of cocane The producton, dstrbuton and sae of cocane products s restrcted (and ega n most contexts) n most countres as reguated by the Snge Conventon on Narcotc Drugs, and the Unted Natons Conventon Aganst Ict Traffc n Narcotc Drugs and Psychotropc Substances. In the Unted States the manufacture, mportaton, possesson, and dstrbuton of cocane s addtonay reguated by the 1970 Controed Substances Act. Some countres, such as Peru and Bova permt the cutvaton of coca eaf for tradtona consumpton by the oca ndgenous popuaton, but nevertheess prohbt the producton, sae and consumpton of cocane. In addton, some parts of Europe and Austraa aow processed cocane for medcna uses ony. Interdcton In 2004, accordng to the Unted Natons, 589 tonnes of cocane were sezed gobay by aw enforcement authortes. Coomba sezed 188 t, the Unted States 166 t, Europe 79 t, Peru 14 t, Bova 9 t, and the rest of the word 133 t.|118| Ict trade Because of the extensve processng t undergoes durng preparaton, cocane s generay treated as a 'hard drug', wth severe penates for possesson and traffckng. Demand remans hgh, and consequenty back market cocane s qute expensve. Unprocessed cocane, such as coca eaves, are occasonay purchased and sod, but ths s exceedngy rare as t s much easer and more proftabe to concea and smugge t n powdered form. The scae of the market s mmense: 770 tonnes tmes $100 per gram reta = up to $77 bon.|ctaton needed| Producton Unt 2012, Coomba was the word's eadng producer of cocane.|119||120| Three-quarters of the word's annua yed of cocane has been produced n Coomba, both from cocane base mported from Peru (prmary the Huaaga Vaey) and Bova, and from ocay grown coca. There was a 28% ncrease from the amount of potentay harvestabe coca pants whch were grown n Coomba n 1998. Ths, combned wth crop reductons n Bova and Peru, made Coomba the naton wth the argest area of coca under cutvaton after the md-1990s. Coca grown for tradtona purposes by ndgenous communtes, a use whch s st present and s permtted by Coomban aws, ony makes up a sma fragment of tota coca producton, most of whch s used for the ega drug trade. An ntervew wth a coca farmer pubshed n 2003 descrbed a mode of producton by acd-base extracton that has changed tte snce 1905. Roughy 625 pounds of eaves were harvested per hectare, sx tmes per year. The eaves were dred for haf a day, then chopped nto sma peces wth a strmmer and sprnked wth a sma amount of powdered cement (repacng sodum carbonate from former tmes). Severa hundred pounds of ths mxture was soaked n 50 US gaons (190 L) of gasone for a day, then the gasone was removed and the eaves were pressed for remanng qud, after whch they coud be dscarded. Then battery acd (weak sufurc acd) was used, one bucket per 25 kg (55 b) of eaves, to create a phase separaton n whch the cocane free base n the gasone was acdfed and extracted nto a few buckets of "murky-ookng smey qud". Once powdered caustc soda was added to ths, the cocane precptated and coud be removed by ftraton through a coth. The resutng matera, when dred, was termed pasta and sod by the farmer. The 3750 pound yeary harvest of eaves from a hectare produced 2.5 kg (6 b) of pasta, approxmatey 40-60% cocane. Repeated recrystazaton from sovents, producng pasta avada and eventuay crystane cocane, were performed at specazed aboratores after the sae.|121| Attempts to eradcate coca feds through the use of defoants have devastated part of the farmng economy n some coca growng regons of Coomba, and strans appear to have been deveoped that are more resstant or mmune to ther use. Whether these strans are natura mutatons or the product of human tamperng s uncear. These strans have aso shown to be more potent than those prevousy grown, ncreasng profts for the drug cartes responsbe for the exportng of cocane. Athough producton fe temporary, coca crops rebounded n numerous smaer feds n Coomba, rather than the arger pantatons. The cutvaton of coca has become an attractve, and n some cases even necessary, economc decson on the part of many growers due to the combnaton of severa factors, ncudng the persstence of wordwde demand, the ack of other empoyment aternatves, the ower proftabty of aternatve crops n offca crop substtuton programs, the eradcaton- reated damages to non-drug farms, and the spread of new strans of the coca pant. Estmated Andean regon coca cutvaton and potenta pure cocane producton|122| 2000 2001 2002 2003 2004 Net cutvaton (km2) 1875 2218 2007.5 1663 1662 Potenta pure cocane producton (tonnes) 770 925 830 680 645 The atest estmate provded by the U.S. authortes on the annua producton of cocane n Coomba refers to 290 metrc tons. As of the end of 2011, the sezure operatons of Coomban cocane carred out n dfferent countres have totaed 351.8 metrc tons of cocane, .e. 121.3% of Coombas annua producton accordng to the U.S. Department of States estmates. |123||124| Synthess Synthetc cocane woud be hghy desrabe to the ega drug ndustry, as t woud emnate the hgh vsbty and ow reabty of offshore sources and nternatona smuggng, repacng them wth candestne domestc aboratores, as are common for ct methamphetamne. However, natura cocane remans the owest cost and hghest quaty suppy of cocane. Actua fu synthess of cocane s rarey done. Formaton of nactve enantomers (cocane has 4 chra centres - 1R,2R,3S,5S - hence a tota potenta of 16 possbe enantomers and dastereosomers) pus synthetc by-products mts the yed and purty. Names ke "synthetc cocane" and "new cocane" have been msapped to phencycdne (PCP) and varous desgner drugs.
List of Precursors and Chemicals Frequently Used in The Illicit Manufacture of Narcotic Drugs and Psychotropic Substances Under International Control (11th Ed.) - Various