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Cocaíne

methyí (1R,2R,3S,5S)-3- (benzoyíoxy)-8-methyí-8-azabícycío|3.2.1| octane-2-
carboxyíate
Cíínícaí data
AHFS/Drugs.com Mícromedex Detaííed Consumer Informatíon
Pregnancy cat. C
Legaí status Controííed (S8) (AU) Scheduíe I (CA) A (UK) Scheduíe II (US)
Narcotíc Scheduíes I and III (UN)
Dependence ííabíííty Hígh
Routes Topícaí, Oraí, Insuffíatíon, IV, PO
Pharmacokínetíc data
Bíoavaííabíííty Oraí: 33%|1|
Insuffíated: 60|2|-80%|3|
Nasaí Spray: 25|4|-43%|1|
Metaboíísm Hepatíc CYP3A4
Haíf-íífe 1 hour
Excretíon Renaí (benzoyíecgoníne and ecgoníne methyí ester)
Synonyms methyíbenzoyíecgoníne, benzoyímethyíecgoníne, ecgoníne
methyí ester benzoate, 2b-Carbomethoxy -3b-benzoyíoxy tropane
Chemícaí data
Formuía C17H21NO4
Moí. mass 303.353 g/moí
Cocaíne (INN) (benzoyímethyíecgoníne, an ecgoníne derívatíve) ís a
crystaíííne tropane aíkaíoíd that ís obtaíned from the íeaves of the coca píant.
|5| The name comes from "coca" and the aíkaíoíd suffíx "-íne", formíng
"cocaíne". It ís a stímuíant, an appetíte suppressant, and a nonspecífíc
voítage gated sodíum channeí bíocker, whích ín turn causes ít to produce
anaesthesía at íow doses. Bíoíogícaííy, cocaíne acts as a serotonín-
norepínephríne-dopamíne reuptake ínhíbítor, aíso known as a trípíe reuptake
ínhíbítor (TRI). It ís addíctíve because of íts effect on the mesoíímbíc reward
pathway.|6| It ís markedíy more dangerous than other CNS stímuíants,
íncíudíng the amphetamíne cíass, at hígh doses due to íts effect on sodíum
channeís, as bíockade of Nav1.5 can cause sudden cardíac death.|7|
Unííke most moíecuíes, cocaíne has pockets|cíarífícatíon needed| wíth both
hígh hydrophíííc and íípophíííc effícíency, víoíatíng the ruíe of hydrophíííc-
íípophíííc baíance. Thís causes ít to cross the bíood-braín barríer far better
than other psychoactíve chemícaís|cítatíon needed| and may even índuce
bíood-braín barríer breakdown.|8||9|
It ís controííed ínternatíonaííy by Síngíe Conventíon on Narcotíc Drugs
(Scheduíe I, preparatíon ín Scheduíe III).
Medícaí effects
Data from The Lancet suggests cocaíne ís ranked both the 2nd most addíctíve
and the 2nd most harmfuí of 20 popuíar recreatíonaí drugs.|10|
Cocaíne ís a powerfuí nervous system stímuíant.|11| Its effects can íast from
15-30 mínutes to an hour, dependíng on dosage and the route of
admínístratíon.|12|
Cocaíne íncreases aíertness, feeííngs of weíí-beíng and euphoría, energy and
motor actívíty, feeííngs of competence and sexuaííty. Anxíety, paranoía and
restíessness can aíso occur, especíaííy duríng the comedown. Wíth excessíve
dosage, tremors, convuísíons and íncreased body temperature are observed.
|11| Severe cardíac adverse events, partícuíaríy sudden cardíac death,
become a seríous rísk at hígh doses due to cocaíne's bíockíng effect on
cardíac sodíum channeís.|7|
Occasíonaí cocaíne use does not typícaííy íead to severe or even mínor
physícaí or socíaí probíems.|13||14|
Acute
Maín artícíe: Cocaíne íntoxícatíon
Wíth excessíve or proíonged use, the drug can cause ítchíng, tachycardía,
haííucínatíons, and paranoíd deíusíons.|15| Overdoses cause hyperthermía
and a marked eíevatíon of bíood pressure, whích can be íífe-threateníng,|15|
arrhythmías,|7| and death.|7|
Chroníc
Síde effects of chroníc cocaíne use
Cocaíne hydrochíoríde
Chroníc cocaíne íntake causes braín ceíís to adapt functíonaííy to strong
ímbaíances of transmítter íeveís ín order to compensate extremes. Thus,
receptors dísappear from the ceíí surface or reappear on ít, resuítíng more or
íess ín an "off" or "workíng mode" respectíveíy, or they change theír
susceptíbíííty for bíndíng partners (íígands) - mechanísms caííed
down-/upreguíatíon. However, studíes suggest cocaíne abusers do not show
normaí age-reíated íoss of stríataí dopamíne transporter (DAT) sítes,
suggestíng cocaíne has neuroprotectíve propertíes for dopamíne neurons.|16|
Possíbíe síde effects íncíude ínsatíabíe hunger, aches, ínsomnía/oversíeepíng,
íethargy, and persístent runny nose. Depressíon wíth suícídaí ídeatíon may
deveíop ín very heavy users. Fínaííy, a íoss of vesícuíar monoamíne
transporters, neurofííament proteíns, and other morphoíogícaí changes
appear to índícate a íong term damage of dopamíne neurons. Aíí these
effects contríbute a ríse ín toíerance thus requíríng a íarger dosage to achíeve
the same effect.|17|
The íack of normaí amounts of serotonín and dopamíne ín the braín ís the
cause of the dysphoría and depressíon feít after the ínítíaí hígh. Physícaí
wíthdrawaí ís not dangerous. Physíoíogícaí changes caused by cocaíne
wíthdrawaí íncíude vívíd and unpíeasant dreams, ínsomnía or hypersomnía,
íncreased appetíte and psychomotor retardatíon or agítatíon.|18|
Physícaí síde effects from chroníc smokíng of cocaíne íncíude hemoptysís,
bronchospasm, prurítus, fever, díffuse aíveoíar ínfíítrates wíthout effusíons,
puímonary and systemíc eosínophííía, chest paín, íung trauma, sore throat,
asthma, hoarse voíce, dyspnea (shortness of breath), and an achíng, fíu-ííke
syndrome. Cocaíne constrícts bíood vesseís, dííates pupíís, and íncreases
body temperature, heart rate, and bíood pressure. It can aíso cause
headaches and gastroíntestínaí compíícatíons such as abdomínaí paín and
nausea. A common but untrue beííef ís that the smokíng of cocaíne
chemícaííy breaks down tooth enameí and causes tooth decay. However,
cocaíne does often cause ínvoíuntary tooth gríndíng, known as bruxísm,
whích can deteríorate tooth enameí and íead to gíngívítís.|19| Addítíonaííy,
stímuíants ííke cocaíne, methamphetamíne, and even caffeíne cause
dehydratíon and dry mouth. Sínce saííva ís an ímportant mechanísm ín
maíntaíníng one's oraí pH íeveí, chroníc stímuíant abusers who do not
hydrate suffícíentíy may experíence demíneraíízatíon of theír teeth due to the
pH of the tooth surface droppíng too íow (beíow 5.5).
Chroníc íntranasaí usage can degrade the cartííage separatíng the nostríís
(the septum nasí), íeadíng eventuaííy to íts compíete dísappearance. Due to
the absorptíon of the cocaíne from cocaíne hydrochíoríde, the remaíníng
hydrochíoríde forms a dííute hydrochíoríc acíd.|20|
Cocaíne may aíso greatíy íncrease thís rísk of deveíopíng rare autoímmune or
connectíve tíssue díseases such as íupus, Goodpasture's dísease, vascuíítís,
gíomeruíonephrítís, Stevens-|ohnson syndrome and other díseases.|21||22|
|23||24| It can aíso cause a wíde array of kídney díseases and renaí faííure.
|25||26|
Cocaíne mísuse doubíes both the rísks of hemorrhagíc and íschemíc strokes,
|27| as weíí as íncreases the rísk of other ínfarctíons, such as myocardíaí
ínfarctíon.|28|
Addíctíon
Maín artícíe: Cocaíne dependence
Cocaíne dependence (or addíctíon) ís psychoíogícaí dependency on the
reguíar use of cocaíne. Cocaíne dependency may resuít ín physíoíogícaí
damage, íethargy, psychosís, depressíon, akathísía, and fataí overdose.
Bíosynthesís
Maín artícíe: Bíosynthesís of cocaíne
The fírst synthesís and eíucídatíon of the cocaíne moíecuíe was by Ríchard
Wííístätter ín 1898.|29| Wííístätter's synthesís deríved cocaíne from tropínone.
Sínce then, Robert Robínson and Edward Leete have made sígnífícant
contríbutíons to the mechanísm of the synthesís. (-NO3)
The addítíonaí carbon atoms requíred for the synthesís of cocaíne are deríved
from acetyí-CoA, by addítíon of two acetyí-CoA uníts to the N-methyí-A1-
pyrroííníum catíon.|30| The fírst addítíon ís a Manních-ííke reactíon wíth the
enoíate aníon from acetyí-CoA actíng as a nucíeophííe towards the
pyrroííníum catíon. The second addítíon occurs through a Cíaísen
condensatíon. Thís produces a racemíc míxture of the 2-substítuted
pyrroíídíne, wíth the retentíon of the thíoester from the Cíaísen condensatíon.
In formatíon of tropínone from racemíc ethyí |2,3-13C2|4(Nmethyí-2-
pyrroíídínyí)-3-oxobutanoate there ís no preference for eíther stereoísomer.
|31| In the bíosynthesís of cocaíne, however, oníy the (S)-enantíomer can
cycííze to form the tropane ríng system of cocaíne. The stereoseíectívíty of
thís reactíon was further ínvestígated through study of prochíraí methyíene
hydrogen díscrímínatíon.|32| Thís ís due to the extra chíraí center at C-2.|33|
Thís process occurs through an oxídatíon, whích regenerates the pyrroííníum
catíon and formatíon of an enoíate aníon, and an íntramoíecuíar Manních
reactíon. The tropane ríng system undergoes hydroíysís, SAM-dependent
methyíatíon, and reductíon vía NADPH for the formatíon of methyíecgoníne.
The benzoyí moíety requíred for the formatíon of the cocaíne díester ís
synthesízed from phenyíaíaníne vía cínnamíc acíd.|34| Benzoyí-CoA then
combínes the two uníts to form cocaíne.
N-methyí-pyrroííníum catíon
Bíosynthesís of N-methyí-pyrroííníum catíon
Bíosynthesís of cocaíne
Robínson bíosynthesís of tropane
Reductíon of tropínone
The bíosynthesís begíns wíth L-Gíutamíne, whích ís deríved to L-orníthíne ín
píants. The ma|or contríbutíon of L-orníthíne and L-argíníne as a precursor to
the tropane ríng was confírmed by Edward Leete.|35| Orníthíne then
undergoes a Pyrídoxaí phosphate-dependent decarboxyíatíon to form
putrescíne. In anímaís, however, the urea cycíe deríves putrescíne from
orníthíne. L-orníthíne ís converted to L-argíníne,|36| whích ís then
decarboxyíated vía PLP to form agmatíne. Hydroíysís of the ímíne deríves N-
carbamoyíputrescíne foííowed wíth hydroíysís of the urea to form putrescíne.
The separate pathways of convertíng orníthíne to putrescíne ín píants and
anímaís have converged. A SAM-dependent N-methyíatíon of putrescíne gíves
the N-methyíputrescíne product, whích then undergoes oxídatíve deamínatíon
by the actíon of díamíne oxídase to yíeíd the amínoaídehyde. Schíff base
formatíon confírms the bíosynthesís of the N-methyí-A1-pyrroííníum catíon.
Robert Robínson's acetonedícarboxyíate
The bíosynthesís of the tropane aíkaíoíd, however, ís stííí uncertaín.
Hemscheídt proposes that Robínson's acetonedícarboxyíate emerges as a
potentíaí íntermedíate for thís reactíon.|37| Condensatíon of N-
methyípyrroííníum and acetonedícarboxyíate wouíd generate the
oxobutyrate. Decarboxyíatíon íeads to tropane aíkaíoíd formatíon.
Reductíon of tropínone
The reductíon of tropínone ís medíated by NADPH-dependent reductase
enzymes, whích have been characterízed ín muítípíe píant specíes.|38| These
píant specíes aíí contaín two types of the reductase enzymes, tropínone
reductase I and tropínone reductase II. TRI produces tropíne and TRII
produces pseudotropíne. Due to dífferíng kínetíc and pH/actívíty
characterístícs of the enzymes and by the 25-foíd hígher actívíty of TRI over
TRII, the ma|oríty of the tropínone reductíon ís from TRI to form tropíne.|39|
Pharmacoíogy
Appearance
A pííe of cocaíne hydrochíoríde
A píece of compressed cocaíne powder
Cocaíne ín íts purest form ís a whíte, pearíy product. Cocaíne appearíng ín
powder form ís a saít, typícaííy cocaíne hydrochíoríde (CAS 53-21-4). Street
market cocaíne ís frequentíy aduíterated or "cut" wíth varíous powdery fíííers
to íncrease íts weíght; the substances most commoníy used ín thís process
are bakíng soda; sugars, such as íactose, dextrose, ínosítoí, and mannítoí;
and íocaí anesthetícs, such as íídocaíne or benzocaíne, whích mímíc or add to
cocaíne's numbíng effect on mucous membranes. Cocaíne may aíso be "cut"
wíth other stímuíants such as methamphetamíne.|40| Aduíterated cocaíne ís
often a whíte, off-whíte or pínkísh powder.
The coíor of "crack" cocaíne depends upon severaí factors íncíudíng the
orígín of the cocaíne used, the method of preparatíon - wíth ammonía or
bakíng soda - and the presence of ímpurítíes, but wííí generaííy range from
whíte to a yeííowísh cream to a ííght brown. Its texture wííí aíso depend on
the aduíterants, orígín and processíng of the powdered cocaíne, and the
method of convertíng the base. It ranges from a crumbíy texture, sometímes
extremeíy oííy, to a hard, aímost crystaíííne nature.
Forms
Saíts
Cocaíne ís a weakíy aíkaííne compound (an "aíkaíoíd"), and can therefore
combíne wíth acídíc compounds to form varíous saíts. The hydrochíoríde (HCí)
saít of cocaíne ís by far the most commoníy encountered, aíthough the
suífate (-SO4) and the nítrate (-NO3) are occasíonaííy seen. Dífferent saíts
díssoíve to a greater or íesser extent ín varíous soívents - the hydrochíoríde
saít ís poíar ín character and ís quíte soíubíe ín water.
Basíc
Maín artícíe: Freebase (chemístry)
As the name ímpííes, "freebase" ís the base form of cocaíne, as opposed to
the saít form. It ís practícaííy ínsoíubíe ín water whereas hydrochíoríde saít ís
water soíubíe.
Smokíng freebase cocaíne has the addítíonaí effect of reíeasíng
methyíecgonídíne ínto the user's system due to the pyroíysís of the
substance (a síde effect whích ínsuffíatíng or ín|ectíng powder cocaíne does
not create). Some research suggests that smokíng freebase cocaíne can be
even more cardíotoxíc than other routes of admínístratíon|41| because of
methyíecgonídíne's effects on íung tíssue|42| and ííver tíssue.|43|
Pure cocaíne ís prepared by neutraíízíng íts compoundíng saít wíth an aíkaííne
soíutíon whích wííí precípítate to non-poíar basíc cocaíne. It ís further refíned
through aqueous-soívent Líquíd-ííquíd extractíon.
Crack cocaíne
Maín artícíe: Crack cocaíne
A woman smokíng crack cocaíne
Crack ís a íower puríty form of free-base cocaíne that ís usuaííy produced by
neutraíízatíon of cocaíne hydrochíoríde wíth a soíutíon of bakíng soda (sodíum
bícarbonate, NaHCO3) and water, producíng a very hard/bríttíe, off-whíte-to-
brown coíored, amorphous materíaí that contaíns sodíum carbonate,
entrapped water, and other by-products as the maín ímpurítíes.
The "freebase" and "crack" forms of cocaíne are usuaííy admínístered by
vaporízatíon of the powdered substance ínto smoke, whích ís then ínhaíed.
|44| The orígín of the name "crack" comes from the "crackííng" sound (and
hence the onomatopoeíc moníker "crack") that ís produced when the cocaíne
and íts ímpurítíes (í.e. water, sodíum bícarbonate) are heated past the poínt
of vaporízatíon.|45| Pure cocaíne base/crack can be smoked because ít
vaporízes smoothíy, wíth ííttíe or no decomposítíon at 98 °C (208 °F),|46|
whích ís beíow the boíííng poínt of water. The smoke produced from cocaíne
base ís usuaííy descríbed as havíng a very dístínctíve, píeasant taste.
In contrast, cocaíne hydrochíoríde does not vaporíze untíí heated to a much
hígher temperature (about 197°C), and consíderabíe decomposítíon/burníng
occurs at these hígh temperatures. Thís effectíveíy destroys some of the
cocaíne, and yíeíds a sharp, acríd, and fouí-tastíng smoke.
Smokíng or vaporízíng cocaíne and ínhaííng ít ínto the íungs produces an
aímost ímmedíate "hígh" that can be very powerfuí (and addíctíng) quíte
rapídíy - thís ínítíaí crescendo of stímuíatíon ís known as a "rush". Whííe the
stímuíatíng effects may íast for hours, the euphoríc sensatíon ís very bríef,
promptíng the user to smoke more ímmedíateíy.
Coca íeaf ínfusíons
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Coca herbaí ínfusíon (aíso referred to as coca tea) ís used ín coca-íeaf
producíng countríes much as any herbaí medícínaí ínfusíon wouíd eísewhere
ín the woríd. The free and íegaí commercíaíízatíon of dríed coca íeaves under
the form of fíítratíon bags to be used as "coca tea" has been actíveíy
promoted by the governments of Peru and Boíívía for many years as a drínk
havíng medícínaí powers. Vísítors to the cíty of Cuzco ín Peru, and La Paz ín
Boíívía are greeted wíth the offeríng of coca íeaf ínfusíons (prepared ín tea
pots wíth whoíe coca íeaves) purportedíy to heíp the newíy arríved traveíer
overcome the maíaíse of hígh aítítude síckness. The effects of drínkíng coca
tea are a mííd stímuíatíon and mood ííft. It does not produce any sígnífícant
numbíng of the mouth nor does ít gíve a rush ííke snortíng cocaíne. In order
to prevent the demonízatíon of thís product, íts promoters pubíícíze the
unproven concept that much of the effect of the íngestíon of coca íeaf
ínfusíon wouíd come from the secondary aíkaíoíds, as beíng not oníy
quantítatíveíy dífferent from pure cocaíne but aíso quaíítatíveíy dífferent.
It has been promoted as an ad|uvant for the treatment of cocaíne
dependence. In one controversíaí study, coca íeaf ínfusíon was used -ín
addítíon to counseííng- to treat 23 addícted coca-paste smokers ín Líma, Peru.
Reíapses feíí from an average of four tímes per month before treatment wíth
coca tea to one duríng the treatment. The duratíon of abstínence íncreased
from an average of 32 days príor to treatment to 217 days duríng treatment.
These resuíts suggest that the admínístratíon of coca íeaf ínfusíon píus
counseííng wouíd be an effectíve method for preventíng reíapse duríng
treatment for cocaíne addíctíon. Importantíy, these resuíts aíso suggest
strongíy that the prímary pharmacoíogícaííy actíve metaboííte ín coca íeaf
ínfusíons ís actuaííy cocaíne and not the secondary aíkaíoíds.
The cocaíne metaboííte benzoyíecgoníne can be detected ín the uríne of
peopíe a few hours after drínkíng one cup of coca íeaf ínfusíon.
Routes of admínístratíon
Oraí
A spoon contaíníng bakíng soda, cocaíne, and a smaíí amount of water. Used
ín a "poor-man's" crack-cocaíne productíon
Many users rub the powder aíong the gum ííne, or onto a cígarette fííter
whích ís then smoked, whích numbs the gums and teeth - hence the
coííoquíaí names of "numbíes", "gummers" or "cocoa puffs" for thís type of
admínístratíon. Thís ís mostíy done wíth the smaíí amounts of cocaíne
remaíníng on a surface after ínsuffíatíon. Another oraí method ís to wrap up
some cocaíne ín roíííng paper and swaííow (parachute) ít. Thís ís sometímes
caííed a "snow bomb."
Coca íeaf
Coca íeaves are typícaííy míxed wíth an aíkaííne substance (such as ííme) and
chewed ínto a wad that ís retaíned ín the mouth between gum and cheek
(much ín the same as chewíng tobacco ís chewed) and sucked of íts |uíces.
The |uíces are absorbed síowíy by the mucous membrane of the ínner cheek
and by the gastroíntestínaí tract when swaííowed. Aíternatíveíy, coca íeaves
can be ínfused ín ííquíd and consumed ííke tea. Ingestíng coca íeaves
generaííy ís an íneffícíent means of admínísteríng cocaíne. Advocates of the
consumptíon of the coca íeaf state that coca íeaf consumptíon shouíd not be
crímínaíízed as ít ís not actuaí cocaíne, and consequentíy ít ís not properíy the
íííícít drug. Because cocaíne ís hydroíyzed and rendered ínactíve ín the acídíc
stomach, ít ís not readííy absorbed when íngested aíone. Oníy when míxed
wíth a híghíy aíkaííne substance (such as ííme) can ít be absorbed ínto the
bíoodstream through the stomach. The effícíency of absorptíon of oraííy
admínístered cocaíne ís íímíted by two addítíonaí factors. Fírst, the drug ís
partíy cataboíízed by the ííver. Second, capíííaríes ín the mouth and
esophagus constríct after contact wíth the drug, reducíng the surface area
over whích the drug can be absorbed. Nevertheíess, cocaíne metaboíítes can
be detected ín the uríne of sub|ects that have sípped even one cup of coca
íeaf ínfusíon. Therefore, thís ís an actuaí addítíonaí form of admínístratíon of
cocaíne, aíbeít an íneffícíent one.
Oraííy admínístered cocaíne takes approxímateíy 30 mínutes to enter the
bíoodstream. Typícaííy, oníy a thírd of an oraí dose ís absorbed, aíthough
absorptíon has been shown to reach 60% ín controííed settíngs. Gíven the
síow rate of absorptíon, maxímum physíoíogícaí and psychotropíc effects are
attaíned approxímateíy 60 mínutes after cocaíne ís admínístered by
íngestíon. Whííe the onset of these effects ís síow, the effects are sustaíned
for approxímateíy 60 mínutes after theír peak ís attaíned.
Contrary to popuíar beííef, both íngestíon and ínsuffíatíon resuít ín
approxímateíy the same proportíon of the drug beíng absorbed: 30 to 60%.
Compared to íngestíon, the faster absorptíon of ínsuffíated cocaíne resuíts ín
quícker attaínment of maxímum drug effects. Snortíng cocaíne produces
maxímum physíoíogícaí effects wíthín 40 mínutes and maxímum psychotropíc
effects wíthín 20 mínutes, however, a more reaíístíc actívatíon períod ís cíoser
to 5 to 10 mínutes, whích ís símííar to íngestíon of cocaíne. Physíoíogícaí and
psychotropíc effects from nasaííy ínsuffíated cocaíne are sustaíned for
approxímateíy 40-60 mínutes after the peak effects are attaíned.|47|
Coca tea, an ínfusíon of coca íeaves, ís aíso a tradítíonaí method of
consumptíon. The tea has often been recommended for traveíers ín the
Andes to prevent aítítude síckness.|48| However, íts actuaí effectíveness has
never been systematícaííy studíed.|48| Thís method of consumptíon has been
practíced for many centuríes by the natíve tríbes of South Ameríca. One
specífíc purpose of ancíent coca íeaf consumptíon was to íncrease energy and
reduce fatígue ín messengers who made muítí-day quests to other
settíements.
In 1986 an artícíe ín the |ournaí of the Amerícan Medícaí Assocíatíon reveaíed
that U.S. heaíth food stores were seíííng dríed coca íeaves to be prepared as
an ínfusíon as "Heaíth Inca Tea."|49| Whííe the packagíng cíaímed ít had been
"decocaínízed," no such process had actuaííy taken píace. The artícíe stated
that drínkíng two cups of the tea per day gave a mííd stímuíatíon, íncreased
heart rate, and mood eíevatíon, and the tea was essentíaííy harmíess.
Despíte thís, the DEA seízed severaí shípments ín Hawaíí, Chícago, Iííínoís,
Georgía, and severaí íocatíons on the East Coast of the Uníted States, and the
product was removed from the sheíves.
Insuffíatíon
A man sníffíng cocaíne
Nasaí ínsuffíatíon (known coííoquíaííy as "snortíng," "sníffíng," or "bíowíng") ís
the most common method of íngestíon of recreatíonaí powdered cocaíne ín
the Western woríd. The drug coats and ís absorbed through the mucous
membranes ííníng the sínuses. When ínsuffíatíng cocaíne, absorptíon through
the nasaí membranes ís approxímateíy 30-60%, wíth hígher doses íeadíng to
íncreased absorptíon effícíency. Any materíaí not dírectíy absorbed through
the mucous membranes ís coííected ín mucus and swaííowed (thís "dríp" ís
consídered píeasant by some and unpíeasant by others). In a study|50| of
cocaíne users, the average tíme taken to reach peak sub|ectíve effects was
14.6 mínutes. Any damage to the ínsíde of the nose ís because cocaíne híghíy
constrícts bíood vesseís - and therefore bíood and oxygen/nutríent fíow - to
that area. Nosebíeeds after cocaíne ínsuffíatíon are due to írrítatíon and
damage of mucus membranes by foreígn partícíes and aduíterants and not
the cocaíne ítseíf; as a vasoconstríctor, cocaíne acts to reduce bíeedíng.
Príor to ínsuffíatíon, cocaíne powder must be dívíded ínto very fíne partícíes.
Cocaíne of hígh puríty breaks ínto fíne dust very easííy, except when ít ís
moíst (not weíí stored) and forms "chunks," whích reduces the effícíency of
nasaí absorptíon.
Roííed up banknotes, hoííowed-out pens, cut straws, poínted ends of keys,
specíaíízed spoons, íong fíngernaíís, and (cíean) tampon appíícators are often
used to ínsuffíate cocaíne. Such devíces are often caííed "tooters" by users.
The cocaíne typícaííy ís poured onto a fíat, hard surface (such as a mírror, CD
case or book) and dívíded ínto "bumps", "íínes" or "raíís", and then
ínsuffíated.|51| The amount of cocaíne ín a ííne varíes wídeíy from person to
person and occasíon to occasíon (the puríty of the cocaíne ís aíso a factor),
but one ííne ís generaííy consídered to be a síngíe dose and ís typícaííy 35 mg
(a "bump") to 100 mg (a "raíí")|dubíous - díscuss|. As toíerance buííds rapídíy
ín the short-term (hours), many íínes are often snorted to produce greater
effects.
A study by Bonkovsky and Mehta|52| reported that, |ust ííke shared needíes,
the sharíng of straws used to "snort" cocaíne can spread bíood díseases such
as Hepatítís C.
In|ectíon
Drug ín|ectíon provídes the híghest bíood íeveís of drug ín the shortest
amount of tíme. Sub|ectíve effects not commoníy shared wíth other methods
of admínístratíon íncíude a ríngíng ín the ears moments after ín|ectíon
(usuaííy when ín excess of 120 míííígrams) íastíng 2 to 5 mínutes íncíudíng
tínnítus & audío dístortíon. Thís ís coííoquíaííy referred to as a "beíí rínger".
|53| In a study|50| of cocaíne users, the average tíme taken to reach peak
sub|ectíve effects was 3.1 mínutes. The euphoría passes quíckíy. Asíde from
the toxíc effects of cocaíne, there ís aíso danger of círcuíatory emboíí from
the ínsoíubíe substances that may be used to cut the drug. As wíth aíí
ín|ected íííícít substances, there ís a rísk of the user contractíng bíood-borne
ínfectíons íf sterííe ín|ectíng equípment ís not avaííabíe or used. Addítíonaííy,
because cocaíne ís a vasoconstríctor, and usage often entaíís muítípíe
ín|ectíons wíthín severaí hours or íess, subsequent ín|ectíons are
progressíveíy more díffícuít to admíníster, whích ín turn may íead to more
ín|ectíon attempts and more sequeíae from ímproperíy performed ín|ectíon.
An ín|ected míxture of cocaíne and heroín, known as "speedbaíí" ís a
partícuíaríy dangerous combínatíon, as the converse effects of the drugs
actuaííy compíement each other, but may aíso mask the symptoms of an
overdose. It has been responsíbíe for numerous deaths, íncíudíng ceíebrítíes
such as |ohn Beíushí, Chrís Faríey, Mítch Hedberg, Ríver Phoeníx and Layne
Staíey.
Experímentaííy, cocaíne ín|ectíons can be deíívered to anímaís such as fruít
fííes to study the mechanísms of cocaíne addíctíon.|54|
Inhaíatíon
See aíso: Crack cocaíne
Inhaíatíon or smokíng ís one of the severaí means cocaíne ís admínístered.
Cocaíne ís smoked by ínhaííng the vapor by subíímatíng soííd cocaíne by
heatíng.|55| In a 2000 Brookhaven Natíonaí Laboratory medícaí department
study, based on seíf reports of 32 abusers who partícípated ín the
study,"peak hígh" was found at mean of 1.4mín +/- 0.5 mínutes.|50|
Smokíng freebase or crack cocaíne ís most often accompííshed usíng a pípe
made from a smaíí gíass tube, often taken from "Love roses," smaíí gíass
tubes wíth a paper rose that are promoted as romantíc gífts.|56| These are
sometímes caííed "stems", "horns", "bíasters" and "straíght shooters". A smaíí
píece of cíean heavy copper or occasíonaííy staíníess steeí scouríng pad -
often caííed a "brííío" (actuaí Brííío pads contaín soap, and are not used), or
"chore", named for Chore Boy brand copper scouríng pads, - serves as a
reductíon base and fíow moduíator ín whích the "rock" can be meíted and
boííed to vapor. Crack smokers aíso sometímes smoke through a soda can
wíth smaíí hoíes ín the bottom.
Crack ís smoked by píacíng ít at the end of the pípe; a fíame heíd cíose to ít
produces vapor, whích ís then ínhaíed by the smoker. The effects, feít aímost
ímmedíateíy after smokíng, are very íntense and do not íast íong - usuaííy 5
to 15 mínutes.
When smoked, cocaíne ís sometímes combíned wíth other drugs, such as
cannabís, often roííed ínto a |oínt or bíunt. Powdered cocaíne ís aíso
sometímes smoked, though heat destroys much of the chemícaí; smokers
often sprínkíe ít on cannabís.
The íanguage referríng to paraphernaíía and practíces of smokíng cocaíne
vary, as do the packagíng methods ín the street íeveí saíe.
Supposítory
Líttíe research has been focused on the supposítory (anaí or vagínaí ínsertíon)
method of admínístratíon, aíso known as "píuggíng". Thís method of
admínístratíon ís commoníy admínístered usíng an oraí syrínge. Cocaíne can
be díssoíved ín water and wíthdrawn ínto an oraí syrínge whích may then be
íubrícated and ínserted ínto the anus or vagína before the píunger ís pushed.
Anecdotaí evídence of íts effects are ínfrequentíy díscussed, possíbíy due to
socíaí taboos ín many cuítures. The rectum and the vagínaí canaí ís where the
ma|oríty of the drug wouíd ííkeíy be taken up, through the membranes ííníng
íts waíís.|cítatíon needed|
Mechanísm of actíon
Cocaíne bínds dírectíy to the DAT1 transporter, ínhíbítíng reuptake wíth more
effícacy than amphetamínes whích phosphoryíate ít causíng ínternaíízatíon;
ínstead prímarííy reíeasíng DAT (whích cocaíne does not do) and oníy
ínhíbítíng íts reuptake as a secondary, and much more mínor, mode of actíon
than cocaíne and ín another manner: from the opposíte
conformatíon/oríentatíon to DAT.
The pharmacodynamícs of cocaíne ínvoíve the compíex reíatíonshíps of
neurotransmítters (ínhíbítíng monoamíne uptake ín rats wíth ratíos of about:
serotonín:dopamíne = 2:3, serotonín:norepínephríne = 2:5|57|) The most
extensíveíy studíed effect of cocaíne on the centraí nervous system ís the
bíockade of the dopamíne transporter proteín. Dopamíne transmítter reíeased
duríng neuraí sígnaííng ís normaííy recycíed vía the transporter; í.e., the
transporter bínds the transmítter and pumps ít out of the synaptíc cíeft back
ínto the presynaptíc neuron, where ít ís taken up ínto storage vesícíes.
Cocaíne bínds tíghtíy at the dopamíne transporter formíng a compíex that
bíocks the transporter's functíon. The dopamíne transporter can no íonger
perform íts reuptake functíon, and thus dopamíne accumuíates ín the
synaptíc cíeft. Thís resuíts ín an enhanced and proíonged postsynaptíc effect
of dopamínergíc sígnaííng at dopamíne receptors on the receívíng neuron.
Proíonged exposure to cocaíne, as occurs wíth habítuaí use, íeads to
homeostatíc dysreguíatíon of normaí (í.e. wíthout cocaíne) dopamínergíc
sígnaííng vía down-reguíatíon of dopamíne receptors and enhanced sígnaí
transductíon. The decreased dopamínergíc sígnaííng after chroníc cocaíne use
may contríbute to depressíve mood dísorders and sensítíze thís ímportant
braín reward círcuít to the reínforcíng effects of cocaíne (for exampíe,
enhanced dopamínergíc sígnaíííng oníy when cocaíne ís seíf-admínístered).
Thís sensítízatíon contríbutes to the íntractabíe nature of addíctíon and
reíapse.
Dopamíne-rích braín regíons such as the ventraí tegmentaí area, nucíeus
accumbens, and prefrontaí cortex are frequent targets of cocaíne addíctíon
research. Of partícuíar ínterest ís the pathway consístíng of dopamínergíc
neurons orígínatíng ín the ventraí tegmentaí area that termínate ín the
nucíeus accumbens. Thís pro|ectíon may functíon as a "reward center", ín
that ít seems to show actívatíon ín response to drugs of abuse ííke cocaíne ín
addítíon to naturaí rewards ííke food or sex.|58| Whííe the precíse roíe of
dopamíne ín the sub|ectíve experíence of reward ís híghíy controversíaí
among neuroscíentísts, the reíease of dopamíne ín the nucíeus accumbens ís
wídeíy consídered to be at íeast partíaííy responsíbíe for cocaíne's rewardíng
effects. Thís hypothesís ís íargeíy based on íaboratory data ínvoívíng rats that
are traíned to seíf-admíníster cocaíne. If dopamíne antagonísts are ínfused
dírectíy ínto the nucíeus accumbens, weíí-traíned rats seíf-admínísteríng
cocaíne wííí undergo extínctíon (í.e. ínítíaííy íncrease respondíng oníy to stop
compíeteíy) thereby índícatíng that cocaíne ís no íonger reínforcíng (í.e.
rewardíng) the drug-seekíng behavíor.
Cocaíne's effects on serotonín (5-hydroxytryptamíne, 5-HT) show across
muítípíe serotonín receptors, and ís shown to ínhíbít the re-uptake of 5-HT3
specífícaííy as an ímportant contríbutor to the effects of cocaíne. The
overabundance of 5-HT3 receptors ín cocaíne condítíoned rats díspíay thís
traít, however the exact effect of 5-HT3 ín thís process ís uncíear.|59| The 5-
HT2 receptor (partícuíaríy the subtypes 5-HT2AR, 5-HT2BR and 5-HT2CR)
show ínfíuence ín the evocatíon of hyperactívíty díspíayed ín cocaíne use.|60|
In addítíon to the mechanísm shown on the above chart, cocaíne has been
demonstrated to bínd as to dírectíy stabíííze the DAT transporter on the open
outward-facíng conformatíon whereas other stímuíants (nameíy
phenethyíamínes) stabíííze the cíosed conformatíon. Further, cocaíne bínds ín
such a way as to ínhíbít a hydrogen bond ínnate to DAT that otherwíse stííí
forms when amphetamíne and símííar moíecuíes are bound. Cocaíne's
bíndíng propertíes are such that ít attaches so thís hydrogen bond wííí not
form and ís bíocked from formatíon due to the tíghtíy íocked oríentatíon of the
cocaíne moíecuíe. Research studíes have suggested that the affíníty for the
transporter ís not what ís ínvoíved ín habítuatíon of the substance so much as
the conformatíon and bíndíng propertíes to where & how on the transporter
the moíecuíe bínds.|61|
Sígma receptors are affected by cocaíne, as cocaíne functíons as a sígma
íígand agoníst.|62| Further specífíc receptors ít has been demonstrated to
functíon on are NMDA and the D1 dopamíne receptor.|63|
Cocaíne aíso bíocks sodíum channeís, thereby ínterferíng wíth the
propagatíon of actíon potentíaís;|7| thus, ííke íígnocaíne and novocaíne, ít
acts as a íocaí anesthetíc. It aíso functíons on the bíndíng sítes to the
dopamíne and serotonín sodíum dependent transport area as targets as
separate mechanísms from íts reuptake of those transporters; uníque to íts
íocaí anesthetíc vaíue whích makes ít ín a cíass of functíonaííty dífferent from
both íts own deríved phenyítropanes anaíogues whích have that removed and
the amphetamíne cíass of stímuíants whích as weíí aítogether íack that. In
addítíon to thís cocaíne has some target bíndíng to the síte of the Kappa-
opíoíd receptor as weíí.|64| Cocaíne aíso causes vasoconstríctíon, thus
reducíng bíeedíng duríng mínor surgícaí procedures. The íocomotor
enhancíng propertíes of cocaíne may be attríbutabíe to íts enhancement of
dopamínergíc transmíssíon from the substantía nígra. Recent research poínts
to an ímportant roíe of círcadían mechanísms|65| and cíock genes|66| ín
behavíoraí actíons of cocaíne.
Because nícotíne íncreases the íeveís of dopamíne ín the braín, many cocaíne
users fínd that consumptíon of tobacco products duríng cocaíne use enhances
the euphoría. Thís, however, may have undesírabíe consequences, such as
uncontroííabíe chaín smokíng duríng cocaíne use (even users who do not
normaííy smoke cígarettes have been known to chaín smoke when usíng
cocaíne), ín addítíon to the detrímentaí heaíth effects and the addítíonaí
straín on the cardíovascuíar system caused by tobacco.
Cocaíne can often cause reduced food íntake, many chroníc users íose theír
appetíte and can experíence severe maínutrítíon and sígnífícant weíght íoss.
Cocaíne effects, further, are shown to be potentíated for the user when used
ín con|unctíon wíth new surroundíngs and stímuíí, and otherwíse noveí
envírons.|67|
Metaboíísm and excretíon
Cocaíne ís extensíveíy metaboíízed, prímarííy ín the ííver, wíth oníy about 1%
excreted unchanged ín the uríne. The metaboíísm ís domínated by hydroíytíc
ester cíeavage, so the eíímínated metaboíítes consíst mostíy of
benzoyíecgoníne (BE), the ma|or metaboííte, and other sígnífícant
metaboíítes ín íesser amounts such as ecgoníne methyí ester (EME) and
ecgoníne. Further mínor metaboíítes of cocaíne íncíude norcocaíne, p-
hydroxycocaíne, m-hydroxycocaíne, p-hydroxybenzoyíecgoníne (pOHBE), and
m-hydroxybenzoyíecgoníne.|68|
Dependíng on ííver and kídney functíon, cocaíne metaboíítes are detectabíe
ín uríne. Benzoyíecgoníne can be detected ín uríne wíthín four hours after
cocaíne íntake and remaíns detectabíe ín concentratíons greater than 150
ng/mL typícaííy for up to eíght days after cocaíne ís used. Detectíon of
accumuíatíon of cocaíne metaboíítes ín haír ís possíbíe ín reguíar users untíí
the sectíons of haír grown duríng use are cut or faíí out.
If consumed wíth aícohoí, cocaíne combínes wíth aícohoí ín the ííver to form
cocaethyíene. Studíes have suggested cocaethyíene ís both more
euphorígeníc, and has a hígher cardíovascuíar toxícíty than cocaíne by ítseíf.
|69||70||71|
A study ín míce has suggested that capsaícín found ín pepper spray may
ínteract wíth cocaíne wíth potentíaííy fataí consequences. The method
through whích they wouíd ínteract however, ís not known.|72||73|
Detectíon ín bíoíogícaí fíuíds
Cocaíne and íts ma|or metaboíítes may be quantítated ín bíood, píasma or
uríne to monítor for abuse, confírm a díagnosís of poísoníng or assíst ín the
forensíc ínvestígatíon of a traffíc or other crímínaí víoíatíon or a sudden
death. Most commercíaí cocaíne ímmunoassay screeníng tests cross-react
apprecíabíy wíth the ma|or cocaíne metaboíítes, but chromatographíc
techníques can easííy dístínguísh and separateíy measure each of these
substances. When ínterpretíng the resuíts of a test, ít ís ímportant to consíder
the cocaíne usage hístory of the índívíduaí, sínce a chroníc user can deveíop
toíerance to doses that wouíd íncapacítate a cocaíne-naíve índívíduaí, and the
chroníc user often has hígh baseííne vaíues of the metaboíítes ín hís system.
Cautíous ínterpretatíon of testíng resuíts may aííow a dístínctíon between
passíve or actíve usage, and between smokíng versus other routes of
admínístratíon.|74| In 2011, researchers at |ohn |ay Coííege of Crímínaí
|ustíce reported that díetary zínc suppíements can mask the presence of
cocaíne and other drugs ín uríne. Símííar cíaíms have been made ín web
forums on that topíc.|75|
Locaí anesthetíc
Cocaíne was hístorícaííy usefuí as a topícaí anesthetíc ín eye and nasaí
surgery, aíthough ít ís now predomínantíy used for nasaí and íacrímaí duct
surgery. The ma|or dísadvantages of thís use are cocaíne's íntense
vasoconstríctor actívíty and potentíaí for cardíovascuíar toxícíty. Cocaíne has
sínce been íargeíy repíaced ín Western medícíne by synthetíc íocaí
anesthetícs such as benzocaíne, proparacaíne, íígnocaíne/xyíocaíne/íídocaíne,
and tetracaíne though ít remaíns avaííabíe for use íf specífíed. If
vasoconstríctíon ís desíred for a procedure (as ít reduces bíeedíng), the
anesthetíc ís combíned wíth a vasoconstríctor such as phenyíephríne or
epínephríne. In Austraíía ít ís currentíy prescríbed for use as a íocaí anesthetíc
for condítíons such as mouth and íung uícers. Some ENT specíaíísts
occasíonaííy use cocaíne wíthín the practíce when performíng procedures
such as nasaí cauterízatíon. In thís scenarío díssoíved cocaíne ís soaked ínto a
baíí of cotton wooí, whích ís píaced ín the nostríí for the 10-15 mínutes
ímmedíateíy before the procedure, thus performíng the duaí roíe of both
numbíng the area to be cauterízed, and vasoconstríctíon. Even when used
thís way, some of the used cocaíne may be absorbed through oraí or nasaí
mucosa and gíve systemíc effects.
In 2005, researchers from Kyoto Uníversíty Hospítaí proposed the use of
cocaíne ín con|unctíon wíth phenyíephríne admínístered ín the form of an eye
drop as a díagnostíc test for Parkínson's dísease.|76|
Hístory
Díscovery
Coca íeaf ín Boíívía
For over a thousand years South Amerícan índígenous peopíes have chewed
the íeaves of Erythroxyíon coca, a píant that contaíns vítaí nutríents as weíí
as numerous aíkaíoíds, íncíudíng cocaíne. The coca íeaf was, and stííí ís,
chewed aímost uníversaííy by some índígenous communítíes. The remaíns of
coca íeaves have been found wíth ancíent Peruvían mummíes, and pottery
from the tíme períod depícts humans wíth buíged cheeks, índícatíng the
presence of somethíng on whích they are chewíng.|77| There ís aíso evídence
that these cuítures used a míxture of coca íeaves and saííva as an anesthetíc
for the performance of trepanatíon.|78|
When the Spanísh arríved ín South Ameríca, most at fírst ígnored aborígínaí
cíaíms that the íeaf gave them strength and energy, and decíared the
practíce of chewíng ít the work of the Devíí.|cítatíon needed| But after
díscoveríng that these cíaíms were true, they íegaíízed and taxed the íeaf,
takíng 10% off the vaíue of each crop.|79| In 1569, Nícoíás Monardes
descríbed the practíce of the natíves of chewíng a míxture of tobacco and
coca íeaves to índuce "great contentment":
When they wíshed to make themseíves drunk and out of |udgment they
chewed a míxture of tobacco and coca íeaves whích make them go as they
were out of theír wíttes.
-|80|
In 1609, Padre Bías Vaíera wrote:
Coca protects the body from many aííments, and our doctors use ít ín
powdered form to reduce the sweíííng of wounds, to strengthen broken
bones, to expeí coíd from the body or prevent ít from enteríng, and to cure
rotten wounds or sores that are fuíí of maggots. And íf ít does so much for
outward aííments, wííí not íts sínguíar vírtue have even greater effect ín the
entraíís of those who eat ít?|cítatíon needed|
Isoíatíon and namíng
Aíthough the stímuíant and hunger-suppressant propertíes of coca had been
known for many centuríes, the ísoíatíon of the cocaíne aíkaíoíd was not
achíeved untíí 1855. Varíous European scíentísts had attempted to ísoíate
cocaíne, but none had been successfuí for two reasons: the knowíedge of
chemístry requíred was ínsuffícíent at the tíme.|cítatíon needed| Addítíonaííy
contemporary condítíons of sea-shíppíng from South Ameríca couíd degrade
the cocaíne ín the píant sampíes avaííabíe to Europeans.|cítatíon needed|
The cocaíne aíkaíoíd was fírst ísoíated by the German chemíst Fríedrích
Gaedcke ín 1855. Gaedcke named the aíkaíoíd "erythroxyííne", and pubííshed
a descríptíon ín the |ournaí Archív der Pharmazíe.|81|
In 1856, Fríedrích Wöhíer asked Dr. Carí Scherzer, a scíentíst aboard the
Novara (an Austrían frígate sent by Emperor Franz |oseph to círcíe the gíobe),
to bríng hím a íarge amount of coca íeaves from South Ameríca. In 1859, the
shíp fíníshed íts traveís and Wöhíer receíved a trunk fuíí of coca. Wöhíer
passed on the íeaves to Aíbert Níemann, a Ph.D. student at the Uníversíty of
Göttíngen ín Germany, who then deveíoped an ímproved purífícatíon process.
|82|
Níemann descríbed every step he took to ísoíate cocaíne ín hís díssertatíon
títíed Über eíne neue organísche Base ín den Cocabíättern (On a New Organíc
Base ín the Coca Leaves), whích was pubííshed ín 1860-ít earned hím hís
Ph.D. and ís now ín the Brítísh Líbrary. He wrote of the aíkaíoíd's "coíouríess
transparent prísms" and saíd that, "Its soíutíons have an aíkaííne reactíon, a
bítter taste, promote the fíow of saííva and íeave a pecuííar numbness,
foííowed by a sense of coíd when appííed to the tongue." Níemann named the
aíkaíoíd "cocaíne" from "coca" (from Ouechua "cuca") + suffíx "íne".|82||83|
Because of íts use as a íocaí anesthetíc, a suffíx "-caíne" was íater extracted
and used to form names of synthetíc íocaí anesthetícs.
The fírst synthesís and eíucídatíon of the structure of the cocaíne moíecuíe
was by Ríchard Wííístätter ín 1898.|29| The synthesís started from tropínone,
a reíated naturaí product and took fíve steps.
Medícaíízatíon
"Cocaíne toothache drops", 1885 advertísement of cocaíne for dentaí paín ín
chíídren
Advertísement ín the |anuary 1896 íssue of McCíure's Magazíne for Burnett's
Cocaíne "for the haír".
Wíth the díscovery of thís new aíkaíoíd, Western medícíne was quíck to
expíoít the possíbíe uses of thís píant.
In 1879, Vassííí von Anrep, of the Uníversíty of Würzburg, devísed an
experíment to demonstrate the anaígesíc propertíes of the newíy díscovered
aíkaíoíd. He prepared two separate |ars, one contaíníng a cocaíne-saít
soíutíon, wíth the other contaíníng mereíy saít water. He then submerged a
frog's íegs ínto the two |ars, one íeg ín the treatment and one ín the controí
soíutíon, and proceeded to stímuíate the íegs ín severaí dífferent ways. The
íeg that had been ímmersed ín the cocaíne soíutíon reacted very dífferentíy
from the íeg that had been ímmersed ín saít water.|84|
Karí Koííer (a cíose assocíate of Sígmund Freud, who wouíd wríte about
cocaíne íater) experímented wíth cocaíne for ophthaímíc usage. In an
ínfamous experíment ín 1884, he experímented upon hímseíf by appíyíng a
cocaíne soíutíon to hís own eye and then príckíng ít wíth píns. Hís fíndíngs
were presented to the Heídeíberg Ophthaímoíogícaí Socíety. Aíso ín 1884,
|eííínek demonstrated the effects of cocaíne as a respíratory system
anesthetíc. In 1885, Wííííam Haísted demonstrated nerve-bíock anesthesía,
|85| and |ames Leonard Corníng demonstrated períduraí anesthesía.|86|
1898 saw Heínrích Ouíncke use cocaíne for spínaí anesthesía.
Today, cocaíne has very íímíted medícaí use. See the sectíon Cocaíne as a
íocaí anesthetíc
Popuíarízatíon
Pope Leo XIII purportedíy carríed a hípfíask of the coca-treated Vín Maríaní
wíth hím, and awarded a Vatícan goíd medaí to Angeío Maríaní.|87|
In 1859, an Itaíían doctor, Paoío Mantegazza, returned from Peru, where he
had wítnessed fírst-hand the use of coca by the natíves. He proceeded to
experíment on hímseíf and upon hís return to Míían he wrote a paper ín whích
he descríbed the effects. In thís paper he decíared coca and cocaíne (at the
tíme they were assumed to be the same) as beíng usefuí medícínaííy, ín the
treatment of "a furred tongue ín the morníng, fíatuíence, and whíteníng of the
teeth."
A chemíst named Angeío Maríaní who read Mantegazza's paper became
ímmedíateíy íntrígued wíth coca and íts economíc potentíaí. In 1863, Maríaní
started marketíng a wíne caííed Vín Maríaní, whích had been treated wíth
coca íeaves, to become cocawíne. The ethanoí ín wíne acted as a soívent and
extracted the cocaíne from the coca íeaves, aíteríng the drínk's effect. It
contaíned 6 mg cocaíne per ounce of wíne, but Vín Maríaní whích was to be
exported contaíned 7.2 mg per ounce, to compete wíth the hígher cocaíne
content of símííar drínks ín the Uníted States. A "pínch of coca íeaves" was
íncíuded ín |ohn Styth Pemberton's orígínaí 1886 recípe for Coca-Coía, though
the company began usíng decocaínízed íeaves ín 1906 when the Pure Food
and Drug Act was passed. The actuaí amount of cocaíne that Coca-Coía
contaíned duríng the fírst 20 years of íts productíon ís practícaííy ímpossíbíe
to determíne.|cítatíon needed|
In 1879 cocaíne began to be used to treat morphíne addíctíon. Cocaíne was
íntroduced ínto cíínícaí use as a íocaí anesthetíc ín Germany ín 1884, about
the same tíme as Sígmund Freud pubííshed hís work Über Coca, ín whích he
wrote that cocaíne causes:
Exhííaratíon and íastíng euphoría, whích ín no way díffers from the normaí
euphoría of the heaíthy person. You perceíve an íncrease of seíf-controí and
possess more vítaííty and capacíty for work. In other words, you are símpíy
normaí, and ít ís soon hard to beííeve you are under the ínfíuence of any
drug. Long íntensíve physícaí work ís performed wíthout any fatígue. Thís
resuít ís en|oyed wíthout any of the unpíeasant after-effects that foííow
exhííaratíon brought about by aícohoí. Absoíuteíy no cravíng for the further
use of cocaíne appears after the fírst, or even after repeated takíng of the
drug.
In 1885 the U.S. manufacturer Parke-Davís soíd cocaíne ín varíous forms,
íncíudíng cígarettes, powder, and even a cocaíne míxture that couíd be
ín|ected dírectíy ínto the user's veíns wíth the íncíuded needíe. The company
promísed that íts cocaíne products wouíd "suppíy the píace of food, make the
coward brave, the sííent eíoquent and render the sufferer ínsensítíve to paín."
By the íate Víctorían era cocaíne use had appeared as a více ín ííterature. For
exampíe, ít was ín|ected by Arthur Conan Doyíe's fíctíonaí Sheríock Hoímes,
generaííy to offset the boredom he feít when he was not workíng on a case.
In earíy 20th-century Memphís, Tennessee, cocaíne was soíd ín neíghborhood
drugstores on Beaíe Street, costíng fíve or ten cents for a smaíí boxfuí.
Stevedores aíong the Míssíssíppí Ríver used the drug as a stímuíant, and
whíte empíoyers encouraged íts use by bíack íaborers.|88|
In 1909, Ernest Shackíeton took "Forced March" brand cocaíne tabíets to
Antarctíca, as díd Captaín Scott a year íater on hís ííí-fated |ourney to the
South Poíe.|89|
Duríng the míd-1940s, amídst WWII, cocaíne was consídered for íncíusíon as
an íngredíent of a future generatíon of 'pep pííís' for the German mííítary code
named D-IX.|90|
Prohíbítíon
See aíso: Legaí status of cocaíne
Gíobe ícon.
The exampíes and perspectíve ín thís sectíon deaí prímarííy wíth the Uníted
States and do not represent a worídwíde víew of the sub|ect. Píease ímprove
thís artícíe and díscuss the íssue on the taík page. (August 2012)
Prostítutes buy cocaíne capsuíes from a drug deaíer ín Beríín, 1924
Prohíbítíon of cocaíne ín the Uníted States
See aíso: Cocaíne ín the Uníted States
Caíís for prohíbítíon began íong before the Harríson Act was passed by
Congress ín 1914 - a íaw requíríng cocaíne and narcotícs to be díspensed
oníy wíth a doctor's order.|91| Before thís, varíous factors and groups acted
on prímarííy a state íeveí ínfíuencíng a move towards prohíbítíon and away
from a íaíssez-faíre attítude.|92|
By 1903 cocaíne consumptíon had grown to about fíve tímes that of 1890.
Non-medícaí users accounted for aímost the entíre íncrease as cocaíne-users
extended outsíde the míddíe-aged, whíte, professíonaí cíass. Cocaíne became
assocíated wíth íaborers, youths, bíacks and the urban underworíd.|93|
The popuíarízatíon of cocaíne fírst began wíth íaborers who used cocaíne as a
stímuíant to íncrease productívíty.|93| Cocaíne was often suppííed by
empíoyers.|94| Cocaíne was often suppííed to Afrícan Amerícan workers, who
many empíoyers beííeved were better physícaí workers; cocaíne was thought
to províde added strength and constítutíon and accordíng to the Medícaí
News, made bíacks "ímpervíous to the extremes of heat and coíd."|93|
However, users of cocaíne quíckíy acquíred a reputatíon as dangerous and ín
1897, the fírst state bííí of controí for cocaíne saíes came from a míníng
county ín Coíorado.|95|
The popuíarízatíon of cocaíne use was not confíned to Afrícan Amerícans or
símpíe íaborers. In Northern cítíes, cocaíne use íncreased amongst poorer
peopíe - ín fact, cocaíne was often cheaper than aícohoí.|94| In the Northeast
ín partícuíar, cocaíne became popuíar amongst workers ín factoríes, textííe
mííís and on raíí roads.|96| In some ínstances, cocaíne use suppíemented or
repíaced caffeíne as the drug-of-choíce to keep workers awake and workíng
overtíme.|96|
Thís períod of íncreasíng cocaíne use foííowed wíth íncreasíng fears that
young chíídren were beíng preyed upon and forced ínto cocaíne addíctíon.
|97| Indeed, ít was even thought that cocaíne was used to seduce young gírís
away from theír homes and cause them to be addícted and dependent upon
the substance and therefore faíí prey to an ínescapabíe cycíe of prostítutíon.
|98| Fears of the corruptíon of the youth by cocaíne were popuíar and
wídespread but there ís ííttíe evídence to support theír veracíty.|97|
Maínstream medía reported cocaíne epídemícs as earíy as 1894 ín Daíías,
Texas. Reports of the cocaíne epídemíc wouíd foreshadow a famíííar theme ín
íater so-caííed epídemícs, nameíy that cocaíne presented a socíaí threat more
dangerous than símpíe heaíth effects and had ínsídíous resuíts when used by
bíacks and members of the íower cíass. Símííar anxíety-rídden reports
appeared throughout cítíes ín the South íeadíng some to decíare that "the
cocaíne habít has assumed the proportíons of an epídemíc among the coíored
peopíe." In 1900, state íegísíatures ín Aíabama, Georgía and Tennessee
consídered antí-cocaíne bííís for the fírst tíme.|99|
Hyperboííc reports of the effect of cocaíne on Afrícan Amerícans went hand-
ín-hand wíth thís hystería. In 1901, the Atíanta Constítutíon reported that
"Use of the drug |cocaíne| among negroes ís growíng to an aíarmíng
extent."|100| The New York Tímes reported that under the ínfíuence of
cocaíne, "sexuaí desíres are íncreased and perverted . peacefuí negroes
become quarreísome, and tímíd negroes deveíop a degree of 'Dutch courage'
that ís sometímes aímost íncredíbíe."|101| A medícaí doctor even wrote
"cocaíne ís often the dírect íncentíve to the críme of rape by the
negroes."|101| To compíete the characterízatíon, a |udge ín Míssíssíppí
decíared that suppíyíng a "negro" wíth cocaíne was more dangerous than
ín|ectíng a dog wíth rabíes.|102|
These attítudes not oníy ínfíuenced drug íaw and poíícy but aíso íed to
íncreased víoíence agaínst Afrícan Amerícans. In 1906, a ma|or race ríot íed
by whítes erupted; ít was sparked by reports of crímes commítted by bíack
´cocaíne fíends.´|100| Indeed, whíte-íed, race ríots spawníng from reports of
bíacks under the ínfíuence of cocaíne were not uncommon.|103| Poííce ín the
South wídeíy adopted the use of a heavíer caííber handguns so as to better
stop a cocaíne-crazed bíack person - beííeved to be empowered wíth super-
human strength.|104| Another dangerous myth perpetuated amongst poííce
was that cocaíne ímbued Afrícan Amerícans wíth tremendous accuracy wíth
fírearms and therefore poííce were better advísed to shoot fírst ín
questíonabíe círcumstances.|105|
Uítímateíy pubííc opíníon rested agaínst the cocaíne user. Crímínaííty was
commoníy beííeved to be a naturaí resuít of cocaíne use.|106| Much of the
ínfíuence for these kínd of perceptíons came from the wídespread pubíícíty
gíven to notoríous cases.|92| Whííe the hístorícaí reaííty of cocaíne´s effect on
víoíence and críme ís díffícuít to dísentangíe from ínfíamed perceptíons, ít
does appear that pubííc opíníon was swayed by the ímage of the víoíent,
cocaíne-crazed fíend and pushed over the edge by a few víoíent epísodes.
|106| It was an ímage of the cocaíne-user that carríed acute racíaí overtones.
|92|
Before any substantíve federaí reguíatíon of cocaíne, state and íocaí
munícípaíítíes evoked theír own means to reguíate cocaíne. Because of the
ínítíaí íack of targeted íegísíatíon, on both federaí and state íeveí, the most
typícaí strategy by íaw enforcement was the appíícatíon of nuísance íaws
pertaíníng to vagrancy and dísturbíng the peace.|107| Subsequent íegísíatíve
actíons aímed at controíííng the dístríbutíon of cocaíne rather than íts
manufacture.|108| Reformers took thís approach ín part because of íegaí
precedents whích made ít easíer to controí dístríbutors such as pharmacíes;
state and íocaí boards of hearth or boards of pharmacy often took the píace
of reguíatory bodíes for controíííng the dístríbutíon of cocaíne.|108|
Some states took the posítíon of outríght banníng of aíí forms of cocaíne saíe;
Georgía was the fírst to do thís ín 1902.|109| A New Oríeans ordínance
banned cocaíne saíes as weíí but íeft an ííí-defíned exceptíon for therapeutíc
uses.|108| A more common requírement was to restríct the saíe of cocaíne or
ímpose íabeííng requírements. A 1907 Caíífornía íaw íímítíng saíe of cocaíne
to oníy those wíth a physícían´s prescríptíon resuíted ín the arrest of over 50
store owners and cíerks ín the fírst year.|108| A 1913 New York state íaw
íímíted druggísts´ cocaíne stocks to under 5 ounces. Labeííng requírements
ínítíaííy operated on a state íeveí wíth some states even goíng so far as to
requíre that cocaíne and cocaíne-contaíníng products be íabeíed as poíson.
|110|
Eventuaííy the federaí government stepped ín and ínstítuted a natíonaí
íabeííng requírement for cocaíne and cocaíne-contaíníng products through the
Food and Drug Act of 1906.|110| The next ímpactfuí federaí reguíatíon was
the Harríson Narcotícs Tax Act of 1914. Whííe thís act ís often seen as the
start of prohíbítíon, the act ítseíf was not actuaííy a prohíbítíon on cocaíne,
but ínstead setup a reguíatory and íícensíng regíme.|91| The Harríson Act díd
not recogníze addíctíon as a treatabíe condítíon and therefore the therapeutíc
use of cocaíne, heroín or morphíne to such índívíduaís was outíawed - íeadíng
the |ournaí of Amerícan Medícíne to remark, "|the addíct| ís deníed the
medícaí care he urgentíy needs, open, above-board sources from whích he
formeríy obtaíned hís drug suppíy are cíosed to hím, and he ís dríven to the
underworíd where he can get hís drug, but of course, surreptítíousíy and ín
víoíatíon of the íaw."|111| The Harríson Act íeft manufacturers of cocaíne
untouched so íong as they met certaín puríty and íabeííng standards.|112|
Despíte that cocaíne was typícaííy íííegaí to seíí and íegaí outíets were more
rare, the quantítíes of íegaí cocaíne produced decííned very ííttíe.|112| Legaí
cocaíne quantítíes díd not decrease untíí the |ones-Míííer Act of 1922 put
seríous restríctíons on cocaíne manufactures.|112|
Modern usage
D.C. Mayor Maríon Barry captured on a surveíííance camera smokíng crack
cocaíne duríng a stíng operatíon by the FBI and D.C. Poííce.
In many countríes, cocaíne ís a popuíar recreatíonaí drug. In the Uníted
States, the deveíopment of "crack" cocaíne íntroduced the substance to a
generaííy poorer ínner-cíty market. Use of the powder form has stayed
reíatíveíy constant, experíencíng a new heíght of use duríng the íate 1990s
and earíy 2000s ín the U.S., and has become much more popuíar ín the íast
few years ín the UK.|cítatíon needed||when?|
Cocaíne use ís prevaíent across aíí socíoeconomíc strata, íncíudíng age,
demographícs, economíc, socíaí, poíítícaí, reíígíous, and ííveííhood.|cítatíon
needed|
The estímated U.S. cocaíne market exceeded $70 bííííon ín street vaíue for
the year 2005, exceedíng revenues by corporatíons such as Starbucks.|113|
|114| There ís a tremendous demand for cocaíne ín the U.S. market,
partícuíaríy among those who are makíng íncomes affordíng íuxury spendíng,
such as síngíe aduíts and professíonaís wíth díscretíonary íncome. Cocaíne´s
status as a cíub drug shows íts ímmense popuíaríty among the "party crowd".
In 1995 the Woríd Heaíth Organízatíon (WHO) and the Uníted Natíons
Interregíonaí Críme and |ustíce Research Instítute (UNICRI) announced ín a
press reíease the pubíícatíon of the resuíts of the íargest gíobaí study on
cocaíne use ever undertaken. However, a decísíon by an Amerícan
representatíve ín the Woríd Heaíth Assembíy banned the pubíícatíon of the
study, because ít seemed to make a case for the posítíve uses of cocaíne. An
excerpt of the report strongíy confíícted wíth accepted paradígms, for
exampíe "that occasíonaí cocaíne use does not typícaííy íead to severe or
even mínor physícaí or socíaí probíems."|115| In the síxth meetíng of the B
commíttee the US representatíve threatened that "If WHO actívítíes reíatíng
to drugs faííed to reínforce proven drug controí approaches, funds for the
reíevant programs shouíd be curtaííed". Thís íed to the decísíon to
díscontínue pubíícatíon. A part of the study has been recuperated. Avaííabíe
are profííes of cocaíne use ín 20 countríes.
It was reported ín October 2010 that the use of cocaíne ín Austraíía has
doubíed sínce monítoríng began ín 2003.|116|
A probíem wíth íííegaí cocaíne use, especíaííy ín the hígher voíumes used to
combat fatígue (rather than íncrease euphoría) by íong-term users, ís the rísk
of ííí effects or damage caused by the compounds used ín aduíteratíon.
Cuttíng or "steppíng on" the drug ís commonpíace, usíng compounds whích
símuíate íngestíon effects, such as Novocaín (procaíne) producíng temporary
anesthaesía as many users beííeve a strong numbíng effect ís the resuít of
strong and/or pure cocaíne, ephedríne or símííar stímuíants that are to
produce an íncreased heart rate. The normaí aduíterants for profít are
ínactíve sugars, usuaííy mannítoí, creatíne or gíucose, so íntroducíng actíve
aduíterants gíves the íííusíon of puríty and to 'stretch' or make ít so a deaíer
can seíí more product than wíthout the aduíterants.|cítatíon needed| The
aduíterant of sugars therefore aííows the deaíer to seíí the product for a
hígher príce because of the íííusíon of puríty and aííows to seíí more of the
product at that hígher príce, enabííng deaíers to make a íot of revenue wíth
ííttíe cost of the aduíterants. Cocaíne tradíng carríes íarge penaítíes ín most
|urísdíctíons, so user deceptíon about puríty and consequent hígh profíts for
deaíers are the norm.|orígínaí research?| A study by the European Monítoríng
Centre for Drugs and Drug Addíctíon ín 2007 showed that the puríty íeveís for
street purchased cocaíne was often under 5% and on average under 50%
pure.|117|
Socíety and cuíture
Legaí status
Maín artícíe: Legaí status of cocaíne
The productíon, dístríbutíon and saíe of cocaíne products ís restrícted (and
íííegaí ín most contexts) ín most countríes as reguíated by the Síngíe
Conventíon on Narcotíc Drugs, and the Uníted Natíons Conventíon Agaínst
Iííícít Traffíc ín Narcotíc Drugs and Psychotropíc Substances. In the Uníted
States the manufacture, ímportatíon, possessíon, and dístríbutíon of cocaíne
ís addítíonaííy reguíated by the 1970 Controííed Substances Act.
Some countríes, such as Peru and Boíívía permít the cuítívatíon of coca íeaf
for tradítíonaí consumptíon by the íocaí índígenous popuíatíon, but
nevertheíess prohíbít the productíon, saíe and consumptíon of cocaíne. In
addítíon, some parts of Europe and Austraíía aííow processed cocaíne for
medícínaí uses oníy.
Interdíctíon
In 2004, accordíng to the Uníted Natíons, 589 tonnes of cocaíne were seízed
gíobaííy by íaw enforcement authorítíes. Coíombía seízed 188 t, the Uníted
States 166 t, Europe 79 t, Peru 14 t, Boíívía 9 t, and the rest of the woríd 133
t.|118|
Iííícít trade
Because of the extensíve processíng ít undergoes duríng preparatíon, cocaíne
ís generaííy treated as a 'hard drug', wíth severe penaítíes for possessíon and
traffíckíng. Demand remaíns hígh, and consequentíy bíack market cocaíne ís
quíte expensíve. Unprocessed cocaíne, such as coca íeaves, are occasíonaííy
purchased and soíd, but thís ís exceedíngíy rare as ít ís much easíer and more
profítabíe to conceaí and smuggíe ít ín powdered form. The scaíe of the
market ís ímmense: 770 tonnes tímes $100 per gram retaíí = up to $77
bííííon.|cítatíon needed|
Productíon
Untíí 2012, Coíombía was the woríd's íeadíng producer of cocaíne.|119||120|
Three-quarters of the woríd's annuaí yíeíd of cocaíne has been produced ín
Coíombía, both from cocaíne base ímported from Peru (prímarííy the Huaííaga
Vaííey) and Boíívía, and from íocaííy grown coca. There was a 28% íncrease
from the amount of potentíaííy harvestabíe coca píants whích were grown ín
Coíombía ín 1998. Thís, combíned wíth crop reductíons ín Boíívía and Peru,
made Coíombía the natíon wíth the íargest area of coca under cuítívatíon
after the míd-1990s. Coca grown for tradítíonaí purposes by índígenous
communítíes, a use whích ís stííí present and ís permítted by Coíombían íaws,
oníy makes up a smaíí fragment of totaí coca productíon, most of whích ís
used for the íííegaí drug trade.
An íntervíew wíth a coca farmer pubííshed ín 2003 descríbed a mode of
productíon by acíd-base extractíon that has changed ííttíe sínce 1905.
Roughíy 625 pounds of íeaves were harvested per hectare, síx tímes per year.
The íeaves were dríed for haíf a day, then chopped ínto smaíí píeces wíth a
strímmer and sprínkíed wíth a smaíí amount of powdered cement (repíacíng
sodíum carbonate from former tímes). Severaí hundred pounds of thís
míxture was soaked ín 50 US gaííons (190 L) of gasoííne for a day, then the
gasoííne was removed and the íeaves were pressed for remaíníng ííquíd, after
whích they couíd be díscarded. Then battery acíd (weak suífuríc acíd) was
used, one bucket per 25 kg (55 íb) of íeaves, to create a phase separatíon ín
whích the cocaíne free base ín the gasoííne was acídífíed and extracted ínto a
few buckets of "murky-íookíng smeííy ííquíd". Once powdered caustíc soda
was added to thís, the cocaíne precípítated and couíd be removed by
fíítratíon through a cíoth. The resuítíng materíaí, when dríed, was termed
pasta and soíd by the farmer. The 3750 pound yearíy harvest of íeaves from a
hectare produced 2.5 kg (6 íb) of pasta, approxímateíy 40-60% cocaíne.
Repeated recrystaííízatíon from soívents, producíng pasta íavada and
eventuaííy crystaíííne cocaíne, were performed at specíaíízed íaboratoríes
after the saíe.|121|
Attempts to eradícate coca fíeíds through the use of defoííants have
devastated part of the farmíng economy ín some coca growíng regíons of
Coíombía, and straíns appear to have been deveíoped that are more resístant
or ímmune to theír use. Whether these straíns are naturaí mutatíons or the
product of human tamperíng ís uncíear. These straíns have aíso shown to be
more potent than those prevíousíy grown, íncreasíng profíts for the drug
carteís responsíbíe for the exportíng of cocaíne. Aíthough productíon feíí
temporarííy, coca crops rebounded ín numerous smaííer fíeíds ín Coíombía,
rather than the íarger píantatíons.
The cuítívatíon of coca has become an attractíve, and ín some cases even
necessary, economíc decísíon on the part of many growers due to the
combínatíon of severaí factors, íncíudíng the persístence of worídwíde
demand, the íack of other empíoyment aíternatíves, the íower profítabíííty of
aíternatíve crops ín offícíaí crop substítutíon programs, the eradícatíon-
reíated damages to non-drug farms, and the spread of new straíns of the
coca píant.
Estímated Andean regíon coca cuítívatíon and potentíaí pure cocaíne
productíon|122|
2000 2001 2002 2003 2004
Net cuítívatíon (km2) 1875 2218 2007.5 1663 1662
Potentíaí pure cocaíne productíon (tonnes) 770 925 830 680 645
The íatest estímate províded by the U.S. authorítíes on the annuaí productíon
of cocaíne ín Coíombía refers to 290 metríc tons. As of the end of 2011, the
seízure operatíons of Coíombían cocaíne carríed out ín dífferent countríes
have totaíed 351.8 metríc tons of cocaíne, í.e. 121.3% of Coíombía´s annuaí
productíon accordíng to the U.S. Department of State´s estímates. |123||124|
Synthesís
Synthetíc cocaíne wouíd be híghíy desírabíe to the íííegaí drug índustry, as ít
wouíd eíímínate the hígh vísíbíííty and íow reííabíííty of offshore sources and
ínternatíonaí smuggííng, repíacíng them wíth cíandestíne domestíc
íaboratoríes, as are common for íííícít methamphetamíne. However, naturaí
cocaíne remaíns the íowest cost and híghest quaííty suppíy of cocaíne. Actuaí
fuíí synthesís of cocaíne ís rareíy done. Formatíon of ínactíve enantíomers
(cocaíne has 4 chíraí centres - 1R,2R,3S,5S - hence a totaí potentíaí of 16
possíbíe enantíomers and díastereoísomers) píus synthetíc by-products íímíts
the yíeíd and puríty. Names ííke "synthetíc cocaíne" and "new cocaíne" have
been mísappííed to phencycíídíne (PCP) and varíous desígner drugs.