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Cocaine (from , from , ultimately from
Quechua Quechua may refer to: *Quechua people, several indigenous ethnic groups in South America, especially in Peru *Quechuan languages, a Native South American language family spoken primarily in the Andes, derived from a common ancestral language **Sou ...
: ''kúka'') is a
tropane alkaloid Tropane alkaloids are a class of bicyclic .2.1alkaloid Alkaloids are a class of basic BASIC (Beginners' All-purpose Symbolic Instruction Code) is a family of General-purpose programming language, general-purpose, high-level programming langu ...
and stimulant drug obtained primarily from the leaves of two coca species native to South America, ''
Erythroxylum coca ''Erythroxylum coca'' is one of two species of cultivated coca Coca is any of the four cultivated plants in the family (biology), family Erythroxylaceae, native to western South America. Coca is known worldwide for its Psychoactive plant, psyc ...

Erythroxylum coca
'' and ''
Erythroxylum novogranatense ''Erythroxylum novogranatense'' is a neotropical species In biology, a species is the basic unit of biological classification, classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often define ...

Erythroxylum novogranatense
''. It is most commonly used as a
recreational drug Recreational drug use is the use of a psychoactive drug A psychoactive drug, psychopharmaceutical, psychoactive agent, or psychotropic drug, is a chemical substance that changes nervous system function and results in alterations in perception, ...
and
euphoriant Euphoria ( ) is the experience (or affect Affect may refer to: * Affect (education) * Affect (linguistics), attitude or emotion that a speaker brings to an utterance * Affect (philosophy) * Affect (psychology), the experience of feeling or e ...
. After extraction from coca leaves and further processing into cocaine hydrochloride (powdered cocaine), the drug may be snorted, heated until sublimated and then inhaled, or dissolved and injected into a
vein Veins are blood vessels The blood vessels are the components of the circulatory system The circulatory system, also called the cardiovascular system or the vascular system, is an organ system An organ system is a biological system A b ...

vein
. Mental effects may include an ,
sexual arousal Sexual arousal (also sexual excitement) is typically the arousal Arousal is the physiological and psychological Psychology is the science of mind and behavior. Psychology includes the study of consciousness, conscious and Unconscio ...
, loss of contact with reality, or
agitation Agitation may refer to: * Agitation (action), putting into motion by shaking or stirring, often to achieve mixing * An emotional state of stimulation, excitement or restlessness ** Psychomotor agitation, an extreme form of the above, which can be p ...
. Physical symptoms may include a
fast heart rate Tachycardia, also called tachyarrhythmia, is a heart rateHeart rate is the speed of the heartbeat measured by the number of contractions (beats) of the heart The heart is a muscle, muscular Organ (anatomy), organ in most animals, which pu ...
, sweating, and
dilated pupils Mydriasis is the Pupillary dilation, dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, Physical trauma, trauma, or the use of d ...

dilated pupils
. High doses can result in
high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term Long-Term Capital Management L.P. (LTCM) was a hedge fund''A financial History of the United States Volume II: 1970–2001'', Jerry W. Markham, Chapter 5: "Bank ...

high blood pressure
or
body temperature Thermoregulation is the ability of an organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual contiguous system that embodies the Life#Biology, properties of life. It is a sy ...
. Effects begin within seconds to minutes of use and last between five and ninety minutes. Cocaine crosses the blood-brain barrier via a proton-coupled organic cation antiporter and (to a much lesser extent) via passive diffusion. Cocaine acts as an indirect
sympathomimetic Sympathomimetic drugs (also known as adrenergic drugs and adrenergic amines) are stimulant compounds which mimic the effects of endogenous Endogenous substances and processes are those that originate from within a system such as an organism, Tis ...
by blocking the
dopamine transporter The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dopamine ...
, inhibiting
reuptake 350px, A synapse during re-uptake. Note that some neurotransmitters are lost and not reabsorbed. Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the S ...
of
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical , CH4; is among the simplest organic compounds. In chemistry Chemistry is t ...

dopamine
from the
synaptic cleft Synaptic may refer to: * Synapse SyNAPSE is a DARPA program that aims to develop electronic neuromorphic machine technology, an attempt to build a new kind of cognitive computer with form, function, and architecture similar to the mammalian bra ...
into the pre-synaptic
axon terminal Axon terminals (also called synaptic boutons, terminal boutons, or end-feet) are distal terminations of the telodendria An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences Despite ...
; the higher dopamine levels in the synaptic cleft increase
dopamine receptor Dopamine receptors are a class of G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked recep ...
activation in the post-synaptic neuron, which drives the effects of euphoria and arousal. Cocaine also blocks the
serotonin transporter The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a v ...
and
norepinephrine transporter The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT) and solute carrier family 6 member 2 (SLC6A2), is a protein Proteins are large biomolecules or macromolecules that are comprised of one or more long chains of ...
, inhibiting reuptake of
serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter Monoamine neurotransmitters are s and s that contain one group connected to an by a two-carbon chain (such as -CH2-CH2-). Examples are , and . All monoamines are ...

serotonin
and
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical , CH4; is among the simplest organic compounds. In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and ...

norepinephrine
from the synaptic cleft into the pre-synaptic
axon terminal Axon terminals (also called synaptic boutons, terminal boutons, or end-feet) are distal terminations of the telodendria An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences Despite ...
and increasing activation of
serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors , or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the Central nervous system, central and peripheral nervous systems. They mediate both Neurotr ...
s and norepinephrine receptors in the post-synaptic neuron, contributing to the modulation of consciousness, emotions, and movements that characterize cocaine exposure. Cocaine is
addictive Addiction is a biopsychosocial disorder characterized by repeated use of drugs, or repetitive engagement in a behavior such as gambling, despite harm to self and others. According to the "brain disease model of addiction," while a number ...
due to its effect on the
reward pathway The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain A brain is an organ (anatomy), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It ...

reward pathway
in the brain. A single dose of cocaine induces tolerance to the drug's effects. After a short period of use, dependence is likely. Abstention from cocaine after chronic use results in
drug withdrawal Drug withdrawal, drug withdrawal syndrome, or substance withdrawal syndrome, is the group of symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may b ...
, with symptoms that may include
depression Depression may refer to: Mental health * Depression (mood), a state of low mood and aversion to activity * Mood disorders characterized by depression are commonly referred to as simply ''depression'', including: ** Dysthymia ** Major depressive ...
, decreased libido, decreased ability to feel pleasure and subjective fatigue. Cocaine's use increases the overall risk of death and particularly the risk of trauma, and infectious diseases, such as blood infections and AIDS. It also increases risk of
stroke A stroke is a medical condition A disease is a particular abnormal condition that negatively affects the structure or function (biology), function of all or part of an organism, and that is not due to any immediate external injury. Di ...

stroke
,
heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow Hemodynamics American and British English spelling differences#ae and oe, or haemodynamics are the Fluid dynamics, dynamics of blood flow. The circulatory sy ...

heart attack
, cardiac arrhythmia, lung injury (when smoked), and
sudden cardiac death Cardiac arrest is a sudden loss of blood flow resulting from the failure of the heart The heart is a muscle, muscular Organ (anatomy), organ in most animals, which pumps blood through the blood vessels of the circulatory system. The pump ...
. Illicitly sold cocaine is commonly adulterated with
local anesthetics A local anesthetic (LA) is a medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, therapy, treat, or preventive medicine, preven ...
,
levamisole Levamisole, sold under the brand name Ergamisol among others, is a medication used to treat parasitic worm infections. Specifically it is used for ascariasis and hookworm infections. It is taken by mouth. Side effects may include abdominal pa ...

levamisole
, cornstarch,
quinine Quinine is a medication used to treat malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms Signs and symptoms are the observed or detectable signs, and experienced sympto ...

quinine
, or sugar, which can result in additional toxicity. The Global Burden of Disease study found that cocaine use caused around 7300 deaths in 2007. Globally in 2018, cocaine was used by an estimated 19 million people (0.4% of people aged 18 – 64 years). The highest prevalence of cocaine use was in Australia and New Zealand (2.2%), followed by North America (2.1%), Western and Central Europe (1.4%), Central America (0.7%), and South America (1.0%). Coca leaves have been used by
Andean civilizations The Andean civilizations were complex societies A complex society is a concept that is shared by a range of disciplines including anthropology Anthropology is the Science, scientific study of humanity, concerned with human behavior, human ...
since
ancient times Ancient history is the aggregate of past eventsWordNet Search – 3.0
"History"
from t ...
. In ancient
Wari culture The Wari ( es, Huari) were a Middle Horizon civilization that flourished in the south-central Andes The Andes, Andes Mountains or Andean Mountains ( es, Cordillera de los Andes) are the List of mountain ranges#Mountain ranges by length, long ...
,
Incan The Inca Empire, also known as Incan Empire and the Inka Empire, and at the time known as the Realm of the Four Parts,,  "four parts together" was the largest empire in pre-Columbian America. The administrative, political and military ce ...
culture, through successor cultures in modern
indigenous Indigenous may refer to: *Indigenous peoples Indigenous peoples, also referred to as First people, Aboriginal people, Native people, or autochthonous people, are culturally distinct ethnic groups who are native to a particular place. The term ' ...
cultures of the
Andes mountains The Andes, Andes Mountains or Andean Mountains ( es, Cordillera de los Andes) are the longest continental mountain range in the world, forming a continuous highland along the western edge of South America South America is a continent e ...

Andes mountains
, coca leaves are chewed, taken orally in the form of a
tea Tea is an aromatic beverage prepared by pouring hot or boiling water over cured A cure is a completely effective treatment for a disease. Cure, or similar, may also refer to: Places * Cure (river), a river in France * Cures, Sabinum, an ...

tea
, or alternatively, prepared in a sachet wrapped around alkaline burnt ashes, and held in the mouth against the cheek, and used to combat the effects of cold, hunger, and altitude sickness. Cocaine was first isolated from the leaves in 1860. Since 1961, the international
Single Convention on Narcotic Drugs The Single Convention on Narcotic Drugs of 1961 is an international treaty that prohibits production and supply of specific narcotic Heroin, a powerful opioid and narcotic The term narcotic (, from ancient Greek Ancient Greek incl ...
has required countries to make recreational use of cocaine a
crime In ordinary language, a crime is an unlawful act punishable by a state State may refer to: Arts, entertainment, and media Literature * ''State Magazine'', a monthly magazine published by the U.S. Department of State * The State (newspaper ...

crime
.


Uses


Medical

Topical cocaine can be used as a local numbing agent to help with painful procedures in the mouth or nose. Cocaine may be used for nasal and
lacrimal duct The lacrimal canaliculi, (sing. canaliculus), are the small channels in each eyelid that drain lacrimal fluid, from the Lacrimal punctum, lacrimal puncta to the lacrimal sac. This forms part of the lacrimal apparatus that drains lacrimal fluid fro ...
surgery. The major disadvantages of this use are cocaine's potential for
cardiovascular The circulatory system, also called the cardiovascular system or the vascular system, is an organ system An organ system is a group of organs An organ is a group of tissues with similar functions. Plant life and animal life rely on many o ...
toxicity,
glaucoma Glaucoma is a group of eye diseases which result in damage to the optic nerve The optic nerve, also known as cranial nerve II, or simply as CN II, is a paired cranial nerve Cranial nerves are the nerve A nerve is an enclosed, cable-l ...

glaucoma
, and
pupil dilation Pupillary response is a physiological Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology Biology is the natural science that studies life and living organisms, includin ...

pupil dilation
. Medicinal use of cocaine has decreased as other synthetic local anesthetics such as
benzocaine Benzocaine, sold under the brand name Orajel amongst others, is an ester An ester is a chemical compound derived from an acid (organic or inorganic) in which at least one –OH hydroxyl group is replaced by an –O– alkyl (alkoxy) group, as ...

benzocaine
, ,
lidocaine Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates ...

lidocaine
, and
tetracaine Tetracaine, also known as amethocaine, is an ester local anesthetic A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates an absence of pain in a specific location of ...

tetracaine
are now used more often. If vasoconstriction is desired for a procedure (as it reduces bleeding), the anesthetic is combined with a vasoconstrictor such as
phenylephrine Phenylephrine is a medication primarily used as a decongestant, to dilate the pupil, to increase blood pressure Blood pressure (BP) is the pressure Pressure (symbol: ''p'' or ''P'') is the force In physics Physics (from ...

phenylephrine
or
epinephrine Adrenaline, also known as epinephrine, is a hormone A hormone (from the Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a co ...
. Some
otolaryngology Otorhinolaryngology ( ; abbreviated ORL; also called otolaryngology; other terms include otolaryngology–head and neck surgery (ORL–H&N, OHNS) and ear, nose, and throat, often called ENT) is a surgical subspecialty within medicine that de ...
(ENT) specialists occasionally use cocaine within the practice when performing procedures such as nasal
cauterization Cauterization (or cauterisation, or cautery) is a medical practice or technique of burning Combustion, or burning, is a high-temperature exothermic redox chemical reaction A chemical reaction is a process that leads to the chemical transfo ...
. In this scenario dissolved cocaine is soaked into a ball of cotton wool, which is placed in the nostril for the 10–15 minutes immediately before the procedure, thus performing the dual role of both numbing the area to be cauterized, and vasoconstriction. Even when used this way, some of the used cocaine may be absorbed through oral or nasal mucosa and give systemic effects. An alternative method of administration for ENT surgery is mixed with
adrenaline Adrenaline, also known as epinephrine, is a hormone A hormone (from the Greek participle , "setting in motion") is any member of a class of signaling molecules in multicellular organisms, that are transported to distant organs to regulate p ...

adrenaline
and
sodium bicarbonate Sodium bicarbonate ( IUPAC name: sodium hydrogen carbonate), commonly known as baking soda or bicarbonate of soda, is a chemical compound with the formula NaHCO3. It is a salt composed of a sodium cation (Na+) and a bicarbonate anion ( HCO3 ...

sodium bicarbonate
, as Moffett's solution. Cocaine
hydrochlorideIn chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution ...
(Goprelto), an ester local anesthetic, was approved for medical use in the United States in December 2017, and is indicated for the introduction of local anesthesia of the mucous membranes for diagnostic procedures and surgeries on or through the nasal cavities of adults. Cocaine hydrochloride (Numbrino) was approved for medical use in the United States in January 2020. The most common adverse reactions in people treated with Goprelto are headache and
epistaxis A nosebleed, also known as epistaxis, is bleeding from the nose A nose is a protuberance in vertebrates that houses the nostrils, or nares, which receive and expel air for Respiration (physiology), respiration alongside the mouth. Behind th ...
. The most common adverse reactions in people treated with Numbrino are hypertension, tachycardia, and sinus tachycardia.


Recreational

Cocaine is a nervous system stimulant. Its effects can last from 15 minutes to an hour. The duration of cocaine's effects depends on the amount taken and the route of administration. Cocaine can be in the form of fine white powder, bitter to the taste.
Crack cocaine Crack cocaine, commonly known simply as crack, and also known as rock, is a free base Free base (freebase, free-base) is the conjugate base (deprotonated) form of an amine In organic chemistry, amines (, ) are organic compound, compounds ...
is a smokeable form of cocaine made into small "rocks" by processing cocaine with sodium bicarbonate (baking soda) and water. Crack cocaine is referred to as "crack" because of the crackling sounds it makes when heated. Cocaine use leads to increases in alertness, feelings of well-being and
euphoria Euphoria ( ) is the experience (or affect Affect may refer to: * Affect (education) * Affect (linguistics), attitude or emotion that a speaker brings to an utterance * Affect (philosophy) * Affect (psychology), the experience of feeling or e ...

euphoria
, increased energy and motor activity, and increased feelings of competence and sexuality. Analysis of the
correlation In statistics Statistics is the discipline that concerns the collection, organization, analysis, interpretation, and presentation of data Data (; ) are individual facts, statistics, or items of information, often numeric. In a m ...
between the use of 18 various
psychoactive substance A psychoactive drug, psychopharmaceutical, psychoactive agent, or psychotropic drug, is a chemical substance that changes nervous system function and results in alterations in perception, mood (psychology), mood, consciousness, cognition, or beha ...
s shows that cocaine use correlates with other " party drugs" (such as
ecstasy Ecstasy may refer to: * Ecstasy (emotion), a trance or trance-like state in which a person transcends normal consciousness * Religious ecstasy, a state of consciousness, visions or absolute euphoria * Ecstasy (philosophy), to be or stand outside on ...
or
amphetamines#REDIRECT Substituted amphetamine#REDIRECT Substituted amphetamine Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative In mathematics Mathematics (from Ancient Greek, Gre ...
), as well as with
heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is an opioid Opioids are substances that act on opioid receptor Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. T ...

heroin
and
benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of psychoactive drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. The first such drug, chlordiazepoxide (Librium), was role of chance ...

benzodiazepine
s use, and can be considered as a bridge between the use of different groups of drugs.


Coca leaves

Coca Coca is any of the four cultivated plants in the family In , family (from la, familia) is a of people related either by (by recognized birth) or (by marriage or other relationship). The purpose of families is to maintain the well-bei ...

Coca
leaves are legal in some Andean nations, such as Peru and Bolivia, where they are chewed, consumed in the form of tea, or are sometimes incorporated into food products.
Coca Coca is any of the four cultivated plants in the family In , family (from la, familia) is a of people related either by (by recognized birth) or (by marriage or other relationship). The purpose of families is to maintain the well-bei ...

Coca
leaves are typically mixed with an alkaline substance (such as
lime Lime refers to: * Lime (fruit), a green citrus fruit * Lime (material), inorganic materials containing calcium, usually calcium oxide or calcium hydroxide * Lime (color), a color between yellow and green Lime may also refer to: Botany * Austra ...

lime
) and chewed into a wad that is retained in the
buccal pouch Cheek pouches are pockets on both sides of the head of some mammals between the jaw and the cheek. They can be found on mammals including the platypus, some rodents, and most monkeys, as well as the marsupial koala. The cheek pouches of chipmunks ...
(mouth between gum and cheek, much the same as
chewing tobacco Chewing tobacco is a type of smokeless tobacco, smokeless tobacco product that is placed between the cheek and lower gum to draw out its flavor. Some users chew it, others do not. It consists of coarsely chopped aged tobacco that is flavored and o ...
is chewed) and sucked of its juices. The juices are absorbed slowly by the mucous membrane of the inner cheek and by the gastrointestinal tract when swallowed. Alternatively, coca leaves can be infused in liquid and consumed like tea. , an infusion of coca leaves, is also a traditional method of consumption. The tea has often been recommended for travelers in the Andes to prevent
altitude sickness Altitude sickness, the mildest form being acute mountain sickness (AMS), is the harmful effect of high altitude, caused by rapid exposure to low amounts of oxygen at high elevation. People can respond to high altitude in different ways. Symptom ...
. Its actual effectiveness has never been systematically studied. In 1986 an article in the ''
Journal of the American Medical Association ''JAMA: The Journal of the American Medical Association'' is a peer-reviewed medical journalA medical journal is a peer-reviewed scientific journal that communicates medicine, medical information to physicians and other health professionals. Jou ...
'' revealed that U.S.
health food store A health food store (or health food shop) is a type of grocery store A grocery store (North America), grocer or grocery shop (UK), is a store primarily engaged in retailing a general range of food products, which may be fresh or packaged. In ...
s were selling dried coca leaves to be prepared as an infusion as "Health Inca Tea." While the packaging claimed it had been "decocainized," no such process had actually taken place. The article stated that drinking two cups of the tea per day gave a mild
stimulation Stimulation is the encouragement of development or the cause of activity generally. For example, "The press provides stimulation of political discourse." An interesting or fun activity can be described as "stimulating", regardless of its physica ...
, increased
heart rate Heart rate is the speed of the heartbeat Heartbeat or heartbeats may refer to: Physiology *Cardiac cycle, of the heart *Contraction of the cardiac muscle, muscles of the heart, or a perceived effect of it, such as: **Heart sounds, the noises gene ...

heart rate
, and mood elevation, and the tea was essentially harmless. Despite this, the seized several shipments in
Hawaii Hawaii ( ; haw, Hawaii or ) is a state State may refer to: Arts, entertainment, and media Literature * ''State Magazine'', a monthly magazine published by the U.S. Department of State * The State (newspaper), ''The State'' (newspape ...

Hawaii
,
Chicago (''City in a Garden''); I Will , image_map = , map_caption = Interactive map of Chicago , coordinates = , coordinates_footnotes = , subdivision_type = Country , subdivision_name ...

Chicago
,
Georgia Georgia usually refers to: * Georgia (country) Georgia (, ; ) is a country located at the intersection of Eastern Europe and Western Asia. It is a part of the Caucasus region, bounded to the west by the Black Sea, to the north and east by ...
, and several locations on the
East Coast of the United States The East Coast of the United States, also known as the Eastern Seaboard, the Atlantic Coast, and the Atlantic Seaboard, is the coast The coast, also known as the coastline or seashore, is defined as the area where land meets the sea or ocean ...
, and the product was removed from the shelves.


Insufflation

Nasal
insufflation In religious and magical practice, insufflation and exsufflation are ritual acts of blowing, breathing, hissing, or puffing that signify variously expulsion or renunciation of evil or of the devil (the Evil One), or infilling or blessing with good ...
(known colloquially as "snorting", "sniffing", or "blowing") is a common method of ingestion of recreational powdered cocaine. The drug coats and is absorbed through the
mucous membrane A mucous membrane or mucosa is a biological membrane, membrane that lines various cavities in the body and covers the surface of internal organs. It consists of one or more layers of Epithelium, epithelial cells overlying a layer of loose connect ...
s lining the nasal passages. Cocaine's desired euphoric effects are delayed when snorted through the nose by about five minutes. This occurs because cocaine's absorption is slowed by its constricting effect on the blood vessels of the nose. Insufflation of cocaine also leads to the longest duration of its effects (60–90 minutes). When insufflating cocaine, absorption through the nasal membranes is approximately 30–60% In a study of cocaine users, the average time taken to reach peak subjective effects was 14.6 minutes. Any damage to the inside of the nose is because cocaine highly constricts blood vessels – and therefore blood and oxygen/nutrient flow – to that area. Rolled up
banknotes A banknote (often known as a bill (in the US and Canada), paper money, or simply a note) is a type of negotiable instrument, negotiable promissory note, made by a bank or other licensed authority, payable to the bearer on demand. Banknotes w ...

banknotes
, hollowed-out
pen A pen is a common writing instrument A writing implement or writing instrument is an object used to produce writing Writing is a medium of human communication that involves the representation of a language with written symbols. Writing sy ...

pen
s, cut straws, pointed ends of keys, specialized spoons, long
fingernails A nail is a claw-like keratinous plate at the tip of the fingers and toes in most primates. Nails correspond to claws found in other animals. Fingernails and toenails are made of a tough protective protein called alpha-keratin which is a polymer a ...

fingernails
, and (clean) tampon applicators are often used to insufflate cocaine. The cocaine typically is poured onto a flat, hard surface (such as a mirror, CD case or book) and divided into "bumps," "lines" or "rails," and then insufflated. A 2001 study reported that the sharing of straws used to "snort" cocaine can spread blood diseases such as
hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...

hepatitis C
.


Injection

Subjective effects not commonly shared with other methods of administration include a ringing in the ears moments after injection (usually when over 120 milligrams) lasting two to 5 minutes including
tinnitus Tinnitus is the perception of sound when no corresponding external sound is present. Nearly everyone will experience a faint "normal tinnitus" in a completely quiet room but it is only of concern if it is bothersome or interferes with normal h ...

tinnitus
and audio distortion. This is colloquially referred to as a "bell ringer". In a study of cocaine users, the average time taken to reach peak subjective effects was 3.1 minutes. The euphoria passes quickly. Aside from the toxic effects of cocaine, there is also the danger of circulatory
emboli An embolism is the lodging of an embolus An embolus (; plural emboli; from the Greek ἔμβολος "wedge", "plug") is an unattached mass that travels through the bloodstream The circulatory system, also called the cardiovascular system ...
from the insoluble substances that may be used to cut the drug. As with all injected illicit substances, there is a risk of the user contracting blood-borne infections if sterile injecting equipment is not available or used. An injected mixture of cocaine and
heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is an opioid Opioids are substances that act on opioid receptor Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. T ...

heroin
, known as " speedball", is a particularly dangerous combination, as the converse effects of the drugs actually complement each other, but may also mask the symptoms of an overdose. It has been responsible for numerous deaths, including celebrities such as comedians/actors
John Belushi John Adam Belushi (January 24, 1949 – March 5, 1982) was an American actor, comedian and singer, and one of the seven original cast members of the NBC sketch comedy show ''Saturday Night Live'' (''SNL''). Throughout his career, Belushi had a ...
and
Chris Farley Christopher Crosby Farley (February 15, 1964 – December 18, 1997) was an American actor and comedian. Farley was known for his loud, energetic comedic style, and was a member of Chicago's The Second City, Second City Theatre and later a Sat ...
,
Mitch Hedberg Mitchell Lee Hedberg (February 24, 1968 – March 29, 2005) was an American stand-up comedian known for his surreal humor and deadpan delivery. His comedy typically featured short, sometimes one-line jokes mixed with absurd elements and non ...
,
River Phoenix River Jude Phoenix (Given name, né Bottom; August 23, 1970 – October 31, 1993) was an American actor, musician, and activist. Phoenix grew up in an Wikt:itinerant, itinerant family, as older brother of Rain Phoenix, Joaquin Phoenix, Liberty ...

River Phoenix
, grunge singer
Layne Staley Layne Thomas Staley (born Layne Rutherford Staley; August 22, 1967 – April 5, 2002) was an American musician best known as the original lead singer and co-songwriter of the rock band Alice in Chains, which rose to international fame in the earl ...

Layne Staley
and actor
Philip Seymour Hoffman Philip Seymour Hoffman (July 23, 1967 – February 2, 2014) was an American actor, director, and producer. Best known for his distinctive supporting and character roles A character actor is a supporting actor who plays unusual, interest ...

Philip Seymour Hoffman
. Experimentally, cocaine injections can be delivered to animals such as
fruit flies Fruit fly may refer to: Organisms * Drosophilidae, a family of smaller flies, including: ** ''Drosophila'', the genus of small fruit flies and vinegar flies ** ''Drosophila melanogaster'' or common fruit fly, an important model organism in modern b ...

fruit flies
to study the mechanisms of cocaine addiction.


Inhalation

The onset of cocaine's desired euphoric effects is fastest with inhaling cocaine and begins after 3–5 seconds. In contrast, inhalation of cocaine leads to the shortest duration of its effects (5–15 minutes). The two main ways cocaine is smoked are freebasing and by using cocaine which has been converted to smokable "
crack cocaine Crack cocaine, commonly known simply as crack, and also known as rock, is a free base Free base (freebase, free-base) is the conjugate base (deprotonated) form of an amine In organic chemistry, amines (, ) are organic compound, compounds ...
". Cocaine is smoked by inhaling the vapor produced when solid cocaine is heated to the point that it sublimates. In a 2000 Brookhaven National Laboratory medical department study, based on self-reports of 32 people who used cocaine who participated in the study,"peak high" was found at a mean of 1.4min +/- 0.5 minutes.
Pyrolysis The pyrolysis (or devolatilization) process is the of materials at elevated temperatures in an inert atmosphere. It involves a change of . The word is coined from the -derived s ''pyro'' "fire" and ' "separating". Pyrolysis is most commonly us ...

Pyrolysis
products of cocaine that occur only when heated/smoked have been shown to change the effect profile, ''i.e.'' anhydroecgonine methyl ester, when co-administered with cocaine, increases the dopamine in CPu and NAc brain regions, and has M1- and M3- receptor affinity. Smoking freebase or crack cocaine is most often accomplished using a pipe made from a small glass tube, often taken from "s", small glass tubes with a paper rose that are promoted as romantic gifts. These are sometimes called "stems", "horns", "blasters" and "straight shooters". A small piece of clean heavy copper or occasionally stainless steel scouring padoften called a "brillo" (actual
Brillo Pad Brillo is a trade name A trade name, trading name, or business name is a pseudonym used by companies that do not operate under their registered company name. The term for this type of alternative name is a "fictitious" business name. Registerin ...
s contain soap, and are not used) or "chore" (named for Chore Boy brand copper scouring pads)serves as a reduction base and flow modulator in which the "rock" can be melted and boiled to vapor. Crack is smoked by placing it at the end of the pipe; a flame held close to it produces vapor, which is then inhaled by the smoker. The effects felt almost immediately after smoking, are very intense and do not last long usually 2 to 10 minutes. When smoked, cocaine is sometimes combined with other drugs, such as cannabis (drug), cannabis, often rolled into a joint or blunt (drug culture), blunt.


Effects

File:US timeline. Opioid involvement in cocaine overdose.jpg, Opioid involvement in cocaine overdose deaths. The green line is cocaine and any opioid (top line in 2017). The gray line is cocaine without any opioids (bottom line in 2017). The yellow line is cocaine and other :Synthetic opioids, synthetic opioids (middle line in 2017). File:Rational harm assessment of drugs radar plot.svg, Delphi method, Delphic analysis regarding 20 popular recreational drugs based on expert opinion. Cocaine was ranked the 2nd in dependence and physical harm and 3rd in social harm.


Acute

Acute exposure to cocaine has many effects on humans, including euphoria, increases in heart rate and blood pressure, and increases in cortisol secretion from the adrenal gland. In humans with acute exposure followed by continuous exposure to cocaine at a constant blood concentration, the acute tolerance to the chronotropic cardiac effects of cocaine begins after about 10 minutes, while acute tolerance to the euphoric effects of cocaine begins after about one hour. With excessive or prolonged use, the drug can cause itching,
fast heart rate Tachycardia, also called tachyarrhythmia, is a heart rateHeart rate is the speed of the heartbeat measured by the number of contractions (beats) of the heart The heart is a muscle, muscular Organ (anatomy), organ in most animals, which pu ...
, and formication, paranoid delusions or sensations of insects crawling on the skin. Intranasal cocaine and crack use are both associated with pharmacological violence. Aggressive behavior may be displayed by both addicts and casual users. Cocaine can induce psychosis characterized by paranoia, impaired reality testing, hallucinations, irritability, and physical aggression. Cocaine intoxication can cause hyperawareness, hypervigilance, and psychomotor agitation and delirium. Consumption of large doses of cocaine can cause violent outbursts, especially by those with preexisting psychosis. Crack-related violence is also systemic, relating to disputes between crack dealers and users. Acute exposure may induce cardiac arrhythmias, including atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, and ventricular fibrillation. Acute exposure may also lead to angina,
heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow Hemodynamics American and British English spelling differences#ae and oe, or haemodynamics are the Fluid dynamics, dynamics of blood flow. The circulatory sy ...

heart attack
, and congestive heart failure. Cocaine overdose may cause seizures, hyperthermia, abnormally high body temperature and a marked elevation of blood pressure, which can be life-threatening, Heart arrhythmia, abnormal heart rhythms, and death. Anxiety, paranoia, and restlessness can also occur, especially during the comedown. With excessive dosage, tremors, convulsions and increased body temperature are observed. Severe cardiac adverse events, particularly
sudden cardiac death Cardiac arrest is a sudden loss of blood flow resulting from the failure of the heart The heart is a muscle, muscular Organ (anatomy), organ in most animals, which pumps blood through the blood vessels of the circulatory system. The pump ...
, become a serious risk at high doses due to cocaine's blocking effect on cardiac sodium channels. Incidental exposure of the eye to sublimated cocaine while smoking crack cocaine can cause serious injury to the cornea and long-term loss of visual acuity.


Chronic

Although it has been commonly asserted, the available evidence does not show that chronic use of cocaine is associated with broad cognitive deficits. Research is inconclusive on age-related loss of striatum, striatal
dopamine transporter The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dopamine ...
(DAT) sites, suggesting cocaine has neuroprotective or neurodegenerative properties for dopamine neurons. Exposure to cocaine may lead to the breakdown of the blood-brain barrier. Physical side effects from chronic smoking of cocaine include hemoptysis, coughing up blood, bronchospasm, pruritus, itching, fever, diffuse alveolar infiltrates without effusions, pulmonary and systemic eosinophilia, chest pain, lung trauma, sore throat, asthma, hoarse voice, dyspnea (shortness of breath), and an aching, flu-like syndrome. Cocaine Vasoconstriction, constricts blood vessels, Mydriasis, dilates pupils, and increases body temperature, heart rate, and blood pressure. It can also cause headaches and gastrointestinal complications such as abdominal pain and nausea. A common but untrue belief is that the smoking of cocaine chemically breaks down tooth enamel and causes tooth decay. Cocaine can cause involuntary tooth grinding, known as bruxism, which can deteriorate tooth enamel and lead to gingivitis. Additionally, stimulants like cocaine, methamphetamine, and even caffeine cause dehydration and Xerostomia, dry mouth. Since saliva is an important mechanism in maintaining one's oral pH level, people who use cocaine over a long period of time who do not hydrate sufficiently may experience demineralization of their teeth due to the pH of the tooth surface dropping too low (below 5.5). Cocaine use also promotes the thrombosis, formation of blood clots. This increase in blood clot formation is attributed to cocaine-associated increases in the activity of Plasminogen activator inhibitor-1, plasminogen activator inhibitor, and an increase in the number, activation, and aggregation of platelets. Chronic intranasal usage can degrade the cartilage separating the nostrils (the septum nasi), leading eventually to its complete disappearance. Due to the absorption of the cocaine from cocaine hydrochloride, the remaining hydrochloride forms a dilute hydrochloric acid. Illicitly-sold cocaine may be contaminated with levamisole. Levamisole may accentuate cocaine's effects. Levamisole-adulterated cocaine has been associated with autoimmune disease. Cocaine use leads to an increased risk of hemorrhagic and ischemic
stroke A stroke is a medical condition A disease is a particular abnormal condition that negatively affects the structure or function (biology), function of all or part of an organism, and that is not due to any immediate external injury. Di ...

stroke
s. Cocaine use also increases the risk of having a
heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow Hemodynamics American and British English spelling differences#ae and oe, or haemodynamics are the Fluid dynamics, dynamics of blood flow. The circulatory sy ...

heart attack
.


Addiction

Cocaine addiction occurs through ΔFosB overexpression in the nucleus accumbens, which results in altered transcriptional regulation in neurons within the nucleus accumbens. ΔFosB levels have been found to increase upon the use of cocaine. Each subsequent dose of cocaine continues to increase ΔFosB levels with no ceiling of tolerance. Elevated levels of ΔFosB leads to increases in brain-derived neurotrophic factor (BDNF) levels, which in turn increases the number of dendrite, dendritic branches and dendritic spine, spines present on neurons involved with the nucleus accumbens and prefrontal cortex areas of the brain. This change can be identified rather quickly, and may be sustained weeks after the last dose of the drug. Transgenic mice exhibiting inducible expression of ΔFosB primarily in the nucleus accumbens and dorsal striatum exhibit drug sensitization, sensitized behavioural responses to cocaine. They self-administer cocaine at lower doses than control, but have a greater likelihood of relapse when the drug is withheld. ΔFosB increases the expression of AMPA receptor subunit GluR2 and also decreases expression of dynorphin, thereby enhancing sensitivity to reward.


Dependence and withdrawal

Cocaine dependence develops after even brief periods of regular cocaine use and produces a drug withdrawal, withdrawal state with emotional-motivational deficits upon cessation of cocaine use.


During pregnancy

Cocaine is known to have a number of deleterious effects during pregnancy. Pregnant people who use cocaine have an elevated risk of placental abruption, a condition where the placenta detaches from the uterus and causes bleeding. Due to its vasoconstrictive and hypertensive effects, they are also at risk for Intracerebral hemorrhage, hemorrhagic stroke and myocardial infarction. Cocaine is also teratogenic, meaning that it can cause birth defects and fetal malformations. In-utero exposure to cocaine is associated with behavioral abnormalities, cognitive impairment, cardiovascular malformations, intrauterine growth restriction, preterm birth, urinary tract malformations, and Cleft lip and cleft palate, cleft lip and palate.


Mortality

Persons with regular or problematic use of cocaine have a significantly higher rate of death, and are specifically at higher risk of traumatic deaths and deaths attributable to infectious disease.


Pharmacology


Pharmacokinetics

The extent of absorption of cocaine into the systemic circulation after nasal insufflation is similar to that after oral ingestion. The rate of absorption after nasal insufflation is somewhat limited by cocaine-induced vasoconstriction of capillaries in the nasal mucosa. The onset of absorption after oral ingestion is delayed because cocaine is a weak base with a pKa of 8.6, and is thus in an ionized form that is poorly absorbed from the acidic stomach and easily absorbed from the alkaline duodenum. The rate and extent of absorption from inhalation of cocaine is similar or greater than with intravenous injection, as inhalation provides access directly to the pulmonary capillary bed. The delay in absorption after oral ingestion may account for the popular belief that cocaine bioavailability from the stomach is lower than after insufflation. Compared to ingestion, the faster absorption of insufflated cocaine results in quicker attainment of maximum drug effects. Snorting cocaine produces maximum physiological effects within 40 minutes and maximum psychotropic effects within 20 minutes. Physiological and psychotropic effects from nasally insufflated cocaine are sustained for approximately 40–60 minutes after the peak effects are attained. Cocaine has a short elimination half life of 0.7-1.5 hours and is extensively metabolism, metabolized by Blood plasma, plasma esterases but also by liver cholinesterases, with only about 1% excreted unchanged in the urine. The metabolism is dominated by hydrolysis, hydrolytic ester cleavage, so the eliminated metabolites consist mostly of benzoylecgonine (BE), the major metabolite, and other significant metabolites in lesser amounts such as ecgonine methyl ester (EME) and ecgonine. Further minor metabolites of cocaine include norcocaine, p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine (pOHBE), and m-hydroxybenzoylecgonine. If consumed with ethanol, alcohol, cocaine combines with Alcohol (drug), alcohol in the liver to form cocaethylene. Studies have suggested cocaethylene is both more Euphoria, euphoric, and has a higher
cardiovascular The circulatory system, also called the cardiovascular system or the vascular system, is an organ system An organ system is a group of organs An organ is a group of tissues with similar functions. Plant life and animal life rely on many o ...
toxicity than cocaine by itself. Depending on liver and kidney function, cocaine metabolites are detectable in urine. Benzoylecgonine can be detected in urine within four hours after cocaine intake and remains detectable in concentrations greater than 150 ng/mL typically for up to eight days after cocaine is used. Detection of cocaine metabolites in hair is possible in regular users until the sections of hair grown during use are cut or fall out.


Pharmacodynamics

The pharmacodynamics of cocaine involve the complex relationships of neurotransmitters (inhibiting monoamine uptake in rats with ratios of about: 5HT, serotonin:
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical , CH4; is among the simplest organic compounds. In chemistry Chemistry is t ...

dopamine
= 2:3,
serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter Monoamine neurotransmitters are s and s that contain one group connected to an by a two-carbon chain (such as -CH2-CH2-). Examples are , and . All monoamines are ...

serotonin
:
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical , CH4; is among the simplest organic compounds. In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and ...

norepinephrine
= 2:5). The most extensively studied effect of cocaine on the central nervous system is the blockade of the
dopamine transporter The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dopamine ...
protein. Dopamine transmitter released during neural signaling is normally recycled via the transporter; i.e., the transporter binds the transmitter and pumps it out of the synaptic cleft back into the presynaptic neuron, where it is taken up into storage vesicle (biology), vesicles. Cocaine binds tightly at the dopamine transporter forming a complex that blocks the transporter's function. The dopamine transporter can no longer perform its reuptake function, and thus
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical , CH4; is among the simplest organic compounds. In chemistry Chemistry is t ...

dopamine
accumulates in the
synaptic cleft Synaptic may refer to: * Synapse SyNAPSE is a DARPA program that aims to develop electronic neuromorphic machine technology, an attempt to build a new kind of cognitive computer with form, function, and architecture similar to the mammalian bra ...
. The increased concentration of dopamine in the synapse activates post-synaptic
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical , CH4; is among the simplest organic compounds. In chemistry Chemistry is t ...

dopamine
receptors, which makes the drug Reward system, rewarding and promotes the compulsive use of cocaine. Cocaine affects certain serotonin (5-HT) receptors; in particular, it has been shown to antagonize the 5-HT3 receptor, which is a ligand-gated ion channel. An overabundance of 5-HT3 receptors is reported in cocaine-conditioned rats, though 5-HT3's role is unclear. The 5-HT2 receptor (particularly the subtypes 5-HT2A receptor, 5-HT2A, 5-HT2B receptor, 5-HT2B and 5-HT2C receptor, 5-HT2C) are involved in the locomotor-activating effects of cocaine. Cocaine has been demonstrated to bind as to directly stabilize the Dopamine transporter, DAT transporter on the open outward-facing conformation. Further, cocaine binds in such a way as to inhibit a hydrogen bond innate to Dopamine transporter, DAT. Cocaine's binding properties are such that it attaches so this hydrogen bond will not form and is blocked from formation due to the tightly locked orientation of the cocaine molecule. Research studies have suggested that the affinity for the transporter is not what is involved in the habituation of the substance so much as the conformation and binding properties to where and how on the transporter the molecule binds. Sigma receptors are affected by cocaine, as cocaine functions as a sigma ligand agonist. Further specific receptors it has been demonstrated to function on are NMDA and the D1 dopamine receptor. Cocaine also blocks ion channel, sodium channels, thereby interfering with the propagation of action potentials; thus, like lignocaine and novocaine, it acts as a local anesthetic. It also functions on the binding sites to the dopamine and serotonin sodium dependent transport area as targets as separate mechanisms from its reuptake of those transporters; unique to its local anesthetic value which makes it in a class of functionality different from both its own derived phenyltropanes analogues which have that removed. In addition to this, cocaine has some target binding to the site of the Κ-opioid receptor, Kappa-opioid receptor. Cocaine also causes vasoconstriction, thus reducing bleeding during minor surgical procedures. Recent research points to an important role of circadian mechanisms and clock genes in behavioral actions of cocaine. Cocaine is known to suppress hunger and appetite by increasing co-localization of sigma σ1R receptors and ghrelin GHS-R1a receptors at the neuronal cell surface, thereby increasing ghrelin-mediated signaling of satiety and possibly via other effects on appetitive hormones. Chronic users may lose their appetite and can experience severe malnutrition and significant weight loss. Cocaine effects, further, are shown to be potentiated for the user when used in conjunction with new surroundings and stimuli, and otherwise novel environs.


Chemistry


Appearance

Cocaine in its purest form is a white, pearly product. Cocaine appearing in powder form is a salt (chemistry), salt, typically cocaine
hydrochlorideIn chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution ...
. Street cocaine is often adulterated or "cut" with talc, lactose, sucrose, glucose, mannitol, inositol, caffeine, procaine, phencyclidine, phenytoin, lignocaine, strychnine, amphetamine, or
heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is an opioid Opioids are substances that act on opioid receptor Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. T ...

heroin
. The color of crack cocaine, "crack" cocaine depends upon several factors including the origin of the cocaine used, the method of preparation – with ammonia or baking soda – and the presence of impurities. It will generally range from white to a yellowish cream to a light brown. Its texture will also depend on the adulterants, origin, and processing of the powdered cocaine, and the method of converting the base. It ranges from a crumbly texture, sometimes extremely oily, to a hard, almost crystalline nature.


Forms


Salts

Cocaine – a
tropane alkaloid Tropane alkaloids are a class of bicyclic .2.1alkaloid Alkaloids are a class of basic BASIC (Beginners' All-purpose Symbolic Instruction Code) is a family of General-purpose programming language, general-purpose, high-level programming langu ...
– is a weakly alkaline compound, and can therefore combine with acidic compounds to form salts. The
hydrochlorideIn chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution ...
(HCl) salt of cocaine is by far the most commonly encountered, although the sulfate (SO42-) and the nitrate (NO3) salts are occasionally seen. Different salts dissolve to a greater or lesser extent in various solvents – the hydrochloride salt is polar in character and is quite soluble in water.


Base

As the name implies, "freebase" is the base (chemistry), base form of cocaine, as opposed to the salt (chemistry), salt form. It is practically insoluble in water whereas hydrochloride salt is water-soluble. Smoking freebase cocaine has the additional effect of releasing methylecgonidine into the user's system due to the pyrolysis of the substance (a side effect which insufflating or injecting powder cocaine does not create). Some research suggests that smoking freebase cocaine can be even more cardiotoxic than other routes of administration because of methylecgonidine's effects on lung tissue and liver tissue. Pure cocaine is prepared by neutralizing its compounding salt with an alkaline solution, which will precipitate non-polar basic cocaine. It is further refined through aqueous-solvent liquid–liquid extraction.


Crack cocaine

Smoking or vaporizing cocaine and inhaling it into the lungs produces an almost immediate "high" that can be very powerful (and addicting) quite rapidly – this initial crescendo of stimulation is known as a "rush". While the stimulating effects may last for hours, the euphoric sensation is very brief, prompting the user to smoke more immediately. Powder cocaine (cocaine hydrochloride) must be heated to a high temperature (about 197 °C), and considerable decomposition/burning occurs at these high temperatures. This effectively destroys some of the cocaine and yields a sharp, acrid, and foul-tasting smoke. Cocaine base/crack can be smoked because it vaporizes with little or no decomposition at , which is below the boiling point of water. Crack is a lower purity form of free-base cocaine that is usually produced by neutralization of cocaine hydrochloride with a solution of baking soda (sodium bicarbonate, NaHCO3) and water, producing a very hard/brittle, off-white-to-brown colored, amorphous material that contains sodium carbonate, entrapped water, and other by-products as the main impurities. The origin of the name "crack" comes from the "crackling" sound (and hence the onomatopoeic moniker "crack") that is produced when the cocaine and its impurities (i.e. water, sodium bicarbonate) are heated past the point of vaporization.


Coca leaf infusions

Coca herbal infusion (also referred to as coca tea) is used in coca-leaf producing countries much as any herbal medicinal infusion would elsewhere in the world. The free and legal commercialization of dried coca leaves under the form of filtration bags to be used as "coca tea" has been actively promoted by the governments of Peru and Bolivia for many years as a drink having medicinal powers. In Peru, the National Coca Company, a state-run corporation, sells cocaine-infused teas and other medicinal products and also exports leaves to the U.S. for medicinal use. Visitors to the city of Cuzco in Peru, and La Paz in Bolivia are greeted with the offering of coca leaf infusions (prepared in teapots with whole coca leaves) purportedly to help the newly arrived traveler overcome the malaise of high altitude sickness. The effects of drinking coca tea are mild stimulation and mood lift. It does not produce any significant numbing of the mouth nor does it give a rush like snorting cocaine. To prevent the demonization of this product, its promoters publicize the unproven concept that much of the effect of the ingestion of coca leaf infusion would come from the secondary alkaloids, as being not only quantitatively different from pure cocaine but also qualitatively different. It has been promoted as an adjuvant for the treatment of cocaine dependence. In one controversial study, coca leaf infusion was used—in addition to counseling—to treat 23 addicted coca-paste smokers in Lima, Peru. Relapses fell from an average of four times per month before treatment with coca tea to one during the treatment. The duration of abstinence increased from an average of 32 days before treatment to 217 days during treatment. These results suggest that the administration of coca leaf infusion plus counseling would be an effective method for preventing relapse during treatment for cocaine addiction. Importantly, these results also suggest strongly that the primary pharmacologically active metabolite in coca leaf infusions is actually cocaine and not the secondary alkaloids. The cocaine metabolite benzoylecgonine can be detected in the urine of people a few hours after drinking one cup of coca leaf infusion.


Biosynthesis

The first synthesis and elucidation of the cocaine molecule was by Richard Willstätter in 1898. Willstätter's synthesis derived cocaine from tropinone. Since then, Robert Robinson (organic chemist), Robert Robinson and Edward Leete have made significant contributions to the mechanism of the synthesis. (-NO3) The additional carbon atoms required for the synthesis of cocaine are derived from acetyl-CoA, by addition of two acetyl-CoA units to the ''N''-methyl-Δ1-pyrrolinium cation. The first addition is a Mannich reaction, Mannich-like reaction with the enolate anion from acetyl-CoA acting as a nucleophile towards the pyrrolinium cation. The second addition occurs through a Claisen condensation. This produces a racemic mixture of the 2-substituted pyrrolidine, with the retention of the thioester from the Claisen condensation. In formation of tropinone from racemic ethyl [2,3-13C2]4(Nmethyl-2-pyrrolidinyl)-3-oxobutanoate there is no preference for either stereoisomer. In cocaine biosynthesis, only the (S)-enantiomer can cyclize to form the tropane ring system of cocaine. The stereoselectivity of this reaction was further investigated through study of prochiral methylene hydrogen discrimination. This is due to the extra chiral center at C-2. This process occurs through an oxidation, which regenerates the pyrrolinium cation and formation of an enolate anion, and an intramolecular Mannich reaction. The tropane ring system undergoes hydrolysis, SAM-dependent methylation, and reduction via NADPH for the formation of methylecgonine. The benzoyl moiety required for the formation of the cocaine diester is synthesized from phenylalanine via cinnamic acid. Benzoyl-CoA then combines the two units to form cocaine.


''N''-methyl-pyrrolinium cation

The biosynthesis begins with L-Glutamine, which is derived to L-ornithine in plants. The major contribution of L-ornithine and L-arginine as a precursor to the tropane ring was confirmed by Edward Leete. Ornithine then undergoes a pyridoxal phosphate-dependent decarboxylation to form putrescine. In some animals, the urea cycle derives putrescine from ornithine. L-ornithine is converted to L-arginine, which is then decarboxylated via PLP to form agmatine. Hydrolysis of the imine derives ''N''-carbamoylputrescine followed with hydrolysis of the urea to form putrescine. The separate pathways of converting ornithine to putrescine in plants and animals have converged. A SAM-dependent ''N''-methylation of putrescine gives the ''N''-methylputrescine product, which then undergoes oxidative deamination by the action of diamine oxidase to yield the aminoaldehyde. Schiff base formation confirms the biosynthesis of the ''N''-methyl-Δ1-pyrrolinium cation.


Robert Robinson's acetonedicarboxylate

The biosynthesis of the
tropane alkaloid Tropane alkaloids are a class of bicyclic .2.1alkaloid Alkaloids are a class of basic BASIC (Beginners' All-purpose Symbolic Instruction Code) is a family of General-purpose programming language, general-purpose, high-level programming langu ...
is still not understood. Hemscheidt proposes that Robinson's acetonedicarboxylate emerges as a potential intermediate for this reaction. Condensation of ''N''-methylpyrrolinium and acetonedicarboxylate would generate the oxobutyrate. Decarboxylation leads to tropane alkaloid formation.


Reduction of tropinone

The reduction of tropinone is mediated by NADPH-dependent reductase enzymes, which have been characterized in multiple plant species. These plant species all contain two types of the reductase enzymes, tropinone reductase I and tropinone reductase II. TRI produces tropine and TRII produces pseudotropine. Due to differing kinetic and pH/activity characteristics of the enzymes and by the 25-fold higher activity of TRI over TRII, the majority of the tropinone reduction is from TRI to form tropine.


Detection in body fluids

Cocaine and its major metabolites may be quantified in blood, plasma, or urine to monitor for use, confirm a diagnosis of poisoning, or assist in the forensic investigation of a traffic or other criminal violation or sudden death. Most commercial cocaine immunoassay screening tests cross-react appreciably with the major cocaine metabolites, but chromatographic techniques can easily distinguish and separately measure each of these substances. When interpreting the results of a test, it is important to consider the cocaine usage history of the individual, since a chronic user can develop tolerance to doses that would incapacitate a cocaine-naive individual, and the chronic user often has high baseline values of the metabolites in his system. Cautious interpretation of testing results may allow a distinction between passive or active usage, and between smoking versus other routes of administration.


Field analysis

Cocaine may be detected by law enforcement using the Scott reagent. The test can easily generate false positives for common substances and must be confirmed with a laboratory test. Approximate cocaine purity can be determined using 1 mL 2% cupric sulfate pentahydrate in dilute HCl, 1 mL 2% potassium thiocyanate and 2 mL of chloroform. The shade of brown shown by the chloroform is proportional to the cocaine content. This test is not cross sensitive to heroin, methamphetamine, benzocaine, procaine and a number of other drugs but other chemicals could cause false positives.


Usage

According to a 2016 United Nations report, England and Wales are the countries with the highest rate of cocaine usage (2.4% of adults in the previous year). Other countries where the usage rate meets or exceeds 1.5% are Spain and Scotland (2.2%), the United States (2.1%), Australia (2.1%), Uruguay (1.8%), Brazil (1.75%), Chile (1.73%), the Netherlands (1.5%) and Ireland (1.5%).


Europe

Cocaine is the second most popular illegal recreational drug in Europe (behind cannabis (drug), cannabis). Since the mid-1990s, overall cocaine usage in Europe has been on the rise, but usage rates and attitudes tend to vary between countries. European countries with the highest usage rates are the United Kingdom, Spain, Italy, and the Republic of Ireland. Approximately 17 million Europeans (5.1%) have used cocaine at least once and 3.5 million (1.1%) in the last year. About 1.9% (2.3 million) of young adults (15–34 years old) have used cocaine in the last year (latest data available as of 2018). Usage is particularly prevalent among this demographic: 4% to 7% of males have used cocaine in the last year in Spain, Denmark, the Republic of Ireland, Italy, and the United Kingdom. The ratio of male to female users is approximately 3.8:1, but this statistic varies from 1:1 to 13:1 depending on country. In 2014 London had the highest amount of cocaine in its sewage out of 50 European cities.


United States

Cocaine is the second most popular illegal recreational drug in the United States (behind cannabis (drug), cannabis) and the U.S. is the world's largest consumer of cocaine. Cocaine is commonly used in middle to upper-class communities and is known as a "rich man's drug". It is also popular amongst college students, as a party drug. A study throughout the entire United States has reported that around 48 percent of people who graduated from high school in 1979 have used cocaine recreationally during some point in their lifetime, compared to approximately 20 percent of students who graduated between the years of 1980 and 1995. Its users span over different ages, races, and professions. In the 1970s and 1980s, the drug became particularly popular in the disco culture as cocaine usage was very common and popular in many discos such as Studio 54.


Dependence treatment

Treatment with contingency management, such as providing vouchers for retail items contingent upon objectively-verified abstinence from recent drug use, has been shown in randomized clinical trials to significantly reduce the likelihood of having a positive test for the presence of cocaine.


History


Discovery

Indigenous peoples of South America have chewed the leaves of ''coca, Erythroxylon coca'' — a plant that contains vital nutrients as well as numerous alkaloids, including cocaine — for over a thousand years. The coca leaf was, and still is, chewed almost universally by some indigenous communities. The remains of coca leaves have been found with ancient Peruvian mummies, and pottery from the time period depicts humans with bulged cheeks, indicating the presence of something on which they are chewing. There is also evidence that these cultures used a mixture of coca leaves and saliva as an anesthetic for the performance of Trepanning, trepanation. When the Spanish colonization of the Americas, Spanish arrived in South America, the conquistadors at first banned coca as an "evil agent of devil". But after discovering that without the coca the locals are barely able to work, the conquistadors legalized and taxed the leaf, taking 10% off the value of each crop. In 1569, Spanish botanist Nicolás Monardes described the indigenous peoples' practice of chewing a mixture of tobacco and coca leaves to induce "great contentment": In 1609, Military chaplain, Padre Blas Valera wrote:


Isolation and naming

Although the stimulant and hunger-suppressant properties of coca had been known for many centuries, the isolation of the cocaine alkaloid was not achieved until 1855. Various European scientists had attempted to isolate cocaine, but none had been successful for two reasons: the knowledge of chemistry required was insufficient at the time, and contemporary conditions of sea-shipping from South America could degrade the cocaine in the plant samples available to European chemists. The cocaine alkaloid was first isolated by the German chemist Friedrich Gaedcke in 1855. Gaedcke named the alkaloid "erythroxyline", and published a description in the journal ''Archiv der Pharmazie.'' In 1856, Friedrich Wöhler asked Dr. Carl Scherzer, a scientist aboard the ''SMS Novara (1850), Novara'' (an Austrian frigate sent by Emperor Franz Joseph of Austria, Franz Joseph to circle the globe), to bring him a large amount of coca leaves from South America. In 1859, the ship finished its travels and Wöhler received a trunk full of coca. Wöhler passed on the leaves to Albert Niemann (chemist), Albert Niemann, a Doctor of Philosophy, PhD student at the University of Göttingen in Germany, who then developed an improved purification process. Niemann described every step he took to isolate cocaine in his dissertation titled ''On a New Organic Base in the Coca Leaves, Über eine neue organische Base in den Cocablättern'' (''On a New Organic Base in the Coca Leaves''), which was published in 1860—it earned him his Ph.D. and is now in the British Library. He wrote of the alkaloid's "colourless transparent prisms" and said that "Its solutions have an alkaline reaction, a bitter taste, promote the flow of saliva and leave a peculiar numbness, followed by a sense of cold when applied to the tongue." Niemann named the alkaloid "cocaine" from "coca" (from Quechua languages, Quechua "kúka") + affix, suffix "ine". The first synthesis and elucidation of the structure of the cocaine molecule was by Richard Willstätter in 1898. It was the first biomimetics, biomimetic synthesis of an organic structure recorded in academic chemical literature. The synthesis started from tropinone, a related natural product and took five steps. Because of the former use of cocaine as a local anesthetic, a suffix "-caine" was later extracted and used to form names of synthetic local anesthetics.


Medicalization

With the discovery of this new alkaloid, Western medicine was quick to exploit the possible uses of this plant. In 1879, Vassili von Anrep, of the University of Würzburg, devised an experiment to demonstrate the analgesic properties of the newly discovered alkaloid. He prepared two separate jars, one containing a cocaine-salt solution, with the other containing merely saltwater. He then submerged a frog's legs into the two jars, one leg in the treatment and one in the control solution, and proceeded to stimulate the legs in several different ways. The leg that had been immersed in the cocaine solution reacted very differently from the leg that had been immersed in saltwater. Karl Koller (ophthalmologist), Karl Koller (a close associate of Sigmund Freud, who would write about cocaine later) experimented with cocaine for ophthalmology, ophthalmic usage. In an infamous experiment in 1884, he experimented upon himself by applying a cocaine solution to his own eye and then pricking it with pins. His findings were presented to the Heidelberg Ophthalmological Society. Also in 1884, Jellinek demonstrated the effects of cocaine as a respiratory system anesthetic. In 1885, William Halsted demonstrated nerve-block anesthesia, and James Leonard Corning demonstrated peridural anesthesia. 1898 saw Heinrich Quincke use cocaine for spinal anesthesia.


Popularization

In 1859, an Italian physician, doctor, Paolo Mantegazza, returned from Peru, where he had witnessed first-hand the use of coca by the local indigenous peoples. He proceeded to experiment on himself and upon his return to Milan, he wrote a paper in which he described the effects. In this paper, he declared coca and cocaine (at the time they were assumed to be the same) as being useful medicinally, in the treatment of "a furred tongue in the morning, flatulence, and whitening of the teeth." A chemist named Angelo Mariani (chemist), Angelo Mariani who read Mantegazza's paper became immediately intrigued with coca and its economic potential. In 1863, Mariani started marketing a wine called Vin Mariani, which had been treated with coca leaves, to become coca wine. The ethanol in wine acted as a solvent and extracted the cocaine from the coca leaves, altering the drink's effect. It contained 6 mg cocaine per ounce of wine, but Vin Mariani which was to be exported contained 7.2 mg per ounce, to compete with the higher cocaine content of similar drinks in the United States. A "pinch of coca leaves" was included in John Pemberton, John Styth Pemberton's original 1886 recipe for Coca-Cola, though the company began using decocainized leaves in 1906 when the Pure Food and Drug Act was passed. In 1879 cocaine began to be used to treat morphine addiction. Cocaine was introduced into clinical use as a local anesthetic in Germany in 1884, about the same time as Sigmund Freud published his work ''Über Coca'', in which he wrote that cocaine causes: In 1885 the U.S. manufacturer Parke-Davis sold cocaine in various forms, including cigarettes, powder, and even a cocaine mixture that could be injected directly into the user's veins with the included needle. The company promised that its cocaine products would "supply the place of food, make the coward brave, the silent eloquent and render the sufferer insensitive to pain." By the late Victorian era, cocaine use had appeared as a vice in literature. For example, it was injected by Arthur Conan Doyle's fictional Sherlock Holmes, generally to offset the boredom he felt when he was not working on a case. In early 20th-century Memphis, Tennessee, cocaine was sold in neighborhood drugstores on Beale Street, costing five or ten cents for a small boxful. Stevedores along the Mississippi River used the drug as a stimulant, and white employers encouraged its use by black laborers. In 1909, Ernest Shackleton took "Forced March" brand cocaine tablets to Antarctica, as did Captain Scott a year later on his ill-fated journey to the South Pole. During the mid-1940s, amidst World War II, cocaine was considered for inclusion as an ingredient of a future generation of 'pep pills' for the German military, code named D-IX. In modern popular culture, references to cocaine are common. The drug has a glamorous image associated with the wealthy, famous and powerful, and is said to make users "feel rich and beautiful". In addition the pace of modern society − such as in finance − gives many the incentive to make use of the drug.


Modern usage

In many countries, cocaine is a popular
recreational drug Recreational drug use is the use of a psychoactive drug A psychoactive drug, psychopharmaceutical, psychoactive agent, or psychotropic drug, is a chemical substance that changes nervous system function and results in alterations in perception, ...
. In the United States, the development of crack cocaine, "crack" cocaine introduced the substance to a generally poorer inner-city market. The use of the powder form has stayed relatively constant, experiencing a new height of use during the late 1990s and early 2000s in the U.S., and has become much more popular in the last few years in the UK. Cocaine use is prevalent across all socioeconomic strata, including age, demographics, economic, social, political, religious, and livelihood. The estimated U.S. cocaine market exceeded US$70 billion in street value for the year 2005, exceeding revenues by corporations such as Starbucks. Cocaine's status as a club drug shows its immense popularity among the "party crowd". In 1995 the World Health Organization (WHO) and the United Nations Interregional Crime and Justice Research Institute (UNICRI) announced in a press release the publication of the results of the largest global study on cocaine use ever undertaken. An American representative in the World Health Assembly banned the publication of the study, because it seemed to make a case for the positive uses of cocaine. An excerpt of the report strongly conflicted with accepted paradigms, for example, "that occasional cocaine use does not typically lead to severe or even minor physical or social problems." In the sixth meeting of the B committee, the US representative threatened that "If World Health Organization activities relating to drugs failed to reinforce proven drug control approaches, funds for the relevant programs should be curtailed". This led to the decision to discontinue publication. A part of the study was recuperated and published in 2010, including profiles of cocaine use in 20 countries, but are unavailable . In October 2010 it was reported that the use of cocaine in Australia has doubled since monitoring began in 2003. A problem with illegal cocaine use, especially in the higher volumes used to combat fatigue (rather than increase euphoria) by long-term users, is the risk of ill effects or damage caused by the compounds used in adulteration. Cutting or "stepping on" the drug is commonplace, using compounds which simulate ingestion effects, such as Novocain (procaine) producing temporary anesthesia, as many users believe a strong numbing effect is the result of strong and/or pure cocaine, ephedrine or similar stimulants that are to produce an increased heart rate. The normal adulterants for profit are inactive sugars, usually mannitol, creatine, or glucose, so introducing active adulterants gives the illusion of purity and to 'stretch' or make it so a dealer can sell more product than without the adulterants. The adulterant of sugars allows the dealer to sell the product for a higher price because of the illusion of purity and allows the sale of more of the product at that higher price, enabling dealers to significantly increase revenue with little additional cost for the adulterants. A 2007 study by the European Monitoring Centre for Drugs and Drug Addiction showed that the purity levels for street purchased cocaine was often under 5% and on average under 50% pure.


Society and culture


Legal status

The production, distribution, and sale of cocaine products is restricted (and illegal in most contexts) in most countries as regulated by the
Single Convention on Narcotic Drugs The Single Convention on Narcotic Drugs of 1961 is an international treaty that prohibits production and supply of specific narcotic Heroin, a powerful opioid and narcotic The term narcotic (, from ancient Greek Ancient Greek incl ...
, and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. In the United States the manufacture, importation, possession, and distribution of cocaine are additionally regulated by the 1970 Controlled Substances Act. Some countries, such as Peru and Bolivia, permit the cultivation of coca leaf for traditional consumption by the local indigenous peoples of the Americas, indigenous population, but nevertheless, prohibit the production, sale, and consumption of cocaine. The provisions as to how much a coca farmer can yield annually is protected by laws such as the Bolivian Cato accord. In addition, some parts of Europe, the United States, and Australia allow processed cocaine for medicinal uses only.


Australia

Cocaine is a Standard for the Uniform Scheduling of Medicines and Poisons, Schedule 8 prohibited substance in Australia under the Standard for the Uniform Scheduling of Medicines and Poisons, Poisons Standard (July 2016). A schedule 8 substance is a controlled Drug – Substances which should be available for use but require the restriction of manufacture, supply, distribution, possession and use to reduce abuse, misuse, and physical or psychological dependence. In Western Australia under the Misuse of Drugs Act 1981 4.0g of cocaine is the amount of prohibited drugs determining a court of trial, 2.0g is the amount of cocaine required for the presumption of intention to sell or supply and 28.0g is the amount of cocaine required for purposes of drug trafficking.


United States

The US federal government instituted a national labeling requirement for cocaine and cocaine-containing products through the Pure Food and Drug Act of 1906. The next important federal regulation was the Harrison Narcotics Tax Act of 1914. While this act is often seen as the start of prohibition, the act itself was not actually a prohibition on cocaine, but instead set up a regulatory and licensing regime. The Harrison Act did not recognize addiction as a treatable condition and therefore the therapeutic use of cocaine, heroin, or morphine to such individuals was outlawed leading a 1915 editorial in the journal ''American Medicine'' to remark that the addict "is denied the medical care he urgently needs, open, above-board sources from which he formerly obtained his drug supply are closed to him, and he is driven to the underworld where he can get his drug, but of course, surreptitiously and in violation of the law." The Harrison Act left manufacturers of cocaine untouched so long as they met certain purity and labeling standards. Despite that cocaine was typically illegal to sell and legal outlets were rarer, the quantities of legal cocaine produced declined very little. Legal cocaine quantities did not decrease until the Narcotic Drugs Import and Export Act, Jones–Miller Act of 1922 put serious restrictions on cocaine manufactures. Before the early 1900s, the primary problem caused by cocaine use was portrayed by newspapers to be addiction, not violence or crime, and the cocaine user was represented as an upper- or middle-class White person. In 1914, ''The New York Times'' published an article titled "Negro Cocaine 'Fiends' Are a New Southern Menace", portraying Black cocaine users as dangerous and able to withstand wounds that would normally be fatal. The Anti-Drug Abuse Act of 1986 mandated prison sentences for 500 grams of powdered cocaine and 5 grams of crack cocaine. In the National Survey on Drug Use and Health, Whites reported a higher rate of powdered cocaine use, and Blacks reported a higher rate of crack cocaine use.


Interdiction

In 2004, according to the United Nations, 589 tonnes of cocaine were seized globally by law enforcement authorities. Colombia seized 188 t, the United States 166 t, Europe 79 t, Peru 14 t, Bolivia 9 t, and the rest of the world 133 t.


Production

Colombia is as of 2019 the world's largest cocaine producer, with production more than tripling since 2013.Colombia
. CIA World Factbook
Three-quarters of the world's annual yield of cocaine has been produced in Colombia, both from cocaine base imported from Peru (primarily the Huallaga Valley) and Bolivia and from locally grown coca. There was a 28% increase in the amount of potentially harvestable coca plants which were grown in Colombia in 1998. This, combined with crop reductions in Bolivia and Peru, made Colombia the nation with the largest area of cocaine production in Colombia, coca under cultivation after the mid-1990s. Coca grown for traditional purposes by indigenous communities, a use which is still present and is permitted by Colombian laws, only makes up a small fragment of total coca production, most of which is used for the illegal drug trade. An interview with a coca farmer published in 2003 described a mode of production by acid-base extraction that has changed little since 1905. Roughly of leaves were harvested per hectare, six times per year. The leaves were dried for half a day, then chopped into small pieces with a string trimmer and sprinkled with a small amount of powdered cement (replacing sodium carbonate from former times). Several hundred pounds of this mixture were soaked in of gasoline for a day, then the gasoline was removed and the leaves were pressed for the remaining liquid, after which they could be discarded. Then battery acid (weak sulfuric acid) was used, one bucket per of leaves, to create a phase (matter), phase separation in which the cocaine free base in the gasoline was acidified and extracted into a few buckets of "murky-looking smelly liquid". Once powdered caustic soda was added to this, the cocaine precipitated and could be removed by filtration through a cloth. The resulting material, when dried, was termed ''cocaine paste, pasta'' and sold by the farmer. The 3750 pound yearly harvest of leaves from a hectare produced of ''pasta'', approximately 40–60% cocaine. Repeated recrystallization from solvents, producing ''pasta lavada'' and eventually crystalline cocaine were performed at specialized laboratories after the sale. Attempts to eradicate coca fields through the use of defoliants have devastated part of the farming economy in some coca-growing regions of Colombia, and strains appear to have been developed that are more resistant or immune to their use. Whether these strains are natural mutations or the product of human tampering is unclear. These strains have also shown to be more potent than those previously grown, increasing profits for the drug cartels responsible for the exporting of cocaine. Although production fell temporarily, coca crops rebounded in numerous smaller fields in Colombia, rather than the larger plantations. The cultivation of coca has become an attractive economic decision for many growers due to the combination of several factors, including the lack of other employment alternatives, the lower profitability of alternative crops in official crop substitution programs, the eradication-related damages to non-drug farms, the spread of new strains of the coca plant due to persistent worldwide demand. The latest estimate provided by the U.S. authorities on the annual production of cocaine in Colombia refers to 290 metric tons. As of the end of 2011, the seizure operations of Colombian cocaine carried out in different countries have totaled 351.8 metric tons of cocaine, i.e. 121.3% of Colombia's annual production according to the U.S. Department of State's estimates.


Synthesis

Synthesizing cocaine could eliminate the high visibility and low reliability of offshore sources and international smuggling, replacing them with clandestine domestic laboratories, as are common for illicit methamphetamine, but is rarely done. Natural cocaine remains the lowest cost and highest quality supply of cocaine. Formation of inactive stereoisomers (cocaine has four chiral centres – 1''R'' 2''R'', 3''S'', and 5''S'', two of them dependent, hence eight possible stereoisomers) plus synthetic by-products limits the yield and purity.


Trafficking and distribution

Organized crime, Organized criminal gangs operating on a large scale dominate the cocaine trade. Most cocaine is grown and processed in South America, particularly in Colombia, Bolivia, Peru, and smuggled into the United States and Europe, the United States being the world's largest consumer of cocaine, where it is sold at huge markups; usually in the US at $80–120 for 1 gram, and $250–300 for 3.5 grams ( of an ounce, or an "eight ball").


=Caribbean and Mexican routes

= The primary cocaine importation points in the United States have been in Arizona, southern California, southern Florida, and Texas. Typically, land vehicles are driven across the U.S.–Mexico border. Sixty-five percent of cocaine enters the United States through Mexico, and the vast majority of the rest enters through Florida. , the Sinaloa Cartel is the most active drug cartel involved in smuggling illicit drugs like cocaine into the United States and trafficking them throughout the United States. Cocaine traffickers from Colombia and Mexico have established a labyrinth of smuggling routes throughout the Caribbean, the Bahama Island chain, and South Florida. They often hire traffickers from Mexico or the Dominican Republic to transport the drug using a variety of smuggling techniques to U.S. markets. These include airdrops of in the Bahama Islands or off the coast of Puerto Rico, mid-ocean boat-to-boat transfers of , and the commercial shipment of tonnes of cocaine through the port of Miami.


=Chilean route

= Another route of cocaine traffic goes through Chile, which is primarily used for cocaine produced in Bolivia since the nearest seaports lie in northern Chile. The arid Bolivia–Chile border is easily crossed by 4×4 vehicles that then head to the seaports of Iquique and Antofagasta. While the price of cocaine is higher in Chile than in Peru and Bolivia, the final destination is usually Europe, especially Spain where drug dealing networks exist among South American immigrants.


=Techniques

= Cocaine is also carried in small, concealed, kilogram quantities across the border by couriers known as "mule (smuggling), mules" (or "mulas"), who cross a border either legally, for example, through a port or airport, or illegally elsewhere. The drugs may be strapped to the waist or legs or hidden in bags, or hidden in the body. If the mule gets through without being caught, the gangs will reap most of the profits. If caught, gangs will sever all links and the mule will usually stand trial for trafficking alone. Bulk cargo ships are also used to smuggle cocaine to staging sites in the western Caribbean–Gulf of Mexico area. These vessels are typically 150–250-foot (50–80 m) coastal freighters that carry an average cocaine load of approximately 2.5 tonnes. Commercial fishing vessels are also used for smuggling operations. In areas with a high volume of recreational traffic, smugglers use the same types of vessels, such as go-fast boats, like those used by the local populations. Sophisticated narco-submarine, drug subs are the latest tool drug runners are using to bring cocaine north from Colombia, it was reported on 20 March 2008. Although the vessels were once viewed as a quirky sideshow in the drug war, they are becoming faster, more seaworthy, and capable of carrying bigger loads of drugs than earlier models, according to those charged with catching them.


Sales to consumers

Cocaine is readily available in all major countries' metropolitan areas. According to the ''Summer 1998 Pulse Check'', published by the U.S. Office of National Drug Control Policy, cocaine use had stabilized across the country, with a few increases reported in San Diego, Bridgeport, Connecticut, Bridgeport, Miami, and Boston. In the West, cocaine usage was lower, which was thought to be due to a switch to methamphetamine among some users; methamphetamine is cheaper, three and a half times more powerful, and lasts 12–24 times longer with each dose. Nevertheless, the number of cocaine users remain high, with a large concentration among urban youth. In addition to the amounts previously mentioned, cocaine can be sold in "bill sizes": for example, $10 might purchase a "dime bag", a very small amount (0.1–0.15 g) of cocaine. These amounts and prices are very popular among young people because they are inexpensive and easily concealed on one's body. Quality and price can vary dramatically depending on supply and demand, and on geographic region. In 2008, the European Monitoring Centre for Drugs and Drug Addiction reports that the typical retail price of cocaine varied between €50 and €75 per gram in most European countries, although Cyprus, Romania, Sweden, and Turkey reported much higher values.


Consumption

World annual cocaine consumption, as of 2000, stood at around 600 tonnes, with the United States consuming around 300 t, 50% of the total, Europe about 150 t, 25% of the total, and the rest of the world the remaining 150 t or 25%. It is estimated that 1.5 million people in the United States used cocaine in 2010 down from 2.4 million in 2006. Conversely, cocaine use appears to be increasing in Europe with the highest prevalences in Spain, the United Kingdom, Italy, and Republic of Ireland, Ireland. The 2010 UN World Drug Report concluded that "it appears that the North American cocaine market has declined in value from US$47 billion in 1998 to US$38 billion in 2008. Between 2006 and 2008, the value of the market remained basically stable".


Research

In 2005, researchers proposed the use of cocaine in conjunction with
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phenylephrine
administered in the form of an eye drop as a diagnostic test for Parkinson's disease.


See also

* Black cocaine * Coca alkaloids * Coca eradication * Cocaethylene * Cocaine and amphetamine regulated transcript * Cocaine Anonymous * ''Cocaine Cowboys (2006 film), Cocaine Cowboys'' * Cocaine intoxication * Cocaine paste * * Crack epidemic * Illegal drug trade in Latin America * Coca production in Colombia * Clan del Golfo * Legal status of cocaine * List of cocaine analogues * List of countries by prevalence of cocaine use * Methylphenidate * Modafinil * Pre-Columbian trans-oceanic contact theories#Claims of Egyptian coca and tobacco, Pre-Columbian trans-oceanic evidence for cocaine in ancient Egypt * Prenatal cocaine exposure * Route 36 (bar), Route 36, cocaine bar in Bolivia * Tranquilandia * TA-CD * Ypadu


References


Bibliography

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Further reading

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External links

* * * — A collection of data about cocaine including dose, effects, chemistry, legal status, images and more. * * Data on cocaine trafficking worldwide. {{Authority control Cocaine, Alkaloids found in Erythroxylum Anorectics Benzoate esters Carboxylate esters Cardiac stimulants Euphoriants German inventions Glycine receptor agonists Local anesthetics Methyl esters Otologicals Wikipedia medicine articles ready to translate Secondary metabolites Serotonin–norepinephrine–dopamine reuptake inhibitors Sigma agonists Stimulants Sympathomimetic amines Teratogens Tropane alkaloids found in Erythroxylum coca Vasoconstrictors