Cocaine

Cocaine (Template:Ety, Template:Ety, ultimately Template:Ety)<ref>Template:Cite web</ref> is a tropane alkaloid that acts as a central nervous system (CNS) stimulant.<ref name="EUDA">Template:Cite web</ref><ref>Template:Cite web</ref> Coca has traditionally been used by indigenous South Americans for various purposes for over a thousand years.<ref name="isbn 978-3-906390-24-6"/> As an extract, cocaine is rarely but formally used as a local anaesthetic or diagnostic tool by medical practitioners in some countries. However, most cocaine use today is recreational drug use, consumed illegally to produce euphoria and act as an aphrodisiac.<ref>Template:Cite web</ref><ref name="DEA">Template:Cite web</ref>

Cocaine is primarily obtained from the leaves of two coca species native to South America: Erythroxylum coca and E. novogranatense.<ref>Template:Cite journal</ref><ref name=Pom2012>Template:Cite journal</ref> After extraction from the plant, and further processing into cocaine hydrochloride (powdered cocaine), the drug is administered by being either snorted, applied topically to the mouth, or dissolved and injected into a vein. It can also then be turned into free base form (typically crack cocaine), in which it can be heated until sublimated and then the vapours can be inhaled.<ref name="Zimmerman2012" />

Cocaine stimulates the mesolimbic pathway in the brain,<ref name=Pom2012 /> producing mental effects such as intense happiness, sexual arousal, loss of reality, and agitation, along with physical effects like fast heart rate, sweating, and dilated pupils.<ref name="Zimmerman2012" /> High doses may lead to high blood pressure or elevated body temperature.<ref>Template:Cite journal</ref> Effects typically begin within seconds to minutes and last five to ninety minutes depending on administration route.<ref name="Zimmerman2012" /> Due to its topical anesthetic and vasoconstrictor properties, it is occasionally used in surgeries involving the pharynx or nasopharynx to reduce pain, bleeding, and vocal cord spasm.<ref>Template:Cite book</ref> Cocaine acts as a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI),<ref name="Monoamines: Dopamine, Norepinephrin" /><ref>Template:Cite journal</ref> increasing levels of serotonin, norepinephrine, and dopamine in the synaptic cleft, leading to heightened post-synaptic activation, with dopamine contributing to euphoria and arousal, and the other monoamines enhancing additional effects.<ref name="Monoamines: Dopamine, Norepinephrin" /><ref>Template:Cite journal</ref><ref>Template:Cite web</ref><ref>Template:Cite journal</ref> It crosses the blood–brain barrier mainly via a proton-coupled organic cation antiporter<ref name="How do psychostimulants enter the h">Template:Cite journal</ref><ref name="Structural Requirements for Uptake">Template:Cite journal</ref> and, to a lesser extent, by passive diffusion.<ref name="ReferenceA">Template:Cite journal</ref>

A single dose of cocaine induces tolerance to the drug's effects.<ref name=Ambre1988>Template:Cite journal</ref> Repeated use is likely to result in addiction.<ref>Template:Cite web</ref> Addicts who abstain from cocaine may experience prolonged craving lasting for many months.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Abstaining addicts also experience modest drug withdrawal symptoms lasting up to 24 hours, with sleep disruption, anxiety, irritability, fatigue, lethargy, depression, decreased libido, and decreased ability to feel pleasure.<ref>Template:Cite journal</ref><ref name=Pom2012 /> Use of cocaine increases the overall risk of death, and intravenous use potentially increases the risk of trauma and infectious diseases such as blood infections and HIV through needle sharing. It also increases risk of stroke, heart attack, cardiac arrhythmia, lung injury (when smoked), and sudden cardiac death.<ref name="Pom2012" /><ref name="Sor2014">Template:Cite journal</ref> Illicitly sold cocaine can be adulterated with fentanyl, local anesthetics, levamisole, cornstarch, quinine, or sugar, which can result in additional toxicity.<ref name=Gold2009>Template:Cite journal</ref><ref>Template:Cite web</ref> In 2017, the Global Burden of Disease Study found that cocaine use caused around 7,300 deaths annually.<ref>Template:Cite journal</ref>

Uses

Coca leaves have been used by Andean civilizations since ancient times.<ref name=Gold2009 /> In ancient Wari culture,<ref name="Valdez">Template:Cite journal</ref> Inca culture, and through modern successor indigenous cultures of the Andes mountains, coca leaves are chewed, taken orally in the form of a tea, or alternatively, prepared in a sachet wrapped around alkaline burnt ashes, and held in the mouth against the inner cheek; it has traditionally been used as an anorectic and to combat the effects of cold and altitude sickness.<ref name="Martin">Template:Cite journal</ref><ref name="Plant">Template:Cite journal</ref> Cocaine was first isolated from the leaves in 1860.<ref name=Pom2012 />

Globally, in 2019, cocaine was used by an estimated 20 million people (0.4% of adults aged 15 to 64 years). The highest prevalence of cocaine use was in Australia and New Zealand (2.1%), followed by North America (2.1%), Western and Central Europe (1.4%), and South and Central America (1.0%).<ref name="WDR2021">Template:Cite book</ref> Since 1961, the Single Convention on Narcotic Drugs has required countries to make recreational use of cocaine a crime.<ref>Template:Cite journal</ref> In the United States, cocaine is regulated as a Schedule II drug under the Controlled Substances Act, meaning that it has a high potential for abuse but has an accepted medical use.<ref>Template:Cite web</ref> While rarely used medically today, its accepted uses include serving as a topical local anesthetic for the upper respiratory tract and as an antihemorrhagic agent to stop bleeding in the mouth, throat, and nasal cavities.<ref>Template:Cite web</ref> However, chronic recreational use may lead to severe nasal and sinus damage known as "cocaine nose," which can result in frequent nosebleeds, septal perforation, and even deformities of the nasal structure.

Traditional

Coca leaves

File:20150720 Puno Hotelbreakfast.jpg

Partial view of hotel breakfast table in Puno by the Lake Titicaca in Peru, featuring coca leaves and coca tea.

It is legal for people to use coca leaves in the Andean Community, such as Peru and Bolivia, where they are chewed, consumed in the form of tea, or are sometimes incorporated into food products.<ref>Template:Cite web</ref> Coca leaves are typically mixed with an alkaline substance (such as lime) and chewed into a wad that is retained in the buccal pouch (mouth between gum and cheek, much the same as chewing tobacco 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 by steeping and consumed like tea. Coca tea, an infusion of coca leaves, is also a traditional method of consumption. The tea has often been recommended for travelers in the Andes to prevent altitude sickness.<ref name=luks>Template:Cite journal Template:Link note</ref> Its actual effectiveness has never been systematically studied.<ref name=luks />

In 1986 an article in the Journal of the American Medical Association revealed that U.S. health food stores were selling dried coca leaves to be prepared as an infusion as "Health Inca Tea". While the packaging claimed it had been "decocainized", no such process had actually taken place. The article stated that drinking two cups of the tea per day gave a mild stimulation, increased heart rate, and mood elevation, and the tea was essentially harmless.<ref name="Siegel">Template:Cite journal</ref>

Coca tea

File:Mate de coca Peru.jpg

Two cups of coca tea

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.<ref>Template:Cite web</ref>

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.<ref name="Vera">Template:Cite news</ref> The effects of drinking coca tea are mild stimulation and mood lift.<ref>Template:Cite web</ref> It has also been promoted as an adjuvant for the treatment of cocaine dependence. One study on coca leaf infusion used with counseling in the treatment of 23 addicted coca-paste smokers in Lima, Peru found that the relapses rate fell from 4.35 times per month on average before coca tea treatment to one during treatment. The duration of abstinence increased from an average of 32 days before treatment to 217.2 days during treatment. This suggests that coca leaf infusion plus counseling may be effective at preventing relapse during cocaine addiction treatment.<ref name="Teobaldo">Template:Cite journal</ref>

There is little information on the pharmacological and toxicological effects of consuming coca tea. A chemical analysis by solid-phase extraction and gas chromatography–mass spectrometry (SPE-GC/MS) of Peruvian and Bolivian tea bags indicated the presence of significant amounts of cocaine, the metabolite benzoylecgonine, ecgonine methyl ester and trans-cinnamoylcocaine in coca tea bags and coca tea. Urine specimens were also analyzed from an individual who consumed one cup of coca tea and it was determined that enough cocaine and cocaine-related metabolites were present to produce a positive drug test.<ref name="Jenkins">Template:Cite journal</ref>

Ypadu

File:Mambe indigena coca colombia crista castellanos.jpg

Mambe or ypadu is made from toasted and ground coca leaves with ashes

Ypadú or ypadu (also known as mambé) is an unrefined, unconcentrated powder made from toasted coca leaves and the ash of various other plants. It is traditionally prepared and consumed by indigenous tribes in the Northwest Amazon.<ref>Template:Cite journal</ref> Like coca teas consumed in Peru to adapt to sickness induced by high elevation, it has a long ethnobotanical history and cultural associations.

Medical

Topical

File:Cocaine hydrochloride CII for medicinal use.jpg

Cocaine hydrochloride

Topical cocaine is sometimes used as a local numbing agent and vasoconstrictor to help control pain and bleeding with surgery of the nose, mouth, throat or lacrimal duct. It is also used for topical airway anaesthesia for procedures such as awake fibreoptic bronchoscopy or intubation. Although some absorption and systemic effects may occur, the use of cocaine as a topical anesthetic and vasoconstrictor is generally safe, rarely causing cardiovascular toxicity, glaucoma, and pupil dilation.<ref name="Dwyer2016">Template:Cite journal</ref><ref>Template:Cite journal</ref> Occasionally, cocaine is mixed with adrenaline and sodium bicarbonate and used topically for surgery, a formulation called Moffett's solution.<ref>Template:Cite journal</ref>

Eye drops

Cocaine eye drops are frequently used by neurologists when examining people suspected of having Horner syndrome. In Horner syndrome, sympathetic innervation to the eye is blocked. In a healthy eye, cocaine will stimulate the sympathetic nerves by inhibiting norepinephrine reuptake, and the pupil will dilate; if the patient has Horner syndrome, the sympathetic nervous system are blocked, and the affected eye will remain constricted or dilate to a lesser extent than the opposing (unaffected) eye which also receives the eye drop test. If both eyes dilate equally, the patient does not have Horner syndrome.<ref>Template:Cite book</ref>

Nasal solution

Cocaine hydrochloride (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.<ref>Template:Cite web</ref><ref name="Goprelto FDA label">Template:Cite web</ref> Cocaine hydrochloride (Numbrino) was approved for medical use in the United States in January 2020.<ref>Template:Citation-attribution</ref><ref name="Numbrino FDA label">Template:Cite web</ref>

Headache and epistaxis are the most frequently reported adverse reactions with Goprelto,<ref name="Goprelto FDA label" /> while hypertension and tachycardia-including sinus tachycardia-are most common with Numbrino.<ref name="Numbrino FDA label" />

Recreational

File:Peruvian Flake Cocaine.jpg

Peruvian flake cocaine on a metal milligram scale tray

Cocaine is a central nervous system stimulant.<ref name=WHO2004>Template:Cite book</ref> 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.<ref name=WHO2007>Template:Cite book</ref> Cocaine can be in the form of fine white powder and has a bitter taste. Crack cocaine is a smokeable form of cocaine made into small "rocks" by processing cocaine with sodium bicarbonate (baking soda) and water.<ref name="Zimmerman2012" /><ref name="Sordo2014">Template:Cite journal</ref> Crack cocaine is referred to as "crack" because of the crackling sounds it makes when heated.<ref name="Zimmerman2012" />

Cocaine use leads to increases in alertness, feelings of well-being and euphoria, increased energy and motor activity, and increased feelings of competence and sexuality.<ref name="Donroe2017">Template:Cite journal</ref>

Analysis of the correlation between the use of 18 various psychoactive substances shows that cocaine use correlates with other "party drugs" (such as ecstasy or amphetamines), as well as with heroin and benzodiazepines use, and can be considered as a bridge between the use of different groups of drugs.<ref>Template:Cite book</ref>

Insufflation

File:Cocaine lines 2.jpg

Lines of cocaine prepared for snorting. Contaminated currency such as banknotes might serve as a fomite of diseases like hepatitis C<ref name="LV">Template:Cite web</ref>

Nasal insufflation (known colloquially as "snorting", "sniffing", or "blowing") is a common method of ingestion of recreational powdered cocaine.<ref>Template:Cite web</ref> The drug coats and is absorbed through the mucous membranes lining the nasal passages. Cocaine's desired euphoric effects are delayed when snorted through the nose by about five minutes. This occurs because cocaine's absorption is slowed by its constricting effect on the blood vessels of the nose.<ref name="Zimmerman2012" /> Insufflation of cocaine also leads to the longest duration of its effects (60–90 minutes).<ref name="Zimmerman2012" /> When insufflating cocaine, absorption through the nasal membranes is approximately 30–60%<ref>Template:Cite web</ref>

In a study of cocaine users, the average time taken to reach peak subjective effects was 14.6 minutes.<ref name="Volkow">Template:Cite journal</ref> Any damage to the inside of the nose is due to cocaine constricting blood vessels — and therefore restricting blood and oxygen/nutrient flow — to that area, which, after chronic use, may cause "cocaine nose."

Snuff spoons, rolled up banknotes, hollowed-out pens, cut straws, pointed ends of keys,<ref>Template:Cite web</ref> long fingernails or artificial nails, and (clean) tampon applicators are often used to insufflate cocaine. The cocaine typically is poured onto a flat, hard surface (such as a mobile phone screen, plate, mirror, CD case or book) and divided into "bumps", "lines" or "rails", and then insufflated.<ref>Template:Cite web</ref> A 2001 study reported that the sharing of straws used to "snort" cocaine can spread blood diseases such as hepatitis C.<ref>Template:Cite journal</ref>

Cocaine spoon

File:Stopper, snuff bottle (AM 687402-2).jpg

Chinese snuff bottle stopper with a spoon

Historically, snuff spoons were used for cocaine in the 20th century, hence the names "cocaine spoon" and "coke spoon". Some local statutes in the US treat spoons that are too small and thus "unsuited for the typical, lawful uses of a spoon" as drug paraphernalia.<ref>Template:Cite web</ref><ref>Template:Cite web</ref><ref>Template:Cite web</ref>

In the US, McDonald's provides straight swizzle sticks to stir the coffee, while in the rest of the world a small plastic stirring spoon is used. According to Anthony J. Graybosch, this is due to the 1960s rumor that the spoons can be used to snort cocaine.<ref>Template:Cite book</ref>

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 2 to 5 minutes including 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.<ref name="Volkow" /> The euphoria passes quickly. Aside from the toxic effects of cocaine, there is also the danger of circulatory emboli 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.

Inhalation

Crack cocaine

File:Man smoking crack cocaine in Bogotá, Colombia..jpg

Man smoking crack cocaine in Bogotá, Colombia

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 Template:Convert,<ref>Template:Cite book</ref> which is below the boiling point of water.

Contraindications

Pregnancy

Cocaine can act as a teratogen, having various effects on the developing fetus.<ref name=":5">Template:Cite web</ref> Some common teratogenic defects caused by cocaine include hydronephrosis, cleft palate, polydactyly, and down syndrome.<ref name=":5" /> Cocaine as a drug has a low molecular weight and high water and lipid solubility which enables it to cross the placenta and fetal blood-brain barrier.<ref>Template:Cite journal</ref> Because cocaine is able to pass through the placenta and enter the fetus, the fetus' circulation can be negatively affected. With restriction of fetal circulation, the development of organs in the fetus can be impacted, even resulting in intestines developing outside of the fetus' body.<ref name=":5" /> Cocaine use during pregnancy can also result in obstetric labor complications such as preterm birth or delivery, uterine rupture, miscarriage, and stillbirth.<ref name=":5" />

Breastfeeding

Mothers utilizing recreational drugs, such as cocaine, methamphetamines, PCP, and heroin, should not breastfeed.<ref name="CDC-2021e">Template:Cite web</ref><ref name="Eglash_2020">Template:Cite book</ref>Template:Rp

The March of Dimes said "it is likely that cocaine will reach the baby through breast milk," and advises the following regarding cocaine use during pregnancy: Template:Blockquote

Adverse effects

Cocaine is considered neurotoxic due to its damaging effects on the brain and nervous system. Research has shown that both acute and chronic cocaine use can lead to significant reductions in cerebral blood flow, disrupt neurovascular interactions, and impair brain function. These changes are associated with nerve injury, cognitive deficits, and an increased risk of cerebrovascular accidents such as strokes. Brain imaging studies consistently report that individuals who misuse cocaine exhibit structural and functional abnormalities compared to non-users, supporting the classification of cocaine as a neurotoxic substance.<ref>Template:Cite journal</ref>

Short-term effects

Insufflating (snorting) cocaine commonly causes increased mucus production due to irritation and inflammation of the nasal passages. This irritation leads to symptoms such as a runny nose, nasal congestion, and excessive or thickened mucus.

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.<ref>Template:Cite journal</ref> 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.<ref name=Ambre1988 /><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> With excessive or prolonged use, the drug can cause itching, fast heart rate, and paranoid delusions or sensations of insects crawling on the skin.<ref name="weizhao2008">Template:Cite book</ref> 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, psychomotor agitation, and delirium. Consumption of large doses of cocaine can cause violent outbursts, especially by those with preexisting psychosis.<ref>Template:Cite journal</ref> Acute exposure may induce arrhythmia, including atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, and ventricular fibrillation. Acute exposure may also lead to angina, heart attack, and congestive heart failure.<ref>Template:Cite journal</ref> Cocaine overdose may cause seizures, abnormally high body temperature and a marked elevation of blood pressure, which can be life-threatening,<ref name="weizhao2008" /> abnormal heart rhythms,<ref name="Nav">Template:Cite journal</ref> and death.<ref name="Nav" /> Anxiety, paranoia, and restlessness can also occur, especially during the comedown. With excessive dosage, tremors, convulsions, and increased body temperature are observed.<ref name=WHO2004 /> Severe cardiac adverse events, particularly sudden cardiac death, become a serious risk at high doses due to cocaine's blocking effect on cardiac sodium channels.<ref name="Nav" />

Chronic

File:Side effects of chronic use of Cocaine.png

Side effects of chronic cocaine use

Because cocaine is highly addictive and has poor bioavailability when taken orally, individuals often engage in repeated use by either insufflating it intranasally or converting it to crack cocaine for vaporization. Cocaine’s effects last longest when insufflated (60–90 minutes),<ref name="Zimmerman2012" /> but cocaine has a shorter half-life than most drugs, which further encourages frequent redosing over extended periods. This cycle of repeated use can lead to "cocaine nose," referring to severe nasal tissue damage from intranasal use, and "crack lung," which describes respiratory complications from vaporizing cocaine. Both cocaine nose and crack lung can also affect the throat, leading to additional complications.

Cocaine use leads to an increased risk of hemorrhagic and ischemic strokes.<ref name="Sordo2014" /> Cocaine use also increases the risk of having a heart attack.<ref name="Havakuk2017">Template:Cite journal</ref>

Cocaine use also promotes the formation of blood clots.<ref name="Zimmerman2012" /> This increase in blood clot formation is attributed to cocaine-associated increases in the activity of plasminogen activator inhibitor, and an increase in the number, activation, and aggregation of platelets.<ref name="Zimmerman2012" />

Cocaine constricts blood vessels, dilates pupils, and increases body temperature, heart rate, and blood pressure. It can also cause headaches and gastrointestinal complications such as abdominal pain and nausea. Chronic users may lose their appetite and experience severe malnutrition, leading to being underweight.

Although it has been commonly asserted, the available evidence does not show that chronic use of cocaine is associated with broad cognitive impairment.<ref>Template:Cite journal</ref> Research is inconclusive on age-related loss of striatal dopamine transporter (DAT) sites, suggesting cocaine has neuroprotective or neurodegenerative properties for dopamine neurons.<ref>Template:Cite book</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Exposure to cocaine may lead to the breakdown of the blood–brain barrier.<ref>Template:Cite journal</ref><ref>Template:Cite book</ref>

Chronic cocaine use, but not cocaine itself, can contribute to tooth wear and the development of tooth decay through indirect mechanisms. Cocaine use is frequently associated with involuntary tooth grinding, known as bruxism, which can cause dental attrition and gingivitis.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Additionally, stimulants like cocaine, methamphetamine, and even caffeine cause dehydration and dry mouth. Since saliva is an important mechanism in maintaining one's oral pH level, 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). Poor oral hygiene, which is common among individuals with substance use disorders, may contribute significantly to tooth decay in cocaine users.

Addiction

In humans, cocaine abuse may cause addiction-related structural neuroplasticity, though it is unclear to what extent these changes are permanent.<ref name=Hamp2019>Template:Cite journal</ref>

Relatives of persons with cocaine addiction have an increased risk of cocaine addiction.<ref>Template:Cite journal</ref> 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.<ref name="pmid9668659">Template:Cite journal</ref> Each subsequent dose of cocaine continues to increase ΔFosB levels with no ceiling of tolerance. Elevated levels of ΔFosB leads to increases in brain-derived neurotrophic factor (BDNF) levels, which in turn increases the number of dendritic branches and spines present on neurons involved with the nucleus accumbens and prefrontal cortex areas of the brain. This change can be identified rather quickly, and may be sustained weeks after the last dose of the drug.

Genetically modified mice exhibiting inducible expression of ΔFosB primarily in the nucleus accumbens and dorsal striatum exhibit sensitized behavioural responses to cocaine.<ref name="pmid10499584">Template:Cite journal</ref> They self-administer cocaine at lower doses than control,<ref name="pmid12657709">Template:Cite journal</ref> but have a greater likelihood of relapse when the drug is withheld.<ref name="pmid12657709" /><ref name="pmid11572966">Template:Cite journal</ref> ΔFosB increases the expression of AMPA receptor subunit GluR2<ref name="pmid10499584" /> and also decreases expression of dynorphin, thereby enhancing sensitivity to reward.<ref name="pmid11572966" />

DNA damage is increased in the brain of rodents by administration of cocaine.<ref name="pmid24552452">Template:Cite journal</ref><ref name="pmid19878142">Template:Cite journal</ref> During DNA repair of such damages, persistent chromatin alterations may occur such as methylation of DNA or the acetylation or methylation of histones at the sites of repair.<ref name="pmid27259203">Template:Cite journal</ref> These alterations can be epigenetic Template:Clarify in the chromatin that contribute to the persistent epigenetic changes found in cocaine addiction.

Dependence and withdrawal

Cocaine dependence develops after even brief periods of regular cocaine use<ref>Template:Cite journal</ref> and produces a withdrawal state with emotional-motivational deficits upon cessation of cocaine use.

Cocaine nose

File:Cocaine nose.jpg

Nasal septum perforation caused by cocaine use (pictured)-sometimes referred to as a "cocaine nose hole"-can progress to cocaine-induced midline destructive lesions.

"Cocaine nose" or "coke nose" are informal terms that refer to nasal problems resulting from cocaine use.

Problems associated with cocaine nose include:

• Cocaine-induced midline destructive lesions (CIMDL)<ref name="distribution" />
• Nasal septum perforation<ref name="pmid34360121" /> ("cocaine nose hole") can progress to CIMDL
• Saddle nose<ref name="Schreiber2014">Template:Cite journal</ref>

Cocaine-induced midline destructive lesions

Cocaine-induced midline destructive lesions (CIMDL), colloquially known as "coke nose",<ref name="distribution">Template:Cite journal</ref> is the progressive destruction of nasal architecture with the erosion of the palate, nasal conchae, and ethmoid sinuses associated with prolonged insufflation, colloquially 'snorting', of cocaine.<ref name="pmid34360121">Template:Cite journal</ref>

Chronic intranasal usage can degrade the cartilage separating the nostrils (the septum nasi), leading eventually to its complete disappearance. Due to the absorption of the cocaine from cocaine hydrochloride, the remaining hydrochloride forms a dilute hydrochloric acid.<ref name="pagliaros">Template:Cite book</ref>

Mortality

Persons with regular or problematic use of cocaine have a significantly higher mortality rate, and are specifically at higher risk of traumatic deaths and deaths attributable to infectious disease.<ref>Template:Cite journal</ref> In 2025, the Liberty House Clinic in the United Kingdom noted that chronic cocaine usage in fact had a higher risk of death than alcoholism.<ref>Template:Cite web</ref>

Overdose

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Death rates from cocaine overdoses

File:US timeline. Cocaine deaths.svg

US yearly overdose deaths involving cocaine.<ref name=NIDA-deaths>Overdose Death Rates. By National Institute on Drug Abuse (NIDA).</ref>

According to the European Union Drugs Agency, the estimated minimum lethal dose is 1.2 grams. However, sensitive individuals have died from as little as 30 milligrams applied to mucous membranes-an amount that is 40 times less than the minimum lethal dose. In contrast, addicts may tolerate doses as high as 5 grams per day.<ref name="EUDA" />

Cocaine can be snorted, swallowed, injected, or smoked. Most deaths due to cocaine are accidental but may also be the result of body packing or stuffing with rupture in the gastrointestinal tract. Use of cocaine causes abnormally fast heart rhythms and a marked elevation of blood pressure (hypertension), which can be life-threatening. This can lead to death from acute myocardial infarction, acute respiratory failure (i.e., hypoxemia, with or without hypercapnia), stroke, cerebral hemorrhage, and sudden cardiac arrest.<ref>Template:Cite journal</ref> Cocaine overdose may result in hyperthermia as stimulation and increased muscular activity cause greater heat production. Heat loss is also inhibited by the cocaine-induced vasoconstriction.

Dependence treatment

Numerous medications have been investigated for use in cocaine dependence, but Template:As of, none of them were considered to be effective.<ref name="Minozzi2015">Template:Cite journal</ref>

Interactions

Alcohol

Alcohol interacts with cocaine in vivo to produce cocaethylene, another psychoactive substance which may be substantially more cardiotoxic than either cocaine or alcohol by themselves.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

MAOIs

Monoamine oxidase inhibitors (MAOIs) should not be combined with other psychoactive substances (antidepressants, painkillers, stimulants, including prescribed, OTC and illegally acquired drugs, etc.) except under expert care.

Opioids

File:US timeline. Opioid involvement in cocaine overdose.jpg

US. Opioid involvement in cocaine overdose deaths. Green line is cocaine and any opioid. Gray line is cocaine without any opioids. Yellow line is cocaine and other synthetic opioids.<ref name=NIDA-deaths/>

A mixture of cocaine and opioids, 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.

Common prescription opioids include codeine, fentanyl, methadone, morphine, oxycodone, and tramadol. These substances, as well as heroin, are frequently found on the illicit drug market.

Speedball has been responsible for numerous deaths, including celebrities such as comedians/actors John Belushi and Chris Farley, Mitch Hedberg, River Phoenix, grunge singer Layne Staley and actor Philip Seymour Hoffman.

Pharmacology

Pharmacokinetics

The extent of absorption of cocaine into the circulatory system after nasal insufflation is similar to that after oral ingestion. The rate of absorption after nasal insufflation is limited by cocaine-induced vasoconstriction of capillaries in the nasal mucosa. 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 gastric acid and easily absorbed from the alkaline duodenum.<ref name="Intranasal and oral cocaine kinetic" /> 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 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 with 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.<ref>Template:Cite journal; Jones, supra note 19; Wilkinson et al., Van Dyke et al.</ref>

Cocaine crosses the blood–brain barrier via both a proton-coupled organic cation antiporter<ref name="How do psychostimulants enter the h" /><ref name="Structural Requirements for Uptake" /> and (to a lesser extent) via passive diffusion across cell membranes.<ref name="ReferenceA" /> As of September 2022, the gene or genes encoding the human proton-organic cation antiporter had not been identified.<ref>Template:Cite journal</ref>

Cocaine has a short elimination half life of 0.7–1.5 hours and is extensively metabolized by plasma esterases and also by liver cholinesterases, with only about 1% excreted unchanged in the urine.<ref name="Zimmerman2012" /> The metabolism is dominated by hydrolytic ester cleavage, so the eliminated metabolites consist mostly of benzoylecgonine (BE), the major metabolite, and other metabolites in lesser amounts such as ecgonine methyl ester (EME) and ecgonine.<ref>Template:Cite journal</ref><ref name="Zimmerman2012" /> Further minor metabolites of cocaine include norcocaine, p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine (Template:Chem name), and m-hydroxybenzoylecgonine.<ref>Template:Cite journal</ref>

Depending on liver and kidney functions, cocaine metabolites are detectable in urine between three and eight days. Generally speaking benzoylecgonine is eliminated from someone's urine between three and five days. In urine from heavy cocaine users, benzoylecgonine can be detected within four hours after intake and in concentrations greater than 150 ng/mL for up to eight days later.<ref>Template:Cite web</ref>

Detection in the body

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.<ref>R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 9th edition, Biomedical Publications, Seal Beach, California, 2011, pp. 390–394.</ref>

Hair

Hair analysis can detect cocaine metabolites in regular users until after the sections of hair grown during the period of cocaine use are cut or fall out.<ref>Template:Cite web</ref>

Pharmacodynamics

The pharmacodynamics of cocaine involve the complex relationships of neurotransmitters (inhibiting monoamine uptake in rats with ratios of about: serotonin:dopamine = 2:3, serotonin:norepinephrine = 2:5).<ref>Template:Cite journal (Table V. on page 37)</ref><ref name=Pom2012 /> The most extensively studied effect of cocaine on the central nervous system is the blockade of the dopamine transporter protein. Dopamine neurotransmitter released during neural signaling is normally recycled via the transporter; i.e., the transporter binds the transmitter and pumps it out of the synaptic cleft back into the presynaptic neuron, where it is taken up into storage vesicles. Cocaine binds tightly at the dopamine transporter forming a complex that blocks the transporter's function. The dopamine transporter can no longer perform its reuptake function, and thus dopamine accumulates in the synaptic cleft. The increased concentration of dopamine in the synapse activates post-synaptic dopamine receptors, which makes the drug rewarding and promotes the compulsive use of cocaine.<ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref> The 5-HT₂ receptor (particularly the subtypes 5-HT_2A, 5-HT_2B and 5-HT_2C) are involved in the locomotor-activating effects of cocaine.<ref>Template:Cite journal</ref>

Cocaine has been demonstrated to bind as to directly stabilize the DAT transporter on the open outward-facing conformation. Further, cocaine binds in such a way as to inhibit a hydrogen bond innate to DAT. Cocaine's binding properties are such that it attaches so this hydrogen bond will not form and is blocked from formation due to the tightly locked orientation of the cocaine molecule. Research studies have suggested that the affinity for the transporter is not what is involved in the habituation of the substance so much as the conformation and binding properties to where and how on the transporter the molecule binds.<ref>Template:Cite journal</ref>

Conflicting findings have challenged the widely accepted view that cocaine functions solely as a reuptake inhibitor. To induce euphoria an intravenous dose of 0.3-0.6 mg/kg of cocaine is required, which blocks 66-70% of DAT in the brain.<ref>Template:Cite journal</ref> Re-administering cocaine beyond this threshold does not significantly increase DAT occupancy but still results in an increase of euphoria which cannot be explained by reuptake inhibition alone. This discrepancy is not shared with other dopamine reuptake inhibitors like bupropion, sibutramine, mazindol or tesofensine, which have similar or higher potencies than cocaine as dopamine reuptake inhibitors. Furthermore, a similar response-occupancy discrepancy has been observed with methylphenidate, which also stabilizes the dopamine transporter in an open outward-facing conformation.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> These findings have evoked a hypothesis that cocaine may also function as a so-called "DAT inverse agonist" or "negative allosteric modifier of DAT" resulting in dopamine transporter reversal, and subsequent dopamine release into the synaptic cleft from the axon terminal in a manner similar to but distinct from amphetamines.<ref>Template:Cite journal</ref>

Sigma receptors are affected by cocaine, as cocaine functions as a sigma ligand agonist.<ref>Template:Cite web</ref> Further specific receptors it has been demonstrated to function on are NMDA and the D₁ dopamine receptor.<ref>Template:Cite journal</ref>

Cocaine also blocks sodium channels, thereby interfering with the propagation of action potentials;<ref>Template:Cite journal</ref><ref name="Nav" /> 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.<ref>Template:Cite web</ref>Template:Unreliable medical source Cocaine also causes vasoconstriction, thus reducing bleeding during minor surgical procedures. Recent research points to an important role of circadian mechanisms<ref>Template:Cite journal</ref> and clock genes<ref>Template:Cite journal</ref> 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 cell surface receptors, thereby increasing ghrelin-mediated signaling of satiety<ref>Template:Cite journal</ref> and possibly via other effects on appetitive hormones.<ref>Template:Cite journal</ref>

Cocaine effects, further, are shown to be potentiated for the user when used in conjunction with new surroundings and stimuli, and otherwise novel environs.<ref>Template:Cite journal</ref>

Chemistry

Forms

Salts

File:CocaineHydrochloridePowder cropped.jpg

A pile of micronized cocaine hydrochloride

File:CocaineHCl.jpg

A piece of compressed cocaine hydrochloride

Cocaine in its purest form is a white, pearly product. Cocaine — a tropane alkaloid — is a weakly alkaline compound, and can therefore combine with acidic compounds to form salts. The hydrochloride (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.<ref>Template:Cite web</ref>

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 – 1R 2R, 3S, and 5S, two of them dependent, hence eight possible stereoisomers) plus synthetic by-products limits the yield and purity.<ref name="i893">Template:Cite journal</ref><ref name="y069">Template:Cite journal</ref>

Biosynthesis

File:Biosynthesis of cocaine.png

Biosynthesis of cocaine

The first synthesis and elucidation of the cocaine molecule was by Richard Willstätter in 1898.<ref name="Humphrey2001">Template:Cite journal</ref> Willstätter's synthesis derived cocaine from tropinone. Since then, Robert Robinson and Edward Leete have made significant contributions to the mechanism of the synthesis. (-NO₃)

The additional carbon atoms required for the synthesis of cocaine are derived from acetyl-CoA, by addition of two acetyl-CoA units to the N-methyl-Δ¹-pyrrolinium cation.<ref>Template:Cite book</ref> The first addition is a Mannich-like reaction with the enolate anion from acetyl-CoA acting as a nucleophile toward the pyrrolinium cation. The second addition occurs through a Claisen condensation. This produces a racemic mixture of the 2-substituted pyrrolidine, with the retention of the thioester from the Claisen condensation. In formation of tropinone from racemic ethyl [2,3-13C₂]₄(Nmethyl-2-pyrrolidinyl)-3-oxobutanoate there is no preference for either stereoisomer.<ref>Template:Cite journal</ref>

File:Tropane alkaloids biochemistry.png

Biological source of cocaine molecule in the context of the tropane class of molecules. The biological source of each tropane alkaloid is indicated by species, and below that a phylogenetic map is provided.

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.<ref>Template:Cite journal</ref> This is due to the extra chiral center at C-2.<ref>Template:Cite journal</ref> This process occurs through an oxidation, which regenerates the pyrrolinium cation and formation of an enolate anion, and an intramolecular Mannich reaction. The tropane ring system undergoes hydrolysis, SAM-dependent methylation, and reduction via NADPH for the formation of methylecgonine. The benzoyl moiety required for the formation of the cocaine diester is synthesized from phenylalanine via cinnamic acid.<ref>Template:Cite journal</ref> Benzoyl-CoA then combines the two units to form cocaine.

N-methyl-pyrrolinium cation

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

File:Biosynthesis of N-methyl-pyrrolinium cation.png

Biosynthesis of N-methyl-pyrrolinium cation

Robert Robinson's acetonedicarboxylate

The biosynthesis of the tropane alkaloid is still not understood. Hemscheidt proposes that Robinson's acetonedicarboxylate emerges as a potential intermediate for this reaction.<ref>Template:Cite journal</ref> Condensation of N-methylpyrrolinium and acetonedicarboxylate would generate the oxobutyrate.Template:Which Decarboxylation leads to tropane alkaloid formation.

File:Robinson biosynthesis of tropane.png

Robinson biosynthesis of tropane

Reduction of tropinone

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

File:Reduction of tropinone.png

Reduction of tropinone

Illegal clandestine chemistry

In 1991, the United States Department of Justice released a report detailing the typical process in which leaves from coca plants were ultimately converted into cocaine hydrochloride by Latin American drug cartels:<ref name=USDJ1992>Template:Cite report</ref>

• the exact species of coca to be planted was determined by the location of its cultivation, with Erythroxylum coca being grown in tropical high altitude climates of the eastern Andes in Peru and Bolivia, while Erythroxylum novogranatense was favoured in drier lowland areas of Colombia
• the average cocaine alkaloid content of a sample of coca leaf varied between 0.1 and 0.8 percent, with coca from higher altitudes containing the largest percentages of cocaine alkaloids
• the typical farmer will plant coca on a sloping hill so rainfall will not drown the plants as they reach full maturity over 12 to 24 months after being planted
• the main harvest of coca leaves takes place after the traditional wet season in March, with additional harvesting also taking place in July and November
• the leaves are then taken to a flat area and spread out on tarpaulins to dry in the hot sun for approximately 6 hours, and afterwards placed in Template:Cvt sacks to be transported to market or to a cocaine processing facility depending on location
• in the early 1990s, Peru and Bolivia were the main locations for converting coca leaf to coca paste and cocaine base, while Colombia was the primary location for the final conversion for these products into cocaine hydrochloride
• the conversion of coca leaf into coca paste was typically done very close to the coca fields to minimize the need to transport the coca leaves, with a plastic lined pit in the ground used as a "pozo"
• the leaves are added to the pozo along with fresh water from a nearby river, along with kerosene and sodium carbonate, then a team of several people will repeatedly stomp on the mixture in their bare feet for several hours to help turn the leaves into paste
• the cocaine alkaloids and kerosene eventually separate from the water and coca leaves, which are then drained off / scooped out of the mixture
• the cocaine alkaloids are then extracted from the kerosene and added into a dilute acidic solution, to which more sodium carbonate is added to cause a precipitate to form
• the acid and water are afterwards drained off and the precipitate is filtered and dried to produce an off-white putty-like substance, which is coca paste ready for transportation to cocaine base processing facility
• at the processing facility, coca paste is dissolved in a mixture of sulfuric acid and water, to which potassium permanganate is then added and the solution is left to stand for 6 hours to allow the unwanted alkaloids to break down
• the solution is then filtered and the precipitate is discarded, after which ammonia water is added and another precipitate is formed
• when the solution has finished reacting the liquid is drained, then the remaining precipitate is dried under heating lamps, and resulting powder is cocaine base ready for transfer to a cocaine hydrochloride laboratory
• at the laboratory, acetone is added to the cocaine base and after it has dissolved the solution is filtered to remove undesired material
• hydrochloric acid diluted in ether is added to the solution, which causes the cocaine to precipitate out of the solution as cocaine hydrochloride crystals
• the cocaine hydrochloride crystals are finally dried under lamps or in microwave ovens, then pressed into Template:Cvt blocks and wrapped in plastic ready for export

GMO synthesis

Research

In 2022, a GMO produced N. benthamiana were discovered that were able to produce 25% of the amount of cocaine found in a coca plant.<ref>Template:Cite web</ref>

Field analysis

File:Drugwipe Kokain.jpg

Drugwipe test for cocaine

File:Cocaine lines 2.jpg

A payment card used to line up cocaine can be swabbed to detect cocaine.

Personal cards-including ID cards and driver’s licenses-are frequently swabbed by inspectors to detect drug residue, as these items are commonly used to prepare lines of cocaine. Swabbing can reveal traces of cocaine or other illicit substances, providing evidence of recent drug handling or use. This practice may be employed during security checks at border crossings.

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.<ref>Template:Cite news</ref><ref>Template:Cite news</ref>

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.<ref>Template:Cite journal</ref>

Prevalence

File:List of countries by prevalence of cocaine use.jpg

List of countries by prevalence of cocaine use

World annual cocaine consumption, as of 2000, stood at around 600 tonnes, with the United States consuming around 300 t, 50% of the total, Europe about 150 t, 25% of the total, and the rest of the world the remaining 150 t or 25%.<ref>Template:Cite book</ref> It is estimated that 1.5 million people in the United States used cocaine in 2010, down from 2.4 million in 2006.<ref name="Zimmerman2012" /> Conversely, cocaine use appears to be increasingTemplate:When in Europe with the highest prevalences in Spain, the United Kingdom, Italy, and Ireland.<ref name="Zimmerman2012" />

The 2010 UN World Drug Report concluded that "it appears that the North American cocaine market has declined in value from US$47 billion in 1998 to US$38 billion in 2008. Between 2006 and 2008, the value of the market remained basically stable".<ref name="Nations2010">Template:Cite book</ref>

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).<ref name="unodc">Template:Cite web</ref> 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%).<ref name="unodc" />

Europe

Cocaine is the second most popular illegal recreational drug in Europe (behind 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.

Prevalence estimates for the general population: age ranges are 18-64 and 18-34 for Germany, Greece, France, Italy and Hungary; 16-64 and 16-34 for Denmark, Estonia and Norway; 18-65 for Malta; 17-34 for Sweden. Cocaine use in the general population is highest-ranging from 4.2% to 5.5%-in Denmark, Norway, Ireland, the Netherlands, in that order.<ref>Template:Cite web</ref>

United States

Template:Main Cocaine is the second most popular illegal recreational drug in the United States (behind cannabis)<ref>Template:Cite web</ref> and the U.S. is the world's largest consumer of cocaine.<ref name="WFK Illicit drugs" /> 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.

History

Discovery

File:Folha de coca.jpg

Coca leaf in Bolivia

Indigenous peoples of South America have chewed the leaves of Erythroxylon coca—a plant that contains vital nutrients as well as numerous alkaloids, including cocaine—for over a thousand years.<ref name="isbn 978-3-906390-24-6">Template:Cite book</ref> The oldest evidence for cocaine used dates back to c. 8000 B.C.E in Peru.<ref>Template:Cite journal</ref> The coca leaf was, and still is, chewed almost universally by some indigenous communities. The remains of coca leaves have been found with ancient Peruvian mummies, and pottery from the time period depicts humans with bulged cheeks, indicating the presence of something on which they are chewing.<ref name="mummies">Template:Cite journal</ref> There is also evidence that these cultures used a mixture of coca leaves and saliva as an anesthetic for the performance of trepanation.<ref name="trepanning">Template:Cite journal</ref>

When the Spanish arrived in South America, the conquistadors at first banned coca as an "evil agent of devil". But after discovering that without the coca the locals were barely able to work, the conquistadors legalized and taxed the leaf, taking 10% off the value of each crop.<ref>Template:Cite news</ref> In 1569, Spanish botanist Nicolás Monardes described the indigenous peoples' practice of chewing a mixture of tobacco and coca leaves to induce "great contentment": Template:Blockquote

In 1609, Padre Blas Valera wrote: Template:Blockquote

Isolation and naming

Although the stimulant and hunger-suppressant properties of coca leaves 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, and conditions of sea-shipping from South America at the time would often degrade the quality of the cocaine in the plant samples available to European chemists by the time they arrived.<ref name="Karch">Template:Cite book</ref> However, by 1855, the German chemist Friedrich Gaedcke successfully isolated the cocaine alkaloid for the first time.<ref name="Luch">Template:Cite book</ref> Gaedcke named the alkaloid "erythroxyline", and published a description in the journal Archiv der Pharmazie.<ref>Template:Cite journal</ref>

In 1856, Friedrich Wöhler asked Dr. Carl Scherzer, a scientist aboard the Novara (an Austrian frigate sent by Emperor 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, a PhD student at the University of Göttingen in Germany, who then developed an improved purification process.<ref name=nie1860>Template:Cite journal</ref>

Niemann described every step he took to isolate cocaine in his dissertation titled Über eine neue organische Base in den Cocablättern (On a New Organic Base in the Coca Leaves), which was published in 1860 and earned him his Ph.D. 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 "kúka") + suffix "ine".<ref name=nie1860 /><ref>Template:OEtymD</ref>

The first synthesis and elucidation of the structure of the cocaine molecule was by Richard Willstätter in 1898.<ref name="Humphrey2001" /> It was the first biomimetic synthesis of an organic structure recorded in academic chemical literature.<ref name="Singh2">Template:Cite journal</ref><ref>(a) Template:Cite journal (b) Template:Cite journal (c) Template:Cite journal</ref> 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

File:Cocaine for kids.png

"Cocaine toothache drops", 1885 advertisement of cocaine for dental pain in children

File:Bottle for cocaine solution 2.jpg

Bottle of cocaine solution, Germany, circa 1915

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.<ref name="anrep_frog">Template:Cite journal</ref>

Karl Koller (a close associate of Sigmund Freud, who would write about cocaine later) experimented with cocaine for ophthalmic usage. In an infamous experiment in 1884, he experimented upon himself by applying a cocaine solution to his own eye and then pricking it with pins. His findings were presented to the Heidelberg Ophthalmological Society. Also in 1884, Jellinek demonstrated the effects of cocaine as a respiratory system anesthetic. In 1885, William Halsted demonstrated nerve-block anesthesia,<ref>Template:Cite journal</ref> and James Leonard Corning demonstrated peridural anesthesia.<ref>Template:Cite journal</ref> 1898 saw Heinrich Quincke use cocaine for spinal anesthesia.

Popularization

Template:Toomanyimages In 1859, an Italian 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."

File:Vin mariani publicite156.jpg

Mariani tonic Wine - lithography by Jules Cheret, 1894

File:Mariani pope.jpg

Pope Leo XIII purportedly carried a hip flask of the coca-treated Vin Mariani with him, and awarded a Vatican gold medal to Angelo Mariani.<ref>Template:Cite web</ref>

A chemist named 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.

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,<ref>Template:Cite book</ref> in which he wrote that cocaine causes:<ref>Template:Cite web</ref>

By 1885 the U.S. manufacturer Parke-Davis sold coca-leaf cigarettes and cheroots, a cocaine inhalant, a Coca Cordial, cocaine crystals, and cocaine solution for intravenous injection.<ref>Template:Cite journal</ref> 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."

File:Tri-state Drug sign, Route 80, Shreveport, Louisiana LCCN2017703923.tif

Tri-state Drug sign, Route 80, Shreveport, Louisiana

A "pinch of coca leaves" was included in 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.

File:BEAUTY-COMFORT By Madame Falloppe (1904).jpg

In this 1904 advice column from the Tacoma Times, "Madame Falloppe" recommended that cold sores be treated with a solution of borax, cocaine, and morphine.

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. Dockworkers along the Mississippi River used the drug as a stimulant, and white employers encouraged its use by black laborers.<ref name= barlow>Template:Cite book</ref>

In 1909, Ernest Shackleton took "Forced March" brand cocaine tablets to Antarctica, as did Captain Scott a year later on his ill-fated journey to the South Pole.<ref name="dominic_streatfeild">Template:Cite book</ref>

File:Bundesarchiv Bild 102-07741, Berlin, "Koks Emil" der Kokain-Verkäufer.jpg

Women purchase cocaine capsules in Berlin, 1929

In the 1931 song "Minnie the Moocher", Cab Calloway heavily references cocaine use. He uses the phrase "kicking the gong around", slang for cocaine use; describes titular character Minnie as "tall and skinny;" and describes Smokey Joe as "cokey".<ref>Template:Cite magazine</ref> In the 1932 comedy musical film The Big Broadcast, Cab Calloway performs the song with his orchestra and mimes snorting cocaine in between verses.<ref>Template:Cite AV media</ref>

During the mid-1940s, amidst World War II, cocaine was considered for inclusion as an ingredient of a future generation of 'pep pills' for the German military, code named D-IX.<ref>Template:Cite web</ref>

File:Cocaine Energy Drink (7983571911).jpg

Cocaine Energy Drink

While the caffeinated energy drink Cocaine (also known as Cocaine Energy Supplement) contained no actual cocaine, the product launch attracted criticism from lawmakers and anti-drug organizations, who felt that Cocaine glamorized drug usage to children.<ref name=":0" /><ref name=":2">Template:Cite web</ref>

In modern popular culture, references to cocaine are common. The drug has a glamorous image associated with the upper class, famous and powerful, and is said to make users "feel rich and beautiful".<ref name=nyt1>Template:Cite news</ref><ref>Template:Cite web</ref><ref>Template:Cite book</ref><ref>Template:Cite book</ref> In addition the pace of modern society − such as in finance − gives many the incentive to make use of the drug.<ref name=nyt1 />

Modern usage

File:Cocainaestudiante.jpg

Student dividing cocaine

In many countries, cocaine is a popular recreational drug. Cocaine use is prevalent across all socioeconomic strata, including age, demographics, economic, social, political, religious, and livelihood.<ref name="Current">Template:Cite book</ref>

In the United States, the development of "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 across the 1980s and 1990s in the U.S.<ref name="Kozel">Template:Cite book</ref><ref name="r084">Template:Cite book</ref> However, from 2006 to 2010 cocaine use in the US declined by roughly half before again rising once again from 2017 onwards.<ref>Template:Cite web</ref> In the UK, cocaine use increased significantly between the 1990s and late 2000s, with a similar high consumption in some other European countries, including Spain.<ref name="HOC">Template:Cite book</ref>

The estimated U.S. cocaine market exceeded US$70 billion in street value for the year 2005, exceeding revenues by corporations such as Starbucks.<ref>Template:Cite web</ref><ref>Template:Cite web</ref> Cocaine's status as a club drug shows its immense popularity among the "party crowd".<ref name="Current" />

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 Template:As of.<ref name=TNI>Template:Cite web</ref>

In October 2010 it was reported that the use of cocaine in Australia has doubled since monitoring began in 2003.<ref>Template:Cite news</ref>

Society and culture

Legal status

File:Legal status of cocaine possession.png

Legal status of cocaine possession

The production, distribution, and sale of cocaine products is restricted (and illegal in most contexts) in most countries as regulated by the Single Convention on Narcotic Drugs, and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. In the United States the manufacture, importation, possession, and distribution of cocaine are additionally regulated by the 1970 Controlled Substances Act.

Some countries, such as Bolivia, Colombia, and Peru, permit the cultivation of coca leaf for traditional consumption by the local indigenous population, but nevertheless, prohibit the production, sale, and consumption of cocaine.<ref>Template:Cite news</ref> The provisions as to how much a coca farmer can yield annually is protected by laws such as the Bolivian Cato accord.<ref>Template:Cite web</ref> In addition, some parts of Europe, the United States, and Australia allow processed cocaine for medicinal uses only.

Australia

Cocaine is a Schedule 8 controlled drug in Australia under the Poisons Standard.<ref>Template:Cite web</ref> It is the second most popular illicit recreational drug in Australia behind cannabis.<ref>Template:Cite web</ref>

In Western Australia under the Misuse of Drugs Act 1981 4.0g of cocaine is the amount of prohibited drugs determining a court of trial, 2.0g is the amount of cocaine required for the presumption of intention to sell or supply and 28.0g is the amount of cocaine required for purposes of drug trafficking.<ref>Template:Cite web</ref>

United States

File:George H. W. Bush holds up a bag of crack cocaine during his Address to the Nation on National Drug Control Strategy.jpg

President George H. W. Bush holds up a bag of crack cocaine during his Address to the Nation on National Drug Control Strategy on September 5, 1989.

The US federal government instituted a national drug labelling requirement for cocaine and cocaine-containing products through the Pure Food and Drug Act of 1906.Template:Sfn 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.Template:Sfn 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 outlawedTemplate:Spaced ndash 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."<ref>Template:Cite journal</ref> The Harrison Act left manufacturers of cocaine untouched so long as they met certain purity and labeling standards.Template:Sfn Despite that cocaine was typically illegal to sell and legal outlets were rarer, the quantities of legal cocaine produced declined very little.Template:Sfn Legal cocaine quantities did not decrease until the Jones–Miller Act of 1922 put serious restrictions on cocaine manufactures.Template:Sfn

Before the early 1900s, newspapers primarily portrayed addiction-not violence or crime-as the main problem caused by cocaine use, and depicted cocaine users as upper or middle class White people. In 1914, The New York Times published an article titled "Negro Cocaine 'Fiends' Are a New Southern Menace," portraying Black people who used cocaine as dangerous and able to withstand wounds that would normally be fatal.<ref>Template:Cite book</ref> The Anti-Drug Abuse Act of 1986 mandated the same prison sentences for distributing 500 grams of powdered cocaine and just 5 grams of crack cocaine.<ref>Template:Cite book</ref> In the National Survey on Drug Use and Health, white respondents reported a higher rate of powdered cocaine use, and Black respondents reported a higher rate of crack cocaine use.<ref>Template:Cite book</ref>

Harm reduction

File:Needle Exchange deposit bin.jpg

A drug paraphernalia exchange bin

Harm reduction efforts for cocaine use focus on reducing health risks associated with methods like cocaine injection and smoking crack cocaine. These include providing clean needles and crack cocaine paraphernalia, promoting safer consumption practices, and offering drug-checking services to detect dangerous contaminants such as fentanyl. Such strategies aim to minimize overdose risk and disease transmission while supporting users’ health and access to treatment, forming an essential part of modern drug policy.

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.<ref name="un-wdr2006">Template:Cite book</ref>

Illicit supply chain

File:Global-cocaine-flows-WDR2010.jpg

A map showing how cocaine travels from producers to consumers internationally.

Cocaine is rarely produced entirely through chemical synthesis because the process is prohibitively expensive and complex (see synthesis for more information.) Instead, it is far more economical to extract cocaine from the leaves of the coca plant, which grows abundantly in the tropical regions of South America. The natural habitat of coca is concentrated in countries such as Colombia, Peru, and Bolivia, making South America the primary source of the world’s illicit cocaine supply.

As a result, the global cocaine trade follows a characteristic illicit supply chain. Production begins in South America, where coca is cultivated and processed into cocaine. The drug is then trafficked-often across international borders-using a variety of smuggling routes and methods. After reaching consumer countries, cocaine enters distribution networks, where it is broken down into smaller quantities for local markets. Before reaching end users, the product is frequently adulterated, or “laced,” with various substances to increase profits. Finally, the cocaine is sold at the retail level to consumers. This supply chain-production in South America, trafficking, distribution, lacing, and sales-reflects both the geographic and economic realities of the illicit cocaine market.

Production

File:Drugpackscorpion.png

Cocaine powder is often placed into molds and then compressed-often with hydraulic presses-to create dense, solid bricks, which are sometimes branded to serve as identifiers

Colombia is as of 2019 the world's largest cocaine producer, with production more than tripling since 2013.<ref name="CIA World Factbook">Template:Cite web</ref><ref name="NBC Worldnews">Template:Cite web</ref> Three-quarters of the world's annual yield of cocaine has been produced in Colombia, both from cocaine base imported from Peru (primarily the Huallaga Valley) and Bolivia and from locally grown coca. There was a 28% increase 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 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.<ref name="p625">Template:Cite journal</ref>

Estimated Andean region coca cultivation and potential pure cocaine production<ref>Template:Cite web</ref>

	2000	2001	2002	2003	2004
Net cultivation km2 (sq mi)	Template:Convert	Template:Convert	Template:Convert	Template:Convert	Template:Convert
Potential pure cocaine production (tonnes)	770	925	830	680	645

The latest estimate provided by the U.S. authorities on the annual production of cocaine in Colombia refers to 290 metric tons. As of the end of 2011, the seizure operations of Colombian cocaine carried out in different countries have totaled 351.8 metric tons of cocaine, i.e. 121.3% of Colombia's annual production according to the U.S. Department of State's estimates.<ref>Template:Cite news</ref><ref>Template:Cite web</ref>

Cultivation

File:Women gathering leaves of the coca plant (Erythroxylum coca) Wellcome V0043210.jpg

Women gathering leaves of the coca plant (Erythroxylum coca) in Bolivia. Wood engraving, c. 1867

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.<ref name="j011">Template:Cite journal</ref><ref name="l275">Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref><ref>Template:Cite web</ref>

Cocaine paste

File:Precursor chemicals.gif

A cache of precursor chemicals near a South American cocaine processing lab

In traditional cocaine production, solvents are key precursor chemicals used to extract and process cocaine from coca plant leaves. The process typically involves:

• Kerosene (or paraffin): Used to extract the cocaine alkaloid from the alkaline mixture of coca leaves and water.<ref name="EUDA" />
• Acetone, diethyl ether, ethyl acetate, chloroform: Used in later purification steps to dissolve or precipitate cocaine base or hydrochloride.<ref name="EUDA" />

Cocaine paste (paco, basuco, oxi, pasta) is a crude extract of the coca leaf which contains 40% to 91% cocaine freebase along with companion coca alkaloids and varying quantities of benzoic acid, methanol, and kerosene. In South America, coca paste, also known as cocaine base and, therefore, often confused with cocaine sulfate in North America, is relatively inexpensive and is widely used by working class consumers. The coca paste is smoked in tobacco or cannabis cigarettes and use has become widespread in several Latin American countries. Traditionally, coca paste has been relatively abundant in South American countries such as Colombia where it is processed into cocaine hydrochloride ("street cocaine") for distribution to the rest of the world.<ref name="a">Template:Citation</ref> The caustic reactions associated with the local application of coca paste prevents its use by oral, intranasal, mucosal, or injection routes. Coca paste can only be smoked when combined with a combustible material such as tobacco or cannabis.<ref name="f">Template:Citation</ref>

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 Template:Convert 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 Template:Convert 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 Template:Convert of leaves, to create a 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 pasta and sold by the farmer. The Template:Convert yearly harvest of leaves from a hectare produced Template:Convert 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.<ref>Template:Cite book</ref>

Trafficking

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

Routes

Caribbean route

Cocaine traffickers from Colombia and Mexico have established a labyrinth of smuggling routes throughout the Caribbean, the Bahama Islands 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 Template:Convert in the Bahama Islands or off the coast of Puerto Rico, mid-ocean boat-to-boat transfers of Template:Convert, and the commercial shipment of tonnes of cocaine through the port of Miami.<ref>Template:Cite web</ref><ref name="Zimmerman">Template:Cite book</ref><ref name="Corben">Template:Cite book</ref>

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.<ref>Template:Cite web</ref><ref name="e748">Template:Cite book</ref>

Mexican route

The primary cocaine importation points in the United States have been in Arizona, Southern California, South Florida, and Texas. Typically, land vehicles are driven across the Mexico–United States border. Template:As of, sixty-five percent of cocaine enters the United States through Mexico, where the drug is first transported from South American countries.<ref>Template:Cite book</ref> Template:As of, the Sinaloa Cartel is the most active drug cartel involved in smuggling illicit drugs like cocaine into the United States and trafficking them throughout the United States.<ref name="DEA 2015 assessment">Template:Cite web</ref>

Smuggling methods

Concealment

Cocaine is frequently smuggled within shipping containers, mixed with legitimate cargo such as fruit, clothing, or canned goods. It is also commonly concealed in hidden compartments of vehicles and other objects, and criminal organizations have even created operational businesses to disguise drug shipments.

Additionally, cocaine is often concealed in a variety of everyday items and commercial goods to evade detection by authorities. Smugglers have hidden cocaine inside chocolate candies and other sweets, sometimes disguising the drug to look like ordinary candy bars or lollipops, which can be especially dangerous if accidentally consumed by children. Traffickers also use machinery and equipment-such as cotton-candy machines, construction equipment, and even heavy machinery parts-to hide cocaine, sometimes by impregnating the drug into materials like rubber or plastic components.

Another commonality is creating an operational business to disguise the mass shipments.<ref>Template:Cite book</ref> Notorious drug lord Joaquin 'El Chapo' Guzman is one of many who have mixed legitimate business with their drug activities to conceal their illicit trading. El Chapo opened a cannery in Mexico and began producing canned jalapeños and peppers, and stuffed them with cocaine.<ref name="Fake vegetables, bananas, drones and pastries – here are some of drug smuggler's most bizarre methods">Template:Cite news</ref>

Mules

File:Bolletjes.jpg

Abdominal X-ray showing swallowed packages of cocaine.

Mochileros (Template:Literal translation) are drug couriers in the Latin American drug trade. They move drugs on foot from areas where it is produced, such as cocaine from the Valle de los Ríos Apurímac, Ene y Mantaro in Peru, to pick-up points from which it can be collected by the next link in the transport chain.<ref name=pressly2015>Template:Cite web</ref> The work is highly dangerous.<ref name=pressly2015/>

In Mexico, the people who engage in this type of activity are called "Burreros" (Spanish wordplay that refers to the person as a donkey, a pack animal), these people cross the border between Mexico and United States through the Sonoran Desert into Arizona. They usually trek through the desert in small groups, the journey taking more than a week to complete, each with a square-shaped package on their backs, containing around 55 pounds of illegal substances.<ref>Template:Cite web</ref>

File:CBP Officers Arrest Man at Port Everglades with Cocaine Wrapped Around Ankles (20901225020).jpg

CBP officers arrest man at Port Everglades with cocaine wrapped around ankles

Internationally, cocaine is also carried in small, concealed, kilogram quantities across the border by couriers known as "mules" (or "mulas"), who cross a border either legally, for example, through a port or airport, or illegally elsewhere. If the mule gets through without being caught, the gangs will receive most of the profits. If the mule caught, gangs may sever all links and the mule will usually stand trial for trafficking alone.<ref name="Fleetwood">Template:Cite book</ref> In many cases, mules are often forced into the role, as result of coercion, violence, threats or extreme poverty.<ref name="Fleetwood"/><ref>Template:Cite web</ref>

General smuggling techniques, which also have been used for cocaine, include:

• Concealment: Methods of smuggling include hiding the goods in a large vehicle in secret compartments,<ref>Template:Cite news</ref> luggage, <ref>Template:Cite news</ref> or clothes.<ref>Template:Cite news</ref>
• Body packing: The practice of transporting goods outside or inside of the body is called body packing.<ref>Template:Cite web</ref> This is done by a person usually called a mule or bait. The contraband is attached to the outside of the body using adhesive tape, glue, or straps, often in such places as between the cheeks of the buttocks or between rolls of fat.
• Swallowing: This is often done using a mule's gastrointestinal tract or other body cavities as containers.<ref>Template:Cite web</ref> In some cases, this has resulted in cardiac arrest.<ref>Template:Cite journal</ref>

Maritime cocaine smuggling

File:US Navy 070819-O-0000X-001 U.S. Navy helps seize $352 million in cocaine from semi-submersible in the Eastern Pacific.jpg

U.S. Navy helps seize $352 million in cocaine from semi-submersible in the Eastern Pacific

Bulk cargo ships are also used to smuggle cocaine to staging sites in the Western Caribbean zone–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.<ref name="a110">Template:Cite book</ref><ref>Template:Cite web</ref>

Sophisticated 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.<ref>Template:Cite news</ref>

Distribution

After large-scale trafficking, cocaine is distributed within countries or regions by mid-level networks. These distributors break down bulk shipments into smaller quantities and supply local dealers or retail sellers. Distribution often involves organized groups that manage storage, transportation, and logistics to ensure the drug reaches various markets, preparing it for final sale to consumers.

Lacing

File:Flavcocaine.jpg

Cocaine adulterated with fruit flavoring

Street cocaine is often laced or "cut" with cheaper substances to increase bulk, including talc, lactose, sucrose, glucose, mannitol, inositol, caffeine, procaine, phencyclidine, phenytoin, lidocaine, strychnine, levamisole, and amphetamine.<ref>Template:Citation</ref> Fentanyl has been increasingly found in cocaine samples.<ref>Template:Cite journal</ref>

Because of the nature of trafficking, cocaine typically passes through many intermediaries-sometimes a dozen or more-each seeking to earn a profit, which is why lacing with adulterants becomes so common. This makes it virtually impossible for end consumers to know whether or how the drug has been adulterated. Even when purity tests are performed, it remains difficult to determine if the cocaine is truly pure, as all families of potent chemicals and adulterants must also be specifically tested to detect their presence.

The extent of cutting can vary significantly over time but for the last 15 years drugs such as cocaine ranged in Europe on average from 32% to 65% in purity.<ref>Template:Cite web</ref>

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, however the purity of the cocaine is subsequently lowered.<ref name="q884">Template:Cite journal</ref><ref name="t678">Template:Cite book</ref> 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.<ref>Template:Cite web</ref>

In February 2022, 24 people in Argentina died after using cocaine laced with carfentanil.<ref>Template:Cite news</ref>

Levamisole

File:Levamisole.svg

Levamisole

In the body, levamisole is converted into aminorex, a substance with amphetamine-like stimulant effects and a long duration of action.<ref>Template:Cite journal</ref>

During the mid-2010s, levamisole was found in most cocaine products available in both the United States and Europe.<ref>Template:Cite web</ref> Levamisole is known to cause an acute condition involving a severe and dangerous lowered white blood cell count, known as agranulocytosis, in cocaine users, and may also accentuate cocaine's effects.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Levamisole-adulterated cocaine has been associated with autoimmune disease.<ref>Template:Cite journal</ref>

Levamisole test kits can be utilized to detect the presence of levamisole in cocaine.

Local anesthetics

Cocaine is sometimes cut with lidocaine,<ref>Template:Cite journal</ref><ref name="url599 F.2d 635">Template:Cite web</ref> and procaine. <ref>Template:Cite web</ref>

Sales

File:Bag of cocaine.jpg

Cocaine in a zipper storage bag

Cocaine is readily available in all major countries' metropolitan areas. According to the Summer 1998 Pulse Check, published by the U.S. Office of National Drug Control Policy, cocaine use had stabilized across the country, with a few increases reported in San Diego, Bridgeport, Miami, and Boston. In the Western United States, cocaine usage was lower, which was thought to be due to a switch to methamphetamine among some users; methamphetamine is cheaper, three and a half times more powerful, and lasts 12–24 times longer with each dose.<ref>Template:Cite web</ref><ref>Template:Cite web</ref> 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": Template:As of 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.<ref>Template:Cite news</ref>

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.<ref>Template:Cite book</ref>

Research

Experimentally, cocaine injections can be delivered to animals such as fruit flies to study the mechanisms of cocaine addiction.<ref>Template:Cite journal</ref>

See also

• Cocaine and amphetamine regulated transcript

General and cited references

• Template:Cite book
• Template:Cite book
• Template:Cite book

Further reading

• Template:Cite book