Cocaine

Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, '' Erythroxylum coca'' and '' E. novogranatense'', which are cultivated almost exclusively in the Andes. Indigenous South Americans have traditionally used coca leaves for over a thousand years. Notably, there is no evidence that habitual coca leaf use causes addiction or withdrawal, unlike cocaine.

Medically, cocaine is rarely employed, mainly as a topical medication under controlled settings, due to its high abuse potential, adverse effects, and expensive cost. Despite this, recreational use is widespread, driven by its euphoric and aphrodisiac properties. Levamisole induced necrosis syndrome (LINES)-a complication of the common cocaine cutting agent levamisole-and prenatal cocaine exposure is particularly harmful.

Street cocaine is typically snorted, injected, or smoked as crack cocaine, with effects beginning within seconds to minutes and lasting up to 90 minutes depending on the route. Pharmacologically, it is a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI) that activates the mesolimbic pathway. Intoxication may cause euphoria, psychosis, and physical symptoms like tachycardia and mydriasis. An overdose can lead to stroke, heart attack, or sudden cardiac death. Chronic cocaine use leads to cocaine dependence and can cause nose disorders, commonly referred to as "Cocaine nose", including cocaine-induced midline destructive lesions (CIMDL) when insufflated.

Large-scale chemical synthesis of cocaine is unexplored; Instead, 99% of all global cocaine is made by first harvesting coca leaves by cocaleros from their coca plantations in the Andes. These leaves are then extracted into cocaine paste, which is subsequently processed into powdered hydrochloride salt. Both the pharmaceutical supply chain and the illicit supply chain use all these steps, but they operate under very different controls and oversight. In Peru, for example, legal coca cultivation is monopolized by the state company National Coca Company (ENACO), yet approximately 90% of coca leaves produced in the country are diverted to illegal actors for cocaine manufacturing. As a result, these illicit coca crops are a primary target of ongoing government-led coca eradication efforts.

Cocaine is prohibited globally except for restricted medical and scientific uses under treaties like the Single Convention on Narcotic Drugs. Nevertheless, legal penalties vary by country. Some jurisdictions decriminalize possession of small amounts, leading to inconsistency in the legal status of cocaine worldwide.

Etymology

The word cocaine derives , , ultimately .

Uses

Coca leaves have been used by Andean civilizations since ancient times. In ancient Wari culture, 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, although its actual effectiveness has never been systematically studied.Andrew M. Luks, et al
"Wilderness Medical Society Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2014 Update"
Wilderness & Environmental Medicine, 25, S4–S14 (2014).

Cocaine was first isolated from the leaves in 1860.

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%). Since 1961, the Single Convention on Narcotic Drugs has required countries to make recreational use of cocaine a crime. 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. 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. 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

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. 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.

= 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. The effects of drinking coca tea are mild stimulation and mood lift.

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.

= Ypadu

=

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. Like coca teas consumed in Peru to adapt to sickness induced by high elevation, it has a long ethnobotanical history and cultural associations.

Medical

Karl Koller’s groundbreaking discovery of cocaine as a local anesthetic is regarded as the second most significant advance in the history of anesthesia. Although cocaine was once widely preferred for topical anesthesia, the search for replacement agents intensified due to rising costs, strict regulations, and its habit-forming potential. Today, the US Drug Enforcement Administration (DEA) classifies cocaine as a Schedule II drug, recognizing its high potential for abuse but still permitting its limited use for medical purposes.

However, current pharmacoepidemiological trends suggest that cocaine may soon reach the point where, in practical terms, it is no longer used medically in health care as a Schedule II substance. This report may prompt some states (such as North Dakota) and institutions to reconsider whether further efforts to identify alternative agents are needed. As physician boards—but not pharmacy boards—continue to assess knowledge of licit cocaine, attention may shift toward drugs with more contemporary medical use.

Cocaine is rarely prescribed in modern medicine due to its high potential for abuse and significant risk of adverse effects; its use is now almost exclusively limited to health facilities for specific diagnostic procedures or surgeries.

Topical

Cocaine is used in medical practice as a topical medication. Because it is not absorbed into the bloodstream in significant amounts when used this way, topical application does not produce the psychoactive effects associated with recreational cocaine use.

=Topical anesthetic

=

Cocaine is sometimes used in otorhinolaryngology as a topical anesthetic and vasoconstrictor to help control pain and bleeding during 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. Occasionally, cocaine is mixed with adrenaline and sodium bicarbonate and used topically for surgery, a formulation called Moffett's solution. It is occasionally used in surgeries involving the pharynx or nasopharynx to reduce pain, bleeding, and vocal cord spasm.

Nasal solution cocaine hydrochloride (Goprelto), an ester used for intranasal application, was approved for medical use in the United States in December 2017, and is indicated for the introduction of topical anesthesia of the mucous membranes for diagnostic procedures and surgeries on or through the nasal cavities of adults. Cocaine hydrochloride (Numbrino) was approved for medical use in the United States in January 2020. Headache and epistaxis are the most frequently reported adverse reactions with Goprelto, while hypertension and tachycardia-including sinus tachycardia-are most common with Numbrino.

=Ophthalmological use

=
Cocaine is an ophthalmological agent classified under ATC code S01HA Local anesthetics.

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 stimulates the sympathetic nervous system (SNS) by inhibiting norepinephrine reuptake, causing the pupil to dilate. In patients with Horner syndrome, sympathetic innervation to the eye is disrupted, so the affected pupil does not dilate in response to cocaine and remains constricted, or dilates to a lesser extent than the unaffected eye, which also receives the eye drop test. If both eyes dilate equally, the patient does not have Horner syndrome.

Recreational

Recreational cocaine is typically not taken by mouth due to its poor bioavailability, instead it is usually snorted, injected.
Cocaine hydrochloride can also be chemically converted into its free base form, crack cocaine, which can be vaporized.

Cocaine is a central nervous system stimulant. Its effects can last from 15 minutes to an hour. The duration of cocaine's effects depends on the amount taken and the route of administration. Cocaine can be in the form of fine white powder 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.

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.

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.

In 2023, David Liddell of the Scottish Drugs Forum reported a rise in cocaine use, particularly among people with long-term drug problems, and noted that stigma often delays users from seeking help until their issues become severe.

Insufflation

Nasal insufflation (known colloquially as "snorting", "sniffing", or "blowing") is a common method of ingestion of recreational powdered cocaine. The drug coats and is absorbed through the mucous 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. Insufflation of cocaine also leads to the longest duration of its effects (60–90 minutes). When insufflating cocaine, absorption through the nasal membranes is approximately 30–60%

In a study of cocaine users, the average time taken to reach peak subjective effects was 14.6 minutes. Any damage to the inside of the nose is 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."

Most banknotes have traces of cocaine on them; this has been confirmed by studies done in several countries. In 1994, the U.S. 9th Circuit Court of Appeals cited findings that in Los Angeles, three out of four banknotes were tainted by cocaine or another illicit drug.

Snuff spoons, hollowed-out pens, cut straws, pointed ends of keys, long fingernails or artificial nails, and (clean) tampon applicators are also 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. A 2001 study reported that the sharing of straws used to "snort" cocaine can spread blood diseases such as hepatitis C.

= Cocaine 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.

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.

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. 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

=

Powder cocaine (cocaine hydrochloride) must be heated to a high temperature (about 197 °C), and considerable decomposition/burning occurs at these high temperatures. This effectively destroys some of the cocaine and yields a sharp, acrid, and foul-tasting smoke. Cocaine base/crack can be smoked because it vaporizes with little or no decomposition at , which is below the boiling point of water.

Contraindications

Cocaine should not be used in individuals with a known allergy or hypersensitivity to the drug or any components of its topical formulation. It is also contraindicated in elderly patients and those with a history of hypertension or cardiovascular disease.

Pregnancy

Under the former FDA pregnancy category system, cocaine was classified as a Category C drug. Its potential to cause harm to the fetus is not fully known, so it should only be administered to pregnant women if clearly necessary.

Cocaine can act as a teratogen, having various effects on the developing fetus. Some common teratogenic defects caused by cocaine include hydronephrosis, cleft palate, polydactyly, and down syndrome. 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. 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. Cocaine use during pregnancy can also result in obstetric labor complications such as premature labor, placental abruption, preterm birth or delivery, uterine rupture, miscarriage, and stillbirth.

Breastfeeding

Mothers utilizing recreational drugs, such as cocaine, methamphetamines, PCP, and heroin, should not breastfeed.

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:

Diagnosis

The ICD-10 uses the category "Cocaine-related disorders (F14)", which encompasses a wide range of specific codes—48 in total—organized under the section codes "cocaine abuse" (F14.1), "cocaine dependence" (F14.2), and "cocaine use, unspecified" (F14.9) to classify cocaine-related disorders. For ICD-10, a diagnosis of harmful use or dependence requires that the pattern of use has persisted for at least 1 month or has occurred repeatedly within a 12-month period. In ICD-11, "Disorders due to use of cocaine" is classified under code 6C45. Specific section codes within this category include but are not limited to "Episode of harmful use of cocaine" (6C45.0), "Harmful pattern of use of cocaine" (6C45.1), "cocaine dependence" (6C45.2), "cocaine intoxication" (6C45.3), "cocaine withdrawal" (6C45.4), "cocaine-induced delirium" (6C45.5), and "cocaine-induced psychotic disorder" (6C45.6). The ICD coding system does not use the term "addiction" for cocaine or other substances; instead, it relies on "abuse" and "dependence" to describe problematic use patterns and their consequences. As such, the ICD does not list "cocaine addiction" as a diagnostic term.

In the DSM-5, the concept of cocaine-related disorders is used to classify problems associated with cocaine use. There are a total of 13 specific cocaine-related codes in DSM-5, with 11 of these under code 292, which covers a range of cocaine-induced mental and behavioral disorders—including intoxication, withdrawal, delirium, anxiety, mood, psychotic, sexual, and sleep disorders, as well as other related conditions. Additionally, code 305 refers to cocaine abuse, indicating less severe but still problematic use, and code 304 refers to cocaine dependence, representing more severe and chronic use—all within the DSM-5 coding system. For a diagnosis of cocaine use disorder in DSM-5, at least 2 out of 11 criteria must be met within a 12-month period, indicating a problematic pattern of use that leads to clinically significant impairment or distress.

Adverse effects

Cardiac complications

Cocaine use can cause serious heart problems like sudden death, heart inflammation, arrhythmias, and heart attacks. It triggers coronary artery spasms, increases blood clot risk, and accelerates atherosclerosis, especially with long-term use. The severity of heart disease often relates to how long and how often cocaine is used. It can also become a serious risk at high doses due to cocaine's blocking effect on cardiac sodium channels.

Levamisole syndromes

Cocaine is frequently cut with levamisole.

Levamisole induced necrosis syndrome

Levamisole induced necrosis syndrome (LINES) is a complication characterized by necrosis resulting from exposure to levamisole, a medication with immunomodulatory properties. While LINES can occur with levamisole use alone, most reported cases are associated with the use of cocaine adulterated with levamisole as a cutting agent. This syndrome is marked by skin necrosis, often affecting areas such as the ears, face, and extremities, and is thought to result from levamisole’s effects on blood vessels and the immune system.

Cocaine/levamisole-associated syndromes

The skin necrosis associated with levamisole toxicity ranges from leukocytoclastic vasculitis to occlusive vasculopathy. Several cases of severe agranulocytosis associated with cocaine use have been reported since 2006. With the recently recognized dermal disease, the face and ears are commonly affected, especially the bilateral helices and cheeks. However, there have also been case reports of involvement of the abdomen, chest, lower buttocks and legs.

During the mid-2010s, levamisole was found in most cocaine products available in both the United States and Europe. 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.

=Cocaine- and levamisole-induced vasculitis

=
Cocaine- and levamisole-induced vasculitis (CLIV) is often used as an umbrella term for the vasculitic and necrotic complications seen with levamisole-adulterated cocaine, including both LINES and CLAAS.

Cocaine and levamisole-adulterated cocaine (LAC) can cause cocaine-induced vasculitis (CIV) that mimics primary anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), presenting as cocaine-induced midline destructive lesions, LAC vasculopathy, or CIV. These conditions involve immune activation through NETosis and ANCA formation, leading to tissue damage. Diagnosis is challenging due to symptom overlap and undisclosed drug use, making clinical suspicion and drug history essential for proper management.

Cocaine/levamisole-associated autoimmune syndrome

The broader cocaine/levamisole-associated autoimmune syndrome (CLAAS) includes LINES as a subset and is also common, but LINES is more specifically and frequently cited in the context of street cocaine adulteration.

Levamisole has become a common additive to illicit cocaine. It is thought to intensify the "high" by releasing dopamine in the brain, acts as a bulking agent, and is a difficult adulterant to recognize. Potential risks of levamisole-laced cocaine include autoimmune disease, neutropenia, arthralgias, retiform purpura, skin necrosis, and fever.

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. 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.

Neurotoxicity

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.

Psychosis

Cocaine has a similar potential to induce temporary psychosis with more than half of cocaine abusers reporting at least some psychotic symptoms at some point. Typical symptoms include paranoid delusions that they are being followed and that their drug use is being watched, accompanied by hallucinations that support the delusional beliefs. Delusional parasitosis with formication ("cocaine bugs") is also a fairly common symptom.

Cocaine-induced psychosis shows sensitization toward the psychotic effects of the drug. This means that psychosis becomes more severe with repeated intermittent use.

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. In humans with acute exposure followed by continuous exposure to cocaine at a constant blood concentration, the acute tolerance to the chronotropic cardiac effects of cocaine begins after about 10 minutes, while acute tolerance to the euphoric effects of cocaine begins after about one hour. With excessive or prolonged use, the drug can cause itching, fast heart rate, and paranoid delusions or sensations of insects crawling on the skin. Intranasal cocaine and crack use are both associated with pharmacological violence. Aggressive behavior may be displayed by both addicts and casual users. Cocaine can induce psychosis characterized by paranoia, impaired reality testing, hallucinations, irritability, and physical aggression. Cocaine intoxication can cause hyperawareness, hypervigilance, psychomotor agitation, and delirium. Consumption of large doses of cocaine can cause violent outbursts, especially by those with preexisting psychosis. 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. Cocaine overdose may cause seizures, abnormally high body temperature and a marked elevation of blood pressure, which can be life-threatening, abnormal heart rhythms, and death. Anxiety, paranoia, and restlessness can also occur, especially during the comedown. With excessive dosage, tremors, convulsions, and increased body temperature are observed.

Long-term effects

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), 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. Cocaine use also increases the risk of having a heart attack.

Cocaine use also promotes the formation of blood clots. 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.

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. Research is inconclusive on age-related loss of striatal dopamine transporter (DAT) sites, suggesting cocaine has neuroprotective or neurodegenerative properties for dopamine neurons. Exposure to cocaine may lead to the breakdown of the blood–brain barrier.

The misuse of cocaine has a high correlation with suicide. In those who use cocaine, the risk is greatest during the withdrawal phase.

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. 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.

Cocaine related disorders

= Addiction

=

Cocaine can induce tolerance after a single dose, and repeated use frequently leads to the development of addiction and prolonged craving. Withdrawal symptoms include disrupted sleep, irritability, depression, and reduced ability to experience pleasure ( anhedonia). Chronic nasal use may cause destructive damage to the nasal septum, including cocaine-induced midline destructive lesions ( CIMDL). Illicit cocaine is frequently adulterated with substances such as fentanyl, levamisole, or local anesthetics, increasing its toxicity. Concurrent use with alcohol produces cocaethylene, a metabolite that significantly increases the risk of sudden death. According to the Global Burden of Disease Study, cocaine use is responsible for approximately 7,300 deaths annually.

Cocaine abuse can trigger addiction-related structural neuroplasticity in the human brain, although the permanence of such changes remains uncertain. Family history is a known risk factor, as relatives of cocaine users have an increased likelihood of developing cocaine addiction. A key mechanism involves the overexpression of ΔFosB in the nucleus accumbens, altering transcriptional regulation and reinforcing drug-seeking behavior. Each dose of cocaine raises ΔFosB levels without a known saturation point. This elevation leads to increased brain-derived neurotrophic factor (BDNF) levels, which in turn enhance dendritic branching and spine density in neurons of the nucleus accumbens and prefrontal cortex, potentially persisting for weeks after drug cessation.

In transgenic mice engineered to express ΔFosB in the nucleus accumbens and dorsal striatum, heightened behavioral sensitization to cocaine has been observed. These mice self-administer cocaine at lower doses and display a greater propensity for relapse after withdrawal ΔFosB also enhances sensitivity to reward by upregulating the AMPA receptor subunit GluR2 and downregulating the expression of dynorphin.

Cocaine use has also been shown to increase DNA damage in the brains of rodents. During subsequent DNA repair, enduring alterations in chromatin structure may arise, such as DNA methylation and methylation or acetylation of histones at the repair loci. These modifications may result in lasting epigenetic "scars", which are believed to contribute to the persistent epigenetic changes observed in cocaine addiction.

= Dependence and withdrawal

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

Cocaine nose

"Cocaine nose" or "coke nose" are informal terms that refer to nose disorders resulting from repeated or chronic cocaine use.

Cocaine nose can develop even in individuals who use the drug recreationally or only on weekends, not just in chronic or daily users.

About 30% of people who had snorted cocaine at least 25 times but less than daily, and 47% of daily users, reported experiencing nasal irritation, crusting or scabbing, and frequent nosebleeds. Cocaine use should be considered as a potential cause of persistent or unexplained rhinitis, including in adolescent patients.

Because the nose is a prominent facial feature, such visible damage often leads to embarrassment, stigma, and negative reactions from others. As a result, individuals with cocaine-induced nasal damage frequently withdraw from social activities and relationships, leading to social isolation. In many cases, this isolation is not just likely but almost inevitable, as affected individuals may feel unable to face the outside world due to the noticeable and sometimes severe changes to their appearance.

= Forms

=
Nose disorders associated with cocaine nose include:
* Cocaine-induced midline destructive lesions (CIMDL)
* Nasal septum perforation ("cocaine nose hole")
* Saddle nose

Cocaine-induced midline destructive lesions

Cocaine-induced midline destructive lesions (CIMDL), colloquially known as "coke nose", 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.

Chronic intranasal usage can degrade the cartilage separating the nostrils (the septum nasi), leading eventually to its complete disappearance.

= Causes

=
The cause of "cocaine nose" can be traced to the chemical process that occurs when cocaine hydrochloride is insufflated (snorted). As cocaine is absorbed through the nasal mucosa, the remaining hydrochloride component forms a dilute hydrochloric acid. This acid, combined with the powerful vasoconstrictive effects of cocaine (which restricts blood flow and oxygen to the tissues), leads to irritation, necrosis, and ultimately the breakdown of the nasal septum and surrounding structures.

= Treatment

=
For people with cocaine abuse, mild symptoms may resolve completely with total abstinence from cocaine, making early involvement of addiction services essential.

Repair may involve rhinoplasty, which includes creating a new internal lining with nasolabial flaps and restoring support with costal cartilage grafts.

In 2024, Belgian doctors report a rise in patients needing nose reconstruction due to cocaine use, which damages nasal tissue and cartilage; however, few undergo surgery because it requires at least six months of abstinence from cocaine for proper healing.

Some individuals seek plastic surgery to repair or reconstruct nasal damage caused by cocaine use, although surgical outcomes can be complicated by ongoing tissue loss and poor healing. When nasal damage is too severe for reconstruction, a nose prosthesis may be used to restore appearance and quality of life.

Overdose

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.

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. Alcohol impairment increases the likelihood of risk-taking behaviors and susceptibility to peer pressure, and also raises the risk of overdose due to the formation of cocaethylene (see the alcohol section).

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. Overdose can also cause acute hepatotoxicity—typically due to toxic metabolites—though most cases resolve quickly; however, fatal outcomes from multiple organ dysfunction syndrome are possible, and there is no specific antidote. 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.

In 2024, drug-related deaths in England and Wales reached their highest level in three decades, with a notable increase in fatalities involving cocaine and experts urging urgent government intervention to address the crisis. Martin Powell, from the charity Transform, which campaigns for the legal regulation of drugs, suggested that the recent rise in cocaine-related deaths in the UK may be due to the increased purity of cocaine, leading users to consume it more frequently and alongside other substances.

Dependence treatment

Because there are no medications with an approved indication for cocaine use disorder, psychosocial treatments are the current standard. Effective approaches include group and individual counseling, cognitive behavioral therapy (CBT), and motivational interviewing (MI). Contingency management (CM)—which rewards patients with vouchers for meeting treatment goals—has proven especially effective, particularly for helping patients achieve initial abstinence from cocaine.

Cocaine Anonymous (CA) is a twelve-step program formed in 1982, November 18th for people who seek recovery from drug addiction. It is patterned very closely after Alcoholics Anonymous (AA), although the two groups are unaffiliated. While many C.A. members have been addicted to cocaine, crack, speed or similar substances, C.A. accepts all who desire freedom from "cocaine and all other mind-altering substances" as members.

Numerous medications have been investigated for use in cocaine dependence, but , none of them were considered to be effective. Drugs which help to re-stabilize the glutamate system such as N-acetylcysteine have been proposed for the treatment of addiction to cocaine, nicotine, and alcohol. However, none have sufficient evidence or regulatory approval for routine clinical use, so psychosocial interventions remain the mainstay of treatment.

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.

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

The opioid epidemic now involves more overdose deaths with both opioids and cocaine, especially among non-Hispanic Blacks who are twice as likely to die from combined opioid-stimulant overdoses compared to non-Hispanic whites. Cocaine-related deaths in Blacks are similar to opioid deaths in whites. Risk factors include young age, education, urban living, mental disorders, and stress. It remains unclear if co-use is intentional. Recent studies expand focus beyond heroin to all opioids, reflecting changing overdose patterns.

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. 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.

Cocaine crosses the blood–brain barrier via both a proton-coupled organic cation antiporter and (to a lesser extent) via passive diffusion across cell membranes. As of September 2022, the gene or genes encoding the human proton-organic cation antiporter had not been identified.

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. 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. Further minor metabolites of cocaine include norcocaine, p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine (), and m-hydroxybenzoylecgonine.

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.

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.

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.

Pharmacodynamics

Cocaine acts as a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI). Cocaine increases 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.

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). 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.

Cocaine affects certain serotonin (5-HT) receptors; in particular, it has been shown to antagonize the 5-HT₃ receptor, which is a ligand-gated ion channel. An overabundance of 5-HT₃ receptors is reported in cocaine-conditioned rats, though 5-HT₃'s role is unclear. The 5-HT₂ receptor (particularly the subtypes 5-HT_2A, 5-HT_2B and 5-HT_2C) are involved in the locomotor-activating effects of cocaine.

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.

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. 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. 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.

Sigma receptors are affected by cocaine, as cocaine functions as a sigma ligand agonist. Further specific receptors it has been demonstrated to function on are NMDA and the D₁ dopamine receptor.

Cocaine also blocks sodium channels, thereby interfering with the propagation of action potentials; thus, like lignocaine and novocaine, it acts as a local anesthetic. It also functions on the binding sites to the dopamine and serotonin sodium dependent transport area as targets as separate mechanisms from its reuptake of those transporters; unique to its local anesthetic value which makes it in a class of functionality different from both its own derived phenyltropanes analogues which have that removed. In addition to this, cocaine has some target binding to the site of the κ-opioid receptor. Cocaine also causes vasoconstriction, thus reducing bleeding during minor surgical procedures. Recent research points to an important role of circadian mechanisms and clock genes in behavioral actions of cocaine.

Cocaine is known to suppress hunger and appetite by increasing co-localization of sigma σ₁R receptors and ghrelin GHS-R1a cell surface receptors, thereby increasing ghrelin-mediated signaling of satiety and possibly via other effects on appetitive hormones.

Cocaine effects, further, are shown to be potentiated for the user when used in conjunction with new surroundings and stimuli, and otherwise novel environs.

Chemistry

Forms

Salts

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.

Synthesis

Synthesizing (i.e., not extracting) cocaine is possible but impractical because natural sources provide a lower-cost and higher-quality supply. While domestic clandestine laboratories could, in theory, replace the reliance on offshore sources and international smuggling—as is common with illicit methamphetamine production—this approach is rarely used.

Formation of inactive stereoisomers (cocaine has four chiral centres – 1''R'' 2''R'', 3''S'', and 5''S'', two of them dependent, hence eight possible stereoisomers) plus synthetic by-products limits the yield and purity.

Biosynthesis

The first synthesis and elucidation of the cocaine molecule was by Richard Willstätter in 1898. Willstätter's synthesis derived cocaine from tropinone. Since then, Robert Robinson and Edward Leete have made significant contributions to the mechanism of the synthesis. (-NO₃)

The additional carbon atoms required for the synthesis of cocaine are derived from acetyl-CoA, by addition of two acetyl-CoA units to the ''N''-methyl-Δ¹-pyrrolinium cation. The first addition is a Mannich-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 ,3-13C₂sub>4(Nmethyl-2-pyrrolidinyl)-3-oxobutanoate there is no preference for either stereoisomer.

In cocaine biosynthesis, only the (S)-enantiomer can cyclize to form the tropane ring system of cocaine. The stereoselectivity of this reaction was further investigated through study of prochiral methylene hydrogen discrimination. This is due to the extra chiral center at C-2. This process occurs through an oxidation, which regenerates the pyrrolinium cation and formation of an enolate anion, and an intramolecular Mannich reaction. The tropane ring system undergoes hydrolysis, SAM-dependent methylation, and reduction via NADPH for the formation of methylecgonine. The benzoyl moiety required for the formation of the cocaine diester is synthesized from phenylalanine via cinnamic acid. Benzoyl-CoA then combines the two units to form cocaine.

Large-scale commercial biosynthesis remains unexplored.

= ''N''-methyl-pyrrolinium cation

=

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

= Robert Robinson's acetonedicarboxylate

=
The biosynthesis of the tropane alkaloid is still not understood. Hemscheidt proposes that Robinson's acetonedicarboxylate emerges as a potential intermediate for this reaction. Condensation of ''N''-methylpyrrolinium and acetonedicarboxylate would generate the oxobutyrate. Decarboxylation leads to tropane alkaloid formation.

= Reduction of tropinone

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

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.

However, since ''N. benthamiana'' also naturally contains nicotine, separating the cocaine from nicotine and related alkaloids would be challenging.

Field analysis

Personal data, 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.

A ''Newsbeat'' investigation found that "cocaine torches" used by UK police to detect cocaine use are ineffective on typical street cocaine, as independent lab tests showed they fail to make the drug fluoresce. Experts and drug charities criticized the devices, warning they can give false positives and waste resources, while police forces defended their use as a deterrent. The manufacturer says the torches only work on much purer forms of cocaine than are found on the street.

Cocaine may be detected by law enforcement using the Scott reagent. The test can easily generate False positives and false negatives, false positives for common substances and must be confirmed with a laboratory test.

Approximate cocaine purity can be determined using 1 mL 2% cupric sulfate pentahydrate in dilute HCl, 1 mL 2% potassium thiocyanate and 2 mL of chloroform. The shade of brown shown by the chloroform is proportional to the cocaine content. This test is not cross sensitive to heroin, methamphetamine, benzocaine, procaine and a number of other drugs but other chemicals could cause false positives.

Society and culture

Prevalence

World annual cocaine consumption, as of 2000, stood at around 600 tonnes, with the United States consuming around 300 t, 50% of the total, Europe about 150 t, 25% of the total, and the rest of the world the remaining 150 t or 25%. It is estimated that 1.5 million people in the United States used cocaine in 2010, down from 2.4 million in 2006. Conversely, cocaine use appears to be increasing in Europe with the highest prevalences in Spain, the United Kingdom, Italy, and Republic of Ireland, Ireland.

The 2010 UN World Drug Report concluded that "it appears that the North American cocaine market has declined in value from US$47 billion in 1998 to US$38 billion in 2008. Between 2006 and 2008, the value of the market remained basically stable".

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

Europe

Cocaine is the second most popular illegal recreational drug in Europe (behind cannabis (drug), cannabis). Since the mid-1990s, overall cocaine usage in Europe has been on the rise, but usage rates and attitudes tend to vary between countries.

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.

South America

It is not widely recognized that South America is the world’s third largest market for cocaine use, with approximately 1,981,000 users as of 2004/5. The prevalence rate among people aged 15-64 stands at 0.7%, which is on par with Europe but significantly lower than North America’s 2.3%. In the main coca-producing countries, cocaine use rates are at or above the regional average, underscoring a strong connection between illicit crop cultivation, cocaine production, and local abuse. In Bolivia, where cocaine use is well above the Latin American average, annual prevalence rates have mirrored domestic production trends: after substantial increases in the early 1990s until 1996, rates declined, then began rising again from 2000 to 2005, reaching 1.6% for cocaine hydrochloride and 1.9% for cocaine base in 2005.

United States

Cocaine is the second most popular illegal recreational drug in the United States (behind cannabis (drug), cannabis) and the U.S. is the world's largest consumer of cocaine. 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.

Legal status

The production, distribution, and sale of cocaine products is restricted (and illegal in most contexts) in most countries as regulated by the Single Convention on Narcotic Drugs, 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 peoples of the Americas, indigenous population, but nevertheless, prohibit the production, sale, and consumption of cocaine. The provisions as to how much a coca farmer can yield annually is protected by laws such as the Bolivian Cato accord. In addition, some parts of Europe, the United States, and Australia allow processed cocaine for medicinal uses only.

Australia

Cocaine is a Schedule 8 controlled drug in Australia under the Standard for the Uniform Scheduling of Medicines and Poisons, Poisons Standard. It is the second most popular illicit recreational drug in Australia Cannabis in Australia, behind cannabis.

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

United States

The US federal government instituted a national drug labelling requirement for cocaine and cocaine-containing products through the Pure Food and Drug Act of 1906. The next important federal regulation was the Harrison Narcotics Tax Act of 1914. While this act is often seen as the start of prohibition, the act itself was not actually a prohibition on cocaine, but instead set up a regulatory and licensing regime. The Harrison Act did not recognize addiction as a treatable condition and therefore the therapeutic use of cocaine, heroin, or morphine to such individuals was outlawed leading a 1915 editorial in the journal ''American Medicine'' to remark that the addict "is denied the medical care he urgently needs, open, above-board sources from which he formerly obtained his drug supply are closed to him, and he is driven to the underworld where he can get his drug, but of course, surreptitiously and in violation of the law." The Harrison Act left manufacturers of cocaine untouched so long as they met certain purity and labeling standards. Despite that cocaine was typically illegal to sell and legal outlets were rarer, the quantities of legal cocaine produced declined very little. Legal cocaine quantities did not decrease until the Narcotic Drugs Import and Export Act, Jones–Miller Act of 1922 put serious restrictions on cocaine manufactures.

Before the early 1900s, 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. 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. 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.

Harm reduction

Experts recommend that anyone using stimulants such as cocaine or MDMA, as well as those around them, carry naloxone due to the growing risk of opioid contamination in the drug supply. Having naloxone available can help prevent fatal overdoses, even when opioids weren’t intentionally used. Nasal spray formulations of naloxone are specifically recommended, as they are legal in many regions, easy to carry, and can be administered by anyone, not just medical professionals. The World Health Organization (WHO) includes naloxone on their "WHO Model List of Essential Medicines, List of Essential Medicines", and recommends its availability and utilization for the reversal of opioid overdoses. In the United States, some nasal naloxone are legally available without a prescription.

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.

Reagent testing

List of reagent testing color charts, Reagent testing kits are widely used to identify the presence of cocaine and its common adulterants. The Cobalt(II) thiocyanate, Scott reagent is specifically designed as a presumptive test for cocaine. Morris reagent, which is derived from the Scott reagent, is also used as a presumptive test for cocaine. The Liebermann reagent, Liebermann and Mandelin reagent, Mandelin reagents are commonly used to test for both cocaine, and levamisole, which is a frequent cutting agent found in street cocaine.

Each reagent provides different color indications for various substances. Since adulteration of cocaine with levamisole is widespread, the color reactions produced by these reagents often reflect the presence of both substances. The resulting mixed color can complicate interpretation, making further analysis or additional testing necessary to clarify the sample’s composition.

DanceSafe recommends starting with Morris reagent to identify cocaine. A bright blue color means cocaine is present. Next, use Marquis reagent—no color change or light pink is normal, but orange may indicate amphetamines, so use a test strip if needed. Finally, test a fresh sample with Liebermann; yellow means pure cocaine, while rusty red suggests levamisole or lidocaine.

Enforcement

Coca eradication

Coca eradication is a strategy promoted by the United States Federal government of the United States, government starting in 1961 as part of its "War on Drugs, war on drugs" to eliminate the cultivation of coca, a plant whose leaves are not only traditionally used by Indigenous peoples of the Americas, indigenous cultures but also, in modern society, in the manufacture of cocaine. The strategy was adopted in place of running educational campaigns against drug usage. The prohibition (drugs), prohibitionist strategy is being pursued in the coca-growing regions of Colombia (Plan Colombia), Peru, and formerly Bolivia, where it is highly controversial because of its environmental, health and socioeconomic impact. Furthermore, indigenous cultures living in the ''Altiplano'', such as the Aymara people, Aymaras, use the coca leaf (which they dub the "millenary leaf") in many of their cultural traditions, notably for its medicinal qualities in alleviating the feeling of hunger, fatigue and headaches symptomatic of altitude sicknesses. The growers of coca are named ''Cocaleros'' and part of the coca production for traditional use is legal in Peru, Bolivia and Chile.

Interdiction

The Consolidated Counterdrug Database (CCDB) is a U.S. government dataset created in the 1990s that compiles vetted data on cocaine trafficking and seizures in the Western Hemisphere "transit zone," involving 26 U.S. agencies and 20 foreign partners. It provides a highly reliable, conservative record of cocaine movements and interdiction efforts, revealing that despite large seizures, interdiction captures only a small fraction of trafficking events and has minimal impact on U.S. cocaine prices. The CCDB challenges optimistic views of drug interdiction effectiveness and underscores the need for new policy approaches, yet remains underutilized in research despite being unclassified.

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.

Pharmaceutical supply chain

Production

= Legal coca cultivation

=
In Bolivia, legal coca cultivation is regulated by the Coca and Integral Development agency, which operates under the Ministry of Rural Development (Bolivia), Ministry of Rural Development.

In Colombia, the regulation of legal coca cultivation for traditional and scientific uses falls under the responsibility of government agencies, primarily the Ministry of Justice and Law (Colombia), Ministry of Justice and Law (Ministerio de Justicia y del Derecho).

In Peru, The National Coca Company, National Company of the Coca (Spanish: ''Empresa Nacional de la Coca'', ENACO) is a state company dedicated to the commercialization of the coca leaf and derivatives. It is the only state company that has a monopoly on the commercialization and derivatives of the coca leaf. It was created in 1949. In 1982, it became a state company under private law. Nonetheless, much of this cocaine enters the black market. In 2023, one estimate was 90%. The operation of the company is specified in Law 22095.

= Stepan Company

=

The Stepan Company operates a unique facility in Maywood, New Jersey, which is the only commercial plant in the United States authorized by the Drug Enforcement Administration to import and process coca leaves, primarily sourced from Peru via the National Coca Company. The Stepan Company extracts cocaine from the leaves, producing a cocaine-free coca extract that is supplied to The Coca-Cola Company for use as a flavoring ingredient in its beverages. The separated pharmaceutical-grade cocaine is sold to Mallinckrodt, a pharmaceutical company, for use in medical applications such as local anesthesia.

Distribution

= Mallinckrodt

=
, Mallinckrodt is the only company in the U.S. that is allowed to receive cocaine, which is sold as a prescription drug for use in hospitals as a local anesthetic by eye and Otorhinolaryngology, ear, nose and throat (ENT) doctors.

Illicit supply chain

According to the United Nations Office on Drugs and Crime (UNODC), coca is cultivated almost exclusively in the Andes, Andean region, which spans the western edge of northern and central South America, with nearly all coca plantations located in Bolivia, Colombia, and Peru. The destruction of laboratories and production facilities demonstrates that most coca leaf processing into cocaine takes place near the cultivation areas in these countries. This includes both intermediate products, such as coca paste or base, and the final product, cocaine hydrochloride. UNODC further reports that over 99 percent of global cocaine production is concentrated in these three Andean countries.

As a result, the global cocaine trade operates through a distinct illicit supply chain shaped by geography and economics. Production begins in South America, where coca plants are cultivated and processed through several chemical stages: first into a crude extract known as cocaine paste, then into coca base, and finally refined into cocaine hydrochloride. The drug is then trafficked-often across international borders-using a variety of smuggling routes and methods.

Although most cocaine paste and base are typically processed further within South America, there are cases where they are trafficked directly to other continents, such as Europe, for subsequent refinement into cocaine hydrochloride. In some instances, they are chemically embedded into materials like plastics to avoid detection. Regardless of whether cocaine is incorporated into other chemicals—including cocaine hydrochloride—this method of concealment is referred to as "black cocaine".

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,” most commonly with the Levamisole induced necrosis syndrome, toxic stimulant levamisole to increase profits; in some cases, counterfeit cocaine—substances sold as cocaine but containing little or no actual cocaine—is also distributed. Finally, both genuine and adulterated cocaine products—those containing actual cocaine—as well as counterfeit cocaine (substances sold as cocaine but containing little or no actual cocaine) are sold at the retail level to consumers.

Production

Colombia is as of 2019 the world's largest cocaine producer, with production more than tripling since 2013. Three-quarters of the world's annual yield of cocaine has been produced in Colombia, both from cocaine base imported from Peru (primarily the Huallaga Valley) and Bolivia and from locally grown coca. There was a 28% increase in the amount of potentially harvestable coca plants which were grown in Colombia in 1998. This, combined with crop reductions in Bolivia and Peru, made Colombia the nation with the largest area of cocaine production in Colombia, coca under cultivation after the mid-1990s. Coca grown for traditional purposes by indigenous communities, a use which is still present and is permitted by Colombian laws, only makes up a small fragment of total coca production, most of which is used for the illegal drug trade.

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.

=Overview

=
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 Illegal drug trade in Latin America, Latin American drug cartels:

* 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 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 Infrared heater, 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 blocks and wrapped in plastic ready for export

= Illegal coca cultivation

=

Attempts to eradicate coca fields through the use of defoliants have devastated part of the farming economy in some coca-growing regions of Colombia, and strains appear to have been developed that are more resistant or immune to their use. Whether these strains are natural mutations or the product of human tampering is unclear. These strains have also shown to be more potent than those previously grown, increasing profits for the drug cartels responsible for the exporting of cocaine. Although production fell temporarily, coca crops rebounded in numerous smaller fields in Colombia, rather than the larger plantations.

The cultivation of coca has become an attractive economic decision for many growers due to the combination of several factors, including the lack of other employment alternatives, the lower profitability of alternative crops in official crop substitution programs, the eradication-related damages to non-drug farms, the spread of new strains of the coca plant due to persistent worldwide demand.

= Clandestine chemistry

=

Cocaine paste

In traditional cocaine production, solvents are key precursor chemicals used to extract and process cocaine from coca plant leaves. The process typically involves:
* Kerosene: Used to extract the cocaine alkaloid from the alkaline mixture of coca leaves and water.
* Acetone, diethyl ether, ethyl acetate, chloroform: Used in later purification steps to dissolve or precipitate cocaine base or hydrochloride.

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 often confused with cocaine sulfate in North America—is relatively inexpensive and 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 List of sovereign states and dependent territories in South America, South American countries such as Colombia where it is processed into cocaine hydrochloride ("street cocaine") for distribution to the rest of the world. The caustic reactions associated with the local application of coca paste prevents its use by oral, intranasal, mucosal, or Injection (medicine), injection routes. Coca paste can only be smoked when combined with a combustion, combustible material such as tobacco or cannabis.

An interview with a coca farmer published in 2003 described a mode of production by acid-base extraction that has changed little since 1905. Roughly of leaves were harvested per hectare, six times per year. The leaves were dried for half a day, then chopped into small pieces with a string trimmer and sprinkled with a small amount of powdered cement (replacing sodium carbonate from former times). Several hundred pounds of this mixture were soaked in of gasoline for a day, then the gasoline was removed and the leaves were pressed for the remaining liquid, after which they could be discarded. Then battery acid (weak sulfuric acid) was used, one bucket per of leaves, to create a phase (matter), phase separation in which the cocaine free base in the gasoline was acidified and extracted into a few buckets of "murky-looking smelly liquid". Once powdered caustic soda was added to this, the cocaine precipitated and could be removed by filtration through a cloth. The resulting material, when dried, was termed ''cocaine paste, pasta'' and sold by the farmer. The yearly harvest of leaves from a hectare produced of ''pasta'', approximately 40–60% cocaine. Repeated recrystallization from solvents, producing ''pasta lavada'' and eventually crystalline cocaine were performed at specialized laboratories after the sale.

Secondary extraction

Cocaine processing occurs in several EU Member States, with multiple laboratories dismantled annually. European cocaine processing often involves extracting cocaine that has been chemically concealed in materials like plastics, making detection in shipments challenging. Large quantities of cocaine base and paste are trafficked to Europe for conversion into cocaine hydrochloride. Each year, authorities detect some large-scale processing facilities; for example, six cocaine-processing labs were dismantled in Portugal between 2023 and 2024, resulting in the seizure of cocaine paste and cocaine hydrochloride.

Trafficking

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

= Smuggling methods

=

Concealment

Cocaine is frequently smuggling, 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.

Black cocaine (Spanish: coca negra) is a form of cocaine in which the drug is mixed with various substances to disguise its appearance, interfere with color-based drug tests, and evade detection by drug-sniffing dogs; these additives may include pigments like charcoal, chemicals such as thiocyanates and iron or cobalt salts, and activated carbon to mask odors.

In 2024, Polish authorities seized 44 liters of liquid cocaine hidden in cartons of wine, valued at approximately 7.5 million zlotys ($1.85 million).

Another commonality is creating an operational business to disguise the mass shipments. 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.

At Miami International Airport in 1993, authorities discovered that some of the 312 boa constrictors in a shipment from Colombia had been surgically filled with condoms containing a total of 80 pounds (36 kg) of cocaine, resulting in the death of all the snakes.

Mules

''Mochilero (drug courier), Mochileros'' () 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. The work is highly dangerous.

In Mexico, the people who engage in this type of activity are called "Burreros" (Spanish wordplay that refers to the person as a Donkey#Use, 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.

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

General mule (smuggling)#Techniques, 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, luggage, or clothes.
* Body packing: The practice of transporting goods outside or inside of the body is called body packing. 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 Human gastrointestinal tract, gastrointestinal tract or other Body cavity, body cavities as containers. In some cases, this has resulted in cardiac arrest.

Maritime cocaine smuggling

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.

Sophisticated narco-submarine, drug subs are the latest tool drug runners are using to bring cocaine north from Colombia, it was reported on 20 March 2008. Although the vessels were once viewed as a quirky sideshow in the drug war, they are becoming faster, more seaworthy, and capable of carrying bigger loads of drugs than earlier models, according to those charged with catching them.

In 2022, Spanish police seized three unmanned underwater vehicles used to smuggle drugs across the Strait of Gibraltar from Morocco, the first known interception of such devices. The drones, carrying up to 200 kg of narcotics each, were linked to French cartels. The operation led to eight arrests and exposed a gang using advanced drones and modified vehicles for trafficking across Europe (BBC, 2022).

In 2025, international drug cartels began using sophisticated whale-shaped mini submarines to smuggle cocaine into Australia via Cyprus. These vessels are transported on cargo ships, dropped in international waters, then retrieved by smaller boats to deliver drugs ashore, posing a significant challenge to law enforcement detection efforts.

= Bribery

=
Bribery and corruption play a critical role in facilitating the illicit trafficking of cocaine. Drug trafficking organizations often rely on the bribery of government officials, law enforcement agents, customs officers, and border security personnel to evade detection and enable the smooth passage of cocaine shipments. These corrupt practices can involve payments, gifts, or other forms of illicit incentives aimed at securing cooperation or turning a blind eye to illegal activities.

Bribery helps traffickers circumvent checkpoints, avoid seizures, and reduce the risk of arrest or confiscation. It is particularly prevalent in regions with weak governance, limited law enforcement capacity, or endemic corruption, where officials may be more susceptible to financial inducements. This systemic corruption undermines efforts to combat drug trafficking and contributes to the persistence and expansion of cocaine supply chains.

Efforts to address bribery in the cocaine trade include international cooperation, anti-corruption initiatives, and strengthening institutional transparency and accountability. However, the clandestine nature of bribery makes it difficult to quantify its full impact on the illicit cocaine market.

Bribery has enabled cocaine trafficking in Hamburg’s port, with officials and insiders accepting illicit payments to facilitate smuggling. This corruption exposes systemic vulnerabilities despite Germany’s reputation for low corruption.

= Intercontinental distribution

=

Source regions

;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 in the Bahama Islands or off the coast of Puerto Rico, mid-ocean boat-to-boat transfers of , and the commercial shipment of tonnes of cocaine through the port of Miami.

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

;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. , sixty-five percent of cocaine enters the United States through Mexico, where the drug is first transported from South American countries. , 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.

Destination hubs

;Hamburg
Hamburg, Germany’s largest port, has become a central hub for Europe’s cocaine trade, with record seizures—such as the 16-tonne bust in 2021—exposing deep institutional corruption as drug networks infiltrate police, justice, and port infrastructure; a lead prosecutor is currently on trial for allegedly leaking investigation details to traffickers in exchange for bribes, while insiders like dockworkers and security staff have enabled smuggling, highlighting how the staggering profits from cocaine are fueling violence, bribery, and systemic vulnerabilities in a country long considered among the least corrupt in the world.

= Wholesale distribution

=
After large-scale trafficking, cocaine is distributed within countries or regions by mid-level networks, primarily operating across major areas in both the United States and Europe. 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.

Wholesale prices for cocaine increase dramatically as the drug moves from South America to consumer markets, with the cost in 2004 typically 15 times higher in the United States and 32 times higher in Europe than at the source in South America.

= Retail distribution

=

Cocaine is readily available in all major countries' metropolitan areas. According to the ''Summer 1998 Pulse Check'', published by the U.S. Office of National Drug Control Policy, cocaine use had stabilized across the country, with a few increases reported in San Diego, Bridgeport, Connecticut, Bridgeport, Miami, and Boston. In the 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. Nevertheless, the number of cocaine users remain high, with a large concentration among urban youth.

In 2010, the purity- and inflation-adjusted retail price of cocaine was €191 per gram, based on data from 14 countries for which sufficient purity and price data were available, as reported by UNODC, ARQ, and EUROPOL.

In addition to the amounts previously mentioned, cocaine can be sold in "bill sizes": for example, $10 might purchase a "dime bag", a very small amount (0.1–0.15 g) of cocaine. These amounts and prices are very popular among young people because they are inexpensive and easily concealed on one's body. Quality and price can vary dramatically depending on supply and demand, and on geographic region.

In 2008, the European Monitoring Centre for Drugs and Drug Addiction reports that the typical retail price of cocaine varied between €50 and €75 per gram in most List of sovereign states and dependent territories in Europe, European countries, although Cyprus, Romania, Sweden, and Turkey reported much higher values.

Impact of the cocaine trade in Latin America

Drug war policies in Latin America and the Caribbean have led to more violence, higher incarceration rates, health crises, and deeper poverty, while undermining trust in institutions and worsening inequality. There is increasing support for shifting toward drug policies that focus on sustainable development and human rights instead of punitive measures.

Lacing

Street cocaine is often Lacing (drugs), laced or "cut" with cheaper substances to increase bulk, including talc, lactose, sucrose, glucose, mannitol, inositol, caffeine, procaine, phencyclidine, phenytoin, lidocaine, strychnine, levamisole, fentanyl, and amphetamine. Caffeine, often added to street cocaine, increases cocaine’s reinforcing and motivational effects, making the drug more compelling for users.

Cocaine is rarely prescribed for medical use, so nearly all recreational cocaine is sourced illegally. As it moves through a long chain of traffickers—often a dozen or more—each looking to maximize profit, the drug is commonly mixed with various adulterants. This widespread adulteration significantly raises the risk of poisoning or overdose. For users, this means it is extremely difficult to know what substances have been added to the cocaine they purchase. Even when purity tests or reagent kits are used, these methods may not detect all possible contaminants or dangerous additives, making it nearly impossible to guarantee the drug's safety or purity.

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.

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. 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.

= Levamisole

=

Levamisole has increasingly been used as a cutting agent in cocaine sold around the globe with the highest incidence being in the United States. In 2008–2009, levamisole was found in 69% of cocaine samples seized by the Drug Enforcement Administration (DEA). By April 2011, the DEA reported the adulterant was found in 82% of seizures. By October 2017, this figure had risen further, with the DEA reporting that 87% of seized and analyzed cocaine bricks in the United States contained levamisole, making it the most common adulterant in cocaine at that time.https://www.dea.gov/sites/default/files/2018-07/DIR-040-17_2017-NDTA.pdf

In the body, levamisole is converted into aminorex, a toxic substance with amphetamine-like stimulant effects and a long duration of action.

Cocaine acts as a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), while aminorex is a serotonin–norepinephrine–dopamine releasing agent (SNDRA), which is similar in that it increases the levels of these neurotransmitters but does so by promoting their release rather than inhibiting their reuptake.

= Local anesthetics

=
Cocaine is sometimes cut with lidocaine, and procaine.

= Opioids

=

Fentanyl has been increasingly found in cocaine samples. In February 2022, 24 people in Argentina died after using cocaine laced with the fentanyl-analogue carfentanil.

Nitazenes, a family of potent synthetic opioids, have also been detected.

Counterfeit cocaine

The 2014 Amsterdam drug deaths underscore the dangers of misidentified drugs, as two tourists died after using heroin sold as cocaine.

In 2022, Canberra’s government-backed CanTEST drug checking clinic found that 40% of substances brought in as “cocaine” contained no cocaine at all. Instead, these samples were often made up of benign fillers such as Methylsulfonylmethane, dimethyl sulfone, highlighting significant adulteration in the local cocaine market. The actual cocaine samples tested also had low purity, with none exceeding 27%.

Research

Cocaine haptens are chemically modified derivatives of cocaine designed to retain the molecule’s immunogenic determinants while allowing for conjugation to carrier proteins. This enables the immune system to recognize and mount a response against cocaine. By coupling cocaine haptens to carrier proteins (such as keyhole limpet hemocyanin or bovine serum albumin), researchers have developed vaccines that elicit the production of anti-cocaine antibodies. These antibodies can bind cocaine in the bloodstream, preventing it from reaching the brain and producing psychoactive effects.

Coca tea has 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.

Recent research has also investigated the use of prescription psychostimulants as a treatment for cocaine dependence. This approach is consistent with the Self-medication#Self-medication_hypothesis, Self-Medication Hypothesis, which proposes that individuals may use cocaine to compensate for underlying neurochemical imbalances or psychological distress. Some studies suggest that psychostimulant therapy may help reduce cocaine use and cravings by addressing these underlying factors, though the evidence is mixed and further research is warranted.

In Laboratory mouse, mice, nicotine increased the probability of later consumption of cocaine, and the experiments permitted concrete conclusions on the underlying Molecular biology, molecular biological alteration in the brain. The biological changes in mice correspond to the Epidemiology, epidemiological observations in humans that nicotine consumption is coupled to an increased probability of later use of cannabis and cocaine, as well as other drugs.

In rats, alcohol increased the probability of later addiction to cocaine and again relevant alterations in the reward system were identified. These observations thus correspond to the epidemiological findings that the consumption of alcohol in humans is coupled to a later increased risk of a transition from cocaine use to cocaine addiction.

Experimentally, cocaine injections can be delivered to animals such as Drosophila melanogaster, fruit flies to study the mechanisms of cocaine addiction.

TA-CD

TA-CD is a vaccine developed by the Xenova Group and designed to negate the effects of cocaine, making it suitable for use in treatment of addiction. It is created by combining norcocaine with inactivated cholera toxin.

History

Discovery

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

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

In 1609, Military chaplain, Padre Blas Valera wrote:

Isolation and naming

Although the stimulant and hunger-suppressant properties of coca 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. However, by 1855, the German chemist Friedrich Gaedcke successfully isolated the cocaine alkaloid for the first time. Gaedcke named the alkaloid "erythroxyline", and published a description in the journal ''Archiv der Pharmazie.''

In 1856, Friedrich Wöhler asked Dr. Carl Scherzer, a scientist aboard the ''SMS Novara (1850), Novara'' (an Austrian frigate sent by Emperor Franz Joseph of Austria, Franz Joseph to circle the globe), to bring him a large amount of coca leaves from South America. In 1859, the ship finished its travels and Wöhler received a trunk full of coca. Wöhler passed on the leaves to Albert Niemann (chemist), Albert Niemann, a Doctor of Philosophy, PhD student at the University of Göttingen in Germany, who then developed an improved purification process.

Niemann described every step he took to isolate cocaine in his dissertation titled ''On a New Organic Base in the Coca Leaves, Über eine neue organische Base in den Cocablättern'' (''On a New Organic Base in the Coca Leaves''), which was published in 1860 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 languages, Quechua "kúka") + affix, suffix "ine".

The first synthesis and elucidation of the structure of the cocaine molecule was by Richard Willstätter in 1898. It was the first biomimetics, biomimetic synthesis of an organic structure recorded in academic chemical literature. The synthesis started from tropinone, a related natural product and took five steps.

Because of the former use of cocaine as a local anesthetic, a suffix "-caine" was later extracted and used to form names of synthetic local anesthetics.

Medicalization

With the discovery of this new alkaloid, Western medicine was quick to exploit the possible uses of this plant.

In 1879, Vassili von Anrep, of the University of Würzburg, devised an experiment to demonstrate the analgesic properties of the newly discovered alkaloid. He prepared two separate jars, one containing a cocaine-salt solution, with the other containing merely saltwater. He then submerged a frog's legs into the two jars, one leg in the treatment and one in the control solution, and proceeded to stimulate the legs in several different ways. The leg that had been immersed in the cocaine solution reacted very differently from the leg that had been immersed in saltwater.

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

Although cocaine has traditionally been used for anesthesia in these procedures, substantial evidence shows it can cause severe and unpredictable toxic reactions, even with experienced practitioners. As a result, cocaine is no longer recommended for Endoscopic endonasal surgery, endonasal surgery. Safer and well-tolerated alternatives—such as lidocaine or tetracaine combined with agents like epinephrine, naphazoline, or oxymetazoline—are now preferred for topical and infiltration anesthesia.

Popularization

In 1859, an Italian physician, doctor, Paolo Mantegazza, returned from Peru, where he had witnessed first-hand the use of coca by the local indigenous peoples. He proceeded to experiment on himself and upon his return to Milan, he wrote a paper in which he described the effects. In this paper, he declared coca and cocaine (at the time they were assumed to be the same) as being useful medicinally, in the treatment of "a furred tongue in the morning, flatulence, and whitening of the teeth."

A chemist named Angelo Mariani (chemist), Angelo Mariani who read Mantegazza's paper became immediately intrigued with coca and its economic potential. In 1863, Mariani started marketing a wine called Vin Mariani, which had been treated with coca leaves, to become coca wine. The ethanol in wine acted as a solvent and extracted the cocaine from the coca leaves, altering the drink's effect. It contained 6 mg cocaine per ounce of wine, but Vin Mariani which was to be exported contained 7.2 mg per ounce, to compete with the higher cocaine content of similar drinks in the United States.

In 1879 cocaine began to be used to treat morphine addiction. Cocaine was introduced into clinical use as a local anesthetic in Germany in 1884, about the same time as Sigmund Freud published his work ''Über Coca'', in which he wrote that cocaine causes:

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. 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."

A "pinch of coca leaves" was included in John Pemberton, John Styth Pemberton's original 1886 recipe for Coca-Cola, though the company began using decocainized leaves in 1906 when the Pure Food and Drug Act was passed. Today, Coca-Cola continues to use decocainized coca leaf extract for flavoring, which is processed by the Stepan Company in New Jersey; the leftover cocaine byproduct is sold for medical use.

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.

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.

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". In the 1932 comedy musical film ''The Big Broadcast'', Cab Calloway performs the song with his orchestra and mimes snorting cocaine in between verses.

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.

Cocaine (drink), Cocaine Energy Supplement, also known as "Cocaine Energy Drink", is a highly caffeine, caffeinated energy drink distributed by Hype Beverages. Although the beverage contained no actual cocaine, the product launch attracted criticism from lawmakers and anti-drug organizations, who felt that Cocaine glamorized drug usage to children.

Coca Colla is an energy drink produced in Bolivia with the use of coca extract as its base. It was launched on the Bolivian market in La Paz, Santa Cruz de la Sierra, Santa Cruz and Cochabamba in April 2010.

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". In addition the pace of modern society − such as in finance − gives many the incentive to make use of the drug.

Modern usage

In many countries, cocaine is a popular recreational drug. Cocaine use is prevalent across all socioeconomic strata, including age, demographics, economic, social, political, religious, and livelihood.

In the United States, the development of crack cocaine, "crack" cocaine introduced the substance to a generally poorer inner-city market. The use of the powder form has stayed relatively constant, experiencing a new height of use across the 1980s and 1990s in the U.S. However, from 2006 to 2010 cocaine use in the US declined by roughly half before again rising once again from 2017 onwards. 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.

The estimated U.S. cocaine market exceeded US$70 billion in street value for the year 2005, exceeding revenues by corporations such as Starbucks. Cocaine's status as a club drug shows its immense popularity among the "party crowd".

In 1995 the World Health Organization (WHO) and the United Nations Interregional Crime and Justice Research Institute (UNICRI) announced in a press release the publication of the results of the largest global study on cocaine use ever undertaken. An American representative in the World Health Assembly banned the publication of the study, because it seemed to make a case for the positive uses of cocaine. An excerpt of the report strongly conflicted with accepted paradigms, for example, "that occasional cocaine use does not typically lead to severe or even minor physical or social problems." In the sixth meeting of the B committee, the US representative threatened that "If World Health Organization activities relating to drugs failed to reinforce proven drug control approaches, funds for the relevant programs should be curtailed". This led to the decision to discontinue publication. A part of the study was recuperated and published in 2010, including profiles of cocaine use in 20 countries, but are unavailable .

In October 2010 it was reported that the use of cocaine in Australia has doubled since monitoring began in 2003.

See also

* Cocaine reverse ester
* Cocaine and amphetamine regulated transcript
* MDMA – also acts, to a lesser extent, as an SNDRI like cocaine

References

Further reading

*
*

External links

* Virginia Gewin:
Smoking stokes cocaine cravings: Molecular mechanism found for controversial 'gateway drug' hypothesis
Nature News, November 2, 2011.

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