Coca
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'''Coca''' ('''''Erythroxylum coca''''' Lam.) is a flowering plant in the family Erythroxylaceae, native to the western Andes of South America. The primary pharmacologically active constituent is [[substance:cocaine]], a [[substance_class:chemical/tropane]] alkaloid present at 0.2–1.0% of leaf dry weight that acts as a triple [[glossary:monoamine]] [[glossary:reuptake-inhibitor]]. Coca preparations range from traditional leaf chewing and tea infusion (duration 2–4 hours) to refined cocaine hydrochloride administered intranasally, [[glossary:intravenous|intravenously]], or by inhalation (duration 10–90 minutes depending on route).
Coca has been cultivated and consumed by Andean indigenous populations for thousands of years, with archaeological evidence suggesting use dating to at least 8,000 years before present{{cite|doi=10.3390/molecules24203788|anchor=d93ad961}}. Albert Niemann first isolated cocaine from coca leaves in 1860, catalyzing over a century of pharmaceutical, surgical, and regulatory developments{{cite|doi=10.3390/molecules22081369|anchor=23805b1d}}. Coca leaf and cocaine are listed on [[glossary:schedule-i]] of the 1961 UN Single Convention on Narcotic Drugs; the WHO Expert Committee on Drug Dependence completed a critical review in October 2025, recommending maintenance of Schedule I classification while acknowledging the low public health risk of traditional coca leaf consumption{{cite|url=https://www.who.int/news/item/10-12-2025-who-expert-committee-concludes-critical-review-of-coca-leaf--recommends-maintaining-current-controls|anchor=7fa90c66}}.
Cocaine blocks the [[glossary:dopamine]], [[glossary:norepinephrine]], and [[glossary:serotonin-transporter|serotonin transporters]], with [[glossary:dopamine-transporter]] [[glossary:inhibition]] in mesolimbic [[glossary:circuit|circuits]] mediating the primary reinforcing and euphoriant effects{{cite|doi=10.1016/j.neuropharm.2014.06.012|anchor=5263118e}}. Voltage-gated sodium [[glossary:channel]] [[glossary:blockade]] provides the basis of cocaine's local anesthetic utility and contributes to its arrhythmogenic [[glossary:toxicity]]{{cite|doi=10.2165/00129784-200909030-00005|anchor=f9a22889}}. [[glossary:plasma]] [[glossary:half-life]] is dose-dependent, ranging from approximately 38 to 87 minutes, and oral [[glossary:bioavailability]] is 32–45%{{cite|pubmed=7242115|anchor=f6984ef0}}{{cite|doi=10.1093/jat/bky007|anchor=71c86142}} — explaining why coca leaf preparations produce qualitatively milder effects than refined cocaine administered by faster routes.
Acute effects span [[effect:stimulation]], [[effect:euphoria]], [[effect:appetite-suppression]], increased confidence, and local [[glossary:anesthesia]]; the experiential character varies dramatically by preparation, from mild sustained alertness with coca leaf chewing to intense brief euphoria with smoked cocaine. Effects and duration vary substantially by preparation method, alkaloid content of source material, and individual metabolic factors.
Cocaine carries significant cardiovascular toxicity risk across all preparations, including [[glossary:myocardial-infarction]], [[glossary:arrhythmia|arrhythmias]], and sudden cardiac death{{cite|doi=10.1016/j.cjca.2022.05.003|anchor=0d1ac711}}. [[glossary:psychological-dependence]] develops rapidly, driven by [[glossary:mesolimbic-pathway|mesolimbic dopamine]] [[glossary:reinforcement]]; physical [[glossary:withdrawal]] produces [[effect:dysphoria]], [[glossary:hypersomnia]], and [[effect:anhedonia]] over a timeline of days to weeks{{cite|doi=10.1016/j.neubiorev.2025.106278|anchor=a1ba701c}}. [[glossary:tolerance]] to euphoriant effects develops with repeated dosing, while [[glossary:sensitization]] to psychomotor and [[glossary:psychosis]]-inducing effects occurs paradoxically with [[glossary:chronic-use]]. The illicit cocaine supply is heavily adulterated — levamisole contaminates an estimated 69–80% of cocaine in the United States{{cite|doi=10.1097/MOH.0b013e32834da9ef|anchor=c681a556}}, introducing independent hematological toxicity. No approved pharmacotherapy for cocaine use [[glossary:disorder]] exists as of 2026{{cite|doi=10.1177/02698811251399593|anchor=d7a002fc}}. Preparation-specific pharmacokinetic data for coca leaf preparations remain limited, with most controlled human studies having been conducted using refined cocaine hydrochloride.
'''Coca''' (''Erythroxylum coca'' Lam., Erythroxylaceae) is a flowering shrub native to the western Andes whose leaves contain the [[substance_class:chemical/tropane]] alkaloid [[substance:cocaine]]. Cocaine acts as a triple [[glossary:monoamine]] [[glossary:reuptake-inhibitor]], blocking the [[glossary:dopamine]], [[glossary:norepinephrine]], and [[glossary:serotonin-transporter|serotonin transporters]]{{cite|doi=10.1016/j.neuropharm.2014.06.012|anchor=8322a835}}. [[glossary:dopamine-transporter|Dopamine transporter]] [[glossary:blockade]] in mesolimbic [[glossary:circuit|circuits]] drives the plant's reinforcing and euphoriant properties, while voltage-gated sodium [[glossary:channel]] blockade produces local anesthetic effects and contributes to cardiac [[glossary:toxicity]]{{cite|doi=10.2165/00129784-200909030-00005|anchor=ad2ef96d}}.
Archaeological evidence places Andean coca use at least 8,000 years before present{{cite|doi=10.3390/molecules24203788|anchor=8f00d298}}. Albert Niemann's 1860 isolation of cocaine from the leaf catalyzed rapid pharmaceutical adoption — most notably Carl Koller's 1884 demonstration of topical cocaine [[glossary:anesthesia]] — followed by international regulatory restriction{{cite|doi=10.3390/molecules22081369|anchor=accc7d95}}. In 2025, the WHO Expert Committee recommended maintaining [[glossary:schedule-i]] classification under the 1961 UN Single Convention while acknowledging the low public health risk of traditional leaf consumption{{cite|url=https://www.who.int/news/item/10-12-2025-who-expert-committee-concludes-critical-review-of-coca-leaf--recommends-maintaining-current-controls|anchor=6aa58156}}.
[[index:effects|Subjective effects]] include [[effect:stimulation]], [[effect:euphoria]], [[effect:appetite-suppression]], increased confidence, and local anesthesia. The experiential character varies dramatically by preparation — leaf chewing produces mild sustained alertness comparable to strong tea, while smoked cocaine delivers intense brief euphoria followed by [[glossary:rapid-onset|rapid-onset]] [[effect:craving]] and compulsive [[glossary:redose|redosing]]. [[effect:anxiety]], [[effect:paranoia]], and cardiovascular stress are common unsought effects, particularly at higher doses.
Cocaine carries significant [[glossary:abuse-liability]] and cardiovascular toxicity including [[glossary:myocardial-infarction]], [[glossary:arrhythmia|arrhythmias]], and sudden cardiac death{{cite|doi=10.1016/j.cjca.2022.05.003|anchor=77a8935b}}. Rapid [[glossary:mesolimbic-pathway|mesolimbic dopamine]] [[glossary:reinforcement]] drives [[glossary:psychological-dependence]], while the illicit supply is heavily contaminated — levamisole adulterates an estimated 69–80% of US cocaine, introducing independent hematological toxicity{{cite|doi=10.1097/MOH.0b013e32834da9ef|anchor=18686b80}}. No approved pharmacotherapy for cocaine use [[glossary:disorder]] exists as of 2026{{cite|doi=10.1177/02698811251399593|anchor=62450b9a}}, and controlled clinical data specific to whole-leaf preparations remain sparse.
'''Coca''' (''Erythroxylum coca'' Lam., Erythroxylaceae) is a flowering shrub native to the Andes whose leaves contain the [[substance_class:psychoactive/stimulant]] alkaloid [[substance:cocaine]]. Cocaine determines the pharmacological character of every coca preparation. It blocks the brain's [[glossary:dopamine]] recycling system, flooding [[glossary:mesolimbic-pathway|reward circuits]] and producing the plant's stimulant and euphoric effects{{cite|doi=10.1016/j.neuropharm.2014.06.012|anchor=18c92339}}.
Archaeological evidence places Andean coca use at least 8,000 years before present{{cite|doi=10.3390/molecules24203788|anchor=f96da143}}. Cocaine was first isolated from the leaf in 1860, setting off a wave of pharmaceutical applications and eventually tight international restriction. Today both coca leaf and cocaine are scheduled under the 1961 UN Single Convention, though Bolivia and Peru maintain legal frameworks for traditional leaf use{{cite|url=https://www.who.int/news/item/10-12-2025-who-expert-committee-concludes-critical-review-of-coca-leaf--recommends-maintaining-current-controls|anchor=99348d74}}.
[[index:effects|Subjective effects]] include [[effect:stimulation]], [[effect:euphoria]], [[effect:appetite-suppression]], increased confidence, and local numbness in the mouth and throat. The experience varies enormously by preparation: leaf chewing produces mild, sustained alertness comparable to strong tea, while smoked cocaine delivers a brief, overwhelming rush followed by rapid [[effect:craving]]. [[effect:anxiety]], [[effect:paranoia]], racing heart, and a dysphoric crash are characteristic unsought effects, particularly with refined preparations.
Cocaine carries significant [[glossary:abuse-liability]] and cardiovascular [[glossary:toxicity]] — including risk of [[glossary:myocardial-infarction|heart attack]], [[glossary:arrhythmia]], and sudden cardiac death{{cite|doi=10.1016/j.cjca.2022.05.003|anchor=ab113d47}}. The illicit supply is heavily contaminated: levamisole adulterates an estimated 69–80% of US cocaine, causing blood [[glossary:disorder|disorders]] independent of cocaine's own effects{{cite|doi=10.1097/MOH.0b013e32834da9ef|anchor=7c0b1201}}, and [[substance:fentanyl]] [[glossary:contamination]] is increasingly common. No approved treatment for cocaine use disorder exists as of 2026{{cite|doi=10.1177/02698811251399593|anchor=97011d7f}}, and controlled data on whole-leaf preparations remain sparse.
===Traditional and historical use===
Indigenous peoples of the Andes have cultivated and consumed coca for at least 8,000 years{{cite|doi=10.3390/molecules24203788|anchor=e0de55ee}}. Traditional preparation involves placing fresh or dried leaves in the cheek alongside an alkaline additive — calcium hydroxide, plant ash, or sodium bicarbonate — which raises buccal pH and promotes [[substance:cocaine]] [[glossary:absorption]]{{cite|doi=10.1186/s40794-019-0095-7|anchor=125c4324}}. Documented uses include stamina during physical labor, hunger and [[glossary:fatigue]] suppression, altitude sickness relief, mild [[effect:pain-suppression|analgesia]], and ceremonial purposes{{cite|doi=10.1186/s40794-019-0095-7|anchor=f3308ab0}}{{cite|doi=10.3390/molecules24203788|anchor=15021f1e}}.
===Western discovery and pharmaceutical development===
Albert Niemann first isolated cocaine from coca leaves in 1860 at the University of Göttingen, noting its anesthetic effect on his own tongue{{cite|doi=10.3390/molecules22081369|anchor=64cc7304}}. Carl Koller demonstrated cocaine as a topical anesthetic for eye surgery in 1884, transforming the field{{cite|doi=10.3390/molecules22081369|anchor=3963ffc7}}. Coca-Cola launched in 1886 using coca extract; the product was decocainized by 1903{{cite|doi=10.1186/s40794-019-0095-7|anchor=5e16113c}}.
===Modern era===
The Harrison Narcotics Tax Act (1914) restricted non-medical cocaine in the United States. The 1961 UN Single Convention placed both coca leaf and cocaine on [[glossary:schedule-i]] — an unusual dual scheduling that explicitly controls the plant alongside its isolated alkaloid. In October 2025, the WHO Expert Committee completed a comprehensive review and recommended maintaining Schedule I classification, while acknowledging the low public health risk of traditional consumption and the cultural significance of coca to indigenous peoples{{cite|url=https://www.who.int/news/item/10-12-2025-who-expert-committee-concludes-critical-review-of-coca-leaf--recommends-maintaining-current-controls|anchor=fb2628e4}}.
===Discovery and early record===
''Erythroxylum coca'' was first formally described by Jean-Baptiste Lamarck in ''Encyclopédie Méthodique, Botanique'' 2: 393 (1786){{cite|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:330132-2|anchor=686d0d1e}}. The genus name derives from Greek ''erythros'' (red) and ''xylon'' (wood), referring to the reddish heartwood characteristic of the genus. Archaeological evidence suggests coca use in the Andes dating to at least 8,000 years before present, based on finds at the Huaca Prieta site in Peru{{flag|citation-needed}}. The two primary cultivated species, ''E. coca'' and ''E. novogranatense'', were utilized specifically for their [[substance_class:chemical/tropane]] alkaloid content before formal domestication of either species{{cite|doi=10.3390/molecules24203788|anchor=98176da4}}.
===Traditional use===
Indigenous peoples of the Andes have cultivated and consumed coca for millennia. Traditional preparation involves chewing fresh leaves (20–60 g per session) with an alkaline additive — calcium hydroxide (lime), sodium bicarbonate, or ''llipta'' (plant ash) — which shifts buccal pH to facilitate [[substance:cocaine]] [[glossary:absorption]]{{cite|doi=10.1186/s40794-019-0095-7|anchor=6932ba46}}. Documented traditional applications include stamina enhancement during physical labor, hunger and [[glossary:fatigue]] suppression, altitude sickness mitigation, mild [[effect:pain-suppression|analgesia]], and ritual and ceremonial use{{cite|doi=10.1186/s40794-019-0095-7|anchor=cfeb8443}}{{cite|doi=10.3390/molecules24203788|anchor=f62185c9}}. These accounts derive from ethnographic and anthropological documentation rather than controlled [[glossary:clinical-study|clinical studies]].
===Western encounter and pharmaceutical development===
Spanish chroniclers documented coca use in the 16th century, though knowledge of its [[substance_class:psychoactive/stimulant]] properties spread slowly in Europe. Albert Niemann first isolated pure cocaine from coca leaves in 1860 as part of his doctoral work at the University of Göttingen, noting the anesthetic effect on his tongue in his dissertation{{cite|doi=10.3390/molecules22081369|anchor=234737e5}}. Richard Willstätter established the correct molecular structure of cocaine in 1898{{flag|citation-needed}}.
The isolation catalyzed rapid pharmaceutical adoption. In 1884, Carl Koller demonstrated cocaine as a topical ophthalmic anesthetic, revolutionizing eye surgery{{cite|doi=10.3390/molecules22081369|anchor=4cb6f2bc}}. The same year, Sigmund Freud published ''Über Coca'', promoting cocaine for fatigue, [[effect:depression]], and [[substance:morphine]] [[glossary:addiction]] — a position he later revised. William Halsted pioneered nerve block [[glossary:anesthesia]] using cocaine, subsequently developing [[glossary:dependence]] himself. Commercial applications followed: Coca-Cola was introduced in 1886 using coca extract, though the product was decocainized by 1903{{cite|doi=10.1186/s40794-019-0095-7|anchor=ef4d2cd2}}.
===Regulatory history===
The Harrison Narcotics Tax Act (1914) restricted non-medical cocaine distribution in the United States. [[glossary:international-control|International controls]] followed: the 1961 UN Single Convention on Narcotic Drugs placed both coca leaf and cocaine on [[glossary:schedule-i]], and the 1988 UN Convention Against Illicit Traffic in Narcotic Drugs reinforced controls on cocaine precursors. Bolivia temporarily withdrew from the 1961 Convention in 2012 and reacceded in 2013 with an explicit reservation permitting traditional coca leaf chewing{{flag|citation-needed}}. In October 2025, the WHO Expert Committee on Drug Dependence completed a comprehensive critical review of coca leaf and recommended maintaining Schedule I classification, while acknowledging the low public health risk of traditional consumption and the cultural significance of coca to indigenous peoples{{cite|url=https://www.who.int/news/item/10-12-2025-who-expert-committee-concludes-critical-review-of-coca-leaf--recommends-maintaining-current-controls|anchor=be464595}}.
===Traditional and historical use===
Indigenous peoples of the Andes have cultivated and consumed coca for millennia, with archaeological evidence placing use at least 8,000 years before present{{cite|doi=10.3390/molecules24203788|anchor=62003e2a}}. The two primary cultivated species — ''E. coca'' and ''E. novogranatense'' — were selected for their [[substance_class:chemical/tropane]] alkaloid content before formal domestication of either species{{cite|doi=10.3390/molecules24203788|anchor=8d64440b}}. Traditional preparation involves chewing fresh leaves with an alkaline additive — calcium hydroxide, sodium bicarbonate, or ''llipta'' (plant ash) — to raise buccal pH and facilitate [[substance:cocaine]] [[glossary:absorption]]{{cite|doi=10.1186/s40794-019-0095-7|anchor=65a6cc17}}.
Documented traditional applications include stamina enhancement during physical labor, hunger and [[glossary:fatigue]] suppression, altitude sickness mitigation, mild [[effect:pain-suppression|analgesia]], and ceremonial use{{cite|doi=10.1186/s40794-019-0095-7|anchor=3006d659}}{{cite|doi=10.3390/molecules24203788|anchor=a4769560}}. These accounts derive from ethnographic and anthropological documentation rather than controlled [[glossary:clinical-study|clinical studies]].
===Western discovery and pharmaceutical development===
Spanish chroniclers documented coca use in the 16th century, though knowledge of its [[substance_class:psychoactive/stimulant]] properties spread slowly in Europe. Albert Niemann first isolated cocaine from coca leaves in 1860 at the University of Göttingen, noting the anesthetic effect on his tongue in his dissertation{{cite|doi=10.3390/molecules22081369|anchor=b5c8efce}}. Richard Willstätter established cocaine's correct molecular structure in 1898{{flag|citation-needed}}.
The isolation catalyzed rapid pharmaceutical adoption. Carl Koller demonstrated cocaine as a topical ophthalmic anesthetic in 1884, revolutionizing eye surgery{{cite|doi=10.3390/molecules22081369|anchor=53dd3793}}. William Halsted pioneered nerve block [[glossary:anesthesia]] using the compound but developed [[glossary:dependence]] in the process. Commercial applications followed: Coca-Cola launched in 1886 using coca extract, though the product was decocainized by 1903{{cite|doi=10.1186/s40794-019-0095-7|anchor=d76ef1cb}}.
===Modern era===
The Harrison Narcotics Tax Act (1914) restricted non-medical cocaine distribution in the United States. The 1961 UN Single Convention on Narcotic Drugs placed both coca leaf and cocaine on [[glossary:schedule-i]], and the 1988 Convention reinforced controls on cocaine precursors. Bolivia temporarily withdrew from the 1961 Convention in 2012 and reacceded in 2013 with an explicit reservation permitting traditional coca leaf chewing{{flag|citation-needed}}.
In October 2025, the WHO Expert Committee on Drug Dependence completed a comprehensive critical review of coca leaf and recommended maintaining Schedule I classification, while acknowledging the low public health risk of traditional consumption and the cultural significance of coca to indigenous peoples{{cite|url=https://www.who.int/news/item/10-12-2025-who-expert-committee-concludes-critical-review-of-coca-leaf--recommends-maintaining-current-controls|anchor=ebf80a05}}.
''Erythroxylum coca'' Lam. belongs to the family Erythroxylaceae, a small family of tropical and subtropical shrubs and trees. The genus name derives from Greek ''erythros'' (red) and ''xylon'' (wood), referring to the reddish heartwood characteristic of the group. Two primary cultivated species are recognized: ''E. coca'' (Huánuco coca) and ''E. novogranatense'' (Colombian coca), each with recognized varieties that differ in alkaloid content and geographic distribution.
Coca is native to the eastern slopes of the Andes in Peru and Bolivia, thriving in warm, humid montane forest between roughly 500 and 2,000 meters [[glossary:elevation]]. Bolivia, Peru, and Colombia account for virtually all current cultivation. The plant is not known to persist in the wild independent of human cultivation in any significant population.
The shrub grows 1–3 meters tall with slender, oval leaves 4–8 cm long. Each leaf bears two faint longitudinal lines parallel to the midrib — a diagnostic feature distinguishing ''Erythroxylum'' from superficially similar shrubs. Small yellowish-white flowers produce red drupes approximately 1 cm in length.
Leaves are harvested by hand two to four times per year, sun-dried, and either consumed directly (chewing, tea infusion) or processed into refined alkaloid preparations. Drying method influences alkaloid retention: traditional sun-drying preserves the full alkaloid profile, while industrial extraction targets [[substance:cocaine]] specifically. [[glossary:potency]] varies across cultivars, harvest batches, altitude, and seasonal conditions.
| Family | Erythroxylaceae |
| Order | Malpighiales |
| Genus | ''Erythroxylum'' P. Browne |
| Species | ''Erythroxylum coca'' Lam. |
| Native range | Western South America (Bolivia, Brazil [North], Colombia, Ecuador, Peru) |
| Cultivation status | Exclusively cultivated |
| POWO accepted name | ''Erythroxylum coca'' Lam.{{cite|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:330132-2|anchor=edf15ed2}} |
'''Coca''' belongs to the genus ''Erythroxylum'' and the family Erythroxylaceae — a small family of tropical and subtropical shrubs. Two primary cultivated species are recognized: ''E. coca'' (Huánuco coca) and ''E. novogranatense'' (Colombian coca). Each has varieties that differ in alkaloid content and geographic distribution.
Coca is native to the eastern Andean slopes of Peru and Bolivia, thriving in warm, humid montane forest between roughly 500 and 2,000 meters [[glossary:elevation]]. Bolivia, Peru, and Colombia account for virtually all current cultivation. The plant is not known to persist in the wild independent of human cultivation.
The shrub grows 1–3 meters tall with slender, oval leaves 4–8 cm long. Each leaf carries two faint lines running parallel to the central vein — a diagnostic feature distinguishing ''Erythroxylum'' from similar-looking shrubs. Small yellowish-white flowers produce red drupes approximately 1 cm in length.
[[substance:cocaine]] is the dominant active alkaloid in coca leaf, present at 0.2–1.0% of dry weight. It blocks the brain's [[glossary:dopamine]], [[glossary:norepinephrine]], and [[glossary:serotonin]] recycling systems simultaneously, with an additional local anesthetic effect produced by sodium [[glossary:channel]] [[glossary:blockade]]{{cite|doi=10.1016/j.neuropharm.2014.06.012|anchor=9b054371}}{{cite|doi=10.2165/00129784-200909030-00005|anchor=77137c95}}. The pharmacological character of coca preparations is determined almost entirely by cocaine itself.
Several minor alkaloids are present but poorly understood. Cinnamoylcocaine and its [[glossary:isomer|isomers]] are structurally related to cocaine but pharmacologically weaker. Truxillines are dimeric cocaine [[glossary:derivative|derivatives]] present in trace amounts. Hygrine, a separate alkaloid class, lacks meaningful [[glossary:central-nervous-system]] activity. Traditional users sometimes attribute a qualitative difference between whole-leaf coca and purified cocaine to this full alkaloid matrix — but no [[glossary:controlled-study]] has demonstrated that effect.
''E. novogranatense'' tends toward lower cocaine content with a proportionally higher fraction of minor alkaloids than ''E. coca''. Harvest season, soil conditions, altitude, and drying method all influence the final alkaloid profile of available leaf material.
[[substance:cocaine]] is the dominant pharmacologically active alkaloid in coca, present at 0.2–1.0% of leaf dry weight. It acts as a non-selective [[glossary:monoamine]] [[glossary:reuptake-inhibitor]] — blocking the [[glossary:dopamine]], [[glossary:norepinephrine]], and [[glossary:serotonin-transporter|serotonin transporters]] — with additional voltage-gated sodium [[glossary:channel]] [[glossary:blockade]] that produces local anesthetic effects{{cite|doi=10.1016/j.neuropharm.2014.06.012|anchor=e0943be0}}{{cite|doi=10.2165/00129784-200909030-00005|anchor=e52ea175}}. Cocaine content varies across cultivars, growing conditions, altitude, and harvest timing, with ''E. coca'' var. ''coca'' typically yielding the highest concentrations.
Unlike [[substance:cannabis]] or [[substance:kratom]], coca has no well-characterized entourage effect in which minor alkaloids meaningfully modulate the dominant alkaloid's activity. Traditional users sometimes attribute a qualitative difference between whole-leaf coca and purified cocaine to the full alkaloid matrix, but this has not been demonstrated in any [[glossary:controlled-study]]. The pharmacological character of coca preparations is shaped almost entirely by cocaine itself.
Several minor [[substance_class:chemical/tropane]] and non-tropane alkaloids are present in the leaf. Cinnamoylcocaine and its [[glossary:isomer|isomers]] are structurally related to cocaine but pharmacologically weaker. Truxillines (alpha- and beta-truxilline) are dimeric cocaine [[glossary:derivative|derivatives]] present in trace amounts. Hygrine, a non-tropane [[substance_class:chemical/pyrrolidine]] alkaloid, is present at variable concentrations and lacks significant [[glossary:central-nervous-system]] activity. The relative contribution of these minor alkaloids to the overall pharmacological profile of whole-leaf preparations remains unknown.
Alkaloid concentrations vary across the two cultivated species and their varieties. ''E. novogranatense'' tends toward lower cocaine content with a proportionally higher fraction of minor alkaloids compared to ''E. coca''. Harvest season, soil conditions, and drying method all influence the final alkaloid profile of commercially available leaf material.
===Cocaine — dominant tropane alkaloid===
[[substance:cocaine]] (methyl (1R,2R,3S,5S)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate; C₁₇H₂₁NO₄; MW 303.35 g/mol) is the principal pharmacologically active alkaloid in coca leaves. Published concentration data by cultivar (dry weight basis){{cite|doi=10.1186/s40794-019-0095-7|anchor=29948562}}:
* ''E. coca'' var. ''coca'': average 0.63% (range 0.23–0.96%)
* ''E. coca'' var. ''ipadu'': 0.11–0.41% (lowest cocaine content of cultivated taxa)
* ''E. novogranatense'' var. ''novogranatense'': average 0.77%
* Total alkaloid content across taxa: 0.7–1.5% dry weight
{{flag|safety-citation-needed}} These concentration values derive from secondary review literature; no primary HPLC or GC-MS quantification study was retrieved. A primary analytical chemistry source should be confirmed before these figures are treated as definitive.
Chemotype variation is significant. Geographic origin, altitude, and soil conditions modulate alkaloid [[glossary:expression]] within varieties{{cite|pubmed=15650009|anchor=d6fa2345}}. ''E. coca'' var. ''ipadu'' shows significantly lower genetic diversity than other cultivated taxa, consistent with a genetic bottleneck during Amazonian dispersal.
===Biosynthesis===
Cocaine biosynthesis occurs in the aerial portions of the plant — specifically in the palisade parenchyma and spongy mesophyll of young developing leaves{{cite|doi=10.1104/pp.114.248187|anchor=f2342929}}. This contrasts with [[substance_class:chemical/tropane]] alkaloid biosynthesis in Solanaceae, which occurs in roots. The final biosynthetic step is catalyzed by a BAHD acyltransferase (cocaine synthase), which esterifies methylecgonine with benzoyl-CoA to yield cocaine{{cite|doi=10.1104/pp.114.248187|anchor=0f18583a}}.
===Minor alkaloids===
Comprehensive phytochemical review documents 383 compounds across 53 ''Erythroxylum'' species{{cite|doi=10.1007/s13659-022-00338-z|anchor=91ea7709}}. Minor alkaloids present in coca leaves include:
* ''trans''-Cinnamoylcocaine — second most abundant alkaloid in some accessions
* Truxillines (α-, β-, γ-truxilline)
* Tropacocaine (ecgonine benzoyl ester)
* Hygrine and cuscohygrine ([[substance_class:chemical/pyrrolidine]] alkaloids)
* Ecgonidine
The relative concentrations of these minor alkaloids vary across cultivars and have not been systematically characterized by modern [[glossary:analytical-method|analytical methods]] in most taxa.
===Key metabolites===
Ecgonine (C₉H₁₅NO₃; MW 185.22 g/mol) is the core tropane skeleton present as free ecgonine in leaves and as ecgonine methyl ester after [[glossary:hydrolysis]]. Benzoylecgonine (C₁₆H₁₉NO₄; MW 289.33 g/mol) is the primary inactive [[glossary:metabolite|urinary metabolite]] of cocaine and the principal analyte in standard drug testing. Norcocaine (C₁₆H₁₉NO₄; MW 289.33 g/mol) is an active N-demethylated metabolite formed via [[glossary:cyp3a4]] in human liver; norcocaine is more toxic than the [[glossary:parent-compound]]{{cite|pubmed=8488174|anchor=0e80f135}}.
===Preparation-dependent alterations===
Alkaline additives (lime, bicarbonate, ''llipta'') used during traditional chewing shift buccal pH from ~5.5 to ~8, increasing cocaine extraction from leaf material approximately 4-fold and converting cocaine to its free-base form for enhanced mucosal [[glossary:absorption]]{{cite|doi=10.1186/s40794-019-0095-7|anchor=0664dac9}}. Pyrolysis during smoking converts cocaine to anhydroecgonine methyl ester (AEME), a specific [[glossary:biomarker]] of the smoked route{{cite|pubmed=9323527|anchor=46cb0174}}. Aqueous extraction (coca tea) leaches cocaine and other water-soluble alkaloids into the infusion; typical cocaine content is approximately 2–5 mg per cup from 1–2 g dried leaves{{flag|safety-citation-needed}}.
===Where it acts===
[[substance:cocaine]]'s psychoactive effects arise from blocking [[glossary:dopamine]] recycling in the brain's mesolimbic [[glossary:mesolimbic-pathway]] — the projection from the [[glossary:ventral-tegmental-area]] to the [[glossary:nucleus-accumbens]]{{cite|doi=10.1016/j.neuropharm.2014.06.012|anchor=995a5054}}. This floods synapses with dopamine, producing [[effect:euphoria]] and reinforcing the behavior. Cocaine also blocks [[glossary:norepinephrine]] recycling, driving cardiovascular [[glossary:arousal]] and heightened alertness; sodium [[glossary:channel]] [[glossary:blockade]] produces the local anesthetic effect and creates [[glossary:arrhythmia]] risk{{cite|doi=10.2165/00129784-200909030-00005|anchor=51e6989d}}.
===What it changes===
Repeated cocaine use [[glossary:trigger|triggers]] synaptic changes in the reward pathway that drive compulsive use and increase [[glossary:relapse]] [[glossary:vulnerability]]{{cite|doi=10.3390/molecules24203788|anchor=f1c254bb}}. [[glossary:tolerance]] to euphoria develops rapidly, while [[glossary:sensitivity]] to psychomotor effects and [[glossary:psychosis]] risk increases — chronic users chase a diminishing high while facing escalating psychiatric danger. With prolonged use, cocaine also speeds up its own [[glossary:metabolism|liver metabolism]]{{cite|pubmed=8617431|anchor=0b1de3fb}}, generating a more toxic byproduct called norcocaine{{cite|pubmed=8488174|anchor=3ec98b2c}}.
{{DiscoverMore|Open Questions}}
No neuroimaging studies using coca leaf preparations as administered — rather than refined cocaine — have been published. The contribution of minor coca alkaloids (cinnamoylcocaine, truxillines, hygrine) to whole-leaf pharmacology is unknown. Preparation-specific [[glossary:pharmacokinetics]] for traditional coca leaf chewing and tea infusion remain poorly characterized in controlled human studies.
{{/DiscoverMore}}
===Where it acts===
[[substance:cocaine]]'s principal psychoactive effects arise from [[glossary:blockade]] of the [[glossary:dopamine-transporter]] in the [[glossary:mesolimbic-pathway]] — the projection from the [[glossary:ventral-tegmental-area]] to the [[glossary:nucleus-accumbens]]{{cite|doi=10.1016/j.neuropharm.2014.06.012|anchor=2a3fde1a}}. The resulting surge of synaptic [[glossary:dopamine]] produces [[effect:euphoria]] and behavioral [[glossary:reinforcement]]. A proposed mechanistic refinement suggests cocaine may reverse [[glossary:transporter]] direction, actively pumping dopamine into the synapse rather than simply blocking [[glossary:reuptake]] — potentially explaining why cocaine produces greater euphoria than other [[substance_class:pharmacological/dopamine-reuptake-inhibitor|dopamine reuptake inhibitors]] of comparable binding strength{{cite|doi=10.1016/j.neuropharm.2014.06.012|anchor=be7a8f00}}.
Concurrent [[glossary:norepinephrine-transporter]] blockade drives cardiovascular [[glossary:activation]] and heightened [[glossary:arousal]]. [[glossary:serotonin-transporter|Serotonin transporter]] blockade, the weakest of the three, contributes to mood [[glossary:elevation]]. Sodium [[glossary:channel]] blockade underlies the local anesthetic effect and the arrhythmogenic potential that contributes to cocaine-associated sudden cardiac death{{cite|doi=10.2165/00129784-200909030-00005|anchor=f7a7d03e}}.
===What it changes===
With repeated cocaine exposure, glutamatergic and opioidergic [[glossary:neuroplasticity|plasticity]] at nucleus accumbens synapses contributes to compulsive use and [[glossary:relapse]] [[glossary:vulnerability]]{{cite|doi=10.3390/molecules24203788|anchor=8e32891d}}. [[glossary:tolerance]] to euphoriant effects develops rapidly, while [[glossary:sensitization]] — not tolerance — occurs for psychomotor activation and [[glossary:psychosis]] risk. This explains why chronic users chase a diminishing high while facing escalating psychiatric danger.
Cocaine induces its own hepatic CYP [[glossary:metabolism]] with [[glossary:chronic-use]]{{cite|pubmed=8617431|anchor=071a78b8}}, increasing production of norcocaine — an [[glossary:active-metabolite]] with greater [[glossary:toxicity]] than the [[glossary:parent-compound]]{{cite|pubmed=8488174|anchor=03bd4d27}}.
{{DiscoverMore|Open Questions}}
No neuroimaging studies using coca leaf preparations as administered — rather than refined cocaine — have been published. The contribution of minor coca alkaloids (cinnamoylcocaine, truxillines, hygrine) to whole-leaf pharmacology is unknown. Preparation-specific [[glossary:pharmacokinetics]] for traditional coca leaf chewing and tea infusion remain poorly characterized in controlled human studies.
{{/DiscoverMore}}
===Coca leaf chewing (acullico / pijcheo)===
Traditional preparation involves 20–60 g of fresh coca leaves chewed with an alkaline additive — calcium hydroxide (lime), sodium bicarbonate, or ''llipta'' (plant ash). The alkaline environment shifts buccal pH from ~5.5 to ~8, converting [[substance:cocaine]] to its free-base form and increasing mucosal [[glossary:absorption]] approximately 4-fold{{cite|doi=10.1186/s40794-019-0095-7|anchor=16caf51a}}.
'''Dose:''' Cocaine content per typical chew ranges from approximately 2–40 mg, depending on leaf mass, alkaloid content of the batch, and alkaline additive used{{flag|safety-citation-needed}}. '''Onset:''' 15–45 min. '''Peak:''' 60–90 min. '''Duration:''' 2–4 h. '''Effect character:''' Mild [[effect:stimulation]], [[glossary:fatigue]] suppression, mild [[effect:pain-suppression|analgesia]], [[effect:appetite-suppression]]. Coca leaf chewing at traditional use amounts does not produce the [[effect:euphoria]] characteristic of refined cocaine{{cite|doi=10.1186/s40794-019-0095-7|anchor=02cfddaa}}.
Blood cocaine concentrations from leaf chewing are unlikely to produce drug [[glossary:accumulation]]{{cite|pubmed=7242115|anchor=d0a7279c}}.
===Coca tea (mate de coca)===
Hot water infusion of approximately 1–2 g dried coca leaves yields approximately 2–5 mg cocaine per cup{{flag|safety-citation-needed}}. '''Onset:''' 30–60 min. '''Duration:''' 2–4 h. '''Effect character:''' Mild stimulation and alertness; used traditionally for altitude acclimatization, though clinical evidence for [[glossary:efficacy]] at altitude is limited and controversial{{cite|doi=10.1186/s40794-019-0095-7|anchor=eb31fecf}}. Oral [[glossary:bioavailability]] of cocaine is 32–45%, with significant [[glossary:first-pass-metabolism|first-pass]] [[glossary:metabolism|hepatic metabolism]] producing norcocaine and benzoylecgonine{{cite|doi=10.1093/jat/bky007|anchor=560e4d8e}}.
{{Warning}}Coca leaf chewing and tea consumption produce positive urine drug tests for benzoylecgonine. This has significant legal implications for travelers to Andean regions.{{/Warning}}
===Intranasal cocaine hydrochloride===
'''Dose:''' Threshold approximately 5–10 mg; common 20–75 mg; heavy >100 mg per line{{cite|doi=10.1186/s40794-019-0095-7|anchor=9c9585fd}}{{flag|safety-citation-needed}}. '''Onset:''' 3–5 min. '''Peak:''' 15–30 min. '''Duration:''' 45–90 min. '''Bioavailability:''' Approximately 60–75%{{cite|pubmed=7242115|anchor=16aa8536}}.
'''Effect character:''' Euphoria, stimulation, confidence, decreased appetite, talkativeness, grandiosity, local [[glossary:anesthesia]] of nasal mucosa, and nasal [[effect:vasoconstriction]].
'''Route-specific adverse effects:''' [[glossary:chronic-use]] causes progressive rhinitis, turbinate atrophy, nasal septum perforation, palatal perforation, and saddle nose deformity via [[glossary:ischemia]] and tissue necrosis from sustained vasoconstriction{{cite|doi=10.5867/medwave.2025.01.3012|anchor=6173ef30}}.
===Smoked cocaine (crack / freebase)===
Cocaine hydrochloride is converted to free-base form by treatment with baking soda and water (yielding crack) or solvent extraction. Free-base cocaine vaporizes at lower temperatures than the hydrochloride salt, permitting inhalation.
'''Dose:''' Approximately 50–200 mg per inhalation{{flag|safety-citation-needed}}. '''Onset:''' <1 min. '''Peak:''' 3–5 min. '''Duration:''' 10–20 min. '''Bioavailability:''' Approximately 70–80%.
'''Effect character:''' The most rapid brain delivery of any cocaine preparation. Rapidly administered cocaine preferentially engages mesocorticolimbic [[glossary:circuit|circuits]], promoting psychomotor [[glossary:sensitization]] and accelerating [[glossary:addiction]] progression{{cite|pubmed=15681025|anchor=b8b588a5}}. Cocaine-induced [[glossary:psychosis]] is more prevalent with smoked than [[glossary:insufflation|intranasal]] administration{{cite|doi=10.1080/08897077.2014.933726|anchor=e53400e0}}.
'''Preparation-specific risks:''' "Crack lung" — acute respiratory [[glossary:distress]] with fever, hemoptysis, and dyspnea within 48 hours of inhalation, involving diffuse alveolar hemorrhage, interstitial pneumonia, and eosinophilic infiltration{{cite|doi=10.1016/j.cbi.2013.10.011|anchor=9408be29}}. Pyrolysis produces anhydroecgonine methyl ester (AEME), a specific [[glossary:biomarker]] of the smoked route{{cite|pubmed=9323527|anchor=38e84174}}.
===Intravenous cocaine hydrochloride===
'''Dose:''' 0.2–1.0 mg/kg in controlled studies; street use is highly variable. '''Onset:''' Seconds. '''Duration:''' 20–40 min. '''Bioavailability:''' 100%.
This route carries the highest addiction [[glossary:liability]] and cardiovascular risk profile. [[glossary:injection]] introduces needle-sharing risks including HIV, hepatitis C, bacterial endocarditis, and venous damage.
===Oral cocaine hydrochloride===
'''Bioavailability:''' 32–45% depending on dose{{cite|doi=10.1093/jat/bky007|anchor=4032147b}}; significant first-pass metabolism to norcocaine and benzoylecgonine limits [[glossary:cmax|peak plasma concentrations]]. Late 19th-century cocaine-containing preparations (Vin Mariani, early Coca-Cola) were administered orally; the slow absorption and extensive hepatic metabolism explain their comparatively mild effects.
[[glossary:potency]] varies significantly across preparations and source material. Alkaloid content of coca leaves varies by cultivar, growing conditions, and harvest timing; this variability propagates through all preparations. See the Dose by preparation card for structured dose data.
Coca preparations span a wide experiential range determined almost entirely by preparation method. Traditional leaf chewing produces subtle, sustained alertness with mild [[effect:appetite-suppression]] and gentle mouth numbness — qualitatively closer to a strong cup of tea than to the intense [[effect:euphoria]] associated with refined [[substance:cocaine]]. Smoked or injected cocaine delivers brief, overwhelming euphoria followed almost immediately by [[effect:craving]] and the drive to [[glossary:redose]].
In terms of [[substance_class:psychoactive/stimulant]] [[glossary:intensity]], coca leaf chewing sits somewhere between [[substance:caffeine]] and low-dose [[substance:amphetamine]]. Refined cocaine administered intranasally or by inhalation is closer to [[substance:methamphetamine]] in [[glossary:reinforcement]] [[glossary:potency]] and [[glossary:addiction]] trajectory — though its effects are substantially shorter-lived and its cardiovascular risk profile is distinct.
Coca preparations span a remarkably wide experiential range determined almost entirely by preparation method. Traditional leaf chewing produces subtle, sustained alertness with mild [[effect:pain-suppression|analgesia]] and [[effect:appetite-suppression]] — qualitatively closer to a strong cup of tea than to the intense [[effect:euphoria]] associated with refined [[substance:cocaine]]. Smoked and [[glossary:intravenous]] cocaine deliver brief, overwhelming euphoria followed by [[glossary:rapid-onset|rapid-onset]] [[effect:craving]] that drives compulsive [[glossary:redose|redosing]]. [[glossary:set-and-setting]] modulate the experience but remain secondary to the pharmacokinetic profile determined by preparation.
Coca leaf chewing occupies a pharmacological position between [[substance:caffeine]] and low-dose [[substance:amphetamine]] in terms of [[substance_class:psychoactive/stimulant]] [[glossary:intensity]] and duration. Refined cocaine administered intranasally or by inhalation is more comparable to [[substance:methamphetamine]] in [[glossary:reinforcement]] [[glossary:potency]] and [[glossary:addiction]] trajectory, though with substantially shorter [[glossary:duration-of-action]] and a distinct cardiovascular risk profile.
====Coca leaf chewing (traditional)====
'''Coca leaf chewing''' is the oldest and mildest preparation. Fresh or dried leaves (20–60 g per session) are held in the cheek with an alkaline additive — calcium hydroxide, sodium bicarbonate, or ''llipta'' (plant ash) — which raises buccal pH and promotes [[substance:cocaine]] [[glossary:absorption]]{{cite|doi=10.1186/s40794-019-0095-7|anchor=1db74e41}}. Onset: 15–45 minutes. [[glossary:peak]]: 60–90 minutes. Duration: 2–4 hours. Effects are mild sustained alertness, [[effect:appetite-suppression]], and gentle [[effect:pain-suppression|analgesia]]. [[glossary:accumulation]] from repeated chewing is unlikely given the slow absorption rate{{cite|pubmed=7242115|anchor=a9d7fbfa}}.
====Coca tea (mate de coca)====
'''Coca tea''' is prepared by steeping dried leaves in hot water for 5–15 minutes. Onset: 30–60 minutes. Duration: 2–4 hours. Oral [[glossary:bioavailability]] is approximately 32–45%{{cite|doi=10.1093/jat/bky007|anchor=3c43a4b7}}. Effects are comparable to leaf chewing — mild [[effect:stimulation]] and alertness. Legal and widely consumed in Bolivia, Peru, and parts of Argentina.
====Cocaine hydrochloride (intranasal)====
'''Intranasal cocaine''' ([[glossary:insufflation]] of cocaine hydrochloride powder) produces onset in 3–5 minutes, peak effects at 15–30 minutes, and duration of 45–90 minutes. Bioavailability is approximately 60–75%{{cite|pubmed=7242115|anchor=9c23b2aa}}. Effects are markedly more intense than leaf preparations: strong [[effect:euphoria]], heightened confidence, talkativeness, and a pronounced crash that drives [[glossary:redose|redosing]]. Repeated use causes nasal mucosal damage.
====Smoked cocaine (freebase / crack)====
'''Smoked cocaine''' ([[glossary:freebase]] or crack) produces onset in under one minute. Peak: 3–5 minutes. Duration: 10–20 minutes. Bioavailability is approximately 70–80%. The extreme brevity of effects produces the strongest compulsive redosing drive of any non-[[glossary:intravenous]] preparation. Pulmonary [[glossary:toxicity]], including "crack lung" syndrome, is specific to this route{{cite|doi=10.1016/j.cbi.2013.10.011|anchor=08d4c37e}}.
====Intravenous cocaine====
'''Intravenous cocaine''' produces onset within seconds, peaks at 1–2 minutes, and lasts 20–40 minutes with 100% bioavailability. This route carries the highest risk of acute cardiovascular events and introduces infection risk from [[glossary:injection]] practices. Compulsive redosing frequency is comparable to smoked cocaine.
Per-preparation dose tiers, timelines, and bioavailability data are in the Dose · by preparation card on this page.
====Coca leaf chewing (traditional)====
'''Coca leaf chewing''' is the oldest and mildest preparation. Fresh or dried leaves (20–60 g per session) are placed in the cheek with an alkaline additive — calcium hydroxide, sodium bicarbonate, or ''llipta'' (plant ash) — which raises buccal pH and promotes [[substance:cocaine]] [[glossary:absorption]]{{cite|doi=10.1186/s40794-019-0095-7|anchor=f218a41a}}. Onset occurs over 15–45 minutes, peaking at 60–90 minutes, with a total duration of 2–4 hours. The effect profile is mild sustained alertness, [[effect:appetite-suppression]], and gentle [[effect:pain-suppression|analgesia]]. Drug [[glossary:accumulation]] from repeated chewing is unlikely given the slow absorption rate{{cite|pubmed=7242115|anchor=af34dff1}}.
====Coca tea (mate de coca)====
'''Coca tea''' is prepared by steeping dried coca leaves in hot water for 5–15 minutes. Onset is 30–60 minutes, with effects lasting 2–4 hours. Oral [[glossary:bioavailability]] is approximately 32–45%{{cite|doi=10.1093/jat/bky007|anchor=1278e5fa}}. The experience is comparable to leaf chewing — mild [[effect:stimulation]] and alertness — though absorption occurs via the gastrointestinal tract rather than the buccal mucosa. Coca tea is legal and widely consumed in Bolivia, Peru, and parts of Argentina.
====Cocaine hydrochloride (intranasal)====
'''Intranasal cocaine''' ([[glossary:insufflation]] of cocaine hydrochloride powder) produces onset in 3–5 minutes, peak effects at 15–30 minutes, and duration of 45–90 minutes. Bioavailability is approximately 60–75%{{cite|pubmed=7242115|anchor=377379a8}}. The experience is markedly more intense than leaf preparations: strong [[effect:euphoria]], heightened confidence, talkativeness, and a pronounced crash that drives [[glossary:redose|redosing]]. Nasal mucosal damage occurs with repeated use.
====Smoked cocaine (freebase / crack)====
'''Smoked cocaine''' ([[glossary:freebase]] or crack) produces the fastest onset of any non-[[glossary:intravenous]] preparation — under one minute — with peak effects at 3–5 minutes and total duration of only 10–20 minutes. Bioavailability is approximately 70–80%. The extreme speed of onset and brevity of effect produce the most intense euphoria and the strongest drive toward compulsive redosing. Pulmonary [[glossary:toxicity]], including "crack lung" syndrome, is specific to this preparation{{cite|doi=10.1016/j.cbi.2013.10.011|anchor=7e66d83d}}.
====Intravenous cocaine====
'''Intravenous cocaine''' produces onset within seconds, peaking at 1–2 minutes, with duration of 20–40 minutes and 100% bioavailability. This route carries the highest risk of acute cardiovascular events and introduces infection risk from [[glossary:injection]] practices. Compulsive redosing frequency is comparable to smoked cocaine.
Per-preparation dose tiers, timelines, and bioavailability data are in the Dose · by preparation card on this page.
====Toxicity====
[[substance:cocaine]] [[glossary:intoxication]] is the most frequent cause of drug-related death reported by US medical examiners{{cite|pubmed=20857618|anchor=8aa19b6a}}. No formal human [[glossary:lethal-dose|LD50]] exists. Lethal [[glossary:plasma-concentration|blood concentrations]] typically exceed 1 mg/L, though deaths have occurred at lower levels in the presence of cardiac conditions or co-ingested substances{{flag|safety-citation-needed}}.
Cardiovascular complications represent the most clinically significant [[glossary:toxicity]] across all preparations{{cite|doi=10.1016/j.cjca.2022.05.003|anchor=2ffb9a05}}{{cite|doi=10.2165/00129784-200909030-00005|anchor=f5b0420a}}{{cite|doi=10.1002/clc.20746|anchor=eda039e3}}. Frequent cocaine users face a 7-fold higher risk of myocardial infarction. Mechanisms include coronary artery vasospasm, accelerated atherosclerosis, thrombus formation, and QT prolongation via sodium [[glossary:channel]] [[glossary:blockade]]. [[glossary:arrhythmia|Arrhythmias]] — including ventricular fibrillation and sudden cardiac death — are mediated by sodium channel blockade and catecholamine surge. [[glossary:chronic-use]] produces dilated cardiomyopathy, myocarditis, and left ventricular hypertrophy.
{{Emergency}}Cocaine-associated chest pain should be evaluated as potential myocardial infarction. '''Beta-blockers are contraindicated''' — unopposed alpha-adrenergic [[effect:stimulation]] worsens [[effect:vasoconstriction]] and [[glossary:hypertension]]. First-line management: [[substance_class:chemical/benzodiazepine|benzodiazepines]] for [[glossary:agitation]], nitroglycerin or calcium channel blockers for ischemia, phentolamine for refractory hypertension.{{/Emergency}}
Norcocaine, the [[glossary:cyp3a4]]-generated [[glossary:metabolite]], is hepatotoxic. Documented pathology includes perivenular necrosis and microvesicular fatty change{{cite|pubmed=2328957|anchor=995396c4}}. Multi-organ failure involving rhabdomyolysis, acute kidney injury, and hepatic ischemia has been documented as cocaine-induced C-KLM syndrome{{cite|doi=10.7759/cureus.50745|anchor=bc83e011}}.
Smoked cocaine carries preparation-specific pulmonary risk. "Crack lung" syndrome presents as acute respiratory [[glossary:distress]] with fever, hemoptysis, and diffuse alveolar hemorrhage within 48 hours of inhalation{{cite|doi=10.1016/j.cbi.2013.10.011|anchor=a6c67731}}. Both ischemic and hemorrhagic stroke are documented; cocaine is a recognized independent stroke risk factor. Reversible cerebral vasoconstriction syndrome has been reported even following coca leaf tea at high altitude{{cite|doi=10.1016/j.jstrokecerebrovasdis.2025.108506|anchor=a02ce2a5}}.
'''Contaminant and adulterant risk:''' Levamisole, a veterinary anthelmintic, contaminates an estimated 69–80% of illicit cocaine in the United States{{cite|doi=10.1097/MOH.0b013e32834da9ef|anchor=4308ea94}}{{cite|doi=10.3122/jabfm.2012.04.110177|anchor=00e6bdbc}}. Clinical consequences include agranulocytosis with life-threatening infections, ANCA-associated vasculitis, multifocal leukoencephalopathy, and acquired protein S deficiency. Additional adulterants include local anesthetics (procaine, benzocaine, lidocaine) and, increasingly, [[substance:fentanyl]] — which introduces opioid overdose risk toxicologically distinct from cocaine effects.
Coca leaf products sold in Andean countries carry lower adulterant risk than illicit refined cocaine, but no ISO/IEC-accredited third-party testing programs for commercial coca leaf products have been identified{{flag|citation-needed}}.
====Psychological Risks====
Cocaine-induced [[glossary:psychosis]] is characterized by paranoid [[effect:delusions]], visual and [[effect:auditory-hallucinations]], and [[effect:paranoia]]. Prevalence reaches as high as 86.5% in some clinical populations{{cite|doi=10.1080/08897077.2014.933726|anchor=c605f796}}. Risk factors include high cumulative dose, lifetime duration of use, smoked or [[glossary:intravenous]] route, [[substance:cannabis]] [[glossary:polydrug|co-use]], ADHD comorbidity, and male sex{{cite|doi=10.1080/08897077.2014.933726|anchor=3bcdea6e}}.
Sensitization rather than [[glossary:tolerance]] occurs for psychosis risk — repeated exposure progressively lowers the threshold for psychotic symptoms. [[effect:anxiety]], paranoia, panic reactions, and agitation occur dose-dependently across all preparations. Grandiosity, impaired judgment, and compulsive [[glossary:redose|redosing]] are characteristic at higher doses, particularly with smoked and intravenous preparations.
====Tolerance & Dependence====
Tolerance develops rapidly to cocaine's euphoriant effects. Paradoxically, sensitization occurs for psychomotor [[glossary:activation]] and psychosis risk with prolonged use. This differential neuroadaptation underlies escalating psychiatric danger alongside diminishing [[effect:euphoria]].
[[glossary:dependence]] is primarily psychological, driven by [[glossary:mesolimbic-pathway|mesolimbic dopamine]] [[glossary:reinforcement]]. Physical dependence is present but less prominent than with [[substance_class:psychoactive/opioid|opioids]] or [[substance:alcohol]]. [[glossary:withdrawal]] follows a three-phase pattern{{cite|doi=10.1016/j.neubiorev.2025.106278|anchor=71af5156}}:
* '''Phase 1 — Crash (hours to 4 days):''' [[effect:dysphoria]], [[glossary:fatigue]], hypersomnia with REM rebound effect, [[effect:appetite-enhancement]], temporarily reduced [[effect:craving]].
* '''Phase 2 — Withdrawal (1–10 weeks):''' [[effect:anhedonia]], anxiety, sleep disturbance, intense cue-triggered cravings; highest relapse risk period.
* '''Phase 3 — Extinction (months to years):''' Gradual normalization; intermittent cue-triggered cravings persist{{cite|doi=10.1016/j.neubiorev.2025.106278|anchor=4ae639f3}}.
{{Recovery}}No FDA-approved pharmacotherapy for cocaine use [[glossary:disorder]] exists as of 2026{{cite|doi=10.1177/02698811251399593|anchor=ad0464f2}}. Current evidence supports cognitive behavioral therapy, contingency management, and treatment of comorbid psychiatric conditions.{{/Recovery}}
====Drug Interactions====
'''Ethanol (alcohol):''' The most clinically significant interaction. Hepatic [[glossary:enzyme|enzymes]] catalyze transesterification of cocaine with ethanol to form cocaethylene, a metabolite more toxic than cocaine with a longer duration of action{{cite|doi=10.1037/a0022950|anchor=ea3f31e4}}{{cite|doi=10.1016/j.toxrep.2022.08.001|anchor=8f9d0175}}{{cite|doi=10.1016/j.cbi.2026.112088|anchor=87032fac}}. Cocaethylene yield varies by route: oral (34%) > intravenous (24%) > smoked (18%){{cite|doi=10.1037/a0022950|anchor=ba567ffb}}.
'''Beta-adrenergic blockers:''' Contraindicated. Cocaine's alpha-adrenergic effects become unopposed when beta [[glossary:receptor|receptors]] are blocked, producing severe hypertension and coronary vasospasm.
'''MAO inhibitors:''' Theoretical risk of hypertensive crisis and [[glossary:serotonin-syndrome]] via amplified [[glossary:monoamine]] activity. {{flag|safety-citation-needed}}
'''CYP3A4 inhibitors''' (ketoconazole, clarithromycin, ritonavir): May increase parent cocaine plasma levels by reducing [[glossary:clearance]] while decreasing norcocaine formation{{cite|pubmed=8488174|anchor=7d1b5868}}. {{flag|safety-citation-needed}}
'''Tricyclic antidepressants:''' Additive cardiovascular toxicity via combined sodium channel blockade and [[substance_class:pharmacological/norepinephrine-reuptake-inhibitor]]. {{flag|safety-citation-needed}}
====Contraindications====
'''Pregnancy:''' Absolute [[glossary:contraindication]]. Cocaine use in [[glossary:pregnancy]] is associated with placental abruption, adverse neonatal outcomes, and fetal [[glossary:central-nervous-system|CNS]] development effects{{cite|doi=10.1186/s12884-024-07062-1|anchor=c844725f}}.
'''Cardiovascular disease:''' Absolute contraindication for all preparations. Pre-existing cardiac conditions dramatically elevate myocardial infarction and sudden death risk{{cite|doi=10.1016/j.cjca.2022.05.003|anchor=cf884f97}}.
'''Hepatic impairment:''' Relative contraindication — impaired cocaine and norcocaine [[glossary:metabolism]] increases toxicity duration and [[glossary:severity]].
'''Concurrent beta-blocker therapy:''' Absolute contraindication — unopposed alpha stimulation produces severe hypertension and coronary vasospasm.
'''Concurrent MAOI or tricyclic antidepressant therapy:''' Relative contraindication due to additive cardiovascular and serotonergic risk.
'''Psychiatric vulnerability:''' Relative contraindication. Schizophrenia spectrum disorders and psychosis risk are amplified by cocaine use{{cite|doi=10.1080/08897077.2014.933726|anchor=3c6f8a74}}.
'''Pediatric and neonatal exposure:''' Prenatal cocaine exposure is associated with functional brain connectivity alterations in neonates{{cite|doi=10.1186/s12884-024-07062-1|anchor=cb6c1da7}}.
====Toxicity====
[[substance:cocaine]] is the most frequent cause of drug-related death reported by US medical examiners{{cite|pubmed=20857618|anchor=9ab92f8c}}. The primary risk is cardiovascular: frequent users face a 7-fold higher risk of heart attack{{cite|doi=10.1016/j.cjca.2022.05.003|anchor=d434bc1c}}{{cite|doi=10.2165/00129784-200909030-00005|anchor=fb2c95b5}}{{cite|doi=10.1002/clc.20746|anchor=98a7a196}}. Cocaine narrows coronary arteries, promotes clot formation, and disrupts heart rhythm — any of which can cause sudden death.
{{Emergency}}Cocaine-associated [[glossary:chest-pain]] should be evaluated as potential myocardial infarction. '''Beta-blockers are contraindicated''' — unopposed alpha-adrenergic [[effect:stimulation]] worsens [[effect:vasoconstriction]] and [[glossary:hypertension]]. First-line management: [[substance_class:chemical/benzodiazepine|benzodiazepines]] for [[glossary:agitation]], nitroglycerin or calcium channel [[glossary:blocker|blockers]] for ischemia, phentolamine for refractory hypertension.{{/Emergency}}
[[glossary:chronic-use]] generates norcocaine, a liver-toxic byproduct that causes liver cell death and fatty change{{cite|pubmed=2328957|anchor=40d441cc}}. Multi-organ failure combining [[glossary:rhabdomyolysis|muscle breakdown]], kidney injury, and liver damage is documented{{cite|doi=10.7759/cureus.50745|anchor=ec78fca4}}.
Smoked cocaine can [[glossary:trigger]] "crack lung" — acute respiratory [[glossary:distress]] with fever, blood in the cough, and lung bleeding within 48 hours{{cite|doi=10.1016/j.cbi.2013.10.011|anchor=5736a377}}. Both ischemic and hemorrhagic stroke are documented; reversible cerebral vasoconstriction has been reported even after coca tea at high altitude{{cite|doi=10.1016/j.jstrokecerebrovasdis.2025.108506|anchor=471d58bf}}.
Levamisole contaminates an estimated 69–80% of illicit US cocaine{{cite|doi=10.1097/MOH.0b013e32834da9ef|anchor=2d49b6bb}}{{cite|doi=10.3122/jabfm.2012.04.110177|anchor=24c4d6ce}}, causing dangerously low white blood cell counts and blood vessel inflammation. [[substance:fentanyl]] [[glossary:contamination]] is increasingly common and introduces opioid overdose risk separate from cocaine's own [[glossary:toxicity]].
====Psychological Risks====
Paranoid [[effect:delusions]], [[glossary:hallucination|hallucinations]], and [[effect:thought-disorganization]] can emerge with cocaine use. [[glossary:prevalence]] reaches 86.5% in some clinical populations{{cite|doi=10.1080/08897077.2014.933726|anchor=ac2676c4}}. High cumulative dose, smoked or [[glossary:intravenous]] route, [[substance:cannabis]] [[glossary:polydrug|co-use]], and pre-existing ADHD all increase the risk{{cite|doi=10.1080/08897077.2014.933726|anchor=8289d362}}. Repeated use does not build [[glossary:tolerance]] to [[glossary:psychosis]] — it progressively lowers the threshold for psychotic symptoms. [[effect:anxiety]], panic, grandiosity, and impaired judgment occur across all preparations at sufficient doses.
====Tolerance & Dependence====
Tolerance to [[effect:euphoria]] develops rapidly. Simultaneously, [[glossary:sensitivity]] to psychomotor effects and psychosis risk increases — the opposite of tolerance. [[glossary:dependence]] is primarily psychological, driven by [[glossary:mesolimbic-pathway|mesolimbic dopamine]] [[glossary:reinforcement]], though physical dependence is also present. [[glossary:withdrawal]] follows a three-phase pattern{{cite|doi=10.1016/j.neubiorev.2025.106278|anchor=4570e8de}}:
* '''Phase 1 — Crash (hours to 4 days):''' [[effect:dysphoria]], [[glossary:fatigue]], hypersomnia with REM rebound effect, [[effect:appetite-enhancement]], temporarily reduced [[effect:craving]].
* '''Phase 2 — Withdrawal (1–10 weeks):''' [[effect:anhedonia]], anxiety, sleep disturbance, intense cue-triggered cravings; highest relapse risk period.
* '''Phase 3 — Extinction (months to years):''' Gradual normalization; intermittent cue-triggered cravings persist{{cite|doi=10.1016/j.neubiorev.2025.106278|anchor=80b3106e}}.
{{Recovery}}No [[glossary:fda]]-approved pharmacotherapy for cocaine use [[glossary:disorder]] exists as of 2026{{cite|doi=10.1177/02698811251399593|anchor=6a55167a}}. Current evidence supports cognitive behavioral therapy, contingency management, and treatment of comorbid psychiatric conditions.{{/Recovery}}
====Drug Interactions====
'''Ethanol (alcohol):''' The most clinically significant interaction. [[glossary:liver-enzymes]] convert cocaine and [[substance:alcohol]] together into cocaethylene — more toxic than cocaine itself and longer-lasting{{cite|doi=10.1037/a0022950|anchor=84d32e4d}}{{cite|doi=10.1016/j.toxrep.2022.08.001|anchor=eb0fabe4}}{{cite|doi=10.1016/j.cbi.2026.112088|anchor=6a2b029c}}. Cocaethylene yield varies by route: oral (34%) > intravenous (24%) > smoked (18%){{cite|doi=10.1037/a0022950|anchor=37360220}}.
'''Beta-adrenergic blockers:''' Contraindicated. Blocking beta [[glossary:receptor|receptors]] leaves cocaine's arterial constriction effects unopposed, producing severe hypertension and coronary vasospasm.
'''MAO inhibitors:''' Risk of severe [[glossary:blood-pressure]] crisis and [[glossary:serotonin-syndrome|serotonin overload]] via amplified [[glossary:monoamine]] activity.{{flag|safety-citation-needed}}
'''CYP3A4 inhibitors''' (ketoconazole, clarithromycin, ritonavir): May raise cocaine blood levels by slowing its [[glossary:clearance]] while reducing norcocaine formation{{cite|pubmed=8488174|anchor=3cd52c2c}}.{{flag|safety-citation-needed}}
'''Tricyclic antidepressants:''' Additive cardiovascular toxicity from combined sodium [[glossary:channel]] [[glossary:blockade]] and [[glossary:norepinephrine]] [[glossary:accumulation|buildup]].{{flag|safety-citation-needed}}
====Contraindications====
[[glossary:pregnancy]] is an absolute [[glossary:contraindication]] — associated with placental abruption and fetal brain development effects{{cite|doi=10.1186/s12884-024-07062-1|anchor=beb2c17d}}. Pre-existing cardiovascular disease is an absolute contraindication; the risk of heart attack and sudden death rises dramatically{{cite|doi=10.1016/j.cjca.2022.05.003|anchor=d6f133a8}}. Concurrent beta-blocker therapy is absolutely contraindicated. [[glossary:hepatic-impairment]], concurrent MAOI or tricyclic [[substance_class:psychoactive/antidepressant]] therapy, and personal or family history of schizophrenia or psychosis are relative contraindications{{cite|doi=10.1080/08897077.2014.933726|anchor=2308d381}}.
===Forms & Identification===
Lab testing is the only reliable method for determining the purity and composition of refined [[substance:cocaine]] products. The illicit cocaine supply is extensively adulterated — levamisole alone contaminates the majority of US cocaine, and [[substance:fentanyl]] [[glossary:contamination]] is increasingly common. Fentanyl test strips can detect fentanyl in cocaine samples but do not identify all [[glossary:synthetic]] [[substance_class:psychoactive/opioid]] analogs. [[glossary:reagent-kit|Reagent testing]] (Scott/cobalt thiocyanate) confirms the presence of cocaine but cannot quantify purity or identify all [[glossary:adulterant|adulterants]].
For coca leaf products purchased in Andean countries, adulterant risk is substantially lower, but standardized [[glossary:potency]] testing is unavailable. Alkaloid content varies across batches and cultivars — dose conservatively when switching sources.
===Set & Setting===
The setting in which cocaine is used significantly influences risk. Social environments that normalize compulsive [[glossary:redose|redosing]] — common with [[glossary:insufflation|intranasal]] and smoked preparations — amplify [[glossary:dependence]] risk. Using alone increases the danger of unwitnessed cardiac emergencies or [[glossary:psychotic-episodes]].
A sober companion who can recognize cardiac [[glossary:distress]] or [[glossary:psychosis|psychotic symptoms]] and call emergency services reduces acute [[glossary:mortality]] risk. For traditional coca leaf preparations, risk is substantially lower but not zero — reversible cerebral [[effect:vasoconstriction]] syndrome has been reported with coca tea at high altitude.
{{Guideline}}
===Guidelines===
* Start with the lowest effective amount and wait for full onset before considering redosing — onset varies dramatically by preparation (leaf chewing: 15–45 min; intranasal: 3–5 min)
* Pre-measure amounts before a session to limit compulsive redosing; the rapid offset of smoked and intranasal cocaine drives repeated use
* Test all refined cocaine products with fentanyl test strips before use
* Use in the presence of others who can recognize and respond to medical emergencies
* Stay hydrated and eat before use — cocaine suppresses appetite and masks [[glossary:dehydration]]
* Monitor [[glossary:heart-rate]]; stop immediately and seek medical attention if [[glossary:chest-pain]], palpitations, or difficulty breathing occur
* Alternate nostrils and rinse with saline after intranasal use to reduce mucosal damage
* Avoid binge patterns; set a firm time limit for sessions
{{/Guideline}}
{{Emergency}}
===Emergency Response===
'''Recognizing an emergency:'''
* Chest pain, pressure, or tightness
* Irregular or racing heartbeat
* Difficulty breathing
* Severe [[effect:paranoia]], [[glossary:hallucination|hallucinations]], or psychotic behavior
* [[glossary:seizure|Seizures]] or [[glossary:loss-of-consciousness]]
* Blue lips or extremities
* [[glossary:hyperthermia]] (hot, dry skin)
'''Immediate steps:'''
* '''1.''' Call emergency services (911 or local emergency number) immediately if any of the above are present
* '''2.''' Keep the person calm and in a cool, quiet environment
* '''3.''' If conscious, position sitting upright to ease breathing
* '''4.''' If unconscious and breathing, place in [[glossary:recovery-position]]
* '''5.''' If not breathing, begin CPR
* '''6.''' '''Do not administer beta-blockers''' — they worsen cocaine-related cardiac events
'''What to tell the dispatcher:''' Name the substance (cocaine or coca preparation), estimated amount and time of last use, and current symptoms. [[glossary:good-samaritan-law|Good Samaritan laws]] in many jurisdictions provide legal protection for reporting drug-related emergencies.
'''Reversal agents:''' No specific reversal agent for cocaine [[glossary:toxicity]] exists. If fentanyl contamination is suspected and [[glossary:opioid-overdose]] signs are present (slowed or stopped breathing, pinpoint pupils, blue lips), administer [[substance:naloxone]] immediately.
{{/Emergency}}
{{Aftercare}}
===Aftercare & Integration===
The post-cocaine crash typically involves [[effect:dysphoria]], [[glossary:fatigue]], and [[effect:appetite-enhancement]]. For intranasal and smoked preparations, the crash can begin within minutes of last use and persist for hours to days depending on session length and cumulative dose.
Prioritize sleep, [[glossary:hydration]], and nutrition during the crash period. [[glossary:hypersomnia]] is expected and should not be resisted. Avoid using other [[substance_class:psychoactive/stimulant|stimulants]] to counteract post-cocaine fatigue — this extends recovery time and increases cardiovascular strain. For regular users, the [[glossary:withdrawal]] period (1–10 weeks) involves [[effect:anhedonia]], [[effect:anxiety]], and intense cue-triggered [[effect:craving|cravings]]. Identifying and avoiding environmental cues associated with prior use reduces [[glossary:relapse]] risk during this vulnerable window.
{{/Aftercare}}
{{Recovery}}
===Recovery & Support===
No [[glossary:fda]]-approved pharmacotherapy for cocaine use [[glossary:disorder]] exists as of 2026. Evidence-supported treatments include cognitive behavioral therapy (CBT), contingency management (CM), and integrated treatment of comorbid psychiatric conditions.
For individuals seeking to reduce or stop cocaine use:
* '''SAMHSA National Helpline:''' 1-800-662-4357 (free, confidential, 24/7 [[glossary:referral]] service)
* '''Cocaine Anonymous:''' peer-support fellowship modeled on the 12-step framework
* Outpatient CBT and contingency management programs are available through most [[glossary:addiction]] treatment centers
Abrupt cessation of cocaine is medically safe, though psychologically difficult. The highest relapse risk occurs during weeks 1–10 after last use, when cue-triggered cravings are most intense. Professional support during this period significantly improves outcomes.
{{/Recovery}}
===Forms & Identification===
Lab testing is the only reliable way to determine the purity of refined [[substance:cocaine]]. The illicit supply is extensively adulterated — levamisole contaminates the majority of US cocaine, and [[substance:fentanyl]] is increasingly present. Fentanyl test strips detect fentanyl but not all [[glossary:synthetic]] [[substance_class:psychoactive/opioid]] analogs. [[glossary:reagent-kit|Reagent testing]] (Scott/cobalt thiocyanate) confirms cocaine is present but cannot quantify purity or identify all [[glossary:adulterant|adulterants]].
For coca leaf products purchased in Andean countries, adulterant risk is substantially lower, but standardized [[glossary:potency]] testing is not available. Alkaloid content varies across batches and cultivars — dose conservatively when switching sources.
===Set & Setting===
The setting significantly influences risk. Social environments that normalize compulsive [[glossary:redose|redosing]] — common with [[glossary:insufflation|intranasal]] and smoked preparations — amplify [[glossary:dependence]] risk. Using alone increases the danger of unwitnessed cardiac events or [[glossary:psychotic-episodes]].
A sober companion who can recognize cardiac [[glossary:distress]] or [[glossary:psychosis|psychotic symptoms]] and call emergency services reduces acute [[glossary:mortality]] risk. For traditional coca leaf preparations, risk is substantially lower but not zero — reversible cerebral [[effect:vasoconstriction]] has been reported with coca tea at high altitude.
{{Guideline}}
===Guidelines===
* Start with the lowest effective amount and wait for full onset before considering redosing — onset varies dramatically by preparation (leaf chewing: 15–45 min; intranasal: 3–5 min)
* Pre-measure amounts before a session to limit compulsive redosing; the rapid offset of smoked and intranasal cocaine drives repeated use
* Test all refined cocaine products with fentanyl test strips before use
* Use in the presence of others who can recognize and respond to medical emergencies
* Stay hydrated and eat before use — cocaine suppresses appetite and masks [[glossary:dehydration]]
* Monitor [[glossary:heart-rate]]; stop immediately and seek medical attention if [[glossary:chest-pain]], palpitations, or difficulty breathing occur
* Alternate nostrils and rinse with saline after intranasal use to reduce mucosal damage
* Avoid binge patterns; set a firm time limit for sessions
{{/Guideline}}
{{Emergency}}
===Emergency Response===
'''Recognizing an emergency:'''
* Chest pain, pressure, or tightness
* Irregular or racing heartbeat
* Difficulty breathing
* Severe [[effect:paranoia]], [[glossary:hallucination|hallucinations]], or psychotic behavior
* [[glossary:seizure|Seizures]] or [[glossary:loss-of-consciousness]]
* Blue lips or extremities
* [[glossary:hyperthermia]] (hot, dry skin)
'''Immediate steps:'''
* '''1.''' Call emergency services (911 or local emergency number) immediately if any of the above are present
* '''2.''' Keep the person calm and in a cool, quiet environment
* '''3.''' If conscious, position sitting upright to ease breathing
* '''4.''' If unconscious and breathing, place in [[glossary:recovery-position]]
* '''5.''' If not breathing, begin CPR
* '''6.''' '''Do not administer beta-blockers''' — they worsen cocaine-related cardiac events
'''What to tell the dispatcher:''' Name the substance (cocaine or coca preparation), estimated amount and time of last use, and current symptoms. [[glossary:good-samaritan-law|Good Samaritan laws]] in many jurisdictions provide legal protection for reporting drug-related emergencies.
'''Reversal agents:''' No specific reversal agent for cocaine [[glossary:toxicity]] exists. If fentanyl [[glossary:contamination]] is suspected and [[glossary:opioid-overdose]] signs are present (slowed or stopped breathing, pinpoint pupils, blue lips), administer [[substance:naloxone]] immediately.
{{/Emergency}}
{{Aftercare}}
===Aftercare & Integration===
The post-cocaine crash brings [[effect:dysphoria]], [[glossary:fatigue]], and [[effect:appetite-enhancement]]. For intranasal and smoked preparations, the crash can begin within minutes of last use and persist for hours to days depending on session length and cumulative dose.
Prioritize sleep, [[glossary:hydration]], and nutrition during the crash period. [[glossary:hypersomnia]] is expected and should not be resisted. Avoid using other [[substance_class:psychoactive/stimulant|stimulants]] to counteract post-cocaine fatigue — this extends recovery time and increases cardiovascular strain. For regular users, the [[glossary:withdrawal]] period (1–10 weeks) involves [[effect:anhedonia]], [[effect:anxiety]], and intense cue-triggered [[effect:craving|cravings]]. Identifying and avoiding environmental cues associated with prior use reduces [[glossary:relapse]] risk during this vulnerable window.
{{/Aftercare}}
{{Recovery}}
===Recovery & Support===
No [[glossary:fda]]-approved pharmacotherapy for cocaine use [[glossary:disorder]] exists as of 2026. Evidence-supported treatments include cognitive behavioral therapy (CBT), contingency management (CM), and integrated treatment of comorbid psychiatric conditions.
For individuals seeking to reduce or stop cocaine use:
* '''SAMHSA National Helpline:''' 1-800-662-4357 (free, confidential, 24/7 [[glossary:referral]] service)
* '''Cocaine Anonymous:''' peer-support fellowship modeled on the 12-step framework
* Outpatient CBT and contingency management programs are available through most [[glossary:addiction]] treatment centers
Abrupt cessation of cocaine is medically safe, though psychologically difficult. The highest relapse risk occurs during weeks 1–10 after last use, when cue-triggered cravings are most intense. Professional support during this period significantly improves outcomes.
{{/Recovery}}
Coca leaf and [[substance:cocaine]] are controlled under international treaty in virtually all jurisdictions. The 1961 UN Single Convention places both the plant and its primary alkaloid on [[glossary:schedule-i]] — an unusual arrangement, since most scheduled plants are only controlled at the alkaloid level. In the United States, cocaine is a [[glossary:schedule-ii]] controlled substance with narrow medical approval as a topical nasal anesthetic{{cite|url=https://www.dea.gov/sites/default/files/2025-01/Cocaine-2024-Drug-Fact-Sheet.pdf|anchor=52bfa8aa}}. Bolivia and Peru maintain legal frameworks permitting traditional coca leaf chewing and tea consumption. Colombia — the world's largest producing country — prohibits cultivation and trafficking{{cite|url=https://www.unodc.org/unodc/press/releases/2024/October/colombia_-potential-cocaine-production-increased-by-53-per-cent-in-2023--according-to-new-unodc-survey.html|anchor=a60464b7}}. Argentina allows coca leaf and tea for cultural use in northern provinces. The UK classifies both cocaine and coca leaf as [[glossary:class-a]], with maximum penalties of life imprisonment for supply{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_cocaine|anchor=ad8824e8}}. Bolivia's 2013 reaccession to the 1961 Convention included an explicit reservation for traditional coca use — the only formal treaty-level exception currently in force.
Coca leaf chewing and tea consumption produce positive urine drug tests for benzoylecgonine. Standard workplace tests detect [[glossary:metabolite|metabolites]] for approximately 2–4 days in most individuals. Sensitive [[glossary:assay|assays]] using a 5 ng/mL cutoff extend the [[glossary:detection]] window to 17–22 days{{cite|doi=10.1002/dta.2153|anchor=c9f60224}}{{cite|pubmed=12422991|anchor=caab3cb6}}.
{{Warning}}
Legal status changes frequently. This overview reflects the status as of the article's last update and is not legal advice. Verify current law in the relevant jurisdiction before acting on this information.
{{/Warning}}
===Primary receptor targets===
[[substance:cocaine]] acts as a non-selective [[glossary:monoamine]] [[glossary:reuptake-inhibitor]], blocking three [[glossary:transporter|transporters]] with distinct functional consequences:
'''Dopamine transporter (DAT) blockade''' is the primary mechanism of [[effect:euphoria]] and behavioral [[glossary:reinforcement]]. Cocaine binding to [[glossary:dopamine-transporter]] increases synaptic [[glossary:dopamine]] in the [[glossary:nucleus-accumbens]] and other mesolimbic regions{{cite|doi=10.1016/j.neuropharm.2014.06.012|anchor=97f55dc1}}. A proposed mechanistic refinement suggests cocaine may function as a negative allosteric modulator of DAT, reversing transporter direction to induce firing-dependent retro-transport of dopamine into the synaptic cleft — potentially explaining why cocaine produces greater euphoria than other DAT [[glossary:inhibitor|inhibitors]] of equivalent binding [[glossary:potency]]{{cite|doi=10.1016/j.neuropharm.2014.06.012|anchor=081b7070}}.
'''Norepinephrine transporter (NET) blockade''' increases synaptic [[glossary:norepinephrine]], mediating cardiovascular [[effect:stimulation]] ([[glossary:tachycardia]], [[glossary:hypertension]], [[effect:vasoconstriction]]), [[glossary:arousal]], and a partial contribution to euphoriant effects.
'''Serotonin transporter (SERT) blockade''' is the least potent of the three; it contributes to mood [[glossary:elevation]] and introduces serotonergic [[glossary:toxicity]] risk in combination with [[glossary:serotonergic-drug|serotonergic drugs]].
'''Voltage-gated Na⁺ channel blockade''' produces the membrane-stabilizing local anesthetic effect used clinically in ENT procedures and contributes to the arrhythmogenic potential that underlies cocaine-associated sudden cardiac death{{cite|doi=10.2165/00129784-200909030-00005|anchor=1397f945}}.
===Neural circuits===
The [[glossary:mesolimbic-pathway]] ([[glossary:ventral-tegmental-area]] → nucleus accumbens) mediates acute reinforcement and euphoria. The mesocortical pathway (VTA → [[glossary:prefrontal-cortex]]) mediates cognitive effects including attentional narrowing and [[effect:decision-impairment]]. With repeated exposure, glutamatergic and opioidergic [[glossary:neuroplasticity|plasticity]] at nucleus accumbens synapses contributes to compulsive use and [[glossary:relapse]] susceptibility{{cite|doi=10.3390/molecules24203788|anchor=bfa09af0}}.
Cocaine is highly lipophilic and crosses the [[glossary:blood-brain-barrier]] rapidly; preclinical data indicate a brain extracellular fluid to [[glossary:plasma]] AUC ratio of approximately 2:1, reflecting preferential [[glossary:central-nervous-system|CNS]] distribution{{flag|citation-needed}}.
===Pharmacokinetics by preparation===
Pharmacokinetic parameters vary substantially across preparations, and these differences determine the qualitative character of the experience:
Terminal plasma [[glossary:half-life]] is dose-dependent: t₁/₂(β) = 13.5 + 24.5 × dose (mg/kg) minutes, yielding approximately 38–87 minutes for typical doses of 1–3 mg/kg{{cite|pubmed=7242115|anchor=6594fad5}}. Drug [[glossary:accumulation]] from coca leaf chewing is unlikely given the slow [[glossary:absorption]] rate (~8 min absorption half-life for mucosal routes at low doses){{cite|pubmed=7242115|anchor=80b44cb6}}.
===Metabolism===
[[glossary:cyp3a4]] is the primary [[glossary:enzyme]] responsible for N-demethylation of cocaine to norcocaine, an [[glossary:active-metabolite]] with greater toxicity than the [[glossary:parent-compound]]{{cite|pubmed=8488174|anchor=0d086b60}}. CYP3A4 accounts for 70–90% of cocaine N-demethylase activity in human hepatic microsomes. Cocaine induces its own hepatic CYP [[glossary:metabolism]] with chronic dosing{{cite|pubmed=8617431|anchor=03c17af4}}, potentially increasing norcocaine production over time.
Concurrent ethanol consumption leads to transesterification of cocaine to cocaethylene, catalyzed by hepatic carboxylesterase-1 (CES1) and CYP3A4{{cite|doi=10.1016/j.toxrep.2022.08.001|anchor=7d5703b9}}. Cocaethylene is more toxic than cocaine and extends the [[glossary:duration-of-action]]{{cite|doi=10.1016/j.cbi.2026.112088|anchor=741dd662}}.
===Open questions===
Preparation-specific [[glossary:pharmacokinetics]] for coca leaf chewing and tea infusion remain poorly characterized in controlled human studies. No neuroimaging studies using coca leaf preparations as administered — rather than refined cocaine — have been published. The relative contribution of minor coca alkaloids (cinnamoylcocaine, truxillines, hygrine) to the overall pharmacological profile of whole-leaf preparations is unknown.
| Preparation | Onset | Peak | Duration | Bioavailability |
|---|---|---|---|---|
| Coca leaf chewing | 15–45 min | 60–90 min | 2–4 h | Variable (slow buccal) |
| Coca tea (oral infusion) | 30–60 min | ~60 min | 2–4 h | ~32–45%{{cite|doi=10.1093/jat/bky007|anchor=110441b0}} |
| Intranasal (insufflation) | 3–5 min | 15–30 min | 45–90 min | ~60–75%{{cite|pubmed=7242115|anchor=73af8474}} |
| Smoked (freebase / crack) | <1 min | 3–5 min | 10–20 min | ~70–80% |
| Intravenous | Seconds | 1–2 min | 20–40 min | 100% |
Coca leaf and [[substance:cocaine]] are controlled under international treaty and domestic legislation in virtually all jurisdictions. The 1961 UN Single Convention on Narcotic Drugs places both coca leaf and cocaine on [[glossary:schedule-i]] — unlike some psychoactive plants where only the isolated alkaloid is scheduled, coca leaf itself is explicitly controlled alongside its primary alkaloid. Bolivia and Peru maintain legal frameworks permitting traditional coca leaf consumption, while refined cocaine is universally prohibited outside narrow medical applications. In the United States, cocaine hydrochloride retains limited medical approval as a topical nasal anesthetic{{cite|url=https://www.dea.gov/sites/default/files/2025-01/Cocaine-2024-Drug-Fact-Sheet.pdf|anchor=71938b0a}}.
===Treaty and detection considerations===
Bolivia's 2013 reservation represents the only formal treaty-level exception for traditional coca leaf use. The dual scheduling of both [[glossary:plant-material]] and isolated alkaloid under the 1961 Convention is unusual among psychoactive plants — [[substance:psilocybin-mushrooms]], for example, escape explicit plant-level scheduling in many jurisdictions while the alkaloid itself is controlled. The 2025 WHO Expert Committee critical review recommended maintaining this classification while acknowledging the low public health risk of traditional consumption{{cite|url=https://www.who.int/news/item/10-12-2025-who-expert-committee-concludes-critical-review-of-coca-leaf--recommends-maintaining-current-controls|anchor=6dc5448c}}.
Coca leaf chewing and tea consumption produce positive immunoassay urine drug tests for benzoylecgonine, cocaine's primary [[glossary:metabolite|urinary metabolite]]. Standard workplace drug tests (100–300 ng/mL cutoff) detect metabolites for approximately 2–4 days after last use in most individuals. With sensitive [[glossary:assay|assays]] using a 5 ng/mL cutoff, [[glossary:detection]] windows extend to 17–22 days{{cite|doi=10.1002/dta.2153|anchor=e019b42b}}{{cite|pubmed=12422991|anchor=042e364b}}.
| Jurisdiction | Classification | Key provisions |
|---|---|---|
| International (UN) | Schedule I (1961 Single Convention) | Coca leaf and cocaine both Schedule I; 1988 Convention reinforces precursor controls |
| United States (federal) | Schedule II (Controlled Substances Act) | Cocaine HCl and coca leaf both Schedule II; Goprelto (2017) and Numbrino (2020) approved as topical nasal anesthetics{{cite|url=https://www.dea.gov/sites/default/files/2025-01/Cocaine-2024-Drug-Fact-Sheet.pdf|anchor=de35a8da}} |
| Bolivia | Legal for traditional use | 22,000 ha legally authorized cultivation; coca tea and chewing permitted; reacceded to 1961 Convention in 2013 with reservation for traditional use; actual cultivation ~34,000 ha in 2024{{cite|url=https://www.unodc.org/unodc/press/releases/2024/October/colombia_-potential-cocaine-production-increased-by-53-per-cent-in-2023--according-to-new-unodc-survey.html|anchor=44f8665f}} |
| Peru | Legal for traditional use | ~6 million traditional consumers; ~22,000 ha legal cultivation authorized by DEVIDA; coca tea, chewing, and certain food products legal |
| Colombia | Illegal (cultivation and trafficking) | Largest producing country (~253,000 ha, 61% of global cultivation in 2023); criminal penalties for cultivation and trafficking{{cite|url=https://www.unodc.org/unodc/press/releases/2024/October/colombia_-potential-cocaine-production-increased-by-53-per-cent-in-2023--according-to-new-unodc-survey.html|anchor=77e15fe4}} |
| Argentina | Legal for traditional use (coca leaf/tea) | Coca leaf and tea legal for cultural use in northern provinces; cocaine possession and sale illegal |
| United Kingdom | Class A (Misuse of Drugs Act 1971) | Maximum 7 years imprisonment for possession; life imprisonment for supply; coca leaf also controlled{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_cocaine|anchor=5d7d0e31}} |
| European Union | Schedule I equivalent (member state laws) | Cocaine controlled in all EU member states; second most commonly used illicit drug in Europe after cannabis |
| Australia | Schedule 8 (Poisons Standard) | Prescription-only with very limited medical use; ACT enacted partial decriminalization of small amounts in October 2023{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_cocaine|anchor=c4196f11}} |
The experiential character of coca preparations spans a remarkably wide phenomenological range determined almost entirely by preparation method. Traditional coca leaf chewing produces a subtle, sustained alertness with mild [[effect:pain-suppression|analgesia]] and [[effect:appetite-suppression]] — qualitatively closer to a strong cup of tea than to the intense [[effect:euphoria]] associated with refined [[substance:cocaine]]. Smoked and [[glossary:intravenous]] cocaine, by contrast, produce brief, intense euphoria followed by [[glossary:rapid-onset|rapid-onset]] [[effect:craving]] that drives compulsive [[glossary:redose|redosing]]. [[glossary:set-and-setting]] modulate the experience but play a secondary role relative to preparation-determined [[glossary:pharmacokinetics]].
Coca leaf chewing occupies a pharmacological position between [[substance:caffeine]] and low-dose [[substance:amphetamine]] in terms of [[substance_class:psychoactive/stimulant]] [[glossary:intensity]] and duration. Refined cocaine administered intranasally or by inhalation is more comparable to [[substance:methamphetamine]] in [[glossary:reinforcement]] [[glossary:potency]] and [[glossary:addiction]] trajectory, though with substantially shorter [[glossary:duration-of-action]] and a distinct cardiovascular risk profile.
===Toxicity===
No formal human [[glossary:lethal-dose|LD50]] for [[substance:cocaine]] is established. Cocaine [[glossary:intoxication]] is the most frequent cause of drug-related death reported by medical examiners in the United States{{cite|pubmed=20857618|anchor=e4c54825}}{{flag|additional-citations-needed}}. Lethal blood cocaine concentrations typically exceed 1 mg/L, though deaths have occurred at lower concentrations in the presence of cardiac predisposing conditions or co-ingested substances{{flag|safety-citation-needed}}.
====Cardiovascular toxicity====
Cardiovascular complications represent the most clinically significant [[glossary:toxicity]] of cocaine across all preparations{{cite|doi=10.1016/j.cjca.2022.05.003|anchor=81592b6f}}{{cite|doi=10.2165/00129784-200909030-00005|anchor=1ca4f484}}{{cite|doi=10.1002/clc.20746|anchor=c1ef7e3f}}:
* '''Myocardial infarction:''' Approximately 6% incidence in cocaine-associated chest pain presentations. Frequent cocaine users have a 7-fold higher risk of MI. Mechanisms include coronary artery vasospasm, accelerated atherosclerosis, thrombus formation, and QT prolongation via Na⁺ [[glossary:channel]] [[glossary:blockade]].
* '''Arrhythmias:''' Wide complex [[glossary:tachycardia]], ventricular fibrillation, and sudden cardiac death mediated by Na⁺ channel blockade and [[glossary:sympathomimetic]] catecholamine surge.
* '''Cardiomyopathy:''' Dilated cardiomyopathy, myocarditis, and left ventricular hypertrophy with [[glossary:chronic-use]].
* '''Vascular:''' Hypertensive crises, aortic dissection, aortic rupture, and cerebral hemorrhage.
{{Emergency}}Cocaine-associated chest pain should be evaluated as potential myocardial infarction. '''Beta-blockers are contraindicated''' — unopposed alpha-adrenergic [[effect:stimulation]] worsens [[effect:vasoconstriction]] and [[glossary:hypertension]]. First-line management: [[substance_class:chemical/benzodiazepine|benzodiazepines]] for [[glossary:agitation]], nitroglycerin or calcium channel blockers for ischemia, phentolamine for refractory hypertension.{{/Emergency}}
====Hepatotoxicity====
Norcocaine, the [[glossary:cyp3a4]]-generated N-demethylated [[glossary:metabolite]], is hepatotoxic. Documented pathology includes perivenular and midzonal coagulative necrosis and periportal microvesicular fatty change{{cite|pubmed=2328957|anchor=6c2932c4}}. Cocaine induces its own hepatic CYP [[glossary:metabolism]] with chronic dosing, potentially increasing norcocaine production over time{{cite|pubmed=8617431|anchor=ae2a9bdd}}. Multi-organ failure involving rhabdomyolysis (CPK >100,000 U/L), acute kidney injury, and hepatic ischemia has been documented as cocaine-induced C-KLM syndrome{{cite|doi=10.7759/cureus.50745|anchor=42b5dc50}}.
====Pulmonary toxicity====
Smoked cocaine carries preparation-specific pulmonary risk. "Crack lung" syndrome presents as acute respiratory [[glossary:distress]] with fever, hemoptysis, and dyspnea within 48 hours of inhalation, featuring diffuse alveolar hemorrhage, interstitial pneumonia, pulmonary edema, and eosinophilic infiltration{{cite|doi=10.1016/j.cbi.2013.10.011|anchor=a325df3c}}{{flag|additional-citations-needed}}.
====Neurological complications====
Both ischemic and hemorrhagic stroke are documented; cocaine is a recognized independent stroke risk factor. Reversible cerebral vasoconstriction syndrome (RCVS) has been reported following coca leaf tea consumption at high altitude{{cite|doi=10.1016/j.jstrokecerebrovasdis.2025.108506|anchor=d2373e99}}{{flag|additional-citations-needed}} — a rare but documented adverse event even from traditional preparations.
====Contaminant and adulterant risk====
Levamisole, a veterinary anthelmintic, contaminates an estimated 69–80% of illicit cocaine in the United States{{cite|doi=10.1097/MOH.0b013e32834da9ef|anchor=52c70bf3}}{{cite|doi=10.3122/jabfm.2012.04.110177|anchor=465d2170}}. Clinical consequences include:
* '''Agranulocytosis''' (absolute neutrophil count approaching zero) with life-threatening secondary infections — first described in 2009
* '''ANCA-associated vasculitis''' with cutaneous involvement
* '''Multifocal leukoencephalopathy'''
* '''Acquired protein S deficiency'''
Additional adulterants include local anesthetics (procaine, benzocaine, lidocaine) and, increasingly, [[substance:fentanyl]] — which introduces opioid overdose risk toxicologically distinct from cocaine effects. Coca leaf products sold in commerce (primarily in Andean countries) carry lower adulterant risk than illicit refined cocaine, but no ISO/IEC-accredited third-party testing programs for commercial coca leaf products have been identified{{flag|citation-needed}}.
===Psychological risks===
====Cocaine-induced psychosis====
Cocaine-induced [[glossary:psychosis]] (CIP) is characterized by paranoid [[effect:delusions]], visual and [[effect:auditory-hallucinations]], and [[effect:paranoia]]. Prevalence reaches as high as 86.5% in some clinical populations{{cite|doi=10.1080/08897077.2014.933726|anchor=6197b27d}}. Risk factors include high cumulative dose, lifetime duration of use, smoked or [[glossary:intravenous]] route, [[substance:cannabis]] [[glossary:polydrug|co-use]], ADHD comorbidity, and male sex{{cite|doi=10.1080/08897077.2014.933726|anchor=8fceb13f}}. Sensitization rather than [[glossary:tolerance]] occurs for psychosis risk — repeated cocaine exposure progressively lowers the threshold for psychotic symptoms.
====Acute psychological effects====
[[effect:anxiety]], paranoia, panic reactions, and agitation occur dose-dependently across all preparations. Grandiosity, impaired judgment, and risk-taking behavior are characteristic at higher doses. Compulsive [[glossary:redose|redosing]] driven by rapid offset of [[effect:euphoria]] — particularly with smoked and intravenous preparations — is a defining feature of cocaine's abuse pattern.
===Tolerance and dependence===
'''Tolerance''' develops rapidly to the euphoriant effects of cocaine with repeated dosing. Paradoxically, '''sensitization''' — not tolerance — occurs for stereotypy and psychosis risk with prolonged use. This differential neuroadaptation underlies the escalating psychiatric risk seen in chronic cocaine use [[glossary:disorder]].
'''Dependence''' is primarily psychological. Cocaine produces strong [[effect:craving|cravings]] and compulsive use driven by [[glossary:mesolimbic-pathway|mesolimbic dopamine]] [[glossary:reinforcement]]. Physical dependence is present but less prominent than with [[substance_class:psychoactive/opioid|opioids]] or [[substance:alcohol]].
'''Withdrawal''' follows a three-phase pattern{{cite|doi=10.1016/j.neubiorev.2025.106278|anchor=5857c89f}}{{flag|additional-citations-needed}}:
* '''Phase 1 — Crash (hours to 4 days):''' [[effect:dysphoria]], [[glossary:fatigue]], hypersomnia (increased total sleep time and REM rebound effect), [[effect:appetite-enhancement]], temporarily reduced cocaine craving.
* '''Phase 2 — Withdrawal (1–10 weeks):''' [[effect:anhedonia]], anxiety, sleep disturbance, fatigue, intense cue-triggered cravings; highest relapse risk period.
* '''Phase 3 — Extinction (months to years):''' Gradual functional normalization; intermittent cue-triggered cravings persist for months. Sleep architecture normalizes with high inter-subject variability{{cite|doi=10.1016/j.neubiorev.2025.106278|anchor=b3a34ae3}}{{flag|additional-citations-needed}}.
{{Recovery}}No FDA-approved pharmacotherapy for cocaine use disorder exists as of 2026{{cite|doi=10.1177/02698811251399593|anchor=be31cbdb}}{{flag|additional-citations-needed}}. Current evidence supports cognitive behavioral therapy, contingency management, and treatment of comorbid psychiatric conditions. Suvorexant (dual orexin [[glossary:receptor]] antagonist) is under investigation for early [[glossary:withdrawal]] sleep disturbances.{{/Recovery}}
===Drug interactions===
'''Ethanol (alcohol):''' The most clinically significant interaction. Hepatic CES1 and CYP3A4 catalyze transesterification of cocaine with ethanol to form cocaethylene, a metabolite that is more toxic than cocaine, has a longer duration of action, and amplifies cardiovascular risk{{cite|doi=10.1037/a0022950|anchor=25658998}}{{cite|doi=10.1016/j.toxrep.2022.08.001|anchor=a1c35ffe}}{{cite|doi=10.1016/j.cbi.2026.112088|anchor=512e526a}}. Cocaethylene yield varies by cocaine route: oral (34%) > intravenous (24%) > smoked (18%){{cite|doi=10.1037/a0022950|anchor=fda78113}}.
'''Beta-adrenergic blockers:''' Contraindicated. Cocaine's alpha-adrenergic [[glossary:agonist]] effects become unopposed when beta receptors are blocked, producing severe hypertension and coronary vasospasm. This is a well-established clinical [[glossary:contraindication]].
'''MAO inhibitors:''' Theoretical risk of hypertensive crisis via amplified norepinephrine effect; [[glossary:serotonin-syndrome]] risk with combined serotonergic activity. {{flag|safety-citation-needed}} No specific clinical [[glossary:case-report|case reports]] of cocaine–MAOI interaction were identified; [[glossary:severity]] assessment is based on pharmacological mechanism only.
'''CYP3A4 inhibitors''' (ketoconazole, clarithromycin, ritonavir): [[glossary:inhibition]] of CYP3A4 would reduce norcocaine formation while potentially increasing parent cocaine [[glossary:plasma-concentration|plasma levels]] by reducing [[glossary:clearance]]{{cite|pubmed=8488174|anchor=19489d33}}{{flag|additional-citations-needed}}. {{flag|safety-citation-needed}} No formal pharmacokinetic interaction study has been published.
'''Tricyclic antidepressants:''' Additive cardiovascular toxicity via combined Na⁺ channel blockade and [[substance_class:pharmacological/norepinephrine-reuptake-inhibitor]]. {{flag|safety-citation-needed}} Evidence is based on pharmacological mechanism; no controlled clinical study was retrieved.
===Contraindications===
'''Pregnancy:''' Absolute contraindication. Cocaine use in [[glossary:pregnancy]] is associated with increased placental abruption risk, adverse neonatal outcomes, and fetal [[glossary:central-nervous-system|CNS]] development effects{{cite|doi=10.1186/s12884-024-07062-1|anchor=3cfda78c}}{{flag|additional-citations-needed}}.
'''Cardiovascular disease:''' Absolute contraindication for all preparations. Pre-existing cardiac conditions dramatically elevate the risk of myocardial infarction and sudden death{{cite|doi=10.1016/j.cjca.2022.05.003|anchor=b251b1af}}{{flag|additional-citations-needed}}.
'''Hepatic impairment:''' Relative contraindication. Impaired cocaine and norcocaine metabolism increases toxicity duration and severity.
'''Concurrent beta-blocker therapy:''' Absolute contraindication for cocaine use — unopposed alpha stimulation produces severe hypertension and coronary vasospasm.
'''Concurrent MAOI or tricyclic antidepressant therapy:''' Relative contraindication due to additive cardiovascular and serotonergic risk.
'''Psychiatric vulnerability:''' Relative contraindication. Schizophrenia spectrum disorders and psychosis risk are amplified by cocaine use{{cite|doi=10.1080/08897077.2014.933726|anchor=aea08c2f}}{{flag|additional-citations-needed}}.
'''Pediatric and neonatal exposure:''' Prenatal cocaine exposure is associated with functional brain connectivity alterations in neonates{{cite|doi=10.1186/s12884-024-07062-1|anchor=df3b842f}}{{flag|additional-citations-needed}}.
Coca leaf and its primary alkaloid, [[substance:cocaine]], are controlled under international treaty and national legislation across virtually all jurisdictions. The 1961 UN Single Convention on Narcotic Drugs places both coca leaf and cocaine on [[glossary:schedule-i]] — the strictest tier, requiring limitation of production, trade, use, and [[glossary:possession]] to medical and scientific purposes. The 1988 UN Convention Against Illicit Traffic in Narcotic Drugs reinforces controls on cocaine precursors. The 2025 WHO Expert Committee on Drug Dependence critical review recommended maintaining Schedule I classification, while acknowledging the low public health risk of traditional coca leaf consumption{{cite|url=https://www.who.int/news/item/10-12-2025-who-expert-committee-concludes-critical-review-of-coca-leaf--recommends-maintaining-current-controls|anchor=be8d7eb6}}.
===Treaty considerations===
Unlike some psychoactive plants where the plant itself escapes international scheduling while its alkaloids are controlled (e.g., psilocybin-containing mushrooms in some jurisdictions), coca leaf is ''explicitly'' scheduled under the 1961 Single Convention alongside cocaine. This dual scheduling means that both raw coca leaf and refined cocaine are [[glossary:international-control|internationally controlled]] substances. Bolivia's 2013 reservation represents the only formal treaty-level exception for traditional coca leaf use.
===Detection===
Coca leaf chewing and tea consumption produce positive immunoassay urine drug tests for benzoylecgonine, cocaine's primary [[glossary:metabolite|urinary metabolite]]. In chronic cocaine users, mean time to first negative specimen (benzoylecgonine equivalents <300 ng/mL) is 43.6 ± 17.1 hours after cessation{{cite|pubmed=12422991|anchor=37a08e37}}. With sensitive [[glossary:assay|assays]] using a 5 ng/mL cutoff, [[glossary:detection]] windows extend to 17–22 days{{cite|doi=10.1002/dta.2153|anchor=4f06338a}}. Standard workplace drug tests (100–300 ng/mL cutoff) detect cocaine metabolites for approximately 2–4 days after last use in most individuals.
| Jurisdiction | Classification | Key provisions |
|---|---|---|
| International (UN) | Schedule I (1961 Single Convention) | Coca leaf and cocaine both Schedule I; Article 49 originally permitted traditional chewing temporarily; 1988 Convention reinforces precursor controls |
| United States (federal) | Schedule II (Controlled Substances Act) | Cocaine HCl and coca leaf both Schedule II; narrow accepted medical use — Goprelto (2017) and Numbrino (2020) approved as topical nasal anesthetics for adult ENT procedures{{cite|url=https://www.dea.gov/sites/default/files/2025-01/Cocaine-2024-Drug-Fact-Sheet.pdf|anchor=d89360cc}} |
| Bolivia | Legal for traditional use | 22,000 ha legally authorized cultivation; coca tea and chewing permitted; reacceded to 1961 Convention in 2013 with explicit reservation for traditional chewing; actual cultivation ~34,000 ha in 2024{{cite|url=https://www.unodc.org/unodc/press/releases/2024/October/colombia_-potential-cocaine-production-increased-by-53-per-cent-in-2023--according-to-new-unodc-survey.html|anchor=1ade87c6}} |
| Peru | Legal for traditional use | ~6 million traditional consumers; ~22,000 ha legal cultivation zone authorized by DEVIDA; coca tea, chewing, and certain food products legal; cocaine export prohibited |
| Colombia | Illegal (cultivation and trafficking) | Largest producing country (~253,000 ha, 61% of global cultivation in 2023); coca cultivation and cocaine production/trafficking carry criminal penalties{{cite|url=https://www.unodc.org/unodc/press/releases/2024/October/colombia_-potential-cocaine-production-increased-by-53-per-cent-in-2023--according-to-new-unodc-survey.html|anchor=d648dbd0}} |
| Argentina | Legal for traditional use (coca leaf/tea) | Coca leaf and tea legal for cultural and traditional use in northern provinces; cocaine possession and sale illegal |
| United Kingdom | Class A (Misuse of Drugs Act 1971) | Maximum 7 years imprisonment + unlimited fine for possession; life imprisonment for supply; coca leaf also controlled{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_cocaine|anchor=e0d07ff1}} |
| European Union | Schedule I equivalent (member state laws) | Cocaine controlled in all EU member states; no legalization exceptions; EUDA reports cocaine as second most commonly used illicit drug in Europe after cannabis |
| Australia | Schedule 8 (Poisons Standard) | Prescription-only with very limited medical use; illegal to possess otherwise; ACT enacted partial decriminalization of small amounts including cocaine in October 2023{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_cocaine|anchor=50715cea}} |
Evidence Changes39 added
+Restrepo DA, Saenz E, Jara-Muñoz OA, Calixto-Botía IF, Rodríguez-Suárez S, Zuleta P, Chavez BG, Sanchez JA, D'Auria JC 2019— Erythroxylum in Focus: An Interdisciplinary Review of an Overlooked Genus
+Tsuchiya H 2017— Anesthetic Agents of Plant Origin: A Review of Phytochemicals with Anesthetic Activity
+World Health Organization 2025— WHO Expert Committee concludes critical review of coca leaf, recommends maintaining current controls (December 2025)
+Heal DJ, Gosden J, Smith SL 2014— Dopamine reuptake transporter (DAT) 'inverse agonism' — a novel hypothesis to explain the enigmatic pharmacology of cocaine
+Phillips K, Luk A, Soor GS, Abraham JR, Leong S, Butany J 2009— Cocaine cardiotoxicity: a review of the pathophysiology, pathology, and treatment options
+Barnett G, Hawks R, Resnick R 1981— Cocaine pharmacokinetics in humans
+Coe MA, Jufer Phipps RA, Cone EJ, Walsh SL 2018— Bioavailability and Pharmacokinetics of Oral Cocaine in Humans
+Medigue I, Catoire S, Peyron C et al. 2025— Longitudinal disturbances of objective sleep architecture in cocaine use disorder: A translational systematic review
+Buchanan JA, Lavonas EJ 2012— Agranulocytosis and other consequences due to use of illicit cocaine contaminated with levamisole
+Sinclair JM, Kalk NJ, Kaar SJ, et al. 2026— Evidence-based consensus guidelines for the pharmacological management of substance dependence: Recommendations from the British Association for Psychopharmacology
+Bauer I 2019— Travel medicine, coca and cocaine: demystifying and rehabilitating Erythroxylum – a comprehensive review
+Lv Y, Tian T, Wang YJ, Huang JP, Huang SX 2022— Advances in chemistry and bioactivity of the genus Erythroxylum
+Johnson EL, Zhang D, Emche SD 2005— Inter- and intra-specific variation among five Erythroxylum taxa assessed by AFLP
+White DM, Islam MB, Mason-Gamer RJ 2019— Phylogenetic inference in section Archerythroxylum informs taxonomy, biogeography, and the domestication of coca (Erythroxylum species)
+United Nations Office on Drugs and Crime 2024— Colombia: Potential cocaine production increased by 53% in 2023 — UNODC
+Schmidt GW, Jirschitzka J, Porta T, Reichelt M, Luck K, Torre JC, Dolke F, Varesio E, Hopfgartner G, Gershenzon J, D'Auria JC 2015— The last step in cocaine biosynthesis is catalyzed by a BAHD acyltransferase
+LeDuc BW, Sinclair PR, Shuster L, Sinclair JF, Evans JE, Greenblatt DJ 1993— Norcocaine and N-hydroxynorcocaine formation in human liver microsomes: role of cytochrome P-450 3A4
+Cone EJ, Oyler J, Darwin WD 1997— Cocaine disposition in saliva following intravenous, intranasal, and smoked administration
+Pellinen P, Stenbäck F, Kojo A, Honkakoski P, Gelboin HV, Pasanen M 1996— Regenerative changes in hepatic morphology and enhanced expression of CYP2B10 and CYP3A during daily administration of cocaine
+Vergara MJ, Cordero Escalona J, Veloso Casado V 2025— Cocaine-induced oronasal communication of the midline of the palate: A case report
+Samaha AN, Robinson TE 2005— Why does the rapid delivery of drugs to the brain promote addiction?
+Roncero C, Daigre C, et al. 2014— An international perspective and review of cocaine-induced psychosis
+Mégarbane B, Chevillard L 2013— The large spectrum of pulmonary complications following illicit drug use: features and mechanisms
+Lippi G, Plebani M, Cervellin G 2010— Cocaine in acute myocardial infarction
+Kanel GC, Cassidy W, Shuster L, Reynolds TB 1990— Cocaine-induced liver cell injury: comparison of morphological features in man and in experimental models
+Kwentoh I, Daniel S, Atiku ES 2023— Cocaine-Induced Kidney, Liver, Lung, and Muscle Injury (C-KLM), Presenting With Foot Drop: A Case Report
+Del Brutto OH, Guzmán EJ, Caputi R, Rumbea DA, Del Brutto VJ 2025— Reversible cerebral vasoconstriction syndrome presenting as thunderclap headache following high-altitude exposure and coca leaf tea consumption
+Herbst ED, Harris DS, Everhart ET, Mendelson J, Jacob P, Jones RT 2011— Cocaethylene formation following ethanol and cocaine administration by different routes
+Shang L, Zheng X, Zhang T, Deng J, Zhan CG, Zheng F 2022— Effects of alcohol on metabolism and toxicity of cocaine in rats
+Li Z, Hu Q, Deng X et al. 2026— Substrate specificity and in vivo efficacy of engineered cocaine esterases toward cocaine and its toxic metabolites
+Kandhasamy S, Lepigeon K, Baggio S et al. 2025— Risk of adverse obstetrical and neonatal outcomes in women consuming recreational drugs during pregnancy
+Nickley J, Pesce AJ, Krock K 2017— A sensitive assay for urinary cocaine metabolite benzoylecgonine shows more positive results and longer half-lives than those using traditional cut-offs
+Preston KL, Epstein DH, Cone EJ, Wtsadik AT, Huestis MA, Moolchan ET 2002— Urinary elimination of cocaine metabolites in chronic cocaine users during cessation
+Wikipedia; UK Parliament; EUDA; Australian Police 2024— Legal status of cocaine — UK, EU, Australia
Data Field Changes1 changed · 15 unchanged
| Field | r1 | r2 | |
|---|---|---|---|
| Summary | (empty) | → | Coca is a stimulant plant of the family Erythroxylaceae, native to the western Andes, containing the tropane alkaloid cocaine. Preparations range from traditional leaf chewing and tea to refined cocaine hydrochloride; effects and risk vary dramatically by preparation method. |
Effects Profile Changes47 added
Added (47)
Taste suppressionperception
0.400.60
Appetite suppressionbody
0.700.70
Body highbody
0.400.50
Bruxismbody
0.300.30
Dry mouthbody
0.500.60
Excessive sweatingbody
0.400.40
Heart rate perception changesbody
0.500.60
Insomniabody
0.500.50
Motor control enhancementbody
0.400.50
Muscle tensionbody
0.400.50
Nauseabody
0.400.40
Nausea suppressionbody
0.400.40
Pain suppressionbody
0.600.70
Pupil dilationbody
0.500.60
Respiratory stimulationbody
0.300.40
Restlessnessbody
0.400.50
Salivationbody
0.400.50
Sexual arousal enhancementbody
0.400.40
Stimulationbody
0.800.90
Tingling / electric sensationsbody
0.500.70
Vasoconstrictionbody
0.600.80
Vomitingbody
0.300.20
Wakefulnessbody
0.700.80
Analysis enhancementthinking
0.500.60
Cognitive euphoriathinking
0.600.70
Cognitive flexibilitythinking
0.400.50
Compulsive redosing urgethinking
0.500.50
Creativity enhancementthinking
0.400.40
Focus enhancementthinking
0.700.80
Information processing enhancementthinking
0.600.70
Language enhancementthinking
0.400.50
Memory enhancementthinking
0.400.50
Motivation enhancementthinking
0.600.70
Thought accelerationthinking
0.500.70
Anxietyfeeling
0.500.50
Euphoriafeeling
0.700.80
Irritabilityfeeling
0.400.40
Paranoiafeeling
0.400.30
Communication enhancementself
0.500.60
Cravingself
0.600.60
Disinhibitionself
0.400.50
Ego inflationself
0.400.40
Flow stateself
0.400.40
Sociability enhancementself
0.600.60
Social connectionself
0.500.50
Time alterationtime
0.400.40
Sustained attention (vicara)awareness
0.500.50