Cocaine

methyl (1R,2R,3S,5S)-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate

Overview

Cocaine belongs to Stimulants.

Key safety note: Cocaine carries a high risk of acute cardiovascular events, myocardial infarction, arrhythmia, hypertensive crisis, stroke and sudden death, that is not reliably dose-dependent and can occur even in first-time or occasional users.[3][4]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • Euphoria, increased energy, alertness, confidence and sociability, with reduced appetite and need for sleep.
  • Sympathomimetic effects, raised heart rate and blood pressure, dilated pupils, sweating and raised body temperature, alongside anxiety, restlessness and, at higher doses, paranoia.
  • The effect is short-lived (minutes when smoked or injected, up to ~1–1.5 h insufflated), driving repeated dosing. A 'crash' of fatigue, low mood and craving follows heavier use.
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Insufflated (snorted), smoked as freebase ('crack'), oral or intravenous. Medical use is topical only, as an ENT local anaesthetic. The figures below are commonly cited recreational reference ranges for the insufflated route, not a recommendation or a 'safe' dose. Street purity and adulterants (e.g. levamisole, and increasingly fentanyl) vary enormously, and the short, intense effect strongly drives compulsive redosing. Cardiovascular risk is not reliably dose-dependent and rises further with redosing and with alcohol. Smoked and intravenous use act within seconds and carry higher dependence and overdose risk.

Dose ranges

Threshold

5 mg

Light

10–30 mg

Common

30–60 mg

Strong

60–90 mg

Heavy

90 mg +

Duration

onset

3–10 minutes (insufflated, seconds if smoked or IV)

total

10–90 minutes (insufflated)

after effects

Fatigue, low mood and craving ('crash'). Compulsive redosing

Chemical & Physical Properties
FormulaC17H21NO4
Molar mass303.35 g/mol
StateSolid
Melting point98 °C
Boiling point187 °C at 0.1 mmHg
DensityNot reported
Vapor pressure1.9×10⁻⁷ mmHg
pKa8.7
LogP2.3
Solubility1800 mg/L (at 22 °C), Crystals. Mp 58–63 °C. Freely soluble in water or alcohol, slightly soluble in ether (cocaine nitrate dihydrate)., White, granular, crystalline powder. Soluble in water or alcohol (cocaine sulfate).
Refractive index1.5022 at 98 °C
Identifiers & Synonyms
CAS50-36-2
CAS (enantiomer)
PubChem CID446220
InChIKeyZPUCINDJVBIVPJ-LJISPDSOSA-N
InChIInChI=1S/C17H21NO4/c1-18-12-8-9-13(18)15(17(20)21-2)14(10-12)22-16(19)11-6-4-3-5-7-11/h3-7,12-15H,8-10H2,1-2H3/t12-,13+,14-,15+/m0/s1
SMILESCOC(=O)[C@@H]1C2CCC(C[C@@H]1OC(=O)c1ccccc1)N2C

Synonyms

  • Benzoylmethylecgonine
  • Coke
  • Crack (freebase)
  • Methylbenzoylecgonine
  • Blow
  • Snow
  • Charlie
Pharmacodynamics & Biochemistry

Cocaine is a short-acting stimulant and local anaesthetic. Its stimulant effects come from blocking the dopamine (DAT), norepinephrine (NET) and serotonin (SERT) transporters, so released monoamines accumulate in the synapse. The resulting rise in dopamine in the mesolimbic reward pathway drives the euphoria and the strong addictive potential. Increased noradrenergic tone produces the sympathomimetic effects, tachycardia, hypertension, vasoconstriction, mydriasis and hyperthermia, that underlie its cardiovascular toxicity. Independently of monoamine reuptake, cocaine blocks voltage-gated (including cardiac) sodium channels. This is the basis of its local-anaesthetic action and contributes to cardiac conduction disturbances and arrhythmia in overdose.

Biological targets

  • DAT
  • NET
  • SERT

Binding & functional measurements

TargetMeasurementSpecies
5-HT3ApKi 5.25Human
Dopamine transporterKi 494 ± 37 nMHuman
Dopamine transporterKi 490 ± 40 nMMouse
Noradrenaline transporterKi 1,910 ± 230 nMHuman
Noradrenaline transporterKi 460 ± 60 nMMouse
Serotonin transporterKi 617 ± 45 nMHuman
Serotonin transporterKi 730 ± 120 nMMouse
Pharmacokinetics
BioavailabilityIntranasal ≈60–80%, smoked ≈70%, oral low
TmaxIntranasal ≈30–60 min, smoked ≈minutes
Half-life≈0.7–1.5 h
VdNot reported
Protein bindingNot reported
MetabolismPlasma/hepatic esterases to benzoylecgonine and ecgonine methyl ester
ExcretionRenal. Benzoylecgonine detectable for days
Toxicology & Safety
Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

Not reported

Cocaine carries a high risk of acute cardiovascular events, myocardial infarction, arrhythmia, hypertensive crisis, stroke and sudden death, that is not reliably dose-dependent and can occur even in first-time or occasional users. Its short, intense effect strongly drives compulsive redosing and a high addiction potential. Risk is compounded by unpredictable purity and adulterants (e.g. levamisole, and increasingly fentanyl), by co-use with alcohol (which forms the more cardiotoxic cocaethylene) and with opioids.[3][4]

Legal Status
Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
Interactions & Contraindications

Drug interactions

Stimulants (amphetamines, cocaine) Additive cardiovascular toxicity with other sympathomimetics (amphetamines, cathinones): hypertension, arrhythmia, hyperthermia.[3]
Alcohol Co-metabolism forms cocaethylene, a longer-lived, more cardiotoxic compound linked to a higher risk of sudden death.[4][5]
MAOIs, Other serotonergic drugs Risk of hypertensive crisis and serotonin toxicity.[3]
Non-selective beta-blockers Non-selective beta-blockade can cause unopposed alpha-adrenergic vasoconstriction, worsening hypertension and coronary spasm.[3][4]

Contraindications

Cardiovascular disease, hypertension or arrhythmia coronary artery disease, uncontrolled hypertension or significant arrhythmia.[3][4]
Pregnancy or breastfeeding associated with placental abruption and fetal harm.[4]
Concurrent MAOI, SSRI/SNRI or other serotonergic medication concurrent MAOI use.[3]
Usage & Context
  • Widely used recreationally as a short-acting stimulant, insufflated ('snorted'), smoked as freebase ('crack'), or injected, for euphoria, energy and increased confidence.
  • Retains a narrow legitimate medical use as a topical local anaesthetic and vasoconstrictor, chiefly for ear-nose-throat procedures.
  • One of the most commonly used illicit stimulants worldwide and a major driver of drug-related cardiovascular emergencies and dependence.
Sources & Evidence
  1. PubChem: Cocaine (CID 446220) — identifiers & computed properties
  2. FDA / DailyMed: Cocaine prescribing information — pharmacokinetics & metabolism
  3. Richards JR, Patel P, Laurin EG. Cocaine. StatPearls [Internet] (NCBI Bookshelf, NBK430769) — pharmacology, medical use, toxicity & management
  4. Goldstein RA, DesLauriers C, Burda AM (2009). Cocaine: history, social implications, and toxicity--a review. Dis Mon 55:6-38.

    PMID 19081448 · doi:10.1016/j.disamonth.2008.10.002

  5. Wikipedia: Cocaine (pharmacology, pharmacokinetics, effects & legal status) CC BY-SA 4.0
  6. IUPHAR/BPS Guide to PHARMACOLOGY: cocaine (ligand 2286) — monoamine transporter & 5-HT3 binding data CC BY-SA 4.0
  7. PsychonautWiki: Cocaine — recreational dosage & duration CC BY-SA 4.0
  8. DEA Diversion Control Division: Controlled Substance Schedules (cocaine is Schedule II)
  9. Anlage III BtMG — Betäubungsmittelgesetz (cocaine listing)
  10. Hope AG, Peters JA, Brown AM, et al. (1996). Characterization of a human 5-hydroxytryptamine3 receptor type A (h5-HT3R-AS) subunit stably expressed in HEK 293 cells. Br J Pharmacol 118:1237-45.

    PMID 8818349 · doi:10.1111/j.1476-5381.1996.tb15529.x

  11. Brady CA, Stanford IM, Ali I, et al. (2001). Pharmacological comparison of human homomeric 5-HT3A receptors versus heteromeric 5-HT3A/3B receptors. Neuropharmacology 41:282-4.

    PMID 11489465 · doi:10.1016/s0028-3908(01)00074-0

  12. Simmler LD, Buser TA, Donzelli M, et al. (2013). Pharmacological characterization of designer cathinones in vitro. Br J Pharmacol 168:458-70.

    PMID 22897747 · doi:10.1111/j.1476-5381.2012.02145.x

  13. Eshleman AJ, Wolfrum KM, Reed JF, et al. (2017). Structure-Activity Relationships of Substituted Cathinones, with Transporter Binding, Uptake, and Release. J Pharmacol Exp Ther 360:33-47.

    PMID 27799294 · doi:10.1124/jpet.116.236349

  14. Han DD, Gu HH (2006). Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs. BMC Pharmacol 6:6.

    PMID 16515684 · doi:10.1186/1471-2210-6-6

Further Information