Cocaine
Cocaine is a tropane alkaloid stimulant derived from the leaves of coca plants native to South America.1 It has a long history of medical use as a topical anesthetic owing to its intrinsic vasoconstrictor properties2, though its high abuse potential3 has largely supplanted this role. Cocaine functions as a serotonin–norepinephrine–dopamine reuptake inhibitor1, producing euphoria and heightened alertness.1 It is notably cardiotoxic4 and carries a significant potential for compulsive redosing1 and addiction.1
Contents
Dosage & Duration
Dosage
Insufflation produces rapid onset of effects. Actual doses absorbed can vary considerably depending on the purity of the material.
Duration
Subjective Effects
Effects vary widely by individual, dose, and context.
Physical
The physical effects of cocaine can be broken down into several components which progressively intensify proportional to dosage.
Cognitive
The cognitive effects of cocaine can be broken down into several components which progressively intensify proportional to dosage. The general head space of cocaine is described by many as one of extreme mental stimulation, increased focus, and powerful euphoria. It contains a large number of typical stimulant cognitive effects. Although negative side effects are usually mild at low to moderate dosages, they become increasingly likely to manifest themselves with higher amounts or extended usage. This particularly holds true during the offset of the experience.
Reagent Testing
Loading reagent data
Pharmacology
Pharmacodynamics
Cocaine acts primarily as a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI), blocking the dopamine, serotonin, and norepinephrine transporters to prevent monoamine reuptake into presynaptic neurons.1 In rat models, uptake inhibition potency is greatest for norepinephrine, followed by dopamine and then serotonin.5 Its action at the dopamine transporter, where it stabilizes the transporter in an outward-facing conformation, is considered most responsible for its reinforcing properties.6 Cocaine also reversibly binds to and inactivates voltage-gated sodium channels, producing local anesthetic effects, while its norepinephrine reuptake blockade results in vasoconstriction.1 Additional targets include the 5-HT3 receptor (as an antagonist), sigma-1 receptor (as an agonist), κ-opioid receptor, and muscarinic M1 and M2 acetylcholine receptors (as antagonists), while the 5-HT2A, 5-HT2B, and 5-HT2C receptors have also been implicated in its locomotor-activating effects.1
Pharmacokinetics
Cocaine is absorbed from all sites of application, including mucous membranes and gastrointestinal mucosa, with oral and intranasal bioavailability of approximately 60 to 80%.78 It has a short elimination half-life of 0.7 to 1.5 hours and is extensively metabolized by plasma esterases and liver cholinesterases, with only about 1% excreted unchanged in urine.17 The primary metabolite is benzoylecgonine.7 In the presence of alcohol, the additional active metabolite cocaethylene is formed.1
Dangerous
Highest riskThese combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.
Unsafe
AvoidThere is considerable risk of physical harm when taking these combinations, they should be avoided where possible.
Caution
Use cautionThese combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Tolerance
Other stimulants (amphetamines, though cocaine may partially block amphetamine's dopaminergic effects)
Harm Potential
Addiction & Dependence
Psychological
HighCocaine has a high potential for psychological addiction and compulsive redosing. Its effect on dopamine levels is primarily responsible for its addictive properties.9 Craving can be triggered rapidly by environmental cues, situations, or memories associated with use.9 Tolerance can develop after a single dose, and repeated use frequently leads to addiction and prolonged craving.
Physical
ModeratePhysical dependence develops after even brief periods of regular use. Withdrawal symptoms include disrupted sleep, irritability, depression, fatigue, increased appetite, and reduced ability to experience pleasure.10 While uncomfortable, cocaine withdrawal is not life-threatening.11 Depressive withdrawal symptoms are associated with worse treatment outcomes and increased risk of relapse.10
Toxicity
Chronic intranasal use causes progressive damage to nasal mucosa, septum, and surrounding structures; approximately 30% of regular users and 47% of daily users experience nasal irritation, crusting, and frequent nosebleeds.17 Severe cases progress to cocaine-induced midline destructive lesions with erosion of the palate and sinuses.18
Acute hepatotoxicity can occur with overdose, typically due to toxic metabolites; most cases resolve quickly but fatal outcomes from multiple organ dysfunction are possible.20
Renal impairment can occur as part of cocaine toxicity syndrome, particularly in overdose situations involving rhabdomyolysis and hyperthermia.21
Rhabdomyolysis can occur with acute cocaine toxicity, particularly at high doses or during prolonged physical activity while intoxicated.22
Chronic use is associated with general weakening of immune function. Levamisole-adulterated cocaine causes severe agranulocytosis in a subset of users, with skin necrosis affecting the ears, face, and extremities.23
Psychosis Risk
More than half of people who abuse cocaine report experiencing psychotic symptoms at some point.24 Typical symptoms include paranoid delusions of being followed or watched, accompanied by supporting hallucinations.24 Delusional parasitosis with formication, commonly called 'cocaine bugs,' is a fairly common symptom.25 Cocaine-induced psychosis shows sensitization, meaning psychosis becomes more severe with repeated intermittent use.24
Seizure Risk
Cocaine can cause convulsions and reduces seizure threshold.11 Seizures are more commonly associated with overdose situations and high doses but can occur with acute exposure.21 Overdose may cause seizures alongside abnormally high body temperature and marked blood pressure elevation.11
History & Culture
Traditional Use and Etymology
Coca chewing dates back at least 8,000 years in South America, making it one of the oldest known psychoactive plant practices.26 The leaves were integral to Andean civilizations including the ancient Wari and Inca cultures, where they served both stimulant and…
Legality
International
UN Single Convention on Narcotic Drugs 1961: scheduled
By Country
References
Source Pages
Citations
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- (2020). Clinical Pharmacology Review: Numbrino (Cocaine Hydrochloride) Nasal Solution, NDA 209575. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/209575Orig1s000ClinPharmR.pdf1
- (2022). GOPRELTO (cocaine hydrochloride) nasal solution prescribing information. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/209963s004lbl.pdf1
- Joseph V. Pergolizzi Jr., Peter Magnusson, Jo Ann K. LeQuang, Frank Breve, & Giustino Varrassi. (2021). Cocaine and Cardiotoxicity: A Literature Review. Cureus, 13(4), Article e14594. https://doi.org/10.7759/cureus.145941
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- Volkow ND, Wang GJ, Telang F, Fowler JS, Logan J, Childress AR, Jayne M, Ma Y, & Wong C. (2006). Cocaine Cues and Dopamine in Dorsal Striatum: Mechanism of Craving in Cocaine Addiction. Journal of Neuroscience, 26(24), 6583-6588. https://doi.org/10.1523/jneurosci.1544-06.200612
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- (2022). Cocaine bugs: A brief case report of cocaine-induced delusion of parasitosis. https://pmc.ncbi.nlm.nih.gov/articles/PMC9479874/1
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