Cocaine

Cocaine is a tropane alkaloid derived from the coca plant (Erythroxylum coca), native to the Andes mountains of South America. The coca leaf has been used medicinally in South America for improved fertility, prolongation of virility into old age, prevention of altitude sickness, and various other purposes.

Cocaine
Formula	C₁₇H₂₁NO₄
Type	Tropane alkaloid; local anesthetic; CNS stimulant (dopamine/norepinephrine reuptake inhibitor)
Administration	Insufflation (nasal), smoked (crack), IV injection, oral (coca leaf chewing), topical (medical)
Solubility	Hydrochloride salt: freely soluble in water; freebase (crack): insoluble in water, soluble in lipids
Legal status	Schedule II (US), medical use permitted; illegal for recreational use in most countries
Synonyms	Benzoylmethylecgonine, coke, crack (freebase form), coca, blow, white girl, goey
Bioavailability	Oral: ~33%; Insufflated: ~60-80%; Smoked: ~70%; IV: 100%
Recommended dose
Upper limit
LD50
Ray's verdict	Depends on context Blames malnutrition for coke babies

Weston Price described how the natives of the Andes used coca leaves: they could increase the quantity of the drug used to a point at which they are quite unconscious of pain and able to endure injuries without suffering and operations without discomfort.

In the 19th century in the U.S., cocaine was officially recognized as a therapy for asthma. The popular perception in America was that morphine was "unamerican" because it made you lazy and tired while cocaine was positively American because it increased alertness and efficiency which were much prized qualities in the time of industrialization.

Dosing

Route	Lethal Threshold
IV	As little as 20 mg reported fatal
Oral	Average lethal dose ~`500 mg`
Rat teratogenic threshold	50 mg/kg IP (no effect at 40 mg/kg); 80 mg/kg lethal to dam

In Ray Peat's words: "In animal studies, doses equivalent to thousands of milligrams per day in humans are injected into rats before harmful effects are seen in the fetuses... the only doses that caused measurable fetal harm in rats were doses that, on a weight basis, almost certainly would have caused nearly instantaneous death in humans."

Structure / Chemical properties

Cocaine (benzoylmethylecgonine) is a tropane alkaloid, the same bicyclic nitrogen-ring family as atropine and scopolamine. Structurally it is the methyl ester and benzoate ester of ecgonine. Chemical formula C₁₇H₂₁NO₄, molar mass ~303 g/mol.

The hydrochloride salt is a water-soluble white powder, used for insufflation, oral, or IV routes. The freebase form (crack) is not water-soluble but vaporizes at a lower temperature than the hydrochloride salt, which is what makes it smokable.

Function / Mechanism of action

Julius Axelrod's research demonstrated: Cats pretreated with cocaine showed a dramatic decrease in tissue H³-noradrenaline... cocaine markedly reduces the uptake of noradrenaline in tissues, presumably the sympathetic neurone. The inhibition of uptake by cocaine thus raised the extraneural concentration of noradrenaline... By blocking uptake into the nerves, cocaine caused an elevated concentration of noradrenaline to reach the receptor.

Additionally, cocaine increases progesterone production and probably has antihistamine action. Cocaine increases the production of the pituitary gonadotrophin, LH (luteinizing hormone), which increases ovarian progesterone production. In men, LH increases testosterone production.

Research citation: "Cocaine (0.8 mg/kg) stimulated a significant increase in luteinizing hormone (LH) within 10 to 20 min (P < .01) and LH reached peak levels (59-60% above base line) within 30 min after cocaine administration... Male testosterone increased by 50% above average base-line levels 50 min after the LH peak."

Medical uses / Effects

Traditional Uses

The Andean people who use coca regularly appear to suffer no harmful effects. Coca chewing prevents the hypoglycemia that can be produced by extremely high altitude. It is common to keep a wad of the leaf in the mouth all day. The dental health of coca-chewers is so good that a Bolivian company has marketed a toothpaste containing coca leaf.

Local Anesthetic Class

Novocaine (procaine) was introduced as a substitute for cocaine, but it has been found to have protective effects on the organism, as an adaptogen. Lidocaine and other local anesthetics have many important protective effects.

The "local anesthetics," which generally have a broad range of effects, are an important class of adaptogens. Procaine has been found to normalize almost every system studied. Doses far too small to have an anesthetic effect have clear biological effects. After three matched intranasal doses in drug-experienced subjects, psychological ratings for cocaine and lidocaine were similar; subjects were unable to discriminate between the drugs. By intravenous route, cocaine's subjective profile differed from lidocaine, and lidocaine was indistinguishable from placebo.

Side / Adverse effects

Cardiovascular effects

Cocaine acts through catecholamine excess and direct myocardial toxicity. It also causes vasospasm and thrombosis through endothelin-1 and blocks sodium and potassium channels. Presentations include chest pain, acute coronary syndrome, arrhythmias, cardiomyopathy, and sudden cardiac death, and can be more severe in younger patients without traditional risk factors, so any chest pain, arm pain, palpitations, or irregular pulse after use warrants emergency evaluation, not self-treatment. The mainstream and longest-standing emergency approach favors benzodiazepines, nitrates, and aspirin, with beta-blockers (including mixed alpha/beta agents) traditionally avoided on the theoretical concern that blocking beta receptors could leave alpha-driven vasospasm and hypertension unopposed. A 2026 review instead describes emergency management centering on sedation, antihypertensives, and dual antiplatelet therapy, with beta-blockers that have alpha-blocking properties possibly helpful in selected patients, so this remains a live clinical controversy rather than settled guidance, and the choice is made by emergency physicians, not before arrival. Call emergency services for chest pain or collapse.

Overdose and emergency care

Emergency care for cocaine toxicity uses benzodiazepines for agitation, seizures, sympathomimetic symptoms, and hyperthermia, oxygen to keep saturation at 93% or higher, and body temperature monitoring. On-site festival protocols for sympathomimetic toxicity combined benzodiazepines, cold intravenous fluid, and cooling with ice, misted water, and convection; rapidly lowering body temperature was key to success. Call emergency services. Cardiac complications are covered under cardiovascular effects.

Alcohol combination (cocaethylene)

Cocaethylene, formed when alcohol and cocaine are used together, potentiates the direct cardiotoxic and indirect neurotoxic effects of either drug alone. The combination is associated with more neurological and cardiac emergencies, including cerebral infarction, intracranial hemorrhage, myocardial infarction, cardiomyopathy, and arrhythmias. Separately from cocaethylene specifically, chronic cocaine use (with or without alcohol) is associated with heart valve damage, via the same endothelial injury and vasoconstriction that drive its other cardiovascular effects.

Dopamine and addiction

In cocaine abusers, PET showed reduced dopamine D2 receptor availability that persisted 3 to 4 months after detoxification, associated with reduced frontal-lobe metabolism. Addicts also showed reduced striatal dopamine release and a reduced high in response to methylphenidate compared with controls. This down-regulation of D2 receptors over repeated use is proposed as a mechanism of addiction itself: as everyday rewards produce less dopamine signal than before, motivation for non-drug activities falls while the drug, which still produces a large dopamine spike, becomes comparatively more reinforcing. See also Dopamine, Addiction, and Methylphenidate.

Oral and dental effects

Dissolved in saliva, cocaine hydrochloride is acidic (around pH 4.5), and repeated exposure of this kind erodes tooth enamel and exposes the underlying dentine to decay-causing bacteria. Cocaine and crack cocaine also cause dry mouth (xerostomia) by constricting blood flow to the salivary glands, which removes saliva's natural buffering and rinsing action and further raises decay risk; the stimulant effect also increases tooth grinding (bruxism), which wears teeth down mechanically on top of the chemical erosion.

Rubbing cocaine directly on the gums, a common route for recreational use, causes local gingival ulceration and, with repeated use, loss of the underlying alveolar bone, raising infection risk in the jaw. Separately, frequent insufflation (snorting) damages the nasal septum and hard palate through a different mechanism: cocaine's vasoconstriction cuts off blood supply to that tissue, causing ischemic necrosis rather than acid erosion; heavy, chronic snorting can progress to a perforated septum or palate. So "cocaine eats at your bones" has two distinct real mechanisms depending on route: acid/dry-mouth erosion of tooth enamel and jaw bone from oral/gum contact, and vasoconstrictive ischemic bone and cartilage loss in the nose/palate from insufflation.

Harm-reduction measures for the oral/acid component focus on restoring saliva's natural buffering rather than any direct "neutralizer": rinsing the mouth with water or a dilute baking-soda (sodium bicarbonate) rinse after use, chewing sugar-free/xylitol gum to stimulate saliva flow, staying hydrated, and avoiding rubbing the drug directly on gum tissue. None of this reverses existing enamel loss, bone loss, or septal/palate damage, which require dental or ENT evaluation.

Appetite Suppression & Malnutrition

Cocaine suppresses appetite. When pregnant animals are fed the same limited amount of food consumed by cocaine-treated animals, their undernourished offspring show most of the same effects seen in the litters that were exposed to cocaine.

As a stimulant, cocaine increases the metabolic rate, which in turn can lead to the wastage of protein, to provide energy. Conventional first aid for a cocaine overdose includes providing glucose and thiamine, to provide energy.

Teratogenicity Evidence

Some researchers have concluded that cocaine might not be a behavioral teratogen. Others have described it as "not a potent neuroteratogen."

Research citation: "Despite treatment during the major periods of organogenesis and brain development, few congenital abnormalities were observed... Despite suppression of maternal weight gain, there was preservation of fetal weights at cocaine doses up to and including 80 mg/kg/day, suggesting some protection of fetal growth."

Confounding Factors

Despite extensive adverse publicity, tobacco use continues in approximately 25% of all pregnancies in the United States, overshadowing illicit drugs of abuse, including cocaine... In light of the fact that nearly all crack cocaine users smoke cigarettes, the identification of specific developmental effects of cocaine may prove difficult to detect.

Harm reduction

• Fentanyl contamination: illicit cocaine supply is increasingly cut with fentanyl, mostly unintentionally during trafficking/packaging; this is now a leading cause of stimulant-involved overdose deaths in people with no opioid tolerance. Fentanyl test strips are cheap and can detect it, though a negative result does not rule out contamination and they cannot identify which fentanyl analog is present. Naloxone (see Naloxone) reverses the opioid-driven respiratory depression from contaminated supply even though it does nothing for cocaine itself; keep it on hand and never use alone.
• Route-specific risk: IV carries the highest overdose/lethality risk at the lowest dose (see dosing table); smoking crack produces the fastest, most intense onset and is most associated with addiction/binging; insufflation has lower acute lethality but drives the nasal/palate damage described under oral and dental effects.
• Cardiovascular and overdose emergencies: see cardiovascular effects and overdose and emergency care. Call emergency services for chest pain, seizure, or collapse.
• Alcohol: avoid combining with alcohol; the cocaethylene formed is more cardio- and neurotoxic than either drug alone (see alcohol combination).
• Oral and dental care: see oral and dental effects for the mechanism and basic mitigation (rinsing, hydration, avoiding direct gum contact).
• Redosing and binging: tolerance to the euphoric effect builds within a session faster than tolerance to cardiovascular strain, which pushes redosing toward cumulative cardiac risk rather than cumulative high; pacing and hard dose limits reduce this. Common harm-reduction guidance is to wait at least 30 minutes before taking more, since the high (5 to 30 minutes insufflated, shorter if smoked) fades well before the drug is cleared, and redosing before it clears compounds overdose risk.
• MDMA combination: combining cocaine with MDMA adds serotonin and additional norepinephrine release on top of cocaine's effects, raising the risk of seizure, stroke, heart attack, and serotonin-related overheating beyond either drug alone; animal data also show more combined neurotoxic effect than either drug given separately. Cocaine can also precipitate serotonin syndrome on its own, including in combination with fentanyl-contaminated supply (see fentanyl contamination above); a documented case resolved with the serotonin antagonist cyproheptadine after benzodiazepines alone were not enough, but this is a hospital treatment, not something to take at home.
• Panic and overstimulation: a racing heart, anxiety, and overbreathing are common and usually resolve with a calm environment and slow, paced breathing. This is self-care for anxiety only, not a substitute for emergency care: chest pain or an irregular pulse needs emergency services, not breathing exercises, since the underlying cause could be cardiac rather than anxiety.

Brands and sources

Traditional: Coca leaf (Erythroxylum coca), chewed or brewed as tea in Andean cultures

Medical derivatives:

• Procaine (Novocaine): synthetic substitute
• Lidocaine: widely used local anesthetic
• Cocaine hydrochloride: still used in ENT surgery (topical)

Mexican Coca-Cola still contains coca leaf extractives (with cocaine removed): "I think the coca leaf extractives are really biologically active, doing something very different from the caffeine content... when they compared Pepsi to Coke... Coke was very high in potassium, and the plant extractives are the only logical source for potassium."

Legal status: Schedule II (US), medical use permitted under strict controls; illegal for recreational use globally.