Cocaine is a natural product extracted from the leaves of Erythroxylon coca Lam (coca leaves). This tropical shrub is cultivated widely on the Andean ridge in South America and is the only known natural source of cocaine. Normally produced as the hydrochloride salt, it has limited medical use as a topical anaesthetic. The free base, sometimes known as crack, is a smokable form of cocaine. Coca leaves have been used as a stimulant by some indigenous people of South America since historical times. Purified cocaine has been misused as a central nervous system (CNS) stimulant since the early years of the twentieth century. Cocaine is under international control.
Molecular formula: C17H21NO4
Molecular weight: 303.4 g/mol
The systematic name (IUPAC) is [1R-(exo,exo)] -3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid methyl ester. Cocaine is the methyl ester of benzoylecgonine and is also known as 3β-hydroxy-1αH,5α-H-tropane-2β-carboxylic acid methyl ester benzoate. Although four pairs of enantiomers are theoretically possible, only one (commonly termed l-cocaine) occurs naturally. Cocaine is structurally related to atropine (hyoscamine) and hyoscine (scopolamine), substances with quite different pharmacological properties.
Cocaine has a similar psychomotor stimulant effect to that of amphetamine and related compounds. It increases transmitter concentrations in both the noradrenergic and the dopaminergic synapse and also acts as an anaesthetic agent. Like amphetamine, it produces euphoria, tachycardia, hypertension and appetite suppression. Cocaine has a strong reinforcing action, causing a rapid psychological dependence, an effect even more pronounced in those who smoke cocaine base. Following a 25-mg dose, blood levels peak in the range 400–700 μg/L depending on the route of administration. The main metabolites are benzoylecgonine, ecgonine and ecgonine methyl ester, all of which are inactive. When consumed with alcohol, cocaine also produces the metabolite cocaethylene. Some unchanged cocaine is found in the urine. The plasma half-life of cocaine is 0.7–1.5 hours and is dose dependent. The estimated minimal lethal dose is 1.2 g, but susceptible individuals have died from as little as 30 mg applied to mucous membranes, whereas addicts may tolerate up to 5 g daily.
Dried coca leaves contain up to 1 % cocaine. They are processed into cocaine hydrochloride in clandestine laboratories. The leaves are moistened with lime water or other alkali and extracted with kerosene (paraffin). The dissolved cocaine is extracted from the kerosene with sulfuric acid to produce an aqueous solution of cocaine sulfate. This solution is neutralised with lime, causing cocaine base (coca paste) to precipitate. Coca paste is redissolved in sulfuric acid and potassium permanganate is added to destroy cinnamoylcocaine and other impurities. The filtered solution is again treated with alkali to precipitate the free base, which is dissolved in acetone or other solvents. Concentrated hydrochloric acid is added to the solution, causing cocaine hydrochloride to settle out as a solid residue. Sulfuric and hydrochloric acids, acetone and certain other solvents are listed in Table II, and potassium permanganate is listed in Table I, of the United Nations 1988 Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. The corresponding EU legislation is set out in Council Regulation (EEC) No 3677/90 (as later amended), which governs trade between the EU and third countries.
Although various methods exist for the synthesis of cocaine, they are less economic than extraction of the natural product. Typical precursors include atropine, tropinone and carbomethoxytropinone, none of which is listed in Table 1 of the above-mentioned United Nations 1988 Convention.
Crack is manufactured from cocaine hydrochloride by one of two main methods: either microwaving a wet mixture with sodium bicarbonate or by adding alkali to a hot saturated solution of cocaine and allowing the denser base to settle and solidify.
In illicit use, cocaine is typically snorted (insufflated), following which it is absorbed through the nasal mucosa. Ingestion leads to loss of activity through enzymic hydrolysis in the gut. Crack is a smokable form of cocaine. Injection of cocaine is less common. A typical dose of cocaine or crack is 100–200 mg at ‘street’ purity.
Street terms include coke, snow, charlie and a wide variety of others in use depending on location and setting.
The Marquis field test does not form a coloured product with cocaine. A more satisfactory presumptive test is based on either cobalt thiocyanate (blue coloration) or p-dimethylbenzaldehyde (red coloration). Cocaine also produces the characteristic odour of methyl benzoate when heated with a mixture of methanol and sodium hydroxide solution. In the mass spectrum, the major ions are m/z = 82, 182, 83, 105, 303, 77, 94 and 96. Using gas chromatography, the limit of detection in blood is 20 μg/L.
Cocaine is listed in Schedule I of the United Nations 1961 Single Convention on Narcotic Drugs. The esters and derivatives of ecgonine, which are convertible to ecgonine and cocaine, are also controlled according to that Convention. Coca leaf is separately listed in Schedule I and is defined by Article 1, Paragraph 1, as: ‘The leaf of the coca bush, except a leaf from which all ecgonine, cocaine and any other ecgonine alkaloids have been removed.’
Solutions of cocaine hydrochloride have limited medical use as a topical anaesthetic for surgical procedures involving the eye, ear, nose and throat.