Cocaine.

Cocaine, derived from the shrub Erythroxylon coca, was both chemically extracted and reported to be psychotogenic in 1859. Included in the original formulation of ‘Coca-Cola’, it was declared illegal under the Harrison Act of 1914. It has been used as a local anaesthetic and in analgesic cocktails. In one study, the main routes of administration were: smoking, 40%; intranasal, 32%; and injecting, 24%; injecting being associated with the highest level of dependence. ‘Crack’, dating from 1983, is a pure form of cocaine which consists of white crystals that ‘crack’ into small rocks. Crack is smoked, giving an immediate effect; a rapid rise in blood pressure and a powerful ‘hit’. Cocaine blocks dopamine (DA) uptake into presynaptic dopaminergic terminals, causing a great increase in extracellular levels of DA in the nucleus accumbens and activation of the ‘reward system’. The ‘high’ in chronic cocaine use is directly related to the amount of striatal DA blockade, and hence the availability of free DA, whereas craving in detoxified cases related to enhanced thalamic response to DA. Withdrawal is due to DA depletion. The enzyme necessary for acetyl choline production is unaffected.