Chronic administration of cocaine results in presynaptic dopamine depletion followed by upregulation of postsynaptic dopamine receptors and increased dopamine hydroxylase. Dysphoria associated with use of high doses of cocaine may result from depletion of presynaptic dopamine and craving for cocaine may result from upregulation of post synaptic dopamine receptors. Cardiovascular toxicity includes generation of arrhythmias, cocaine-induced cell death, reduced oxygenation, myocarditis, dilated cardiomyopathy and intravascular coagulopathy. However, frequent users often increase their daily intake. The dependence liability of cocaine is among the highest for all drugs of abuse.
Dependence is both physical and psychological.
Exhaustion, psychic depression, extended but restless sleep with increased REM activity, and hunger upon awakening may occur after abrupt termination of cocaine use. The severity of withdrawal depends on the length of use, the amount of the drug used and the route of administration. Intravenous users and free basers tend to suffer the most intense post-drug symptoms. As a CNS stimulant, cocaine has many psychological effects that are predictable and similar to those of other stimulants such as amphetamines and caffeine. It is a sympathomimetic drug.