Effects of cocaine on the hypothalamic-pituitary-adrenal axis

Cocaine hydrochloride is a psychoactive substance extracted from the leaves of plants called Erythroxylum coca. Cocaine is the second most commonly used drug in the world after cannabis; 20 % of cocaine users will become long-term cocaine-dependent patients. Different routes of administration may be recognized: smokable modality, intranasal and intravenous. Cocaine is a potent stimulant of the sympathetic nervous system and causes structural changes on the brain, heart, lung, liver and kidney. It has long been known that use of cocaine may produce alterations to the endocrine system. Research on behavioral and neuroendocrine effects of cocaine dates back several years ago and has increasingly focused on alterations of the hypothalamic-pituitary-adrenal (HPA) axis, which appears to be the chief target of cocaine effects.

Animal (mainly rats and monkeys) and human studies have clearly shown a close relation between cocaine consumption and overdrive of the HPA axis. Such activation is likely involved, though via a still undefined mechanism, in the behavioral and cardiovascular changes of drug abusers as well as in the reinforcement/relapse phenomena. Further studies of the pathophysiology of cocaine addicts will help to devise new therapeutic strategies for these patients.