Clonidine: inpatient studies from 1978 to 1981.

We have studied and reviewed data reported by others, which support a norepinephrine (NE) hyperactivity hypothesis for opiate withdrawal. Other hypotheses explained parts of the opiate withdrawal syndrome but the NE hypothesis had the potential to explain most of the clinical manifestations of abrupt opiate discontinuation in addicted persons. Clonidine's ability to almost completely reverse the opiate withdrawal syndrome in acute withdrawal studies supported the NE hypothesis and suggested a new use of clonidine. Lofexidine's efficacy was additional support for the NE hypothesis. Clonidine is an effective emergency treatment for acute opiate withdrawal and in the detoxification of methadone, heroin, and other opiate addictions. Clonidine reverses the cognitive, affective, and physiological signs and symptoms and continues to suppress their re-emergence when given for 10-14 days in a detoxification protocol. NE hyperactivity in withdrawal may result from endorphin system dysfunction at the level of the locus coeruleus (LC), the mismatch between needed NE, opiate and other inhibition at the LC in the person addicted to high doses of powerful exogenous opiate LC inhibitors and available endogenous inhibitory substances or other mechanisms.