Alcohol Tolerance, Dependence and Withdrawal: an Overview of Current Issues

Publisher Website
Google Scholar
Abstract
Recent research has shown that tolerance is the composite result of a complex interaction among pharmacological factors (dose, frequency, and duration of administration), environmental modification of the alcohol effects, opportunity for test practice while intoxicated, and classical conditioning of environmental cues that signal alcohol. The same factors affect the development of cross‐tolerance to other drugs which share certain effects with ethanol, and of physical dependence, which develops concurrently with tolerance and probably results from the same adaptive changes. Though current interest centres on the neuronal cell membrane, including neurotransmitter receptors, ion channels and second messenger systems, the basis adaptive changes responsible for tolerance have not yet been identified. Genetic factors affect virtually every aspect of the biological response to alcohol, including the development of tolerance. Tolerance contributes to organ damage by making possible the ingestion of sufficiently large amounts of alcohol to cause cytotoxicity. At the same time, tolerance contributes to the strength of alcohol relative to its rewarding or reinforcing effects. Conditioned tolerance probably contributes to the risk of relapse by generating a withdrawal‐like reaction that reinitiates a “need” to drink. The implications for treatment are discussed.