Physical dependence on ethanol: conceptual considerations.

The mechanism of physical dependence is defined as a chain of events that begins at the physical level of membrane organization and that progresses through the various levels of biological organization to the behavioral level. An ethanol-induced alteration may be (1) cause, (2) effect, (3) an unrelated covariate of physical dependence, or (4) an experimental artifact. A variety of criteria in addition to correlation must be met before the significance of an ethanol-induced effect can be assessed. The reasons are summarized for assuming that physical effects of ethanol on membranes are the primary initiators of the cascade of events that leads to physical dependence.