One of the most important concerns about alcohol harm is on the psychophysiological sphere, especially in conditions of longterm alcohol use. in fact this remains a very important concern to alcohol users too. Hence, indices of psychophysiological functions could well serve the most important indicators for defining “moderate” and “problematic” level of use. While up-todate definition of moderate alcohol use varies across scientific studies, there is a growing need for unification and guidelines for unit specification. The different concentrations of endogenous synthesized ethanol in different categories of people also compound the problem of guideline unification, besides differences in the definition of endogenous synthesis. in this study we analyze the range of values for moderate and problematic alcohol use, based on solid and flexible psychophysiological parameters. We also analyze the frequency and number of peer-reviewed literature (in scientific databases) defining moderate, and problematic use, and non-alcohol use, and their corresponding dose classification. The results of this study show that cells are very sensitive to slight increase in endogenous alcohol (caused by increased endogenous and exogenous intake or variations in internal and external milieu). The resultant effect is the remodeling of physiological functions of the cells; both intracellular and extracellular signaling mechanisms are affected. Physiological cellular changes resulting from increase in both intracellular and extracellular ethanol concentration will serve a useful criterion for formulating moderate threshold of exogenous ethanol.