Intravenous (IV) alcohol administration techniques document a relationship between the alcohol concentration time course and its effects, including the role of rate of change of brain exposure. The alcohol clamp comprises a linear rise to a target BrAC, which is then maintained for hours, thus eliminating rate of change as a contributing factor to measurements obtained during the clamp. Outcomes include subjective and physiological responses to both the investigator‐defined initial positive rate of change of BrAC (initial response to alcohol) and changes in the response during maintenance of a steady BrAC (acute tolerance). The clamp paradigm has successfully examined family history of AUD, 22 , 23 , 24 genetic association of acute tolerance, 25 recent drinking history, 24 and other indicators of risk. 26 Conversely, using a paradigm where specific rates of BrAC ascent and descent were prescribed, we reported increased perceptions of “high” and “intoxicated” measured at the same BrAC and elapsed time on the ascending versus descending limb in moderate drinkers, and the reverse of that pattern in light drinkers. 27 Thus, the precise exposure control provided by
