There has been substantial disagreement among clinicians and researchers as to whether AUD is progressive, what behavioral or subjective changes occur in response to alcohol over extended periods of use, and what processes underlie neuroadaptive changes that result from chronic drinking. It is known that chronic exposure to alcohol leads to pharmacodynamic tolerance such that users can withstand higher BrAC than inexperienced drinkers before experiencing stupor, coma and eventual death (50). Although tolerance to the subjective effects of alcohol is a hallmark symptom of AUD, it has been challenging to track the development of such tolerance in humans. In a similar vein, it has been difficult to document the progressive stages of allostasis, another construct believed to contribute to the disorder.
