What is the mechanism behind "acquired" alcohol tolerance?

Question

I can understand natural variation in alcohol dehydrogenase (ADH) in a population leading to variation in rate of inebriation (after controlling for other variables -- e.g., mass, food consumption, etc.). But what physiological (adaptive?) process leads to increased alcohol tolerance over the long term in a single individual?

Answer 1

Think about how much more smooth endoplasmic reticulum is present in the liver of a person who consumes a lot of alcohol compared to a non-drinker. The smooth ER is used to remove or destroy toxins like alcohol that have entered the bloodstream. Over time the amount of smooth ER will increase as the abuse increases.

Answer 2

There are different types of tolerance to alcohol: functional, acute, environmental, learned and metabolic. I think you are interested in functional and metabolic tolerance, reading your question. Brain and body functions are impaired with alcohol consumption of course depends on the quantity. But tolerance results when brain functions adapt to compensate for the disruption caused by alcohol in both behavior and bodily functions. Because of this, the person can drink more than usual amounts of alcohol, because of tolerance, but this is what leads to liver failure. Tolerance can develop from both low and high levels of alcohol consumption. Repeated low level drinking can lead to tolerance because of environmental cues, and processes related to learning and memory. In case of high alcohol consumption, tolerance results independent of environmental factors. Why? one factor is ADH is up-regulated to compensate for metabolizing of the increased alcohol in the system, so it is metabolized faster to toxic aldehyde but the effects of alcohol are short lived thus tolerance. I don't want to go into genetic tolerance which I'm not as convinced from literature.