Can someone explain drug tolerance at the cellular level?

You pointed out that the liver plays a role in detoxification. Within those liver cells, you will find the SER, smooth endoplasmic reticulum, which possesses enzymes that neutralize toxins. When toxins are observed by these cells, these cells naturally will produce more SER. So, over exposing your body to a toxin, like alcohol, or something else over a long period of time will make you have more SER. As a result, you will need to increase the dosage next time around to over compensate the amount of SER that has been made as a result of over exposure, creating this tolerance effect.