Multiple forms of tolerance develop to the effects of alcohol, but they can generally be divided into two major types: dispositional tolerance and functional tolerance. With dispositional tolerance, chronic alcohol use can lead to an increased ability to metabolize alcohol through the induction of alcohol dehydrogenase and other metabolic enzymes. Such metabolism can double, reaching 30–40 mg/dl/h compared with a nontolerant adult who metabolizes alcohol at about 15–20 mg/dl/h. This dispositional tolerance requires 3–14 days of drinking and can take several weeks of abstinence to return to normal.
Functional tolerance requires a higher blood alcohol level to achieve intoxication and is mediated by neuroadaptational changes in the central nervous system. It can be divided into three categories: acute, chronic, and behavioral. Acute functional tolerance was originally defined as the “Mellanby effect,” in which a greater degree of impairment was observed at a given concentration of alcohol on the ascending limb of the blood alcohol curve than at the same concentration on the descending limb. Similarly to other drugs of abuse, rapid initial tolerance occurs within one drinking session. The subjective sense of intoxication follows the ascending limb of the blood alcohol curve but not the descending limb (Figure 6.5). Importantly, such tolerance to the intoxicating effects of alcohol is not necessarily accompanied by any marked increase in the lethal dose.
Chronic functional tolerance in humans is reflected by an increase in intake needed to produce intoxication (that is, a shift to the right of the concentration-response function). Heavy drinkers were shown to be less sensitive to alcohol than moderate drinkers or abstainers in the “finger-finger” motor coordination test (Figure 6.6). Behavioral tolerance can be defined as learning to compensate for the effects of the drug. One example of behavioral tolerance is someone who practices performing a task (like walking) while intoxicated.