Researchers and clinicians have long noted that alcohol’s effects are often biphasic during a drinking episode. “Biphasic” refers to the fact that stimulant effects of alcohol tend to precede sedative alcohol effects during a drinking episode. There are substantial individual differences in the magnitude of stimulant effects of alcohol and the BACs at which they occur. Alcohol’s stimulant effects are reflected in increased motor activity, talkativeness, and euphoric or positive mood at lower doses and during rising BACs. Stimulant effects have been assessed in humans using a variety of psychophysiological, motor activity, and self-report measures, and in animals using measures such as spontaneous motor activity. Stimulant effects are present in some drinkers at BACs as low as 20 to 30 mg/dl, and may persist on the rising BAC limb well past 100 mg/dl. Some current theories hold that stimulant effects reflect alcohol’s reinforcing qualities, and that the magnitude of stimulant effects will predict future drinking and the development of alcohol dependence.

Some research suggests that the rate of change of rising BACs helps determine the degree of alcohol effects. A faster rise of ascending BACs is associated with greater euphoria and intoxication, as well as increased behavioral impairment.  It is interesting to speculate that the drinking patterns shown by many heavy drinkers and alcoholics may reflect an attempt to produce a rapid rise in BACs. These patterns include gulping drinks, drinking on an empty stomach, and using progressively fewer mixers to dilute distilled spirits. Sedative effects of alcohol usually occur at higher BACs and on the descending limb of the BAC curve. Sedation has been measured in humans using EEG patterns and self-reports of anesthetic sensations and dysphoric mood, and in animals with low motor activity and the onset of alcohol-induced sleep. Robust sedative effects tend to first appear at peak BACs near 60 to 80 mg/dl in many drinkers, although in persons with higher tolerance sedative effects are not apparent until BACs are above 100 mg/dl. Sedative effects of alcohol are negatively correlated with drinking practices, and lower levels of sedation after alcohol consumption may characterize persons at increased risk for the future development of alcoholism.

Research has clearly demonstrated that alcohol-related impairment is greater on the ascending compared to the descending limb of the BAC curve. This finding appears consistently across different doses and impairment tests. The most straightforward explanation for this effect is acute tolerance.

Acute Tolerance

There are many different types of tolerance identified by researchers. Metabolic tolerance refers to an acquired increase in the rate of alcohol metabolism. Functional tolerance can be defined as an acquired decrease in an effect of alcohol at a given BAC. There are several different types of functional tolerance. Chronic tolerance refers to an acquired decrease in an effect of alcohol across multiple exposures to the drug. This section focuses on acute tolerance, defined as a decrease over time in an effect of alcohol within a single exposure to alcohol, which occurs independently of changes in BAC. Acute tolerance is one of the most robust effects that occur in laboratory alcohol administration research. In 1919, Mellanby demonstrated that effects of alcohol were greater during the rising compared to the falling limb of the BAC curve, a phenomenon known as the “Mellanby Effect”.

A number of laboratory studies in humans and animals have replicated the Mellanby effect using numerous measures, such as motor coordination, self-reported intoxication, sleep time, and body temperature. One early question raised about the Mellanby effect was whether it was the result of a methodological artifact in the measurement of alcohol concentration in blood. Venous BAC, which is sampled for alcohol measurement, is known to lag behind arterial BAC during the ascending limb of the BAC curve, before the distribution of alcohol throughout body water compartments is complete. It is arterial blood that is closest to brain levels of alcohol. Thus, some wondered whether the Mellanby effect was an artifact because it actually compared impairment at different concentrations of alcohol in the brain. It has been established, however, that acute tolerance and the Mellanby effect occur beyond any differences between arterial and venous BAC. First, the Mellanby effect is robust when BACs are assessed via breath alcohol; breath measures are closer to arterial than to venous BACs during the ascending limb of the BAC curve. Second, researchers have demonstrated the presence of acute tolerance using numerous alternative methods. When BACs are at a steady state, acute tolerance has been demonstrated by decreases in the effects of alcohol that occur over time. Furthermore, the rate of decrease in alcohol effects are significantly greater than the rate of decrease in descending BACs. Another demonstration of acute tolerance comes from social drinkers who report themselves as feeling completely sober when descending BACs are substantial (e.g., 30 to 50 mg/dl). Investigators have demonstrated that decreased effects over time within an exposure to alcohol are not due to practice or other repeated-measures effects. Treating alcoholism to remove long-term tolerance is attainable through professional healthcare services that may include counselling, therapy and alcohol rehabilitation facilities where a detoxification can be performed under medical supervision.