Ethanol is the type of alcohol present in beer, wine and hard liquor. In fact, ethanol is the active ingredient in all ingested alcoholic beverages. Ingestion of fermented beverages containing ethanol has been known since the beginning of recorded history. It was first thought to have strong medicinal properties but later recognized that its therapeutic value is extremely limited. It is now known that chronic consumption of excessive amounts of alcohol is a major source of social and medical problems. Ethanol is a depressant drug that disturbs the normal chemical actions of nerve cells resulting in reduced efficiency of neural impulse conductance.

• History of Ethanol
• Behavioral Effects in Humans
• Mechanism of Action
• Thought Questions and Quick Quiz
• Additional Sources of Information

Humans have consumed ethanol for at least several thousand years. The earliest known written record of an alcoholic beverage was in the Egyptian Book of the Dead, dated approximately 3000 B.C. Nondistilled alcoholic beverages were likely to have first been made inadvertently as a result of natural fermentation. When humans discovered the pleasing properties of these beverages, they probably began more systematically preparing them and sharing them with friends. Beer is produced by fermentation using grains, wine is produced by fermentation using grapes, and hard liquors are produced by distillation of fermented beverages. Despite differences in the taste and appearance of these beverages, the active ingredient in each is ethanol.

Alcohol has had an important role in societies throughout history. Its use has ranged from social to religious to medical. In the Middle Ages alchemists belived that alcohol was a remedy for practically all diseases. In fact, a French professor in the thirteenth century dubbed alcohol "aqua vitae," meaning "water of life". It is now recognized that the therapeutic value of ethanol is extremely limited and that chronic consumption of excessive amounts is a major source of social and medical problems.

With the advent of distillation, which appears to have been discovered first in ancient Arabia, people were able to obtain beverages with a higher ethanol content. Normal fermentation processes typically cease when a beverage has achieved an alcohol content of 10 to 15 percent. Distillation is the process by which ethanol is boiled from the fermented mixture and captured, producing a liquid with a much higher concentration of alcohol.

Back to top

Ethanol produces a variety of physiological and behavioral effects. The most prominent effect is referred to broadly as "intoxication". At low doses, users experience a mild excitement and become more talkative. This is accompanied by a decrease in perceived stress and anxiety and a mild euphoria. At higher doses individuals become cheerful, loud, boisterous and begin to lose self-restraint. Memory, concentration and insight become impaired, which is accompanied by incoordination and changes in sensory function. These effects are typically followed by sleepiness. At higher doses, subjects often experience nausea and vomiting, followed by lethargy and stupor.

The primary effect of ethanol on the central nervous system is as a depressant. Although the effects at low doses appear to be stimulatory, the increase in mood and behavior is the result of "disinhibition", the inhibition of normal inhibitions. In other words, behavior that is normally suppressed by fear or anxiety is released by the inhibitory effects of ethanol.

Chronic use of high doses of ethanol leads to changes in the brain and behavior. One of the first changes is tolerance, a decrease in the effects of ethanol. As a result of tolerance, higher doses of ethanol are necessary to achieve the same effects. Tolerance to ethanol is the result of several processes. First, the enzyme responsible for the destruction of ethanol in the liver, alcohol dehydrogenase, is upregulated by chronic use. The increased activity of this enzyme breaks down ethanol more rapidly, leading to decreased effects. This form of tolerance is known as metabolic tolerance, since the metabolism (or breakdown) of alcohol is decreased. However, metabolic tolerance does not completely explain the dramatic decreases in effects seen with chronic ingestion. In addition to changes in the metabolism of ethanol, there appear to be decreases in the neuronal response to this drug. With chronic use, the response of neurons to the presence of alcohol is diminished. This form of tolerance is known as "physiological" tolerance, since the physiology of the central nervous system appears to change in response to chronic alcohol.

The second major change seen in response to chronic ingestion of ethanol is physical dependence. Following chronic use, there are physiological changes that lead to a requirement for the drug. With the development of physical dependence, further administration of ethanol is necessary to avoid a physiological disturbance. This disturbance is known as a withdrawal (or abstinence) syndrome. The withdrawal syndrome for ethanol is severe and can be life-threatening. The symptoms of withdrawal are generally opposite the the acute actions of the drug. Thus, where the acute actions of ethanol are depressant, the withdrawal syndrome involves hyperexcitability. With lower levels of physical dependence symptoms include agitation, tremors, muscle cramps, nausea, vomiting, sweating and vivid dreaming. With higher levels, these progress to disorientation, confusion, hallucinations and seizures. Without treatment, a severe case of ethanol withdrawal often leads to death.

Back to top

Despite the long history and widespread use of ethanol, as well as decades of research into its effects, the mechanism of action remains among the least understood of nearly all psychoactive drugs. Unlike most psychoactive compounds, which act by binding to specific receptor sites on neurons, ethanol appears to act by modifying cell membranes. Like general anesthetics, alcohol dissolves in the lipid layer of membranes, causing an increase in the fluidity of the membranes. This change in fluidity may, in turn, modify the actions of specific receptors or ion channels, resulting in the many behavioral effects of ethanol. Specific receptors that have been associated with the effects of alcohol include gamma aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA). The inhibitory effects of ethanol may result from an enhancement of GABA-A receptor function, increasing the effects of this inhibitory receptor, and a blockade of NMDA receptor function, interfering with the effects of this excitatory receptor. However, pinpointing a site of action or single mechanism of alcohol effects is difficult because the drug affects virtually all neurochemical and endocrine systems.

Back to top

Thought Questions

• On the one hand, ethanol appears to have fairly indiscriminant effects on cell membranes. On the other hand, its behavioral and psychological effects are not all that indiscriminant. What are potential neurobiological reasons for its relatively selective behavioral and psychological effects?

• Relative to other available drugs, both legal and illegal, ethanol is quite toxic after acute or chronic administration. Why do you think that ethanol intake is acceptable to society, while intake of many other drugs is not?

Quick Quiz

Back to top

To Drugs and Brain Home Page