Alcohol, Chemistry and
"Approximately 14 million Americans (7.4%) of the population meet the diagnostic criteria for alcohol abuse or alcoholism. More than one-half of American adults have a close family member who has or has had alcoholism Approximately one in four children younger than 18 years old in the United States is exposed to alcohol abuse or alcohol dependence in the family. The estimated economic cost of alcohol abuse was $184.6 billion for 1998 alone, or roughly $638 for every man, woman, and child living in the United States that year These statements comprise part of the beginning of the first Chapter of the 10th Special report to the U.S. Congress on Alcohol and Health (2000). Unfortunately they dramatically illustrate the deleterious side of ethanol use and abuse. Fortunately, most people who drink do so safely. It is only a minority who consumes alcohol heavily and produces the dramatic impact on self, family, friends and the community.
Some individuals are more vulnerable than others to becoming addicted. This enhanced vulnerability can be ascribed to genetic (biochemically regulated vulnerability) as well as environmental factors (situational impact). It is also clear that people without an apparent enhanced vulnerability can be addicted to ethanol.
What is the current thinking about biochemical basis of addition? Two general processes contribute to alcohol addiction.
Types of rewarding (positive) experiences gained after drinking include the taste of the alcohol itself and the feelings (e.g. relaxation) gained after drinking ethanol. One can also gain a positive experience by avoiding negative situations such as those felt in anxiety provoking situations (public speaking, attending a party) or avoiding the effects of withdrawal from ethanol (see below). The rewarding aspects of ethanol use involve the brains reward system. This system is comprised of brain structures and circuitry (e.g. ventral tegmental area, extended amygdala and the nucleus accumbens within) that appears to be important in the reinforcing (rewarding) properties of a variety of drugs.
The second process important in addiction has to do with the ability of the brain to adapt to influences, which affect its normal function. The ability is called neuroadaptation. For example, the drinking of one or two beers or one or two drinks (acute intake of ethanol) activates a variety of processes in the body and in particular impacts the functioning of the brain.
In order to keep the brain functioning normally, the brain attempts to chemically counteract whatever ethanol is doing to disrupt its action. A simple illustration is the reaction of the body if someone starts pushing it. The natural reaction is to compensate by correcting the balance and attempting to counteract the pressure of the push until the push is gone and the body returns to normal. Interestingly, neuroadaptation also sometimes results in an increased response to the drug (sensitization). Whether there is a diminished response or an enhanced response depends upon a variety of factors including the amount of the compound taken in and the timing of the intake. The development of sensitization to drugs such as cocaine may be more likely with intermittent exposure than with continuous exposure.
Ethanol acts at specific sites on a specific subset of GABA and glutamate receptors (protein molecules upon which the neurotransmitters act). By influencing the action of these receptors, ethanol "slows down" the functioning of the nervous system. Thus, ethanol is called a central nervous system (CNS) depressant.
With neuroadaptation, the brain attempts to counteract this depressant effect by increasing the activity of the glutamate system and decreasing the activity of the GABA system. This in part can be accomplished by altering the number or function of the receptors.
GABA and glutamate receptors are only two of a number of key players in the transmission of information from one cell to the next. Activation of receptors is the occasion for intracellular signaling, meaning that a series of events within the cell take place when a neurotransmitter binds to the receptor. Thus, neuroadaptation can also take place at other locations within the cascade of events that take place in the brain.
Just as there is adaptation upon the presence of something new, there is neuroadaptation when the compound leaves the brain. Thus, through neuroadaptation the brain is able in many instances to up-regulate (increase) or down-regulate (decrease) its function to compensate for the presence or absence of ethanol. (It should be recognized that the body and the brain have an amazing ability to adapt and only in extreme situations or after damage, such as seen in alcoholism, do the regulatory processes fail).
If a person chooses to drink more regularly (chronic intake), the brain attempts to adapt to the increasing amounts of ethanol. Generally, neuroadaptation can take place up to a point. After chronic consumption and ongoing adaptation, it will now take more ethanol to produce the same effect as the first drink. When this is the case, tolerance has developed and substantial adaptation has taken place. If the person now chooses to quit drinking the body tries to return to its original state in doing so causes a number of withdrawal signs including tremors, seizures, nausea, and negative emotional states. Since further drinking will delay, diminish, or prevent withdrawal, the person often chooses to drink again. Even if the person stops drinking, the neuroadaptations that took place in the brain may persist for a period of time well beyond the time when ethanol is no longer present in the body. It has been speculated that these may be the source of the urges to drink again.
For most people it is relatively easy to modulate ethanol intake. Depending upon the vulnerability of the individual, as drinking progresses regulation of drinking becomes more difficult. Simultaneously, the ability of the brain to adapt is diminished or lost. Systems become increasingly disregulated, perhaps due to damage, so that in the brain communication and coordination diminishes or fails. This is particularly true after repeated withdrawals from ethanol, since the severity of withdrawal increases. Perhaps this is the reason for saying the drink appears to take on a life of its own.
"First the person takes a drink, then the drink takes a drink, then the drink takes the person".
In general there appears to be a general loss of control. The individual has lost control over drinking and neuroadaptive mechanisms have been overwhelmed. Thus alcoholism can be characterized as a disease with takes over the body and brain.
The environment associated with drinking is now known to play a crucial role in the addictive process. The environment associated with the drinking becomes associated with the positive attributes of drinking. Thus, it common knowledge that if one always drinks in a particular bar, or with cigarette in their hand, or with a certain group of friends, then the bar, cigarette, and friends can trigger the urge to drink. This is because the bar, cigarette, and friends have become cues associated with drinking and can trigger the brain reward system in a manner somewhat similar to that seen with the ethanol. Attempts to help alcoholics return to normal functioning must include understanding of the important role of cues in addiction.
Tenth Special Report to the U.S. Congress on Alcohol and Health, June 2000. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism.