Substance Abuse: CNS Depressants - Alcohol
Biochemistry of Alcohol
Ethyl alcohol (C2H5OH) is a central nervous system depressant. It is a clear, colorless, hydrophilic molecule, absorbed primarily from the stomach and intestine and distributed into the total body water, and from there to virtually every cell in the body. (Note: Ethyl alcohol is very different from rubbing alcohol, methyl alcohol, which is poisonous if taken internally).
Although ethanol is a CNS depressant, at lower doses it has a stimulating effect which is due to a lessening of inhibitions rather than due to true physical stimulation. As the dose is increased, there is progressive depression of cerebral function. The dose needed to produce the depressant effect depends upon variables such as the individual's age, weight, sex, physical condition, co-ingestion of food, and level of tolerance.
At blood alcohol levels (BAL) of 0.05% (measured in milligrams per deciliter, mg/dl), most people can be expected to have impaired coordination and euphoria. At BAL 100 to 199 mg/dl (0.10-0.19%), ataxia, decreased mentation, poor judgement, and a labile mood set in. When the BAL reaches 200 to 299 mg/dl (0.20-0.29%), most people will have marked ataxia and slurred speech, poor judgement, nausea and vomiting, as well as a labile mood. By 300 to 399 mg/dl (0.30-0.39%), the drinker will be in stage I anesthesia with memory lapse and a labile mood. Finally, at BAL levels of 400 to 700 mg/dl (0.40-0.70%) and higher, respiratory failure, coma, and ultimately death occurs. However, tolerant individuals have been known to be awake and talking with a BAL of 700+ mg/dl.
Ethanol has the ability to damage or destroy every cell in the body. First, because it is found in all body fluids surrounding the cells, including blood, urine, saliva, spinal fluid, and tears. Second because, repeated use in certain concentrations is toxic to body tissue. Third, because it converts to acetaldehyde, a metabolite that is even more toxic than the parent compound, ethanol. After ingestion, ethanol is absorbed primarily from the stomach and the small intestine. About 5-15% is eliminated through the lungs, kidneys, and sweat glands. The remainder is metabolized in the liver where it is converted to acetaldehyde by the enzyme alcohol dehydrogenase (ADH). Acetaldehyde, more toxic than ethanol, is quickly converted by another liver enzyme aldehyde dehydrogenase (ALDH) to acetic acid which is broken down into carbon dioxide and water and eliminated through the kidneys and lungs.
This is the normal process that occurs when an individual drinks alcohol. However, the metabolism of alcohol is dramatically different in one important way. Although most of the ethanol is broken down by the usual process into carbon dioxide and water and is eliminated through the kidneys and lungs, about 1% is diverted to an alternative fate. Biochemical dependency on ethanol is due to this small portion of diverted acetaldehyde. Acetaldehyde combines with the neurotransmitter dopamine to form an addictive alkaloid called tetrahydraisoquardrelone (THIQ). This alkaloid is closely related to the opiods. In addition, THIQ combines with other neurotransmitters in the central nervous system, forming other addictive alkaloids.
Most now believe that these substances are not metabolized or eliminated, but remain in the body, and act much like heroin does. Because they remain in the body, once a person is an alcoholic, he will always be one, similar to the reasons that opiod dependency recurs. Thus, even though an alcoholic may abstain from alcohol for 20 years, if he starts drinking again, he will be unable to control his intake.
The metabolism of ethanol requires in addition to ADH, a coenzyme called nicotinamide adenine nucleotide diphosphate (NAD), also found in the liver. If an insufficient amount of ADH is produced in the liver, the individual will not be able to metabolize ethanol. Thus, the active ingredients in ethanol remain in the system longer. A second enzyme, aldehyde dehydrogenase (ALDH), has at least four clinically significant isoenzymes. ALDH I, the most active, is missing in up to 50% of Asian people. The lack of this enzyme has often been tied to the facial flushing that occurs in many Asian people when they drink alcoholic beverages. There is also a high rate of facial flushing and alcoholism among American Indians and Eskimos,
Oxidation of alcohol also leads to release of excess hydrogen in the liver causing an overabundance of a reduced form of NAD. Inadequate feedback regulation of the metabolism of alcohol results in imbalances in the liver, which ultimately lead to alcohol-related liver disease.
Continue to Altered States