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IS THERE A DEFICIENT BRAIN CHEMISTRY IN ADDICTS?

20 Mayıs
IS THERE A DEFICIENT BRAIN CHEMISTRY IN ADDICTS?
CHEMISTRY IN ADDICTS


If everyone with a brain can become an addict, why are there (relatively) so few addicts? Could there be a unique group of people whose pleasure circuits are abnormal in some way so that these drugs feel particularly good? Or could there be a group of people whose pleasure circuits don't work very well, so that they are inclined to drink alcohol, smoke, or take cocaine to feel normal? There are probably people in each of these catego­ries. In studying these questions in human addicts, there is a real "chicken and egg" problem. If brain function is abnormal, it is impossible to know whether the abnormality was caused by years of substance abuse or was present before. This is one challenge about the aforementioned dopamine receptor finding. Some scientists have tried to solve this problem by studying the children of alcoholics. There are certain EEG (brain wave) changes that have been noted in some alcoholics and in their sons. How­ever, we don't really understand the significance of this EEG anomaly yet. The only way to be sure is to study these children until they become adults to see if this difference predicted alcoholism. Such studies are underway, but they take a long time. We can do these experiments in animals, and we have found that even with free access to cocaine, only a certain per­centage of animals (about a fifth) progress to the stage of compulsive use. Are these differences due to a deficient gene that could simply be repaired? The mapping of the human genome has really speeded up the search for genes related to addiction as well as other diseases. Many candi­dates have been identified. Some are specific to specific addictions. A vari­ant of one gene for the receptor through which ethanol acts is associated with alcoholism, and a variant for a receptor that narcotics act upon is associated with narcotic addiction. Others, like the dopamine D2 receptor, are related to all addictions. Others have been surprises. One of the best
genetic "predictors' of nicotine dependence is a gene that controls the breakdown of nicotine in the liver—not anything related to brain function at all. Finally, there are genes that seem to protect people from addictions.
Two genes involved in alcohol degradation fit into this category (see the
chapter on alcohol). So, as many scientists predicted, drug addiction is a complicated disorder that can involve many genes. Can we fix the affected genes? Not yet. Do we want to? Because most or these genes affect normal brain activities, we are not even vaguely close to knowing if changing them would treat addiction without causing other troubles. And even if we
could, the ethical questions raised by such manipulations are huge. Finally, it is important to realize that biology is not destiny. People are more than bags of genes that produce behavior. They are influenced bytheir environment and can control their behavior voluntarily. Simply possessing a particular gene that has been found in the brains of some alco‑ holics does not mean that an individual must become an alcoholic. If he or she abstains from alcohol, for one thing, there will never be a problem.


Maybe these slightly abnormal genes provide some benefit to the person that we don't fully understand. On the other hand, people with no genetic predisposition may experience such traumatic life circumstances (being sexually abused during childhood, for example) that they develop com­pulsive use of alcohol or other substances in an attempt to self-medicate their psychological trauma. The bottom line is that everyone with a brain can become an addict. Given the diversity of human brains, it is likely that some people will find the experience more compelling than others, but we have not really defined exactly what brain chemistry leads to this vulnerability yet.

MEANS AND GOALS FOR TREATMENT

15 Mayıs
MEANS AND GOALS FOR TREATMENT

The DDTC considered complete abstinence from both illegal drugs and legally prescribed opioids (e.g., methadone) to be a desirable goal of treatment. However, based both upon the literature in the field and their own experience, DDTC staff members were skeptical of this as a realistic goal with most drug addicts, particularly in the short run. Instead, the preference was to approach such a goal gradually, under planned conditions, and with the necessary "supports- intact. The main idea was that the addict should be in a stable situation before abstinence—including detoxification—was attempted, since failure was so prevalent with such attempts.
The AFP staff also suffered no illusions, at the outset, as to the difficulty of this endeavor. In fact, relative to some others in the family field, the AFP standards might not even be considered rigorous—especially at the outset—because detoxification was not necessarily espoused as a goal. Rather than labor under the pretense that -cure" was possible, the idea instead was to see whether significant change could be effected in the extent to which patients stayed off legal and illegal drugs over a given time period—the percentage of -days free,- as described in Chapter 17. There was awareness that we were experi-menting—trying to find out what worked with these families—and that some recognition should be given to the lore that existed in the drug-abuse field up to that time.
On the other hand, the PCGC contingent saw addiction as (primarily) part of a fami ly process in which the addict was only one of a number of actors (Chapter 1). The view was that this process must be interrupted and a new process set in motion, one that did not include addictive behavior. Further, it was held that stopping the drug taking might require that a crisis be induced in the family (see Chapters 6, 8, and 9) as a way to, in a sense, -get them out of a rut.- This contrasted starkly with the notion of a gradual, careful detoxification regimen. The therapy model also dictated that goals be clearly defined and that pressure be put on the addict (within a family context) to get off drugs.
How were these differences resolved? As the work progressed several confluential processes evolved. First, partly to obtain coopera-tion from DDTC staff and partly because it seemed to have merit, the family clinicians did tentatively embrace the DDTC idea of having -all the ducks in line- before detoxification. A reluctance developed toward prematurely rushing headlong into detoxification.
On the other hand, as the family therapists grew more ex-perienced, and the techniques began to be identified and refined, confidence increased to move more rapidly in family treatment. This practice was also dictated by the urgency of having to accomplish something within 10 sessions. Eventually, it became more common-place for a therapist to pose to the family the question, -When is he going to detoxify?" in the first or second session, whereas in early cases therapists tended to sidestep this issue initially. Interestingly, as a treatment paradigm emerged, and some successes were achieved, DDTC personnel grew more amenable to rapid action, moving some-what from their previous cautionary posture. They began to accept that working with the family to pressure the addict against drug taking was a viable and feasible procedure, especially when there were no indi-cations of a possible suicidal reaction. The eventual outcome was a paradigm that drew from the philosophies and practices of both
camps.

MONITORING OF PROGRESS AND PROCEDURES

There were at least two areas in which the AFP had interesting effects on the DDTC. The first of these concerned the monitoring of urine reports. Progress and changes in drug taking were a key part of family therapy. Clear contingencies were established for -dirty- urines given by family (and movie) therapy cases—especially in the two -paid-conditions. The treatment was sharply focused on this behavior. Thus it was essential that the urinalysis results processed at DDTC be obtained and recorded accurately and efficiently. In the early stages of the program, however, it was discovered that the DDTC was going through a -slippage phase'' regarding strict adherence to urine test results: records were sometimes -lost,- patients were able to get away with denying that dirty urines were their own, and (previously firm) established rules preventing clients with dirty urines from obtaining certain privileges, or even remaining in the program, were not being strictly followed. The AFP attention to, and insistance on, (1) clarity and efficiency of urinalysis results, and (2) adherance to program strictures based on urine results highlighted areas where slack had set in. As a result, the DDTC tightened up its urine-monitoring procedure and the total urine-reporting system was improved.*
Paralleling the above, a number of areas were uncovered by the AFP in which patients were finding it easy to manipulate the DDTC system. These included ways of getting around program rules, tricks for obtaining permission from staff for higher methadone dosages, methods for triangulating staff members and instigating or exacer-bating conflicts between them, and so forth. Some of these are described in Chapter 16. As they came to light with AFP cases, or within AFP team meetings, they were responded to and corrected by DDTC staff, thus allowing improvement in the overall drug-treatment
program.

BRAIN AND BEHAVIOR

09 Mayıs
BRAIN AND BEHAVIOR

Once alcohol has been absorbed and distributed, it has many different effects on the brain and behavior. To a large extent these effects vary with the pattern of drinking. Therefore, we discuss the effects of acute, chronic, and prenatal alcohol exposure separately.
ACUTE EXPOSURE
Effects on Behavior and Physical State


Although the effects that a given dose of alcohol will have on an individ­ual vary considerably, the following table shows the general effects of a range of alcohol doses:
Still, there is often a substantial difference between being impaired and appearing impaired. In one study, trained observers were asked to rate whether a person was intoxicated after drinking. At low blood alcohol con­centrations (about half the legal limit for intoxication), only about 10 per­cent of the drinkers appeared intoxicated, and at very high concentrations (greater than twice the legal limit), all of the drinkers appeared intoxicated. However, only 64 percent of people who had blood alcohol concentrations of 100-150 mg/100 ml (well above the legal limit in most states) were judged to be intoxicated. So, in casual social interactions, many people who are significantly impaired—and who would pose a real threat behind the wheel of a car—may not appear impaired even to trained observers.
Alcohol and Brain Cells

You've probably heard some variation of the following statement: "Every time you take a drink of alcohol you kill ten thousand brain cells." Although it is highly unlikely that anyone would drink enough alcohol in a given sitting to kill brain cells directly, as with many such generaliza­tions there is a grain of truth in the warning.
One way that researchers have tried to determine which brain regions control which behaviors in animals is by destroying, or lesioning, a specific brain region and then testing the animal on a particular behavioral task.

Early in the use of this lesioning technique, some researchers found that if they injected a very high concentration of alcohol into the brain (far higher than would be achieved by a drinking person), the cells in that region would die. There is also another grain of truth in the warning about alcohol and brain cells: chronic, repeated drinking damages and sometimes kills the cells in specific brain areas. And it turns out that it might not take a very long history of heavy drinking to do so. We will address this in the "Chronic Exposure" section of this chapter.
There are fundamentally only two types of actions that a chemical can have on nerve cells—excitatory or inhibitory. That is, a drug can either increase or decrease the probability that a given cell will become active and communicate with the other cells to which it is connected. Alcohol generally depresses this type of communication, or synaptic activity, and thus its actions are similar to those of other sedative drugs, like barbiturates (such as phenobarbital) and benzodiazepines (such as Valium). Despite this general suppression of neuronal activ­ity, however, many people report that alcohol activates or stimulates them, particularly soon after drinking, when the concentration of alcohol in the blood is increasing. Although we don't know exactly why alcohol produces feelings of stimulation, there are a couple of possibilities. First, there is the biphasic action of alcohol. This refers to the fact that at low concentrations alcohol actually activates some nerve cells. As the alcohol concentration increases, however, these same cells decrease their firing rates and their activity becomes sup­pressed. Or it might be that some nerve cells send excitatory signals to the other cells with which they communicate, prompting them to send inhibitory messages, actually suppressing the activity of the next cell in the circuit. So, if alcohol suppresses the activity of one of these "inhibitory" cells, the net effect in the circuit would be one of activa­tion. Whatever the exact mechanism, it appears that there are several ways in which alcohol can have activating as well as suppressing effects on neural circuits.
Effects on Specific Neurotransmitters GABA and Glutamate

For many years it was generally thought that alcohol treated all nerve cells equally, simply inhibiting their activity by disturbing the structure of the membrane that surrounds each cell. In this sense the effects of alcohol on the brain were thought to be very nonspecific. However, it is now clear that alcohol has specific and powerful effects on the function of at least two particular types of neuronal receptors: GABA receptors and glutamate receptors. GABA and glutamate are chemical neu­rotransmitters that account for much of the inhibitory and excitatory activity in the brain. When the terminals of one cell release GABA onto GABA receptors on the next cell, that cell becomes less active. When glutamate lands on a glutamate receptor, that cell becomes more active. It is in this way that many circuits in the brain maintain the delicate balance between excitation and inhibition. Small shifts in this balance can change the activity of the circuits and, ultimately, the functioning
of the brain.
Alcohol increases the inhibitory activity of GABA receptors and decreases the excitatory activity of glutamate receptors. These are the two primary ways alcohol suppresses brain activity. While the enhance­ment of GABA activity is probably responsible for many of the general sedating effects of alcohol, the suppression of glutamate activity may have a more specific effect: impairment in the ability to form new memo­ries or think in complex ways while intoxicated. We know that the activ­ity of a particular subtype of glutamate receptor, called the NIVIDA receptor, is very powerfully inhibited by alcohol—even in very low doses. The NMDA receptor is also known to be critical for the formation of new memory. Alcohol's powerful suppression of activity at the NMDA recep­tor may therefore account Mr the memory deficits that people experience after drinking. Dopamine
The neurotransmitter dopamine is known to underlie the rewarding effects of such highly addictive drugs as cocaine and amphetamine. In fact, dopamine is thought to be the main chemical messenger in the reward centers of the brain, which promote the experience of pleasure. Alcohol drinking increases the release of dopamine in these reward cen­ters, probably through the action of GABA neurons, which connect to the dopamine neurons. Studies in animals show that the increase in dopa­mine activity occurs only while the concentration of alcohol in the blood is rising—not while it is falling. So, during the first minutes after drinking the pleasure circuits in the brain are activated, but this "dopamine rush"
disappears after the alcohol level stops rising. This may motivate the drinker to consume more alcohol to start the pleasure sequence again—"chasing the high." The problem is that although the dopamine rush is over, there is still plenty of alcohol in the body. Continued drink­ing in pursuit of the pleasure signals could push the blood alcohol con­centration up to dangerous levels.

Effects on Memory


One of the most common experiences people report after drinking is a failure to remember accurately what happened "the night before." In more extreme cases, after heavy drinking, people often report that whole chunks of time simply appear to be blank, with no memory at all having been recorded. This type of memory impairment is often called a "blackout." (Less extreme versions of this type of memory loss have been called "brown outs" or "gray outs," in which the person may have only very hazy or incomplete memory for the events that occurred during the period of intoxication. In these instances, and even in black­outs, the drinker may remember more about events when reminded of them.) In the past, blackouts were thought to be relatively rare and were viewed as a strong indicator of alcoholism by many clinicians. However, it turns out that blackouts are far more common than previously thought and don't just occur in people with serious alcohol problems. Researchers are now beginning to look more closely at how and when blackouts occur, and there appear to be some disturbing trends. First of all, blackouts appear to be quite frequent among college students, with as many as 40 percent reporting them. But it's not just the memory loss that's disturbing--it's what happens during the periods for which no new memories are made. In one survey, students reported that after a night of heavy drinking they later learned about sexual activity, fights with friends, and driving, for which they had no memory at all. So it seems that blackouts may well be a serious health risk over and above the direct effects that alcohol has on the brain. Sadly, many people joke about blackouts as an embarrassingly funny result of heavy drinking. But they are no joke. Think about it this way: anything that impairs brain function enough to interrupt memory formation is very danger­ous. If it were a blow to the head, exposure to a toxic chemical, or a buildup of pressure in the brain that caused the blackout, it would be taken very seriously. Alcohol-induced blackouts should be taken seriously as well. Short of blackouts, though, it is also clear that alcohol impairs the ability to form new memories even after relatively low doses. Therefore, having a couple of beers while studying for an exam or pre­paring for a presentation at work is probably not a good strategy. The alcohol may promote relaxation, but it will also compromise learning and memory.

Hangover

One of the best-known symptoms of a hangover is a pounding head­ache. The cause is not exactly clear, but it is probably related to the effects of alcohol on blood vessels and fluid balances in the body. In any case, it is much easier to prevent the onset of pain than it is to relieve the pain once it has started. Therefore, the sooner a pain reliever is taken, the better. Some people take one before going to bed after a night of drinking. This way the chemicals in the pain reliever can prevent the pain signals in the brain from getting started as the alcohol is elimi­nated from the body. However, Tylenol (acetaminophen) should not be taken to treat a hangover because it can interact in a very dangerous way with alcohol and its by-products and damage the liver in some peo­ple. Aspirin or ibuprofen can be used instead, but both of these drugs can irritate the stomach and small intestine and together with alcohol may cause gastric upset.
The upset stomach and nausea associated with a hangover are harder to deal with. These may be caused by the toxic by-products of alcohol elimi­nation, irritation to the stomach, or both. No medicines treat these effects specifically. Rather, the best strategy is to eat foods that are gentle on the stomach and to drink plenty of fluids. Morning coffee may help to start the day after a night on the town, but its irritating effects on the stomach may make it an unpleasant waking. And because caffeine is a diuretic, it may also contribute to the dehydration that often accompanies alcohol drinking.

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