The Addicted Brain (20 page)

Figure 11-1. The relationship between the addicting properties of a substance and the physical harm that it causes to organs and bodily systems. Efforts have been made to relate addiction (dependence) and physical harm, and, according to one of the devised procedures, there is a relationship. In general, the more addicting a substance, the more harm it can cause, which makes sense. But it is not a perfect relationship. Tobacco more readily produces addiction than it causes harm, whereas anabolic steroids tend to produce more harm relative to their addicting properties. Not all of the drugs in this figure have been discussed in this book. Note that according to this classification scheme, heroin and cocaine are number one and two in both addiction and harm. (Graphical summary from Table 3, Nutt, D et al. “Development of a Rational Scale to Assess the Harm of Drugs of Potential Misuse.
The Lancet
, 369: 1047, 2007, as described in
http://en.wikipedia.org/wiki/Cocaine#Acute
.)

Alcohol is practically ubiquitous, and this availability creates serious difficulties for the abuser. Alcohol, in certain ways, is one of the most dangerous of the abused drugs. It interferes with judgment and performance, promotes aggressive behavior, is associated with accidents and fatalities, and changes brain structure, function, and chemical
makeup (see
Figure 11-2
). In the emergency room, about 50 percent of patients have alcohol in their blood to varying levels. Forty-four percent of fatal motor vehicle accidents and about 30 percent of fatal falls in the home involve alcohol. It is often found in perpetrators of violent crimes such as murder and brutal domestic disputes. Pregnant mothers who use alcohol put their unborn babies at risk for Fetal Alcohol Syndrome that can cause brain damage and other abnormalities in the infant.

Figure 11-2. The volume of the prefrontal cortex is significantly reduced in alcoholics and is comparable to that in schizophrenics who are serious, chronic, mentally ill patients. The reduction in this brain region is likely associated with a loss of emotional regulation, degradation of judgment, and loss of inhibitions. (Summarized from Mathalon, D.H. et al. Compounded Brain Volume Deficits in Schizophrenia-Alcoholism Comorbidity.
Arch of Gen Psych
, 60: 245–252, 2003.)

Blood levels of alcohol and their association with its behavioral and physiologic effects have been thoroughly studied. Drinking even relatively small amounts of alcohol elevates one’s mood, reduces anxiety, and makes you tired. Very large amounts of alcohol can produce respiratory depression that can be followed by coma and even death. Cases of this type have been found where large amounts of alcohol were almost forcibly taken, for example, at a hazing party. Rare complications of alcohol ingestion include an alcohol-induced psychotic disorder with hallucinations and persecutory delusions, and a life-threatening disease called Wernicke’s encephalopathy, which is characterized by mental confusion and loss of muscle control. These require immediate treatment.

The best known complication of long-term use of alcohol is liver disease, of which there are two types, fatty liver and liver cirrhosis. These can lead to liver failure and result in expensive medical care or death. Chronic drinking is also associated with vitamin B and thiamin deficiencies. Vitamin B deficiency can manifest as peripheral neuropathies, which is damage to peripheral nerves in the arms and legs. Thiamin deficiency can cause a short-term memory loss syndrome called Korsakoff’s syndrome. Again, these serious problems require medical attention.

Heavy drinkers who stop imbibing can experience a severe withdrawal syndrome called delirium tremens (the DTs). After a few hours of abstaining from alcohol, shakiness, sweating, and palpitations appear. One to two days after abstinence, the DTs appear, which include hallucinations, seizures, and sometimes a sensation of insects crawling over the skin. Five to 15 percent of subjects in DTs actually die. Withdrawal from alcohol is obviously very serious, especially in those who drink larger quantities.

Other conditions that can be caused by or made worse by alcohol include: skin conditions, shaking of the limbs, high blood pressure, esophageal reflux, stomach ulcers, gastritis, reduced endocrine function in certain organs, autoimmune diseases, gout, and blood disorders.
Overall, alcohol is certainly one of the most dangerous drugs
, and chronic alcoholism is quite a toxic life style. It is true that light or moderate drinking can be beneficial. It has been associated with lower risks of heart disease, death from a heart attack, some strokes, gallstones, and perhaps even diabetes. But, if someone can’t limit drinking and has a tendency to drink more and more, perhaps the risk of harm does not outweigh the potential benefit. A discussion with your doctor can provide helpful guidance.

As has been discussed earlier in this book, drugs of abuse interfere with normal neurotransmission, and alcohol is the same. Alcohol affects several neurotransmitter systems, notably the one for GABA, an inhibitory neurotransmitter. There are several subtypes of GABA
receptors, and alcohol enhances the function of the GABA-A receptor. The drug also blocks some of the receptors for glutamate, an excitatory neurotransmitter. The enhancement of inhibition and blockade of excitation underlie the depressant actions of alcohol. Interactions with other neurotransmitters such as acetylcholine and serotonin have been noted as well.

When we talk about nicotine, we are basically talking about smoking, because nicotine is the addictive ingredient in cigarettes that promotes repeated smoking. Experiments have shown that the rate and frequency of smoking are adjusted to keep blood levels of nicotine in a certain range where the rewarding effects are experienced. A first cigarette usually produces negative reactions like choking and stomach upset, but with continued use, these negative feelings subside, and the addicting properties of nicotine begin to take hold. Nicotine stimulates receptors for the neurotransmitter acetylcholine, specifically the nicotinic receptors. Stimulation of these receptors causes a release of dopamine in the nucleus accumbens, a neural effect common with many other addicting drugs.

The behavioral effects of nicotine are subtle and less of a worry compared to other drugs. The drug alleviates anxiety and stress, reduces aggression and anger, and causes a pleasant state of relaxation and euphoria. These effects tend to be positive, but it has become clear that smoking produces a state of dependence. In fact, both animals and humans self-administer it, and tolerance occurs. There is a withdrawal syndrome, and those who try to stop smoking often relapse. Somewhere between a third and a half of smokers become dependent.

Withdrawal signs include craving and depression, and it may be that some smokers try to treat their depression by smoking. Additional signs of withdrawal include weight gain, insomnia, anxiety, irritability, restlessness, and difficulty in concentration. Smoking is so widespread that probably most of us have known friends or family
members who experience these withdrawal signs. Smoking tobacco is more of a problem than ingesting pure nicotine. Our lungs take a serious battering from constituents of smoke and carbon monoxide, and other organs are affected as well. Dr. Dorothy Hatsukami and colleagues have noted that the level of exposure to lung toxins, even though real, is variable among individuals,
¹
and because one heavy smoker is apparently okay does not mean that others will be okay. The fatal damage done by smoking is described in
Table 11-1
. Fortunately, laws have been enacted that have raised the price of cigarettes, which makes them less available. Other laws have caused manufacturers to advertise the risk of cancer on each pack. Treatments for nicotine dependence, which are vital for public health, are covered in
Chapter 13
, “Treatment: How Do I Get Better?”

Table 11-1. Causes of Death Attributable to Smoking in Men and Women During the Period 1997–2001

As mentioned in
Chapter 4
, “The ABCs of Drug Action in the Brain,” nicotine acts at receptors for the neurotransmitter acetylcholine. Historically, acetylcholine was the first neurotransmitter that was discovered, which opened a doorway into the brain that has lead to many major discoveries. Acetylcholine acts at two major types of
receptors: the nicotinic receptor and the muscarinic receptor. These subtypes were discovered originally using the substances nicotine and muscarine, which are derived from plants, and how the receptors subtypes got their name. Nicotinic receptors are ion channel receptors, and muscarinic receptors are G-protein coupled receptors (see
Chapter 4
,
Figure 4-2
).

Imagine that several students are preparing for an exam. They take a study break and smoke a joint, saying that it relaxes them and they do better on tests when they aren’t uptight. They confidently go back to studying. Could they be wrong?

Marijuana is the most widely used illicit drug. A recent survey by the National Institute on Drug Abuse found that more than 20 percent of high school seniors have used marijuana within the last 30 days! Echoing the previous paragraph is the question of whether it’s use affects student performance. Marijuana or the hemp plant (cannabis sativa) is often smoked or eaten to get high. A major active ingredient is delta-9-THC (tetrahydrocannabinol), but there are probably others such as cannabidiol. The strength or percent of the plant that is drug has increased over the past few decades, presumably because of selection. Several different strains of the plant are known. Dronabinol (synthetic THC, whose proprietary name is Marinol) is a marketed medication indicated for appetite stimulation and reduction of vomiting. Hashish, an extract of the plant that is a more pure form of the drug, is made of resinous secretions of the plants which are dried, compressed, and smoked. Delta-9-THC and other ingredients act at receptors for anandamide (and other substances referred to as endogenous cannabinoids), a naturally occurring neurotransmitter in the brain.

The psychological effects at recreational doses of marijuana include euphoria, a sense of well being, and relaxation. But there are also problematic effects such as disorientation, lack of concentration,
impaired learning and memory, sedation, panic reactions, and paranoia. The physiological effects are the well known reddening of the eyes, dry mouth and throat, the “munchies” (increased appetite), vasodilation, increased heart rate, urinary retention, constipation, and loss of coordination. Withdrawal symptoms have been reported and include craving, mood changes, headache, weight gain, and sleep disturbances.
²
It is interesting that the quantity of tar inhaled and the amount of carbon monoxide absorbed is three to five times greater than what occurs with tobacco smokers! National surveys from 2005–2007 indicate positive associations between duration of marijuana use and bronchitis and lung cancer, as well as anxiety, depression, and sexually transmitted diseases.
³

Back to the students described at the beginning of this section. Does smoking pot while you are studying help? No! It doesn’t. Effects of the drug include, as mentioned, impairment of concentration, learning, and memory. The students are worse off. Consider a study published on airline pilots who were allowed to smoke marijuana in order to test its effects. They smoked a cigarette containing 20 mg of delta-9-THC, and had their performance examined in a flight simulator. Impairments were found up to 24 hours (a full day) later. The effect of the drug did wear off but it took a long time.
⁴
So, beware! Impairments can last a long time. If someone has a demanding task or job or a role as a parent, can he or she afford this risk? Someone might argue that the dose the pilots took was higher than one normally takes or that the flight simulator was especially sensitive. Nevertheless, the dangers are real.