Caffeine

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Editors: Stacey L. Blachford and Kristine Krapp
Date: 2003
Document Type: Drug overview
Pages: 8
Content Level: (Level 4)

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Page 58

CAFFEINE

OFFICIAL NAMES: Caffeine

STREET NAMES: None

DRUG CLASSIFICATIONS: Not scheduled, stimulant

OVERVIEW

Doubtlessly the most widely used drug today, caffeine is consumed daily by 90% of the world's people. Evidence of its use exists as far back as the Stone Age, and today, children, teens, and adults everywhere ingest it in coffee, tea, and soft drinks.

Legend has it that the stimulant effect of the coffee bean was first noted by an Ethiopian shepherd guarding his flock, a thousand years ago. Sufi monks steeped the berries in hot water and found that the brew helped them stay awake for long nights of prayer. Meanwhile, written records show that, during the Tang dynasty, which lasted from the seventh to the tenth century, the Chinese were already steeping and consuming tea as a drink believed to lengthen life.

By the Middle Ages, coffee was a popular drink of Muslims. In fact, the word coffee is derived from the Arabic, qahweh (pronounced kahveh). It was the Turks, however, who controlled much of the world's trade in coffee by the Middle Ages. The Turkish Empire, attempting to expand into Europe, laid siege to Vienna in1683. The war failed, but the retreating Turks left behind 500 sacks of coffee beans, which an entrepreneur used to open the first coffeehouse in Vienna. Coffee use spread throughout Europe.

In 1675, King Charles II issued an order to close the coffeehouses that were already widespread throughout England, citing idleness as the chief complaint. Two days before the proclamation was to take effect, however, Charles backed down, fearing massive protests by coffee drinkers. Ironically, in the ensuing decades, the British came to prefer tea, probably due to the acquisition of its colony in India and the establishment of the tea trade there.

The social use of coffee then spread to America. By the eighteenth century, plantations devoted to the coffee plant were actively producing the bean in Indonesia and the West Indies.

Later, during the Vietnam War, coffee also played a part in the protest movement growing at home. Coffee bars flourished near military bases across the United States, where discussions flowed, along with the coffee, over strategies to aid war protestors.

Both health claims and controversies have followed caffeine through the centuries. By the 1960s, health concerns over coffee use were raised in the medical literature as well as the popular press. Research linked coffee consumption to medical conditions such as pancreatic cancer, breast lumps, and elevated levels of cholesterol.

In 1979, a Swiss company developed a distillation method to remove the caffeine from coffee, creating decaffeinated coffee. The Swiss water process proved popular among young urban professionals as it was considered to make a more "natural" product in comparison to the earlier method of making decaffeinated coffee,Page 59  |  Top of Article which used chemicals such as methylene chloride. The Swiss method also retained more of the flavorful oils residing in the coffee bean. Caffeine-free versions of colas soon followed.

Most follow-ups to earlier studies warning of the adverse effects of caffeine have failed to duplicate the initial findings, especially for the moderate use of caffeine. However, at the start of the new millennium, youth culture thrived on the excessive use of caffeine. New drinks were purposely formulated to contain large amounts of the mild stimulant, increasing the risk of possible adverse effects.

Critics of popular beverages such as Red Bull and Adrenaline Rush suggest that the high caffeine and sugar content pose a potential risk of dehydration for athletes, and that they could also pose a significant danger for adverse effects on the heart. In addition, these high caffeine drinks are used as mixer beverages for alcohol, a potentially dangerous combination.

Some body builders tout the combination of caffeine with the herbal stimulant ephedra as harmless, and suggest the combination helps turn fat into muscle. A study published in 2001 does support the claim that caffeine and ephedrine can boost results in laboratory attempts to mimic the tasks of competing athletes. However, ephedra, the herbal drug containing the chemical ephedrine, has been linked to several deaths.

In 1980, the Food and Drug Administration (FDA) proposed to remove caffeine from its Generally Recognized As Safe list. But the FDA concluded in 1992 that, after reviewing the scientific literature, no harm is posed by a person's intake of up to 100 mg per day. As of 2001, the FDA recognized caffeine as a substance that is a food additive with a provisional listing status.

CHEMICAL/ORGANIC COMPOSITION

Caffeine, the active substance responsible for the stimulant effect of the coffee plant's berry, is a methylxanthine, one of the family of stimulants present in more than 60 species of plants. The pure chemical forms white, bitter-tasting crystals, which were first isolated from coffee in 1820. Other family members are theophylline, found in tea leaves, and theobromine, found in the cacao pods that are ground to make chocolate. The most potent component in the coffee family by unit weight is theophylline, while theobromine, the weakest component by unit weight, stays in the body longer than does caffeine.

Caffeine is also a trimethylxanthine, which is made up of three methyl groups. Efforts by the liver to deactivate caffeine at first appear counterproductive. Liver enzymes usually detoxify potentially harmful chemicals obtained through food, or those naturally present in the body. But what is left after the liver initially removes a methyl from caffeine are theophylline and paraxanthine, both of which are still active. Only when the final methyl is stripped away is the chemical inert. This production of active metabolites is why the stimulant lasts a relatively long time. It is also why people with liver disease, or those who consume other drugs that engage the liver enzymes, cannot efficiently clear caffeine from their body. Impaired caffeine metabolism is also evident in women taking estrogen for birth control or who are at the high estrogen phase of their monthly cycle. Newborn babies whose livers are not yet fully developed also break down caffeine more slowly until the enzymes are fully activated.

The methylxanthine molecule is built on a foundation common to many biologic compounds, the xanthine double ring of carbons. The three methylxanthines, caffeine, theophylline, and theobromine, all block the action of the body's adenosine molecule, sending a signal that helps slow the chemical buildup inside cells. Because the methylxanthines closely resemble adenosine at the molecular level, they can occupy the molecular sites on cells that normally recognize, and react to, adenosine. Caffeine prevents the normal slowing action of adenosine at the cellular level, in both nerves and muscle.

Scientists working with cell and tissue preparations recognized that caffeine and the other methylxanthines can block an enzyme called phosphodiesterase. It seems now, however, that this action is carried out at caffeine doses that are much higher than what people normally

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Popular drinks are purposely formulated to contain large doses of caffeine, a mild stimulant. The drinks are designed for people who do not like coffee but want a caffeine jolt. Photo by Charles Bennett, AP/Wide World Photos. Reproduced by permission. Popular drinks are purposely formulated to contain large doses of caffeine, a mild stimulant. The drinks are designed for people who do not like coffee but want a caffeine jolt. Photo by Charles Bennett, AP/Wide World Photos. Reproduced by permission.

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consume. A similar caveat goes for the supposed action of caffeine on calcium stores in muscle. It is an effect only evident at high doses.

Caffeine is present in coffee, tea, and chocolate. These plant-derived beverages and foods also contain the other methylxanthines, which some scientists say serve as defense chemicals for leaves and berries produced in climates where there is no winter to kill off chewing bugs. Tea contains mostly caffeine, with small amounts of theophylline and theobromine, but tea is a weaker plant extract than the stronger brew, coffee. Theobromine is the primary methylxanthine found in cocoa, which also contains a small amount of caffeine per cup. Caffeine content ranges from as little as 5 mg in a cup of hot cocoa to 300 mg in 6 oz (177 ml) of espresso. Colas have about 50 mg per 12 fl oz (355 ml).

The robusta strain of coffee plant cultivated in Indonesia and Africa contains about 2.2% caffeine, while the arabica variety, grown in Central and South America, contains half that concentration. The caffeine in tea was purified in 1827, and was initially given its own name of "theine," as chemists of the day thought it different from the caffeine in coffee.

The kola nut, source of some of the flavoring of cola drinks, also has a bit of caffeine. About 5% of the 35 mg in a standard 9.5 oz (280 ml) serving of cola is naturally present from the kola nuts. The caffeine in sodas is added by the manufacturer.

Caffeine is available by prescription as a solution of caffeine citrate. Caffeine is also an active ingredient in many headache medicines, both by prescription and sold over the counter, as well as in nonprescription aids and herbal preparations for alertness and dieting. Body builders may readily buy and use a "stack," a pill comprising of ephedra, caffeine, and aspirin. Often caffeine is added intentionally to the mixes in today's energy drinks. Many abused illegal drugs, as well as some drugs sold legally, contain caffeine, either for added effect, or as a "filler," used in powder form to cut the potency of street drugs.

INGESTION METHODS

The vast majority of caffeine is ingested in a beverage such as coffee, tea, or soda. Beyond beverages, caffeine is also consumed in snacks such as chocolate candy bars, or as a component in drug medications.

THERAPEUTIC USES

Caffeine is approved as a prescription drug for treating premature infants who are born before their lungs and brain are mature enough for automatic breathing. These babies may have a condition called apnea, in which they cease breathing, which could cause damage to the brain and other organs. Caffeine has been demonstrated to aid in keeping premature babies breathing regularly. But a study published in 2001 found that very-low-birth-weight preemies also failed to gain weight when treated for their apnea with caffeine. Apparently the caffeine raised the babies' metabolic rate, causing them to burn more calories.

Many headache medications also contain caffeine, which can increase the effectiveness of the other drugs that alleviate both tension and migraine headaches. People who get migraines can have their headaches controlled by pills that combine caffeine with aspirin or acetaminophen. A study in 2000 showed that the effect of caffeine also increases the effectiveness of ibuprofen.

A study in 1999 confirmed that rebound headaches will occur if regular caffeine users suddenly cease taking the stimulant. To cut down on heavy caffeine use, it was recommended that all forms of caffeine (including caffeine-containing medications) be temporarily eliminated.

In 1999, it was reported that caffeine combined with alcohol could prevent damage from strokes. However, the doses that provide the benefit are quite specific, and the treatment has to be given at a time quite close to the stroke. Another study casts doubt on these findings, and indeed suggests that caffeine cuts blood flow in the brain, an action that would be harmful in people suffering strokes. Then, a report published in 2001 concluded that caffeine could have adverse consequences for patients trying to recover from stroke. By slowing blood flow through the brain, caffeine could starve already struggling nerve cells.

A functional magnetic resonance imaging (fMRI) study of the brain can actually determine between the regular and the occasional coffee drinker. Caffeine consistently slows blood flow by 25% to the gray matter of the brain, which contains the cells, and by 20% to the white matter, which contains the connecting nerve fibers. Heavy users of caffeine show more blood flow in the gray matter in the front of the brain when they had abstained for 30 hours, compared to those who infrequently ingest caffeine. With fMRI, the doctor can look inside the brain and observe the phenomenon of caffeine withdrawal in action.

The therapeutic treatment of obesity with caffeine is another controversial area of interest. Many over-the-counter diet aids contain caffeine, but it has not yet been determined whether there is a medically safe way to use caffeine as a fat fighter. A 2000 study showed that a combination of herbal ephedra and caffeine lowered participants' body weight by both decreasing fat and decreasing the body mass index (BMI). Losses were 15 and 7 pounds for those taking the herbal supplement and a placebo, respectively.

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Green tea with caffeine also seeks to weigh in as an herbal fat fighter. The thermogenic effect of tea is carried out at various control points in the adrenergic pathway. Caffeine, through the action of phosphodiesterase enzymes, indirectly boosts the adrenergic signals. However, there is no direct evidence that green tea successfully allows people to lose weight and keep it off.

USAGE TRENDS

Caffeine is widely used due to its relative safety as compared to other stimulants. In fact, in 2001 the U.S. military endorsed the usefulness of caffeine, recommending it as a safe and effective stimulant for its soldiers.

Scope and severity

Ninety-five percent of all caffeine is consumed in the form of tea and coffee. Following water, tea is the most popular beverage in the world. About 1.5 billion cups of coffee are consumed every day throughout the world.

Since water that is not boiled is unsafe to drink in many areas of the world, travelers are advised to drink coffee and tea instead. However, the diuretic effect of caffeine can cause dehydration.

Age, ethnic, and gender trends

The average daily consumption of caffeine for adults in the United States is about 210 mg. Coffee accounts for 60% of the total caffeine consumed in the United States, while soft drinks and tea each represent 16% of the total. In the United Kingdom, by comparison, caffeine intake is twice the American rate, and tea accounts for 72% of the British total. In Scandinavian countries, coffee is the preferred beverage. For instance, in Sweden, coffee makes up 85% of the total per capita of caffeine consumption. Finland is renowned for the practice of brewing particularly potent coffee, boiled and decanted directly from ground beans.

MENTAL EFFECTS

Within minutes of consumption, a caffeinated beverage will cause the drinker to feel more alert. Simple intellectual tasks are performed more readily, as are physical jobs that require endurance. However, while reaction time is shortened by caffeine, fine motor control suffers, perhaps due to the slight tremor that becomes more pronounced with higher doses of caffeine. The larger doses of caffeine, especially for people who do not use it regularly, cause headache and nervousness.

Caffeine decreases the duration of slow waves in the electroencephalogram (EEG) for about five hours after it is ingested. Taken near bedtime, caffeine will delay the time it takes for the consumer to fall asleep, and will reduce the depth and quality of sleep. Sleepers will also move more and waken more easily. These effects are evident with the amount of caffeine present in a cup or two of coffee, approximately 75–150 mg.

PHYSIOLOGICAL EFFECTS

Caffeine, by blocking the action of the body's adenosine, affects a wide variety of organs, as well as the brain, the gut, and basic metabolism. Theophylline works more actively on respiration and the heart. Caffeine is more active in the gut and in the central nervous system. Theobromine has very weak, if any, effect on the brain, but it retains the methylxanthine effect on the kidneys, increasing urination.

Caffeine dissolves easily in fats, so it encounters no barrier as it spreads in the body when taken by mouth. It rapidly crosses the mucosa of the stomach and soaks through the blood-brain barrier. In the bloodstream, the peak level of caffeine is achieved within half an hour. It takes four hours for the body to clear half a dose of the drug. This rate of metabolism of caffeine is slower inPage 63  |  Top of Article newborns and in women late in pregnancy. Smokers, though, rid caffeine more rapidly. Children also rid their bodies of caffeine more readily than adults.

Metabolic processes speed up appreciably under the influence of caffeine. Fatty acids are released into the blood, and a general increase in metabolism is evident as there is increased muscle activity, raised temperature, or both. More calcium is made available through caffeine's action in the muscles for contraction, but this effect is evident only at caffeine doses higher than people commonly use. Gut motility and secretion increase with a release of stomach acid and digestive enzymes. Urination is also stimulated; caffeine directly affects the kidneys, cutting into their ability to reabsorb electrolytes and water. For every cup of coffee or two to three cans of caffeinated soft drink consumed, about 5 mg of calcium is lost in the urine.

Breathing rate increases in response to caffeine. The effect on respiration occurs at the level of the brain stem's respiration control center. Theophylline has the most potent action of all the methylxanthines, affecting the smooth muscle of the bronchial tree in the lungs. This is why theophylline is a treatment for asthma. Doctors may recommend weak tea for their asthmatic patients with colds; this bronchodilating action of the theophylline in the tea will aid in clearing mucus.

Caffeine temporarily increases blood pressure, but the body readily compensates and adjusts back to its normal blood pressure. However, people with hypertension may have a more sensitive response to the drug, as caffeine may raise the blood pressure to a higher level in those with chronic high blood pressure.

For migraine patients, the effect of caffeine on the blood vessels around the brain is beneficial; it constricts both the inner and outer vessels, relieving pain. Also, because caffeine increases the acidity in the stomach, it speeds the absorption of pain medications.

Sports competitors recognize that caffeine can boost performance. Large amounts of caffeine release free fatty acids into the bloodstream, reserving the stores of glycogen in muscle for later use. Two to four cups of coffee contain the amount of caffeine that can enhance exercise performance in the average man weighing about 165 lb (75 kg), and it is two to three cups for a 130-lb (59 kg) woman. A down side to caffeine use during a sporting event is the need to urinate, caused by caffeine's diuretic effect on the kidneys.

Harmful side effects

Some people find that caffeine irritates their gastrointestinal tract. It is still unclear if the effect is from caffeine itself, or from another as-yet-undetermined substance that could be in coffee. Regardless, people with stomach ulcers or irritation may not find relief by switching from caffeinated to decaffeinated coffee.


Chart by Argosy. Chart by Argosy.

Caffeine content of common dietary and medicinal sources
SOURCE: Center for Science in the Public Interest.
Source Standard amount
(in milligrams)
Bottled beverages (12 oz)
Red bull 115.5
Jolt 72
Mountain Dew 55
Diet Coke 45
Dr. Pepper 41
Coca-Cola Classic 34
Coffee (8 oz)
Brewed 80–135
Instant 65–100
Decaf brew 3–4
Tea (8 oz)
Ice tea 47
Brewed 40–60
Instant 30
Green tea 15
Chocolate
Hot cocoa (8 oz) 14
Chocolate milk (6 oz) 4
Chocolate bar (1 oz) 3–6
Medications (per tablet)
Vivarin 200
No-doz 100
Midol, Maximum Strength 65
Anacin 32
Dristan 30

Effects of caffeine on the heart can be considerable. Rapid or irregular heartbeats can result from ingesting large amounts of caffeine. People at risk for heart attacks might be ill advised to drink coffee or indulge in other sources of caffeine. Caffeine intake exceeding the amount found in five or more cups of drip coffee a day results in a statistically increased risk of cardiac arrest.

Frankly toxic effects, such as persistent insomnia and anxiety, only become evident when people drink more than eight or nine cups of coffee or tea a day. Convulsions and delirium can follow enormous doses, and a near-fatal dose can induce a state similar to that of a diabetic lacking insulin. Blood sugar surges, and ketones appear in the urine. The lowest recorded fatal dose of caffeine was 3200 mg, which was given by accident directly into the bloodstream. It takes the equivalent of 40 cups of coffee consumed by mouth in a short interval for caffeine to kill a person.

Long-term health effects

When studies in the 1980s raised concern about possible adverse effects, including miscarriage, birth defects, and infertility, doctors advised pregnant women to cut out caffeine entirely. Most of these studies have not been confirmed. Certainly, the amounts of caffeinePage 64  |  Top of Article used to cause birth defects in rodents exceed the usual amounts consumed by people. By the year 2000, doctors simply told women who were pregnant or planning pregnancy, to keep caffeine consumption within the bounds of a cup or two of coffee a day.

Most studies find that moderate use of caffeine does not impair fertility, risk miscarriage, or increase the chance of having a baby with birth defects. The March of Dimes has concluded that moderate caffeine is of low risk to pregnant and nursing women.

A study in the early 1990s compared more than 2,800 women who had recently given birth to 1,800 women diagnosed as infertile. Caffeine habits had little or no impact on the reported time it took to conceive in those who had given birth, and was not a risk factor in the infertile. A similar study in Denmark only pointed to smoking as a factor in delayed conception.

Babies born to women who consumed large amounts of caffeine during pregnancy might demonstrate delayed growth or delayed mental or physical development. However, caffeine consumption equivalent to about a cup and a half of coffee a day had no effect on a child's birth weight, length, and head circumference; nor did it have an effect on follow-up exams of the children at eight months of age and at seven years. In a study of 1,500 women, neither the motor skills nor the intelligence of these children was affected by their mother's caffeine consumption. Review of more than 20 studies since the 1980s show no evidence that caffeine causes either low birth weight babies, or early birth.

One study carried out between 1959 and 1966 found that very high levels of a caffeine metabolite is a marker for spontaneous abortion. Measured at 11 weeks gestation, the amount of the metabolite, paraxanthine, in blood serum was higher in women who had lost a pregnancy than in women in the control group. The risk of spontaneous abortion in women with the very highest level of paraxanthine was twice that than for the women with the lowest recorded levels. The levels were measured more than 30 years later, and the findings reported in 2000.

Caffeine can enter the milk of breastfeeding mothers. Babies younger than six months cannot metabolize caffeine as well as do adults. Mothers are advised, however, that up to three cups of coffee, or several cans of soda, can be consumed without passing caffeine on to their nursing infants.

The American Cancer Society states that there does not seem to be any relationship between caffeine and cancer. However, other adverse effects for women remain a concern, such as the possibility that large amounts of caffeine could contribute to osteoporosis (thinned and fragile bones), particularly in elderly women. As caffeine is a diuretic, which increases loss of fluids and electrolytes in the urine, it could rob the body of calcium. Nevertheless, a study published in 2001 concluded that the net effect of carbonated sodas on the body's calcium is negligible, and that the loss of calcium in urine due to carbonated drinks is too small to affect calcium balance.

REACTIONS WITH OTHER DRUGS OR SUBSTANCES

Caffeine cannot sober a drunk or save someone who is lethargic or unconscious from an overdose of a sedating drug. However, because caffeine lowers stomach pH, it can affect the absorption of other substances. Other drugs such as oral contraceptives, cimetidine, disulfiram, and alcohol can delay the body's ability to rid itself of caffeine.

TREATMENT AND REHABILITATION

Legally, caffeine is not regulated as a dangerously addictive substance. Yet, withdrawal from caffeine is documented as a recognized set of symptoms in the medical literature. Many people who regularly consume caffeine and then suddenly stop will experiencePage 65  |  Top of Article headache, irritability, muscle aches, and lethargy, including impaired concentration.

As with any active agent that produces a withdrawal syndrome, the common-sense approach is to gradually wean oneself from caffeine in order to minimize any symptoms. Those wishing to decrease their use should taper off slowly and perhaps substitute cups of caffeinated drinks with decaffeinated varieties or other caffeine-free beverages.

The extent to which people suffer withdrawal from caffeine use remains controversial. However, a study reported that 11,000 subjects were interviewed about their daily consumption of caffeine, among a host of other questions about lifestyle. Only 11% reported withdrawal symptoms from stopping caffeine intake, and only 3% said their symptoms interfered with daily living. Notably, that figure breaks down differently for the genders: 5.5% of women, but only 0.9% of men, reported symptoms from stopping caffeine intake that affected daily activities. Nevertheless, the study concluded that caffeine withdrawal remains a well-documented phenomenon. A major symptom of abrupt cessation of caffeine use is a headache of moderate to severe intensity that generally begins within 18 hours of the last dose. It peaks at about three to six hours of onset. The feeling is of fullness in the head that continues to a diffuse, throbbing pain, and is worsened by physical activity. Sadness and mild nausea are also reported by a quarter of those who show the withdrawal headache. Those who chronically consume 500 to 600 mg of caffeine per day are more likely to experience withdrawal if they suddenly cease their habit.

PERSONAL AND SOCIAL CONSEQUENCES

A caffeine roundtable discussion by experts concluded that there is no evidence that caffeine is linked to the socially damaging behaviors that characterize drugs of abuse.

LEGAL CONSEQUENCES

There are no legal consequences since caffeine is not a scheduled substance.

Legal history

In 1909, the federal government seized a shipment of Coca-Cola syrup, citing the added caffeine as a poisonous and deleterious substance. In 1959, caffeine was listed in the Code of Federal Regulations as generally recognized as safe, when used in cola type drinks at a level set at 0.02%, based on industry standards at that time. In 1997, the FDA required labeling of the caffeine content of foods and drinks.

Federal guidelines, regulations, and penalties

The FDA allows soft drink manufacturers to add caffeine to a limit of 72 mg per 12-ounce (355 ml) serving. Coffee and tea, containing caffeine naturally rather than as an additive, are not regulated for caffeine content.

See also Ephedra ; Herbal drugs

RESOURCES

Books

Braun, Stephen. Buzz. New York: Oxford University Press, 1996.

Pendergrast, Mark. Uncommon Grounds. New York: Basic Books, 1999.

Periodicals

Bell, Douglas. "Effect of Caffeine and Ephedrine Ingestion on Anaerobic Exercise and Performance." Medicine and Science in Sports and Exercise 33 (August 2001): 1399-1403.

Cordes, Helen. "Generation Wired." The Nation (April 27,1998) On-line edition. .

Sparano, Nicole. "Is the Combination of Ibuprofen Plus Caffeine Effective for the Treatment of Tension-type Headache?" Journal of Family Practice 50 (January 2001): 312-319.

Other

Center for the Evaluation of Risks to Human Reproduction Web site. .

Cohen, Elizabeth. "Energy Drinks Pack a Punch, But Is It Too Much?" CNN.com. . May 29, 2001 (January 30,2002).

Organizations

American College of Sports Medicine, 401 Michigan Street, Indianapolis, IN, USA, 46202-3233, (317) 637-9200, (317) 634-7817, mkeckhaver@acsm.org, .

National Headache Foundation, 428 W. St. James Place, 2nd Floor, Chicago, IL, USA, 60614-2750, (888) 643-5552, (773) 525-7357, (888) 643-5552, info@headaches.org, .

Roberta L. Friedman, Ph.D.

Source Citation

Source Citation   

Gale Document Number: GALE|CX3402000037

Disclaimer:   This information is not a tool for self-diagnosis or a substitute for professional care.