CAFFEINE THE WORLD'S MOST COMMON PSYCHOSTIMULANT

Oakley Ray, Drugs, Society and Human Behaviour, pp. 291-295, 304-310

On a daily basis, more people use caffeine than any other psychoactive drug. Many use it regularly, and there is evidence for dependence and some evidence that regular use may interfere with the very activities people believe that it helps them with. It is now so domesticated that most modern kitchens contain a specialized device for extracting the chemical from plant products (a coffee maker), but Western societies were not always so accepting of this drug. How many drugs can lay claim to divine intervention in their introduction to humankind? The xanthines, of which caffeine is the best known, have three such legends, and that fact alone tells you that this has been an important class of drugs throughout the ages . COFFEE The legends surrounding the origin of coffee are at least geographically correct. The best concerns an Arabian goatherd named Kaldi who couldn't understand why his goats were bouncing around the hillside like a bunch of kids. One day he followed them up the mountain and ate some of the red berries the goats were munching. "The results were amazing. Kaldi became a happy goatherd. Whenever his goats danced he danced and whirled and leaped and rolled about on the ground." Kaldi took the first coffee trip! A holy man took in the scene, and "that night he danced with Kaldi and the goats." A veritable orgy. The legend continues with Mohammed telling the holy man to boil the berries in water and have the brothers in the monastery drink the liquid so they could keep awake and continue their prayers. Coffee use expanded as the West was won, and the amount consumed by each person showed steady increases. Some experts became worried about the tendency to have another cup of coffee, although they believed they could explain it. From the 1950s to the 1970s coffee drinking declined while use of soft drinks rose. In 1970, Americans still drank more gallons of coffee per capita than of any other nonalcoholic beverage product, but by 1992 soft drink consumption was much higher than either coffee or milk. If the national drink is not as national as it once was, neither is it as simple. Kaldi and his friends could just munch on the coffee beans or put them in hot water and be content. Somewhere in the dark past, probably when the warehouses were burned down, the Middle East discovered that roasting the green coffee bean did not ruin it but, in fact, improved the flavor, aroma, and colour of the drink made from the bean. For years housewives, storekeepers, and coffeehouse owners bought the green bean, then roasted and ground it just before use. Commercial roasting started in 1790 in New York City, and the process gradually spread through the country. One problem is that, although the green bean can be stored indefinitely, the roasted bean deteriorates seriously within a month. Ground coffee can be maintained at its peak level in the home only for a week or two, and then only if it is in a closed container and refrigerated. Vacuum packing of ground coffee was introduced in 1900, a process that maintains the quality until the seal is broken. Coffee growing spread worldwide when the Dutch began cultivation in the East Indies in 1696. Latin America had an ideal climate for coffee growing, and with the world's greatest coffee-drinking nation just up the road several thousand miles, it became the world's largest producer. Different varieties of the coffee tree and different growing and processing conditions provide many opportunities for varying the characteristics of coffee. In the early 1950s about 94% of American coffee was from Latin America, but that percentage has steadily declined; today less than half is grown in this hemisphere. Brazil is the principal exporter to the United States, with Colombia second. Both countries grow arabica, which has a caffeine content of about 1%. Robusta, with a caffeine level at 2%, is the variety grown in Africa and is usually of a lower grade and price. The economics of coffee (it is number two in international trade, far behind oil) have as much to do with coffee consumption as does our changing life-style. A price increase in the early fifties-to a dollar a pound!-shifted us from a 40-cups-per-pound to a 60-cups-per-pound nation. This dilution reduced the cost but also the quality of the beverage. Two things happen when prices go up: the quality of the coffee decreases and people drink less coffee. Instant coffee has been around since before the turn of the century, but sales began their marked increase in the hustle and bustle after World War II: another decrease in the quality of the beverage, but an

increase in the convenience. Interestingly, Brazil imports many inexpensive African coffee beans to use in manufacturing instant coffee, since they believe that their coffee is too good to be used in that way. Today's supermarket shelves are filled with an amazing variety of products derived from this simple bean-pure Colombian, French Roast, decaf, half-caf, flavored coffees, instants, mixes, and even cold coffee beverages. The competition for the consumer's coffee money has never been greater, it seems. CAFFEINE PHARMACOLOGY Xanthines are the oldest stimulants known. Xanthine is a Greek word meaning yellow, the color of the residue if the xanthines are heated with nitric acid until dry. The three xanthines of primary importance are caffeine, theophylline, and theobromine. These three chemicals are methylated xanthines and are closely related alkaloids. Most alkaloids are insoluble in water, but these are unique, since they are slightly water soluble. These three xanthines all have similar effects on the body, with caffeine having the greatest and theobromine almost no stimulant effect on the central nervous system and the skeletal muscles. Theophylline is the most potent, and caffeine the least potent, agent on the cardiovascular system. Caffeine, so named because it was isolated from coffee in 1820, has been the most extensively studied and, unless otherwise indicated, is the drug under discussion here. Time Course In humans, absorption of caffeine is rapid after oral intake; peak blood levels are reached 30 minutes after ingestion. Although maximal CNS effects are not reached for about 2 hours, the onset of effects may begin within half an hour after intake. The half-life of caffeine in humans is about 3 hours, and no more than 10% is excreted unchanged. Cross-tolerance exists among the methylated xanthines; loss of tolerance may take more than 2 months of abstinence. The tolerance, however, is low grade, and, by increasing the dose two to four times, an effect can be obtained even in the tolerant individual. There is less tolerance to the CNS stimulation effect of caffeine than to most of its other effects. The direct action on the kidneys, to increase urine output, and the increase of salivary flow do show tolerance. Dependence on caffeine is real. Whereas people who are not coffee drinkers or who have been drinking only decaffeinated coffee often report unpleasant effects (nervousness, anxiety) after being given caffeinated coffee, those who regularly consume caffeine report mostly pleasant mood states after drinking coffee. Various experiments have reported on the reinforcing properties of caffeine in regular coffee drinkers; one of the most clear-cut allowed patients on a research ward to choose between two coded instant coffees, identical except that one contained caffeine. Subjects had to choose at the beginning of each day which coffee they would drink for the rest of that day. Subjects who had been drinking caffeine-containing coffee before this experiment almost always chose the caffeine-containing coffee. Thus the reinforcing effect of caffeine probably contributes to psychological dependence. There has long been clear evidence of physical dependence on caffeine as well. The most reliable withdrawal sign is a headache, which occurs on an average of 18 to 19 hours after the most recent caffeine intake. Other symptoms include increased fatigue and decreased sense of vigor. These withdrawal symptoms are strongest during the first 2 days of withdrawal, then decline over the next 5 or 6 days. Physiological Effects The pharmacological effects on the CNS and the skeletal muscles are probably the basis for the wide use of caffeine-containing beverages. With two cups of coffee taken close together (about 200 mg of caffeine), the cortex is activated; the EEG shows an arousal pattern, and drowsiness and fatigue decrease. This CNS stimulation is also the basis for "coffee nerves," which can occur at low doses in sensitive individuals and in others when they have consumed large amounts of caffeine. In the absence of tolerance, even 200 mg will increase the time it takes to fall asleep and will cause disturbances in the sleep. There is a good relationship between the mood-elevating effect of caffeine and the extent to which it will keep the individual awake. Higher dose levels (about 500 mg) are needed to affect the autonomic centers of the brain, and heart rate and respiration may be increased at this dose. The direct effect on the cardiovascular system is in opposition to the effects mediated by the autonomic centers. Caffeine acts directly on the vascular muscles to cause dilation, whereas stimulation of the autonomic centers results in constriction of blood vessels. Usually dilation occurs, but in the brain the blood vessels are constricted, and this constriction may be the basis for caffeine's ability to reduce migraine headaches. The opposing effects of caffeine, directly on the heart and indirectly through effects on the medulla, make it very difficult to predict the results of normal (that is, less than 500 mg) caffeine intake. At higher

levels there is an increase in heart rate, and continued use of large amounts of caffeine may produce an irregular heartbeat in some individuals. The basal metabolic rate may be increased slightly (10%) in chronic caffeine users, since 500 mg has frequently been shown to have this effect. This action probably combines with the stimulant effects on skeletal muscles to increase physical work output and decrease fatigue after use of caffeine. Hyperactivity Many studies have looked at the effect of caffeine on the behavior of hyperkinetic children and most have not shown any therapeutic effect. One report of the effects of 3 and 10 mg per kg of caffeine on normal 8- to 13-year-old boys showed decreased reaction times and increased vigilance along with increased motor activity. That's pretty much what might be expected from a mild stimulant. Sobering up Even the television ads tell you-make that one last drink for the road coffee. There is not a lot of evidence to support the value of this. Caffeine will not lower blood alcohol concentration-but it may arouse the drinker. As they say-put coffee in a sleepy drunk, you get a wide-awake drunk. You can easily imagine that this might be more dangerous than if the drunk had been left to sleep it off. Caffeine is one of those drugs that seem to always be in trouble. It's always suspected of doing bad things. Since it is probably the most widely used psychoactive drug in the world (it's acceptable to those in the Judaic-Christian as well as Islamic traditions). It is understandable that it would elicit both good and bad reports. Although it is important to point out that there is not yet clear evidence that moderate caffeine consumption is dangerous, the scientific literature has investigated the possible effects of caffeine in cancer, benign breast disease, reproduction, and heart disease. Part of the problem in knowing for certain about some of these things is that epidemiological research on caffeine consumption is difficult to do well. Coffee drinkers also tend to smoke more, for example, so the statistics have to correct for smoking behaviour. Also, some studies have asked only how many cups of coffee people drink per day, without correcting for decaffeinated coffee, tea, colas, or other sources of caffeine, or without correcting for differences between weekend and weekday coffee drinking. Heart Disease There are many reasons for believing that caffeine might increase the risk of heart attacks, including the fact that it increases heart rate and blood pressure. Until recently, there were about as many studies that found no relationship between caffeine use and heart attacks as there were studies that found such a relationship. One very interesting report used a somewhat different approach. Rather than asking people who had just had heart attacks about their prior caffeine consumption and comparing them with people who were hospitalized for some other ailment (the typical retrospective study), this study began in 1948 to track male medical students enrolled in the Johns Hopkins Medical School. More than 1000 of these subjects were followed for 20 years or more after graduation and periodically asked about various habits including drinking, smoking, and coffee consumption. Thus this was a prospective study, to see which of these habits might predict future health problems. Those who drank five or more cups per day were about 2.5 times as likely to suffer from coronary heart disease. This result and recent indications that coffee drinking may increase blood cholesterol levels has stimulated more research, including a large-scale retrospective study which reported that the incidence of nonfatal heart attacks in men under 55 years old was directly related to the amount of coffee consumed, among both smokers and nonsmokers. Those drinking five or more cups per day were about twice as likely to suffer a heart attack as those who drank no coffee. The best research, then, gives a strong suggestion that caffeine may increase the risk of heart attacks. This would be of special concern to those with other risk factors (e.g., smoking, family history of heart disease, overweight, high blood pressure, high cholesterol levels). Caffeinism Caffeine is not terribly toxic, and overdose deaths are extremely rare. It is estimated that over 10 g (equivalent to 100 cups of coffee) would be required to cause death from oral caffeine, and one person has died after an intravenous injection of 3.2 g. Death is produced by convulsions, which lead to respiratory arrest. However, caffeinism (high intake of caffeine) can cause a variety of unpleasant symptoms, and because of caffeine's domesticated social status it may be overlooked as the cause. For example, nervousness, irritability, tremulousness, muscle twitching, insomnia, flushed appearance, and elevated temperature may all result from excessive caffeine use. There may also be palpitations, heart arrhythmias, and gastrointestinal disturbances. In several cases in which serious disease has been suspected, the symptoms have miraculously improved when coffee was restricted.