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Centuries of Craving

Caffeine, particularly in the form of tea and coffee, has enjoyed a long history of adoration and exaltation the world over, dating back nearly 5000 years to ancient China. When coffee was introduced in Europe in the seventeenth century, its powers of wakefulness were immediately recognized as a fortuitous boon, coming, as it did, in the midst of the Enlightenment. Artists such as Voltaire, Bach and Rousseau are said to have extolled the intellectual benefits of the new drink.

As Wolfgang Schivelbusch writes in Tastes of Paradise: A Social History of Spices, Stimulants, and Intoxicants, "[Coffee] spread through the body and achieved chemically and pharmacologically what rationalism and the Protestant ethic sought to fulfill spiritually and ideologically. With coffee the principle of rationality entered human physiology."

At least part of the reason for the proliferation of the use of caffeine?then and now?is the practically ubiquitous presence of plants containing it. Caffeine comes from an alkaloid family of generally poisonous nitrogen-containing compounds that includes the likes of strychnine, nicotine, morphine, mescaline, and emetine (the deadly ingredient in hemlock): a veritable who's who of nasty narcotics and poisons. Unlike the other compounds in this family, though, which are mostly associated with just one plant, caffeine occurs naturally in an extraordinary variety of plants?more than 100, in fact?including those as dissimilar as some lilacs and cacti.

In modern times, caffeine has handily maintained its prominence in daily life. After the consumption of water, beverages containing caffeine are the most popular on the planet?even more popular than alcohol. The United States, for example, averages 168 mg of caffeine per person every day, or about a cup and a half of coffee for each of its 275 million inhabitants each and every day. Which, as it turns out, is nothing compared to the 414 mg per day?or four cups a day per person?for the inhabitants of the Netherlands.

Caffeine, in a Nutshell

Though people have been ingesting caffeine for millennia, not until 1820 was the chemical structure of caffeine?the stimulant in coffee and tea that inspires its devotion?finally identified. Only in the last 200 years, then, have we come to have anything close to a true grasp on how this deceptively powerful drug affects our body and brain.

Caffeine is a rather lumpy molecule that, unlike alcohol?which is shaped in a way so as to make it fairly indiscriminant about what it binds to?tends to attach itself to very few molecules in the body. When an attachment is made, however, the fit is tight, and the interaction much stronger than that of alcohol. This is why one cup of coffee?which holds about 100 milligrams of caffeine?can have a physiological effect on the body that is as powerful, although different, as one beer, which holds about 14,200 milligrams of alcohol.

Astrid Nehlig and her colleagues at the French National Institute for Health and Medical Research, for instance, have probed the possibility that caffeine shares some effects with addictive drugs like cocaine. The researchers injected rats with a radioactive form of glucose, as well as with varying amounts of caffeine?between the human equivalents of one and ten cups of coffee?and then they examined levels of blood flow to regions of the brain known to be involved in the brain's reward system. One such region, called the nucleus accumbens, has been shown to be affected by cocaine. Nehlig's results showed that caffeine did not seem to affect the nucleus accumbens; however, one region that did show a surge of activity, the caudate-putamen, has also been linked to drug addiction, though less formidably than the nucleus accumbens.

So, the verdict is still out on whether caffeine should be considered a drug.

Your Brain and its Buzz

Scientists are fairly confident, however, that caffeine's most famous effect?that of excitation and heightened awareness?is understood.

In Buzz: The Science and Lore of Alcohol and Caffeine, Stephen Braun explains: "The brain...resembles a car with several brake pedals and several accelerators. Interfere with any one of these pedals, and you'll affect the speed and action of the car."

One of the brake pedals to which Braun refers comes in the form of a molecule called adenosine, which is one of the key players in sleep and wakefulness and, consequently, in the way caffeine affects the brain. Adenosine, which is found in most areas of the body, is a by-product of any working cell; the harder the cell works, the more adenosine is produced. After the brain is fully active, adenosine then works to gradually quiet the brain back down. In a 1994 Science article, Harvard Medical School's Robert Greene explained how the accumulation of adenosine triggers a brake on adenosine production. Adenosine, then, is an important link in a cyclical and self-governing chain affecting sleep and wakefulness.

Caffeine enters the picture in that its structure is nearly identical to adenosine's. In fact, the caffeine molecule is slightly smaller than adenosine, so when it comes in contact with adenosine-receptors on neurons, it binds more readily than even adenosine. Although the fit is snug, it is not perfect. Thus caffeine does not initiate the chain reaction in the cell that adenosine does; it just fills the space so that adenosine can't do its job of quieting the brain.

Caffeine's stimulant reaction, then, is not as we might imagine. Coffee is not some energy form that excites our nervous system; it simply thwarts one of the main processes by which the nervous system is generally kept calm.

Caffeine as Panacea?

In the tradition of the Enlightenment philosophers, many scientists and coffee enthusiasts are eulogizing caffeine today for its seemingly myriad advantageous effects on body and mind.

A prominent example of this is the case of memory, which some studies have shown is aided by caffeine. As Stephen Braun writes, "Neurons bathed in modest levels of caffeine respond more vigorously to stimulation and form longer-lasting changes in their connections with other neurons." It has also been speculated that because caffeine increases levels of adrenaline?the "fight or flight" hormone, which plays a role in our memories of important and shocking events?it might prompt improved memory in other ways.

Additionally, caffeine has been shown to improve athletic performance, astoundingly in some cases, by up to 70 percent. This is why the Olympic Committee lists caffeine as a "doping agent" and has straightforward (though fairly reasonable) rules for what is an acceptable amount of caffeine in an athlete's blood. The legal limit, 12 micrograms per milliliter, equals about six cups of coffee in a half hour.

Perhaps most obviously, caffeine has been shown in recent studies?confirming hundreds of years of folk wisdom?to improve rapidity and accuracy of performance in certain intellectual tasks. Braun writes that caffeine is most helpful in "relatively passive, automatic, data-driven tasks such as auditory reaction time, visual-choice reaction time, and performing simple arithmetic," and is less useful in more complicated processes, like "logical and numerical reasoning, reading comprehension, and complicated arithmetic."

Caffeine as Poison

But of course caffeine has its opponents?and, no doubt, its negative effects.

Like the other members of its family, caffeine, as a poison of sorts, can actually be toxic?even lethal. But a person would have to consume a really huge amount of caffeine to die from it. A deadly dose of coffee?or any of the other caffeine-bearing products, like chocolate or cola?is equivalent to 40 strong cups (5,000 milligrams) and your body would most certainly reject it before it could do any harm. An injection of this amount of pure caffeine, however, would more than likely do the trick.

It probably won't come as a surprise, then, to discover that the human body indeed responds to caffeine as it would a poison?very similarly, in fact, to the manner in which it responds to alcohol. Liver enzymes are called on to assail the caffeine molecules and break them down as quickly as possible. This is achieved by reversing the chemical processes by which caffeine was constructed in the plants from which it comes. Groups of molecules?the methyl groups of theophylline, theobromine, and paraxanthine?are separated one by one.

This process has an interesting net effect on humans. It turns out that one of these molecules called paraxanthine is very similar to caffeine in structure and in its effect on the brain. Paraxanthine is even more potent than caffeine itself, and since 70 percent of a dose of caffeine is broken down into paraxanthine, a healthy percentage of the buzz that coffee gives us is not from caffeine at all, but from the dismantling of caffeine into paraxanthine.

As with most other drugs, everyone's body reacts a little differently to the intake of caffeine. For some, the smallest amount of caffeine is enough to keep them awake all night. Others profess to drinking ten?even twenty?cups a day without a disruption of sleep. Caffeine is known to upset stomachs and exacerbate anxiety in some people (though not in others), but to also ease headaches and bodily pains. It's often tied to irritability, depression, nervousness, and headaches.

In short, caffeine is not everyone's cup of tea. It is no simple chemical, and the reasons for the wild variation in its effects are not rooted in mere myth, but are the result of the chemical's complicated and not altogether understood interaction with each individual human body and mind it comes in contact with.

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