How does coffee stimulate the brain

Coffee: The everyday drug caffeine

For this reason, athletes also view caffeine as a doping agent that increases breathing capacity and endurance. However, to be caught red-handed, you have to drink more than five cups of coffee in a day. The team of the Dutch triathlete and cyclist Asker Jeukendrup, who teaches exercise physiology and nutrition for athletes at the University of Birmingham, determined the benefits of various measures on a virtual bike course over forty kilometers. According to his computer simulation, exercise is still the most effective: it improves time by one to seven minutes. A few minutes can also be gained with an aerodynamically favorable posture. But even caffeine in moderate doses still brings 55 to 84 seconds, while a longer stay at high altitude only takes around 30 seconds to prepare.

By constricting the blood vessels, caffeine also reduces the blood flow to the brain and thus its supply of glucose. The brain is extremely sensitive to hypoglycaemia, i.e. the drop in blood sugar levels below normal values. Long before the muscles notice this energy deficit, headaches, sweats and dizziness or even fainting spells occur. Caffeine increases the effects of hypoglycaemia on the brain, so that the alarm signals set in prematurely. Therefore, it is recommended that people at risk of hypoglycaemia take the drug in moderate doses - especially those taking anti-diabetic drugs.

What Causes Caffeine's Diuretic Effects? Ultimately, it is an indirect effect based on the contraction of the vessel walls. In response to the increased blood pressure, the kidneys increase the rate of filtration, thereby reducing blood volume. With three cups of coffee in two hours, the amount of urine increases by thirty percent.

But now we come to the most important property of caffeine: its ability to keep you awake. This effect is also based on its binding to the adenosine receptor. Its role in sleep has been explored for over a century. In 1912, the physiologists René Legendre and Henri Piéron kept dogs artificially awake for several days. They then took cerebrospinal fluid (liquor cerebro-spinalis) from them and injected it into the brains of animals that had just been awakened. They immediately fell asleep again. According to this, substances accumulate in the brain when they are awake, which play "sandmen" as it were. Since the 1970s there has been increasing evidence that one of these substances is adenosine.

Regulation of the need for sleep

The proof of this was provided in 1997 by Tarja Porkka-Heiskanen and her colleagues at the University of Helsinki. They let cats play non-stop for hours, preventing them from falling asleep. At the same time, they measured the adenosine concentration in the brain with the help of probes that they had inserted through the skull. This increased steadily, while the cats in their artificial wakefulness became more and more tired from hour to hour. As soon as the animals fell asleep, however, it sank again.

The longer one is awake, the more adenosine accumulates in the brain: it forms a kind of "tiredness signal". By increasingly saturating its receptors, it inhibits adenylate cyclase more and more, so that the production of cAMP steadily decreases. Various molecular cascades then cause critical changes in the waking and sleeping centers and overturn the balance from waking to sleeping.

Adenosine is therefore a highly effective regulator of the need for sleep. Because it builds up in the brain when we are awake, the longer we stay awake the more tired we get. It is then released and consumed again during sleep. Since caffeine acts as an antagonist to adenosine, it can be viewed as an anti-fatigue agent. When it binds to the adenosine receptors, it activates adenylate cyclase, triggering molecular cascades that prolong the wakefulness. Thereby it acts as a stimulant.

Sometimes pilots are on duty for a long time - for example on long-haul flights that last 10 to 15 hours and which are preceded by extensive preparation times. They have to have a clear head at all times. In a research project with Didier Lagarde and Maurice Beaumont from the military health service in Brétigny-sur-Orge and Françoise Chauffard from the Nestlé research center in Lausanne, we therefore examined the behavior of pilots during long awake times and researched the effects of caffeine. We wanted to find out how to benefit from the positive effects without being exposed to the negative ones that occasionally occur, especially with high doses. As mentioned at the beginning, such undesirable side effects of coffee consumption include, in addition to the diuretic effect, above all phenomena such as palpitations, tremors and nervousness.

In our project we tested different ways of administering caffeine. So we looked at a "slow release caffeine". 300 milligrams of the pure substance are packed in gelatine capsules, and a binding agent ensures that the active ingredient is only gradually released into the intestines and blood. The caffeine concentration is distributed more evenly over longer periods of time. This means that it stays above the effectiveness threshold for much longer. That is the value that, on average, maintains the state of being awake. At the same time, the side effects, which mainly result from a sharp increase in concentration, are avoided.

During normal coffee drinking, the caffeine level in the blood skyrockets and then drops again just as quickly. As a result, it is only high enough for around two hours to produce the usual effects. If the caffeine intake is prolonged, however, the effective concentration remains for almost ten hours.

In our experiments, the participants also had to undergo so-called survival tests. During this training they suffered from stress and lack of sleep, which impaired skills such as mental arithmetic, map reading and motor skills. Over time, dexterity and alertness decreased and a feeling of weakness set in. Spiritual achievements, which we used as a measure, lasted longer and longer. Dosed released caffeine in gelatine capsules mitigates all these negative effects - this is the conclusion of our research. The test participants, who remained constantly under the influence of the stimulant, were able to perform their tasks better. However, they ended up feeling more irritable and less sociable than their colleagues who hadn't taken anything.

In another study, we prevented volunteers from sleeping for 64 hours. If they swallowed a caffeine capsule every twelve hours, the ability to concentrate and psychomotor performance remained fully intact until the second day. Otherwise, these abilities decreased significantly in the first night.

Adjusting the internal clock

However, caffeine can not only keep you awake, it can also help you adjust your internal clock, for example, to adapt it to a different time zone. The epiphysis or pineal gland in the brain usually secretes the hormone melatonin at night, which regulates the rhythm of waking and sleeping. Daylight blocks the nerve pathways that stimulate this secretion. The ups and downs in the release of melatonin therefore exactly follow the alternation of day and night. If one of the parameters is changed, the equilibrium is overturned. After a night flight from New York to Berlin it gets light "too early". The pineal gland therefore releases melatonin even during the day, and you feel sleepy. The traveler suffers from jet lag because his internal clock and the external conditions are out of sync.

What can you do about it? Melatonin is sometimes prescribed in the United States to help alleviate jet lag. Taken in the early evening, it is said to increase the concentration of the hormone towards the beginning of the night. In this way, one hopes to readjust the sleep phase and thus adjust the internal clock.

In an experiment we compared the effectiveness of melatonin and caffeine against jet lag. Test pilots flew from San Antonio in Texas to Mont-de-Marsan in France, a ten-hour flight with a time difference of seven hours. Before starting, they had to undergo cognitive and psychomotor tests that provided information about their performance. Various physiological parameters such as pulse and blood pressure were also measured.

Some participants took melatonin in the late afternoon two days before to three days after the flight. Others were given an extended-release caffeine capsule in the morning for five days after the flight. Still others swallowed a placebo, a drug without an active ingredient, but which looked exactly like the melatonin or caffeine capsules. After the flight, we again checked the cognitive and psychomotor skills and measured the physiological parameters in order to obtain information about the shift in the biological rhythms due to the time difference.

In this experiment, caffeine was found to be very effective. Taken in the morning, it becomes bound to the adenosine receptors of the pineal gland and inhibits the release of melatonin. By suppressing the release of the hormone at the right moment, it increases the effect of daylight. As a result, the internal clock adjusts itself to the new light-dark rhythm by one hour per day. The test participants therefore overcame the time difference four days earlier than the members of the control group with placebo. Compared to melatonin, caffeine had the advantage that it didn't make you sleepy.

If a driver loses control of his vehicle, it is usually due to a lack of alertness - after all, ten to twenty percent of all traffic accidents have this cause. That is why it is important to keep regular rest periods. In addition, the international conference on signs of fatigue and the risk of accidents in road traffic also recommends the consumption of caffeine. Elke de Valck's working group at the University of Brussels tested the ability of drivers to control their car after certain periods of time without sleep. Taking delayed-release caffeine proved to be extremely beneficial: the risk of losing control of the vehicle was significantly lower afterwards.

When sailing, the watch on the bridge is often monotonous, so that attention gradually wears off. Here, too, the consumption of caffeine improves concentration considerably and in particular increases the ability to perceive objects appearing on the horizon, which is of eminent importance in order to avoid collisions.

Is coffee addicting?

After highlighting all of these positive properties of caffeine, with few relatively harmless side effects, the question arises whether it might not cause serious health problems in the long run and at high doses. What about the cancer risk, for example? To gauge it, the Swedes, who are among the most avid coffee drinkers in the world, conducted a large-scale epidemiological study. It covered 59,000 women between the ages of 40 and 76. However, the analysis of the data did not reveal any connection between coffee consumption and the incidence of breast cancer. Likewise, there was no association with pancreatic, colon or ovarian cancer.

As far as negative long-term effects are concerned, coffee is suspected of raising cholesterol levels. However, caffeine does not play a role. The accumulation of fat in the blood may come from the lipids in coffee. Their content is particularly high if the powder is boiled together with the water.

As a drug, coffee naturally has to put up with the question of whether it is addictive. Consumed in high doses, it can actually create a type of addiction, but it is different from that resulting from tobacco and alcohol abuse, or from the use of drugs such as cocaine, cannabis, or heroin. A positive neural amplifier system in the form of a reward spiral, as occurs with hard drugs, does not play a role with caffeine.

The pleasure a person experiences while using drugs has many causes. Psychological factors play a role as well as physiological and cognitive processes and the sense of taste. Dependence requires regular and usually increasing drug consumption.

Characteristic addictive behavior, which includes withdrawal symptoms, compulsive drug procurement, and self-administration, involves a well-defined ensemble of neurons spanning five brain areas: the ventricular roof, the substantia nigra, the corpus striatum, the cortex, and the nucleus accumbens. The interconnection of these centers creates a permanent link between the gain in pleasure and the conscious action that brings it about - for example lighting a cigarette.

Caffeine, on the other hand, activates neurons from another region of the brain, namely the caudate nucleus (tail nucleus). This region does not belong to the strongly connected neuronal system just mentioned. It can release dopamine, which means increased pleasure, and pass this positive feeling on to the cortex. However, the connections are not so strong that the pleasant sensation is experienced as indispensable. So if there is an addiction, it is in no way comparable to that of hard drugs, tobacco or alcohol.

Accordingly, the withdrawal symptoms when you suddenly stop consuming caffeine are usually quite mild. Sometimes a headache occurs, and the more coffee the person has drunk on a regular basis, the worse. But they don't last long: they start about 12 to 24 hours after the last cup of coffee, peak after 48 hours and disappear again after a week at the latest. This withdrawal symptom probably explains the headache that some people experience on weekends. During the week, they habitually drink large amounts of coffee at work, which narrows the blood vessels in the brain. At the weekend, consumption suddenly drops. As a result, the vessels expand and create headaches due to the pressure in the skull.

Prevention of paralysis

In the long run, however, excessive caffeine consumption can lead to caffeinism, a syndrome characterized by tremors, anxiety, irritability, nervousness and sleep disorders. In some cases, you also experience palpitations, an increase in pulse and breathing rate, and anorexia. Women are more prone to such disorders than men - perhaps because, as mentioned, caffeine in their blood is broken down less quickly.

On the other hand, regular coffee consumption seems to provide some protection against Parkinson's disease. In this degenerative disease, which usually occurs in old age, the death of nerve cells in the brain that produce the neurotransmitter dopamine leads to motor and attention disorders. A study of 8,000 people over thirty years found that Parkinson's syndrome was less common in people who drink coffee. In addition, the disease is less severe with high coffee consumption. This is reasonable in that caffeine causes the release of dopamine, which Parkinson's disease lacks. The usual treatment also consists of the administration of L-Dopa, which is converted into dopamine in the brain.

So caffeine definitely has pharmacological effects. At the same time, it is consumed daily by billions of people around the world. So is it a drug or a stimulant? If caffeine in the form of gelatin capsules were called a drug, it would require a prescription. On the other hand, if it were freely sold, many people could benefit from this stimulant molecule, provided they do not abuse it. The situation is paradoxical: the use of psychostimulants is usually advised against; but caffeine, in the form of coffee or soft drinks, is de facto the most widely consumed psychostimulant in the world.


Décalage horaire, mélatonine et caféine à liberation prolongée. M. Beaumont et al. in: Médicine et armées, vol. 30, p. 135 (2002).

Slow-Release Caffeine: a New Response to the Effects of a Limited Sleep Deprivation. By D. Lagarde et al. in: Sleep, Vol. 23, p. 5 (2000).

The Effects of 600 mg of Slow Release Caffeine on Mood and Alertness. By B. Sicard in Aviation Space and Environmental Medicine, Vol. 67, p. 859 (1996).

From: Spektrum der Wissenschaft 6/2003, page 64
© Spektrum der Wissenschaft Verlagsgesellschaft mbH