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THE SITUATION was very troubling. Counsellors at the Hazelden Foundation in
Center City, Minnesota, a leading drug treatment clinic, had learned that some
of the residents were smuggling in an addictive stimulant and sharing it with
their friends. This was a clear violation of the rules, but the clinic’s staff
concluded that they would fight no longer, and rescinded the unpopular ban on
coffee.

Some of the staff felt relieved. Why withhold a harmless substance that
helped the patients stay off alcohol or crack cocaine? After all, the founder of
Alcoholics Anonymous famously drank vast amounts of coffee, and almost all AA
meetings take place around a coffee pot. But others were concerned that some
patients were drinking so much coffee they weren’t getting enough sleep. And
there was a principle at stake. They felt that the caffeine in coffee was, quite
frankly, an addictive drug.

If that’s the case, the whole world is cheerfully addicted. In the US, almost
everyone drinks coffee. In Britain and Australia people drink coffee and tea.
And for Nigerians there’s the cola nut to chew on. People consume vast
quantities of caffeine in chocolate and soft drinks, and even in a pure pill
form. But is it truly a drug of abuse like cocaine or heroin? And if so, should
we kick the habit?

These are remarkably tricky questions. Headlines around the world last year
proclaimed that French researchers had proved that caffeine wasn’t really
addictive. In July, Astrid Nehlig from the Strasbourg laboratory of INSERM, the
French National Health and Medical Research Institute, announced that giving
rats moderate amounts of caffeine does not promote activity in a brain region
called the nucleus accumbens, thought to play a role in addiction (
ChemTech, vol 29, p 30). Even low doses of cocaine, amphetamines, nicotine
and morphine all activate this part of the brain. “The activation of the shell
of the nucleus accumbens seems to be one of the key mechanisms of addiction of
psychostimulants,” Nehlig says.

But what of the other mechanisms and brain structures thought to be involved
in drug addiction, such as the dopamine system? Caffeine makes us feel alert
because it blocks the receptors for a brain chemical called adenosine, which
normally dampens the activity of other neurotransmitters. Blocking adenosine
boosts brain activity, and may indirectly boost dopamine levels. Cocaine,
alcohol, nicotine and heroin also raise dopamine levels. “Obviously caffeine
shares some properties with the drugs of abuse,” Nehlig admits.

But she rejects the notion that caffeine could be considered an abused drug.
Some scientists think that rises in dopamine levels may be a general pleasure
response, not anything specifically linked to addiction. The main mechanisms of
action of caffeine and the other drugs are different, Nehlig insists. She points
out that with caffeine, “the extent of tolerance, withdrawal, or reinforcement
is never as dramatic as those observed with the drugs of abuse”.

Other researchers don’t dismiss these shared properties so lightly. “I
usually steer clear of the word addiction because it’s loaded with additional
baggage,” says Roland Griffiths, an expert on caffeine at the Johns Hopkins
Medical Institutions in Baltimore, Maryland. But he points to the behavioural
changes that caffeine can bring about. “Over the last ten years there has been a
greater appreciation in the general public that caffeine is a drug and produces
withdrawal, but I would guess that caffeine users are unaware of the extent to
which their behaviour is controlled by caffeine.”

Take, for example, a simple study in which Griffiths gave moderate caffeine
users red or blue capsules containing either a dose of caffeine or an inert
powder. On one day everybody got a caffeine pill of one colour, and on the next
day they got an inert pill that was the other colour. The following day they got
to choose whichever colour they preferred, and 80 per cent of the time they
chose the caffeine pill, regardless of whether this was red or blue. He told the
participants that they were testing the effects of compounds found in common
foods, so they had no idea what they were taking.

People clearly seek out caffeine, and when they can’t get it they’re not
happy. This fact should be obvious to anyone who has ever tried to function in
the morning without their usual cuppa, but until recently most researchers
assumed that caffeine withdrawal was mild and transient. “There seemed to be an
almost flat-out denial on the part of many that this is of any relevance and/or
importance,” says Griffiths. “Caffeine withdrawal occurs at much lower doses
than we had previously recognised.”

Withdrawal can occur in people who have as little as 100 milligrams of
caffeine a day, about the amount in two cups of tea or one cup of instant
coffee. Symptoms include headache, fatigue, difficulty concentrating and
drowsiness. The ill effects peak after a day or two without caffeine, and can
continue for more than a week. Surprisingly, Griffiths says, withdrawal can be
suppressed by rather low levels of caffeine. If you usually imbibe three cups of
coffee a day, or around 300 milligrams of caffeine, you can alleviate withdrawal
symptoms with as little as 25 milligrams. “There may be lots of people who are
dependent who think they are immune to withdrawal,” notes Griffiths. Someone who
skips their morning coffee and then has a cola with lunch won’t suffer as
badly.

Slow reactions

Some researchers worry that children are especially vulnerable to withdrawal,
as they often don’t have steady access to caffeine. Gail Bernstein at the
University of Minnesota in Minneapolis studied 30 children at times when they
were drinking caffeine regularly and during withdrawal periods. She showed that
they had slower reactions in tests that required them to watch a computer screen
and click a mouse in response to certain images during periods of withdrawal
(Journal of the American Academy of Child & Adolescent Psychiatry,
vol 37, p 858). “It’s maybe hard to say what you can transfer from the lab to
the real world,” she admits, but thinks the issue deserves more study, given the
aggressive promotion of soft drinks to children.

Although adults tend to drink the same amount of caffeine from day to day,
Griffiths says there is no convincing evidence that people can monitor and
regulate their caffeine intake. But in one study he did show that if people are
given coffee containing different doses of caffeine, they tend to drink more
when the dose is low. He notes that “if you put someone in withdrawal, they’re
going to head towards caffeinated foods”.

Researchers have also found that as people get used to drinking coffee, they
acquire tolerance to its effects. In one study, people given 400 milligrams of
caffeine a day initially experienced sleep problems. But after a week, their
total sleep time, and the number of times they awoke, returned to normal. In
another study, people got either caffeine or a placebo for 18 days. The two
groups did not differ significantly in ratings of mood, until they were given a
300-milligram dose of caffeine: this made people in the placebo group nervous
and jittery, but had no such effect on the group that was chronically exposed to
caffeine.

At a biochemical level, caffeine increases levels of catecholamines, the
neurotransmitters involved in the fight-or-flight response. So your body reacts
in the way it would if you were facing down a lion: your pupils dilate, your
breathing tubes open up, and your muscles get ready for action. Individuals
differ in their reaction to caffeine. Part of this is down to genes, but there
are other influences too. The half-life of caffeine is normally four to six
hours, but this doubles in women taking oral contraceptives and is halved in
smokers. Smokers are more likely than non-smokers to be coffee drinkers, and
ex-smokers consume more coffee than non-smokers but less than smokers. If
someone quits smoking but keeps drinking their usual amount of coffee or tea,
their caffeine levels can suddenly rise to levels that make most people feel
jittery, complicating efforts to stay off the cigarettes.

We all know why people should quit smoking. But does continually drinking
coffee or tea have any health risks that might make it worth giving up? Large
quantities of caffeine are deadly: tea or coffee could kill you, if you managed
to drink between 50 and 100 cups in one go. Your liver treats caffeine like any
other poison, and plants produce it to keep pests at bay. Yet evidence for
coffee’s contribution to common diseases remains far from clear. “You’ll find
that most people go into hyperbole on one side or the other,” says Griffiths.

Health worries have been around since at least 1674, when women in London
claimed it made their men impotent, according to Mark Pendergrast’s 500-page
opus on coffee, Uncommon Grounds. The most recent coffee concerns began
in the 1970s, when epidemiologists linked coffee consumption to heart disease,
pancreatic cancer and reproductive problems. More than twenty years later, these
links remain controversial, and scientists have yet to confirm any of them.
Several large epidemiological studies have failed to find any association
between coffee consumption and heart disease.

James Lane of Duke University Medical Center in Durham, North Carolina, is
convinced that there are risks, however. Caffeine raises blood pressure, and so
could contribute to heart disease later in life, he says. Over the past ten
years Lane has shown that the caffeine in four or five cups of coffee can raise
blood pressure by about five points and increase production of stress hormones
such as cortisol and catecholamines. “People in high-stress jobs become
dependent on caffeine. But the caffeine is making the stress in their life
worse,” says Lane.

Lane believes that we haven’t picked up this increase in risk because people
don’t report their caffeine intake accurately. They just don’t realise how much
they take in, he says, especially when one cup doesn’t always equal another. A
large coffee from Starbucks, for example, can contain a whopping half-gram of
caffeine, while a small cup of instant may contain less than 100 milligrams
(see figure). And consumption isn’t necessarily consistent over
the years.

There are further complications, too. Coffee and tea are a soup of many
chemicals, not just a vehicle for caffeine, says Peter Martin, of Vanderbilt
University’s new Institute for Coffee Studies in Nashville, Tennessee. Studies
by Lane and others that use pure caffeine miss the point, Martin says, because
substances such as chlorogenic acids are more abundant in coffee than caffeine.
“There may be pharmacological interactions that counteract the effects of
caffeine,” Martin says. He notes that chlorogenic acids have been shown to
affect opiate receptors in the same way as naltrexone, a medication that blocks
the “high” feeling that makes people want to use narcotics and alcohol.

Even the way coffee is prepared can create different compounds with effects
of their own. In 1996, Dutch investigators reported that unfiltered coffee made
in a cafetière or “French press” raised levels of harmful cholesterol by
9 to 14 per cent, while the same amounts of filtered coffee had no effect. The
researchers attributed the effect to cafestol and kahweol, alcohols found in
coffee oils (British Medical Journal, vol 313, p 8). It’s perhaps not
surprising that there is no clear picture of the effects of caffeine on
health.

Mark Klebanoff of the National Institute of Child Health and Human
Development near Washington DC decided that rather than relying on his
volunteers to report their own caffeine intake, he would look for a metabolite
of caffeine called paraxanthine in blood samples to test whether caffeine has
any effect on rates of miscarriage. “It’s not perfect, but at least it’s looking
at the issues in another way,” says Klebanoff. The study found an increased risk
of miscarriage only in women with the very highest levels of paraxanthine,
corresponding to more than five cups of coffee a day. Klebanoff views the
results as “at least reasonably reassuring for women”. Many pregnant women say
they quit drinking coffee anyway, because they lose the taste for it.

Brenda Eskenazi of the University of California School of Public Health in
Berkeley thinks that women should minimise their caffeine intake during
pregnancy just to be safe. She notes that caffeine can cross the placenta, is
present in breast milk, and has a longer half-life in a pregnant woman’s body
(11 hours compared to 6). Studies have shown that low doses of caffeine can
change a fetal heart rate even when the caffeine has no apparent effect on the
mother.

The debate over health effects is likely to continue for as long as people
keep drinking coffee and tea. But Klebanoff doesn’t think we should worry too
much about caffeine. “It didn’t take us long to figure out that cigarettes were
bad for you,” he points out. “If there was something terrible that it does to
us, we would have found it by now.” But caffeine consumption is so widespread
that even small risks for individuals could add up to major problems for society
as a whole. “It’s such a popular drug,” says Lane. “I think we really need to
have more people investigating it, just for peace of mind.”

Most people who come to work in Griffiths’s lab decide that they want to give
up caffeine, once they see the evidence of their dependence and how it
influences their daily life. If you want to quit, Griffiths suggests that you
first spend a week keeping a careful log of your intake. Then taper off slowly,
rather than quitting cold turkey, to minimise withdrawal symptoms. But be
warned: caffeine has a powerful allure. “Without exception, people in time have
decided to go back,” says Griffiths, who admits to drinking an occasional
caffeinated beverage. “If I have a message it’s that people should know that
caffeine is a drug and that they should treat it with respect.”