a
parametric analysis of caffeine dosing
conditions
Evans SM, Griffiths RR
Department of Psychiatry,
The Johns Hopkins University School of
Medicine
Baltimore, Maryland,
USA.
Although caffeine is the most widely used
behaviorally active drug in the world, caffeine
physical dependence has been only moderately
well characterized in humans. Four double-blind
experiments were conducted in independent groups
of healthy participants to assess the conditions
under which withdrawal symptoms occur upon
cessation of low to moderate doses of caffeine.
In experiment 1, there was no evidence that
the range or magnitude of caffeine withdrawal
symptoms differed when 300 mg of caffeine was
consumed as a single dose in the morning versus
100 mg at three time points across the day.
In experiment 2, both the range and severity
of withdrawal increased as a function of
caffeine maintenance dose (100, 300, and 600
mg/day), with even the lowest dose (100 mg)
producing significant caffeine withdrawal.
Experiment 3 showed that when individuals
were maintained on 300 mg caffeine/day and
tested with a range of lower doses (200, 100,
50, 25, and 0 mg/day), a substantial reduction
in caffeine consumption (</=100 mg/day) was
necessary for the manifestation of caffeine
withdrawal.
Experiment 4 manipulated duration of
exposure to caffeine (1, 3, 7, or 14 days of 300
mg/day) and showed that caffeine withdrawal
occurred after as little as 3 days of caffeine
exposure, with a somewhat increased severity of
withdrawal observed after 7 or 14 days of
exposure.
As a whole, this set of experiments provides
the most complete parametric characterization of
caffeine withdrawal to date and suggests that
caffeine physical dependence can occur under
more modest conditions (i.e., fewer doses per
day, lower daily dose, shorter duration of
exposure) than previously recognized.
Discussion
The present study provides the most
comprehensive parametric experimental analysis
to date of the dosing conditions necessary for
the development of caffeine physical dependence
as expressed by caffeine withdrawal symptoms
upon abrupt cessation of caffeine
administration. A particular strength of the
present study is that each of the four
parametric experiments was conducted using the
same general procedure in a different group of
moderate daily caffeine consumers.
Caffeine Withdrawal Symptoms.
The present studyconfirms and extends
previous findings regarding the symptoms
associated with the cessation of caffeine
consumption. The major symptom clusters that
were affected significantly in each of the four
experiments were increases in Headache,
Headache/Poor Mood (including irritability,
anxiety, feelings of depression), Tiredness
(drowsy, yawning, lethargy), Fatigue
(POMS), and Total Mood Disturbance (POMS) and
decreases in Activity/Alertness (alertness, well
being, desire to socialize, urge to do
task-related activities, concentration, energy,
satisfaction, self-confidence) and Vigor (POMS).
These symptom clusters overlap with the four
most prominent symptom clusters summarized in a
recent comprehensive review by Griffiths and
Mumford (1995) of the caffeine withdrawal
literature: headache, drowsiness, work
difficulty (decreased motivation for work/tasks,
impaired concentration), and decreased well
being/contentment (including decreased
self-confidence, increased irritability). The
present results also provide weak support for
two less prominent symptom clusters cited in the
Griffiths and Mumford (1995) review: decreased
friendliness and flu-like symptoms. As shown in
Table 2, decreased Friendly (POMS) and Flu-Like
Symptoms were intermittently sensitive to the
caffeine withdrawal manipulations across the
four experiments.
In summary, the present series of
parametric experiments confirms and extends
previous studies of caffeine withdrawal (see
reviews by Griffiths and Woodson, 1988a;
Griffiths and Mumford, 1995) and suggests that
caffeine physical dependence can occur under
more modest conditions (i.e., fewer doses per
day, lower daily dose, and shorter duration of
exposure) than previously recognized.
Significant caffeine withdrawal symptoms can
occur reliably when individuals are maintained
on as little as 100 mg caffeine each day, and
the severity of caffeine withdrawal is an
increasing function of the caffeine maintenance
dose.
Administration of caffeine as a single daily
dose produces physical dependence similar to
that produced by three divided doses over the
day, suggesting that the daily dose of caffeine
consumed is more relevant to the development of
caffeine dependence than the pattern of caffeine
intake within the day. Furthermore, caffeine
withdrawal occurs after as little as 3
consecutive days of caffeine exposure, with a
somewhat increased severity ofwithdrawal
observed after a week of caffeine exposure.
A final experiment showed that, when
individuals were maintained on 300 mg
caffeine/day, a substantial reduction in
caffeine consumption, or complete elimination,
is necessary for the manifestation of the full,
classic withdrawal syndrome.
As a whole, this set of experiments provides
the most complete parametric characterization of
caffeine withdrawal to date.
-Evans SM,
Griffiths RR. Caffeine withdrawal: a
parametric analysis of caffeine dosing
conditions. J Pharmacol Exp Ther.
1999;289(1):285-294.
-Phillips-Bute BG,
Lane JD.Caffeine withdrawal symptoms
following brief caffeine deprivation. Physiol
Behav 199763(1):35-39
-Lane JD
Effects of brief caffeinated-beverage
deprivation on mood, symptoms, and psychomotor
performance. Pharmacol Biochem Behav.
1997;58(1):203-208
