Sanford Bolton, Ph.D. and Gary Null, M.S.
Note: The information on this website is not a substitute for
diagnosis and treatment by a qualified, licensed professional.
http://garynull.com/articles/Caffeine_April.19.08.doc
ABSTRACT
Caffeine, probably the most widely used drug, affects the psychological
state of those who consume it. Abuse results in symptoms of caffeinism
which include agitation, disorientation and a syndrome which may be
mistaken for anxiety/neurosis. It is a habit-forming drug in which
tolerance develops. It affects sleep in a dose related manner which is
dependent on the daily caffeine intake, i.e., high users have less
effect. Its central nervous system stimulation can cause pleasant
effects with improved attention and concentration at lower doses. At
high doses, the reverse may occur. Used judiciously, it may be a useful
therapy in the treatment of hyperkinetic children. These and other
effects of caffeine are discussed in this review article.
INTRODUCTION
Caffeine is among the most widely used drugs because of its ubiquitous
occurrence in commonly consumed beverages such as coffee, tea and cola.
Many drugs contain caffeine and are readily accessible to the public in
the form of OTC stimulants and combination analgesics. Clearly caffeine
is an important drug-food substance in our society which deserves
attention. According to an in depth 1999 article in Pharmacological
Review which discusses the ways that caffeine affect our neural biology,
on average, people drink between 70-76 mg of caffeine a day, between
210-238 mg in North America, and about double that in the Netherlands .
To begin to have a new consciousness about caffeine so that we can
become aware of how this drug can affect our physiology and psychology
is a problem. The reasons for this are certainly complicated, but we can
start by considering a factor dominating all of our lives, our "habits."
When we become aware of and take responsibility to change habits, we are
taking a first step in the process of awakening. The result must be not
only an improvement in the quality of our lives but the world itself
will be changed for the better.
The use and abuse of caffeine is a major public "habit' and may be as
important a factor as heredity and environment in the etiology of
physiological and psychological disorders. To recognize this, we must
know that we are creatures of habit. Most people are caffeine consumers
because from birth this food-drug is set before us, if not offered
directly, along with orange juice, cereal, dessert and cigarettes.
This paper reviews the literature relating to the psychological effects
of caffeine. Caffeine is a potent central nervous system stimulant and
much of its "psychological" activity may be related to this action of
the drug. Its effects on the nervous system are obviously adverse at
high doses. It may not be obvious that at lower doses when used in
moderation, it may have beneficial effects. For example, its possible
therapeutic use in hyperkinetic children certainly would seem
advantageous when compared to the current treatment with more powerful
stimulants which have concomitant adverse reactions. Also, with the
intense day to day pressures imposed on and accepted by many of us, is
there any harm in "relaxing" with a hot cup of coffee? On the other
hand, caffeine is a drug which is subject to abuse. The fact that it is
a drug with a potentially powerful physiological effect escapes most of
us who think of coffee as a relatively harmless beverage. Recently
published studies and reports of personal observations have shown
without doubt that caffeine abuse (caffeinism) may result in a syndrome
which resembles and may be confused or confounded with true psychotic
states. This may lead to misdiagnosis and mistreatment. A question
arises from the varied reports of caffeine consumption in psychiatric
populations: Does caffeine stimulate psychosis or does psychosis
stimulate caffeine consumption?
These are not trivial findings because of the ready availability of
caffeine and the epidemic of psychological problems which we are
experiencing in this era. This report reviews some of the knowledge of
caffeine's effects with the hope that we will all be more educated and
more careful in the use of this commonly ingested drug.
The physiological action of caffeine is briefly reviewed, as
psychological and physiological effects must go hand-in-hand. In
addition to its central nervous system effects, caffeine has significant
effects on the cardiovascular system, gastric acid secretion and
catecholamine (adrenaline) release. In large doses, it has been shown to
be a mutagen in animals, plants and bacteria, and has been shown to
exhibit teratogenic properties in various animal species.
PHYSIOLOGICAL AND PHARMACOLOGICAL EFFECTS
J. Murdoch Ritchie, in Goodman and Gilman's Pharmacology Text (Ritchie,
1975) described the pharmacological effects of caffeine. The largest
sources of caffeine are from the plants used to make coffee, tea, cocoa
and kola (the basis of cola beverages), although it is also found in
Latin America as mate' and guarana. Caffeine particularly has a profound
effect on the central nervous system, but it also affects, to a lesser
degree the heart muscle, gastric secretion and diuresis. Interestingly,
caffeine is ingested daily by a vast number of people and is unique in
that it is a potent drug, considered to be part of our normal diet.
Caffeine stimulates the central nervous system first at the higher
levels, the cortex and medulla, and finally the spinal cord at higher
doses. Mild cortex stimulation appears to be beneficial resulting in
more clear thinking and less fatigue. Caffeine has been shown to improve
attention in a study which simulated night driving (Leinart, 1966). The
onset of the effect of caffeine occurs within one hour and lasts for
three to four hours (Baker, 1972).
The equivalent of one or two cups of coffee (150 to 250 mg of caffeine)
is sufficient to induce adverse effects. The occurrence of
hyperesthesia, an unpleasant sensory sensation, can be stimulated by
large doses of caffeine.
The medullary, respiratory, vasomotor and vagal centers are stimulated
by caffeine. This effect is due to an increased sensitization to carbon
dioxide but needs large doses to elicit this effect, 150 to 250 mg,
parenterally. The spinal cord is stimulated at higher doses and
convulsions and death may result. More than 10 g are needed for such
toxicity to occur in man (Ritchie, 1975).
Stimulation of the CNS is followed by depression (Klein and Salzman,
1975), although the effect is small at low doses e.g. a single cup of
coffee. After two hours, Klein reported that males (but not females)
showed a lower CNS stimulation compared to placebo. The post stimulation
"let down" with caffeine results in fatigue and lethargy and the
constant stimulation caused by chronic caffeine dosing could be
disastrous (Abrams, 1977; Dowell, 1965).
Children, because of their smaller size, are more susceptible to
caffeine. One report noted that hyperactivity and insomnia observed in
children could be attributed to excess caffeine intake from cola drinks
(Consumer Research, 1973). According to Dr. Page, "There is no doubt
that children should be kept from using coffee and the popular caffeine
containing soft drinks." (Abrams, 1977).
Caffeine's effect on the cardiovascular system predominates at very
large doses with rapid heart rate and, eventually, irregular heart beats
result. For example, a Middlesex, UK hospital discusses a 2007 case
study of a person who had swelling of the heart muscle due to too much
caffeine in the diet. The report noted that after half a year of
abstaining from caffeine, the symptoms went away. The authors of the
article mention that this case study could have relevance to the wider
population, because in a portion of people who have irregular heart beat
also have inflamed heart muscle that make beating of the heart
difficult, which is caused by rapid beating of the heart. This has
relevance to those who drink too much caffeine . Caffeine seems to have
a non-discrimminatory effect on the cardiovascular system: in a 1983
study in the journal Psychosomatic Medicine, an experiment shoed that in
young men, even non-extreme caffeine intake raised blood pressure both
during periods of stillness and during times of bodily demand .
Adenosine receptors may be the mechanism through which caffeine works in
the heart. Adenosine receptors are found throughout the body, and tend
to depress the function of that particular organ. For example, in the
brain adenosine slows bodily functions by manipulating the speed at
which various neurons fire. In the heart, adenosine works by slowing the
heart-beat, by affecting the neural pathways that stimulate the pacemaker .
This is one of the reasons for many of the recent studies on caffeine
and its relevance to heart functioning--caffeine and various its
immediate byproducts such as —theophilline – act against those adenosine
receptors and, as a result speed up neuronal firing.
A 2002 rodent study confirmed the involvement of adenosine receptors in
cardiac conditions --by the use of drugs which blocked specific receptor
action—and showed that animals given caffeine laced water had a faster
heart beat and elevated blood pressure as compared to non-caffeinated
animals .
Recently, a whole field of science for Parkinson's sufferers has opened
up on the use of adenosine blockers—called 'adenosine antagonists .'
Coffee, by action of its caffeine content, is an adenosine antagonist,
and we will look at some of its effects:
Therapeutic effects have been suggested for caffeine because it inhibits
the "freezing of gait" difficulties of advanced Parkinson's sufferers
for a short period of time. In one study however the patients regained a
tolerance to caffeine, and the effect disappeared until the patient
stopped the use of caffeine for a time . In fact, many studies have
examined the link between low incidence of Parkinson's and coffee
drinking, and low incidence of Parkinson's and cigarette smoking:
Neuroepidemiology. 2003 Sep-Oct;22(5):297-304. Links
A case-control study on cigarette, alcohol, and coffee consumption
preceding Parkinson's disease. "results suggest an inverse association
between coffee drinking, alcohol consumption and PD."
Neurology. 2001 Apr 10;56(7):984-5.
Smoking, alcohol, and coffee consumption preceding Parkinson's disease:
a case-control study. "These findings suggest an inverse association
between coffee drinking and PD; however, this association does not imply
that coffee has a direct protective effect against PD. Alternative
explanations for the association should be considered"
Please note, however, that the authors of the article in Neurology above
do not say that the inverse relationship found between the activity of
coffee drinking and Parkinson's disease means that the activity of
coffee drinking or cigarette smoking prevents Parkinson's. It says that
further study of the relationship is warranted.
Although we know that caffeine is directly an adenosine antagonist, it
also increases nerve cell firing.
1) "Caffeine acts as a competitive antagonist to the inhibitory effects
of adenosine… One of these effects is to increase the release of the
excitatory neurotransmitters serotonin and noradrenaline." Journal of
Physiology (2002), 545.2, pp. 671-679 Effect of caffeine on
self-sustained firing in human motor units University, Toronto, ON, Canada
2)2001 Elsevier Science B.V. All rights reserved.
Caffeine increases paragigantocellularis neuronal firing rate and
induces withdrawal signs in morphine-dependent rats
3) "caffeine increased spontaneous firing of neurons between 12 and 80
min after treatment" Caffeine Regulates Neuronal Expression of the
Dopamine 2 Receptor Gene The Neurosciences Institute, San Diego,
California accepted August 19, 2003
Excess firing of neurons is suggestive of brain damage in human and
animals as well:
1)"Caffeine has been used clinically to increase seizure length in
electroconvulsive treatment (ECT)"Caffeine augmentation of
electroconvulsive seizures Journal Psychopharmacology 8 December 1993
University, Toronto, ON, Canada
2) "Caffeine adversely affects outcome after concussive head injury,
possibly as a result of blockade of adenosine receptors." Caffeine
Impairs Short-term Neurological Outcome after Concussive Head Injury in
Rats. Neurosurgery. 53(3):704-712, September 2003.
3)Is Caffeine an Effective Pesticide Against Drosophila (fruit fly)?
Science project at PJAS Region 1B, first at PJAS States, second at
Montgomery County Science Research Competition, and third at Delaware
Valley Science Research Competition. "The overactive nervous system
placed an extremely heavy emphasis on the gravitational stimuli, an
emphasis so extreme that the flies suffocated themselves in the foam
stoppers while responding to it."
And, finally, in layman's English:
"The average consumer may unwittingly consume excessive amounts of
caffeine that may lead to adverse physiological side effects."Is
Caffeine Excess Part of Your Differential Diagnosis?. Nurse
Practitioner. 29(4):39-44, April 2004.
Bridle, Leisa RN; Remick, June BSN, RN; Duffy, Evelyn MS, RN, CS
Caffeine studies on various areas of the body, including bone and sperm
show that caffeine causes oxidative stress . Caffeine has been shown to
kill rodent brain cells in laboratory studies. Cell cultures of outer
brain cells were killed at concentrations of 300 Molar of caffeine.
Initial living animal studies have begun to show toxic effects of
caffeine at very high doses. In newborn rodents, concentrations of 50
mg/kg of caffeine killed brain cells in assorted areas of the brain.
This, of course, is a lot of caffeine. (For a person weighing 154
pounds, this comes out to 3500 mg of caffeine 3x per day)
Conversely, however, a study on the preventive use of caffeine on the
blood vasculature is underwhelming: This experiment, published in the
American Journal of Clinical Nutrition in 2007, showed that those who
drank liquids containing caffeine, had a smaller likelihood of
cardiovascular illness and death only if they did not have extreme
levels of high blood pressure to begin with. Additionally this caffeine
consumption did not protect those who were younger than 65, nor did it
prevent death related to blood vessel disease in the brain . Since
American caffeine consumption comes, for the most part, through drinking
coffee, physician Joe Vinson suggests that it may be a causal factor in
the development of high blood pressure to begin with.
In addition to the conflicting information on the cardiovascular system
and brain, seemingly condradictive data has been found between drinking
coffee and diabetes. Apparently, studies since the year 2000 showed that
caffeine increased blood glucose levels after eating. However, a large
review showed that drinking coffee was related to a lower risk of
developing diabetes type 2 .
Bodily levels of magnesium may have something to do with the risk of
developing diabetes : A 1999 Netherlands study notes the inclination of
diabetes type 2 sufferers to be lacking in magnesium and that magnesium
given supplementally increases the body's ability to process blood
glucose . Data has also shown that coffee leaches magnesium from the
body. A 1994 study entitled, "Effect of caffeine on circadian excretion
of urinary calcium and magnesium," showed that the kidney was not able
to overcompensate for mineral loss due to caffeine consumption early in
the day, and that net losses of calcium and magnesium occurred by the
evening. .
The clinical literature is also starting to show that we can create
environmentally low levels of essential minerals in our bodies through
what we consume: There are now numerous studies starting to show that
caffeine consumption is related to the leaching essential minerals from
the body. For example,
A 1993 Journal of Nutrition article states that the intake of
caffeinated beverages raises the level of mineral elimination of the
body for a minimum of one eighth of the day after caffeine intake. The
article further notes that elderly females do not have enough dietary
intake of minerals to compensate for the loss due to caffeine. .
A 2007 study on the effects of dietary caffeine on the risk of
developing diabetes showed that blood magnesium levels were lower in
those who consumed dietary caffeine, versus those who did not .
Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL. Caffeine intake
increases the rate of bone loss in elderly women and interacts with
vitamin D receptor genotypes. Am J Clin Nutr 2001;74; 694–700.
A study published in the Journal of the American College of Nutrition
shows that caffeine consumption had a negative association with bone
mineral density in women throughout the body when a person consumed
200-300 mg/day of caffeine .
We also have examples from the literature examining the possible links
between nutrient depletion and neurological illness:
Mechanisms of Action on the Nervous System in Magnesium Deficiency and
Dementia Magnes Res. 1997 Dec;10(4):339-53.
Are age-related neurodegenerative diseases linked with various types of
magnesium depletion?
Durlach J, Bac P, Durlach V, Durlach A, Bara M, Guiet-Bara A.
Caffeine also seems to have a direct effect independent of those we
already mentioned) on certain tissues within the body:
An interesting 2007 animal study done at the University of Massachusetts
Medical School shows that caffeine and its byproducts affect heart
cells, independent of other mechanisms and that that irregular heart
beat may be related to activation of a specific ion channel by caffeine
and its biochemical products .
Although caffeine dilates blood vessels by a direct action, its central
effect is one of constriction. At higher doses, the dilating effect is
apparent (Peach, 1972; Poisner, 1973).
Similarly, because its direct and central effects are antagonistic, the
resultant effect of caffeine on blood pressure is unpredictable. The net
effect is usually of less than 10 mm of Hg in blood pressure (Ritchie et
al., 1975). Caffeine's purported efficacy in hypertensive headaches may
be due to a decrease in blood flow as a result of the increased cerebral
resistance (Ritchie et al., 1975).
Caffeine also stimulates releases of catecholamines from the adrenal
medulla and norepinephrine is released from nerve endings in the
isolated heart (Bellett et al., 1971). .
It has been shown that prolonged augmentation of gastric 'secretion
results from caffeine administration and that ulcer patients have
sustained elevation of acid as opposed to normals (Ritchie et al., 1975).
Although a dose of approximately 10 g or more taken orally can be fatal,
an oral (3.2 g IV) one gram dose will cause adverse effects (Gleason et
al., 1969). The toxic effects are due to CNS and circulatory system
stimulation and include some well recognized prominent symptoms in
addition to those which can result at high doses or in hypersensitive
persons: insomnia, restlessness, excitement, tinnitus, flashes of light,
quivering muscles, tachycardia, extrasystoles, and even low grade fever
and mild delirium have been observed.
Harrie (1970) described a patient whose constant headaches were due to
excessive caffeine consumption. He states, "I suspect that the condition
is much more common than supposed and could well be one of the more
frequent causes of chronic recurrent headache." Headaches can also be
precipitated by caffeine withdrawal especially by those who have the
"habit".
Although caffeine is well absorbed when taken orally, its absorption may
be erratic because of its low solubility and because it may cause
gastric irritation. Caffeine is principally metabolized with only 10
percent excreted in the urine unchanged (Ritchie et al., 1975).
Caffeine has a physiological half-life of three and a half hours
(Parsons and Neims, 1978) to six hours (Aranda et al., 1979). Its
physiological effects are observed in less than one hour (Parsons and
Neims, 1978). Infants do not metabolize caffeine as well as adults and
thus have a half-life of about four days (Aranda et al., 1975).
Certainly, continuous ingestion of caffeine by infants can be dangerous.
If a cup of coffee is consumed by an adult six or seven times a day it
would result in a high steady concentration of caffeine in the blood. As
little as four cups a day can result in appreciable omnipresent amounts
of caffeine in the body.
Caffeine can accumulate in severe liver disease (Stratland, 1976) when
its half-life can increase to 96 hours. If these patients drink coffe(~
they should be closely monitored.
Caffeine is known to interact with other drugs resulting in a modified
effect. For example, caffeine administered with nardil (an MAO
inhibitor) caused headaches and high blood pressure (Pakes, 1979). This
potentially dangerous interaction was first noted by Berkowitz et al.,
(1971) and implicated serotonin in the mechanism.
Caffeine and barbitol are antagonistic, with caffeine (in coffee)
reducing the sleeping time induced by barbitol. Decaffeinated coffee had
no effect (Aeschbacher et al., 1975). In another study, caffeine
resulted in reduced sleeping time which was counteracted by
pentobarbitol in hospitalized patients (Forrest et al., 1972).
PSYCHOLOGICAL EFFECTS OF CAFFEINE
Because of the wide spread use of caffeine and its known potent
physiological effects, caffeine has been the subject of research in
psychological related studies. This work has been stimulated by personal
experiences and observations as well as by efforts to understand its
action and mechanism.
Habituation and Tolerance: Caffeine ingestion and coffee drinking have
been investigated with regard to the degree that this habit results in
tolerance and withdrawal effects. These studies look beyond the obvious
social implications and psychic dependence (Ritchie et al., 1975) of
coffee consumption which may be related to the "first cup of coffee to
wake me up" or "the coffee break" or to its association with smoking. In
the latter case, it is of interest that coffee drinkers were shown to
take more nicotine when deprived of coffee (Kozlowski, 1976).
Caffeine has not only been considered habit forming, but also addicting.
Crothers considered morphinism and caffeinism to be similar, with
caffeine causing loss of self-control, spells of agitation and
depression as well as psychotic behavior (Stephenson, 1977). Ritchie
mentions a report by Colton that tolerance can develop for the diuretic,
salivary stimulation and sleep disturbance effects of caffeine.
Cola consumed in amounts of 48 to 111 ounces per day (144 to 333 mg of
caffeine per day) was reported to have caused physical effects on
withdrawal (Diamond and Pfifferling, 1974). The resultant effects were
depression, nervousness, decreased alertness, sleeping difficulty,
frequent mood changes, and various other behavioral difficulties which
were attributed to caffeine withdrawal.
The dependence of coffee drinkers on caffeine was illustrated in a study
by Kozlowski (1976) in which coffee drinkers drank more coffee if the
caffeine content was lowered.
Abrams (1977) says "There is no doubt that a certain degree of psychic
dependence, that is habituation, develops from the use of xanthine
beverages".
A questionnaire completed by more than 200 young housewives showed that
the perceived effects of caffeine depended on previous use (Goldstein et
al., 1969). The heavy coffee drinkers had few sleep disturbances and
less evidence of nervousness after their morning coffee as compared to
nondrinkers. if the morning coffee was stopped, the habitual coffee
drinkers experienced nervousness, headache and irritation. The
non-coffee drinkers reacted negatively to coffee, experiencing effects
opposite to the coffee drinkers. An experiment was devised to verify the
results of the questionnaire involving 18 housewives, non-coffee
drinkers, and 38 who drank five or more cups per day. The results
confirmed those obtained from the questionnaire previously administered
(Goldstein et al., 1969). This experiment was double-blind and placebo
controlled and caffeine was administered in coffee at 0, 150 and 300 mg.
Coffee drinkers showed a dose-response effect whereas non-coffee
drinkers showed signs such as nervousness, jitters and upset stomachs at
all doses of caffeine but not on placebo.
Ritchie (1975) says that tolerance and psychological dependence to
caffeine beverages does occur to some extent but he feels that this
does-not present a problem. He says that coffee or tea drinking are
socially acceptable and are apparently not harmful when practiced in
moderation.
However, it does appear that at least in some persons excess consumption
of caffeine can result in severe phychological dependence and withdrawal
effects and is a problem to be reckoned with.
Behavioral Effects: Caffeine's stimulating activity on the central
nervous system as well as other body organs results in certain
physiological effects which may be considered to be behavior oriented.
Caffeine produces more rapid, clearer flow of thought, allays drowsiness
and fatigue, increases the capability of a greater sustained
intellectual effort and more perfect association of ideas. It also
causes a keener appreciation of sensory stimuli, and reaction time is
diminished. Motor activity is increased; typists, for example, work
faster with fewer errors. Tasks requiring delicate muscular cobrdination
and accurate timing may, however, be adversely affected. All of this
occurs at doses of 150 to 250 mg of caffeine (approximately two cups of
coffee) according to Ritchie (1975).
In 1912, Hollingsworth who was a psychologist reported caffeine's effect
on mental and motor efficiency in a study sponsored by Coca-Cola. In
nine double-blind tests, he found beneficial effects for both mental and
motor performance at doses of 65 to 130 mg of caffeine. At a dose of 300
mg, caffeine caused tremors, poor motor performance and insomnia. These
results have withstood the test of time (Stephenson, 1977).
Goldstein (1965) showed no effect of caffeine on objective measures of
performance although most subjects "felt" more alert and physically
active. However, some subjects felt nervous.
Mitchell, Ross and Hurst showed caffeine to prevent attention lapses in
a visual monitoring test which simulated night driving. The effect
persisted for the two to three hour experiment (Stephenson, 1977).
A 200 mg dose of caffeine resulted in decreased decision time scores and
improved motor time scores in volunteers (Smith et al., 1977). Hand
steadiness, however, was impaired. After a caffeine intake of 200 mg,
introverts performed less well on a verbal ability test as compared to
extroverts when time pressure was applied (Ritchie et al., 1975).
Wayner et al. (1976) reported on the effects of caffeine on schedule
dependent'and schedule induced behavior in mice. Caffeine, (3.125, 6.25,
12.5, 25, 50 and 100 mg/kg) was tested on lever pressing, schedule
induced licking and water consumption of mice. The effect on mice at 80
percent of body weight was different than when mice were allowed to
recover the lost weight. At the lower weight, caffeine had little effect
except at the highest dose (equivalent to 100 cups of coffee given at
once). At their ordinary weight, the mice were more sensitive to
caffeine, with all measures enhanced, even at the lowest dose
(equivalent to approximately three cups of coffee). At high doses, all
measures decreased; the mice became tolerant.
Castellano (1976) studied mice behavior under two sets of conditions.
One involved a natural preference (swimming towards a light-"L" ) and
the other involved an acquired behavior pattern (swimming toward the
dark-"D"). A facilitation of learning and consolidation after caffeine
dosing was noted in naive mice after the -D" procedure. Natural
tendencies were also enhanced by caffeine as noted by improved
performance in the "L" procedure. Animals pretrained in the "D"
procedure exhibited behavioral disruption after treatment. Animals
pretrained in the natural -U procedure needed very high doses to cause
disruption. Caffeine decreases five HT turnover in rat brain.
Amphetamines do not show the results as demonstrated in this paper,
whereas other drugs such as hallucinogens show a similar effect. The
implication is that the mechanism of caffeine's action may be similar to
hallucinogenic drugs.
Effect on Sleep: Caffeine is known to cause insomnia because of its
central nervous system stimulating activity. In fact, its major
therapeutic use is to allay sleep and drowsiness, being the only OTC
stimulant approved by the FDA. Several studies investigating this action
in some detail have been published.
Karacan (1976) found that caffeine given half an hour before sleep
adversely affected the sleeping process in normal sublects. The effect
is dose related. Caffeine's effect simulates clinical insomnia and gave
the same response as coffee containing an equivalent amount of caffeine.
Decaffeinated coffee showed no effect on sleep.
Dorfman and Jarvick (1970) showed a dose-response effect of caffeine on
the self estimation of sleep latency (which was increased) and quality
(which was decreased). This was a double-blind study in which 0, 60,
120, and 250 mg of caffeine was administered one hour before bedtime.
Mikkelsen (1978) notes that caffeine seems to inhibit deeper stages of
sleep as opposed to disturbances of the REM stage. Other studies show
contradictory evidence, REM being affected by caffeine, leaving the
situation to be resolved.
The tolerance developed to caffeine's effect on sleep by coffee drinkers
has been documented by Colton (Stephenson, 1977). Non-coffee drinkers
were more sensitive to coffee's insomnic effect whereas coffee drinkers
were relatively insensitive in this regard. Non-coffee drinkers
experienced disturbed sleep patterns and delayed onset of sleep.
Mueller-Limmroth (Stephenson, 1977) showed that the quality of the first
three hours of sleep was impaired by the ingestion of coffee before
retiring. This is approximately equal to the half-life of caffeine in
the body.
Goldstein did extensive work on the effect of coffee and showed that
coffee drinkers slept more soundly when they took placebo as opposed to
caffeine in coffee. If 150 to 200 mg of caffeine was taken before
bedtime, there was an increased sleep latency which was less pronounced
in persons who were heavy ingestors of caffeine (Goldstein et al., 1965).
These studies show that caffeine has a profound effect on sleep. Heavy
and continued use of caffeine results in tolerance so that heavy users
have less sleep disturbance or need more to obtain its stimulating effect.
Treatment of Hyperkinetic Children: Hyperkinetic children have been
shown to respond to central nervous system stimulants, resulting in
improved attention, concentration, -and decreased activity. Side effects
are usually disturbing with the more powerful drugs and include
insomnia, anorexia, nervousness, weight loss and abdominal pain.
A study by Schnackenberg (1975) showed that 200 to 300 mg of caffeine
was similar in effect to methylpheniclate in treating hyperkinetic
impulse disorder secondary to minimal brain dysfunction syndrome. Some
hyperkinetic children, he observed, drank coffee to calm down. Sixteen
children who had shown improvement on methylphenidate but who had
annoying side effects were given one cup of coffee at breakfast and
lunch. Test scores showed a similar im-provement with coffee as compared
to methylpheniclate and the annoying side effects disappeared when the
children were on caffeine. Schnackenberg recommends 200 to 300 mg of
caffeine in a time-release form.
In 1977, Reichard and Elder published an article on caffeine's effect on
reaction time in hyperkinetic children. They tested the effect on a
choice reaction time task and simple reaction time as compared to normal
children. Caffeine increased the accuracy of stimulus identification and
processing and decreased lapse of attention in the hyperkinetic group.
This is what might be expected based on caffeine's known effects on such
tasks in normals. Hyperkinetic children have a slower reaction time, are
less able to maintain attention and have a lower rate of correct
responses on a vigilance performance task as compared to normal
children. In this study, six normal and six hyperkinetic children were
compared in a double-blind design. Caffeine significantly raised the
rate of correct responses on simple reaction time in the hyperkinetic
group. The reaction time was reduced with caffeine but was not
significantly less than the control period or placebo. Similar results
were found with choice reaction time. The response is a function of the
initial state of the children, i.e., the more severely afflicted had a
larger response. The authors note that other studies have shown
methylpheniclate was more effective than caffeine in controlling certain
aspects of clinical behavior (impulsivity and hyperactivity). This
result does not contradict those obtained in this study; they are
compatible.
Garfinkel was unable to confirm the results of caffeine's effectiveness
in controlling the behavior of children with minimal brain damage
(Stephenson, 1977). Children responding to methylpheniclate did not
necessarily respond to caffeine.
Firestone and associates in a study funded by the Ontario Mental Health
Foundation (1978) showed a significant improvement with methylphenidate
as rated by mothers and teachers on tests of impulsivity and motor
control. No significant improvement was noted with caffeine although
some children showed a slight improvement. Side effects with both drugs
were minimal. Each of 21 hyperactive children received 500 mg of
caffeine, 300 mg of caffeine, and 20 mg methylpheniclate. This was' a
carefully controlled study consisting of 17 boys and four girls. In
1978, Firestone did a study comparing 300 mg of caffeine with placebo in
a double-blind crossover design. In this study, subjective ratings by
teachers and parents as well as a reaction time task showed caffeine to
be better than placebo although the difference was not statistically
significant. Firestone concludes on the basis of the most recent study
that caffeine is not a meaningful alternative as a treatment for
hyperkinetic children.
The use of caffeine in the treatment of hyperkinetic children remains
unresolved at this time. Further work seems warranted to ensure that if
caffeine is useful in this prevalent condition that it be available as a
viable alternate treatment in lieu of more powerful CNS stimulants.
"Restless Legs, Anxiety and Caffeinism" (Lutz, 1978)
Restless legs is a syndrome which may be associated with anxious -
depressed as well as other clinical states. Dr. Lutz, in an article
titled as above, suggests that this syndrome is primarily caused by
caffeine. Anxiety is not a causative factor. Caffeine stimulates the
nervous system and has a direct contractile effect on striated muscle.
This is reflected in anxiety, depression, insomnia: and the heightened
proprioceptive awareness may result in restless legs. This manifestation
consists of nervousness and movement of legs as a result of a
distressing creeping sensation. Its symptoms are most obvious at night
when the patient is trying to be still, and results in insomnia. Dr.
Lutz describes cases of this disorder in detail and cites examples, all
of which were alleviated when caffeine was removed from the diet. This
condition has been attributed to many causes including psychiatric
disturbances, e.g. restless legs is a frequent symptom of hysteria,
anxiety, depression. In periods of stress, "normal" persons are also
afflicted. All of these states are associated with high central nervous
system arousal. Also, restless legs syndrome, was first described in
England at the time when coffee and tea first were introduced in the
country. Thus, diagnosis of the restless legs syndrome, as has also been
observed in certain psychological disorders, may simply be the result of
overdosage of ubiquitous caffeine.
Psychological Disorders: Dr. John Greden, a professor of psychiatry at
the University of Michigan, says, "caffeinism can be found among those
who have psychiatric problems". Symptoms of excessive caffeine
consumption are similar to anxiety neurosis (Avery, 1980) and include
nervousness, irritability, recurrent headache. twitching, and
gastrointestinal disturbance among other symptoms (Greden, 1974). This
is a known effect of caffeine and Greden adds "...all medications
including caffeine have a potential for abuse and many individuals
clearly ingest symptom-producing doses daily".
Other studies support the relationship indicated above. For example, a
prisoner with severe anxiety symptoms admitted to drinking 50 cups of
coffee per day (Niolde, 1975). The symptoms remitted after the coffee
drinking stopped. Excess drinking of coffee by prisoners is not uncommon
and may initiate a vicious cycle: a bored person drinking more coffee
resulting in caffeinism which may result in more consumption.
The intake of caffeine (coffee, etc.) has been correlated with the
degree of mental illness in psychiatric patients. It is not clear if the
caffeine intake intensifies the psychiatric disorder or whether those
with more severe problems tend to drink more coffee. In any event, in
another study by Dr. Greden and associates (Greden, 1978) 83
hospitalized psychiatric patients were interviewed and showed an
association of symptoms with high caffeine intake. This may provide an
explanation of some problems which have been experienced in diagnosing
out-patient disorders. Eighteen of the 83 patients (22 percent) were
high caffeine consumers (7~0 mg or more). They scored significantlv
higher on the State-Trait anxiety index and the Beck Depression Scale
than lower caffeine consumers. The high consumers had more clinical
symptoms: their physical health was worse; they used more sedatives,
hypnotics, and minor tranquilizers. These patients showed a tolerance to
sleep effects which could be due to a change in body kinetics or
metabolism. Catecholamines contribute to the anxiety profile and
patients may drink more coffee in response to stress, accentuating a
neuro-transmitter response cycle. Since caffeine affects catecholamine
levels and inhibits phosphodiesterase breakdown of C-AMP, sensitizing
receptor sites, the association of caffeine with anxiety and depressive
symptoms is indeed a possibility.
Dr. Greden considers caffeine to be a psychotropic drug and 25 percent
of the population may take more than 500 mg per day, a large
physiologically active dose. He describes three cases in which
caffeinism may be misdiagnosed as an anxiety syndrome.
Dr. Greden concludes that caffeine is found among a fairly large
percentage of hospitalized patients with psychiatric symptoms. Caffeine
should not be used as part of psychiatric treatment routines, e.g., to
reduce drowsiness from psychotropic medications as has been occasionally
suggested.
Dr. John Neil and associates (1978) reported on the possible
complication of caffeinism in diagnosing psychiatric patients. He
suggests that self-medication may confound behaviors of patients.
Caffeine has been considered the most popular "psychotropic" drug in
North America and coffee and tea drinking are not usually in the records
of psychiatric patients. In this experiment, hypersomnic patients with
various diagnoses and caffeine consumption participated, The authors
conclude that "self medication with large doses of caffeine is a likely
response to the anergia and hypersomnia experienced during certain types
of depression". This may lqad to diagnostic confusion and a complicated
course of therapy. Mixed depressive states may be caused by excess
caffeine consumption and they suggest, also, that unipolar 11
depressives may use more caffeine as they become depressed.
Caffeine, in these patients, provides only transitory relief as it is
not a true antidepressant. Caffeine also may render anxiolytic and
antipsychotic medications less effective.
Mikkelsen (1978) noted caffeine's involvement in schizophrenic-like
states similar to that observed by Greden in anxiety/neurosis symptoms
of patients who consumed large quantities of caffeine (coffee). One case
cited was of a white male in a catatonic state who threatened his mother
after having gone on a coffee jag over injustices caused to him by his
mother. He developed paranoid delusions which he felt were, at least in
part, due to the coffee. A 30 year old white single female exhibited
paranoid and auditory hallucinations. An anxiety state had resulted in
increased coffee consumption. in the hospital she noted the correlation
of these strange feelings with coffee consumption. Other examples of
psychotic behavior as noted in the literature are described in this
paper. Forty years ago a case of psychosis was reported in which a 24
year old female took 60 gr (about four g) of caffeine. Manic symptoms
developed. He theorizes that adenyl cyclase which is increased by
caffeine may be a receptor for dopamine. If this system is abnormal in
schizophrenics, caffeine may further sensitize the patient. Certainly,
coffee should be considered as a factor in this disease.
Reimann (1967) noted that symptoms of a psychoneurotic woman disappeared
when coffee was reduced. She presented with an irregular fever,
insomnia, anorexia and irritability, having consumed large amounts of
coffee.
Clearly, as recommended by Drs. Greden, Mikkelsen and Neil, caffeine
intake should be considered as a factor in diagnosing and treating
psychiatric patients.
CAFFEINE AND WOMEN
According to a 1999 study in Pharmacological Review, caffeine passes
through the gut quickly and becomes almost entirely active in three
quarters of an hour. Additionally, it is not prevented from going into
the human brain or the fetus, by any biological mechanism, so, in
effect, what you drink, is what you get .
Caffeine seems to have a deleterious effect upon women of childbearing
years. A 2004 study showed that consuming caffeine while the fetus is in
early gestation has been shown to increase its risk of being rejected
from the mother's body .This study was supported by data that down's
syndrome fetuses were more likely to die than genetically normal fetuses
when the mother consumed caffeinated beverages.
There does not seem to be a good time to drink coffee while pregnant: A
Danish review of clinical data over the course of 8 years (from
1996-2002) indicated that drinking coffee was related to higher levels
of mortality in the fetus, especially late in the second trimester .
Another study done in the same year at the University of Leeds showed
that drinking greater than 300 milligrams of caffeine per day while
pregnant increased the likelihood of miscarriage by 100% . Similarly, a
Scandinavian study showed that more than 375 mg of caffeine per day
increased likelihood of the loss of the fetus .
One 2003 study showed that low birth weight was found to be a factor
particularly for boy-babies born to mothers who drank more caffeine in
the last three months of pregnancy . Additionally, a Johns Hopkins study
showed that higher caffeine intake in the last 3 months of pregnancy
especially along with smoking increases likelihood of having a small baby .
Even post birth, children born to caffeine consuming mothers are more
likely to die of Crib-death .
Caffeine drinking in men may even deter conception. According to a 2002
Iranian study, caffeine caused DNA damage in human sperm, indicating
that caffeine can negatively affect a man's semen to fertilize an egg
.These changes were due to damage by oxidation.
Genetic susceptibility may play a role in the body's sensitivity to
caffeine.
Caffeine may mediate illness in the body through several genetic
variations, having to do with processing of toxins and making them
inactive in order to eliminate them from the body. Some of the initial
by-products of these initial compounds --mediated by the particular gene
(CYP1A1) have toxic and oxidative properties in the body, and several
experiments have hypothesized whether caffeine intake and these genetic
variants influence the risk of various cancers .
For some women who the specific genotype:(CYP1B1 432 Val/Val), they were
more likely to have a miscarriage during the first three months of their
pregnancy, and caffeine was also shown to influence this risk.
There is also a variant of gene called CYP1A1 that is related to higher
probability of developing cancer of the ovary when a person drinks more
than an average amount of caffeine.
And even after child bearing years, caffeine may have deleterious
effects upon the body. Drinks that have caffeine heighten the body's
process of getting rid of its stores of calcium, magnesium, zinc, and
potassium, respectively .
There is a relationship between the intake of caffeine and breaks in the
hip bones of women in the age range of 45-65 .
Additionally after menopause, intake of greater than 300 mg of caffeine
increases the likelihood of losing bone matrix in the vertebral column .
Similarly, cola intake was shown to be related to lower bone mass in
women . According to a 2005 master's degree thesis, oxidative stress due
to caffeine consumption may be a reason for development of osteoporosis
in women . The paper suggested that bone-culture cells initiated
pre-programmed cell death pathways when treated with caffeine.
SUMMARY
A review of the literature reveals that caffeine is an important factor
in modifying the psychological state of its consumers under the present
condition of usage. Caffeine is probably the most widely used drug and
those who drink coffee, tea, cola or take OTC caffeine containing drugs
are all potential and susceptible candidates. Those of us who are
"normal" can expect manifestations which may be subtle at low doses,
overt at high doses, with the possibility of being the victims of a
habit which results in tolerance and possible severe withdrawal
symptoms. The pleasant stimulant feeling which often occurs at low doses
may be replaced by psychological symptoms which resemble anxiety and
depressive neuroses at high doses. Those with more severe psychological
problems may have their symptoms exaggerated with excessive caffeine
usage, or such symptoms can actually be caused by excess. Diagnosis of
such conditions must take caffeine usage into account.
As a result of its potent physiological activity, caffeine can alter our
behavior. it affects our sleeping habits generally resulting in insomnia
and hyperactivity. Task oriented performance, attention, and
concentrations may be modified by caffeine. At lower doses, these
effects appear to be beneficial. At higher doses, we can expect the
reverse, including toxic and rebound effects.
The common "Restless Legs Syndrome" which has often been related to
psychological disturbances may, in fact, be primarily a symptom of
caffeinism according to Lutz.
Caffeine has been investigated as a possible treatment for hyperkinetic
children since central nervous system stimulants have been shown to be
effective in this condition. Results of caffeine treatment are
controversial, some studies showing a beneficial effect with little
adverse reactions and other studies showing little or no benefit.
Caffeine's effect on our body, our nervous system, our mind, our
psychology is no illusion. It is a potent drug. That it may cause
symptoms of mental illness as recently published is no small concern.
With these findings we see that caffeine abuse is more prevalent than we
may imagine. These facts should be brought to the attention of the
medical community as well as the public in order that we may have the
opportunity of being aware of the possible interactions between
ourselves and our environment.
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