caffeine psyc 760
TRANSCRIPT
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CaffeineCaffeine
Tamie MiuraTamie Miura
Psychology 760Psychology 760
San Diego State UniversitySan Diego State University
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I.I. IntroductionIntroduction
II.II. Mechanism of actionMechanism of action
III.III. Properties of adenosineProperties of adenosine
IV.IV. Pharmacodynamics of caffeinePharmacodynamics of caffeine
V.V. Pharmacokinetics of caffeinePharmacokinetics of caffeineVI.VI. Effect of caffeine on neurotransmittersEffect of caffeine on neurotransmitters
VII.VII. Studies on the behavioral effects of caffeineStudies on the behavioral effects of caffeine
VIII.VIII. ToleranceToleranceIX.IX. Withdrawal and physical dependenceWithdrawal and physical dependence
X.X. Health concerns and therapeutic usesHealth concerns and therapeutic uses
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CaffeineCaffeine
Caffeine is often considered the most widely consumedCaffeine is often considered the most widely consumedstimulant in the world.stimulant in the world.
Roughly about 80% of adults in the United States drinkRoughly about 80% of adults in the United States drink
coffee or tea daily.coffee or tea daily. Intake of caffeine also occurs from ingesting chocolate,Intake of caffeine also occurs from ingesting chocolate,
cold and headache medicines and appetite suppressants.cold and headache medicines and appetite suppressants. Every year in the U.S. consumers spend around 30 millionEvery year in the U.S. consumers spend around 30 million
dollars on caffeine tablets and 50 billion dollars ondollars on caffeine tablets and 50 billion dollars oncaffeinated sodacaffeinated soda
Benowitz, 1990Benowitz, 1990
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Amount of Caffeine ConsumptionAmount of Caffeine Consumption
Beverages / Food:Beverages / Food: Cup of coffee: 65-120 mg caffeineCup of coffee: 65-120 mg caffeine
Espresso 1oz shot: 40 mgEspresso 1oz shot: 40 mg Cup of tea: 40-60 mgCup of tea: 40-60 mg
Can of soda: 30-60 mgCan of soda: 30-60 mg Red Bull (8.3oz): 80 mgRed Bull (8.3oz): 80 mg Hersheys milk chocolate almond bar (6oz): 25mgHersheys milk chocolate almond bar (6oz): 25mg
Over the counter medicines:Over the counter medicines: No-Doze: 100 200 mgNo-Doze: 100 200 mg Midol: 20-100 mgMidol: 20-100 mg Excedrin: 30-65 mgExcedrin: 30-65 mgBenowitz, 1990Benowitz, 1990
Total consumption of caffeine per person per day is estimated atTotal consumption of caffeine per person per day is estimated at210 to 238 mg210 to 238 mg (Barone and Roberts, 1996)(Barone and Roberts, 1996)
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Chemical PropertiesChemical Properties
Caffeine, an alkaloidCaffeine, an alkaloid
of the methylxanthineof the methylxanthine
family.family. Similar compoundsSimilar compounds
included in theincluded in the
methylxanthine familymethylxanthine family
are theophylline andare theophylline andtheobrominetheobromine
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Mechanism of ActionMechanism of Action
Three main hypotheses:Three main hypotheses:1.1. Mobilization of intracellular calciumMobilization of intracellular calcium Biphasic effect on intracellular calcium levelsBiphasic effect on intracellular calcium levels *Toxic amounts of caffeine*Toxic amounts of caffeine
2.2. Inhibition of phosphodiesteraseInhibition of phosphodiesterase Inhibition of enzyme that breaks down cyclic adenosineInhibition of enzyme that breaks down cyclic adenosine
monophosphate (cAMP)monophosphate (cAMP) *Toxic amounts of caffeine*Toxic amounts of caffeine
3.3.Antagonism of inhibitory presynaptic adenosine receptorsAntagonism of inhibitory presynaptic adenosine receptors Caffeine blocks adenosine receptorsCaffeine blocks adenosine receptors Resulting in the inhibition of the breakdown of cAMPResulting in the inhibition of the breakdown of cAMP Blocking the inhibitory effects of adenosineBlocking the inhibitory effects of adenosine
Nehlig et al., 1992Nehlig et al., 1992
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Properties of AdenosineProperties of Adenosine
Adenosine is an endogenous inhibitoryAdenosine is an endogenous inhibitory
neurotransmitter or neuromodulator that acts onneurotransmitter or neuromodulator that acts on
adenosine receptors located throughout theadenosine receptors located throughout thebodybody Reduction in firing rate of neuronsReduction in firing rate of neurons
Inhibition of synaptic transmissionInhibition of synaptic transmission
Inhibition of neuronal release of manyInhibition of neuronal release of manyneurotransmitters (i.e. acetylcholine, norepinephrine,neurotransmitters (i.e. acetylcholine, norepinephrine,
dopamine, serotonin, and glutamate)dopamine, serotonin, and glutamate)
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Subclasses of Adenosine ReceptorsSubclasses of Adenosine Receptors
Two Main subclasses:Two Main subclasses:A1 receptors high affinity for adenosineA1 receptors high affinity for adenosine
Located throughout the brain (hippocampus,Located throughout the brain (hippocampus,thalamus, cerebral and cerebellar cortex)thalamus, cerebral and cerebellar cortex)
A2 receptors low affinity for adenosineA2 receptors low affinity for adenosine Located mainly in the striatum, basal ganglia andLocated mainly in the striatum, basal ganglia and
nucleus accumbensnucleus accumbens
A2a and A2bA2a and A2b
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Antagonism of AdenosineAntagonism of Adenosine
ReceptorsReceptors Caffeine competitively binds to both A1Caffeine competitively binds to both A1
and A2a adenosine receptors therebyand A2a adenosine receptors thereby
inhibiting the actions of adenosine inhibiting the actions of adenosine resulting in an increase in theresulting in an increase in therelease/turnover of manyrelease/turnover of manyneurotransmitters like monoamines andneurotransmitters like monoamines and
acetylcholine.acetylcholine.
Nehlig et al., 1992; Nehlig et al., 1999Nehlig et al., 1992; Nehlig et al., 1999
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PharmacodynamicsPharmacodynamicsCaffeine
Central Nervous System Enhances neurotransmitter release
Stimulates locomotor activity
Decreases cerebral blood flow
Cardiovascular Release of epinephrine (adrenaline) which
Increases heart rate
Increases blood pressure
Increases blood flow to the muscles
Decreases blood flow to skin and inner organs
Renal Diuresis; stimulates renal release
Vasculature Peripheral: Dilation
Central: Constriction
Gastrointestinal Increases gastric secretions
Respiratory Bronchodilation
Increases respiratory rateGarrett and Griffiths 1997
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Chronic Consumption of CaffeineChronic Consumption of Caffeine
During Development on the DensityDuring Development on the Density
of Adenosine Receptorsof Adenosine Receptors Study by Guillet and Kellogg 1991Study by Guillet and Kellogg 1991
Doses of caffeine given to rat pups during developmentDoses of caffeine given to rat pups during development 20mg/kg (postnatal day 2) and 15mg/kg (postnatal20mg/kg (postnatal day 2) and 15mg/kg (postnatal
days 3-6)days 3-6) Density of adenosine receptors examined acrossDensity of adenosine receptors examined across
different ages (14 90 postnatal days)different ages (14 90 postnatal days) Significant increase in specific binding after neonatalSignificant increase in specific binding after neonatal
exposure to caffeine in the cortex, cerebellum, andexposure to caffeine in the cortex, cerebellum, andhippocampus due to an increase in A1 receptors.hippocampus due to an increase in A1 receptors.
Changes in A1 receptors lasted for several weeks afterChanges in A1 receptors lasted for several weeks aftercessation of caffeinecessation of caffeine
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Chronic Consumption of CaffeineChronic Consumption of Caffeine
During Development on the DensityDuring Development on the Density
of Benzodiazepine Receptorsof Benzodiazepine Receptors Research by Boulenger and Marangos 1989Research by Boulenger and Marangos 1989
Mice pups were given a diet enriched with caffeine for 15 daysMice pups were given a diet enriched with caffeine for 15 days No increase in benzodiazepine receptors, after chronic oral administrationNo increase in benzodiazepine receptors, after chronic oral administration
of caffeine.of caffeine. Controlled environment and housing to minimize stressControlled environment and housing to minimize stress
Contradictory results on chronic caffeine consumption and the densityContradictory results on chronic caffeine consumption and the densityof benzodiazepine receptorsof benzodiazepine receptors
Stress rather than caffeine-enriched diet induces an upregulation ofStress rather than caffeine-enriched diet induces an upregulation ofbenzodiazepine receptorsbenzodiazepine receptors
5 10 times higher concentration of caffeine required to produce an5 10 times higher concentration of caffeine required to produce anantagonistic effect on benzodiazepine receptors than adenosineantagonistic effect on benzodiazepine receptors than adenosinereceptorsreceptors
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PharmacokineticsPharmacokinetics
AbsorptionAbsorption Gastrointestinal tract and stomachGastrointestinal tract and stomach
Rapid rate, peak blood level in 30-60 min.Rapid rate, peak blood level in 30-60 min. Crosses lipid-membrane (not water soluble)Crosses lipid-membrane (not water soluble)
DistributionDistribution Diffuses throughout the organism and crossesDiffuses throughout the organism and crosses
BBBBBB Including placenta and placental BBBIncluding placenta and placental BBB
Nehlig et al., 1999; Fredholm et al., 1999Nehlig et al., 1999; Fredholm et al., 1999
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PharmacokineticsPharmacokinetics
MetabolismMetabolism Metabolized through liver biotransformation initially by demethylation intoMetabolized through liver biotransformation initially by demethylation into
dimethylxanthines.dimethylxanthines. *Dimethylxanthines are pharmacologically active and may add to the*Dimethylxanthines are pharmacologically active and may add to the
effects of caffeine consumption in humans.effects of caffeine consumption in humans. This process is unique to humans, no other animal species metabolizesThis process is unique to humans, no other animal species metabolizes
caffeine in a similar waycaffeine in a similar way Half life of caffeineHalf life of caffeine
Three to eight hours; varies with age and other external factorsThree to eight hours; varies with age and other external factors Newborns cannot metabolize caffeine, mainly eliminated byNewborns cannot metabolize caffeine, mainly eliminated by
excretionexcretion
Half life 80 +/_ 23 hoursHalf life 80 +/_ 23 hours Smokers, half life is reduced up to 50%Smokers, half life is reduced up to 50% Pregnant women and those taking oral contraceptive, half life upPregnant women and those taking oral contraceptive, half life up
to 15 hours longerto 15 hours longer
Nehlig et al., 1999; Fredholm et al., 1999Nehlig et al., 1999; Fredholm et al., 1999
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Effects of Caffeine onEffects of Caffeine on
NeurotransmittersNeurotransmitters Caffeine modifies the release and turnover ofCaffeine modifies the release and turnover of
several neurotransmitters by inhibitingseveral neurotransmitters by inhibitingpresynaptic adenosine receptors.presynaptic adenosine receptors. serotonin, acetylcholine, glutamate, norepinephrine,serotonin, acetylcholine, glutamate, norepinephrine,
and dopamineand dopamine Caffeine may also act at postsynaptic receptors.Caffeine may also act at postsynaptic receptors. The threshold necessary for caffeine to induceThe threshold necessary for caffeine to induce
changes in neurotransmitter function is anchanges in neurotransmitter function is anprominent area currently being explored toprominent area currently being explored tobetter understand the effects of caffeine onbetter understand the effects of caffeine onneurotransmission.neurotransmission.
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Caffeine and SerotoninCaffeine and Serotonin
Increased in vitro serotonin concentrationsIncreased in vitro serotonin concentrationsin the brain stem, cerebral cortex, andin the brain stem, cerebral cortex, and
cerebellumcerebellum Inconsistent results on the impact on theInconsistent results on the impact on the
rate of release, uptake, synthesis andrate of release, uptake, synthesis andturnoverturnover
Decreased serotonin accessibilityDecreased serotonin accessibilitypostsynapticallypostsynaptically
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Caffeine and AcetylcholineCaffeine and Acetylcholine
Increased Ach release from the cerebralIncreased Ach release from the cerebral
cortexcortex 15 and 30 mg/kg I.P. in anesthetized rats15 and 30 mg/kg I.P. in anesthetized rats
Increased Ach turnover in theIncreased Ach turnover in the
hippocampushippocampus Intracerebral injections of theophyllineIntracerebral injections of theophylline
Relatively unexplored areaRelatively unexplored area
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Caffeine and Amino AcidsCaffeine and Amino Acids
Increased amount of glutamate in theIncreased amount of glutamate in the
whole brain of micewhole brain of mice
Decreased amounts of GABA and glycine,Decreased amounts of GABA and glycine,specifically posterior region of the brainspecifically posterior region of the brain Dose of caffeineDose of caffeine
.5 mg/ml in drinking water for 7 days.5 mg/ml in drinking water for 7 daysthenthen
1.0 mg/ml for 14 days1.0 mg/ml for 14 days
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Caffeine and CatecholaminesCaffeine and Catecholamines
Norepinephrine (noradrenaline): increased rate ofNorepinephrine (noradrenaline): increased rate ofsynthesis and turnoversynthesis and turnover Increase firing rate of noradrenergic neurons in the locusIncrease firing rate of noradrenergic neurons in the locus
coeruleuscoeruleus Exact mechanism of how caffeine activates norepinephrineExact mechanism of how caffeine activates norepinephrine
neurons is not clearneurons is not clear Epinephrine (adrenaline): increased circulating rateEpinephrine (adrenaline): increased circulating rate DopamineDopamine
Inconsistent findings: increased, decreased and no change in rateInconsistent findings: increased, decreased and no change in rate
of synthesis and turnoverof synthesis and turnover Animal model (rat): caffeine inhibits firing rate of dopamineAnimal model (rat): caffeine inhibits firing rate of dopamine
neurons in the ventral tegmental area that projects to theneurons in the ventral tegmental area that projects to themesolimbic and mesocortical areas; no significant change in themesolimbic and mesocortical areas; no significant change in thefiring rate of dopamine neurons in the substantia nigra thatfiring rate of dopamine neurons in the substantia nigra thatprojects to the caudate nucleusprojects to the caudate nucleus
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Caffeine and DopamineCaffeine and Dopamine
Indirect action on dopamine receptors throughIndirect action on dopamine receptors throughcaffeines antagonistic effect on adenosinecaffeines antagonistic effect on adenosinereceptorsreceptors A2 adenosine receptors are co-localizedA2 adenosine receptors are co-localized
postsynaptically with D2 dopamine receptors on striatalpostsynaptically with D2 dopamine receptors on striatalneuronal cells and extends to the core and shell of theneuronal cells and extends to the core and shell of thenucleus accumbensnucleus accumbens Revealing direct evidence for a central functional interactionRevealing direct evidence for a central functional interaction
between the two receptorsbetween the two receptors
Stimulation of A2 receptors with a selective A2 agonistStimulation of A2 receptors with a selective A2 agonistdecreases the affinity of D2 receptors for dopaminedecreases the affinity of D2 receptors for dopamine
Fredholm et al., 1999Fredholm et al., 1999
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The Behavioral Effects of CaffeineThe Behavioral Effects of Caffeine
Motor activityMotor activity
VigilanceVigilance
AttentionAttention
Learning and memoryLearning and memory
MoodMoodArousalArousal
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Caffeine and Locomotor ActivityCaffeine and Locomotor Activity
Study by Solinas et al. 2002Study by Solinas et al. 2002Animal modelAnimal model
I.P. injections of caffeineI.P. injections of caffeine
3 mg/kg; 10 mg/kg; 30 mg/kg; 100mg/kg3 mg/kg; 10 mg/kg; 30 mg/kg; 100mg/kg Total motor activity after I.P. injection resultedTotal motor activity after I.P. injection resulted
in a dose response curve that had an inverted u-in a dose response curve that had an inverted u-
shapeshape Significant motor activity with caffeine doses of 10 andSignificant motor activity with caffeine doses of 10 and
30mg/kg; 3 and 100mg/kg are ineffective30mg/kg; 3 and 100mg/kg are ineffective
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Effects of Caffeine on DopamineEffects of Caffeine on Dopamine
and Glutamate Releaseand Glutamate Release Study by Solinas et al., 2002Study by Solinas et al., 2002
In vivo study where probes were implanted in the shellIn vivo study where probes were implanted in the shell
or core of the nucleus accumbens in adult Sprague-or core of the nucleus accumbens in adult Sprague-Dawley ratsDawley rats
10 and 30 mg/kg doses of caffeine induced significant10 and 30 mg/kg doses of caffeine induced significant
increase in extracellular concentrations of dopamineincrease in extracellular concentrations of dopamine
and glutamate in the shell of the nucleus accumbensand glutamate in the shell of the nucleus accumbens
30 mg/kg dose of caffeine significantly increased level30 mg/kg dose of caffeine significantly increased level
of dopamine in the core of nucleus accumbensof dopamine in the core of nucleus accumbens
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Caffeine and Motor ActivityCaffeine and Motor Activity
Garrett and Holtzman 1996Garrett and Holtzman 1996Animal ModelAnimal Model Rotational behavioral experimentRotational behavioral experiment
Animals with unilateral nigrostriatal lesionsAnimals with unilateral nigrostriatal lesions
Doses of caffeine 10-100 mg/kgDoses of caffeine 10-100 mg/kg ~30 mg/kg produced peak contralateral rotational behavior~30 mg/kg produced peak contralateral rotational behavior
Locomotor activity experimentLocomotor activity experiment Doses of caffeine 3100 mg/kgDoses of caffeine 3100 mg/kg 10 30 mg/kg produced peak increases in locomotor activity10 30 mg/kg produced peak increases in locomotor activity
Both motor behaviors were affected in a biphasic mannerBoth motor behaviors were affected in a biphasic mannerby caffeineby caffeine Two different mechanisms by which caffeine affectsTwo different mechanisms by which caffeine affects
rotational and locomotor activityrotational and locomotor activity
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Caffeine and VigilanceCaffeine and Vigilance
16 Human subjects16 Human subjects 28 hrs of sleep deprivation28 hrs of sleep deprivation Subjects given a 400mg dose of caffeine and two subsequentSubjects given a 400mg dose of caffeine and two subsequent
100mg doses of caffeine100mg doses of caffeine hour after first dose of caffeine a 2 hr march, followed by hour after first dose of caffeine a 2 hr march, followed by
sandbag pilling taskssandbag pilling tasks Second day treadmill run to exhaustionSecond day treadmill run to exhaustion Subjects that received caffeine performed the sandbag pilling taskSubjects that received caffeine performed the sandbag pilling task
in a significantly shorter amount of time than the placebo groupin a significantly shorter amount of time than the placebo group Caffeine group had significantly longer time until they reachedCaffeine group had significantly longer time until they reached
exhaustion compared to placebo (25% longer treadmill run)exhaustion compared to placebo (25% longer treadmill run)
McLellan et al., 2004McLellan et al., 2004
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Caffeine and Learning and MemoryCaffeine and Learning and Memory
Inconclusive results on the relationship ofInconclusive results on the relationship ofcaffeine and learning and memory abilitiescaffeine and learning and memory abilities
Some studies have shown improvements inSome studies have shown improvements inlearning and memorylearning and memory Fewer errors and decreased latency in maze tasksFewer errors and decreased latency in maze tasks
Others have shown no change in performanceOthers have shown no change in performance
Researchers agree that caffeine does influenceResearchers agree that caffeine does influenceattention levels, vigilance, and exploratoryattention levels, vigilance, and exploratorybehavior which may impact the learning processbehavior which may impact the learning process
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Caffeine and MoodCaffeine and Mood
Low doses of caffeine are associated withLow doses of caffeine are associated withaffecting ones mood in a positive manner.affecting ones mood in a positive manner.
Subjective reports of changes in energy,Subjective reports of changes in energy,imagination, efficiency, increased self-confidenceimagination, efficiency, increased self-confidenceand feeling of well being.and feeling of well being.
High doses of caffeine (over 200mg) mayHigh doses of caffeine (over 200mg) mayproduce feelings of insomnia, anxiousness,produce feelings of insomnia, anxiousness,nervousness and restlessnessnervousness and restlessness
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Caffeine and SleepCaffeine and Sleep
Human Study:Human Study: 200mg of caffeine200mg of caffeine
Prolonged onset of sleep (33 min.)Prolonged onset of sleep (33 min.) Decreased quality of sleep (self report)Decreased quality of sleep (self report) Regular coffee drinkers have relativelyRegular coffee drinkers have relatively
mild effects of caffeine on sleep comparedmild effects of caffeine on sleep comparedto non-habitual coffee drinkersto non-habitual coffee drinkers
Nehlig et al., 1992Nehlig et al., 1992
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Tolerance to the Effects of CaffeineTolerance to the Effects of Caffeine
A change in the sensitivity of a subject to an agent after continuousA change in the sensitivity of a subject to an agent after continuousexposure has occurred, in which larger doses are needed to produceexposure has occurred, in which larger doses are needed to producethe original effectthe original effect
Tolerance to various behavioral effects of caffeine have been shownTolerance to various behavioral effects of caffeine have been shown
extensively in animal studies, relatively few human studiesextensively in animal studies, relatively few human studies Tolerance occurs quiet rapidly in animalsTolerance occurs quiet rapidly in animals
Animal ModelAnimal Model Rats had more than 50mg/kg of caffeine per day available in their drinkingRats had more than 50mg/kg of caffeine per day available in their drinking
water (7 days total)water (7 days total)
After a week, the rats were given a series of doses of caffeine (3-100mg/kg)After a week, the rats were given a series of doses of caffeine (3-100mg/kg)and locomotor activity was assessedand locomotor activity was assessed Non exposed rats had a 50% increase in locomotor activity when given aNon exposed rats had a 50% increase in locomotor activity when given a
single 3.0mg/kg dose of caffeinesingle 3.0mg/kg dose of caffeine Rats previously exposed to caffeine did not have an increase in locomotorRats previously exposed to caffeine did not have an increase in locomotor
activity more than by 25% and this occurred at the higher caffeine doseactivity more than by 25% and this occurred at the higher caffeine doselevelslevels
Finn and Holtzman 1986Finn and Holtzman 1986
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Tolerance to the Effects of CaffeineTolerance to the Effects of Caffeine
Human StudiesHuman Studies Tolerance to the effect of caffeine on bloodTolerance to the effect of caffeine on blood
pressure, heart rate and diuresis have beenpressure, heart rate and diuresis have beenfound to develop within a few days of caffeinefound to develop within a few days of caffeine
consumptionconsumption
Tolerance to certain behavioral effects ofTolerance to certain behavioral effects of
caffeine have also been demonstratedcaffeine have also been demonstratedAnxiety, jitteriness, nervousness, insomniaAnxiety, jitteriness, nervousness, insomnia
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Mechanism of the Development ofMechanism of the Development of
ToleranceTolerance An increase in the number of adenosine receptors mayAn increase in the number of adenosine receptors may
contribute to the sedative effects on activity observed incontribute to the sedative effects on activity observed inboth animal and human studies after caffeine consumptionboth animal and human studies after caffeine consumptionhas stoppedhas stopped Increased sensitivity to endogenous adenosineIncreased sensitivity to endogenous adenosine
Adaptive changes in adenosine receptors doesnt explainAdaptive changes in adenosine receptors doesnt explainthe development of tolerance to stimulant action ofthe development of tolerance to stimulant action ofcaffeine in cases of locomotor activitycaffeine in cases of locomotor activity
Compensatory changes in the dopaminergic systemCompensatory changes in the dopaminergic systemresulting from chronic antagonism at adenosine receptorsresulting from chronic antagonism at adenosine receptorsmay play a role in the development of tolerance to caffeinemay play a role in the development of tolerance to caffeine
Dews et al., 2002; Nehlig et al., 1999Dews et al., 2002; Nehlig et al., 1999
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Caffeine Dependence andCaffeine Dependence and
WithdrawalWithdrawal Withdrawal symptoms usually occur if toleranceWithdrawal symptoms usually occur if tolerance
has developed; and the presence of withdrawalhas developed; and the presence of withdrawalsymptoms after discontinuation of a substancesymptoms after discontinuation of a substance
generally defines physical dependencegenerally defines physical dependence Withdrawal symptoms have been reported withinWithdrawal symptoms have been reported within
12-24 hours after termination of caffeine intake12-24 hours after termination of caffeine intake And generally peaks around 20-48 hours afterAnd generally peaks around 20-48 hours after
cessation of caffeinecessation of caffeineBenowitz 1990Benowitz 1990
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Withdrawal ContinuedWithdrawal Continued
Caffeine withdrawal: Human studiesCaffeine withdrawal: Human studies Increases cerebral blood flowIncreases cerebral blood flow Headaches, irritability, sleepiness, lethargy, impairedHeadaches, irritability, sleepiness, lethargy, impaired
mental function, weakness, hand or limb tremors,mental function, weakness, hand or limb tremors,dysphoria, restlessness, nausea and anxietydysphoria, restlessness, nausea and anxiety
Caffeine withdrawal: Animal studiesCaffeine withdrawal: Animal studies Decreased locomotor activityDecreased locomotor activity Decreased operant behaviorDecreased operant behavior Changes in sleepChanges in sleep
Dews et al., 2002; Nehlig et al., 1999Dews et al., 2002; Nehlig et al., 1999
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Caffeine Related DisordersCaffeine Related Disorders
Caffeinism: A condition due to an excessiveCaffeinism: A condition due to an excessive
intake of caffeine resulting in:intake of caffeine resulting in:
diarrhea, elevated blood pressure, rapid breathing,diarrhea, elevated blood pressure, rapid breathing,heart palpitations, and insomnia.heart palpitations, and insomnia.
Caffeine-Related Disorders listed in the DSMCaffeine-Related Disorders listed in the DSM Caffeine intoxicationCaffeine intoxication Caffeine induced anxiety disorderCaffeine induced anxiety disorder
Caffeine induced sleep disorderCaffeine induced sleep disorder
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Caffeine and Health ConcernsCaffeine and Health Concerns
Conflicting findings on any association between caffeine andConflicting findings on any association between caffeine andimpaired health.impaired health. Moderate consumption of caffeine does not seem to pose health risksModerate consumption of caffeine does not seem to pose health risks
Dose response relationship between the amount of coffeeDose response relationship between the amount of coffee
consumption and the risk of cardiovascular diseaseconsumption and the risk of cardiovascular disease Elevated levels of total and LDL cholesterol (more than 2-3 cups per day)Elevated levels of total and LDL cholesterol (more than 2-3 cups per day)
A correlation reported between caffeine consumption in pregnantA correlation reported between caffeine consumption in pregnantindividuals and lower newborn birth weightsindividuals and lower newborn birth weights Neonatal do exhibit withdrawal symptoms born to mother who consumeNeonatal do exhibit withdrawal symptoms born to mother who consume
a large amount of caffeine during pregnancya large amount of caffeine during pregnancy
High doses of caffeine shown to elicit mental disturbances likeHigh doses of caffeine shown to elicit mental disturbances likeanxiety, restlessness, nervousness, and insomnia (exacerbates inanxiety, restlessness, nervousness, and insomnia (exacerbates inindividuals who are more sensitive to anxiety and may produceindividuals who are more sensitive to anxiety and may producepanic attacks at high doses, but not in healthy controls)panic attacks at high doses, but not in healthy controls)
Benowitz 1990; Nawrot et al., 2003Benowitz 1990; Nawrot et al., 2003
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Therapeutic Uses for CaffeineTherapeutic Uses for Caffeine
Treatment of apnea in newbornsTreatment of apnea in newborns Caffeine helps regularize breathingCaffeine helps regularize breathing
Treatment of migraine headaches whenTreatment of migraine headaches whencombined with aspirincombined with aspirin