Caffeine Psyc 760

8/2/2019 Caffeine Psyc 760

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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

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Caffeine Psyc 760