1 STIMULANTS Allen Fowler Mycheal Scott Psyc 472

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STIMULANTSSTIMULANTS

Allen FowlerAllen FowlerMycheal ScottMycheal Scott

Psyc 472Psyc 472

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DEFINITIONDEFINITIONStimulants are a substance which tends to Stimulants are a substance which tends to

increase behavioral activity when increase behavioral activity when administeredadministeredElevate MoodElevate Mood Increase Motor ActivityIncrease Motor Activity Increase AlertnessIncrease AlertnessDecrease need for SleepDecrease need for Sleep Increase the brains metabolic and neuronal Increase the brains metabolic and neuronal

activityactivity

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PROCESSESPROCESSES

While all stimulants increase behavioral While all stimulants increase behavioral activity the component processes involved activity the component processes involved differ.differ.Neurotransmitter or receptor processesNeurotransmitter or receptor processes

Increase neurotransmitters releaseIncrease neurotransmitters releaseBlock reuptakeBlock reuptake

Inhibition of inhibitory neurotransmittersInhibition of inhibitory neurotransmitters disinhibitiondisinhibition

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COMMONLY USED STIMULANTSCOMMONLY USED STIMULANTS

CaffeineCaffeineNicotineNicotineAmphetamineAmphetamineCocaineCocaineEphedrineEphedrineRitalinRitalin

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CAFFEINE AND NICOTINECAFFEINE AND NICOTINE

Allen FowlerAllen Fowler

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CAFFEINE (picture courtesy Erowid web site)

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CAFFEINE Most commonly consumed psychoactive

drug in the world Average intake per person per day is

between 80 to 400 milligrams Consumption of caffeine is not considered

drug abuse No regulation on sale or use

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CAFFEINE CONTENT Item

Coffee (5 oz)Tea (5oz)Cocoa (5oz)Chocolate (1oz)Chocolate milk (1oz)Cola drink (12oz)OTC stimulants OTC analgesics (aspirin)OTC cold remedies

Average (mg)100505

255

100+100+35-65

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EFFECTSEFFECTS

Caffeine elicits positive effects such asCaffeine elicits positive effects such asEnhanced mental alertnessEnhanced mental alertness

Sustained intellectual effort Sustained intellectual effort No substantial disruption of coordinated intellectual No substantial disruption of coordinated intellectual

thought or motor activitythought or motor activity Increased energyIncreased energyA sense of well-beingA sense of well-beingFaster and clearer flow of thoughtFaster and clearer flow of thoughtReduced fatigueReduced fatigueNeed for sleep is delayedNeed for sleep is delayed

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EffectsEffects Caffeine may adversely effect tasks involvingCaffeine may adversely effect tasks involving

delicate muscle coordination delicate muscle coordination Accurate timingAccurate timing Arithmetic skillsArithmetic skills

Heavy doses - 1.5 grams Heavy doses - 1.5 grams AgitationAgitation AnxietyAnxiety TremorsTremors Rapid breathingRapid breathing InsomniaInsomnia

Lethal dose – 10 gramsLethal dose – 10 grams 100 cups of coffee100 cups of coffee 100 OTC stimulant capsules100 OTC stimulant capsules

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EffectsEffects

Caffeine causes a slight stimulant action Caffeine causes a slight stimulant action on the hearton the heart Increases the workload Increases the workload

cardiac contractilitycardiac contractility

Increases cardiac outputIncreases cardiac output

Dilates coronary arteriesDilates coronary arteriesMore oxygen to the heartMore oxygen to the heart

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EffectsEffects

Caffeine constricts cerebral blood vesselsCaffeine constricts cerebral blood vessels Decreases blood flow by about 30%Decreases blood flow by about 30% Can relieve headachesCan relieve headaches

Bronchial relaxationBronchial relaxation

Increased secretion of gastric acidIncreased secretion of gastric acid

Increased urineIncreased urine

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EffectsEffects

Chronic use associated with habituation Chronic use associated with habituation and toleranceand tolerance

Quitting may cause withdrawalQuitting may cause withdrawalHeadachesHeadachesDrowsinessDrowsinessFatigueFatigueNegative moodNegative mood

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Reproductive EffectsReproductive Effects Freely crosses the placenta to the fetusFreely crosses the placenta to the fetus

Consumed by estimated 75% of pregnant womenConsumed by estimated 75% of pregnant women

Breast milk contains levels equal or higher in concentration than mothers Breast milk contains levels equal or higher in concentration than mothers plasmaplasma

Safety still unresolvedSafety still unresolved One study shows 300 mg relatively safeOne study shows 300 mg relatively safe

Higher doses increased intrauterine growth retardationHigher doses increased intrauterine growth retardation

Another study shows 160 mg may cause growth retardationAnother study shows 160 mg may cause growth retardation 300mg intake even in the month before doubled the risk of spontaneous abortion300mg intake even in the month before doubled the risk of spontaneous abortion

Recent study shows 6-10 cups per day is associated with increased risk of Recent study shows 6-10 cups per day is associated with increased risk of spontaneous abortionspontaneous abortion

Moderate consumption does not increase the riskModerate consumption does not increase the risk

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Therapeutic UsesTherapeutic Uses AsthmaAsthma

Bronchial relaxation effectsBronchial relaxation effects

NarcolepsyNarcolepsy To help maintain daytime wakefulnessTo help maintain daytime wakefulness

MigraineMigraine Restricts blood flow in the cerebral cortexRestricts blood flow in the cerebral cortex

Headache and other minor pain syndromesHeadache and other minor pain syndromes In conjunction with aspirin In conjunction with aspirin

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PharmacokineticsPharmacokinetics

Caffeine is rapidly and completely absorbedCaffeine is rapidly and completely absorbed Significant blood levels reached in 30-45 minutesSignificant blood levels reached in 30-45 minutes Levels peak in about 2 hoursLevels peak in about 2 hours

Caffeine is freely and equally distributed through total Caffeine is freely and equally distributed through total body waterbody water

Caffeine can be found in almost equal concentrations Caffeine can be found in almost equal concentrations throughout body and brainthroughout body and brain

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Caffeine has 3.5 to 5 hours half lifeCaffeine has 3.5 to 5 hours half lifeExtended half life forExtended half life for

ElderlyElderlyPregnant women Pregnant women

Up to ten hoursUp to ten hours

InfantsInfants

Decreased half life for smokersDecreased half life for smokers

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Caffeine is metabolized in the liver by the Caffeine is metabolized in the liver by the CYP1A2 subgroup of enzymes into three CYP1A2 subgroup of enzymes into three metabolitesmetabolites Theophylline Theophylline

Bronchial relaxationBronchial relaxation ParaxanthineParaxanthine TheobromineTheobromine Theophylline and Paraxanthine act similar to caffeineTheophylline and Paraxanthine act similar to caffeine

About 10% is excreted unchangedAbout 10% is excreted unchanged

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Mechanism of ActionMechanism of Action

Major site of action Major site of action – Adenosine receptorsAdenosine receptors– Most potent at adenosine AMost potent at adenosine A11 and A and A2A2A

Caffeine works as an antagonism agentCaffeine works as an antagonism agent– Blocks the adenosine receptorBlocks the adenosine receptor

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Mechanism of ActionMechanism of Action– Adenosine is a neuromodulator Adenosine is a neuromodulator

Modulatory effect increasing or decreasing the rate at which Modulatory effect increasing or decreasing the rate at which neurons fireneurons fireWorks in conjunction with the G protein processesWorks in conjunction with the G protein processes

– Adenosine appears to exert sedative, depressant, and anticonvulsant Adenosine appears to exert sedative, depressant, and anticonvulsant actions actions

Works to slow down the systemWorks to slow down the systemImportant to sleeping Important to sleeping

– Adenosinergic neurons form a diffuse systemAdenosinergic neurons form a diffuse systemNo exclusively adenosinergic pathwaysNo exclusively adenosinergic pathwaysAdenosine stimulates GABAAdenosine stimulates GABAAA inhibitory neurons inhibitory neurons

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– Adenosine is created from the process by Adenosine is created from the process by which the body breaks down ATP for energywhich the body breaks down ATP for energy

ATP is used throughout the body for energyATP is used throughout the body for energy

Used for high energy bursts such as exercising Used for high energy bursts such as exercising and runningand running

Phosphates form a high energy bondPhosphates form a high energy bond

Cells break the phosphate bond to extrapolate the Cells break the phosphate bond to extrapolate the energyenergy

When the phosphates are pulled off the adenosine When the phosphates are pulled off the adenosine is now free to have an effect in the bodyis now free to have an effect in the body

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AA11 receptors inhibit excitatory neurons receptors inhibit excitatory neurons– Dopamine, glutamate, and ACh Dopamine, glutamate, and ACh

secreting neuronssecreting neurons

– Reduces production of cAMP Reduces production of cAMP

– Slows the activity of the kinaseSlows the activity of the kinase

– Reduces occurrence of the action Reduces occurrence of the action potentialpotential

A2A2AA receptors stimulate inhibitory receptors stimulate inhibitory neuronsneurons

– GABAGABAAA neurons neurons

– Stimulates production of cAMP Stimulates production of cAMP

– Increases activity of the kinaseIncreases activity of the kinase

– Increases occurrence of the action Increases occurrence of the action potentialpotential

picture courtesy “The Brain a Neuroscience Primerpicture courtesy “The Brain a Neuroscience Primer””

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Adenosine AAdenosine A11 receptors receptors– Inhibit the release of dopamine and glutamateInhibit the release of dopamine and glutamate– Limit the release of acetylcholineLimit the release of acetylcholine

Blockade of ABlockade of A11 receptors receptors– Modest rewardModest reward– Increased vigilance and mental acuity Increased vigilance and mental acuity – Creates arousal effectCreates arousal effect

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Adenosine AAdenosine A2A2A receptors receptors– Stimulate GABAStimulate GABAAA neurons of inhibitory neurons of inhibitory

pathwayspathways– Inhibit dopamine activityInhibit dopamine activity

Blockade of ABlockade of A2A2A receptors receptors– Increases the potency of endogenous Increases the potency of endogenous

dopaminedopamine

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Caffeine facilitates a disinhibition process Caffeine facilitates a disinhibition process at adenosine receptor sitesat adenosine receptor sites

Caffeine removes the negative effects of Caffeine removes the negative effects of adenosine from dopamine receptors adenosine from dopamine receptors increasing dopamine activityincreasing dopamine activity– Caffeine does not stimulate dopamine releaseCaffeine does not stimulate dopamine release

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NICOTINE (picture courtesy Erowid web site)

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NICOTINE Primary active ingredient in tobacco One of the three most widely used

psychoactive drugs Caffeine Alcohol

Few or no therapeutic applications Important because of widespread use and

toxicity

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Background Information Indigenous to the Americas 1492 Columbus beaches in West Indies

Natives offer them tobacco as gift

1556 first plants taken to Europe 1571 believed to have curing properties for

36 different ailments 1575-1600 becomes “duty” of every man of

fashion – worth its weight in silver

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Background Information

1881 Cigarette rolling machine invented 1889 2.4 billion cigarettes produced annually in

U.S. 1904 3 billion cigarettes sold in U.S. 1912 13 billion cigarettes sold in U.S. WWII through mid-1960’s smoking considered

cool Now beginning to be shunned as unhealthy and

unwise

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Background Information Responsible for the deaths of 1100 Americans

every day Each day

6000 American teenagers try their first cigarette 3000 children become regular smokers 1000 of these will die from smoking related disease

9 in 10 smokers become addicted before age 21

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Background Information ½ of all people who have smoked have quit % American adults who smoke has fallen

from 50 in 1965 to 25 in 1998 Smoking identified as the major

preventable cause death and disability As far as 30 years ago

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Background Informationo Nicotine is only one of about 4000

compounds released by burning tobacco

o Adverse cardiovascular, pulmonary, and carcinogenic effects are from the other compounds

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EffectsEffects

Nicotine exerts powerful effects onNicotine exerts powerful effects onBrainBrainSpinal cordSpinal cordPeripheral nervous systemPeripheral nervous systemHeartHeartVarious other body structuresVarious other body structures

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EffectsEffects

Stimulation of the vomit center in the brain Stimulation of the vomit center in the brain stem and sensory receptors in the stem and sensory receptors in the stomachstomachNausea in early stages of smokingNausea in early stages of smokingTolerance develops rapidlyTolerance develops rapidly

Reduces weight gain Reduces weight gain probably by suppressing appetiteprobably by suppressing appetite

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EffectsEffects Stimulates release of ADH (antidiuretic hormone) Stimulates release of ADH (antidiuretic hormone)

causing fluid retentioncausing fluid retention

Reduces activity of afferent nerve fibers from musclesReduces activity of afferent nerve fibers from muscles Reduction in muscle toneReduction in muscle tone May be partially involved with relaxation effectMay be partially involved with relaxation effect

Higher dosesHigher doses Can induce nervousness and tremorsCan induce nervousness and tremors Seizures in toxic overdoseSeizures in toxic overdose

Smoking associated with increased occurrence of panic Smoking associated with increased occurrence of panic attacks and panic disordersattacks and panic disorders

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EffectsEffects

In the CNS nicotine increasesIn the CNS nicotine increasesPsychomotor activityPsychomotor activityCognitive functioning Cognitive functioning Sensorimotor performanceSensorimotor performanceAttentionAttentionMemory consolidationMemory consolidation

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EffectEffect

Nicotine can improve performance on Nicotine can improve performance on vigilance and rapid information processingvigilance and rapid information processingEffects are greater for working memory rather Effects are greater for working memory rather

than long term memorythan long term memory

Nicotine exerts an antidepressant effectNicotine exerts an antidepressant effectHigh smoking rates among depressed High smoking rates among depressed

individuals may be an attempt at self individuals may be an attempt at self medication medication

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EffectsEffects

Nicotine exerts a potent reinforcing actionNicotine exerts a potent reinforcing action Indirect activation of midbrain dopamine Indirect activation of midbrain dopamine

neurons neurons Greatest in early phasesGreatest in early phasesDiminishes over time Diminishes over time Smoking is continued to avoid withdrawal Smoking is continued to avoid withdrawal

symptomssymptoms

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Reproductive EffectsReproductive Effects

Smoking during pregnancy increases rates Smoking during pregnancy increases rates spontaneous abortionspontaneous abortion StillbirthStillbirth Early postpartum deathEarly postpartum death Preterm deliveriesPreterm deliveries

Intrauterine growth retardation is increased 40%Intrauterine growth retardation is increased 40%

2000 infant deaths per year attributed to 2000 infant deaths per year attributed to smokingsmoking

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Reproductive EffectsReproductive Effects

Smoking reduces oxygen delivery to the Smoking reduces oxygen delivery to the fetus resulting in varying degree of fetal fetus resulting in varying degree of fetal hypoxiahypoxiaFetus does not receive as much oxygenFetus does not receive as much oxygen

Smoking may result in irreversible Smoking may result in irreversible intellectual and physical deficienciesintellectual and physical deficiencies Increased prevalence of ADHDIncreased prevalence of ADHDLower IQ scoresLower IQ scores

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Tolerance Tolerance

Nicotine does not appear induce a pronounced Nicotine does not appear induce a pronounced degree of biological tolerancedegree of biological tolerance Increased use in early stages which usually levels off Increased use in early stages which usually levels off

as smoking is continuedas smoking is continued Smokers adjust nicotine intake to maintain 20 to 40 Smokers adjust nicotine intake to maintain 20 to 40

nanograms per milliliter of plasmananograms per milliliter of plasma

Does induce physiological and psychological Does induce physiological and psychological dependencedependence Habituation Habituation Rebound effectRebound effect

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Withdrawal SymptomsWithdrawal Symptoms Intense nicotine cravingIntense nicotine craving IrritabilityIrritability AnxietyAnxiety AngerAnger Difficulty concentratingDifficulty concentrating RestlessnessRestlessness ImpatienceImpatience Increased appetiteIncreased appetite Weight gainWeight gain InsomniaInsomnia

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TherapyTherapy

Nicotine replacement therapy doubles Nicotine replacement therapy doubles successful quit ratessuccessful quit ratesSkin patchesSkin patchesGumGumNicotine nasal sprayNicotine nasal spray

The use of Zyban has also been shown to The use of Zyban has also been shown to increase successful quit rates increase successful quit rates

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Pharmacokinetics Pharmacokinetics Easily absorbed in the bodyEasily absorbed in the body

Lungs Lungs Buccal and nasal mucosaBuccal and nasal mucosa SkinSkin Gastrointestinal tractGastrointestinal tract

Nicotine is suspended in the minute Nicotine is suspended in the minute particles (tars) in smokeparticles (tars) in smoke

Orally administered blood levels of Orally administered blood levels of nicotine are comparable to smokingnicotine are comparable to smoking

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Pharmacokinetics Pharmacokinetics Only about 20% of the nicotine in a cigarette Only about 20% of the nicotine in a cigarette

is inhaled and absorbed into the bloodstreamis inhaled and absorbed into the bloodstream

Nicotine which is not immediately absorbed Nicotine which is not immediately absorbed is rapidly metabolized by the hepatic enzyme is rapidly metabolized by the hepatic enzyme CYP2A6CYP2A6

Inhalation allows controllability of doseInhalation allows controllability of dose Frequency of breathsFrequency of breaths Depth of breathsDepth of breaths Time in lungsTime in lungs Number of cigarettesNumber of cigarettes

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Pharmacokinetics Pharmacokinetics Nicotine is thoroughly distributed in the Nicotine is thoroughly distributed in the

bodybody No barriers to nicotine distributionNo barriers to nicotine distribution Rapid brain penetrationRapid brain penetration Crosses placental barrierCrosses placental barrier Appears in all bodily fluidsAppears in all bodily fluids

The liver metabolizes 80 to 90% before The liver metabolizes 80 to 90% before excretion to the kidneysexcretion to the kidneys Primary metabolite is cotinine Primary metabolite is cotinine

The elimination half life in chronic users is The elimination half life in chronic users is about 2 hrsabout 2 hrs

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Nicotine activates specific acetylcholine Nicotine activates specific acetylcholine (ACh) receptors known as nicotinic (ACh) receptors known as nicotinic receptorsreceptors

Nicotinic receptors are located throughout Nicotinic receptors are located throughout the bodythe body– Skeletal muscleSkeletal muscle– Sympathetic and parasympathetic neuronsSympathetic and parasympathetic neurons– CNS CNS

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ACh is released, broken down, and ACh is released, broken down, and reabsorbed very quickly (microsecond) reabsorbed very quickly (microsecond) allowing the receptor to respond to new allowing the receptor to respond to new AchAch

ACh receptors work as a fast first ACh receptors work as a fast first messenger systemmessenger system– Attached directly to ion channelsAttached directly to ion channels– Binding has an immediate responseBinding has an immediate response

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picture courtesy pharyngula.orgpicture courtesy pharyngula.org

Nicotine replaces ACh at nicotinic receptorNicotine replaces ACh at nicotinic receptor Beats out the ACh at the binding siteBeats out the ACh at the binding site Works as an agonist Works as an agonist Opens ion channel allowing depolarization to occurOpens ion channel allowing depolarization to occur

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Peripheral Nervous Peripheral Nervous SystemSystem

Activation of nicotinic receptors in Activation of nicotinic receptors in the PNSthe PNS Increases blood pressure and heart rateIncreases blood pressure and heart rate Causes the release of epinephrine from Causes the release of epinephrine from

the adrenal glandsthe adrenal glands Increases the tone, secretions, and Increases the tone, secretions, and

activity of the gastrointestinal tractactivity of the gastrointestinal tract

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Central Nervous SystemCentral Nervous System

Nicotinic receptors are widely distributed Nicotinic receptors are widely distributed and may be present at the presynaptic and may be present at the presynaptic terminals of neurons which secrete terminals of neurons which secrete DopamineDopamine AcetylcholineAcetylcholine GlutamineGlutamine

Activation by nicotine facilitates the Activation by nicotine facilitates the release and increases the action in the release and increases the action in the brain of these neurotransmittersbrain of these neurotransmitters

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Dopamine levels are increased in theDopamine levels are increased in the Ventral tegmentumVentral tegmentum Nucleus accumbensNucleus accumbens ForebrainForebrain

Stimulation of these areas account Stimulation of these areas account for the behavioral reinforcement, for the behavioral reinforcement, stimulant, antidepressant, and stimulant, antidepressant, and addictive properties of nicotineaddictive properties of nicotine

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Increases in acetylcholine contribute Increases in acetylcholine contribute to the cognitive potentiation and to the cognitive potentiation and memory facilitation properties of memory facilitation properties of nicotinenicotine

Facilitation of glutaminergic Facilitation of glutaminergic neurotransmissions contribute to the neurotransmissions contribute to the improvement in memory functioning improvement in memory functioning

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Smoking DiseasesSmoking Diseases

Smoking accelerates the Smoking accelerates the depositing of fat in the arteriesdepositing of fat in the arteries

Increased risk of heart attack Increased risk of heart attack and strokeand stroke

Smoking weakens the immune Smoking weakens the immune systemsystem

Smoking irritates the lining in Smoking irritates the lining in the lungs impairing respirationthe lungs impairing respiration

Smokers coughSmokers cough EmphysemaEmphysema

picture courtesy picture courtesy quantumclinic.comquantumclinic.com

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Lung cancerLung cancer 90-95% of male 90-95% of male

deathsdeaths 70-75% of female 70-75% of female

deathsdeaths

Cancer of the Cancer of the mouth and throatmouth and throat Chewing tobaccoChewing tobaccoPicture courtesy quantumclinic.comPicture courtesy quantumclinic.com

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Cardiovascular diseaseCardiovascular disease Carbon monoxide decreases amount of oxygen Carbon monoxide decreases amount of oxygen

delivered to the heart while nicotine increases delivered to the heart while nicotine increases the workloadthe workload

Carbon monoxide and nicotine increase Carbon monoxide and nicotine increase narrowing (atherosclerosis) and clotting narrowing (atherosclerosis) and clotting (thrombosis) in the coronary arteries(thrombosis) in the coronary arteries

Increased risk of coronary heart diseaseIncreased risk of coronary heart disease

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About 4000 Americans per year die About 4000 Americans per year die from lung cancer caused by second-from lung cancer caused by second-hand smokehand smoke

37000 deaths per year from heart 37000 deaths per year from heart disease caused by second hand disease caused by second hand smoke smoke

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Sources Sources

Julien, Robert M. (2001). A Primer of Drug Action (ninth ed.). Julien, Robert M. (2001). A Primer of Drug Action (ninth ed.). Caffeine and Nicotine Caffeine and Nicotine (pp 220-248). NY, New York: Worth (pp 220-248). NY, New York: Worth Publishers. Publishers.

Tompson, Richard M. (2000). Tompson, Richard M. (2000). The Brain: A Neuroscience The Brain: A Neuroscience Primer (third edPrimer (third ed.). NY, New York: Worth Publishers..). NY, New York: Worth Publishers.

http://www.erowid.org/psychoactives/psychoactives.shtmlhttp://www.erowid.org/psychoactives/psychoactives.shtml http://home.howstuffworks.com/caffeine.htmhttp://home.howstuffworks.com/caffeine.htm http://www.nida.nih.govhttp://www.nida.nih.gov http://pharyngula.org/~pzmyers/neuro/synapse/index.php?http://pharyngula.org/~pzmyers/neuro/synapse/index.php?

printprint

http://www.quantumclinic.com/quitsmoking/quit-smoking-sthttp://www.quantumclinic.com/quitsmoking/quit-smoking-stop-addiction-cigarettes-nicotine-lung-cancer-photos.htmop-addiction-cigarettes-nicotine-lung-cancer-photos.htm

http://www.ccc.nottingham.ac.uk/~mqzwww/adenosine.html

http://www.pbs.org/wgbh/nova/cigarette/nicotine.html

http://www.erowid.org/psychoactives/psychoactives.shtml

http://home.howstuffworks.com/caffeine.htm

http://www.nida.nih.gov/

http://pharyngula.org/~pzmyers/neuro/synapse/index.php?print

http://pharyngula.org/~pzmyers/neuro/synapse/index.php?print

http://www.quantumclinic.com/quitsmoking/quit-smoking-stop-addiction-cigarettes-nicotine-lung-cancer-photos.htm

http://www.quantumclinic.com/quitsmoking/quit-smoking-stop-addiction-cigarettes-nicotine-lung-cancer-photos.htm



http://www.pbs.org/wgbh/nova/cigarette/nicotine.html

Documents

1 STIMULANTS Allen Fowler Mycheal Scott Psyc 472