Psychology 210Psychology 210

Lecture 3Lecture 3

Kevin R SmithKevin R Smith

Chemical MessengersChemical Messengers NeurotransmittersNeurotransmitters

• Act on neurons locallyAct on neurons locally At one synapseAt one synapse

NeuromodulatorsNeuromodulators• Act on clusters of neurons Act on clusters of neurons • May not be in the May not be in the

immediate vicinity of immediate vicinity of where they were releasedwhere they were released

NeurohormonesNeurohormones• Act on neurons distant Act on neurons distant

from their point of releasefrom their point of release• May enter blood flowMay enter blood flow

Releasing Neuron

Releasing Neuron

To other brain areas or body organs

Properties of NeurotransmittersProperties of Neurotransmitters Must be synthesized Must be synthesized

within the neuronwithin the neuron Released in response to Released in response to

an action potentialan action potential Can experimentally Can experimentally

duplicate the action of a duplicate the action of a NT on a postsynaptic cellNT on a postsynaptic cell

There is some There is some mechanism that will stop mechanism that will stop the effects of the NT on the effects of the NT on the postsynaptic cellthe postsynaptic cell

Types of NTsTypes of NTs

Small-molecule Small-molecule transmitterstransmitters• Amino acidsAmino acids

NeuropeptidesNeuropeptides• Groups of amino Groups of amino

acidsacids

Small molecule NTsSmall molecule NTs

Acetylcholine (ACh)Acetylcholine (ACh) CatecholaminesCatecholamines IndoleaminesIndoleamines Amino Acid NTsAmino Acid NTs ATP and ATP and

byproductsbyproducts

ACh

Dopamine

Serotonin

Glutamate

ATP

Cholinergic NeuronsCholinergic Neurons Use ACh as their major Use ACh as their major

NTNT AcetylcholinesteraseAcetylcholinesterase

• Released into the synaptic Released into the synaptic cleft to break down extra cleft to break down extra AChACh

Found at neuromuscular Found at neuromuscular junctionsjunctions

Also found in the brain Also found in the brain in lower level structuresin lower level structures• Believed to be involved in Believed to be involved in

learning and memorylearning and memory Alzheimer's DiseaseAlzheimer's Disease

Cholinergic NeuronsCholinergic Neurons

Two main typesTwo main types• Nicotinic receptorsNicotinic receptors

Reacts to both ACh Reacts to both ACh and nicotineand nicotine

ionotropicionotropic

• Muscarinic Muscarinic receptorsreceptors

Reacts to both ACh Reacts to both ACh and muscarineand muscarine

• Found in Found in hallucinogenic hallucinogenic mushroomsmushrooms

• metabotropicmetabotropic

Action of NTs at synapseAction of NTs at synapse

Can be Can be either single either single step or step or multiple multiple stepssteps• Ionotropic: Ionotropic:

single stepsingle step• NT binds to NT binds to

channels channels and opens and opens themthem

Metabotropic receptorsMetabotropic receptors

Multi-step processMulti-step process NT binds to receptor- triggers G protein NT binds to receptor- triggers G protein

to bind to ion channel and open itto bind to ion channel and open it

Catecholamines and IndoleaminesCatecholamines and Indoleamines

CatecholaminesCatecholamines• DopamineDopamine• EpinephrineEpinephrine• NorepinephrineNorepinephrine

IndoleaminesIndoleamines• SerotoninSerotonin• MelatoninMelatonin

How to make catecholaminesHow to make catecholamines

Tyrosine (an amine acid)Tyrosine (an amine acid) Turns to L-DopaTurns to L-Dopa Turns to DopamineTurns to Dopamine Turns to NorepinephrineTurns to Norepinephrine Turns to EpinephrineTurns to Epinephrine They all have the same starting materialThey all have the same starting material

• They’re just different steps in the processThey’re just different steps in the process• Steps occur when enzymes are added to the Steps occur when enzymes are added to the

moleculesmolecules

Dopaminergic NeuronsDopaminergic Neurons Use dopamineUse dopamine 3 main pathways3 main pathways

• Substantia nigra-Substantia nigra-basal gangliabasal ganglia

MovementMovement Parkinson’s diseaseParkinson’s disease

• Midbrain- limbic Midbrain- limbic system system (hippocampus, (hippocampus, amygdala, nucleus amygdala, nucleus accumbens)accumbens)

Feelings of rewardFeelings of reward May play a role in May play a role in

addictionaddiction• Midbrain- frontal lobeMidbrain- frontal lobe

Higher level Higher level cognitive functionscognitive functions

Planning behaviorPlanning behavior

Norepinephrine and Norepinephrine and EpinephrineEpinephrine

Act on noradrenergic and Act on noradrenergic and adrenergic receptorsadrenergic receptors• Named this because epinephrine Named this because epinephrine

used to be called adrenalineused to be called adrenaline Both are NTs and hormonesBoth are NTs and hormones NorepinephrineNorepinephrine

• Important for attention and focusImportant for attention and focus• Important in sympathetic nervous Important in sympathetic nervous

systemsystem EpinephrineEpinephrine

• Important for short-term stressImportant for short-term stress• Also important in sympathetic Also important in sympathetic

nervous systemnervous system Side note: ACh is the NT for the Side note: ACh is the NT for the

parasympathetic nervous systemparasympathetic nervous system

CatecholaminesCatecholamines Many types of receptorsMany types of receptors At least 5 different dopaminergic receptorsAt least 5 different dopaminergic receptors At least 4 different receptors that respond At least 4 different receptors that respond

to both norepinephrine and epinephrineto both norepinephrine and epinephrine All are metabotropicAll are metabotropic

IndoleaminesIndoleamines

Trytophan – 5HTP – Serotonin - MelatoninTrytophan – 5HTP – Serotonin - Melatonin SerotoninSerotonin

• Widespread throughout the brain, few in Widespread throughout the brain, few in numbernumber

• Most use metabotropic receptorsMost use metabotropic receptors• Important for sleep, mood, and appetiteImportant for sleep, mood, and appetite

MelatoninMelatonin• Secreted by the pineal glandSecreted by the pineal gland• Acts on metabotropic receptorsActs on metabotropic receptors• Important for sleep wake cyclesImportant for sleep wake cycles

Amino acid neurotransmittersAmino acid neurotransmitters

Eight identified amino Eight identified amino acid NTsacid NTs

Glutamate and GABA Glutamate and GABA most importantmost important

Glutamate is the most Glutamate is the most used excitatory NT in used excitatory NT in the CNSthe CNS

GABA is the most used GABA is the most used inhibitory NT in the inhibitory NT in the CNSCNS

GlutamateGlutamate

An amino acid An amino acid • Synthesized from Synthesized from

glutamineglutamine Works on both Works on both

ionotropic and ionotropic and metabotropic metabotropic receptorsreceptors

3 major ionotropic 3 major ionotropic receptorsreceptors• NMDANMDA• AMPAAMPA• KainateKainate

NMDANMDA Both voltage dependent and Both voltage dependent and

glutamate dependentglutamate dependent Usually located near AMPA Usually located near AMPA

receptorsreceptors AMPA depolarizes the AMPA depolarizes the

postsynaptic cellpostsynaptic cell• Raises the voltage for the Raises the voltage for the

NMDA receptorsNMDA receptors• Magnesium responsible for Magnesium responsible for

blocking the NMDA receptors blocking the NMDA receptors until high enough voltageuntil high enough voltage

NMDA allows both CaNMDA allows both Ca2+2+ and and NaNa++ to enter to enter

CaCa2+2+ causes long term causes long term changes in the cellchanges in the cell• Thought to be involved in Thought to be involved in

long term memorylong term memory

GABAGABA

Synthesized from Synthesized from glutamateglutamate

Two different GABA Two different GABA receptorsreceptors• One ionotropic, one One ionotropic, one

metabotropicmetabotropic Works by allowing ClWorks by allowing Cl--

to enter the cell or to enter the cell or allowing Kallowing K++ to leave to leave the cellthe cell

ATPATP

Involved in perception Involved in perception of painof pain

Major byproduct Major byproduct adenosine is also a NTadenosine is also a NT

Acts upon autonomic Acts upon autonomic nervous systemnervous system• Vas deferens, bladder, Vas deferens, bladder,

heart, gutheart, gut Frequently coexists Frequently coexists

with other enzymeswith other enzymes Also the bodies major Also the bodies major

source of energysource of energy

NeuropeptidesNeuropeptides

Chains of amino acidsChains of amino acids Over 40 different types of Over 40 different types of

neuropeptides that are NTsneuropeptides that are NTs Can be both hormones and NTsCan be both hormones and NTs Reuptake from the synaptic cleft is Reuptake from the synaptic cleft is

quite slowquite slow Ex. InsulinEx. Insulin

• Involved in digestion and is also a NTInvolved in digestion and is also a NT

Drugs, Drugs, and More DrugsDrugs, Drugs, and More Drugs

AgonistsAgonists• Enhance the activity of the NTEnhance the activity of the NT

AntagonistsAntagonists• Reduce the activity of the NTReduce the activity of the NT

Don’t think of agonists and Don’t think of agonists and antagonists in terms of inhibition and antagonists in terms of inhibition and excitationexcitation

An agonist to GABA enhances the An agonist to GABA enhances the inhibition of the postsynaptic cellinhibition of the postsynaptic cell

Different Effects of DrugsDifferent Effects of Drugs NT productionNT production

• Can reduce or enhance the amount of NT producedCan reduce or enhance the amount of NT produced• Either reduces or enhances the action of that NT, Either reduces or enhances the action of that NT,

respectivelyrespectively• If it interferes early enough, it could effect multiple NTs If it interferes early enough, it could effect multiple NTs

(ie the dopamine, norepinephrine, epinephrine sequence)(ie the dopamine, norepinephrine, epinephrine sequence) NT StorageNT Storage

• Can reduce the amount of NT storedCan reduce the amount of NT stored• Causes less NT to be available for releaseCauses less NT to be available for release

NT ReleaseNT Release• Can promote or prevent exocytosis (NT release)Can promote or prevent exocytosis (NT release)• Agonists promoteAgonists promote• Antagonists preventAntagonists prevent

Different Effects of DrugsDifferent Effects of Drugs Receptor EffectsReceptor Effects

• Mimic the action of NTsMimic the action of NTs• Agonists: act just as the NT would, activating Agonists: act just as the NT would, activating

the receptorsthe receptors• Antagonists: bind to the receptor without Antagonists: bind to the receptor without

activating it, but blocking the NT from bindingactivating it, but blocking the NT from binding Reuptake EffectsReuptake Effects

• Reuptake inhibitorsReuptake inhibitors• Attack the enzymes responsible for the Attack the enzymes responsible for the

deterioration of NTs in the synaptic cleftdeterioration of NTs in the synaptic cleft

Examples: Effects on NT Examples: Effects on NT ProductionProduction

Increasing dairy intake Increasing dairy intake leads to an increase in leads to an increase in tryptophan levelstryptophan levels• Leads to an increase in Leads to an increase in

serotonin levelsserotonin levels AMPTAMPT

• Interferes with the Interferes with the activity of tyrosine activity of tyrosine hydroxylasehydroxylase

• Leads to a decrease in Leads to a decrease in the amount of the amount of dopamine,dopamine, norepinephrine, and norepinephrine, and epinephrineepinephrine

Examples: Effects on NT StorageExamples: Effects on NT Storage

ReserpineReserpine• Used to lower blood Used to lower blood

pressurepressure• Interferes with the Interferes with the

uptake of some NTs uptake of some NTs (serotonin) into (serotonin) into synaptic vesiclessynaptic vesicles

• Has lead to Has lead to depressiondepression

• Rarely prescribed Rarely prescribed nownow

Examples: Effects on NT ReleaseExamples: Effects on NT Release Black widow venomBlack widow venom

• An agonist: leads to an An agonist: leads to an increase in ACh releaseincrease in ACh release

• Leads to Leads to overstimulation of overstimulation of muscle fibers and muscle fibers and convulsions- leads to convulsions- leads to the neuron “running the neuron “running out” of release ACh out” of release ACh and paralysisand paralysis

BotulinBotulin• An antagonist: leads to An antagonist: leads to

a decrease in ACh a decrease in ACh • Leads to paralysisLeads to paralysis

Examples: Effects on NT ReceptorsExamples: Effects on NT Receptors

CurareCurare• Used on arrowheads Used on arrowheads

and dartsand darts• Occupies nicotinic ACh Occupies nicotinic ACh

receptors and leads to receptors and leads to paralysisparalysis

Examples: Effects on NT ReuptakeExamples: Effects on NT Reuptake

Dopamine Dopamine reuptake inhibitorsreuptake inhibitors• Cocaine, Cocaine,

amphetamine, amphetamine, RitalinRitalin

Serotonin reuptake Serotonin reuptake inhibitorsinhibitors• ProzacProzac

More on this later More on this later in the classin the class

Basic Principles of Drug EffectsBasic Principles of Drug Effects Drugs may or may not have Drugs may or may not have

different effects depending different effects depending upon their method of upon their method of administrationadministration

Frequently the level of drug in Frequently the level of drug in the body is different based the body is different based upon the method of upon the method of administrationadministration

Also, different side effects may Also, different side effects may occuroccur• Cocaine Cocaine

Ingesting may cause bowel Ingesting may cause bowel gangrenegangrene

Snorting causes nasal Snorting causes nasal problems, such as nose bleeds, problems, such as nose bleeds, problems swallowing etcproblems swallowing etc

Injecting may cause liver Injecting may cause liver problems and allergic reactionsproblems and allergic reactions

Placebo EffectsPlacebo Effects When pharmaceutical When pharmaceutical

companies are testing companies are testing drugs, must worry about drugs, must worry about placebo effectsplacebo effects

When patients are told When patients are told they are getting a new they are getting a new depression drug, dopamine depression drug, dopamine levels rise and may levels rise and may contribute to a lessening of contribute to a lessening of the depression (before the the depression (before the drug even takes placedrug even takes place

Give subjects a placebo Give subjects a placebo instead (sugar pills, saline)instead (sugar pills, saline)

Don’t tell subjects whether Don’t tell subjects whether they are receiving the drug they are receiving the drug or the placeboor the placebo• Controls for placebo Controls for placebo

effectseffects

Experimenter EffectsExperimenter Effects Some doctors may view Some doctors may view

a subject as less a subject as less depressed if on the drug depressed if on the drug than if notthan if not• Power of suggestionPower of suggestion

Studies are frequently Studies are frequently run as double blindrun as double blind• Neither the subject nor Neither the subject nor

the experimenter knows the experimenter knows whether the subject is whether the subject is getting the placebo or getting the placebo or the drugthe drug

• Records are kept by a Records are kept by a second experimenter second experimenter that doesn’t have that doesn’t have contact with the subjectscontact with the subjects

ToleranceTolerance ToleranceTolerance

• Changes in the body’s Changes in the body’s response to the drug to response to the drug to maintain a constant maintain a constant environmentenvironment

ie. If a drug causes an ie. If a drug causes an increase in heart rate, increase in heart rate, the body may prepare the body may prepare for the drug by for the drug by decreasing its heart decreasing its heart raterate

This causes users to This causes users to gradually increase the gradually increase the amount of the drug to amount of the drug to get the same effectsget the same effects

Interesting Note about ToleranceInteresting Note about Tolerance

Imagine that every day for a year you Imagine that every day for a year you injected heroin in your arm at 5:45 outside injected heroin in your arm at 5:45 outside of the door before this classof the door before this class

As the year went on, you would As the year went on, you would progressively need more and more heroin progressively need more and more heroin to get the same effect (tolerance)to get the same effect (tolerance)

One day, you decided to skip class and One day, you decided to skip class and injected heroin in front of your injected heroin in front of your neighborhood McDonalds insteadneighborhood McDonalds instead• There is a very high danger of overdose hereThere is a very high danger of overdose here• Why?Why?

Why is there a higher danger of Why is there a higher danger of overdose?overdose?

Because your tolerance is not just to the Because your tolerance is not just to the drug but to the situationdrug but to the situation

Your body, when you see the classroom, Your body, when you see the classroom, begins to prepare for the drug well before begins to prepare for the drug well before you bring out the needleyou bring out the needle

It sees the situation and knows what is It sees the situation and knows what is comingcoming

Once the situation is changed, the body Once the situation is changed, the body does not prepare itself as well, and your does not prepare itself as well, and your tolerance is loweredtolerance is lowered

This leads to an increase in overdosesThis leads to an increase in overdoses

ToleranceTolerance

WithdrawalWithdrawal

Similar to toleranceSimilar to tolerance Occurs after a user Occurs after a user

stops usingstops using Occurs because the Occurs because the

body is trying to body is trying to maintain a constant maintain a constant environment and is environment and is preparing for the drug preparing for the drug (that never comes)(that never comes)

AddictionAddiction Compulsive need for Compulsive need for

repeated use of the repeated use of the drugdrug

Linked to neural Linked to neural reward systemsreward systems• DopamineDopamine• Nucleus accumbensNucleus accumbens

Some drugs don’t Some drugs don’t activate this circuitactivate this circuit• LSD- no strong LSD- no strong

addictions usuallyaddictions usually Nucleus Accumbens

AddictionAddiction

Removal of nucleus accumbens or Removal of nucleus accumbens or damage to this dopaminergic circuit damage to this dopaminergic circuit leads to reductions in addictionleads to reductions in addiction• Not a viable option for treating addictsNot a viable option for treating addicts• May lead to no feelings of rewardMay lead to no feelings of reward

TreatmentTreatment Very hard to Very hard to

end an end an addictionaddiction• Once you’re an Once you’re an

alcoholic your alcoholic your always an always an alcoholicalcoholic

Relapses are Relapses are very commonvery common

Multistep Multistep programs programs addressing addressing many different many different areas seem to areas seem to be the most be the most affectiveaffective

TreatmentsTreatments Drugs are being Drugs are being

developed to try and developed to try and help addictshelp addicts• may cause unpleasant may cause unpleasant

effects when addict effects when addict takes the drugtakes the drug

Unpleasant effects Unpleasant effects become associated become associated with taking the drug with taking the drug and the addict quitsand the addict quits

• May block the drug May block the drug from workingfrom working

The addict loses The addict loses interest in taking the interest in taking the drugdrug

Types of Psychoactive DrugsTypes of Psychoactive Drugs

StimulantsStimulants OpiatesOpiates Marijuana and Marijuana and

other other HallucinogensHallucinogens

AlcoholAlcohol

StimulantsStimulants Typical EffectsTypical Effects

• Increase heart rateIncrease heart rate• Increase blood pressureIncrease blood pressure• Increase alertnessIncrease alertness• Increase concentrationIncrease concentration• Increase mobilityIncrease mobility

StimulantsStimulants Caffeine!!!!Caffeine!!!!

• Mechanism not Mechanism not completely understoodcompletely understood

• Antagonist to adenosineAntagonist to adenosine• Adenosine is an Adenosine is an

inhibitory NTinhibitory NT Eliminates the Eliminates the

inhibition – thus things inhibition – thus things speed upspeed up

• May cause an increase May cause an increase in reward feelings, in reward feelings, arousal, and reaction arousal, and reaction time time

• Caffeine use is actually Caffeine use is actually correlated with correlated with decreases in decreases in Parkinson’s DiseaseParkinson’s Disease

Caffeine- FMRICaffeine- FMRI

Subjects performing a task with no caffeine

Subjects performing a task after taking caffeine

StimulantsStimulants

NicotineNicotine• Acts upon nicotinic Acts upon nicotinic

cholinergic neuronscholinergic neurons• 50% of cigarettes 50% of cigarettes

consumed are by consumed are by people with mental people with mental disordersdisorders

May be self medicatingMay be self medicating May also be that May also be that

nicotine contributes to nicotine contributes to mental disordersmental disorders

Implications of Smoking on Implications of Smoking on Nicotinic ReceptorsNicotinic Receptors

An ionotropic receptorAn ionotropic receptor Smokers report an Smokers report an

increase in functioning increase in functioning capabilitiescapabilities• Increase in auditory Increase in auditory

capabilitiescapabilities• Memory functionsMemory functions

Nicotine may be a Nicotine may be a substitute for ACh but it substitute for ACh but it is not a very good oneis not a very good one

After longer use, After longer use, nicotine actually nicotine actually deadens the receptorsdeadens the receptors

Na+

Inside of the cell

Nicotine or ACh

Outside of the cell

StimulantsStimulants CocaineCocaine

• Works as a Dopamine reuptake Works as a Dopamine reuptake inhibitorinhibitor

AmphetamineAmphetamine• Stimulates dopamine and Stimulates dopamine and

norepinephrine (at norepinephrine (at dopaminergic neurons) release dopaminergic neurons) release and inhibits reuptake as welland inhibits reuptake as well

Very addictive: due to their Very addictive: due to their power on the dopaminergic power on the dopaminergic reward systemreward system• A single dose could cause A single dose could cause

addiction in miceaddiction in mice May lead to hallucinationsMay lead to hallucinations

• May be due to an May be due to an overstimulation of the sensory overstimulation of the sensory systemssystems

Why is Cocaine so addictive?Why is Cocaine so addictive?Temporary Effects in certain areas

Cocaine on the Brain Cocaine on the Brain Cocaine also blocks Sodium receptors, in some areas; Long term effects are a decrease in activity

StimulantsStimulants

EcstasyEcstasy• Aka MDMAAka MDMA• Relative to Relative to

amphetamineamphetamine• Stimulates the release Stimulates the release

of serotoninof serotonin• Over stimulates Over stimulates

serotonin synapses and serotonin synapses and may lead to the death may lead to the death of serotonin receptorsof serotonin receptors

Since serotonin is one Since serotonin is one of the main of the main mechanisms for mechanisms for happiness, prolonged happiness, prolonged ecstasy use leads to ecstasy use leads to depressiondepression

Effects of ecstasy on the brainEffects of ecstasy on the brain

OpiatesOpiates

Typical EffectsTypical Effects• Pain managementPain management• RelaxationRelaxation• EuphoriaEuphoria• EndorphinesEndorphines

Natural opiatesNatural opiates

MorphineMorphine Mechanisms of action are unclearMechanisms of action are unclear

• Opiates have their own receptorsOpiates have their own receptors Recent evidence points to increasing the Recent evidence points to increasing the

release of serotoninrelease of serotonin• Leads to feelings of pleasureLeads to feelings of pleasure

When coupled with magnesium, NMDA When coupled with magnesium, NMDA receptors appear to be blockedreceptors appear to be blocked• MAY lead to the pain relieving effects foundMAY lead to the pain relieving effects found

Codeine is a relative to morphineCodeine is a relative to morphine• Has similar effectsHas similar effects• Not quite as strongNot quite as strong

HeroinHeroin

Heroin is actually Heroin is actually a prodruga prodrug• It is inactive as a It is inactive as a

drug in its normal drug in its normal statestate

Once in the body, Once in the body, it is metabolized it is metabolized into morphineinto morphine

HallucinogensHallucinogens MarijuanaMarijuana

• A hallucinogen at high A hallucinogen at high levelslevels

• May cause excitation and May cause excitation and euphoria or depression euphoria or depression and social withdrawaland social withdrawal

• Contains over sixty Contains over sixty different psychoactive different psychoactive substancessubstances

Amanita Amanita MushroomsMushrooms• GABA agonistGABA agonist

Lysergic Acid Lysergic Acid DiethylamideDiethylamide• Similar to serotoninSimilar to serotonin

Produces feelings of Produces feelings of pleasurepleasure

Mechanism for Mechanism for hallucinations not hallucinations not understoodunderstood

PET of marijuana usersPET of marijuana users

Marijuana abuser: a long term user of marijuana

Cannabinoid Receptors all overCannabinoid Receptors all over

Rat cortex:Rat cortex:

AlcoholAlcohol Dilates blood vesselsDilates blood vessels Relieves anxietyRelieves anxiety Reduces behavioral Reduces behavioral

inhibitionsinhibitions Works at GABA receptors, Works at GABA receptors,

dopaminergic receptors, dopaminergic receptors, NMDA receptorsNMDA receptors

Tolerance develops very Tolerance develops very quicklyquickly

Great effects in the Great effects in the cerebellumcerebellum• Leads to movement deficitsLeads to movement deficits

PET study of alcohol and tobaccoPET study of alcohol and tobacco

addicts

non- addicts

Presence and severity of Presence and severity of characteristic withdrawal symptomscharacteristic withdrawal symptoms

Reinforcement: A measure of Reinforcement: A measure of the substance's ability, in the substance's ability, in human and animal tests, to get human and animal tests, to get users to take it again and users to take it again and again, and in preference to again, and in preference to other substances. other substances.

Tolerance: How much of the Tolerance: How much of the substance is needed to satisfy substance is needed to satisfy increasing cravings for it, and increasing cravings for it, and the level of stable need that is the level of stable need that is eventually reached. eventually reached.

Dependence: How difficult it is Dependence: How difficult it is for the user to quit, the relapse for the user to quit, the relapse rate, the percentage of people rate, the percentage of people who eventually become who eventually become dependent, the rating users dependent, the rating users give their own need for the give their own need for the substance and the degree to substance and the degree to which the substance will be which the substance will be used in the face of evidence used in the face of evidence that it causes harm. that it causes harm.

Intoxication: Associated with Intoxication: Associated with addiction and increases the addiction and increases the personal and social damage a personal and social damage a substance may do.substance may do.

Source: Jack E. Henningfield, PhD for NIDA, Reported Source: Jack E. Henningfield, PhD for NIDA, Reported by Philip J. Hilts, New York Times, Aug. 2, 1994 "Is by Philip J. Hilts, New York Times, Aug. 2, 1994 "Is Nicotine Addictive? It Depends on Whose Criteria You Nicotine Addictive? It Depends on Whose Criteria You Use."Use."Herbal TreatmentsHerbal Treatments