Addiction is a Brain Disease

Michael L. Johnson, MSNancy A. Roget, MS

Brain DiseaseBrain Disease

Drug addiction is a brain diseaseDrug addiction is a brain disease Every type of psychoactive drug Every type of psychoactive drug

has its own individual has its own individual mechanism for changing how mechanism for changing how the brain functionsthe brain functions

Drug use changes the Drug use changes the individual's brain and its individual's brain and its functioning in critical waysfunctioning in critical ways

Leshner, 2001Leshner, 2001

Addiction is a Brain DiseaseAddiction is a Brain Disease

Addiction is a Brain Disease Addiction is a Brain Disease BECAUSE:BECAUSE: Using drugs over time changes Using drugs over time changes

brain structure and functionbrain structure and function Some brain changes may persist Some brain changes may persist

after use stops after use stops Long-lasting brain changes Long-lasting brain changes

effecteffect cognitive functioningcognitive functioning emotional functioningemotional functioning

Addiction is a Brain Disease Addiction is a Brain Disease

Addiction is a brain diseaseAddiction is a brain disease addicted brain is different from the non-addicted brain is different from the non-

addicted brainaddicted brain Prolonged drug use causes pervasive Prolonged drug use causes pervasive

changes in brain functionchanges in brain function

Essence of AddictionEssence of Addiction

Compulsive craving that Compulsive craving that overwhelms all other overwhelms all other motivations (drug use motivations (drug use despite negative and social despite negative and social consequences)consequences)

root cause of health and root cause of health and social problemssocial problems

Paradox of AddictionParadox of Addiction

Initially Voluntary

Addiction’s Similarities with Addiction’s Similarities with Other Brain DiseasesOther Brain Diseases

Some brain diseases are NOT Some brain diseases are NOT simply biological in nature and simply biological in nature and expressionexpression

Most have social/behavioral Most have social/behavioral aspectsaspects

Examples: Examples: Alzheimer'sAlzheimer's SchizophreniaSchizophrenia Clinical DepressionClinical Depression

The Adult BrainThe Adult Brain, , and how it worksand how it works

An Adult An Adult brain brain weighs weighs about 3 about 3 pounds and pounds and has billions has billions of cellsof cells NeuronsNeurons Glial cellsGlial cells

The BrainThe Brain

Organ on thinking, behavior, Organ on thinking, behavior, homeostasishomeostasis

Different Areas of the brain regulate Different Areas of the brain regulate different functionsdifferent functions

Complex tasks are split up into Complex tasks are split up into specialized areasspecialized areas Damage to these areas leads to specific Damage to these areas leads to specific

deficitsdeficits

““Division of labor” allows for Parallel Division of labor” allows for Parallel ProcessingProcessing

Brain Region & FunctionBrain Region & Function

Splits larger tasks into smaller Splits larger tasks into smaller onesones

Component tasks are further Component tasks are further broken into sub component broken into sub component taskstasks Driving Driving

SeeingSeeingHearingHearingMovingMoving

Understanding Understanding HowHow the the

Brain Brain Works Works

UnderstandiUnderstanding Howng How

the the Brain Brain WorksWorks

Function of Brain RegionsFunction of Brain Regions

BrainstemBrainstem= basic function= basic function Heart rate, breathing, digestion, sleepHeart rate, breathing, digestion, sleep

CerebellumCerebellum =skilled repetitive =skilled repetitive movements, balancemovements, balance

Limbic SystemLimbic System=emotions & =emotions & motivationsmotivations

DiencephalonDiencephalon=sensory perception=sensory perception

Function of Brain RegionsFunction of Brain Regions

Cerebral CortexCerebral Cortex = thinking, = thinking, perceiving, producing languageperceiving, producing language Vision, hearing, touch, movement, Vision, hearing, touch, movement,

smell, thinking & reasoningsmell, thinking & reasoning

Frontal LobeFrontal Lobe = social behavior = social behavior Limbic SystemLimbic System Uses memories, information about Uses memories, information about

how the body is working and how the body is working and sensory inputsensory input

Function and Brain RegionsFunction and Brain Regions

Phineas GagePhineas Gage 1848 Railroad worker1848 Railroad worker Explosion- tamping Explosion- tamping

rodrod Rod entered brainRod entered brain Temperament Temperament

changeschanges 20 years post 20 years post

accidentaccident Correlated accident Correlated accident

to behavioral to behavioral changeschanges

Frontal lobe = social Frontal lobe = social behaviorbehavior

Neurons, Brain Chemistry & Neurons, Brain Chemistry & NeurotransmissionNeurotransmission

The The NeuronNeuron

Basic signaling unit of Basic signaling unit of brainbrain

Precise connections allow Precise connections allow for different actionsfor different actions NeuronsNeurons Sensory receptorsSensory receptors MusclesMuscles

The The NeuronNeuron

Cell BodyCell Body–NucleusNucleus

–Metabolic centerMetabolic center

DendritesDendrites–Input from other Input from other neuronsneurons

AxonAxon–Carry high Carry high speed messages speed messages away from away from neuronneuron

–Branches into Branches into presynaptic presynaptic terminalsterminals

The SynapseThe Synapse

The SynapseThe Synapse

NN EE UU RR OO TT RR AA NN SS MM II TT T T EE RR SS

TheThe

S S y y n n a a p p s s e e

End of axonEnd of axon Typical neuron has 1000 synapses with Typical neuron has 1000 synapses with

other neuronsother neurons Intercellular space between neuronsIntercellular space between neurons

Synaptic cleftSynaptic cleft

Synapses are DynamicSynapses are Dynamic

Neurons can strengthen Neurons can strengthen synaptic connectionssynaptic connections

New synapses form (protein New synapses form (protein synthesis)synthesis)

Synapses can be lostSynapses can be lost Responses to life experiences Responses to life experiences

(and aging)(and aging) Cellular basis of learningCellular basis of learning

Synaptic TransmissionSynaptic Transmission

Neurons communicate via Neurons communicate via electrical and chemical electrical and chemical signalssignals Electrical signal converted to a Electrical signal converted to a

chemical signal– a chemical signal– a neurotransmitterneurotransmitter

Electrical signal within a Electrical signal within a neuron is an action potentialneuron is an action potentialWave-like flow of ions (electrical Wave-like flow of ions (electrical impulse) down axonimpulse) down axon

Transient depolarization of axonTransient depolarization of axon

Synaptic TransmissionSynaptic Transmission

At the axon At the axon terminal, the terminal, the electrical impulse electrical impulse leads to release of leads to release of a a neurotransmitterneurotransmitter Stored in vesicles Stored in vesicles

which fuse with which fuse with the neuronal the neuronal membrane and membrane and release their release their contents into the contents into the cleftcleft

Synaptic TransmissionSynaptic Transmission

Neurotransmitters diffuse into Neurotransmitters diffuse into intercellular spaceintercellular space

Bind to receptors on dendrite of Bind to receptors on dendrite of another cellanother cell

Postsynaptic cellPostsynaptic cell

Receptors are specific Receptors are specific Dopamine receptors will only bind Dopamine receptors will only bind dopaminedopamine

Synaptic TransmissionSynaptic Transmission Chemical binding Chemical binding

of transmitter of transmitter with receptor with receptor leads to changes leads to changes in the post-in the post-synaptic cellsynaptic cell May generate an May generate an

action potentialaction potential Post-synaptic cell Post-synaptic cell

may use a may use a different different neurotransmitter neurotransmitter to communicate to communicate “down stream”“down stream”

NeurotransmissionNeurotransmission

Synaptic TransmissionSynaptic Transmission

After binding, After binding, neurotransmitters neurotransmitters releases from releases from receptor and goes receptor and goes back into the cleftback into the cleft

Removed by Removed by enzymes or reuptake enzymes or reuptake pump/ transporter pump/ transporter back into terminalback into terminal quick removal of quick removal of

transmitters allow for transmitters allow for precise precise communication communication between neuronsbetween neurons

Types of NeurotransmittersTypes of Neurotransmitters

A neuron receives many many A neuron receives many many messages from connecting neuronsmessages from connecting neurons

Neuron’s response is the “sum”Neuron’s response is the “sum” Excitatory TransmittersExcitatory Transmitters

Lead to (generation of A’s and) stimulate Lead to (generation of A’s and) stimulate firing of post-synaptic neuronfiring of post-synaptic neuron

Inhibitory TransmittersInhibitory Transmitters Lead to decreased firing in post-synaptic Lead to decreased firing in post-synaptic

neuronneuron

Routes of AdministrationRoutes of Administration

InhaleInhale InsuflateInsuflate IngestIngest InjectInject EnemaEnema Contact Absorption (patch)Contact Absorption (patch)

Drug Ingestion

ORALORAL

20 to 30 minutes

INHALINGINHALING

7 to 10 Seconds

INJECTINGINJECTING

15 to 30 seconds- IV

3 to 5 minutes- skin popping

SNORTINGSNORTING

3 to 5 minutes

CONTACTCONTACT

Limbic SystemLimbic System

Reward Reward SystemSystem

Nucleus Nucleus accumbensaccumbens

Prefrontal Prefrontal cortexcortex

Ventral Ventral tegmental tegmental areaarea

Limbic SystemLimbic System

Link between higher cortical Link between higher cortical activity and the “lower” systems activity and the “lower” systems that control emotional behaviorthat control emotional behavior

Limbic LobeLimbic Lobe Deep lying structuresDeep lying structures

amygdalaamygdala hippocampushippocampus mamillary bodiesmamillary bodies

Limbic SystemLimbic System

Specialized brain areas for Specialized brain areas for producing and regulating producing and regulating PLEASUREPLEASURE Ventral Tegmental AreaVentral Tegmental Area Nucleus AccumbensNucleus Accumbens Prefrontal CortexPrefrontal Cortex Areas of Limbic system– Areas of Limbic system–

amygdala, hippocampus, amygdala, hippocampus, hypothalamushypothalamus

Limbic SystemLimbic System

Generates primitive emotional Generates primitive emotional responses to situationsresponses to situations

Allows for SURVIVALAllows for SURVIVAL Identify danger/ threatsIdentify danger/ threats

Fear and aggressionFear and aggression Identify pleasure– “natural Identify pleasure– “natural

rewards”rewards”EatingEatingSexSexSocial InteractionSocial Interaction

RReewwaarrdd

P Paatthh

VTA and NAVTA and NA Primitive brain stem and limbic areasPrimitive brain stem and limbic areas

Activated by drugs of abuseActivated by drugs of abuse Activation of these primitive areas can Activation of these primitive areas can

OVERRIDE more evolved cortical areasOVERRIDE more evolved cortical areas

Reward PathwayReward Pathway

Also the site of action for addictionsAlso the site of action for addictions Drugs activate the pathway with Drugs activate the pathway with

force and persistence not seen with force and persistence not seen with natural rewardsnatural rewards

Drug Effects On Drug Effects On NeurotransmissionNeurotransmission

Alcohol, heroin, nicotine excite the Alcohol, heroin, nicotine excite the dopamine neurons in the VTA to dopamine neurons in the VTA to increase dopamine releaseincrease dopamine release

Drug Effects on CellDrug Effects on Cell

Increased cAMP levelsIncreased cAMP levels Activation of transcription factor CREB Activation of transcription factor CREB

and changes in gene expressionand changes in gene expression Changes in synapses, cell structure and Changes in synapses, cell structure and

functionfunction

The resulting intracellular changes The resulting intracellular changes appear to be the molecular and cellular appear to be the molecular and cellular basis of addiction (persistent behavioral basis of addiction (persistent behavioral abnormalities)abnormalities)

Nestler Am J Addiction 2001; 201-217Nestler Am J Addiction 2001; 201-217

Drug Effects on Cell and Drug Effects on Cell and LearningLearning

Intracellular changes for Intracellular changes for addiction the same as for addiction the same as for learninglearning Both activities share Both activities share

intracellular signaling intracellular signaling cascades (cAMP) and cascades (cAMP) and depend on activity of CREBdepend on activity of CREB

Drug Effects on Cell and Drug Effects on Cell and LearningLearning

Learning and addiction show Learning and addiction show similar changes in neuron similar changes in neuron morphologymorphology

Similar changes at the level of Similar changes at the level of the synapsethe synapse

Multiple similar changes in the Multiple similar changes in the neuronneuron Long term changesLong term changes Addiction is long termAddiction is long term

Nestler 2001 Science 292 (5525) pp 2266-67Nestler 2001 Science 292 (5525) pp 2266-67

Drug EffectsDrug Effects on the Cell on the Cell

Drugs of abuse all directly or indirectly Drugs of abuse all directly or indirectly increase dopamine binding to post synaptic increase dopamine binding to post synaptic receptor with acute behavioral effectsreceptor with acute behavioral effects

Chronically, this increases cAMP levels and Chronically, this increases cAMP levels and leads to a cascade of changed cell activityleads to a cascade of changed cell activity

Other Chronic Drug EffectsOther Chronic Drug Effects

Cell DeathCell Death Neurons Neurons

don’t grow don’t grow backback

Alcohol, Alcohol, ecstasy, ecstasy, methmeth

Effect Effect memory, memory, mood, mood, learninglearning

Chronic Drug EffectsChronic Drug Effects

Nature VideoNature Video Cocaine VideoCocaine Video

Front of BrainFront of Brain

Back of BrainBack of Brain

AmygdalaAmygdalanot lit upnot lit up

AmygdalaAmygdalaactivatedactivated

Persistent Effects of Drug UsePersistent Effects of Drug Use

Brain ImagingBrain Imaging

PETPET Brain FunctioningBrain Functioning

Radiolabeled glucose for levels of Radiolabeled glucose for levels of activityactivity

Effects of DrugsEffects of DrugsDistribution in bodyDistribution in bodyMeasure local concentration at Measure local concentration at

binding sitesbinding sites

Spatial Resolution of 4 mmSpatial Resolution of 4 mm

Positron Emission Tomography (PET)Positron Emission Tomography (PET)

NIDA ResearchNIDA Research

Overall goal of NIDA Overall goal of NIDA research to:research to: Reverse the brain changes Reverse the brain changes

that underlie addictionthat underlie addiction Roll back the loss of Roll back the loss of

cognitive and motor cognitive and motor functions that occurfunctions that occur

Develop interventions to Develop interventions to stop brain damage, repair stop brain damage, repair damage, and retrain the damage, and retrain the brainbrain

Restore brain function Restore brain function after it has been changed after it has been changed by drug useby drug use

PET ScanPET Scan Brighter Brighter

red red indicates indicates higher higher levels of levels of activity activity (glucose (glucose utilization)utilization)

Your Brain on DrugsYour Brain on Drugs

1-2 Min 3-4 5-6

6-7 7-8 8-9

9-10 10-20 20-30

Your Brain After Drugs

Drugs HaveDrugs HaveLong-term Long-term ConsequencesConsequences

Stimulant StudiesStimulant Studies

London et al. (2004)London et al. (2004) PET images of brain activityPET images of brain activity Patients in acute Patients in acute

methamphetamine withdrawal methamphetamine withdrawal (4 to 7 days)(4 to 7 days)

PatientsPatients 10 year history10 year history 4 grams per week4 grams per week 18 days of use out of 3018 days of use out of 30

Stimulant Studies Stimulant Studies London et al. (2004)London et al. (2004) levels of depression and anxiety levels of depression and anxiety

measuredmeasured PET ScansPET Scans Patient ReportPatient Report

brain- glucose metabolism-brain- glucose metabolism-depressed mood, sadness, depressed mood, sadness, anxiety, and drug cravinganxiety, and drug craving

Beck’s Depression Inventory Beck’s Depression Inventory ratings averaged 9.5 for ratings averaged 9.5 for methamphetamine patients and methamphetamine patients and 1.1 for control1.1 for control

Examples of Brain Studies Examples of Brain Studies Treatment ApplicationTreatment Application

London et al. (2004)London et al. (2004)Treatment of Methamphetamine UsersTreatment of Methamphetamine Users

Mood disorder symptoms Mood disorder symptoms may create an acute may create an acute barrier to treatment for barrier to treatment for methamphetamine abusersmethamphetamine abusers

Stimulant StudiesStimulant Studies

Treatment Applications Treatment Applications from London’s Stimulant from London’s Stimulant

StudiesStudies Implications for treatmentImplications for treatment

Expect clients to feel poorlyExpect clients to feel poorly Treatment engagement strategies should Treatment engagement strategies should

focus on helping patients to deal with focus on helping patients to deal with negative emotional states (Depression and negative emotional states (Depression and Anxiety)Anxiety)

Avoid counseling techniques that are Avoid counseling techniques that are confrontationalconfrontational

Relapse potential is high because clients Relapse potential is high because clients feel poorlyfeel poorly

Be aware of clients’ turning to self Be aware of clients’ turning to self medication activities to relieve the negative medication activities to relieve the negative feeling statesfeeling states

Cues for Cocaine and Normal Cues for Cocaine and Normal Pleasures Activate Brain Sites Pleasures Activate Brain Sites

Childress, 1999Childress, 1999

Cues for CocaineCues for Cocaine Cocaine abusers may experience Cocaine abusers may experience

a powerful urge to use when a powerful urge to use when they encounter environmental they encounter environmental cues associated with usecues associated with use

Limbic regions of the brain are Limbic regions of the brain are activated when watching activated when watching cocaine- related videoscocaine- related videos

Childress, 1999Childress, 1999

Persistent Effects of DrugPersistent Effects of Drug

As a result of intracellular As a result of intracellular changes, the previously cocaine changes, the previously cocaine addicted brain has persistently addicted brain has persistently altered functioning (craving)altered functioning (craving)

Environmental CuesEnvironmental Cues

Implications for TreatmentImplications for Treatment Understand the importance Understand the importance

environmental cues play in initiating environmental cues play in initiating the craving processthe craving process

Review program educational materials Review program educational materials to ensure that potential environmental to ensure that potential environmental cues for drug use are eliminatedcues for drug use are eliminated

Normalize cue and craving responses Normalize cue and craving responses for clientsfor clients

Teach clients how to “urge surf” and Teach clients how to “urge surf” and to identify potential environmental to identify potential environmental cuescues

Treatment Applications for Childress’ Cue-Induced Cocaine

Craving Study

Recovery of Dopamine Recovery of Dopamine TransportersTransporters

Pet scanPet scan shows levels of dopamine transportersshows levels of dopamine transporters Lower levels of dopamine transporters were Lower levels of dopamine transporters were

associated with poorer performance on tests of associated with poorer performance on tests of memory and motor skillsmemory and motor skills

Impairments in motor skills and memory Impairments in motor skills and memory continuedcontinued

Volkow, et al. 2001Volkow, et al. 2001

Poor Motor & Memory PerformancePoor Motor & Memory Performance 33 year old male- 80 days post 33 year old male- 80 days post

detoxdetox Low Severity- Parkinson DiseaseLow Severity- Parkinson Disease transporter losses may not recovertransporter losses may not recover Volkow, et al. 2001Volkow, et al. 2001

Simon, et al. 2002 Simon, et al. 2002 Cognitive Effects of Cognitive Effects of

StimulantsStimulants Studied 40 current Studied 40 current

Methamphetamine UsersMethamphetamine Users ImpairmentsImpairments

memorymemory abstract thinkingabstract thinking changing points of viewchanging points of view ability to manipulate informationability to manipulate information comprehension deficitscomprehension deficits Word recallWord recall

Simon, et al. 2002 Simon, et al. 2002 Cognitive Effects of Cognitive Effects of

StimulantsStimulants Help clients who are mandated into Help clients who are mandated into

treatment deal with cognitive treatment deal with cognitive problems associated comprehension problems associated comprehension

Ensure that clients understand Ensure that clients understand what counts as compliance with what counts as compliance with

treatment services treatment services counselor recommendationscounselor recommendations consequences for failure to complyconsequences for failure to comply

Give concrete, specific informationGive concrete, specific information Develop methods to help clients Develop methods to help clients

remember treatment remember treatment recommendations or medicationsrecommendations or medications

Treatment Applications for Treatment Applications for Simon, et al.’s studySimon, et al.’s study

Treatment Implications:Treatment Implications: Drugs’ impact on brain chemistry Drugs’ impact on brain chemistry

may have permanent or long term may have permanent or long term effects (impairment 2 years)effects (impairment 2 years) Extend length of treatmentExtend length of treatment Inform/educate clientInform/educate client Structure accessible services Structure accessible services Avoid changing service delivery timesAvoid changing service delivery times Simplify client paperworkSimplify client paperwork