addiction is a brain disease michael l. johnson, ms nancy a. roget, ms
TRANSCRIPT
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Addiction is a Brain Disease
Michael L. Johnson, MSNancy A. Roget, MS
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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
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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
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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
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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
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Paradox of AddictionParadox of Addiction
Initially Voluntary
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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
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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
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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
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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
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Understanding Understanding HowHow the the
Brain Brain Works Works
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UnderstandiUnderstanding Howng How
the the Brain Brain WorksWorks
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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
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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
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Function and Brain RegionsFunction and Brain Regions
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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
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Neurons, Brain Chemistry & Neurons, Brain Chemistry & NeurotransmissionNeurotransmission
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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
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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
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The SynapseThe Synapse
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The SynapseThe Synapse
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NN EE UU RR OO TT RR AA NN SS MM II TT T T EE RR SS
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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
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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
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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
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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
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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
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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”
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NeurotransmissionNeurotransmission
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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
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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
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Routes of AdministrationRoutes of Administration
InhaleInhale InsuflateInsuflate IngestIngest InjectInject EnemaEnema Contact Absorption (patch)Contact Absorption (patch)
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Drug Ingestion
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ORALORAL
20 to 30 minutes
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INHALINGINHALING
7 to 10 Seconds
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INJECTINGINJECTING
15 to 30 seconds- IV
3 to 5 minutes- skin popping
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SNORTINGSNORTING
3 to 5 minutes
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CONTACTCONTACT
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Limbic SystemLimbic System
Reward Reward SystemSystem
Nucleus Nucleus accumbensaccumbens
Prefrontal Prefrontal cortexcortex
Ventral Ventral tegmental tegmental areaarea
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Chronic Drug EffectsChronic Drug Effects
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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
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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
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Positron Emission Tomography (PET)Positron Emission Tomography (PET)
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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
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PET ScanPET Scan Brighter Brighter
red red indicates indicates higher higher levels of levels of activity activity (glucose (glucose utilization)utilization)
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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
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Your Brain After Drugs
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Drugs HaveDrugs HaveLong-term Long-term ConsequencesConsequences
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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
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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
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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
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Stimulant StudiesStimulant Studies
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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
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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
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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)
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Environmental CuesEnvironmental Cues
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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
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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
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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
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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
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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
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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