Addiction is a Chronic Relapsing Disease of the Brain

1
Addiction is a Brain Disease
Michael L. Johnson, MS Nancy A. Roget, MS
2
Brain Disease

• Drug addiction is a brain disease
• Every type of psychoactive drug has its own
  individual mechanism for changing how the brain
  functions
• Drug use changes the individual's brain and its
  functioning in critical ways
• Leshner, 2001

3
Addiction is a Brain Disease

• Addiction is a Brain Disease BECAUSE
• Using drugs over time changes brain structure and
  function
• Some brain changes may persist after use stops
• Long-lasting brain changes effect
• cognitive functioning
• emotional functioning

4
Addiction is a Brain Disease

• Addiction is a brain disease
• addicted brain is different from the
  non-addicted brain
• Prolonged drug use causes pervasive changes in
  brain function

5
Essence of Addiction

• Compulsive craving that overwhelms all other
  motivations (drug use despite negative and social
  consequences)
• root cause of health and social problems

6
Paradox of Addiction
Initially Voluntary
7
Addictions Similarities with Other Brain Diseases

• Some brain diseases are NOT simply biological in
  nature and expression
• Most have social/behavioral aspects
• Examples
• Alzheimer's
• Schizophrenia
• Clinical Depression

8
The Adult Brain, and how it works

• An Adult brain weighs about 3 pounds and has
  billions of cells
• Neurons
• Glial cells

9
(No Transcript)
10
The Brain

• Organ on thinking, behavior, homeostasis
• Different Areas of the brain regulate different
  functions
• Complex tasks are split up into specialized areas
• Damage to these areas leads to specific deficits
• Division of labor allows for Parallel Processing

11
Brain Region Function

• Splits larger tasks into smaller ones
• Component tasks are further broken into sub
  component tasks
• Driving
• Seeing
• Hearing
• Moving

12
Understanding How the Brain Works
13
Understanding How the Brain Works
14
Function of Brain Regions

• Brainstem basic function
• Heart rate, breathing, digestion, sleep
• Cerebellum skilled repetitive movements, balance
• Limbic Systememotions motivations
• Diencephalonsensory perception

15
Function of Brain Regions

• Cerebral Cortex thinking, perceiving, producing
  language
• Vision, hearing, touch, movement, smell, thinking
  reasoning
• Frontal Lobe social behavior Limbic System
• Uses memories, information about how the body is
  working and sensory input

16
Function and Brain Regions
17
Phineas Gage

• 1848 Railroad worker
• Explosion- tamping rod
• Rod entered brain
• Temperament changes
• 20 years post accident
• Correlated accident to behavioral changes
• Frontal lobe social behavior

18
Neurons, Brain Chemistry Neurotransmission
19
The Neuron

• Basic signaling unit of brain
• Precise connections allow for different actions
• Neurons
• Sensory receptors
• Muscles

20
The Neuron

• Cell Body
• Nucleus
• Metabolic center
• Dendrites
• Input from other neurons
• Axon
• Carry high speed messages away from neuron
• Branches into presynaptic terminals

21
The Synapse
22
The Synapse
23

• N
• E
• U
• R
• O
• T
• R
• A
• N
• S
• M
• I
• T
• T
• E
• R
• S

24
The S y n a p
s e

• End of axon
• Typical neuron has 1000 synapses with other
  neurons
• Intercellular space between neurons
• Synaptic cleft

25
Synapses are Dynamic

• Neurons can strengthen synaptic connections
• New synapses form (protein synthesis)
• Synapses can be lost
• Responses to life experiences (and aging)
• Cellular basis of learning

26
Synaptic Transmission

• Neurons communicate via electrical and chemical
  signals
• Electrical signal converted to a chemical signal
  a neurotransmitter
• Electrical signal within a neuron is an action
  potential
• Wave-like flow of ions (electrical impulse) down
  axon
• Transient depolarization of axon

27
Synaptic Transmission

• At the axon terminal, the electrical impulse
  leads to release of a neurotransmitter
• Stored in vesicles which fuse with the neuronal
  membrane and release their contents into the cleft

28
Synaptic Transmission

• Neurotransmitters diffuse into intercellular
  space
• Bind to receptors on dendrite of another cell
• Postsynaptic cell
• Receptors are specific Dopamine receptors
  will only bind dopamine

29
Synaptic Transmission

• Chemical binding of transmitter with receptor
  leads to changes in the post-synaptic cell
• May generate an action potential
• Post-synaptic cell may use a different
  neurotransmitter to communicate down stream

30
Neurotransmission
31
Synaptic Transmission

• After binding, neurotransmitters releases from
  receptor and goes back into the cleft
• Removed by enzymes or reuptake pump/ transporter
  back into terminal
• quick removal of transmitters allow for precise
  communication between neurons

32
Types of Neurotransmitters

• A neuron receives many many messages from
  connecting neurons
• Neurons response is the sum
• Excitatory Transmitters
• Lead to (generation of As and) stimulate firing
  of post-synaptic neuron
• Inhibitory Transmitters
• Lead to decreased firing in post-synaptic neuron

33
(No Transcript)
34
Routes of Administration

• Inhale
• Insuflate
• Ingest
• Inject
• Enema
• Contact Absorption (patch)

35
Drug Ingestion
36

• ORAL

20 to 30 minutes
37

• INHALING

7 to 10 Seconds
38

• INJECTING

3 to 5 minutes- skin popping
15 to 30 seconds- IV
39

• SNORTING

3 to 5 minutes
40

• CONTACT

41
Limbic System

• Reward System
• Nucleus accumbens
• Prefrontal cortex
• Ventral tegmental area

42
Limbic System

• Link between higher cortical activity and the
  lower systems that control emotional behavior
• Limbic Lobe
• Deep lying structures
• amygdala
• hippocampus
• mamillary bodies

43
Limbic System

• Specialized brain areas for producing and
  regulating PLEASURE
• Ventral Tegmental Area
• Nucleus Accumbens
• Prefrontal Cortex
• Areas of Limbic system amygdala, hippocampus,
  hypothalamus

44
Limbic System

• Generates primitive emotional responses to
  situations
• Allows for SURVIVAL
• Identify danger/ threats
• Fear and aggression
• Identify pleasure natural rewards
• Eating
• Sex
• Social Interaction

45
Reward Path

• VTA and NA
• Primitive brain stem and limbic areas
• Activated by drugs of abuse
• Activation of these primitive areas can OVERRIDE
  more evolved cortical areas

46
Reward Pathway

• Also the site of action for addictions
• Drugs activate the pathway with force and
  persistence not seen with natural rewards

47
Drug Effects On Neurotransmission

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

48
Drug Effects on Cell

• Increased cAMP levels
• Activation of transcription factor CREB and
  changes in gene expression
• Changes in synapses, cell structure and function
• The resulting intracellular changes appear to be
  the molecular and cellular basis of addiction
  (persistent behavioral abnormalities)
• Nestler Am J Addiction 2001 201-217

49
Drug Effects on Cell and Learning

• Intracellular changes for addiction the same as
  for learning
• Both activities share intracellular signaling
  cascades (cAMP) and depend on activity of CREB

50
Drug Effects on Cell and Learning

• Learning and addiction show similar changes in
  neuron morphology
• Similar changes at the level of the synapse
• Multiple similar changes in the neuron
• Long term changes
• Addiction is long term
• Nestler 2001 Science 292 (5525) pp 2266-67

51
Drug Effects on the Cell

• Drugs of abuse all directly or indirectly
  increase dopamine binding to post synaptic
  receptor with acute behavioral effects
• Chronically, this increases cAMP levels and leads
  to a cascade of changed cell activity

52
Other Chronic Drug Effects

• Cell Death
• Neurons dont grow back
• Alcohol, ecstasy, meth
• Effect memory, mood, learning

53
Chronic Drug Effects
54
Persistent Effects of Drug Use
Amygdalaactivated
Amygdalanot lit up
Front of Brain
Back of Brain
Nature Video
Cocaine Video
55
Brain Imaging

• PET
• Brain Functioning
• Radiolabeled glucose for levels of activity
• Effects of Drugs
• Distribution in body
• Measure local concentration at binding sites
• Spatial Resolution of 4 mm

56
Positron Emission Tomography (PET)
57
NIDA Research

• Overall goal of NIDA research to
• Reverse the brain changes that underlie addiction
• Roll back the loss of cognitive and motor
  functions that occur
• Develop interventions to stop brain damage,
  repair damage, and retrain the brain
• Restore brain function after it has been changed
  by drug use

58
PET Scan

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

59
Your Brain on Drugs
5-6
1-2 Min
3-4
6-7
7-8
8-9
9-10
10-20
20-30
60
Your Brain After Drugs
61
Drugs Have Long-term Consequences
62
Stimulant Studies

• London et al. (2004)
• PET images of brain activity
• Patients in acute methamphetamine withdrawal (4
  to 7 days)
• Patients
• 10 year history
• 4 grams per week
• 18 days of use out of 30

63
Stimulant Studies

• London et al. (2004)
• levels of depression and anxiety measured
• PET Scans
• Patient Report
• brain- glucose metabolism-depressed mood,
  sadness, anxiety, and drug craving
• Becks Depression Inventory ratings averaged 9.5
  for methamphetamine patients and 1.1 for control

64
Examples of Brain Studies Treatment Application

• London et al. (2004)Treatment of Methamphetamine
  Users
• Mood disorder symptoms may create an acute
  barrier to treatment for methamphetamine abusers

65
Stimulant Studies

66
Treatment Applications from Londons Stimulant
Studies

• Implications for treatment
• Expect clients to feel poorly
• Treatment engagement strategies should focus on
  helping patients to deal with negative emotional
  states (Depression and Anxiety)
• Avoid counseling techniques that are
  confrontational
• Relapse potential is high because clients feel
  poorly
• Be aware of clients turning to self medication
  activities to relieve the negative feeling states

67
Cues for Cocaine and Normal Pleasures Activate
Brain Sites Childress, 1999

• Cues for Cocaine
• Cocaine abusers may experience a powerful urge
  to use when they encounter environmental cues
  associated with use
• Limbic regions of the brain are activated when
  watching cocaine- related videos
• Childress, 1999

68
Persistent Effects of Drug

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

69
Environmental Cues
70

Treatment Applications for Childress Cue-Induced
Cocaine Craving Study

• Implications for Treatment
• Understand the importance environmental cues
  play in initiating the craving process
• Review program educational materials to ensure
  that potential environmental cues for drug use
  are eliminated
• Normalize cue and craving responses for clients
• Teach clients how to urge surf and to identify
  potential environmental cues

71
Recovery of Dopamine Transporters

• Pet scan
• shows levels of dopamine transporters
• Lower levels of dopamine transporters were
  associated with poorer performance on tests of
  memory and motor skills
• Impairments in motor skills and memory continued
• Volkow, et al. 2001

72

• Poor Motor Memory Performance
• 33 year old male- 80 days post detox
• Low Severity- Parkinson Disease
• transporter losses may not recover
• Volkow, et al. 2001

73
Simon, et al. 2002 Cognitive Effects of
Stimulants

• Studied 40 current Methamphetamine Users
• Impairments
• memory
• abstract thinking
• changing points of view
• ability to manipulate information
• comprehension deficits
• Word recall

74
Simon, et al. 2002 Cognitive Effects of
Stimulants

• Help clients who are mandated into treatment
  deal with cognitive problems associated
  comprehension
• Ensure that clients understand
• what counts as compliance with treatment services
  
• counselor recommendations
• consequences for failure to comply
• Give concrete, specific information
• Develop methods to help clients remember
  treatment recommendations or medications

75
Treatment Applications for Simon, et al.s study

• Treatment Implications
• Drugs impact on brain chemistry may have
  permanent or long term effects (impairment 2
  years)
• Extend length of treatment
• Inform/educate client
• Structure accessible services
• Avoid changing service delivery times
• Simplify client paperwork