Neurobiology of addiction
Stephen JurdUniversity of Sydney
Australia
Addiction
• Not simply withdrawal
• Persists well after use has stopped – DSM
says ‘early remission’ to 12 months
• Common problem
• Social impact
• Medical impact
• Many psychiatric complications
Reward
• There must be a system of reward, hard
wired into mammalian brains
• Attempts to track it down have identified
dopamine as the relevant neurotransmitter
The “new” dopamine hypothesis
• DA is not merely a vector for the
production of psychosis
• DA is crucial for all reinforcement
• DA in the shell of the nucleus accumbens
causes reward = attention, memory and learning
• Addiction subsumes this basic mechanism
Schematic diagram that represents the dopamine pathway projecting from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc), indicating how substances of abuse can alter the activity of this pathway to produce their rewarding effects.
The Brain
• Obviously the site of addiction
• Subtle interplay between various brain
functions
• Wise old Griffith Edwards: “salience”
• Responds to stimuli not consciously
encoded (Childress et al 2008)
Alcohol Dependence Syndrome
• Tolerance
• Repeated withdrawal symptoms
• Relief of withdrawal by further drinking
• Salience of drink seeking behaviour
• Subjective awareness of a compulsion to drink
• Narrowing of the drinking repertoire
• Reinstatement after abstinence
Prelude to Passion (Childress
2008)
fMRI showed limbic activation to “unseen”cocaine and sexual images of 33 milliseconds duration in 22 male cocaine patients.
• Brain reward circuitry responds to drug and sexual cues presented outside awareness.
• 48 hours later, addict ‘liked’ visible versions of the same cues.
• This study displays unconscious vulnerability in addiction.
Substance Dependence – DSM IV
• Maladaptive pattern of substance use
• Leading to clinically significant impairment
or distress
• Manifested by three or more criteria
• Occurring at any time in the same 12
month period
DSM IV Dependence criteria
• Tolerance
• Withdrawal
• Substance taken more or longer than intended
• Problem cutting down or controlling use
• Great deal of time spent obtaining, using, recovering from substance
• Important activities given up or reduced
• Continued use despite knowledge of harm
Genetics 1
• Twin studies (Kaij 1961, Prescott 1999)
• Adoptee studies ( Goodwin 1973,
Cloninger 1979, Sigvaardson 1996,
Cadoret 1995)
• Long term follow up study (Vaillant 1983)
Nano evidence
• GABA a2 receptor subtypes associated with alcohol dependence (Soyka 2008)
• A1 allele of D2 DA receptor (Blum & Noble 1990)
• Serotonin transporter gene(Lichterman 2000, Herman et al 2003)
• Alcohol dehydrogenase (protective)
Old Effective Treatments
• Opioid substitution (‘done, bupe, LAAM)
• Disulfiram
Newer Treatments
• Naltrexone
• Acamprosate (rat model = alcoholisation)
• Nalmefene
• Ondansetron
• Topiramate
• Baclofen
Latt, Jurd et al (2002)
Sass, Soyka et al New Drugs - Old Concepts
• Addiction is a disease
• Craving is a physical phenomenon
• Addicts reward themselves chemically
New Drugs - New Concepts
• Several neurotransmitters are relevant
• Combination drug treatment may be
appropriate
• There may be pharmacological subtypes of alcohol dependence
Brain Plasticity
• Synaptic structures are highly dynamic
• Synapse count per cell body changes from
2,500 in infants to 15,000 in adolescents
to 7,500 in adults
• Mature brains can generate new neurones
• Exercise increases neural production
• Cells move within the CNS
Recovery
• The previous slide outlined a mechanism
for the biological basis of recovery:
• New behaviours
• New thoughts
• New feelings
• In new cells, synapses and pathways
A Day Without Pain:
Alternative Non-Pharmacologic
Treatments for Pain Recovery
Medical Director
Las Vegas Recovery Center
Mel Pohl, MD, FASAMMel Pohl, MD, FASAMMel Pohl, MD, FASAMMel Pohl, MD, FASAM
KEYSKEYS
� Understand pain and the brain
� Characterize suffering
� Become familiar with treatments (meds, other)
� Learn about co-occurring pain and addiction.
� Review effects of emotions and explain “Pain
Recovery”
Pain Definitions:Pain Definitions:
“An unpleasant sensory and emotional
experience associated with actual or potential
tissue damage ….”
The International Association for the Study of Pain
(Mesky,1979)
Pain is influenced by:
� Culture
� Context
� Anticipation and previous experience
� Emotional and cognitive factors
Types of PainTypes of Pain
• NociceptiveNociceptiveNociceptiveNociceptive
• InflammatoryInflammatoryInflammatoryInflammatory
• NeuropathicNeuropathicNeuropathicNeuropathic
• CentralCentralCentralCentral
Pain SwitchboardPain Switchboard
PP
AA
II
NN
NN
OO
CC
II
CC
EE
PP
TT
II
OO
NN
GENETICS
COMT
TRAUMA
Sustainedcurrents
PeripheralNociceptive
Fibers
Transient Activation
ACUTEPAIN
Woolf CJ, et al. Ann Intern Med. 2004;140:441-451; Petersen-Felix S, et al. Swiss Med Weekly. 2002;132:273-278; Woolf CJ. Nature.1983;306:686-688; Woolf CJ, et al. Nature. 1992;355:75-78.
Surgery
orinjury
causes
inflammation
How does acute pain become chronic pain?How does acute pain become chronic pain?
SustainedActivation
PeripheralNociceptive
Fibers
Sensitization
CHRONIC PAIN
CNS
Neuroplasticity
Hyperactivity
Structural
Remodeling
The BuddhaThe BuddhaThe BuddhaThe Buddha
“…When touched with a feeling of pain, the ordinary
uninstructed person sorrows, grieves, and laments, beats
his breast, becomes distraught.
So he feels two pains, physical and mental.
Just as if they were to shoot a man with an arrow and, right
afterward, were to shoot him with another one, so that he
would feel the pains of two arrows…”
Chronic Pain SyndromeChronic Pain Syndrome
� Pain > 6 months
� Depression, anxiety, anger, fear
� Restriction in daily activities
� Excessive use of medications and medical services
� Multiple, non-productive tests, treatment, surgeries
� No clear relationship to organic disorder
Pain Assessment ScalePain Assessment Scale
Clinical definition of pain:
“Whatever the patient states it is unless proven otherwise.”
No Moderate Worst
Pain Pain Pain
0 1 2 3 4 5 6 7 8 9 10
Pain Outcome Profile (POP)Pain Outcome Profile (POP)
20 questions, multiple measurements across treatment
� Pain intensity right now (0-10)
� Pain on average past week (0-10)
� Mobility (5 questions)
� ADL’s (4 questions)
� Negative affect (5 questions), fear (2 questions)
� Vitality (3 questions)
American Academy of Pain Management
Reasonable Goals of Pain ManagementReasonable Goals of Pain Management
Enhance Quality of Life!!Enhance Quality of Life!!
� Maintain function.
� Improve function.
� Reduce discomfort by 50%.
Pharmacologic NonPharmacologic Non--OpioidOpioid
� NSAID’S, COX 2S
� Tricyclics, SNRI’S
� Anticonvulsants
� Muscle Relaxants— (AVOID AVOID AVOID AVOID SOMASOMASOMASOMA////carisoprodolcarisoprodolcarisoprodolcarisoprodol)
� Topicals
Hippocratic OathHippocratic Oath
“I will apply, for the benefit of the sick,
all measures that are required,
avoiding those twin traps of over-treatment
and therapeutic nihilism…”
Treating Chronic Pain withTreating Chronic Pain with OpioidsOpioids
� Clinical Trial
� Ongoing assessment
� Need exit strategy
Problems withProblems with OpioidsOpioids� Side Effects
� Tolerance and physical dependence
� Loss of function
� Perceive emotional pain as physical pain
(chemical copers)
� Hyperalgesia
NEJM, Ballantyne & Mao
Nov 2003
Unintentional drug overdose death rates &
sales of Rx painkillers in US
0
1
2
3
4
5
6
7
8
'90 '91 '92 '93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05 '06
Cru
de r
ate
per
100
,000
0
100
200
300
400
500
600
Sale
s in
mg
/pers
on
Deaths/100,000
Opioid sales(mg/person)
8
Addiction
Characterized by:� compulsive use
� loss of control
� continued use despite harm
� craving
Approved by the Boards of Directors of the AAPM, APS, and ASAM
February 2001
AddictionAddictionAddiction
Physical ProblemsPhysical ProblemsPhysical ProblemsPhysical Problems
Sleep DisturbanceSleep DisturbanceSleep DisturbanceSleep Disturbance
DepressionDepressionDepressionDepression
AnxietyAnxietyAnxietyAnxiety
FunctionalFunctionalFunctionalFunctional
DisabilityDisabilityDisabilityDisability
IncreasedIncreasedIncreasedIncreased StressesStressesStressesStresses
Substance Substance Substance Substance
AbuseAbuseAbuseAbuse
Seddon Savage, M.D.
Chronic
Pain
Chronic Chronic
PainPain
Physical ProblemsPhysical ProblemsPhysical ProblemsPhysical Problems
SleepSleepSleepSleep DisturbanceDisturbanceDisturbanceDisturbance
DepressionDepressionDepressionDepression
AnxietyAnxietyAnxietyAnxiety
FunctionalFunctionalFunctionalFunctional
DisabilityDisabilityDisabilityDisability
IncreasedIncreasedIncreasedIncreased StressesStressesStressesStresses
SubstanceSubstanceSubstanceSubstance
AbuseAbuseAbuseAbuse
AddictionAddictionAddiction
PhysicalPhysicalPhysicalPhysical
ProblemsProblemsProblemsProblems
Sleep DisturbanceSleep DisturbanceSleep DisturbanceSleep Disturbance
DepressionDepressionDepressionDepressionAnxietyAnxietyAnxietyAnxiety
FunctionalFunctionalFunctionalFunctional
DisabilityDisabilityDisabilityDisability
Increased StressesIncreased StressesIncreased StressesIncreased Stresses
PainPainPain
SubstanceSubstanceSubstanceSubstance
AbuseAbuseAbuseAbuse
SeddonSeddonSeddonSeddonSeddonSeddonSeddonSeddon Savage, M.D.Savage, M.D.Savage, M.D.Savage, M.D.Savage, M.D.Savage, M.D.Savage, M.D.Savage, M.D.
Diagnosis: Substance DependenceDiagnosis: Substance Dependence
� DSM-IV Criteria
� Aberrant Behaviors
� 4 Types of Clients
� Brain Disease – Dopamine
Opioid Receptors
Emotional IntensifiersEmotional Intensifiers
� Fear
� Guilt
� Anger - Resentments
� Loneliness
� Helplessness
Ways to reduce pain intensityWays to reduce pain intensity
� Cognitive/Behavioral Therapies
� Attention/Distraction
� Control/Placebo effect
� Fear reduction
Cycle of Uncontrolled Pain and FearCycle of Uncontrolled Pain and Fear
Pain
Altered Functional
Status
Decreased Mobility
AvoidanceBehaviors
Social Limitations Diminished
Self-Efficacy
FEARFEAR
FEAR
FEARFEAR
FEAR
Daily Log of Exposure Therapy
VlaeyenVlaeyen et al., 2002. In Psychological Approaches et al., 2002. In Psychological Approaches to Pain management. (Turk &to Pain management. (Turk & GatchelGatchel, eds.), eds.)
Daily measures of painDaily measures of pain--
related fear and pain of related fear and pain of
Mr. A during baselineMr. A during baseline
(A(A--B) and exposureB) and exposure
treatment (Btreatment (B--C).C).
Reversal of Cycle of Fear and PainReversal of Cycle of Fear and Pain
Pain
Improved Function
Increased Mobility
Exercise
LessPain
Enhanced Self-
Efficacy
� Conditioning Increases Pain.
� Pain Patients Are A Pain.
� Secondary Gain Prevents Getting Well.
Pain Pearls Pain Pearls Treatment ImplicationsTreatment Implications
� Surrender
� Utilize body awareness
� Develop “relaxed attention”
� Involved with others
� Pain Recovery – Develop Balance
Pain Recovery Pain Recovery –– Develop BalanceDevelop Balance
�Mental
�Emotional
�Physical
�Spiritual
RESULTING CHANGES• Relationships
• Positive actions and behaviors
NonNon--Medication Treatments at LVRCMedication Treatments at LVRC
� Exercise - Physical Therapy
� Chiropractic Treatments
� Therapeutic Massage
� Reiki
� Acupuncture
� Individual + group therapy
� Mindfulness-Based Stress Reduction (Kabat-Zinn)
� Yoga - Chi Gong
Creating Presence
IDAA 2012
Dr. Kelly Brady
LEARNING MODEL
Receive
Investigate
Meditate
Integrate Kung Fu Therapist!!
3 circles2.jpg
Benefits of MeditationBenefits of MeditationBenefits of MeditationBenefits of MeditationIncreases gray matter in the insula, hippocampus,
and prefrontal cortex
Reduces cortical thinning due to agingin the prefrontal regions
Improves psychological functions related to these areas including attention, compassion,
and empathy
Increases activation of the left prefrontal cortex,which lifts mood
WhatWhatWhatWhat’’’’ssssFiringFiringFiringFiringisisisis
WiringWiringWiringWiring
Mind Seeds The Muses
Creativity is an act of finding
what’s already there
Life in Balance
Food and Nurturance
Sex and Love
Activity (work)
Creativity
Reflection
Our Bodies and Emotions
Safety: Principle governing solar plexus downward
Love: Principle governing solar plexus to suprasternal
notch
Freedom: Principle governing suprasternal notch to tip
of nose
Peace: Principle governing tip of nose to top of
forehead
Soul: Principle governing top of forehead to top of
skull
ArchetypeVisual symbols or energetic imprints that
exist in our psyches
Primordial patterns that repeat globally and
that are informed by the culture they are
expressed in. You become aware of them in
meditation, dreamtime, remote viewing or
other out-of-body experiences, and in myth,
art, and all forms of creative expression
Snow WhiteA teaching tale
Mirror Meditation
A Psychology of Abundance
The BioCognitive awareness of how
much health, wealth, and love you
require to lead a life of wellness.
Repetition Creates Relevance
Repetition Creates Relevance
Repetition Creates Relevance
Repetition Creates Relevance
Stress vs Distress
Abundance
Meditation
Creative PotentialCreative PotentialCreative PotentialCreative Potential
Seed Syllables.jpg OpennessOpennessOpennessOpenness
PAINPAINPAINPAIN Connection to Infinite AwarenessConnection to Infinite AwarenessConnection to Infinite AwarenessConnection to Infinite Awareness
JOYJOYJOYJOY Plant your seeds carefullyPlant your seeds carefullyPlant your seeds carefullyPlant your seeds carefully
Fire/PassionFire/PassionFire/PassionFire/Passion What is Your Passion?What is Your Passion?What is Your Passion?What is Your Passion?
Action Through UnionAction Through UnionAction Through UnionAction Through Union Ghost StoryGhost StoryGhost StoryGhost Story