reward the “new” dopamine hypothesis - idaa ... · pdf filethe “new”...

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



IncreasedIncreasedIncreasedIncreased StressesStressesStressesStresses

SubstanceSubstanceSubstanceSubstance


AddictionAddictionAddiction

PhysicalPhysicalPhysicalPhysical

ProblemsProblemsProblemsProblems

Sleep DisturbanceSleep DisturbanceSleep DisturbanceSleep Disturbance

DepressionDepressionDepressionDepressionAnxietyAnxietyAnxietyAnxiety



Increased StressesIncreased StressesIncreased StressesIncreased Stresses

PainPainPain

SubstanceSubstanceSubstanceSubstance


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

QUESTIONS?QUESTIONS?QUESTIONS?QUESTIONS?

Mel Pohl, MD, FASAM

[email protected]

adaywithoutpain.com

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




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

Make it RealMake it RealMake it RealMake it Real Coming to a Close

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