Addictions and the Brain - La Hacienda...9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 1 Addictions and the Brain TAAP Conference September 14, 2012 Acknowledgements9/18/2012

9/18/2012

© 2012 La Hacienda Treatment Center.

All rights reserved. 1

Addictions and the Brain

TAAP Conference

September 14, 2012

Acknowledgements

• La Hacienda Treatment Center

• American Society of Addiction

Medicine

• National Institute of Drug Abuse

9/18/2012



Definition

• A primary, progressive biochemical,

psychosocial, genetically transmitted

chronic disease of relapse who’s

hallmarks are denial, loss of control and

unmanageability.

DSM IV Criteria for dependency:

At least 3 of the 7 below

1. Withdrawal

2. Tolerance

3. The substance is taken in larger amounts or over a longer period than was intended.

4. There is a persistent desire or unsuccessful efforts to cut down or control substance use.

5. A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects.

6. Important social, occupational, or recreational activities are given up or reduced because of the substance use.

7. The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance.

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Dispute between behavior and disease

Present understanding of the

Hypothalamus location of the

disease hypothesis.

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Dispute regarding behavior versus

disease

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0

50

100

150

200

0 60 120 180

Time (min)

% o

f B

asal

DA

Ou

tpu

t

NAc shell

Empty

Box Feeding

Source: Di Chiara et al.

FOOD

100

150

200

DA

Co

ncen

trati

on

(%

Baselin

e)

Mounts Intromissions Ejaculations

15

0

5

10

Co

pu

latio

n F

req

ue

nc

y

Sample

Number

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Scr Scr

Bas Female 1 Present

Scr Female 2 Present

Scr

Source: Fiorino and Phillips

SEX

Natural Rewards Elevate Dopamine

Levels

0

100

200

300

400

500

600

700

800

900

1000

1100

0 1 2 3 4 5 hr

Time After Amphetamine

% o

f B

as

al R

ele

as

e

DA DOPAC HVA

Accumbens AMPHETAMINE

0

100

200

300

400

0 1 2 3 4 5 hr Time After Cocaine

% o

f B

as

al R

ele

as

e

DA DOPAC HVA

Accumbens COCAINE

0

100

150

200

250

0 1 2 3 4 5hr Time After Morphine

% o

f B

as

al R

ele

as

e Accumbens

0.5 1.0 2.5 10

Dose (mg/kg)

MORPHINE

0

100

150

200

250

0 1 2 3 hr

Time After Nicotine

% o

f B

as

al R

ele

as

e

Accumbens Caudate

NICOTINE

Source: Di Chiara and Imperato

Effects of Drugs on Dopamine Levels

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Post-Chronic Amphetamine (10 days)

Pre-Amphetamine/Control

Striatal FDOPA Activity

4 weeks

6 months

1 year

2 years

Superior Inferior

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Dopamine Transporters in Methamphetamine Abusers

Methamphetamine abusers have significant reductions in dopamine

transporters.

Normal Control

Methamphetamine Abuser p < 0.0002

Dopam

ine T

ransport

ers

(B

max/K

d)

Normal

Controls

Meth

Abusers

1.0

1.2

1.4

1.6

1.8

2.0

2.2

2.4

BNL - UCLA - SUNY

NIDA - ONDCP - DOE

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Dopamine Transporters in Methamphetamine Abusers

BNL/UCLA/SUNY

NIDA, ONDCP, DOE

Motor Task

Loss of dopamine transporters

in the meth abusers may result

in slowing of motor reactions.

Memory Task Loss of dopamine transporters

in the meth abusers may result

in memory impairment.

7 8 9 10 11 12 13 1.0 1.2 1.4 1.6 1.8 2.0

Time Gait (seconds)

4 6 8 10 12 14 16 1.0 1.2 1.4 1.6 1.8 2.0

Delayed Recall (words remembered)

Do

pa

min

e T

ran

sp

ort

er

Bm

ax/K

d

Cocaine

Food

Meth

Alcohol

Dopamine D2 Receptors in Addiction

Experimental

groups

Control

groups

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Drug Use Addiction Treatment Normal

Challenge:

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Three Major Relapse Pathways

I. Cross Addicting Drugs

II. People/Place/Things

III. B.H.A.L.T.

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Cross Addicting Drugs

a. Chemical of choice

b. Related drugs

c. Tobacco

d. Life long relapse pathway

People/Place/Things

a. History of discovery

b. Three month limit for relapse

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B.H.A.L.T.

a. Boredom

b. Hunger

c. Anger/emotions

d. Loneliness

e. Tiredness

Relapse Prevention Medications

I. Antabuse

II. Campral

III. ReVia

IV. Vivitrol

V. Off label

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Antabuse

a. Mechanism of action

b. Dosing

c. Side Effects

d. Efficacy

Campral


b. Dosing

c. Side Effects

d. Efficacy

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ReVia


b. Dosing

c. Side Effects

d. Efficacy

Vivitrol


b. Dosing

c. Side Effects

d. Efficacy

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Off label

Phase 3 Clinical Trials

On A Number of Promising Drugs

Cabergoline

Disulfiram (Antabuse)

Reserpine

Selegiline

Cocaine Methamphetamine

Bupropion Lofexidine

Opiates

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Cocaine Medication Development ProjectsCocaine Medication Development Projects

Phase II ScreenPhase II Screen Phase IIIPhase III

Disulfiram

Selegiline TS

Disulfiram

Selegiline TS

Phase IPhase I Phase IIPhase II

Butorphanol

DAS 431

GBR 12909

Metyrapone

Modafinil

NS 2359

Tolcapone

Butorphanol

DAS 431

GBR 12909

Metyrapone

Modafinil

NS 2359

Tolcapone

BP 4897

Cocaine Vaccine

Dextromethorphan

Isradipine

Lamotrigine

Memantine

Ondansetron

Sibutramine

BP 4897

Cocaine Vaccine

Dextromethorphan

Isradipine

Lamotrigine

Memantine

Ondansetron

Sibutramine

AmantadineAmlodipineBaclofenBupropionButorphanolCabergolineCaptoprilClopidogrelDisulfiramGabapentinMemantineMethylphenidateNaltrexoneOxazepamPemolinePropranololReserpineRisperidoneSertralineTaurineTiagabineVenlafaxine

AmantadineAmlodipineBaclofenBupropionButorphanolCabergolineCaptoprilClopidogrelDisulfiramGabapentinMemantineMethylphenidateNaltrexoneOxazepamPemolinePropranololReserpineRisperidoneSertralineTaurineTiagabineVenlafaxine

Opiate Medication Development ProjectsOpiate Medication Development Projects

Phase IPhase I

CycloserineCycloserine

Depot NaltrexoneDepot Naltrexone

EnadolineEnadoline

LamotrigineLamotrigine

TramadolTramadol

Phase IIPhase II Phase IIIPhase III

BuprenorphineBuprenorphine

Buprenorphine/Naloxone

Lofexidine

Buprenorphine/Naloxone

Lofexidine

Bupropion

Buspirone

Clonidine

Lofexidine

Memantine

Methylphenidate

Midazolam/N20

Naloxone

Naltrexone

Nefazedone

Bupropion

Buspirone

Clonidine

Lofexidine

Memantine

Methylphenidate

Midazolam/N20

Naloxone

Naltrexone

Nefazedone

Methamphetamine Addiction Pharmacotherapies

in Clinical Trials

Methamphetamine Addiction Pharmacotherapies

in Clinical Trials

Amlodipine

Baclofen

Desipramine

Fluoxetine

Flupenthixol

Gabapentin

Isradipine

Olanzapine

Ondansetron

Pemoline

Selegiline

Venlafaxine

Amlodipine

Baclofen

Desipramine

Fluoxetine

Flupenthixol

Gabapentin

Isradipine

Olanzapine

Ondansetron

Pemoline

Selegiline

Venlafaxine

Phase IPhase I Phase IIPhase II

Bupropion

Disulfiram

Lobeline

Reserpine

Selegiline

Bupropion

Disulfiram

Lobeline

Reserpine

Selegiline

Dual Diagnosis

1. Prevalence

2. Testing

3. Treatment

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Co-Occurring Disorders

Mood, Anxiety, ADD

Psychotic

Substance Use

Disorder

37% of alcohol dependent another disorder

53% of drug dependent another disorder

Etiology

– Symptoms

– Social skills

– Medication side effects

Mental Illness Substance

Use

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Etiology

– Dependence ↑ psychosis, depression, anxiety

– Withdrawal ↑ depression and anxiety

– ? Shared genetics

Mental Illness Substance

Use

Anxiety

• Generalized – Pervasive

• Panic – Sudden onset and resolution

• Social (9% same as general population)

– Associated with social situations

• PTSD – Hypervigilence resulting from trauma

• OCD – Germs, organizing, checking and re-checking

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Social

PTSD

Panic

Generalized

OCD

Withdrawal from alcohol, benzodiazepines, opiates, and

other sedatives mimics anxious state

Normal Emotional States

Treatment – Anxiety • Behavioral

– Therapy as good as medications in most research trials

– Hypnosis, Biofeedback, Exercise

– The Anxiety Cure – Author Dupont

• Medications

– SSRIs (Prozac, Paxil, Lexapro, Celexa, Zoloft)

– SNRIs (Cymbalta, Effexor, Pristiq)

– Buspar

– Short- term: Inderal, Vistaril, Neurontin

– Trazodone

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Mood • Depression

– Major Depression

– Dysthymia

• Mania – Mania

– Hypomania

• Bipolar – I – Manic Episode(s) with or without Depressive Episode(s)

– II – Depressive Episodes(s) with Hypomania

– Cyclothymia – Hypomania and dysthymic episodes

Normal Emotional States

dysthymia

Mania

Major Depression

Withdrawal can mimic mania or depression

hypomania

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Treatment - Mood

• Medications

– SSRIs, SNRIs

– Wellbutrin (Bupropion)

– Mood Stabilizers/Augmenters – Lithium, Depakote,

Risperidone, Seroquel, Topamax, Lamictal, Trileptal,

Abilify, Geodon, Zyprexa

• Behavioral

– Therapy = medications for depression

– Exercise, diet, sunlight useful

ADD/ADHD

• 25 fold h in Adderall use last

decade

• USA = 80 % of Ritalin used

worldwide

• No study shown long term use

stimulants in adults is good

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Symptoms

- Not listening

- Fails to finish tasks

- Difficulty organizing

- Loses things

- Easily distracted

Just gotta be me!

Are you talking to me?

Gotta Dance!

I’m molting……..

Other Causes

• Anxiety

• Mania

• Withdrawal

• Learning Disorders

Treating for ADD first can lead to

worsening of above

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Treatment - ADD

• Therapy and treatment of any underlying

learning disability

• Exercise

• Atypical stimulants – Strattera (amoxetine)

• Guanfacine (Tenex, Intuniv)

• SNRIs – Effexor, Prestiq

• Wellbutrin (Bupropion)

Personality Disorders

• Disorders?

• Phases?

• Artifacts of Addiction?

“so you are anti-social, histrionic, borderline,

and narcissistic but otherwise well.”

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PERSONALITY DISORDERS

• Totality of Emotional + Behavioral Traits

• Onset Teens

• Enduring, Inflexible, Consistent,

Maladaptive

Causes Significant Impairment

and/or Distress

Personality Characteristics

Cluster B – Dramatic, Emotional, or Erratic ASPD Aggressive, Unlawful, Impulsive

Borderline Unstable, Chaotic, Impulsive

Histrionic Dramatic, Seductive but not Unlawful

Narcissistic Self-Centered, Entitled, Lacks Empathy, but

not Unlawful

Cluster A – Eccentric or Odd Paranoid Suspicious, Jealous, but not

Psychotic or Unlawful

Schizoid Unemotional, Cold, Indifferent

Schizotypal Odd /Magical, not Paranoid

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Personality Characteristics

Cluster C – Anxious or Fearful Avoidant Needs people but Fears Relationships

Dependent Needs Relationships, Indecisive,

Fears Abandonment

Obsessive- Rigid, Perfectionist + Inefficient

Compulsive

Passive- Negative Attitudes with Passive Aggressive

Resistance to Demands

Summary

• Very common to have both a substance

use disorder and another disorder

• Even more common to feel like you have

one when using or withdrawing

• The six month challenge

• The twelve month reward

9/18/2012



Spiritual Component of Recovery

9/18/2012



Dr. Daniel Boone

La Hacienda Treatment Center

800-749-6160

[email protected]

Documents

Addictions and the Brain - La Hacienda...9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 1 Addictions and the Brain TAAP Conference September 14, 2012 Acknowledgements9/18/2012