drugaddiction-pharmainfo.pptx

1. THE NEUROSCIENCE OF
DRUG ADDICTION AND THERAPY
Yvette Carpintero, BSW, MSSW, LMSW, LCDC-I

2. ► Introduction
► Key Definitions
►Reward pathway responsible for
Addictive Changes
► Stages of the Addiction Cycle
►Neurochemical Changes Associated
with the Drug Use, Dependence and
Relapse
► Therapy
► Conclusion
CONTENTS

3. INTRODUCTION
• From 1990 to 2001, the number of people who used prescription painkillers
recreationally for the first time grew by 335% to include almost 2.5 million people.
• Estimated Prevalence Among 15-54 Year Olds of Nonmedical
Use and Dependence Among Users (1990-1992) (NCS)
• Alcohol
•
– 18 million Americans abuse or are dependent on Alcohol.
• Smoking
--In US, approximately 440,000 persons die per year of a cigarette smoking & attributable illness
Opioid Dependency
– Dependency has been growing rapidly:
Ever Used
Prevalence of
Dependence
Dependence
Among Users
Drugs
Tobacco 75.6 24.1 31.9
Alcohol 91.5 14.1 15.4
Illicit Drugs 51.0 7.5 14.7
Cannabis 46.3 4.2 9.1
Cocaine 16.2 2.7 16.7

4. KEY DEFINITIONS
Drug Addiction — Chronically relapsing disorder that is characterized by a compulsion to seek and take drug,
loss of control in limiting intake, and emergence of a negative emotional state (e.g. dysphoria, anxiety,
irritability) when access to the drug is prevented (here, defined as the “dark side” of addiction)
Nucleus Accumbens and Extended Amygdala — Forebrain structures involved in the rewarding effects of
drugs of abuse. Composed of central nucleus of the amygdala, bed nucleus of the stria terminalis, and a
transition zone in the medial part of the nucleus accumbens
Reward pathway responsible for Addictive Changes

5. Reward pathway responsible for Addictive Changes

6. NEUROCHEMICAL CIRCUITRY IN DRUG
REWARD

7. CONVERGING ACUTE ACTIONS OF DRUGS OF ABUSE ON THE
VENTRAL TEGMENTAL AREA AND NUCLEUS ACCUMBENS

8. SUMMARY- NEUROCIRCUITRY OF
ADDICTION
• Reward Circuit- nucleus accumbens and
extended amygdala (bed nucleus of the stria
terminalis and central nucleus of the amygdala)
• “Craving” Circuit- dorsal prefrontal cortex,
basolateral amygdala
• “Compulsivity” Circuit- ventral striatum, ventral
pallidum,medial thalamic- orbitofrontal cortical
loop

9. STAGES OF THE
ADDICTION CYCLE

10. STAGES OF THE
ADDICTION CYCLE

11. Neurobiological Substrates for the Acute Reinforcing Effects of Drugs of Abuse
Neurotransmitter
Dopamine
Opioid Peptides
GABA
Glutamate
Site
Ventral tegmental area, nucleus accumbens
Nucleus accumbens, amygdala, ventral tegmental area
Amygdala, bed nucleus of stria terminalis
Nucleus accumbens
NEUROCHEMICAL CHANGES ASSOCIATED WITH
THE DRUG USE, DEPENDENCE AND
RELAPSE

12. Dopamine … “dysphoria”
Serotonin … “dysphoria”
GABA … anxiety, panic attacks
NPY … anti-stress
Dynorphin … “dysphoria”
CRF … stress
Norepinephrine … stress
Glutamate….hyperexcitability
Common Molecular Changes Associated with Dependence
• Dopamine D-2 receptor binding- decreased in human imaging studies in dependent subjects
• CREB ( cyclic adenosine monophosphate response element binding protein) transcription factor-
decreased in nucleus accumbens and extended amygdala during the development of
dependence
REWARD TRANSMITTERS IMPLICATED IN THE POSITIVE MOTIVATIONAL
EFFECTS OF DRUGS OF ABUSE
Positive Hedonic Effects
Dopamine
Opioid peptides
GABA
Glutamate
Neurotransmitters Implicated in the Motivational Effects of Withdrawal
from Drug of Abuse

14. Chronic Use: Hedonic Homeostatic Dysregulation
H
ed
on
ic
Sca
le
Normal Affective Response
to Drugs/Alcohol
Altered Dysregulated Set-Point
following chronic drug use
HEDONIC SET POINT IS ALTERED WITH
CHRONIC DRUG USE
Initially use to
get high…
Now use to
“get normal”
“Cravings”
“Feel good”
“Feel bad”

15. ANIMAL MODELS FOR THE DIFFERENT STAGES OF
THE ADDICTION CYCLE
• Animal Models for the Binge/Intoxication Stage
1. Oral or intravenous drug self-administration
2. Brain stimulation reward
3. Place preference
• Animal models for the Withdrawal/Negative Affect Stage
1. Brain stimulation reward
2. Place aversion
• Animal Models for the Transition to Addiction
1. Dependence-induced drug taking
2. Escalation in drug self-administration with prolonged access
3. Drug taking despite aversive consequences
• Animal Models for the Preoccupation/Anticipation (“Craving”) Stage
1. Drug- induced reinstatement
2. Cue- induced reinstatement
3. Alcohol Deprivation Effect
4. Stress- induced reinstatement

16. MOODCHANGES ASSOCIATED WITH PLASMA
LEVELS OF COCAINE DURING COCA PASTE
SMOKING

17. COCAINE SELF-
ADMINISTRATION

18. EXTRACELLULAR DA AND 5-HT IN THE NUCLEUS
ACCUMBENS DURING COCAINE SELF-
ADMINISTRATION AND WITHDRAWAL

19. CNS ACTIONS OF CORTICOTROPIN RELEASING
FACTOR (CRF)

20. ETHANOL DEPENDENCE
INDUCTION

21. EXTRACELLULAR CRF LEVELS IN THE
CENTRAL AMYGDALA DURING ETHANOL
WITHDRAWAL

22. EFFECT OF CRF ANTAGONIST D-PHE-CRF12-41
– CENTRAL NUCLEUS OF THE AMYGDALA –

23. CRAVING-TYPE 1
• “Craving”- induced by stimuli that have been paired with
ethanol self-administration such as environmental cues
• Termed conditioned positive reinforcement in experimental
psychology
• An animal model of craving- type 1 is cue induced
reinstatement where a cue previously paired with access to
ethanol reinstates responding for a lever that has been
extinguished.

24. Reinstatement
NEUROBIOLOGICAL EFFECTS OF
EXPOSURE TO DRUG-
ASSOCIATED CONTEXTUAL
STIMULI
SA EXT S- S+
Daily Sessions of Self-Administration

25. COMMON MOLECULAR CHANGES
ASSOCIATED WITH DEPENDENCE
• Dopamine D-2 receptor binding- decreased in human
imaging studies in dependent subjects
• CREB ( cyclic adenosine monophosphate response
element binding protein) transcription factor- decreased
in nucleus accumbens and extended amygdala during
the development of dependence
• Delta-FosB transcription factor-changed during
protracted abstinence to drugs of abuse

26. KEY COMMON NEUROCIRCUITRY ELEMENTS
IN DRUG SEEKING BEHAVIOR OF
ADDICTION

27. Craving-Type 1
• “Craving”- induced by stimuli that have been paired with ethanol self-administration such as
environmental cues
• Termed conditioned positive reinforcement in experimental psychology
Craving-Type 2
• State of protracted abstinence in alcoholics weeks after acute withdrawal
• Conceptualized as a state change characterized by anxiety and dysphoria or a residual negative
affective state that combines with Craving-Type 1 situations to produce relapse to excessive
drinking

28. THERAPY
• No single treatment is appropriate for all individuals
• Effective treatment attends to multiple needs of the individual, not just his/her drug use
• Treatment must address medical, psychological, social, vocational, and legal problems
Duration of Treatment
• Depends on patient problems/needs
• Less than 90 days is of limited/no effectiveness for residential/outpatient setting
• A minimum of 12 months is required for methadone maintenance
• Longer treatment is often indicated
Medical Detoxification
• Detoxification safely manages the physical symptoms of withdrawa
• lOnly first stage of addiction treatment
• Alone, does little to change long-term drug use

29. MEDICATIONS FOR ALCOHOL DEPENDENCE
• Disulfiram (Antabuse)
- FDA approved 1954
• Naltrexone (ReVia)
- FDA approved 1994
• Acamprosate
- FDA approved 2004

30. THERAPY
Counseling and Other Behavioral Therapies
Drug
Resistance
Skills
Replace
Drug
Using
Activities
Motivation
Problem
Solving Skills
Interpersonal
Relationships

31. CONCLUSION
• Drug abuse is an issue of global concern especially among the youth and adolescent population.
• Drug addiction is the major cause of behavioral disturbances and major cause of criminal
activity.
• The main objective of study of neuroscience of drug addiction is to effectively develop therapy
for the individuals to rid of their drug seeking behavior and to stabilize their behavior.
• Based on the studies, newer, more effective pharmacotherapeutic strategies may be developed.
References
• www.nida.nih.gov
• www.drugabuse.gov
• National Institute on Alcohol Abuse and Alcoholism
• National Institute on Drug Abuse
• Goodman & Gilmann’s Pharmacological Basis of Therapeutics