Pathological Drug Dependence and Its Treatment

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Pathological Drug Dependence and Its Treatment

• Carlton Erickson, Ph.D.
• Director, Addiction Science Research and
  Education Center
• University of Texas at Austin, USA
• 
  APIA-Singapore, 2004

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RESEARCH VALIDITY ESTIMATE (RVE)
(A Thoughtful Appraisal of High-Quality
Scientific Research)

• High RVE
• many large, well-controlled studies
• replicable results
• much peer-reviewed, published literature
• Low RVE
• few replicable studies
• highly speculative results
• little peer-reviewed, published literature

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The essential feature of dependence is impaired
control

• Two components (Ch. 2, Big Book)
• 1. loss of control (within an episode)
• 2. inability to abstain (between episodes)

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Well, how does impaired control develop?
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Model of Impaired Control
MFB Circuits

• Circuit 1 LIKE (pleasure) circuit.
• Circuit 2 WANT (desire, urge) circuit.
• Robinson
  and Berridge, 1993

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Model of Impaired Control
MFB Circuits

• Circuit 1 LIKE (pleasure) circuit.
• Circuit 2 WANT (desire, urge) circuit.
• Circuit 3 NEED (pathological desire, demand)
  circuit. This is associated with sensitization
  (severe dependence).

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Features of the Need Circuit

• We know where it is (MFB)
• How does it become sensitized?
• Some people talk about an addictive switch -
  is this it?
• Lets look at the neurochemistry

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The Mesolimbic Dopamine System Model of
Impaired Control___________________
a.k.a. Medial Forebrain Bundle (MFB)
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Dependence Brain Areas

• mesolimbic dopamine system
• key elements of a basal forebrain
  macrostructure
• extended amygdala (Koob)
• - central nucleus of amygdala
• - bed nucleus of the stria terminalis
• - transition zone, medial (shell) of NAc

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Medial Forebrain Bundle

• ventral tegmental area (VTA)
• (lateral) hypothalamus (LH)
• nucleus accumbens (NAcc)
• frontal cortex (FC) - key portions
• - prefrontal cortex (PFC)
• - orbitofrontal cortex (OFC)

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Drugs Associated wth Neurotransmitters

• Why do people have drugs of choice?
• Dopamine - amphets, cocaine, ETOH
• Serotonin - LSD, ETOH
• Endorphins - opioids, ETOH
• Gamma-aminobutyric acid - benzos, ETOH
• Glutamate -ETOH
• Acetylcholine - nicotine, ETOH
• (Marijuana?)

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What Goes Wrong With The Neurotransmitter
System(s)?

• genetic malfunctions?
• drug-induced changes?
• other aspects of the
• environment, besides drugs?

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Genetics of Alcohol Dependence

• family, twin, adoption studies
• the tendency to become alcohol dependent is
  inherited
• major question what is passed from parent to
  child?
• alcohol dependence (perhaps other
  dependencies?) is polygenetic!

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Rationale Based on Genetics

• abnormal genes abnormal proteins
• abnormal transmitter synthesizing enzymes
• abnormal transmitter breakdown enzymes
• abnormal receptors
• neurotransmitter dysfunction in the pleasure
  pathway
• impaired control

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A Brain Chemistry Disease!

• addicting drugs seem to match the transmitter
  system that is not normal
• cases range from mild to severe
• detox is the first step, followed by accessing
  the wreckage of the past
• methadone and nicotine maintenance is evidence
  that some people require a chemical to overcome
  the non-normal transmitter system

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Treatment of Dependence
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Todays Options (Its all about options.)

• traditional 12 step programs (abstinence)
• talk inpatient/outpatient/aftercare
• misunderstood harm reduction, MM
• new brief motivational counseling, CBT, MET,
  SO-involved therapy, vouchers
• medical tx new medications to enhance
  abstinence - anticraving meds, methadone,
  buprenorphine, vaccines
• (MM Moderation Management, CBT cognitive
  behavioral therapy,
• MET motivational enhancement therapy, SO
  significant other)

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Newer Medications

• naltrexone (ReVia) - alcohol
• ondansetron (Zofran) - alcohol
• acamprosate (Campral) - alcohol
• topiramate (Topamax) - alcohol
• buprenorphine (Subutex) - heroin
• bupropion (Zyban) - nicotine
• Not yet approved for dependence treatment

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Question

• What is the similarity between behavioral
  (talk) therapies and pharmacotherapies in the way
  they work?
• grief anger learning
• talking to others in an
• emotional group setting?

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Logic Says Behavioral Therapies Probably Change
Brain Chemistry!

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New Brain Scan Research

• Psychotherapy and meds work on the basal
  ganglia in treatment of depression (Martin et
  al., 2001)
• CBT and meds work on the same brain areas in
  treating social anxiety (Furmark et al., 2002)
• CBT appears to modify bad circuits associated
  with anxiety disorders (Paquette et al., 2003)

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Remember the Best Academic Website in the World!

• www.utexas.edu/research/asrec