Methamphetamine: What can Brain Imaging Tell Us?

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Methamphetamine What can Brain Imaging Tell Us?

• Richard A. Rawson, Ph.D
• Adjunct Associate Professor
• Semel Institute for Neuroscience and Human
  Behavior
• David Geffen School of Medicine
• University of California at Los Angeles
• www.uclaisap.org
• rrawson_at_mednet.ucla.edu
• Supported by
• Supported by
• National Institute on Drug Abuse (NIDA)
• Pacific Southwest Technology Transfer Center
  (SAMHSA)
• International Network of Treatment and
  Rehabilitation Resource Centres (UNODC)

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Methamphetamine

• Methamphetamine is a powerful central nervous
  system stimulant that strongly activates multiple
  systems in the brain. Methamphetamine is closely
  related chemically to amphetamine, but the
  central nervous system effects of methamphetamine
  are greater.

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Forms of Methamphetamine
Methamphetamine Powder IDU Description
Beige/yellowy/off-white powder
Base / Paste Methamphetamine IDU Description
Oily, gunky, gluggy gel, moist, waxy
Crystalline Methamphetamine IDU Description
White/clear crystals/rocks crushed glass /
rock salt
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EPHEDRINE
H
H
H
C
C
N
CH
CH
OH
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3
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The Methamphetamine EpidemicAdmissions/100,000
1992-2003
It keeps going up
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A Major Reason People Take a Drug is they Like
What It Does to Their Brains
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Natural Rewards Elevate Dopamine Levels
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Effects of Drugs on Dopamine Release
Source Shoblock and Sullivan Di Chiara and
Imperato
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What Can Imaging Tell Us?

• In design of new medications knowledge of
  affected circuitry can point to chemical
  dysfunction that may be helped by medication.
• In the design of behavioral treatments it can
  tell you the types and severity of deficits and
  dysfunctions in the brain and the timetable of
  their recovery (or not). This information can be
  helpful in guiding the behavioral targets for
  treatment and the types and durations of
  treatment that can best accommodate the brain
  recovery
• Brain imaging can show how much viable tissue
  there is to work with. And, it can show the
  affect of treatment.

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Imaging Modalities
Regional Function Specific Neurochemistry
PET Metabolism Blood Flow Neurotransmitters their Receptors
SPECT Blood Flow poor-mans PET Neurotransmitters their Receptors
MRI Correlates of Blood Flow Spectroscopy Diffusion Tensor Imaging
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Brain Function in Methamphetamine Abusers

• Do METH abusers show abnormalities in brain
  metabolites?
• Do brain metabolite abnormalities relate to
  cognitive performance such as selective
  attention?
• Does the brain recover following cessation of
  METH use?

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Prolonged Drug Use Changes the Brain In
Fundamental and Long-Lasting Ways
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Decreased dopamine transporter binding in METH
users resembles that in Parkinsons Disease
patients
Control Meth PD
Source McCann U.D.. et al.,Journal of
Neuroscience, 18, pp. 8417-8422, October 15, 1998.
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Partial Recovery of Brain Dopamine Transporters
in Methamphetamine (METH) Abuser After Protracted
Abstinence
3
0
ml/gm
METH Abuser (1 month detox)
Normal Control
METH Abuser (24 months detox)
Source Volkow, ND et al., Journal of
Neuroscience 21, 9414-9418, 2001.
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Their Brains have been
Re-Wired by Drug Use
Because
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Some Recent Findings

• Methamphetamine abusers have deficits in
• prefrontal cortex (working memory) Edythe London
  et al
• anterior cingulate gyrus (selective attention)
  Nordahl, Salo et al, Salo, Nordahl et al, Taylor
  et al
• temporal lobe (episodic memory, depression)
  London et al

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Speculation

• Cognitive deficits in methamphetamine abusers are
  likely to reflect damage in anterior brain
  regions, such as anterior cingulum, that could
  contribute to their clinical presentation of
  inattention and distractibility.

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Control gt MA
4
3
2
1
0
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MA gt Control
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Methamphetamine

• Cognitive and Memory Effects

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Memory Difference between Stimulant and
Comparison Groups
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Differences between Stimulant and Comparison
Groups on tests requiring perceptual speed
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Longitudinal Memory Performance
number correct
test
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Defining Domains Executive Systems Functioning

• a.k.a. frontal lobe functioning.
• Deficits on executive tasks assoc. w/
• Poor judgment.
• Lack of insight.
• Poor strategy formation.
• Impulsivity.
• Reduced capacity to determine consequences of
  actions.

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Brain Serotonin Transporter Density and
Aggression in Abstinent Methamphetamine
Abusers

• Sekine, Y, Ouchi, Y, Takei, N, et al. Brain
  Serotonin Transporter Density and Aggression in
  Abstinent Methamphetamine Abusers. Arch Gen
  Psychiatry. 20066390-100.

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Objective of Study

• Investigate the status of brain serotonin neurons
  and their possible relationship with clinical
  characteristics in currently abstinent
  methamphetamine abusers.

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Results

• Serotonin transporter density in global brain
  regions was significantly lower in
  methamphetamine abusers
• Suggests that abuse of methamphetamine leads to a
  global and severe reduction in the density of
  human brain serotonin transporters
• Values of serotonin transporter density in widely
  distributed brain regions were found to
  negatively correlate with the duration of
  methamphetamine use.
• Suggests that the longer methamphetamine is used,
  the more severe the decrease in serotonin
  transporter density.

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Results (Continued)

• Magnitude of aggression in methamphetamine
  abusers increased significantly with decreasing
  serotonin transporter densities in some brain
  regions.
• Bitofrontal cortex, anterior cingulate, temporal
  cortex
• No correlation between a representative measure
  of serotonin transporter density and the duration
  of methamphetamine abstinence. Individuals
  abstinent for gt 1 year still had a substantial
  decrease in serotonin transporter density.
• Suggests reductions in the density of the
  serotonin transporter in the brain could persist
  long after methamphetamine use ceases.

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Methamphetamine Use, Self-Reported Violent Crime,
and Recidivism Among Offenders in California Who
Abuse Substances

• Cartier J, Farabee D, Prendergast M.
  Methamphetamine Use, Self-Reported Violent Crime,
  and Recidivism Among Offenders in California Who
  Abuse Substances. Journal of Interpersonal
  Violence. 200621435-445.

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Objective of Study

• Examine the associations between methamphetamine
  (MA) use and three measures of criminal behavior
  (a) self-reported violent criminal behavior, (b)
  return to prison for a violent offense, and (c)
  return to prison for any reason.

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Methods

• Participants
• 808 low- to medium-level inmates
• Clear history of substance abuse
• Within 12 months of release
• Half the sample entering an in-prison substance
  abuse (SA) program and the other half from a
  neighboring prison that offered no formal SA
  treatment
• Matched by age, ethnicity, sex offender status,
  and commitment offense

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Methods Continued

• Baseline and 12-Month Follow-Up Interviews
• Modified versions of criminal justice treatment
  evaluation forms developed by researchers at
  Texas Christian University
• Sections on sociodemographic background, family
  and peer relations, health and psychological
  status, criminal involvement, in-depth drug-use
  history, and an AIDS-risk assessment

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Results

• Those who used MA (81.6) were significantly more
  likely than those who did not use MA (53.9) to
  have been returned to custody for any reason or
  to report committing any violent acts in the 30
  days prior to follow-up (23.6 vs. 6.8,
  respectively)

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Results Continued

• After controlling for drug trade involvement, MA
  use was still significantly predictive of
  self-reported violent crime and general
  recidivism

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Implications of Results

• These findings suggest that offenders who use MA
  may differ significantly from their peers who do
  not use MA and may require more intensive
  treatment interventions and parole supervision
  than other types of offenders who use drugs

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Neural Activation Patterns of Methamphetamine-Depe
ndent Subjects During Decision Making Predict
Relapse

• Paulus M, Tapert S, Schuckit M. Neural Activation
  Patterns of Methamphetamine-Dependent Subjects
  During Decision Making Predict Relapse. Arch Gen
  Psychiatry. 200562761-768.

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Objective of Study

• To determine whether functional magnetic
  resonance imaging (fMRI) during a decision-making
  task can be used to predict relapse in
  treatment-seeking methamphetamine-dependent
  individuals

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Methods

• Participants
• 46 treatment-seeking males
• Met criteria for current dependence on
  methamphetamine (MA)
• Not dependent on any other drug or on alcohol
• Voluntarily entered and completed a 28-day
  inpatient program
• At the time of scanning, abstinent from MA

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Methods Continued

• Interview-based symptomatic assessment
• fMRI tasks
• 2-choice prediction task
• Response task
• Outcome measure
• Blood oxygen level-dependent fMRI activation
  during tasks

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Methods Continued

• Follow-Up
• Contacted 1 year after imaging session
• Sobriety assessed using a questionnaire
• Relapse defined as any use of MA during any time
  after discharge

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Results

• 18 of 40 subjects relapsed
• Bilateral prefrontal cortex, striatum, posterior
  parietal cortex, and anterior insula were more
  active during the prediction task than the
  response task

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Results Continued

• 9 areas within these regions differentiated
  relapsing and nonrelapsing participants
• Areas included prefrontal, parietal, and insular
  cortex
• Nonrelapsing individuals showed more activation
  in these areas

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Results Continued

• Right insula, right posterior cingulate, and
  right middle temporal gyrus response best
  differentiated between relapsing and nonrelapsing
  participants
• Cross-validation analysis was able to correctly
  predict 19 of 22 who did not relapse and 17 of 18
  who relapsed
• Right middle frontal gyrus, right middle temporal
  gyrus, and right posterior cingulate cortex
  activation best predicted time to relapse

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Implications of Results

• Neural activation differences are part of a
  system involved with the processing of decision
  making. Attenuated activation may represent
• Defective assessment abilities and subsequent
  reliance on habitual behaviors
• Diminished ability to differentiate choices that
  lead to good vs. poor outcomes
• fMRI may prove to be a useful clinical tool to
  assess relapse susceptibility

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Methamphetamine Abuse, HIV Infection Causes
Changes in Brain StructureJernigan,T, et al
American Jnl of Psychiatry Aug 2005

• Methamphetamine abuse and HIV infection cause
  significant alterations in the size of certain
  brain structures, and in both cases the changes
  may be associated with impaired cognitive
  functions, such as difficulties in learning new
  information, solving problems, maintaining
  attention and quickly processing information.
• Co-occurring methamphetamine abuse and HIV
  infection appears to result in greater impairment
  than each condition alone

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Methamphetamine Abuse, HIV Infection Causes
Changes in Brain StructureJernigan,T, et al
American Jnl of Psychiatry Aug 2005

• Brain scans to analyze structural volume changes
  in 103 adults divided among four populations
  methamphetamine abusers who were HIV-positive
  methamphetamine abusers who were HIV-negative
  nonabusers who were HIV-positive and nonabusers
  who were HIV-negative.
• They also assessed the ability to think and
  reason using a detailed battery of tests that
  examined speed of information processing,
  attention/working memory, learning and delayed
  recall, abstraction/executive functioning, verbal
  fluency, and motor functioning.

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Methamphetamine Abuse, HIV Infection Causes
Changes in Brain StructureJernigan,T, et al
American Jnl of Psychiatry Aug 2005

• Methamphetamine abuse is associated with changes
  in the the brains parietal cortex (which helps
  people to understand and pay attention to whats
  going on around them) and basal ganglia (linked
  to motor function and motivation).
• The degree of change in the parietal cortex was
  associated with worse cognitive function
• HIV infection is associated with prominent volume
  losses in the cerebral cortex (involved in higher
  thought, reasoning, and memory), basal ganglia,
  and hippocampus (involved in memory and learning

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Methamphetamine Abuse, HIV Infection Causes
Changes in Brain StructureJernigan,T, et al
American Jnl of Psychiatry Aug 2005

• In HIV-infected people, the cognitive
  impairments are associated with decreased
  employment and vocational abilities, difficulties
  with medication management, impaired driving
  performance, and problems with general activities
  of daily living, such as managing money,
• The impact of methamphetamine could potentially
  affect treatment and relapse prevention efforts,
  as well as things like money management and
  driving performance.

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Methamphetamine Abuse, HIV Infection Causes
Changes in Brain StructureJernigan,T, et al
American Jnl of Psychiatry Aug 2005

• Younger methamphetamine abusers showed larger
  effects in some brain regions.
• Among HIV-infected individuals, the researchers
  noted a direct association between the severity
  of the infection and greater loss of brain
  matter.
• In methamphetamine abusers who are also
  HIV-positive, decreased volumes are correlated
  with increased cognitive impairment in one brain
  region, the hippocampus.

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