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Methamphetamine: What can Brain Imaging Tell Us

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Title: Methamphetamine: What can Brain Imaging Tell Us


1
Methamphetamine What can Brain Imaging Tell Us?
  • Thomas E. Freese, Ph.D
  • Director
  • Pacific Southwest Addiction Technology Transfer
    Center
  • Asst. Research Psychologist
  • Semel Institute for Neuroscience and Human
    Behavior
  • David Geffen School of Medicine
  • University of California at Los Angeles
  • www.psattc.org
  • www.uclaisap.org
  • tefreese_at_ix.netcom.com
  • Supported by
  • Supported by
  • National Institute on Drug Abuse (NIDA)
  • Pacific Southwest Technology Transfer Center
    (SAMHSA)

May 24, 2006 Orlanndo, Florida
2
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.

3
Forms of Methamphetamine
Methamphetamine Powder Description
Beige/yellowy/off-white powder
Base / Paste Methamphetamine Description Oily,
gunky, gluggy gel, moist, waxy
Crystalline Methamphetamine IDU Description
White/clear crystals/rocks crushed glass /
rock salt
4
EPHEDRINE
H
H
H
C
C
N
CH
CH
OH
3
3
5
The Methamphetamine EpidemicAdmissions/100,000
1992-2003
It keeps going up
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  • People use drugs for two reasons
  • To feel good.
  • To feel better

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In other words 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
12
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.

13
Imaging Modalities
14
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?

15
Prolonged Drug Use Changes the Brain In
Fundamental and Long-Lasting Ways
16
Decreased dopamine transporter binding in METH
users resembles that in Parkinsons Disease
Control Meth PD
Source McCann U.D.. et al.,Journal of
Neuroscience, 18, pp. 8417-8422, October 15, 1998.
17
Partial Recovery of Brain Dopamine Transporters
in Methamphetamine 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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Meth
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Meth
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Meth
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Meth
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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

28
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.

29
Control gt MA
4
3
2
1
0
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MA gt Control
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  • Cognitive and
  • Memory Effects

32
Differences between Stimulant and Comparison
Groups on tests requiring perceptual speed
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Memory Difference between Stimulant and
Comparison Groups
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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.

37
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.

38
Objective of Study
  • Investigate the status of brain serotonin neurons
    and their possible relationship with clinical
    characteristics in currently abstinent
    methamphetamine abusers.

39
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.

40
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.

41
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.

42
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.

43
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

44
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

45
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)

46
Results Continued
  • After controlling for drug trade involvement, MA
    use was still significantly predictive of
    self-reported violent crime and general
    recidivism

47
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

48
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.

49
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

50
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

51
Methods Continued
  • Interview-based symptomatic assessment
  • fMRI tasks
  • 2-choice prediction task
  • Response task
  • Outcome measure
  • Blood oxygen level-dependent fMRI activation
    during tasks

52
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

53
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

54
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

55
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

56
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

57
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

58
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.

59
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)

60
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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  • For more information, contact
  • Thomas E. Freese, Ph.D.
  • 310-445-0874 x304
  • tefreese_at_ix.netcom.com
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