Title: Methamphetamine: What can Brain Imaging Tell Us
1Methamphetamine 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)
2- 33-year-old man, high on methamphetamine,
attempts suicide with a nail gun - Man initially entered the hospital complaining of
a headache. - Doctors did not see the nails during the initial
examination, but x-rays revealed 12 nails, 1 ½ to
2 inches long, embedded in his head. - Source Skidmore, S. (2006, April 21) Oregon Man
Survives 12 Nails to the Head. The Associated
Press.
3- The man at first claimed it was an accident, but
he later admitted that it was a suicide attempt. - The nails were removed, and the man survived
without any serious permanent damage. - He was eventually transferred to psychiatric
care he stayed for almost one month under court
order but then left against doctors orders
MSNBC-TV
4Methamphetamine
- 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.
5Forms 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
6EPHEDRINE
H
H
H
C
C
N
CH
CH
OH
3
3
7The Methamphetamine EpidemicAdmissions/100,000
1992-2003
It keeps going up
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9What 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.
10Imaging Modalities
11Brain 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?
12Prolonged Drug Use Changes the Brain In
Fundamental and Long-Lasting Ways
13Decreased 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.
14Partial 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.
15Some 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
16Speculation
- 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.
17Control gt MA
4
3
2
1
0
18MA gt Control
19Methamphetamine
- Cognitive and Memory Effects
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21Defining 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.
22Anhydrous Ammonia Tank Tips Officers to Possible
Meth Lab
5/4/04 Omaha, Neb. A large anhydrous ammonia
tank helped Sarpy County Sheriffs deputies
bust a suspected methamphetamine lab Tuesday.
SOURCE TheOmahaChannel.com
23Brain 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.
24Objective of Study
- Investigate the status of brain serotonin neurons
and their possible relationship with clinical
characteristics in currently abstinent
methamphetamine abusers.
25Results
- 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.
26 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.
27Methamphetamine 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.
28Objective 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.
29Methods
- 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
30Methods 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
31Results
- 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)
32Results Continued
- After controlling for drug trade involvement, MA
use was still significantly predictive of
self-reported violent crime and general
recidivism
33Implications 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
34Neural 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.
35Objective 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
36Methods
- 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
37Methods Continued
- Interview-based symptomatic assessment
- fMRI tasks
- 2-choice prediction task
- Response task
- Outcome measure
- Blood oxygen level-dependent fMRI activation
during tasks
38Methods 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
39Results
- 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
40Results 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
41Results 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
42Implications 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
43Methamphetamine 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
44Methamphetamine 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.
45Methamphetamine 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
46Methamphetamine 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.
47Methamphetamine 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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52Hepatitis C by Route
Plt.05
53High-Risk Sexual Behaviors of Day Laborers
- 2005 study conducted by Charles Drew University
and Bienestar - 450 Latino immigrant day laborers at six sites in
LA where websites reported day laborers could be
hired for sexual activity - 38 reported they had been approached for sex, of
which almost 10 participated in sexual
activities - Approximately three-fourths of those engaging in
sex reported unsafe practices - Day laborers who were more likely to have sex
tended to also experience drug dependency, have
lower education levels, and had been day laborers
for a longer period (five or more years)
54Crystal Methamphetamine Use By Latino Men
- Study conducted by Los Angeles Countys HIV
Epidemiology Program - Over 1500 participants of all race and ethnic
groups - Newly diagnosed HIV-positive Latino men who have
sex with men were almost 9 times more likely to
report crystal use than HIV-negative men - Crystal use was highest among Latinos (20)
- Crystal was associated with a higher prevalence
of unprotected anal sex and with newly diagnosed
HIV - Source Bienestar (March 21, 2006). State and
local Leaders Call for Action on Alarming New
Latino HIV/AIDS Trends. Day Laborers, Crystal
Meth emerge on Latino HIV prevention agenda.
Press release.