Methamphetamine: New Knowledge, Neurobiology and Clinical Issues

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Methamphetamine New Knowledge, Neurobiology and
Clinical Issues

• Richard A. Rawson, Ph.D
• 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
• 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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Types of Stimulant Drugs

• Amphetamine Type Stimulants (ATS)
• Amphetamine Speed
• Dexamphetamine Ice
• Methylphenidate Crank
• Methamphetamine Yaba
• Shabu

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Methamphetamine vs. Cocaine

• Cocaine half-life 1-2 hours
• Methamphetamine half-life 8-12 hours
• Cocaine paranoia 4 -8 hours following drug
  cessation
• Methamphetamine paranoia 7-14 days
• Methamphetamine psychosis - May require
  medication/hospitalization and may not be
  reversible
• Neurotoxicity Appears to be more profound with
  amphetamine-like substances

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EPHEDRINE
H
H
H
C
C
N
CH
CH
OH
3
3
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The Methamphetamine EpidemicAdmissions/100,000
1992-2003
It keeps going up
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National Longitudinal Study of Adolescent Health
(Add Health).

• In 20012002, 2.8 of young adults reported using
  crystal methamphetamine in the past year.
• Blacks 0.6 Northeast 1
• Asians 1.8 Midwest 2.2
• Hispanics 1.8 South 2.8
• Whites 3.3 West 5.3
• Native Americans 12.8

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Admissions for AI/AN Participants in LA County
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Primary Admissions For Female AI/AN Participants
in LA County
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Effects of Drugs on Dopamine Release
Source Shoblock and Sullivan Di Chiara and
Imperato
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Prolonged Drug Use Changes the Brain In
Fundamental and Long-Lasting Ways
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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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Control gt MA
4
3
2
1
0
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MA gt Control
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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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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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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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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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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
• 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

• 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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• 33 year old man, high on methamphetamine admitted
  to emergency room complaining of severe headache
  in Portland Oregon.
• X-ray revealed 12, 2 inch nails (6 on each side)
  in his head, administered with aq nail gun.
• 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
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MA Psychosis Inpatients from 4 Countries
No. of patients having symptoms ()
Psychotic symptom Lifetime Current
Persecutory delusion Auditory hallucinations Strange or unusual beliefs Thought reading Visual hallucinations Delusion of reference Thought insertion or made act Negative psychotic symptoms Disorganized speech Disorganized or catatonic behavior 130 (77.4) 122 (72.6) 98 (58.3) 89 (53.0) 64 (38.1) 64 (38.1) 56 (33.3) 35 (20.8) 75 (44.6) 39 (23.2) 27 (16.1) 38 (22.6) 20 (11.9) 18 (10.7) 36 (21.4) 19 (11.3) 14 (8.3)
Srisurapanont et al., 2003
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MA Psychosis

• 69 physically healthy, incarcerated Japanese
  females with hx MA use
• 22 (31.8) no psychosis
• 47 (68.2) psychosis
• 19 resolved (mean276.2222.8 days)
• 8 persistent (mean17.610.5 months)
• 20 flashbackers (mean215.4208.2 days to initial
  resolution)
• 11 single flashback
• 9 Recurrent flashbacks
  Yui et al., 2001
• Polymorphism in DAT Gene associated with MA
  psychosis in Japanese
• Ujike et al., 2003

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Prenatal Meth. Exposure

• Preliminary findings on infants exposed
  prenatally to methamphetamine (MA) and nonexposed
  infants suggest
• Prenatal exposure to MA is associated with an
  increase in SGA (Small-for-Gestational-Age).
• Neurobehavioral deficits at birth were identified
  in NNNS (Neonatal Intensive Care Unit Network
  Neurobehavioral Scale) neurobehavior, including
  dose response relationships and acoustical
  analysis of the infants cry (Lester et al.,
  2005).

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Adolescent Meth. Abuse Treatment Admissions

• Matrix (Boys) (Girls)
• 2002 16 63
• 2003 25 67
• 2004 22 69
• Phoenix (Boys) (Girls)
• 2002 25 43
• 2003 23 51
• 2004 27 53

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My Sexual Pleasure is Enhanced by the use of
(Rawson et al., 2002)
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My Sexual Performance is Improved by the use of
(Rawson et al., 2002)
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Female Methamphetamine Users Social
Characteristics and Sexual Risk Behavior

• Semple SJ, Grant I, Patterson TLWomen and
  HealthVol. 40(3), 2004

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Introduction

• In San Diego county, a sizable percentage of meth
  users were welfare mothers who lived in
  subsidized housing.
• The majority of women had started using meth
  during their teenage years and had become
  long-term, chronic users.

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Introduction

• Another study reported that womens motivations
  for using meth centered on
• Weight loss
• Enhanced self-confidence
• Increased energy for dealing with demands of
  childrearing and household activities
• Enhanced sexual pleasure
• Other studies have also reported that women, like
  men, experience
• Increased sexual desire and sex drive
• Prolonged sexual activity associated with meth use

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Reasons for Meth Use

• Reasons for using meth were wide-ranging
• To get high (56)
• To get more energy (37)
• To cope with mood (34)
• To lose weight/feel more attractive (29)
• To party (28)
• To escape (27)
• To enhance sexual pleasure (18)

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Sexual Partners of Meth-Using Women

• On average women had 7.8 sexual partners in a
  two-month period (SD10.7, range 1-74).
• 84 had casual partners during the past two
  months.
• 90 of all casual partners were reported to be
  meth users.
• 31 had an anonymous partner in the past two
  months.
• 76 of anonymous sex partners were meth users.
• No spouses or live-in partners were reported to
  be HIV-positive.

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Sexual Risk Behavior

• Participants engaged in an average of 79.2 sex
  acts over a two-month period.
• Most sexual activity was unprotected. The
  average number of unprotected and protected sex
  acts over the two-month period was 70.3 and 8.8,
  respectively.
• In terms of unprotected sex
• 56 of all vaginal sex acts were unprotected
• 83 of all anal sex acts were unprotected
• 98 of all oral sex acts were unprotected

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Social Networks and Meth Use

• The influence of social network on the meth use
  of women represents another understudied area of
  research.
• For the most part, womens sexual partners were
  also meth users. Not surprisingly, the sexual
  enhancement properties of meth make it a drug
  that is used most often with a sexual partner.
• Research on drug-using women has shown an
  association between partners use of drugs and
  womens experience of physical abuse and sexual
  coercion.

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Social Networks and Meth Use

• It is plausible that the drug use behaviors and
  sexual risk practices of some meth-using women
  are influenced by perceived threats from
  drug-using male partners.
• Data also suggests that women limit their meth
  use to private locations, and use primarily with
  sexual partners and friends.
• Thus, unless womens meth use is exposed through
  an event, such as an encounter with law
  enforcement, they are likely to remain hidden for
  long periods of time.

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Treatment
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Treatment Outcomes for AI/AN in LA County 2005

• Drug Category Days of Use
• Admission Discharge
• Alcohol 14.1 5.4
• Cocaine 13.1 3.7
• Heroin 19.1 10.5
• Methamphetamine 12.0 3.0

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Methamphetamine Treatment Statistics

• Drop out rates
• Retention in treatment rates
• Re-incarceration rates
• Other measures of outcome
• All these measures indicate that MA users
  respond in an equivalent manner as individuals
  admitted for other drug abuse problems.
• Analysis of data from 3 other large data sets and
  3 clinical trials data sets suggest treatment
  response (using psychosocial treatments) of MA
  and cocaine users is indistinguishable.

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Why the MA Treatment Does Not Work Perceptions?

• Many of the geographic regions impacted by MA do
  not have extensive treatment systems for severe
  drug dependence.
• Medical and psychiatric aspects of MA dependence
  exceeds program capabilities.
• High rate of use by women, their treatment needs
  and the needs of their children can be daunting.
• Although some traditional elements may be
  appropriate, many staff report feeling unprepared
  to address many of the clinical challenges
  presented by these patients

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Special Treatment Consideration Should Be Made
for the Following Groups of Individuals

• Female MA users (higher rates of depression very
  high rates of previous and present sexual and
  physical abuse responsibilities for children).
• Injection MA users (very high rates of
  psychiatric symptoms severe withdrawal
  syndromes high rates of hepatitis).
• MA users who take MA daily or in very high doses.
• Homeless, chronically mentally ill and/or
  individuals with high levels of psychiatric
  symptoms at admission.
• Individuals under the age of 21.
• Gay men (at very high risk for HIV and
  hepatitis).

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Behavioral/Cognitive Behavioral Treatments

• Cognitive/Behavioral Therapy-CBT
• Motivational Interviewing-MI
• Contingency Management-CM
• 12-Step Facilitation Therapy
• Community Reinforcement Approach-CRA
• Matrix Model of Outpatient Treatment

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Thank yourrawson_at_mednet.ucla.eduwww.uclaisap.org
www.methamphetamine.org