Methamphetamine: New Knowledge, Neurobiology and Clinical ...

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@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)

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.

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’

Types of Stimulant Drugs
Amphetamine Type Stimulants (ATS)
• Amphetamine
• Dexamphetamine
• Methylphenidate
• Methamphetamine
“Speed”
“Ice”
“Crank”
“Yaba”
“Shabu”

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

Scope of the Methamphetamine
Problem Worldwide
• According to surveys and estimates by WHO
and UNODC, methamphetamine is the most
widely used illicit drug in the world except for
cannabis.
• World wide it is estimated there are over 26
million regular users of
amphetamine/methamphetamine, as
compared to approximately 16 million heroin
users and 14 million cocaine users

EPHEDRINE
H
H
H
C
C
N
OH
CH3
CH3
METHAMPHETAMINE
H
H
H
C
C
N
H
CH3
CH3

The Methamphetamine Epidemic:
Admissions/100,000: 1992-2003
350
It keeps going up
300
250
200
150
100
50
California
Hawaii
Iowa
Oregon
Washington
0
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003

Figure 2. Methamphetamine/Amphetamine Treatment
Admissions, by Route of Administration: 1992-2002
Source: 2002 SAMHSA Treatment Episode Data Set (TEDS).

A Major Reason People
Take a Drug is they Like
What It Does to Their Brains

Natural Rewards Elevate Dopamine
% of Basal DA Output
200
150
100
50
0
Empty
FOOD
Box Feeding
NAc shell
0 60 120 180
Time (min)
Source: Di Chiara et al.
Levels
DA Concentration (% Baseline)
200
150
100
ScrScr
BasFemale 1 Present
SEX
Scr
Scr
Female 2 Present
Sample
11 22 33 44 55 66 77 88 99 10 11 12 13 14 15 16 17
Number
Mounts
Intromissions
Ejaculations
Source: Fiorino and Phillips
15
10
5
0
Copulation Frequency

% Basal Release
1500
1000
500
Effects of Drugs on Dopamine Release
0
Accumbens
METHAMPHETAMINE
0 1 2 3hr
Time After Methamphetamine
% of Basal Release
400
300
200
100
00
Accumbens
COCAINE
Time After Cocaine
DA
DOPAC
HVA
% of Basal Release
250
200
150
100
00
00 11 22 3 hr
Time After Nicotine
NICOTINE
Accumbens
Caudate
% of Basal Release
250
200
150
100
Accumbens
Source: Shoblock and Sullivan; Di Chiara and Imperato
0
ETHANOL
Dose (g/kg ip)
0.25
0.5
1
2.5
0 1 2 3 4hr
Time After Ethanol

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.

Prolonged Drug Use Changes
the Brain In Fundamental
and Long-Lasting Lasting Ways

Decreased dopamine transporter
binding in METH users
resembles that in
Parkinson’s Disease patients
Control Meth PD
Source: McCann U.D.. et al.,Journal of Neuroscience, 18, pp. 8417-8422, October 15, 1998.

Partial Recovery of Brain Dopamine
Transporters in Methamphetamine
(METH)
Abuser After Protracted Abstinence
3
0
Normal Control
METH Abuser
(1 month detox)
METH Abuser
(24 months detox)
ml/gm
Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001.

Because…
Brains
Their have been
Re-Wired
by Drug Use

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.

Control
> MA
4
3
2
1
0

MA >
Control
5
4
3
2
1
0

Methamphetamine
Cognitive and Memory Effects

Frequency of Impairment by Neuropsychological Domain
60
Controls
MA Users
60
50
50
40
40
% Impaired
30
20
30
20
10
10
0
Attention/
Psychomotor
Speed
Learning
and
Memory
Working
Memory
Fluency
Executive Systems Function
Inhibition
0

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.

Elements of Assessment
• What does a neuropsychological assessment
provide
– Objective assessment of cognitive function
• Intellectual function
• Attention/concentration
• Language
• Visuospatial functioning
• Memory
• Executive systems functioning
• Mood/Personality

Defining Domains:
Attention/Concentration
Defined: Ability to focus and/or track information over
brief or lengthy periods of time
Examples: Digit Span
Trailmaking Tests
Continuous Performance Test (CPT)
Relevance: attending to conversation, tracking
information in a relapse prevention class

Defining Domains:
Memory – Verbal Learning
Defined: Ability to acquire, store, and retrieve verbal
information for more than a few minutes
Example:
California Verbal
Learning Test
drill paprika chisel slacks
plums tangerines wrench grapes
pliers apricots nutmeg jacket
vest sweater parsley chives
Relevance: Remembering Rx, turning off the stove,
recalling an appointment, rehabilitation info

Defining Domains:
Executive Systems Functioning
• a.k.a. frontal lobe functioning.
• Deficits on executive tasks associated with:
– Poor judgment
– Lack of insight
– Poor strategy formation
– Impulsivity
– Reduced capacity to determine consequences
of actions

Defining Domains –
Motor/Psychomotor Speed
Simple Reaction Time Test
- Participants presented with the following
letters: A,a,G,g,T,t,H,h
- 30 trials
- Instruction: Press red button on control
pad as quickly as possible when letters
appear

Executive Systems Functioning
– Working Memory
Defined: Ability to hold information “on line” in a
temporary store and/or to manipulate the information
Example:
Letter-Number
Sequencing
Test
K3B4 ----
A1G8C
-----
R8C3G5 ------
Relevance: Switching between tasks, decisionmaking,
impulse control, strategy formation

Executive Systems Functioning
– Working Memory
Choice Reaction Time Test
- Stimuli presented: A,a,G,g,T,t,H,h (30 trials)
- Instructions:
- Press red button when A,a,G,g appear
- Press blue button when T,t,H,h appear
- Variables of interest
- Reaction time
- Accuracy of responses

Executive Systems Functioning
– Working Memory
1-back Test
- Stimuli presented: A,a,G,g,T,t,H,h (20 trials)
- Instructions:
- Press red button if previous letter matches current
letter
- Press blue button if previous letter does not match
current letter
- Example: If A – a appears, press Red button
: If A – T appears, press Blue button

Executive Systems Functioning –
Working Memory
2-back Test
- Stimuli presented: A,a,G,g,T,t,H,h (20 trials)
- Instructions:
- Press red button if letter from 2 trials back
matches current letter
- Press blue button if letter from 2 trials back does
not match current letter
- Example: If A – g – a appears, press Red
button
: If A – T – H appears, press Blue
button

Neurocognitive Consequences of
Methamphetamine Dependence
Timeframe
Number of
Studies
Pre-1990 1
1990 – 2000 1
2000 – present 9

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. 2006;63:90-100.

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. 2006;21:435-445.

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)

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

Neural Activation Patterns of
Methamphetamine-Dependent
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. 2005;62:761-768.
*

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

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

Methamphetamine Abuse, HIV Infection
Causes Changes in Brain Structure
Jernigan,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

Methamphetamine Abuse, HIV Infection
Causes Changes in Brain Structure
Jernigan,T, et al American Jnl of Psychiatry Aug 2005
• Methamphetamine abuse is associated with changes in the the
brain’s parietal cortex (which helps people to understand and
pay attention to what’s 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

Methamphetamine Abuse, HIV Infection
Causes Changes in Brain Structure
Jernigan,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 HIVpositive,
decreased volumes are correlated with
increased cognitive impairment in one brain region,
the hippocampus.

Structural and Metabolic Brain
Changes in the Striatum Associated
with Methamphetamine Abuse*
*Chang L, Alicata D, Ernst T, et al. Structural and
metabolic brain changes in the striatum associated with
methamphetamine abuse. Addiction. 2007;102 (Suppl.
1):16-32.

– 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

Methamphetamine
Psychiatric Consequences
• Paranoid reactions
• Long term memory loss
• Depressive reactions
• Hallucinations
• Psychotic reactions
• Panic disorders
• Rapid addiction

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

MA Psychosis
• 69 physically healthy, incarcerated Japanese
females with hx MA use
– 22 (31.8%) no psychosis
– 47 (68.2%) psychosis
• 19 resolved (mean=276.2±222.8 days)
• 8 persistent (mean=17.6±10.5 months)
• 20 flashbackers (mean=215.4±208.2 days to
initial resolution)
– 11 single flashback
– 9 Recurrent flashbacks Yui et al.,
2001
• Polymorphism in DAT Gene associated with MA
psychosis in Japanese
2003
Ujike et al.,

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 infant’s cry (Lester et al., 2005).

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%

My Sexual Pleasure is
Enhanced by the use of:
Percent Responding
"Yes"
100
90
80
70
60
50
40
30
20
10
0
16.0 18.2
38.2
24.4
44.7
11.1
73.5
66.7
opiates alcohol cocaine meth
male
female
Primary Drug of Abuse
(Rawson et al., 2002)

My Sexual Performance is
Improved by the use of:
Percent Responding
"Yes"
100
90
80
70
60
50
40
30
20
10
0
19.1
15.9
32.4
24.4
18.4
11.1
58.8 61.1
opiates alcohol cocaine meth
male
female
Primary Drug of Abuse
(Rawson et al., 2002)

Female Methamphetamine Users:
Social Characteristics and Sexual
Risk Behavior
Semple SJ, Grant I, Patterson TL
Women and Health
Vol. 40(3), 2004

Introduction
• Research on female meth users has not
kept pace with the increased number of
women who use this drug.
• To date, the majority of meth studies have
focused on gay and bisexual men; within
this population, meth is reputed to be a
party drug that enhances sexual pleasure.

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.

Introduction
• Another study reported that women’s 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

Demographics (n=98)
• Ethnicity
– 44% Caucasian
– 33% African American
– 16% Latina
– 2% Native American
– 5% Other
• Education
– 96% had less than a college education
• Marital Status
– 54% had never been married
• Employment
– 77% were unemployed

Demographics
• Psychiatric Health Status
– 38% reported having a psychiatric diagnosis
• 53% depression
• 17% bipolar
• 14% schizophrenia
• Patterns of Use
– 83% smoked
• Context of Meth Use
– Meth was used primarily with either a friend
(95%) or a sexual partner (84%).
• Social and Legal Problems
– 36% reported having a felony conviction.

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%)

Sexual Partners of Meth-Using
Women
• On average women had 7.8 sexual partners in a
two-month period (SD=10.7, 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.

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

• The high risk of HIV/STD transmission associated
with unprotected anal and vaginal intercourse
suggests the need for intervention programs that
educate meth-using women about the risk
associated with these sexual activities, and
provide them with the skills needed to convince
their sexual partners to use condoms for these
high risk activities.
Sexual Risk Behavior
• In the present study, female users of meth
reported high levels of sexual risk behavior that
place them at risk for contracting HIV and other
STS’s.

• Because the positive sexual consequences
associated with meth use are likely to be highly
reinforcing, the sexual risks behaviors of methusing
women are not likely to be changed easily.
Sexual Risk Behavior
• These data also revealed that women’s
subjective sexual pleasure was tied to their use of
meth.
• Although sexual pleasure was not the primary
stated motivation behind women’s meth use,
intensity of meth use was positively correlated
with women’s subjective positive experience of
sex.

Disadvantages
• The women in this study were also characterized
by high levels of personal and social
disadvantage.
– Had modest levels of education
– Unstable living arrangements
– Low income
– Low rates of employment
– High rates of psychiatric diagnoses
• As demonstrated by in previous research, women
who experience these forms of disadvantage may
be more likely to engage in both drug use and
HIV risk behaviors.

• For example, programs could be designed
to:
– Help women enhance their education
– Improve their job skills
– Find suitable and stable housing for
themselves and their children.
Interventions
• Approaches to addressing issues of social
disadvantage include personal
empowerment and the enhancement of
social functioning through life skills training
and effective coping skills.

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, women’s 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
women’s experience of physical abuse and sexual
coercion.

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 drugusing
male partners.
• Data also suggests that women limit their meth
use to private locations, and use primarily with
sexual partners and friends.
• Thus, unless women’s 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.

Study Limitations
• Study was conducted with a relatively small sample of
women.
• Participants were recruited into the study on the basis of
their sexual risk behavior. Thus, the rates of unprotected
sex in this sample may be higher than those in the
broader population of female meth users.
• Accordingly, the women in this study should not be
considered representative of all female meth users.
• Another limitation stems from the use of self-report data,
such as inaccurate recall or response bias as a result of
the highly sensitive nature of the sex and drug questions.

Behavior Symptom Inventory
(BSI) Scores at Baseline
1.60
1.40
all significant at p< .001
1.20
Female
Male
1.00
0.80
0.60
0.40
0.20
0.00
Somatization
Obsessive-Compulsive
Interpersonal Sensitivity
Depression
Anxiety
Hostility
Phobic Anxiety
Paranoid Ideation
Psychoticism
Mean BSI Score

BSI Psychiatric
Symptoms by Route
30
Positive Symptom Total (PST)
25
20
15
10
5
0
IN SM IDU
BL PST
TX-End PST
6-Mo PST
12-Mo PST
P

% Prevelance
Hepatitis C by Route
50
45
40
35
30
25
20
15
10
5
0
12
7
44
15
IN (n=99
SM (N=478)
IDU (n=146)
Total (n=723)
P

Treatment

Is Treatment for
Methamphetamine Effective
• A pervasive rumor has surfaced in
many geographic areas with
elevated MA problems:
– MA users are virtually untreatable with
negligible recovery rates.
– Rates from 5% to less than 1% have
been quoted in newspaper articles and
reported in conferences.

Meth. Treatment Statistics
During the 2002-2003 fiscal year:
• 35,947 individuals were admitted to treatment
in California under the Substance Abuse and
Crime Prevention Act funding.
• Of this group, 53% reported MA as their
primary drug problem

Statistics
Analysis of:
• 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.

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

Bupropion: An Efficacious
Pharmacotherapy
• Newton et al., (2005):
– Bupropion reduces craving and
reinforcing effects of meth
• Elkashef (recently completed):
– Bupropion reduces meth use in an
outpatient trial, with particularly strong
effect with less severe users.

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).

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

Cognitive Behavioral Therapy
• Based upon Social Learning Theory
(Bandura and others)
• Also referred to as Relapse
Prevention Therapy
• Applied to treatment of alcoholism,
cocaine dependence, nicotine
dependence and marijuana abuse.

Cognitive Behavioral Therapy
• Key Concepts
– Encouraging and reinforcing behavior change
– Recognizing and avoiding high risk settings
– Behavioral planning (scheduling)
– Coping skills
– Conditioned “triggers”
– Understanding and dealing with craving
– Abstinence violation effect
– Understanding basic psychopharmacology
principles
– Self-efficacy

Motivational Interviewing
• Based upon Prochaska and DiClemente
Stages of Change Theoretical Model
• Also referred to as Motivational
Enhancement Therapy
• Applied with many substances, data
primarily with alcoholics
• Major Publications/Studies: Miller and
Rollnick, 1991; Project MATCH

Motivational Interviewing
• Basic Assumptions
– People change their thinking and behavior
according to a series of stages
– Individuals may enter treatment at different
“stages of change”
– It is possible to influence the natural change
process with MI techniques
– MI can be used to engage individuals in longer
term treatment and to promote specific behavior
changes
– Confrontation of “denial” can be counterproductive
and or harmful to some individuals

Motivational Interviewing
• Key Concepts
– Empathy and therapeutic alliance
– Give feedback and reframe
– Create dissonance
– Focus of discrepancy of expected and actual
– Reinforce change
– Roll with resistance

Community Reinforcement
Approach
• Basic assumptions
– Drug and alcohol use are positively reinforced
behaviors. They can be reduced/eliminated by proper
application of behavioral techniques.
– To successfully build an effective intervention, some
techniques should focus on reducing drug and alcohol
use and others should focus on acquisition of new
incompatible behaviors

Community Reinforcement
Approach
• Key concepts
– Behavioral analysis and teach conditioning
information.
– Positive reinforcement with vouchers for drug free
urine samples
– Behavioral marriage counseling
– Shape and reinforce new behavioral repertoire.
– Coping skill/Drug refusal skill training
– Vocational Counseling
– Frequent urine testing

Contingency Management
• A technique employing the systematic
delivery of positive reinforcement for desired
behaviors. In the treatment of
methamphetamine dependence, vouchers or
prizes can be “earned” for submission of
methamphetamine-free urine samples.

Contingency Management
• Basic Assumptions
– Drug and alcohol use behavior can be controlled
using operant reinforcement procedures
– Vouchers can be used as proxy’s for money or
goods
– Vouchers should be redeemed for items
incompatible with drug use
– Escalating the value of the voucher for
consecutive weeks of abstinence promotes better
performance
– Counseling/therapy may or may not be required in
conjunction with CM procedure

Contingency Management
• Key concepts
– Behavior to be modified must be objectively
measured
– Behavior to be modified (e.g. urine test results) must
be monitored frequently
– Reinforcement must be immediate
– Penalties for unsuccessful behavior (e.g. positive Ua)
can reduce voucher amount
– Vouchers may be applied to a wide range of prosocial
alternative behaviors

Contingency Management for treatment
of methamphetamine dependence
Design: RTC
• Method: 113 patients diagnosed with methamphetamine abuse
or dependence were randomly assigned to receive either
treatment as usual (TAU) or TAU plus contingency
management.
• Results indicate that both groups were retained in treatment for
equivalent times but those in the combined group accrued more
abstinence and were abstinent for a longer period of time.
These results suggest that contingency management has
promise as a component in methamphetamine use disorder
treatment strategies.
• Contingency Management for the Treatment of
Methamphetamine Use Disorders. Roll, JM et al, Archives of
General Psychiatry, (In Press)

Cognitive Behavioral Therapy and
Contingency Management for Stimulant
Dependence
• Design Randomized clinical trial.
• Participants Stimulant-dependent individuals (n = 171).
• Intervention CM, CBT, or combined CM and CBT, 16-week treatment
conditions. CM condition participants received vouchers for stimulant-free
urine samples. CBT condition participants attended three 90-minute group
sessions each week. CM procedures produced better retention and lower
rates of stimulant use during the study period.
• Results Self-reported stimulant use was reduced from baseline levels at
all follow-up points for all groups and urinalysis data did not differ
between groups at follow-up. While CM produced robust evidence of
efficacy during treatment application, CBT produced comparable longerterm
outcomes. There was no evidence of an additive effect when the two
treatments were combined. The response of cocaine and
methamphetamine users appeared comparable.
• Conclusions: This study suggests that CM is an efficacious treatment for
reducing stimulant use and is superior during treatment to a CBT
approach. CM is useful in engaging substance abusers, retaining them in
treatment, and helping them achieve abstinence from stimulant use. CBT
also reduces drug use from baseline levels and produces comparable
outcomes on all measures at follow-up.
• Rawson, RA et al. Addiction, Jan 2006

Contingency Management: A
Meta-analysis
• A recent meta-analysis reports that CM
results in a successful treatment
episode 61% of the time while other
treatments with which it has been
compared result in a successful
treatment episode 39% of the time
(Prendergast, Podus, Finney, Greenwell &
Roll, submitted)

12-Step Facilitation Therapy
• “The therapist acts as a resource and
advocate of the 12-Step approach to
recovery”:
– Explains the AA view of alcoholism, analyzes
slips and resistance to AA in terms of disease
of alcoholism and denial.
– Introduces AA-Steps and concepts by applying
these to patient history
– Advocates Reliance on fellowship of AA and its
role in ongoing recovery
– 12 sessions 1:1

12-Step Facilitation Therapy
• 12-step Facilitation Manual can be
downloaded from the NIAAA web
site
• Book: 12-Step Facilitation
Handbook, by Nowitzki and Baker

Matrix Model in Treatment of
Methamphetamine Dependence
• Design: The study was conducted as an eight-site randomized clinical trial.
• Method: 978 treatment-seeking, MA-dependent persons were randomly
assigned to receive either TAU at each site, or a manualized 16-week treatment
(Matrix Model) for their MA dependence.
• Results: Analyses of study data indicate that in the overall sample, and in the
majority of sites, those who were assigned to Matrix treatment attended more
clinical sessions, stayed in treatment longer, provided more MA-free urine
samples during the treatment period, and had longer periods of MA abstinence
than those assigned to receive TAU. Measures of drug use and functioning
collected at treatment discharge and 6 months post-admission indicate
significant improvement by participants in all sites and conditions when
compared to baseline levels, but the superiority of the Matrix approach did not
persist at these two time points.
• Conclusions: Study results demonstrate a significant initial step in documenting
the efficacy of the Matrix approach. Although the superiority of the Matrix
approach over TAU was not maintained at the posttreatment time points, the intreatment
benefit is an important demonstration of empirical support for this
psychosocial treatment approach.
• Rawson, R et al Addiction vol 99, 2004

12
10
8
6
4
2
0
Mean Number of Weeks in
Treatment
Matrix
TAU
CostaMesa
Concord
Billings
SanDiego
Honolulu
Hayward
SanMateoPyra
SanMateoODAS
Site
Mean Number of Visits

Mean Number of UA’s That Were
MA-free During Treatment
10
8
6
4
2
0
Billings
CostaMesa
Concord
Honolulu
Hayward
SanMateoODAS
SanDiego
SanMateoPyra
Mean number of MA-free UA's
Site
Matrix
TAU

Urinalysis Results
• Results of Ua Tests at Discharge, 6
months and 12 Months post admission**
Matrix Group TAU Group
D/C: 66% MA-free 65% MA-free
6 Ms: 69% MA-free 67% MA-free
12 Ms: 59% MA-free 55% MA-free
**Over 80% follow up rate in both groups at all points

Drug Courts and
Methamphetamine Users
• Recently the marketing material for an experimental
methamphetamine procedure costing $15,000
(Prometa/Hythiam) has reported what they considered
extraordinarily high rates (98%+) of drug-free urine specimens in
2 pilot trials in drug court programs in Michigan and Washington
State.
• An examination was conducted of the urinalysis data from 2
California drug court programs using more traditional
treatments.
– In one program treating meth users in Rancho
Cucamonga Calif, over a 6 year period and over 40,000
urine samples, the rate of drug free samples was 96.5%
– In a second drug court program in Hayward, California,
over a 2 year period, with exclusively a meth population,
the rate of drug free urine samples was 97.2%.

Methamphetamine Abuse:
Treatment as Prevention
Richard A. Rawson, Cathy J. Reback,
Steven Shoptaw
UCLA Integrated Substance Abuse Programs

Overview
• Substance abuse concomitant with risky
sex for MSM (Stall & Wiley, 1988)
• Different drugs have differing
prevalence of HIV among MSM
• Drug abuse treatments dramatically
reduce methamphetamine use and
high-risk sex
– Reductions are sustained!
• Policy implications

Summary
• Use of psychostimulants is a significant public
health problem in the US.
• In California (and worldwide),
methamphetamine is and has been for some
time the most widely used illicit drug other
than cannabis.
• Cocaine and methamphetamine produce
many similar acute and chronic effects.
• Psychosocial treatments currently have
greatest empirical support, although research
on pharmacotherpies is promising.

THE MATRIX MODEL
OF INTENSIVE OUTPATIENT
TREATMENT
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@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)

Outpatient Treatment Recommendations:
Empirically-Supported
• Multiple Weekly Sessions for at least 90-
120 days
• 3 visits per week minimum,
recommended.
• Family involvement important
• 12-step facilitation and participation
valuable
• Urinalysis and breath alcohol testing
needed
• Medications of value with some patients

Treatment Components of the
Matrix Model
Individual Sessions
Early Recovery Groups
Relapse Prevention
Groups
Family Education Group
12-Step Meetings
Social Support Groups
Relapse Analysis
Urine Testing
MATRIX

The Matrix Model:
Organizing Principles
• Program components based upon scientific literature
on promotion of behavior change.
• Program elements and schedule selected based on
empirical support in literature and application.
• Program focus is on current behavior change in the
present and not underlying “causes” or presumed
“psychopathology”.
• Matrix “treatment” is a process of “coaching”, educating,
supporting and reinforcing positive behavior change.

The Matrix Model:
Organizing Principles
Extensive Use of Positive Reinforcement Techniques
• Non-judgmental, non-confrontational relationship
between therapist and patient creates positive
bond which promotes program participation.
• Therapist as a “coach”
• Positive reinforcement used extensively to promote
treatment engagement and retention.
• Verbal praise, group support and encouragement
other incentives and reinforcers.

The Matrix Model:
Organizing Principles
Accurate, understandable, scientific information used to
educate patient and family member
• Effects of drugs and alcohol
• Addiction as a “brain disease”
• Critical issues in “recovering” from addiction
• Meth and sex
• Conditioned cues and craving

The Matrix Model:
Organizing Principles
Behavioral strategies used to promote cessation of drug
use and behavior change
• Scheduling time to create “structure”
• Educating and reinforcing abstinence from all
drugs and alcohol
• Promoting and reinforcing participation in nondrug-related
activities

The Matrix Model:
Organizing Principles
Cognitive-Behavioral strategies used to promote
cessation of drug use and prevention of relapse.
• Teaching the avoidance of “high risk” situations
• Educating about “triggers” and “craving”
• Training in “thought stopping” technique
• Teaching about the “abstinence violation effect”
• Reinforcing application of principles with verbal
praise by therapist and peers

The Matrix Model:
Organizing Principles
• Involvement of family members to support recovery.
• Encourage participation in self-help meetings
• Urine testing to monitor drug use and reinforce
abstinence
• Social support activities to maintain abstinence

Outpatient Treatment Strategies
Create explicit structure and expectations
Monday Wednesday Friday
Early Recovery
Skills
Family/education
Early Recovery
Skills
Weeks1-4
Relapse
Prevention
Weeks 1-12
Social Support
Weeks1-4
Relapse
Prevention
Weeks 13-16
Weeks 1-16
Weeks 1-16
*** Weekly urine testing, breath alcohol testing and individual sessions

MATRIX MODEL TREATMENT
INFORMATION

MATRIX MODEL TREATMENT
Information - What
- Substance abuse - Sex and recovery
and the brain
- Relapse prevention issues
- Triggers and cravings - Emotional readjustment
- Stages of recovery - Medical effects
- Relationships and recovery - Alcohol/marijuana

MATRIX MODEL TREATMENT
Information - Why
•Reduces confusion and guilt
•Explains addict behavior
•Gives a roadmap for recovery
•Clarifies alcohol/marijuana issue
•Aids acceptance of addiction
•Gives hope/realistic perspective for family

Trigger
Definition
A trigger is a stimulus which has been repeatedly
associated with the preparation for,
anticipation of or the use of drugs and/or alcohol.
These stimuli include people, things, places, times
of day, and emotional states.

Triggers and Cravings
(1849-1936)

Triggers and Cravings
Pavlov’s Dog

Triggers and Cravings
Human Brain

Cognitive Process During Addiction
Introductory Phase
Relief From
Depression
Anxiety
Loneliness AOD
Insomnia
Euphoria
Increased Status
Increased Energy
Increased Sexual/Social Confidence
Increased Work Output
Increased Thinking Ability
May Be Illegal
May Be Expensive
Hangover/Feeling Ill
May Miss Work

Conditioning Process During Addiction
Introductory Phase
Strength of Conditioned Connection
Triggers
•Parties
•Special Occasions
Mild
Responses
•Pleasant Thoughts
about AOD
•No Physiological
Response
•Infrequent Use

Development of Obsessive Thinking
Introductory Phase
Food
Sports School
TV
Girlfriend
Hobbies
Job
Family AOD
Parties
Exercise

Development of Craving Response
Introductory Phase
Entering
Using Site
Use of AODs
AOD Effects
Heart/Pulse Rate
Respiration
Adrenaline
Energy
Taste

Cognitive Process During Addiction
Maintenance Phase
Depression Relief
Confidence Boost
Boredom Relief
Sexual Enhancement
Social Lubricant
Vocational Disruption
Relationship Concerns
Financial Problems
Beginnings of Physiological
Dependence

Conditioning Process During
Addiction
Maintenance Phase
Strength of Conditioned Connection
Triggers
•Parties
•Friday Nights
•Friends
•Concerts
•Alcohol
•“Good Times”
•Sexual Situations
Moderate
Responses
•Thoughts of AOD
•Eager Anticipation
of AOD Use
•Mild Physiological
Arousal
•Cravings Occur as
Use Approaches
•Occasional Use

Development of Obsessive Thinking
Maintenance Phase
AOD
Food
TV
School
Girlfriend
Hobbies
Job
Family AOD
Exercise
Parties

Development of Craving Response
Maintenance Phase
Entering
Using Site
Physiological
Response
Use of
AODs
AOD
Effects
Heart
Heart
Breathing
Adrenaline
Blood
Effects
Pressure
Energy
Taste
Energy

Cognitive Process During Addiction
Disenchantment Phase
Social Currency
Occasional Euphoria
Relief From Lethargy
Relief From Stress
Nose Bleeds
Infections
Relationship Disruption
Family Distress
Impending Job Loss

Conditioning Process During Addiction
Disenchantment Phase
Strength of Conditioned Connection
Triggers
•Weekends
•All Friends
•Stress
•Boredom
•Anxiety
•After Work
•Loneliness
STRONG
Responses
•Continual Thoughts
of AOD
•Strong
Physiological
Arousal
•Psychological
Dependency
•Strong Cravings
•Frequent Use

Development of Obsessive Thinking
Disenchantment Phase
Food
AOD
TV
Girlfriend
Job
Family
AOD
AOD
AOD
AOD
Parties
AOD

Development of Craving Response
Thinking of
Using
Disenchantment Phase
Mild Physiological
Response
Heart Rate
Breathing Rate
Energy
Adrenaline Effects
Entering Using
Site
Powerful Physiological
Response
Heart Rate
Breathing Rate
Energy
Adrenaline Effects
Use of AODs
AOD Effects
Heart
Blood Pressure
Energy

Cognitive Process During Addiction
Relief From
Fatigue
Relief From Stress
Relief From
Depression
Disaster Phase
Weight Loss
Paranoia
Loss of Family
Seizures
Severe Depression
Unemployment
Bankruptcy

Conditioning Process During Addiction
Disaster Phase
Strength of Conditioned Connection
Triggers
•Any Emotion
•Day
•Night
•Work
•Non-Work
OVERPOWERING
Responses
•Obsessive Thoughts
About AOD
•Powerful
Autonomic
Response
•Powerful
Physiological
Dependence
•Automatic Use

Development of Obsessive Thinking
Disaster Phase
AOD
AOD
AOD
AOD
AOD
AOD
AOD
AOD
AOD
AOD
AOD

Development of Craving Response
Disaster Phase
Thoughts of AOD
Using Place
Powerful Physiological
Response
Heart Rate
Breathing Rate
Energy
Adrenaline
Effects

Triggers & Cravings
Trigger Thought Craving Use

Triggers & Cravings
Trigger
Thought
Craving
Use

MATRIX MODEL TREATMENT
Structure - Ways to Create
•Time scheduling
•Attending 12-step meetings
•Going to treatment
•Exercising
•Attending school
•Going to work
•Performing athletic activities
•Attending church

MATRIX MODEL TREATMENT
Structure - Pitfalls
•Scheduling unrealistically
•Neglecting recreation
•Being perfectionistic
•Therapist imposing schedule
•Spouse/parent imposing schedule

Outpatient Recovery Issues
TRIGGERS

MATRIX MODEL TREATMENT
Triggers - People
•Drug-using friends/dealer
•Voices of drug friends/dealer
•Absence of significant other
•Sexual partners in illicit sex
•Groups discussing drug use

MATRIX MODEL TREATMENT
Triggers - Places
•Drug dealer’s home
•Bars and clubs
•Drug use neighborhoods
•Freeway offramps
•Worksite
•Street corners

MATRIX MODEL TREATMENT
Triggers - Things
•Paraphernalia
•Sexually explicit magazines/movies
•Money/bank machines
•Music
•Movies/TV shows about alcohol and other drugs
•Secondary alcohol or other drug use

MATRIX MODEL TREATMENT
Triggers - Times
•Periods of idle time
•Periods of extended stress
•After work
•Payday/AFDC payment day
•Holidays
•Friday/Saturday night
•Birthdays/Anniversaries

MATRIX MODEL TREATMENT
Triggers - Emotional States
• Anxiety
• Anger
• Frustration
• Sexual arousal
• Fatigue
• Boredom
• Adrenalized states
• Sexual deprivation
• Gradually building emotional states with no
expected relief

MATRIX MODEL TREATMENT
Key Concept: Thought Stopping
Thought Stopping
Trigger
Thought
Continued Thoughts
Cravings
•Prevents the thought from developing into an
overpowering craving
Use
•Requires practice

Stages of Recovery - Stimulants
THE WALL
PROBLEMS
ENCOUNTERED
•Inertia
DAY
DAY
45
120
•Depression
•Return to Cocaine Stimuli
•Relapse Justification
•Cognitive Rehearsal
•Treatment Termination
• Alcohol Use
• Relapse

“The Wall”
One Patient’s Account
Physical Symptoms:
“Lack of energy was almost constant even if I slept for
hours. Lack of memory, inability to concentrate and a grey
film over my vision clouded my world. My sleep became
mixed-up. I would be dead tired during the day and
experience insomnia at night.”

“The Wall”
One Patient’s Account
Apathy:
“Throughout The Wall I didn’t care about anything or
anybody. Including myself. Nothing seemed important,
nothing felt good. Boredom and hopelessness were constant
companions. I felt the whole thing would never end.”

“The Wall”
One Patient’s Account
Loneliness and Isolation:
“More than anything I felt alone. I felt like I was the only
person in the world who knew how I felt. Even my therapist
and my C.A group didn’t understand. I went to meetings
and often still felt alone.”

MATRIX MODEL TREATMENT
Relapse Factors - The Wall Stage
- Increased emotions - Dissolution of structure
- Interpersonal conflict - Behavioral drift
- Relapse justification - Secondary alcohol or
- Anhedonia/loss of other drug use
motivation
- Resistance to exercise
- Insomnia/low energy/fatigue - Paranoia

Outpatient Recovery Issues
RELAPSE FACTORS

Outpatient Recovery Issues
Relapse Factors - Sexual
Behavior
•Concern about sexual dysfunction
•Concern over sexual abstinence
•Concern over sexual disinterest
•Loss of intensity of sexual enjoyment
•Shame/guilt about sexual behavior
•Sexual arousal producing craving
•Sexual behavior and intimacy
•Sobriety and monogamy

Outpatient Recovery Issues
Relapse Factors - Alcohol/Marijuana
•Cortical disinhibition
•Stimulant craving induction
•Pharmacologic coping method
•12-Step philosophy conflict
•Abstinence violation effect
•Marijuana amotivational syndrome
•Interferes with new behaviors

Outpatient Recovery Issues
Relapse Factors - Time Periods
•Unstructured time
•Transition periods
•Protracted abstinence
•Holidays
•Chronic stress, fatigue, or boredom
•Anniversary dates
•Periods of emotional turmoil

Outpatient Recovery Issues
Relapse Factors - Addict Behavior
•Lying/stealing
•Having extramarital/illicit sex
•Using secondary substances
•Returning to bars/drug friends
•Being unreliable/irresponsible
•Behaving compulsively/impulsively
•Isolating

Outpatient Recovery Issues
Relapse Factors - Addict Thinking
•Paranoia
•Relapse justifications:
•“I’m not an addict anymore”
•“I’m testing myself”
•“I need to work”
•“Other drugs/alcohol are OK”
•“Catastrophic events”
•“Negative emotional states”

Outpatient Recovery Issues
Relapse Factors - Relationships
•Addict must deal with family’s:
•Extreme anger and blaming
•Unwillingness to change/trust
•Hypervigilance - excessive monitoring
•Sexual anxieties
•Adjustment to non-victim status
•Conflict with recovery activities

Roadmap for Recovery
When To Use Thought Stopping
River of Relapse
(Relapse Drift)

Thank you
rrawson@mednet.ucla.edu
www.uclaisap.org
www.methamphetamine.org