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Methamphetamine
Senior Residents Lecture
Your name
Title
Institution
Objective
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Prevalence data
Diagnostic criteria
Review of methods of abuse
Review of methods of action
Review of effects of use
Review of symptoms of intoxication
Review of symptoms of withdrawal
Review of treatment principles
Review of pharmacological treatments
Review of non-pharmacological treatments
Practical pearls
Discussion of clinical vignettes
Treatment outcomes data
Co-morbidity
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Prevalence:
The number of people that have a
condition at any given time.
Lifetime Prevalence:
The number of people that will have
the condition at some point in their
life.
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Prevalence
• Lifetime prevalence of approximately 5.8%
• 14 million Americans age >12 have used
methamphetamine
(http://www.drugabuse.gov/infofacts/methamphetamine.html)
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Methamphetamine:
Epidemiology
Percentage of Individuals Reporting
Methamphetamine Use by Age Group, 2006
Age Group
12–17
18–25
26–34
> 35
> 12 (Total)
Lifetime
Annual
Last 30 days
1.3%
6.4%
8.5%
0.7%
0.3%
1.7%
1.3%
0.5%
0.8%
0.2%
0.4%
5.7%
5.8%
0.2%
0.3%
Substance Abuse and Mental Health Services Administration survey data
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Past Year Methamphetamine Use
among Persons Aged 12+, by Age:
2002-2006
Percent Using in Past Year
2002
2003
2004
2005
2006
3
2.0
2
1.9 1.9
1.8
1.7
1.0+
1
0.7 0.7
0.8
0.7
0.8
0.7 0.7 0.7 0.7
0.5 0.5
0.6
0.5
0.6
0
12 or Older
12 to 17
18 to 25
26 or Older
Age in Years
Note: Estimates are based on new 2006 questions. 2002-2005 estimates are adjusted for comparability.
+
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Difference between this estimate and the 2006 estimate is statistically significant at the .05 level.
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Methamphetamine:
Epidemiology
High School Students Reporting
Methamphetamine Use, 2006
Last 30
days
Grade
Lifetime Annual
8th
1.8%
1.1%
0.6%
10th
2.8%
1.6%
0.4%
12th
3.0%
1.7%
0.6%
National Institute on Drug Abuse and University of Michigan, Monitoring the Future Data from In-School
Surveys of 8th-, 10th-, and 12th- Grade Students, 2007.
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According to the Monitoring the Future Study
Methamphetamine is not Increasing
5.0
4.0
3.0
*
2.0
P < .05
1.0
0.0
99
00
01
8th Grade
02
03
10th Grade
04
05
06
12th Grade
Percent of Students Reporting Use of
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Education
Methamphetamine
Past
Year, by Grade 8
Past Year Methamphetamine Use
among Persons Aged 12+, by Region:
2002 and 2006
Percent Using in Past Year
2.0
1.6
2002
2006
1.5
1.6
1.0
0.7
0.6
0.5
0.5
0.6
0.3
0.1
0.0
Northeast
Midwest
South
West
Note: Estimates are based on new 2006 questions. 2002 estimates are adjusted for comparability.
+
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Difference between this estimate and the 2006 estimate is statistically significant at the .05 level.
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Primary Methamphetamine/amphetamine admission
rates (per 100,000 population aged 12 and over)
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Methamphetamine Treatment Admissions
Number of Admissions
160000
140000
120000
100000
80000
60000
40000
20000
0
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
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2005 SAMHSA Treatment Episode Data Set
11
Diagnostic Criteria
Based on the Diagnostic and Statistical
Manual of Psychiatric Diseases IVth Edition
(DSMIV)
• Abuse
• Dependence
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Diagnostic Criteria
Methamphetamine Abuse
•
•
A maladaptive pattern of substance use leading to clinically significant impairment or
distress, as manifested by one (or more) of the following, occurring within a 12-month
period:
–
recurrent substance use resulting in a failure to fulfill major role obligations at
work, school, home (e.g., repeated absences or poor work performance related to
substance use; substance-related absences, suspensions, or expulsions from
school; neglect of children or household)
–
recurrent substance use in situations in which it is physically hazardous (e.g.,
driving an automobile or operating a machine when impaired by substance use)
–
recurrent substance-related legal problems (e.g., arrests for substance-related
disorderly conduct)
–
continued substance use despite having persistent or recurrent social or
interpersonal problems caused or exacerbated by the effects of the substance (e.g.,
arguments with spouse about consequences of intoxication, physical fights)
The symptoms have never met the criteria for Substance Dependence for this class of
substances.
[DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, ed. 4. Washington DC: American Psychiatric Association (AMA). 1994.]
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Diagnostic Criteria
Methamphetamine Dependence
•
•
–
–
•
–
–
•
•
•
•
•
A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as
manifested by three (or more) of the following, occurring at any time in the same 12-month period:
tolerance, as defined by either of the following:
a need for markedly increased amounts of the substance to achieve intoxication or desired
effect
markedly diminished effect with continued use of the same amount of substance
withdrawal, as manifested by either of the following:
the characteristic withdrawal syndrome for the substance
the same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms
the substance is often taken in larger amounts or over a longer period than was intended
there is a persistent desire or unsuccessful efforts to cut down or control substance use
a great deal of time is spent in activities to obtain the substance, use the substance, or recover from
its effects
important social, occupational or recreational activities are given up or reduced because of
substance use
the substance use is continued despite knowledge of having a persistent or recurrent physical or
psychological problem that is likely to have been caused or exacerbated by the substance (e.g.,
continued drinking despite recognition that an ulcer was made worse by alcohol consumption)
[DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, ed. 4. Washington DC: American Psychiatric Association (AMA). 1994.]
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Video clip
• Diagnostic interview
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Methods of abusing
Methamphetamine
•
•
•
•
•
Ingesting
Snorting
Smoking
Injecting
Skin popping
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Mechanism of Action
•
•
•
•
Increased release of Serotonin
Increased release of nor-epinephrine
Increased release of dopamine levels
(primary mechanism of feeling high)
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Action
potential
transporter
Vmat
/serotonin
DA/5HT
200
% of Basal DA Output
NAc shell
150
100
Empty
50
Box Feeding
200
150
100
15
10
5
0
0
0
60
120
Time (min)
180
ScrScr
BasFemale 1 Present
Sample 1 2 3 4 5 6 7 8
Number
Scr
Copulation Frequency
DA Concentration (% Baseline)
Natural Rewards Elevate Dopamine
Levels
FOOD
SEX
Scr
Female 2 Present
9 10 11 12 13 14 15 16 17
Mounts
Intromissions
Ejaculations
Source: Di Chiara et al.; Fiorino and Phillips
transporter
Vmat
/serotonin
• Release DA from vesicles and reverse
transporter
Methamphetamine
DA/5HT
Effects of Drugs on Dopamine Release
METHAMPHETAMINE
% of Basal Release
1000
500
0
% of Basal Release
400
0
1
2
3hr
Time After Methamphetamine
250
NICOTINE
200
Accumbens
Caudate
150
100
Accumbens
COCAINE
DA
DOPAC
HVA
300
200
100
0
0
250
% of Basal Release
% of Basal Release
1500
1
2
3
4
Time After Cocaine
Accumbens
5 hr
ETHANOL
Dose (g/kg ip)
200
0.25
0.5
1
2.5
150
100
0
0
1
2
3 hr
Time After Nicotine
0
0
1
2
3
Time After Ethanol
4hr
Source: Shoblock and Sullivan; Di Chiara and Imperato
How do drugs work in the brain?
We Know That Despite
Their Many Differences, most
Abused Substances Enhance the
Dopamine and Serotonin Pathways
Dopamine Pathways
Serotonin Pathways
striatum
frontal
cortex
hippocampus
substantia
nigra/VTA
Functions
•reward (motivation) nucleus
•pleasure, euphoria accumbens
•motor function
(fine tuning)
•compulsion
•perseveration
raphe
Functions
•mood
•memory
processing
•sleep
•cognition
Science Has Generated A Lot of
Evidence Showing That…
Prolonged Drug Use Changes
the Brain In Fundamental
and Long-Lasting Ways
AND…
We Have Evidence That
These Changes Can Be Both
Structural and Functional
Structurally…
NA
C
Saline
Amph
Source: Robinson & Kolb, Journal of Neuroscience, 1997
Functionally…
Dopamine D2 Receptors are Lower in Addiction
DADA
Cocaine
DA
DA DA DA
DA
DA DA
DADA
DA
Meth
Reward Circuits
Non-Drug Abuser
DADA
Alcohol
DA
DA
DA
DA
Heroin
Reward Circuits
Control
Addicted
Drug Abuser
Effect of Methamphetamines
Courtesy of Jane Koropsak, Brookhaven National Lab.
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Normal Control
Dopamine Transporter
Bmax/Kd
Dopamine Transporters in Methamphetamine Abusers
2.0
1.8
1.6
1.4
1.2
1.07
Motor Task
Loss of dopamine
transporters in the meth
abusers may result in
slowing of motor
reactions.
8
9 10 11 12 13
Time Gait
(seconds)
2.0
1.8
1.6
1.4
1.2
1.0
16 14 12 10 8
Memory task
Loss of dopamine transporters
in the meth abusers may result
in memory impairment.
6
4
Delayed Recall
(words remembered)
Methamphetamine Abuser
Source: Volkow et al., Am. J. Psychiatry, 2001.
Partial Recovery of Brain Dopamine
Transporters in Methamphetamine
(METH)
Abuser After Protracted Abstinence
3
0
ml/gm
Normal Control
METH Abuser
(1 month abstinent)
METH Abuser
(24 months abstinent)
Source: Volkow, ND et al., Journal of Neuroscience, 2001.
Short-Term Effects
•
•
•
•
•
•
•
•
•
Increased attention and decreased fatigue
Increased activity and wakefulness
Decreased appetite
Euphoria and rush
Increased respiration
Rapid/irregular heartbeat
Hyperthermia
A distorted sense of well-being
Effects that can last 8 to 24 hours
http://www.drugabuse.gov/ResearchReports/methamph/methamph3.html#short
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Long Term effects
Behavior Changes
Medical
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Addiction
Psychosis, including:
Paranoia and delusions
hallucinations
repetitive motor activity
Changes in brain structure and
function
Memory Loss
Aggressive or violent behavior
Anxiety and Mood disturbances
Severe dental problems
Weight loss
Fatigue
High blood pressure
Tachycardia
Tachypnea
Myocardial infarctions
Skin lesions
Stroke
Dehydration
Weight loss
Death
http://www.drugabuse.gov/ResearchReports/methamph/methamph3.html#short
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Video clip
• Effects of
Methamphetamine use
QuickTime™ and a
DV/DVCPRO - NTSC decompressor
are needed to see this picture.
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Drug Use Has Played a Prominent
Role in the HIV/AIDS Epidemic
In Several Ways
Disease Transmission
• IV Drug Use
• Drug User Disinhibition Leading to
High Risk Sexual Behaviors
Progression of Disease
Fetal Effects of Methamphetamine
Preliminary evidence suggests that prenatal
methamphetamine exposure is associated with subtle
physical and neurobehavioral effects including:
•
•
•
•
•
•
Lower arousal
Poorer self-regulation
Poorer quality of movement
Increased central nervous system stress
Small for gestational age
Long-term consequences???
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Clinical Presentation
Intoxication
• Rush (5-30 min) –
–
–
–
–
Adrenal gland release of epinephrine
Explosive release of dopamine
Intensely euphoric
Tacchycardia, BP spike, heart rhythm
abnormalities
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Clinical Presentation
Intoxication
• High (4-16 hrs)
– Continuation of the physical and mental
hyperactivity
• Binge (3-15 days)
–
–
–
–
Continuation of the high
Larger doses required to achieve same intensity
Little or no rush or high felt
Physical and mental hyperactivity
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Clinical Presentation
Withdrawals
• “Crash”
– Follows a binge
– Feelings of emptiness and dysphoria
– Often repeat use of this drug or alcohol/other
drugs used to self-medicate withdrawal
symptoms
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Clinical Presentation
Withdrawals
• “Crash” (1-3 days)
– Tired, lifeless and sleepy
• Withdrawal (30-90 days)
– Slow progression to depression, lethargy,
cravings, suicidal thoughts
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Treatment options
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Basic Principles of Treatment
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
No single treatment is appropriate for all individuals.
Treatment needs to be readily available.
Effective treatment attends to multiple needs of the individual, not just his or her
drug use.
An individual's treatment and services plan must be assessed continually and
modified as necessary to ensure that the plan meets the person's changing needs.
Remaining in treatment for an adequate period of time is critical for treatment
effectiveness.
Counseling (individual and/or group) and other behavioral therapies are critical
components of effective treatment for addiction.
Medications are an important element of treatment for many patients, especially
when combined with counseling and other behavioral therapies.
Addicted or drug-abusing individuals with coexisting mental disorders should have
both disorders treated in an integrated way.
Medical detoxification is only the first stage of addiction treatment and by itself
does little to change long-term drug use.
Treatment does not need to be voluntary to be effective.
Possible drug use during treatment must be monitored continuously.
Treatment programs should provide assessment for HIV/AIDS, hepatitis B and C,
tuberculosis and other infectious diseases, and counseling to help patients modify
or change behaviors that place themselves or others at risk of infection.
Recovery from drug addiction can be a long-term process and frequently requires
multiple episodes of treatment.
(National Institute on Drug Abuse, Principles of Drug Addiction Treatment: A Research-Based Guide )
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Why Can’t Addicts Just Quit?
Non-Addicted Brain
Addicted Brain
Control
Control
Saliency
Drive
Memory
NO
GO
Saliency
Drive GO
Memory
Because Addiction Changes Brain Circuits
Source: Adapted from Volkow et al., Neuropharmacology, 2004.
Treating the ADDICTED Brain
CONTROL
REWARD
DRIVE
Decrease
the
rewarding
value of
drugs
CONTROL
REWARD
MEMORY
MEMORY
CONTROL
REWARD
DRIVE
MEMORY
DRIVE
Increase the
rewarding
value
of non-drug
reinforcers
Weaken
learned
positive
associations
with drugs
and drug
cues
CONTROL
REWARD
DRIVE
MEMORY
Strengthen
frontal
control
Pharmacological treatments
• No approved medications
• Off label use / treatment of co-morbid
conditions
– Antidepressants
– Mood stabilizers
– Antipsychotic medications
• Supportive treatment
(http://www.drugabuse.gov/about/Legislation/MethReport/Introduction.html)
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Non-pharmacological Treatments
•
•
•
•
•
•
•
Motivation Enhancement Therapy
Cognitive Behavioral Therapy
Contingency Management
MATRIX Model
Family Education
Group therapy
Self-Help Groups (12 step program)
http://www.drugabuse.gov/pdf/news/Meth1106.pdf
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Video clip 3 & 4
• Traditional /
Interventional model
– Video Clip 3
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Video clip 3 & 4
• Motivational Enhancement
Therapy (MET)
– Video Clip 4
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Role of Spirituality
Specific information on role of religion for
methamphetamine limited
Data on general drug use suggests principles of:
• Honesty
• Open mindedness
• Willingness
Spirituality:
• promotes treatment adherence
• promotes mental health
• promotes decreased use
http://www.drugabuse.gov/TXManuals/IDCA/IDCA3.html
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Pearls
• Methamphetamine users like stimulants and
often abuse caffeine.
• Methamphetamine users often get depressed
and suicidal when coming off of
methamphetamines
• Methamphetamine may seek stimulants for
ADHD.
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Clinical Vignette # 1
A 22 year old white male is admitted to the ER with
paranoia, olfactory, tactile, auditory and visual
hallucinations, agitation and behavior disturbances.
This is atypical behavior for him. Acute
management should include:
• Medical assessment, including CT of head, EEG
• Urine Drug Screen
• Pharmacotherapy with tranquilizers
(Benzodiazepines and antipsychotics) , IV fluids and
general supportive treatment
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Clinical Vignette # 2
A 62 year old white male is admitted to the ER with
history of alcohol and IV drug use history. He is
very depressed, tired and suicidal with some
paranoia. His ADL are poor. Acute management
should include:
• Medical assessment, blood workup and CT of head
• Urine Drug Screen
• Pharmacotherapy with tranquilizers
(Benzodiazepines and antipsychotics), IV fluids and
general supportive treatment
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Clinical Vignette # 3
•
•
•
•
•
A 32 year old, 30 weeks pregnant white female, with a
previous history of Bipolar Disorder presents to the Obstetric
Clinic for a routine well check. She has facial sores, that she
says are acne related to her pregnancy. She is also presenting
with symptoms of hypomania. She is denying any alcohol or
drug use. Her grooming and hygiene are poor.
Medical/Obstetric assessment, blood workup
Urine Drug Screen
IV fluids and general supportive treatment
Benzodiazepine treatment to control agitation
Social work consult
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Comparison to Other Chronic
Diseases
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Drug
Addiction
Type I
Diabetes
Hypertension
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Source: McLellan, A.T. et al., JAMA, Vol 284(13), October 4, 2000.
50 to 70%
50 to 70%
90
80
70
60
50
40
30
20
10
0
30 to 50%
100
40 to 60%
Percent of Patients Who Relapse
Relapse Rates Are Similar for Drug
Addiction & Other Chronic Illnesses
Asthma
54
Co-morbidity:
Co-morbidity is Common in SUD
• 2 / 3 of the individuals have a co-morbid diagnosis
• Most common is another substance use disorder
(Kaplan and Sadock, Text Book of psychiatry)
• Most are Conduct disorder/Anti Social Personality
Disorder and/or another substance use disorder
• Others might be medical and/or psychiatric
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Suggested reading
• NIDA InfoFacts: Methamphetamine. Summary of
research findings on methamphetamine for a
general audience.
• NIDA Research Report: Methamphetamine: Abuse
and Addiction. More detailed look at the latest
research findings. For a general audience.
• http://www.drugabuse.gov/TXManuals/IDCA/IDC
A1.html
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Suggested reading
• Meredith CW, Jaffe C, Ang-Lee K, Saxon AJ.
Implications of chronic methamphetamine use: a
literature review. Harv Rev Psychiatry. 2005 MayJun;13(3):141-54.
• Barr AM, Panenka WJ, MacEwan GW, Thornton
AE, Lang DJ, Honer WG, Lecomte T. The need
for speed: an update on methamphetamine
addiction. J Psychiatry Neurosci. 2006
Sep;31(5):301-13.
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Assessment Questions:
1. For a diagnosis of methamphetamine
abuse, a maladaptive pattern of abuse
needs to be present over a period of:
1.
2.
3.
4.
One month
One year
One week
One decade
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Assessment Questions:
2. Diagnosis of Methamphetamine
dependence requires the presence of the
following number of criteria out of the
possible seven:
1.
2.
3.
4.
5.
Three
Four
Five
Six
Seven
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Assessment Questions:
3. Methamphetamine works primarily by:
1.
2.
3.
4.
Increasing dopamine breakdown
Increasing serotonin release
Increasing acetylcholine blockade
Increasing nor epinephrine synthesis
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Assessment Questions:
4. Methamphetamine can cause death by:
1.
2.
3.
4.
Respiratory depression
Hyperthermia
Metabolic acidosis
Metabolic Alkalosis
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Assessment Questions:
5. The fastest way to get a high form
methamphetamine use is:
1.
2.
3.
4.
Skin popping
Ingesting
Snorting
Smoking
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Assessment Questions:
6. Approximately the following percentage of
people can be expected to have used
methamphetamine in the United Sates:
1.
2.
3.
4.
10%
4%
2%
1%
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Assessment Questions:
7. The effects of methamphetamine can
generally last for:
1.
2.
3.
4.
60 seconds or less
1 hours
2 hours
Methamphetamine’s effects can last for a long
time, perhaps up to 24 hours
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Assessment Questions:
8. Methamphetamine dependence can be
successfully treated with:
1.
2.
3.
4.
Naltrexone
Disulfiram
Antidepressant medications
Behavioral therapies
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Assessment Questions:
9. Cues that produce cravings can:
1.
2.
3.
4.
5.
Stimulate the amygdala
Stimulate the frontal cortex
Stimulate the nigrostriatal pathway
Can inhibit the nucleus accumbens
Can stimulate the temporal lobe
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Assessment Questions:
10. The treatment of substance use disorders
is:
1. Less effective than treatment of other chornic
diseases.
2. More effective than the treatment of other
chronic diseases.
3. Has similar efficacy to the treatment of other
chronic diseases.
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Assessment Questions:
11. Methamphetamine use most commonly
presents with another co-morbid condition
that is:
1.
2.
3.
4.
Bipolar disorder
Hypertension
Suicidal disorder
Another substance use disorder
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Assessment Questions:
12. In the treatment of methamphetamine use
disorders:
1. A high stimulus environment is required to
ensure that the patient stays awake
2. Hydralazine treatment is often required
3. Haloperidol treatment is contraindicated as it
can lower the seizure threshold.
4. Antidepressant are prescribed to decrease
their depression.
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