Methamphetamines
University of Pittsburgh Graduate
Learning objectives
1. To provide a historical context of
methamphetamine use and abuse
2. To overview medicinal uses of
methamphetamine
3. To discuss mechanisms and outcomes of
methamphetamine abuse
4. To discuss the challenges of
methamphetamine research
What is methamphetamine?
Formula C10H15 N
Molecular mass: 149.233 g/mol
Half life: 9-15 hours
Excretion: renal
What is methamphetamine?
Source – NIDA Research Report – 1998
History of meth
• Amphetamine created in Germany in 1887
• Used widely during WWII by the Nazi
and Japanese armies
• Japanese kamikaze pilots were
documented to be high on meth
• Major challenge in postwar Japan
• Biker gangs in California after WWII
began to distribute meth
Source – Nebraska State Patrol
Methamphetamine: medical uses
• Narcolepsy
• Attention deficit disorder
• Obesity (short term use)
Forms of Distribution
What does meth look like?
• Typically an odorless powder that
dissolves quickly in water
• Another form of meth is clear chunky
crystals referred to as crystal meth or
ice
• May be in the form of small brightly
colored tablets, referred to as YABA
How is meth used?
• Injected
• Snorted
• Smoked
• Orally
Methamphetamine/Amphetamine Treatment Admissions
by Route of Administration: 1992-2002
Source: 2002 SAMHSA Treatment Episode Data Set (TEDS).
Meth causes…
• Increased alertness
• Decreased appetite
• A distorted sense of wellbeing
• Effects that can last 8 to 24
hours
U.S. Emergency Dept. Mentions of
Meth/amphetamines 1995-2002
45000
40000
35000
30000
25000
20000
15000
10000
5000
0
1995
DAWN, July 2004
1996
1997
1998
1999
2000
2001
2002
Demographics of MA-related
ED visits in U.S., 2002
58% male and 42% female
Race/ethnicicty
White
Latino
African American
Age
Under 18
18-34 years
Over 34
DAWN, 2004
11%
56%
33%
65%
11%
6%
Behavior changes
Psychotic behavior
Paranoia
Aggression
Anxiety
Fatigue
Depression
Delusions
Mood swings
Confusion
Insomnia
Hallucinations
Health changes
Stroke
Brain damage
Weight loss
Death
Source – Congressional Research Sites
How does methamphetamine
work?
Methamphetamine releases large
amounts of dopamine in the brain,
causing feelings of pleasure and
euphoria.
Source: National Institute on Drug Abuse. April 1998,
Reprinted January 2002. Research Report Series: Methamphetamine
Abuse and Addiction.
www.nida.nih.gov/ResearchReports/methamph/methamph.html
Effects of meth on dopamine
Researchers report that the
dopamine-producing cells in
the brain can be damaged
after prolonged exposure to
relatively low levels of
methamphetamine.
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
Scr
Female 2 Present
9 10 11 12 13 14 15 16 17
Mounts
Intromissions
Ejaculations
Source: Di Chiara et al.
Source: Fiorino and Phillips
Copulation Frequency
DA Concentration (% Baseline)
Natural Rewards Elevate Dopamine
Levels
FOOD
SEX
Accumbens
1100
1000
900
800
700
600
500
400
300
200
100
0
AMPHETAMINE
Accumbens
% of Basal Release
400
DA
DOPAC
HVA
0
1
2
3
4
250
200
100
0
5 hr
0
NICOTINE
Accumbens
Caudate
150
100
0
0
1
2
3 hr
Time After Nicotine
1
Accumbens
250
% of Basal Release
200
COCAINE
DA
DOPAC
HVA
300
Time After Amphetamine
% of Basal Release
% of Basal Release
Effects of Drugs on Dopamine Levels
2
3
4
Time After Cocaine
5 hr
MORPHINE
Dose (mg/kg)
0.5
1.0
2.5
10
200
150
100
0
0
Source: Di Chiara and Imperato
1
2
3
4
Time After Morphine
5hr
PET Scan of Long-Term Meth Brain Damage
Long-term effects: What will happen
in the future
Methamphetamine destroys the endings of dopamine
containing nerve cells
(NIDA 2)
Partial Recovery of Brain from
Methamphetamine After Abstinence
3
0
ml/gm
Normal Control
METH Abuser
(1 month abstinent)
METH Abuser
(14 months abstinent)
Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001.
Dopamine improvements after 1 year, but not cognitive and motor functioning
Methamphetamine
Acute Physical Effects
Increases
Heart rate
Blood pressure
Pupil size
Respiration
Sensory acuity
Energy
Decreases
– Appetite
– Sleep
– Reaction time
Methamphetamine
Acute Psychological Effects
Increases
Confidence
Alertness
Mood
Sex drive
Energy
Talkativeness
Decreases
Boredom
Loneliness
Timidity
Highly Toxic Substances
Drain cleaner
Battery acid
Antifreeze
Over-the-counter asthma medicine
containing ephedrine or pseudoephedrine
Match-box striker (Red phosphorous)
Hydrochloric acid
Lye
Lantern fuel
(KCI)
Methamphetamine use and
pregnancy
Possible effects found in the few human
studies that exist include increased rates of
premature delivery, placental abruption
(early separation of a normal placenta from
the wall of the uterus), retarded fetal growth,
and cardiac and brain abnormalities.
Source: Volkow, Nora, M.D., Director, NIDA. April 21, 2005. Testimony Before the Subcommittee on Labor, Health,
and Human Services; Education; and Related Agencies. Committee on Appropriations, U.S. Senate.
www.hhs.gov/asl/testify/t050425b.html
Meth Mouth: Myth and Reality
How many Americans use
methamphetamines?
Lifetime use: 4.9 percent of those aged 12 and
over (12 million people)
Past-year use: 0.6 percent of those aged 12
and over (1.4 million people)
Past-month use: 0.2 percent of those aged 12
and over (600,000 people)
Source: The Substance Abuse and Mental Health Services Administration/Office of Applied Studies. September 16,
2005. The NSDUH Report: Methamphetamine Use, Abuse, and Dependence: 2002, 2003, and 2004, In Brief.
http://oas.samhsa.gov/2k5/meth/meth.htm
Environmental effects of meth
• Meth production leaves behind 5 to 6 pounds
of toxic waste per pound of meth produced.
• Toxic by-products contaminate sites where
meth is produced, posing serious health and
environmental hazards to those nearby.
• The cost to clean up one meth lab often
exceeds $4,000.
Source – Koch Crime Institute
Impacts on families
• Danger of children being exposed
to toxic fumes
• Children are more at risk than
adults to environmental hazards,
as their bodies are immature
• Risk of explosion, fire, and
chemical burns
• Exposure to weapons, finished
drugs, and unsanitary conditions
More impacts on families
• Increase in child abuse and neglect
cases
• Increased risk for substance abuse
among children in later life
• A rise in domestic disputes
Is there an effective treatment for
methamphetamine abuse?
At this time the most effective treatments for
methamphetamine addiction are cognitive
behavioral interventions. These approaches are
designed to help modify the patient's thinking,
expectancies, and behaviors and to increase skills in
coping with various life stressors.
Methamphetamine recovery support groups also
appear to be effective adjuncts to behavioral
interventions that can lead to long-term drug-free
recovery.
U.S. admissions for
MA drug treatment
SAMSHA, 2004
Epidemiology
High prevalence of HIV in patients who use crystal
MA
• Shoptaw, et al, J Addict Dis 2002 showed in a CA study that
61% of men seeking tx for MA had HIV infection
–
–
–
–
77% of men were white, 17% were Latino
All were in their mid 30’s and had some college education
Reported a mean of 66 different partners in 6 months
Persons with HIV were more likely to have injected MA,
contracted an STD and had more UAI
• Klitzman, et al Am J Psychiatry 2000 reported strong
association between MDMA use and high-risk sexual behavior
• 2001 report in MMWR found that in an outbreak of 130 cases
of syphilis in CA, 51% were MSM and 18% reported use of
MA
Epidemiology
Study of 25 HIV+ gay men using MA
(Semple et al., J Subst Abuse Treat 2002)
– “provided temporary escape from being HIV+”
– “helps manage negative self-perception and
social rejection associated with being HIV+
– “method of coping with the specter of death”
Key points on methamphetamine
Methamphetamine is a drug that can be effectively used for several
medical conditions
When used illegally, Meth is a powerful, highly addictive stimulant
that can be made easily from legally available products.
Twelve million Americans ages 12 and over have used meth at least
once; use is most common between ages 19 and 40.
Meth labs use and produce toxic, explosive chemicals; meth labs
are dangerous and expensive to clean up.
Exposure to chemicals used to make meth may cause cancer,
damage the brain and other organs, and result in birth defects.