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 well-

being•Effects that can last 8 to 24

hours

U.S. Emergency Dept. Mentions of Meth/amphetamines 1995-2002

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

1995 1996 1997 1998 1999 2000 2001 2002

DAWN, July 2004

Demographics of MA-related ED visits in U.S., 2002

58% male and 42% femaleRace/ethnicicty

White 65%Latino 11%African American 6%

AgeUnder 18 11%18-34 years 56%Over 34 33%

DAWN, 2004

Behavior changes Health changes

Psychotic behaviorParanoiaAggressionAnxietyFatigueDepressionDelusionsMood swingsConfusionInsomniaHallucinations

StrokeBrain damageWeight lossDeath

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

Researchers report that the dopamine-producing cells in the brain can be damaged

after prolonged exposure to relatively low levels of

methamphetamine.

Effects of meth on dopamine

00

5050

100100

150150

200200

00 6060 120120 180180

Time (min)Time (min)

% o

f B

asal

DA

Ou

tpu

t%

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A O

utp

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NAc shellNAc shell

EmptyEmpty

BoxBox FeedingFeeding

Source: Di Chiara et al.Source: Di Chiara et al.

FOODFOOD

100100

150150

200200

DA

Co

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ntr

ati

on

(%

Bas

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A C

on

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MountsMountsIntromissionsIntromissionsEjaculationsEjaculations

1515

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latio

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req

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yC

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tion

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SampleNumberSampleNumber

11 22 33 44 55 66 77 88 99 1010 1111 1212 1313 1414 1515 1616 1717

ScrScrScrScrBasBasFemale 1 PresentFemale 1 Present

ScrScrFemale 2 PresentFemale 2 Present

ScrScr

Source: Fiorino and PhillipsSource: Fiorino and Phillips

SEXSEX

Natural Rewards Elevate Dopamine Natural Rewards Elevate Dopamine LevelsLevels

Natural Rewards Elevate Dopamine Natural Rewards Elevate Dopamine LevelsLevels

00100100200200300300400400500500600600700700800800900900

1000100011001100

00 11 22 33 44 5 hr5 hr

Time After AmphetamineTime After Amphetamine

% o

f B

as

al

Re

lea

se

% o

f B

as

al

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lea

se

DADADOPACDOPACHVAHVA

AccumbensAccumbens AMPHETAMINEAMPHETAMINE

00

100100

200200

300300

400400

00 11 22 33 44 5 hr5 hrTime After CocaineTime After Cocaine

% o

f B

as

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se

% o

f B

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DADADOPACDOPACHVAHVA

AccumbensAccumbensCOCAINECOCAINE

00

100100

150150

200200

250250

00 11 22 33 44 5hr5hrTime After MorphineTime After Morphine

% o

f B

as

al

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se

% o

f B

as

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AccumbensAccumbens

0.50.51.01.02.52.51010

Dose (mg/kg)Dose (mg/kg)

MORPHINEMORPHINE

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100100

150150

200200

250250

00 11 22 3 hr3 hrTime After NicotineTime After Nicotine

% o

f B

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% o

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AccumbensAccumbensCaudateCaudate

NICOTINENICOTINE

Source: Di Chiara and ImperatoSource: Di Chiara and Imperato

Effects of Drugs on Dopamine LevelsEffects of Drugs on Dopamine LevelsEffects of Drugs on Dopamine LevelsEffects of Drugs on Dopamine Levels

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

Normal Control METH Abuser(1 month abstinent)

METH Abuser(14 months abstinent)

0

3

ml/gm

Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001.

Dopamine improvements after 1 year, but not cognitive and motor functioning

MethamphetamineAcute Physical Effects

Increases

Heart rateBlood pressurePupil size RespirationSensory acuityEnergy

Decreases – Appetite– Sleep– Reaction

time

MethamphetamineAcute Psychological Effects

Increases

Confidence Alertness MoodSex driveEnergyTalkativeness

Decreases BoredomLonelinessTimidity

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.