Methamphetamine: How it Methamphetamine: How it Influences the Brain and Influences the Brain and

Behavior of Users Behavior of Users Richard A. Rawson, Ph.DRichard A. Rawson, Ph.D

Adjunct Associate ProfessorAdjunct Associate ProfessorDepartment of Psychiatry and Biobehavioral SciencesDepartment of Psychiatry and Biobehavioral Sciences

David Geffen School of MedicineDavid Geffen School of MedicineUniversity of California at Los AngelesUniversity of California at Los Angeles

MethamphetamineMethamphetamine

Methamphetamine is a powerful central Methamphetamine is a powerful central nervous system stimulant that strongly nervous system stimulant that strongly activates multiple systems in the brain. activates multiple systems in the brain. Methamphetamine is closely related Methamphetamine is closely related chemically to amphetamine, but the chemically to amphetamine, but the central nervous system effects of central nervous system effects of methamphetamine are greater. methamphetamine are greater.

Methamphetamine: SpeedMethamphetamine: Speed Methamphetamine powder ranging in color from Methamphetamine powder ranging in color from

white, yellow, orange, pink, or brown. white, yellow, orange, pink, or brown. Color variations are due to differences in chemicals Color variations are due to differences in chemicals

used to produce it and the expertise of the cooker. used to produce it and the expertise of the cooker. Other names: shabu, crystal, crystal meth, crank, tina, Other names: shabu, crystal, crystal meth, crank, tina,

yabayaba

Methamphetamine: IceMethamphetamine: Ice

High purity High purity methamphetamine methamphetamine crystals or coarse crystals or coarse powder ranging from powder ranging from translucent to white, translucent to white, sometimes with a sometimes with a green, blue, or pink green, blue, or pink tinge. tinge.

MethamphetamineMethamphetamineA Brief HistoryA Brief History

18871887 19191919 19321932

Amphetamine developedAmphetamine developed

Methamphetamine developedMethamphetamine developed

Amphetamine & Amphetamine & methamphetamine used as methamphetamine used as decongestantdecongestant

MethamphetaminesMethamphetaminesA Brief HistoryA Brief History

WW II Extensive use by:WW II Extensive use by:

- RAF fighter pilots- RAF fighter pilots

- German Panzer - German Panzer troopstroops

- Japanese workers - Japanese workers

- Led to Kamikaze - Led to Kamikaze feverfever

According to surveys and estimates by WHO According to surveys and estimates by WHO and UNDCP, methamphetamine is the most and UNDCP, methamphetamine is the most widely used illicit drug in the world except for widely used illicit drug in the world except for cannabis.cannabis.

World wide it is estimated there are over 42 World wide it is estimated there are over 42 million regular users of methamphetamine, as million regular users of methamphetamine, as compared to approximately 15 million heroin compared to approximately 15 million heroin users and 10 million cocaine usersusers and 10 million cocaine users

Scope of the Methamphetamine Scope of the Methamphetamine Problem WorldwideProblem Worldwide

IHS-Wide Outpatient Encounters for IHS-Wide Outpatient Encounters for Amphetamine Related Visit by Calendar YearAmphetamine Related Visit by Calendar Year

The Eastward Spread The Eastward Spread of Methamphetamineof Methamphetamine

Methamphetamine: A Growing Menace Methamphetamine: A Growing Menace in Rural Americain Rural America

In 1998, rural areas In 1998, rural areas nationwide reported 949 nationwide reported 949 methamphetamine labs. methamphetamine labs.

Last year, 9,385 were Last year, 9,385 were reported. reported.

This year, 4,589 rural labs This year, 4,589 rural labs had been reported as of had been reported as of July 26.July 26.

Source: El Paso Intelligence Center (EPIC), Source: El Paso Intelligence Center (EPIC), U.S. DEAU.S. DEA

Meth Lab SeizuresMeth Lab Seizures A small percentage of labs seized are labeled “Super Labs” and A small percentage of labs seized are labeled “Super Labs” and

are capable of producing over 10 lbs per batch. are capable of producing over 10 lbs per batch. Super Labs are operated by Mexican National Drug Trafficking Super Labs are operated by Mexican National Drug Trafficking

Organizations (MNDTO’s), and supply the majority of meth to Organizations (MNDTO’s), and supply the majority of meth to the market.the market.

Stove Top LabsStove Top Labs

The active ingredient in making The active ingredient in making methamphetamine is ephedrine or methamphetamine is ephedrine or pseudoephedrine, commonly found in over pseudoephedrine, commonly found in over the counter cold remedies.the counter cold remedies.

Toxic Effects of Toxic Effects of Methamphetamine ManufacturingMethamphetamine Manufacturing

FiresFires ExplosionsExplosions Toxic gasesToxic gases Toxic wastesToxic wastes

Toxic Effects of Toxic Effects of Methamphetamine ManufacturingMethamphetamine Manufacturing

ManufacturersManufacturers Law enforcement Law enforcement

officersofficers BystandersBystanders

ChildrenChildren Children who live in and around the area of the Children who live in and around the area of the

meth lab become exposed to the drug and its meth lab become exposed to the drug and its toxic precursors and byproducts.toxic precursors and byproducts.

80-90% of children found in homes where there 80-90% of children found in homes where there are meth labs test positive for exposure to meth. are meth labs test positive for exposure to meth. Some are as young as 19 months old.Some are as young as 19 months old.

ChildrenChildren

Children can test positive for Children can test positive for methamphetamine by:methamphetamine by: Having inhaled fumes during the Having inhaled fumes during the

manufacturing process manufacturing process Coming into direct contact with the drugComing into direct contact with the drug Through second-hand smoke.Through second-hand smoke.

Cardiovascular problemsCardiovascular problems

↑ ↑ heart rateheart rate Palpitations Palpitations Arrhythmia Arrhythmia ↑ ↑ blood pressureblood pressure Chest Pain Chest Pain

Acute Coronary Acute Coronary Syndrome Syndrome

Valve thickening Valve thickening

Neurological problemsNeurological problems

Seizures Seizures Stroke Stroke Cerebral Cerebral

hemorrhage hemorrhage Cerebral vasculitis Cerebral vasculitis

MydriasisMydriasis

Respiratory problemsRespiratory problems

Dyspnea Dyspnea

Pulmonary Pulmonary

hypertension hypertension

Pleuritic chest pain Pleuritic chest pain

Other problemsOther problems

Eye ulcers Eye ulcers

Over-heatingOver-heating Rhabdomyolysis Rhabdomyolysis Obstetric complications Obstetric complications

Anorexia / weight loss Anorexia / weight loss

Tooth wear, cavitiesTooth wear, cavities ““Speed bumps”Speed bumps”

TraumaTrauma

Interpersonal Interpersonal traumatrauma AssaultAssault GunshotGunshot KnifeKnife

Motor VehiclesMotor Vehicles Suicide attemptsSuicide attempts

MethamphetamineMethamphetamineAcute Physical EffectsAcute Physical Effects

- - IncreasesIncreases --DecreasesDecreases

Heart rate Heart rate AppetiteAppetite

Blood pressure Blood pressure Sleep Sleep

Pupil size Pupil size Reaction Reaction timetime

RespirationRespiration

Sensory acuitySensory acuity

EnergyEnergy

MethamphetamineMethamphetamineAcute Psychological EffectsAcute Psychological Effects

IncreasesIncreases Confidence Confidence Alertness Alertness MoodMood Sex driveSex drive EnergyEnergy TalkativenesTalkativenes

ss

DecreasesDecreases BoredomBoredom LonelinessLoneliness TimidityTimidity

MethamphetamineMethamphetamineChronic Physical EffectsChronic Physical Effects

-- Tremor Tremor - Sweating- Sweating- Weakness - Weakness - Burned lips; - Burned lips;

sore nosesore nose- Dry mouth - Dry mouth - Oily - Oily

skin/complexionskin/complexion- Weight loss - Weight loss - Headaches- Headaches- Cough - Cough - Diarrhea- Diarrhea- Sinus infection - Sinus infection - Anorexia- Anorexia

MethamphetamineMethamphetamineChronic Psychological EffectsChronic Psychological Effects

- - Confusion - IrritabilityConfusion - Irritability

- Concentration - Paranoia- Concentration - Paranoia

- Hallucinations - Panic - Hallucinations - Panic reactionsreactions

- Fatigue - Depression- Fatigue - Depression

- Memory loss - Anger- Memory loss - Anger

- Insomnia - Psychosis- Insomnia - Psychosis

MethamphetamineMethamphetaminePsychiatric ConsequencesPsychiatric Consequences

Paranoid reactionsParanoid reactions Permanent memory lossPermanent memory loss Depressive reactionsDepressive reactions HallucinationsHallucinations Psychotic reactionsPsychotic reactions Panic disordersPanic disorders Rapid addictionRapid addiction

A Major Reason People Take a Drug is they Like

What It Does to Their Brains

A Major Reason People Take a Drug is they Like

What It Does to Their Brains

Methamphetamine abusers haveMethamphetamine abusers have abnormal brain activity. abnormal brain activity.

00

5050

100100

150150

200200

00 6060 120120 180180

Time (min)Time (min)

% o

f B

asal

DA

Ou

tpu

t%

of

Bas

al D

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NAc shellNAc shell

EmptyEmpty

BoxBox FeedingFeeding

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

FOODFOOD

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DA

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(%

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MountsMountsIntromissionsIntromissionsEjaculationsEjaculations

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req

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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

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Re

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se

% o

f B

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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

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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

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lea

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% o

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AccumbensAccumbens

0.50.51.01.02.52.51010

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

MORPHINEMORPHINE

00

100100

150150

200200

250250

00 11 22 3 hr3 hrTime After NicotineTime After Nicotine

% 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

Prolonged Drug Use ChangesProlonged Drug Use Changesthe Brain In Fundamentalthe Brain In Fundamentaland Long-Lasting Waysand Long-Lasting Ways

Prolonged Drug Use ChangesProlonged Drug Use Changesthe Brain In Fundamentalthe Brain In Fundamentaland Long-Lasting Waysand Long-Lasting Ways

CompulsiveDrug Use

(Addiction)

CompulsiveDrug Use

(Addiction)

VoluntaryDrug Use

VoluntaryDrug Use

Control > MA

4

3

2

0

1

MA > Control

5

4

2

0

1

3

Treatment Length by RouteTreatment Length by Route

0

1

2

3

4

5

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Treatment Completion by RouteTreatment Completion by Route

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0.4

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0.6

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MA-Free Samples by RouteMA-Free Samples by Route

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0.4

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0.6

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BSI Psychiatric Symptoms by RouteBSI Psychiatric Symptoms by Route

0

5

10

15

20

25

30

IN SM IDU

BL PST

TX-End PST

6-Mo PST

12-Mo PST

P<.05Positive Symptom Total (PST)

Depression Symptoms by Depression Symptoms by RouteRoute

0

24

6

810

12

14

1618

20

IN SM IDU

Dep

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co

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Baseline

Tx-End

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12-Month

P<.05

Psychopathology and RoutePsychopathology and Route

IDUs > likely to have a psychiatric IDUs > likely to have a psychiatric disability.disability.

IDUs > likely to have prior hospitalizations IDUs > likely to have prior hospitalizations for psychiatric problems for psychiatric problems

Hepatitis C by RouteHepatitis C by Route

21.05

10

57

22

0

10

20

30

40

50

60%

Pre

vela

nce

IN (n=38)

SM (n=202)

IDU (n=72)

Total (n=314)

P<.05

Women and MethWomen and Meth

Meth and Women: Meth and Women:

Typical gender ratio of heroin users in Typical gender ratio of heroin users in treatment : treatment : 3 men to 1 woman3 men to 1 woman

Typical gender ratio of cocaine users in Typical gender ratio of cocaine users in treatment : treatment : 2 men to 1 woman2 men to 1 woman

Typical gender ratio of methamphetamine Typical gender ratio of methamphetamine users in treatment : users in treatment : 1 man to 1 woman *1 man to 1 woman *

**among large clinical research populationsamong large clinical research populations

Drug Use by GenderDrug Use by Gender

14.9

63.7

85.1

36.3

0

10

20

30

40

50

60

70

80

90

Meth Other

Males

Females

0%10%20%30%40%50%60%70%80%

* p< .001

female

male

Self-Reported Reasons for Starting Methamphetamine Use

0%

5%

10%

15%

20%

25%

30%

35%

40%

*to lose weight *to relieve depression

*p< .001

Male

Female

Self-Reported Reasons for Starting Methamphetamine Use

My sexual My sexual drivedrive is increased by the use of … is increased by the use of …

18.1 20.5

43.9

70.655.3

11.1

85.3

55.6

0102030405060708090

100

Per

cent

Res

pond

ing

"Yes

"

opiates alcohol cocaine meth

Primary Drug of Abuse

malefemale

(Rawson et al., 2002)

My sexual My sexual pleasurepleasure is enhanced by is enhanced by the use of …the use of …

16.0 18.224.4

38.244.7

11.1

73.5 66.7

0102030405060708090

100

Per

cent

Res

pond

ing

"Yes

"

opiates alcohol cocaine meth

Primary Drug of Abuse

malefemale

(Rawson et al., 2002)

My sexual My sexual performanceperformance is improved by is improved by the use of …the use of …

19.115.9

24.432.4

18.411.1

58.8 61.1

0102030405060708090

100

Per

cent

Res

pond

ing

"Yes

"

opiates alcohol cocaine meth

Primary Drug of Abuse

malefemale

(Rawson et al., 2002)

CSAT Methamphetamine Treatment Project: CSAT Methamphetamine Treatment Project: Cross-Site Sample Description Cross-Site Sample Description

1,016 clients1,016 clients Average age was 32.8 yearsAverage age was 32.8 years 55% female55% female 60% Caucasian60% Caucasian 12.2 years of education on average12.2 years of education on average 16% currently married16% currently married 31% awaiting charges, trial, or sentencing31% awaiting charges, trial, or sentencing

Methamphetamine Use HistoryMethamphetamine Use History

Avg. years of lifetime use:Avg. years of lifetime use: 7.547.54

Avg. days used in past 30:Avg. days used in past 30: 11.5311.53

Percent that usually smoked:Percent that usually smoked: 65%65%

Violence Issues in LifetimeViolence Issues in Lifetime

78% experienced violence78% experienced violence 39% experienced sexual abuse39% experienced sexual abuse 81% experienced one or the other81% experienced one or the other 36% experienced both36% experienced both

Psychological Issues in LifetimePsychological Issues in Lifetime

60% depressed60% depressed 56% anxiety56% anxiety 45% memory problems45% memory problems 43% violence control problems43% violence control problems 34% suicidal thoughts34% suicidal thoughts 32% received medication32% received medication 9% memory problems9% memory problems

Gender Differences in Violence Gender Differences in Violence HistoryHistory

(% Ever)Female(85%)

Male(70%)

Partner 80% 26%

Friend 16% 38%

Other 14% 43%

Gender Differences in Partner Gender Differences in Partner ViolenceViolence

Female Male

Ever threatened 63% 26%

Ever Isolated 65% 37%

Ever Afraid 27% 10%

Gender Differences in Sexual Gender Differences in Sexual Abuse HistoryAbuse History

(% Ever)Female (58%) Male

(16%)

Parent 14% 4%

Sibling 22% 6%

Partner 32% 7%

Analyses reveal that a history of physical or sexual Analyses reveal that a history of physical or sexual violence (controlling for gender) is significantly violence (controlling for gender) is significantly

related to a number of negative outcomes. related to a number of negative outcomes.

These results suggest the importance of These results suggest the importance of understanding client background factors before understanding client background factors before

they enter treatment.they enter treatment.

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

1.60

Somat

izatio

n

Obsess

ive-

Compul

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Inte

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onal S

ensi

tivity

Depress

ion

Anxiet

y

Hostili

ty

Phobic A

nxiety

Parano

id Id

eatio

n

Psychotic

ism

all significant at p< .001

Mea

n B

SI

Sco

re

Female

Male

Behavior Symptom Inventory (BSI) Scores at Baseline

0.00

2.00

4.00

6.00

8.00

10.00

12.00

14.00

16.00

18.00

20.00

Female Male

p < .001

Me

an

BD

I Sc

ore

Beck Depression Inventory (BDI) Scores at Baseline

ImplicationsImplications

Physical and sexual violence is related to Physical and sexual violence is related to psychological problems and drug use psychological problems and drug use pattern differencespattern differences

Different types of traumas may have Different types of traumas may have different outcomes and may affect people different outcomes and may affect people in different waysin different ways

A history of trauma may be related to A history of trauma may be related to treatment engagement and outcome treatment engagement and outcome