Methamphetamine Senior Residents Lecture Your name Title Institution.

MethamphetamineSenior Residents Lecture

Your name

Title

Institution

NIDA COE for Physician Education

2

Objective1. Prevalence data2. Diagnostic criteria3. Review of methods of abuse4. Review of methods of action5. Review of effects of use6. Review of symptoms of intoxication7. Review of symptoms of withdrawal8. Review of treatment principles9. Review of pharmacological treatments10. Review of non-pharmacological treatments11. Practical pearls12. Discussion of clinical vignettes13. Treatment outcomes data14. Co-morbidity


3

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.


4

Prevalence

• Lifetime prevalence of approximately 5.8%

• 14 million Americans age >12 have used methamphetamine

(http://www.drugabuse.gov/infofacts/methamphetamine.html)


5

Methamphetamine: Epidemiology

Age Group Lifetime Annual Last 30 days

12–17 1.3% 0.7% 0.3%18–25 6.4% 1.7% 0.2%

26–34 8.5% 1.3% 0.4%> 35 5.7% 0.5% 0.2%> 12 (Total) 5.8% 0.8% 0.3%

Percentage of Individuals Reporting Methamphetamine Use by Age Group, 2006

Substance Abuse and Mental Health Services Administration survey data


6

Past Year Methamphetamine Use among Persons Aged 12+, by Age:

2002-2006 Percent Using in Past Year

Age in Years

0.7

2.0

0.50.7 0.7

1.9

0.5

0.8 0.7

1.9

0.6

1.8

0.5

1.7

0.6

1.0+

0.70.7 0.70.8

0

1

2

3

12 or Older 12 to 17 18 to 25 26 or Older

20022003200420052006

+ Difference between this estimate and the 2006 estimate is statistically significant at the .05 level.

Note: Estimates are based on new 2006 questions. 2002-2005 estimates are adjusted for comparability.


7

Methamphetamine: Epidemiology

High School Students Reporting Methamphetamine Use, 2006

Grade Lifetime Annual Last 30 days

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.

http://monitoringthefuture.org/data/03data.html#2003data-drugs

NIDA COE for Physician Education 8

0.0

1.0

2.0

3.0

4.0

5.0

99 00 01 02 03 04 05 06

8th Grade 10th Grade 12th Grade

0.0

1.0

2.0

3.0

4.0

5.0

99 00 01 02 03 04 05 06

8th Grade 10th Grade 12th Grade

P < .05P < .05

Percent of Students Reporting Use of Methamphetamine in Past Year, by Grade

Percent of Students Reporting Use of Methamphetamine in Past Year, by Grade

**

According to the Monitoring the Future Study Methamphetamine is not Increasing

According to the Monitoring the Future Study Methamphetamine is not Increasing


9

Past Year Methamphetamine Use among Persons Aged 12+, by Region:

2002 and 2006Percent Using in Past Year

0.1

0.6 0.6

1.6

0.3

0.5

0.7

1.6

0.0

0.5

1.0

1.5

2.0

Northeast Midwest South West

20022006

+ Difference between this estimate and the 2006 estimate is statistically significant at the .05 level.

Note: Estimates are based on new 2006 questions. 2002 estimates are adjusted for comparability.


10

Primary Methamphetamine/amphetamine admission rates (per 100,000 population aged 12 and over)


11

Methamphetamine Treatment Admissions

0

20000

40000

60000

80000

100000

120000

140000

160000

Num

ber

of A

dmis

sion

s

1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

2005 SAMHSA Treatment Episode Data Set2005 SAMHSA Treatment Episode Data Set


12

Diagnostic CriteriaBased on the Diagnostic and Statistical

Manual of Psychiatric Diseases IVth Edition (DSMIV)

• Abuse

• Dependence


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Diagnostic CriteriaMethamphetamine 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.]


14

Diagnostic CriteriaMethamphetamine 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


16

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)

Vmat

transporterActionpotentialActionpotential

DA/5HT DA/5HT

/serotonin/serotonin

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

A O

utp

ut

NAc shellNAc shell

EmptyEmpty

BoxBox FeedingFeeding

FOODFOOD

100100

150150

200200

DA

Co

nce

ntr

ati

on

(%

Bas

elin

e)D

A C

on

cen

tra

tio

n (

% B

asel

ine)

MountsMountsIntromissionsIntromissionsEjaculationsEjaculations

1515

00

55

1010

Co

pu

latio

n F

req

ue

nc

yC

op

ula

tion

Fre

qu

en

cy

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

SEXSEX

Natural Rewards Elevate Dopamine Levels

Natural Rewards Elevate Dopamine Levels

Source: Di Chiara et al.; Fiorino and PhillipsSource: Di Chiara et al.; Fiorino and Phillips

• Release DA from vesicles and reverse transporter

Methamphetamine

Vmat

transporter

/serotonin/serotonin

DA/5HT DA/5HT

100100

150150

200200

250250

00 11 22 33 4hr4hrTime After EthanolTime After Ethanol

% o

f B

as

al

Re

lea

se

% o

f B

as

al

Re

lea

se

0.250.250.50.5112.52.5

AccumbensAccumbens

00

Dose (g/kg ip)Dose (g/kg ip)

ETHANOLETHANOL

00

100100

150150

200200

250250

00 11 22 3 hr3 hr

Time After NicotineTime After Nicotine

% o

f B

as

al

Re

lea

se

% o

f B

as

al

Re

lea

se

AccumbensAccumbensCaudateCaudate

NICOTINENICOTINE

Time After MethamphetamineTime After Methamphetamine

% o

f B

asal

Re

lea

se%

of

Bas

al R

ele

ase

METHAMPHETAMINEMETHAMPHETAMINE

00 11 22 3hr3hr 00

100100

200200

300300

400400

Time After CocaineTime After Cocaine

% o

f B

as

al

Re

lea

se

% o

f B

as

al

Re

lea

se

DADADOPACDOPACHVAHVA

AccumbensAccumbens COCAINECOCAINE

00 11 22 33 44 5 hr5 hr

Source: Shoblock and Sullivan; Di Chiara and Imperato

Effects of Drugs on Dopamine ReleaseEffects of Drugs on Dopamine Release1500

1000

500

0

1500

1000

500

0

We Know That DespiteTheir Many Differences, most

Abused Substances Enhance theDopamine and Serotonin Pathways

We Know That DespiteTheir Many Differences, most

Abused Substances Enhance theDopamine and Serotonin Pathways

How do drugs work in the brain?How do drugs work in the brain?

Dopamine Pathways

Functions•reward (motivation)•pleasure, euphoria•motor function (fine tuning)•compulsion•perseveration

Serotonin Pathways

Functions•mood•memory processing•sleep•cognition

nucleusaccumbens

hippocampus

striatum

frontalcortex

substantianigra/VTA

raphe

Prolonged Drug Use Changesthe Brain In Fundamentaland Long-Lasting Ways

Prolonged Drug Use Changesthe Brain In Fundamentaland Long-Lasting Ways

Science Has Generated A Lot ofEvidence Showing That…

We Have Evidence That These Changes Can Be Both

Structural and Functional

We Have Evidence That These Changes Can Be Both

Structural and Functional

AND…AND…

Amph

NAC

Saline

Source: Robinson & Kolb, Journal of Neuroscience, 1997Source: Robinson & Kolb, Journal of Neuroscience, 1997

Structurally…Structurally…

DA

D2

Rec

epto

r A

vaila

bili

ty

Control Addicted

CocaineCocaine

AlcoholAlcohol

DA

DA

DA DA DA

DA

Reward Circuits

DA DA DA DA

DA

Reward Circuits

DA

DA

DA

DA DA

DA

Drug Abuser

Non-Drug Abuser

HeroinHeroin

MethMeth

Dopamine D2 Receptors are Lower in Addiction

DA

Functionally…Functionally…


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Effect of Methamphetamines

Courtesy of Jane Koropsak, Brookhaven National Lab.

Dopamine Transporters in Methamphetamine AbusersDopamine Transporters in Methamphetamine Abusers

Normal Control

Methamphetamine Abuser

Motor TaskLoss of dopamine transporters in the meth abusers may result in slowing of motor reactions.

Memory taskLoss of dopamine transporters in the meth abusers may result in memory impairment.

7 8 9 10 11 12 131.0

1.2

1.4

1.6

1.8

2.0

Time Gait(seconds)

468101214161.01.2

1.4

1.6

1.8

2.0

Delayed Recall(words remembered)

Do

pam

ine

Tra

nsp

ort

erB

max

/Kd

Source: Volkow et al., Am. J. Psychiatry, 2001.

Partial Recovery of Brain Dopamine Transporters in Methamphetamine

(METH)Abuser After Protracted Abstinence

Normal Control METH Abuser(1 month abstinent)

METH Abuser(24 months abstinent)

0

3

ml/gm

Source: Volkow, ND et al., Journal of Neuroscience, 2001.


31

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


32

Long Term effectsBehavior 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


33

Video clip

• Effects of Methamphetamine use

QuickTime™ and aDV/DVCPRO - NTSC decompressor

are needed to see this picture.

Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic

In Several Ways

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

Disease Transmission

• IV Drug Use• Drug User Disinhibition Leading to

High Risk Sexual Behaviors

Progression of Disease


35

Fetal Effects of MethamphetamineFetal Effects of Methamphetamine

•Lower arousal•Poorer self-regulation•Poorer quality of movement•Increased central nervous system stress•Small for gestational age•Long-term consequences???

Preliminary evidence suggests that prenatal methamphetamine exposure is associated with subtle physical and neurobehavioral effects including:


36

Clinical PresentationIntoxication

• 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 PresentationIntoxication

• 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 PresentationWithdrawals

• “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 PresentationWithdrawals

• “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 Treatment1. No single treatment is appropriate for all individuals. 2. Treatment needs to be readily available. 3. Effective treatment attends to multiple needs of the individual, not just his or her

drug use. 4. 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. 5. Remaining in treatment for an adequate period of time is critical for treatment

effectiveness. 6. Counseling (individual and/or group) and other behavioral therapies are critical

components of effective treatment for addiction. 7. Medications are an important element of treatment for many patients, especially

when combined with counseling and other behavioral therapies. 8. Addicted or drug-abusing individuals with coexisting mental disorders should have

both disorders treated in an integrated way. 9. Medical detoxification is only the first stage of addiction treatment and by itself does

little to change long-term drug use.10. Treatment does not need to be voluntary to be effective. 11. Possible drug use during treatment must be monitored continuously. 12. 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.

13. 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 )

http://www.drugabuse.gov/podat/podatindex.html

Source: Adapted from Volkow et al., Neuropharmacology, 2004.

DriveSaliency

Memory

Control

Non-Addicted Brain

NO GO

Addicted Brain

Drive

Memory

Control

GOSaliency

Why Can’t Addicts Just Quit?

Because Addiction Changes Brain CircuitsBecause Addiction Changes Brain Circuits

CONTROL CONTROL

REWARDREWARD DRIVEDRIVE

CONTROL CONTROL

DRIVEDRIVE

MEMORYMEMORY

CONTROL CONTROL

DRIVEDRIVE

MEMORYMEMORY

CONTROL CONTROL

Strengthen frontal control

Strengthen frontal control

MEMORYMEMORY

Weaken learnedpositiveassociationswith drugsand drugcues

Weaken learnedpositiveassociationswith drugsand drugcues

REWARDREWARD

Decreasethe rewardingvalue ofdrugs

Decreasethe rewardingvalue ofdrugs REWARDREWARD

Increase the rewarding valueof non-drugreinforcers

Increase the rewarding valueof non-drugreinforcers

Treating the ADDICTED BrainTreating the ADDICTED Brain

DRIVEDRIVE

MEMORYMEMORY

REWARDREWARD


44

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 SpiritualitySpecific 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 usehttp://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


52

Clinical Vignette # 3A 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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Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses

Source: McLellan, A.T. et al., JAMA, Vol 284(13), October 4, 2000.

Drug Addiction

Type I Diabetes

0

10

20

30

40

50

60

70

80

90

100

Hypertension Asthma

40 t

o 6

0%40

to

60%

30 t

o 5

0%30

to

50%

50 t

o 7

0%50

to

70%

50 t

o 7

0%50

to

70%

Per

cen

t o

f P

atie

nts

Wh

o R

elap

se


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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


56

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/IDCA1.html


57

Suggested reading

• Meredith CW, Jaffe C, Ang-Lee K, Saxon AJ. Implications of chronic methamphetamine use: a literature review. Harv Rev Psychiatry. 2005 May-Jun;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. One month

2. One year

3. One week

4. One decade


59


2. Diagnosis of Methamphetamine dependence requires the presence of the following number of criteria out of the possible seven:

1. Three2. Four3. Five4. Six5. Seven


60


3. Methamphetamine works primarily by:1. Increasing dopamine breakdown

2. Increasing serotonin release

3. Increasing acetylcholine blockade

4. Increasing nor epinephrine synthesis


61


4. Methamphetamine can cause death by:1. Respiratory depression

2. Hyperthermia

3. Metabolic acidosis

4. Metabolic Alkalosis


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5. The fastest way to get a high form methamphetamine use is:

1. Skin popping

2. Ingesting

3. Snorting

4. Smoking


63


6. Approximately the following percentage of people can be expected to have used methamphetamine in the United Sates:

1. 10%

2. 4%

3. 2%

4. 1%


64


7. The effects of methamphetamine can generally last for:

1. 60 seconds or less

2. 1 hours

3. 2 hours

4. Methamphetamine’s effects can last for a long time, perhaps up to 24 hours


65


8. Methamphetamine dependence can be successfully treated with:

1. Naltrexone

2. Disulfiram

3. Antidepressant medications

4. Behavioral therapies


66


9. Cues that produce cravings can:1. Stimulate the amygdala

2. Stimulate the frontal cortex

3. Stimulate the nigrostriatal pathway

4. Can inhibit the nucleus accumbens

5. Can stimulate the temporal lobe


67


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.


68


11. Methamphetamine use most commonly presents with another co-morbid condition that is:

1. Bipolar disorder

2. Hypertension

3. Suicidal disorder

4. Another substance use disorder


69


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.

Methamphetamine Senior Residents Lecture Your name Title Institution.

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