The American Indian/Alaska Native National Resource Center for Substance Abuse and Mental Health Services

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The American Indian/Alaska Native National
Resource Center for Substance Abuse and Mental
Health Services
What is Methamphetamine and what are its effects?
Dale Walker, MD Patricia Silk Walker, PhD
Michelle Singer August 1, 2007 Sioux Falls,
South Dakota
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Overview

• The issues
• Chemistry
• Pharmacology how the body handles
• the drug
• Pharmacology mechanisms
• The desired effects why people like it
• The problems why people hate it
• Methamphetamine vs other drugs
• Pregnancy mother and child

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Views of the Most Important Problems Facing
Teenagers Today
Harvard School of Public Health/Robert Wood
Johnson Foundation/ICR, July 2000
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National Drug Intelligence Center National Drug
Threat Assessment 2005 - February 2005
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A Major Reason People Take a Drug is they Like
What It Does to Their Brains
The first use is usually voluntary
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Why do people take drugs?
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Effects of Drugs on Dopamine
Dopamine Pathways Principal Pleasure System of
the Brain
COCAINE
AMPHETAMINE
Accumbens
1100
Accumbens
400
1000
900
DA
800
300
DA
700
600
of Basal Release
500
200
of Basal Release
400
300
100
200
100
0
0
0
1
2
3
4
5 hr
0
1
2
3
4
5 hr
Time After Amphetamine
Time After Cocaine
Source Di Chiara and Imperato
Natural Rewards Elevate Dopamine
FOOD
SEX
200
200
NAc shell
150
150
100
100
15
of Basal DA Output
10
Empty
DA Concentration ( Baseline)
50
Copulation Frequency
Box
Feeding
5
0
0
Scr
Scr
Scr
Scr
0
60
120
180
Bas
Female 1 Present
Female 2 Present
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
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Time (min)
Sample Number
Di Chiara et al.
Fiorino and Phillips
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Forms of Methamphetamine
Methamphetamine Powder Beige/yellowy/off-white
powder
Base / Paste Methamphetamine Oily, gunky,
gluggy gel, moist, waxy
Crystalline Methamphetamine White/clear
crystals/rocks crushed glass / rock salt
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Chemistry 1

• Methamphetamine does not occur in nature.
• It is like two chemicals found in the body??
  Adrenaline, released in fight or flight ??
  Dopamine which controls both reward
• and movement in the brain

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Chemistry 2 Methamphetamine is very close to
Amphetamine (speed) in structure
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Chemistry 3

• Compounds from plants that are chemically
• similar are ephedrine and mescaline
• Methamphetamine is easy to make from
• materials that are hard to control
• pseudoephedrine, iodine, and red phosphorus
  from matchbooks
• Waste by-products from the synthesis are toxic
• and environmentally harmful

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Methamphetamine Absorption

• Fat soluble, so easily and rapidly absorbed.
• Gets into the brain faster than amphetamine
• Onset
• ?? oral - about 30-60 minutes
• ?? Snorted - 2-5 minutes
• ?? injected or smoked almost
• instantaneous

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Methamphetamine Elimination

• Elimination half life about 12 hours
• Effects can last 24 hours
• 55 broken down by the liver
• remainder excreted as methamphetamine or
  amphetamine
• Drug and metabolites detectable 2-4 days
• Urine or saliva can be used for testing
• Impurity profiling for medico-legal purposes.
  There are about 245 possible impurities!

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The most important action

• Meth enters the nerve ending, and causes the
  transmitter to be released. It displaces the
  transmitter from the storage site. This means
  that even if the nerve in the reward pathway has
  not been stimulated, the transmitter will be
• released and reward experienced.

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Methamphetamine has several mechanisms

• It directly releases dopamine and
  norepinepherine from the nerve endings in the
  brain (and also outside the brain)
• It inhibits the transporter leading to increased
  material in the synapse (like cocaine)
• It both CAUSES nerves to fire and
• AMPLIFIES existing nerve activity.

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Desired Effects

• Energy, less fatigue, wakefulness enhanced
  performance
• May promote impulsive decision making
• Feelings of joy, power, success, high self-esteem
• Enhanced sexual desire and interest
• Later in the addiction process the user may have
  very little interest in sex.

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Undesired Effects

• Delusional, risky, paranoid, violent
• Itching, welts on the skin
• Nausea, vomiting, diarrhea
• Uncontrolled body movements
• The crash
• Increased blood pressure, heart rate,
• body temperature. Risk of stroke, seizures
• Japan most deaths from meth toxicity
• USA most deaths from homicide/suicide

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Short-Term Effects of Methamphetamine

• PSYCHOLOGICAL
• Confidence
• Alertness
• Mood
• Sex drive
• Energy
• Talkativeness
• Boredom
• Loneliness
• Timidity

• PHYSICAL
• Heart rate
• Respiration
• Blood pressure
• Pupil size
• Sensory acuity
• Energy
• Appetite
• Sleep
• Reaction time

Source Judith Cohen, Ph.D., Presentation to
NASADAD, June 2005
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Long-term Problems

• Disturbed sleep
• Social isolation and withdrawal
• Lifestyle-related accident
• Amphetamine psychosis
• Violent and/or paranoid behavior
• Irritability, nervousness, distractibility,
  difficulty focusing and remembering
• Extreme depression, suicidal ideation
• NOT ALL OF THESE ALWAYS REVERSE WITH ABSTINENCE

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MethamphetamineChronic Physical Effects

• Tremor
• Weakness
• Dry mouth
• Weight loss
• Cough
• Sinus infection

• Sweating
• Burned lips sore nose
• Oily skin/complexion
• Headaches
• Diarrhea
• Anorexia

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MethamphetamineChronic Psychological Effects

• Confusion
• Concentration
• Hallucinations
• Fatigue
• Memory loss
• Insomnia

• Irritability
• Paranoia
• Panic reactions
• Depression
• Anger
• Psychosis

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MethamphetaminePsychiatric Consequences

• Paranoid reactions
• Permanent memory loss
• Depressive reactions
• Hallucinations
• Psychotic reactions
• Panic disorders
• Rapid addiction

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What about brain damage?

• This is often stated as a consequence of
• methamphetamine use. Usually recovers.
• There is convincing evidence in humans and
  animals, both by imaging and behavioral studies,
  that brain damage occurs

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What about behavioral consequences?

• Attention, verbal learning, memory, decision
• making are all impaired during early
  abstinence
• After 8 months abstinence, still slow on some
• tasks
• Headaches and depression may not improve,
• and there may be ongoing cognitive
  impairment.

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Flashbacks (recurrence of methamphetamine
psychosis) do occur

• Associated with frightening/stressful
• experience during use. Mild stress then
• triggers flashbacks
• Longer exposure to the situation makes
• flashbacks more frequent

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Methamphetamine Users Compared to Other Drug
Users

• Use daily
• More likely to be Caucasian, male, gay/bi, HIV
  positive, practice unsafe use (sharing needles
  etc.), have a psychiatric diagnosis, be on
  psychiatric meds
• Develop addiction more rapidly
• Seek treatment earlier
• Use more marijuana and/or less alcohol (but use
  alcohol or sedatives for sleep)
• Have more serious medical and psychiatric
  conditions

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Prenatal Exposure to Methamphetamine

• Methamphetamine easily crosses the placenta
• The fetal brain is very sensitive to any level of
  methamphetamine
• Metabolism of methamphetamine in the fetus is not
  the same as in adults
• We must have a high index of suspicion to
  adequately test moms and infants exposed to
  methamphetamine

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In pregnancy

• Very little data.
• Growth restriction occurs with full-term infants,
  (constriction of the umbilical artery?)
• 4 have a recognizable withdrawal syndrome.
• Evidence of cognitive deficit in children born to
  mothers who use meth
• Weak evidence for physical defects in children
• whose mothers used meth.

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Who to test?

• Maternal red flags
• History of drug use during pregnancy
• Premature birth
• Late, sporadic, or no prenatal care
• Numerous skin lesions
• Extremely poor dentition
• Very rapid labor/delivery

• Infant red flags
• Maternal history of drug use
• Maternal refusal for drug screen
• Excessive irritability
• Excessive jitteriness
• Very poor feeding, not responding to intervention
• Physical features suggestive of alcohol/drug use

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Maternal Effects of Methamphetamine During
Pregnancy

• Increased maternal blood pressure
• Increased maternal heart rate
• Increased risk of premature birth
• Constricts blood flow in the placenta, thereby
  impacting oxygen flow to the fetus

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Effects of Methamphetamine on the Developing
fetus/infant

• Poor fetal growthsmall for gestational age
• Elevated fetal blood pressure (stroke)
• Birth defects (6 times the normal rate)
• Cleft palate/lip
• Heart disease
• Kidney disease
• Intestines born outside the body
• Premature birth
• Placental hemorrhage

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Newborn signs of meth exposure

• Withdrawal
• Jittery
• Poor feeding
• Poor wake /sleep cycle
• Irritable
• High pitched cry
• Tremors
• Hypertonia

• These symptoms may last as long as 6 weeks, in
  contrast to withdrawal from other drugs which may
  only last the first week of life

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ADDICTION INVOLVES MULTIPLE FACTORS
Biology/Genes
Environment
DRUG
Brain Mechanisms
Addiction
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Research Tells Us That STRESS Can Be A Major
Factor In the Initiation of Drug Use
And One of the Most Powerful Triggers for Relapse
In Recovering Addicts
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Contact us at 503-494-3703 E-mail Dale Walker,
MD onesky_at_ohsu.edu Or visit our
website www.oneskycenter.org