March 13 Amphetamine

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March 13 Amphetamine Thursday we will cover
Cocaine and then do Ecstasy after the
break. Paper outline/descriptive paragraph plus 5
papers due Mar 29.
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• Amphetamine
• A. General characteristics
• Psychostimulant that produces effects in CNS and
  PNS more potent in CNS
• In CNS, d amphetamine is 3-4 times more potent
  than l amphetamine
• Methamphetamine is more potent that d amphetamine
  and is the drug of abuse Ice, crystal
• D amphetamine used as a prescription medication
  for attention deficit hyperactivity disorder,
  narcolepsy, and short term treatment of obesity

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• Amphetamine
• Obesity 5-10 mg given 30-60 min before meals
  tolerance in 2-6 weeks
• Narcolepsy 10 mg/day recommended no
  significant tolerance
• ADHD (Adderal) 0.1-0.5 mg/kg/day no tolerance
• Absorbed well orally effects begin in 30 min,
  peak 2-3 hours later may last 7 hours
• Half-life is 12 hours

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• B. Mechanism of action of d-amphetamine
• Increases release of norepinephrine and dopamine
  and serotonin from axon terminals in
  dose-dependent manner
• Low dose mostly norepinephrine alerting
  effect anorectic effect
• Medium dose NE and DA motor stimulation
  reward
• High dose also serotonin psychosis
  hallucinations
• Also blocks reuptake of NE and DA
• Causes increased heart rate, elevated blood
  pressure, tremor, increased alertness, increased
  motor activity,decreased need for sleep appetite
  suppression
• Methamphetamine more potent in CNS and effects
  NE, DA and serotonin at most doses that would be
  taken.

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• Amphetamine
• C. History
• 1930s U.S. benzedrine marketed for treatment of
  asthma, narcolepsy, depression, appetite
  suppression (bennies)
• Also used to keep soldiers alert during combat in
  WWII
• After war, prescribed for fatigue and appetite
  suppression
• Social problems began in 1940s-1950s
• Problems continued particularly students, truck
  drivers, athletes, businessmen - 75 cents for
  1000 tablets in 60s

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• Hippy subculture did not endorse amphetamine use
  a lowly drug speed freaks not calm and
  peaceful but agitated and violent gave other
  mind-expanding drugs a bad name
• All the nice gentle dope fiends are getting
  screwed up by the real horror monster
  Frankenstein speed freaks who are going around
  stealing and bad mouthing everybody Ginsburg,
  1965
• 1965 FDA given authority to regulate
  manufacturing and distribution
• But so easily made by amateur chemists, did not
  work
• 1970s still available but from illegal
  manufacturers
• 1970s- 5-10 for 100 tablets widely used and
  readily available

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• History
• Use declined in 70s and 80s but now back up and
  primarily methamphetamine that is smoked,
  snorted, injected or taken orally Ice, crank,
  crystal, speed, meth, chalk
• San Diego amphetamine capitol of the world
  4-5 tons/year in illegal labs
• Snorting or oral use produces euphoria, but not
  an intense rush
• Ice (glass) heated in glass pipe and smoked or
  melted and vaporized and inhaled Rush in
  seconds, lasting 6-8 hrs
• Ice abusers may smoke 1 gram/day about 500/day
  habit

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D. Research on amphetamine 1. 10 mg oral dose of
d-amphetamine to naïve users causes CNS mostly
NE Wakefulness reduced fatigue Mood
elevation alertness/improved concentration Increa
sed motor activity Increased speech Improved
performance on simple tasks Improved physical
performance in athletes PNS effects at alpha
and beta receptors for NE Increased heart rate
increased blood pressure relaxed bronchial
muscles (helps asthma) tremors sweating
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D. Research on amphetamine 1. 10 mg oral dose to
naïve users 2. Withdrawal following prolonged
use in 10-30 mg range sleep disturbances
depression fatigue. May take 2 months for sleep
to normalize. 3. 15-30 mg range d-amphetamine for
naïve users NE DA and SE toxic
range Restlessness Irritability Euphoria Tremor
weakness confusion Dizziness insomnia anxiety
Fever paranoid hallucinations Panic
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D. Research on amphetamine 1. 10 mg oral dose to
naïve users 2. Withdrawal following prolonged
use in 10-30 mg range 3. 15-30 mg range for
naïve users NE DA and SE 4. 60 mg/day d
amphetamine for at least 2-3 days clear
Amphetamine toxicity lasting about a week after
discontinuation. This applies to regular
methamphetamine use as well. Amphetamine
psychosis paranoia disordered thought
hallucinations Parisitosis (formication) feeling
of having bugs on or under the skin peripheral
nerve endings in skin pick skin may probe with
a knife Stereotyped behaviors (tweaking) repeat
acts over and over for hours. Pacing, cleaning,
stringing beads, etc.
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D. Research on amphetamine 1. 10 mg oral dose to
naïve users 2. Withdrawal following prolonged
use in 10-30 mg range 3. 15-30 mg range for
naïve users NE DA and SE 4. 60 mg/day for at
least 2-3 days (seen in users) clear Amphetamine
toxicity lasting about a week after
discontinuation 5. After stimulant phase
crash Fatigue severe depression increased
appetite Cardiovascular effects headache
chills flushed appearance (look pale) heart
arrhythmias hyper or hypotension Anorexia
nausea vomiting diarrhea abdominal cramps
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• D. Research on amphetamine
• 5. After stimulant phase crash
• 6. Pattern of use several day run of use (4-6
  day binge), then crash and may sleep for 2 days
  cycles. In crash, person is lethargic for days
  then symptoms gone in about a week.
• 7. Lethal dose in naïve users 120 mg/kg d
  amphetamine - overdose reaction stroke
  convulsions coma
• But cardiovascular and mental effects show
  marked tolerance in regular users
• 400-2000 mg can be taken by regular user
• One reported case had 17000 mg intake in 24
  hours without acute illness

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D. Research on amphetamine 8. Nature of
tolerance Fast for effects on heart and appetite
suppression. Fast for euphoria Slowest for
effects on attention and narcolepsy when used at
recommended doses) Receptors for NE, DA, SE down
regulate by reducing sensitivity Then when usage
stopped, more receptors are formed Normal
production of neurotransmitters is inadequate to
stimulate causes craving and anhedonia
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D. Research on amphetamine 9. Pre 80s - Usage
escalation of d amphetamine often at a
1000mg/day level of pill use, users want more
effects and switch to methamphetamine and to
other routes - smoking or IV use Methamphetamine
speed of old days IV methamphetamine
effects felt immediately and last about 5 min.
Rush described as orgasmic and euphoric. May
inject 10x/day (2 g/day) for 4-6 days then crash.
Sleep 2 days then start again. Get Malnourished.
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• D. Research on amphetamine
• 9. Todays use Methamphetamine (crystal crank
  chalk Ice glass)
• Still snort or take orally, but more commonly
  smoked or injected by abusers
• Ingestion 15-20 minutes for effects high, no
  intense rush last 6-8 hours.
• Snorting high, but no intense rush. Feel
  effects in 3-5 minutes. Lasts 6-8 hours.
• Smoking or IV injection immediate intense rush
  that lasts a few minutes
• Rush attributed to dopamine release in reward
  centers

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D. Research on amphetamine 9. Todays use
(crystal crank chalk Ice glass) 12 year olds
and up 10.4 million have tried it 3-4 of 8th
graders 4.5 of H.S. seniors Popularity growing
since 1995
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Ice (glass) heated in glass pipe and smoked or
melted and vaporized and inhaled Rush in
seconds, lasting 12 hrs
Ice abusers may smoke 1 gram/day about 500/day
habit
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• 10. Long term consequences of abuse
• Paranoid psychosis homicidal and suicidal
  thoughts rage violence hallucinations.
  Typically lasts 1 week, but for some, some
  psychosis remains as a problem.
• damage to dopamine-producing neurons
• damage to serotonin neurons
• long term effects on cognition and affect
  (depression)
• damage to heart and blood vessels
• skin abscesses
• increased risk for hepatitis B and C HIV among
  IV users
• (acute lead poisoning due to contamination)

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D. Research on amphetamine 10. Long term
consequences of abuse 11. Fetal effects
increased miscarriage increased prematurity
withdrawal seen in infants long term behavioral
effects suggested in animal studies