Stimulants
Amphetamine and Cocaine
Change in Brain Activity








Amphetamine
Synthetic amine
Activate dopamine in
reward circuits
Other amines involved in
mood
Activates fight or flight
Sympathetic NS
Emergency reaction
Stress response
Ephedra



Natural source of
ephedrine
Stimulant
Source for
amphetamine
Amphetamine



First produced in 1937
Used in WWII by
Germans, British and
Japanese
United States started
using amphetamine
during the Korean War
Post-war Japan






Huge stockpiles of amphetamine
after war
Sold without prescription
Advertised for “elimination of
drowsiness and repletion of the
spirit.
By 1948, one million dependent
Japanese
Tight controls imposed in 1954.
By 1958, problem greatly reduced
Korean War Vets






Returned to US
Entered college on GI
Bill
Study for exams
Remember stimulant
used during war
Available in Rx
Sought another route
Vets found supply source



Long distance truck
drivers had been using
amphetamine.
Became main source for
college vets.
Also supplied to high
achievers in
entertainment and
business.
Weight Control


Amphetamines as very
popular for weight
control and relief from
boredom.
During 1960’s, 99% of
amphetamine Rx written
for weight loss.
Amphetamine Epidemic




In 1967, 31 million prescriptions written for
weight control.
In 1966, 25 tons of legally manufactured
amphetamine was diverted to illegal sale.
90% of legal manufactured drug never made it
to market.
In 1970, FDA put the breaks on.
1970 FDA guidelines




Amphetamine could only be prescribed for three
conditions:
1) nacrolepsy
2) short term weight loss
3) hyperkinesis
Nacrolepsy








Sleep seizure
Sudden onset
Inappropriate times
Loss of muscle tone
Hallucinations
Enter REM sleep
Dreaming
Muscle paralysis
Weight Reduction






More the 50% of US
adults overweight.
Major health problem.
Heart disease, diabetes.
Huge market in diet aids.
95% of pounds lost are
regained.
Need permanent change
in lifestyle, including
regular exercise.
Amphetamine for weight loss








Effective for two weeks.
Lose weight, gain energy, good mood.
Tolerance develops.
Need to increase dose.
Shop for doctors; multiple perscriptions.
Get amphetamine from black market.
Or weight comes back, energy and mood sag.
True with all stimulant weight loss agents.
Diet Pills not a solution







Don’t learn anything about nutrition.
Don’t change exercise habits.
Many make take pills for energy and euphoria.
Tolerance leads to high doses.
Start to develop symptoms of psychosis.
Movie: Requiem for a Dream
Woman wants to lose weight to get on TV quiz show.
Keeps increasing dosage until she has psychotic break.
Hyperkinesis






Hyperactivity
Restless, distractible,
mood swings, act out,
not doing well in school.
90% boys
Most identified in early
grades
Parents and teachers
Rx: Ritalin
Ritalin





Mild stimulant.
How could a stimulant calm a child?
Wouldn’t you expect them to be more active and
distractible?
Early theories: differences in brain structure
and function.
Paradoxical effect in children with hyperactivity.
Attention Deficit Disorder



Loss of attention leads to distractibility and restlessness
Take kids to see cartoon. Hypnotic stillness.
Take kids to see romantic comedy. Suddenly hyperactive
Action of Ritalin






Increase attention.
Increase inhibition (improve brake linings on the
brain).
Reduce hyperactivity.
Acts the same in adults.
Small dose helps concentration, alertness.
Higher doses become too hyper, lose
concentration.
Concerns with Ritalin







Loss of attention could be do to other
problems.
Solve primary cause: family problems.
Long term effects of the drug are unknown.
Chemical solutions not the best.
Retrain the brain through neural feedback.
Teachers forbidden to suggest use of Ritalin to
parents.
Child needs a full exam by a professional.
Other meds for ADD








Adderall
Dexedrine
Cylert (pemoline)
All stimulants
All act on dopamine
Fewer side effects
Longer lasting
Antidepressants such as
Effexor
Cocaine





Action on the brain very similar to amphetamine.
History of stimulant use.
Alternating use of amphetamine and cocaine.
Develop new forms of each.
More addictive and dangerous.
Coca Plant
Rich history
 Used by native
peoples in Peru,
Bolivia and
Columbia

Coca leaves chewed
Combat fatigue
 Slow and steady
 No Rush
 Part of native
religion and
folklore

Spanish invaders




Spanish overseers used
natives as slaves.
Priests opposed coca use.
Natives weren’t able to
work as intensely.
Priest allowed use but
destroyed native culture.
Coca’s use continues today
Coca traded around the world
Coca Wine


Most popular form
in Europe.
For “neuralgia,
sleeplessness (?),
despondency
Mariani Wine



Most popular in 1800’s
Angelo Mariani
Famous endorsers:
Thomas Edison
Jules Verne
Pope Leo XIII
Vin Mariani


“Fortifies and refreshes
body and brain
Restores health and
vitality.”
Patent medicines
Freud and Koller





Medical uses
Experiments with friend
Carl Koller
Noticed relieved pain.
Koller used it to deaden the
cornea before eye surgery
Father of local anesthesia
Koller’s legacy







Local anesthetics
Lidocaine
Procaine
Novacaine
All based on cocaine
Nerve blocks
Stop transmission of
neural pain messages
Freud’s cocaine prescriptions





Freud searching for
another use.
Relieve morphine
addiction.
Rx for colleague, Fleisch.
Morphine addiction
transferred into first
cocaine addiction.
Tolerance and psychosis.
Dr. J.C. Pemberton



Formulated his own
nerve tonic in 1886.
Used extracts from
coca and cola plants to
produce patent
medicine.
“Cure for all nervous
afflictions”
Coca-Cola





“Relieves mental and
physical exhaustion”
“Cures headache”
New idea:
AT ALL SODA
FOUNTAINS
Formulation had to be
changed after 1906 with the
Pure Food and Drug Act
Cocaine illegal




1914 Harrison
Narcotic Act
“Narcotic” as
dangerous drug
Political pressure to
include cocaine with
opiates.
Media hype about
rape and murder.
Cocaine remained popular



Cole Porter 1934 lyric:
“I get no kick from cocaine
I'm sure that if I took even one sniff
It would bore me terrifically too
Yet I get a kick out of you”
New lyric:
“I get perfume from Spain”
Safe drug?






1970’s cocaine returned as rich person’s drug
Advertised as safe
In 1980, Scientific American reported that
“cocaine was addictive as potato chips”
Few ill effects (?)
No tolerance(?), no addiction(?)
Soon, we learned these beliefs were WRONG.
Cocaine is addictive





Most common route was snorting
Effect lasts 20-30 minutes
Euphoria
One NYC user: “It makes you shiver in tune
with the raw volcanic energy of NY. It blends
your senses til you see the city as an epileptic
rainbow, trembling at the speed of light.”
Likened to the pleasure of orgasm
Higher doses







Paranoia
Hallucinations
Symptoms of psychosis
Depression as an after-effect
Strong psychological dependenc
Tolerance with chronic use
High cost as use accelerates
New forms: Freebase





Cocaine water soluble
but not smokeable.
Freebasing
Cocaine is treated with
ether (flammable)
Product can then be
smoked
Smoke reaches lungs and
brain faster
New forms: Crack





Another smokeable
form
Treat cocaine with
chemicals
Cheaper per dose
More doses to
maintain high
More addictive
Methamphetamine







Use patterns cycling back
to amphetamine.
“ice or crystal meth”
Easy to manufacture
Start with ephedrine
Tolerance
Addictive
Scourge of rural
America