Stimulants Amphetamine and Cocaine


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Stimulants


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




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