StimulantsStimulants

Amphetamine and CocaineAmphetamine and Cocaine

Change in Brain ActivityChange in Brain Activity AmphetAmphetamineamine Synthetic amineSynthetic amine Activate dopamine Activate dopamine

in reward circuitsin reward circuits Other amines Other amines

involved in moodinvolved in mood Activates fight or Activates fight or

flightflight Sympathetic NSSympathetic NS Emergency reactionEmergency reaction Stress responseStress response

EphedraEphedra

Natural source Natural source of ephedrineof ephedrine

StimulantStimulant Source for Source for

amphetamineamphetamine

AmphetamineAmphetamine

First produced in First produced in 19371937

Used in WWII by Used in WWII by Germans, British Germans, British and Japaneseand Japanese

United States United States started using started using amphetamine amphetamine during the Korean during the Korean WarWar

Post-war JapanPost-war Japan Huge stockpiles of Huge stockpiles of

amphetamine after waramphetamine after war Sold without prescriptionSold without prescription Advertised for “elimination Advertised for “elimination

of drowsiness and repletion of drowsiness and repletion of the spirit.of the spirit.

By 1948, one million By 1948, one million dependent Japanesedependent Japanese

Tight controls imposed in Tight controls imposed in 1954.1954.

By 1958, problem greatly By 1958, problem greatly reducedreduced

Korean War VetsKorean War Vets

Returned to USReturned to US Entered college on Entered college on

GI BillGI Bill Study for examsStudy for exams Remember Remember

stimulant used stimulant used during warduring war

Available in RxAvailable in Rx Sought another Sought another

routeroute

Vets found supply sourceVets found supply source

Long distance truck Long distance truck drivers had been drivers had been using amphetamine.using amphetamine.

Became main Became main source for college source for college vets.vets.

Also supplied to Also supplied to high achievers in high achievers in entertainment and entertainment and business.business.

Weight ControlWeight Control

Amphetamines as Amphetamines as very popular for very popular for weight control and weight control and relief from relief from boredom.boredom.

During 1960’s, During 1960’s, 99% of 99% of amphetamine Rx amphetamine Rx written for weight written for weight loss.loss.

Amphetamine EpidemicAmphetamine Epidemic

In 1967, 31 million prescriptions In 1967, 31 million prescriptions written for weight control.written for weight control.

In 1966, 25 tons of legally In 1966, 25 tons of legally manufactured amphetamine was manufactured amphetamine was diverted to illegal sale.diverted to illegal sale.

90% of legal manufactured drug 90% of legal manufactured drug never made it to market.never made it to market.

In 1970, FDA put the breaks on.In 1970, FDA put the breaks on.

1970 FDA guidelines1970 FDA guidelines

Amphetamine could only be Amphetamine could only be prescribed for three conditions:prescribed for three conditions:

1) nacrolepsy1) nacrolepsy 2) short term weight loss2) short term weight loss 3) hyperkinesis3) hyperkinesis

NacrolepsyNacrolepsy

Sleep seizureSleep seizure Sudden onset Sudden onset Inappropriate timesInappropriate times Loss of muscle toneLoss of muscle tone HallucinationsHallucinations Enter REM sleepEnter REM sleep DreamingDreaming Muscle paralysisMuscle paralysis

Weight ReductionWeight Reduction More the 50% of US More the 50% of US

adults overweight.adults overweight. Major health problem.Major health problem. Heart disease, Heart disease,

diabetes.diabetes. Huge market in diet Huge market in diet

aids.aids. 95% of pounds lost are 95% of pounds lost are

regained.regained. Need permanent Need permanent

change in lifestyle, change in lifestyle, including regular including regular exercise.exercise.

Amphetamine for weight Amphetamine for weight lossloss

Effective for two weeks.Effective for two weeks. Lose weight, gain energy, good mood.Lose weight, gain energy, good mood. Tolerance develops.Tolerance develops. Need to increase dose.Need to increase dose. Shop for doctors; multiple perscriptions.Shop for doctors; multiple perscriptions. Get amphetamine from black market.Get amphetamine from black market. Or weight comes back, energy and mood Or weight comes back, energy and mood

sag.sag. True with all stimulant weight loss True with all stimulant weight loss

agents.agents.

Diet Pills not a solutionDiet Pills not a solution

Don’t learn anything about nutrition.Don’t learn anything about nutrition. Don’t change exercise habits.Don’t change exercise habits. Many make take pills for energy and Many make take pills for energy and

euphoria.euphoria. Tolerance leads to high doses.Tolerance leads to high doses. Start to develop symptoms of psychosis.Start to develop symptoms of psychosis. Movie: Movie: Requiem for a DreamRequiem for a Dream Woman wants to lose weight to get on TV Woman wants to lose weight to get on TV

quiz show. Keeps increasing dosage until quiz show. Keeps increasing dosage until she has psychotic break.she has psychotic break.

HyperkinesisHyperkinesis

HyperactivityHyperactivity Restless, Restless,

distractible, mood distractible, mood swings, act out, not swings, act out, not doing well in school.doing well in school.

90% boys90% boys Most identified in Most identified in

early gradesearly grades Parents and teachersParents and teachers Rx: RitalinRx: Ritalin

RitalinRitalin

Mild stimulant.Mild stimulant. How could a stimulant calm a child?How could a stimulant calm a child? Wouldn’t you expect them to be Wouldn’t you expect them to be

more active and distractible?more active and distractible? Early theories: differences in brain Early theories: differences in brain

structure and function.structure and function. Paradoxical effect in children with Paradoxical effect in children with

hyperactivity.hyperactivity.

Attention Deficit Attention Deficit DisorderDisorder

Loss of attention leads to distractibility and Loss of attention leads to distractibility and restlessnessrestlessness

Take kids to see cartoon. Hypnotic stillness.Take kids to see cartoon. Hypnotic stillness. Take kids to see romantic comedy. Suddenly Take kids to see romantic comedy. Suddenly

hyperactivehyperactive

Action of RitalinAction of Ritalin

Increase attention.Increase attention. Increase inhibition (improve brake Increase inhibition (improve brake

linings on the brain).linings on the brain). Reduce hyperactivity.Reduce hyperactivity. Acts the same in adults.Acts the same in adults. Small dose helps concentration, Small dose helps concentration,

alertness.alertness. Higher doses become too hyper, lose Higher doses become too hyper, lose

concentration. concentration.

Concerns with RitalinConcerns with Ritalin Loss of attention could be do to other Loss of attention could be do to other

problems.problems. Solve primary cause: family problems.Solve primary cause: family problems. Long term effects of the drug are unknown.Long term effects of the drug are unknown. Chemical solutions not the best.Chemical solutions not the best. Retrain the brain through neural feedback.Retrain the brain through neural feedback. Teachers forbidden to suggest use of Teachers forbidden to suggest use of

Ritalin to parents.Ritalin to parents. Child needs a full exam by a professional.Child needs a full exam by a professional.

Other meds for ADDOther meds for ADD Adderall Adderall DexedrineDexedrine Cylert (pemoline)Cylert (pemoline) All stimulantsAll stimulants All act on All act on

dopaminedopamine Fewer side effectsFewer side effects Longer lastingLonger lasting Antidepressants Antidepressants

such as Effexorsuch as Effexor

CocaineCocaine

Action on the brain very similar to Action on the brain very similar to amphetamine.amphetamine.

History of stimulant use. History of stimulant use. Alternating use of amphetamine and Alternating use of amphetamine and

cocaine.cocaine. Develop new forms of each.Develop new forms of each. More addictive and dangerous.More addictive and dangerous.

Coca PlantCoca Plant

Rich historyRich history Used by native Used by native

peoples in peoples in Peru, Bolivia Peru, Bolivia and Columbiaand Columbia

Coca leaves chewedCoca leaves chewed

Combat fatigueCombat fatigue Slow and Slow and

steadysteady No RushNo Rush Part of native Part of native

religion and religion and folklorefolklore

Spanish invadersSpanish invaders

Spanish overseers Spanish overseers used natives as used natives as slaves.slaves.

Priests opposed Priests opposed coca use.coca use.

Natives weren’t able Natives weren’t able to work as intensely.to work as intensely.

Priest allowed use Priest allowed use but destroyed native but destroyed native culture.culture.

Coca’s use continues Coca’s use continues todaytoday

Coca traded around the Coca traded around the worldworld

Coca WineCoca Wine

Most popular Most popular form in form in Europe.Europe.

For For “neuralgia, “neuralgia, sleeplessness sleeplessness (?), (?), despondencydespondency

Mariani WineMariani Wine

Most popular in Most popular in 1800’s1800’s

Angelo MarianiAngelo Mariani Famous endorsers:Famous endorsers:

Thomas EdisonThomas Edison

Jules VerneJules Verne

Pope Leo XIIIPope Leo XIII

Vin MarianiVin Mariani

““Fortifies and Fortifies and refreshes body refreshes body and brainand brain

Restores health Restores health and vitality.”and vitality.”

Patent medicinesPatent medicines

Freud and KollerFreud and Koller

Medical usesMedical uses Experiments with Experiments with

friend Carl Kollerfriend Carl Koller Noticed relieved pain.Noticed relieved pain. Koller used it to Koller used it to

deaden the cornea deaden the cornea before eye surgerybefore eye surgery

Father of local Father of local anesthesiaanesthesia

Koller’s legacyKoller’s legacy

Local anestheticsLocal anesthetics LidocaineLidocaine ProcaineProcaine NovacaineNovacaine All based on All based on

cocainecocaine Nerve blocksNerve blocks Stop transmission Stop transmission

of neural pain of neural pain messagesmessages

Freud’s cocaine Freud’s cocaine prescriptionsprescriptions

Freud searching for Freud searching for another use.another use.

Relieve morphine Relieve morphine addiction.addiction.

Rx for colleague, Rx for colleague, Fleisch.Fleisch.

Morphine addiction Morphine addiction transferred into first transferred into first cocaine addiction.cocaine addiction.

Tolerance and Tolerance and psychosis.psychosis.

Dr. J.C. PembertonDr. J.C. Pemberton

Formulated his own Formulated his own nerve tonic in 1886.nerve tonic in 1886.

Used extracts from Used extracts from coca and cola plants coca and cola plants to produce patent to produce patent medicine.medicine.

““Cure for all Cure for all nervous afflictions”nervous afflictions”

Coca-ColaCoca-Cola ““Relieves mental and Relieves mental and

physical exhaustion”physical exhaustion” ““Cures headache”Cures headache” New idea:New idea: AT ALL SODA AT ALL SODA

FOUNTAINSFOUNTAINS Formulation had to be Formulation had to be

changed after 1906 changed after 1906 with the Pure Food with the Pure Food and Drug Actand Drug Act

Cocaine illegalCocaine illegal

1914 Harrison 1914 Harrison Narcotic ActNarcotic Act

““Narcotic” as Narcotic” as dangerous drugdangerous drug

Political pressure Political pressure to include to include cocaine with cocaine with opiates.opiates.

Media hype about Media hype about rape and murder.rape and murder.

Cocaine remained Cocaine remained popularpopular

Cole Porter 1934 lyric:Cole Porter 1934 lyric: ““I get no kick from cocaineI get no kick from cocaine

I'm sure that if I took even one sniffI'm sure that if I took even one sniffIt would bore me terrifically tooIt would bore me terrifically tooYet I get a kick out of you”Yet I get a kick out of you”

New lyric:New lyric:

“ “I get perfume from Spain”I get perfume from Spain”

Safe drug?Safe drug?

1970’s cocaine returned as rich person’s 1970’s cocaine returned as rich person’s drugdrug

Advertised as safeAdvertised as safe In 1980, Scientific American reported that In 1980, Scientific American reported that

“cocaine was addictive as potato chips”“cocaine was addictive as potato chips” Few ill effects (?)Few ill effects (?) No tolerance(?), no addiction(?)No tolerance(?), no addiction(?) Soon, we learned these beliefs were Soon, we learned these beliefs were

WRONG.WRONG.

Cocaine is addictiveCocaine is addictive

Most common route was snortingMost common route was snorting Effect lasts 20-30 minutesEffect lasts 20-30 minutes EuphoriaEuphoria One NYC user: “It makes you shiver in One NYC user: “It makes you shiver in

tune with the raw volcanic energy of tune with the raw volcanic energy of NY. It blends your senses til you see NY. It blends your senses til you see the city as an epileptic rainbow, the city as an epileptic rainbow, trembling at the speed of light.”trembling at the speed of light.”

Likened to the pleasure of orgasm Likened to the pleasure of orgasm

Higher dosesHigher doses

ParanoiaParanoia HallucinationsHallucinations Symptoms of psychosisSymptoms of psychosis Depression as an after-effectDepression as an after-effect Strong psychological dependencStrong psychological dependenc Tolerance with chronic useTolerance with chronic use High cost as use acceleratesHigh cost as use accelerates

New forms: FreebaseNew forms: Freebase

Cocaine water Cocaine water soluble but not soluble but not smokeable.smokeable.

FreebasingFreebasing Cocaine is treated Cocaine is treated

with ether with ether (flammable)(flammable)

Product can then be Product can then be smokedsmoked

Smoke reaches lungs Smoke reaches lungs and brain fasterand brain faster

New forms: CrackNew forms: Crack

Another Another smokeable formsmokeable form

Treat cocaine Treat cocaine with chemicalswith chemicals

Cheaper per Cheaper per dosedose

More doses to More doses to maintain highmaintain high

More addictiveMore addictive

MethamphetamineMethamphetamine

Use patterns cycling Use patterns cycling back to back to amphetamine.amphetamine.

““ice or crystal meth”ice or crystal meth” Easy to manufactureEasy to manufacture Start with ephedrineStart with ephedrine ToleranceTolerance AddictiveAddictive Scourge of rural Scourge of rural

AmericaAmerica