the major opiates most common used drug for relief of pain only true narcotics (stupor, sleep,...

The Major OpiatesThe Major Opiates

Most common used drug for relief of pain Most common used drug for relief of pain Only true Narcotics (stupor, sleep, Only true Narcotics (stupor, sleep,

analgesia)analgesia) compare to marijuana and cocaine which compare to marijuana and cocaine which

have other effects such as euphoria, have other effects such as euphoria, stimulant properties.stimulant properties.

Also cough suppressant & antidiarrea Also cough suppressant & antidiarrea propertiesproperties

““Narcotics” is Greek word for “stupor”Narcotics” is Greek word for “stupor” not for illicit psychoactive drugnot for illicit psychoactive drug


Opium derived from juice of poppy plant Opium derived from juice of poppy plant What is an opiate?What is an opiate?

AnalgesicAnalgesic Acts on endorphan/enkephalin receptorsActs on endorphan/enkephalin receptors Antagonized by naloxoneAntagonized by naloxone

Most potent painkiller, but severe dependence Most potent painkiller, but severe dependence


Endogenous OpiodsEndogenous Opiods Endorphine, Enkephalin, DynorphinEndorphine, Enkephalin, Dynorphin

in pituitaryin pituitary in pain sensors (spinal cord & midbrain)in pain sensors (spinal cord & midbrain) affective states (amygdala, hippocampus, locus affective states (amygdala, hippocampus, locus

coeruleus, and cerebral cortex)coeruleus, and cerebral cortex) autonomic system (e.g. medulla)autonomic system (e.g. medulla) stomach and intestinesstomach and intestines

Classification of OpiatesClassification of Opiates

3 specific groups of opiates used3 specific groups of opiates used Natural NarcoticsNatural Narcotics

Opium & extracts (morphine, codeine & thebaine)Opium & extracts (morphine, codeine & thebaine)

Semisynthetic NarcoticsSemisynthetic Narcotics Slight changes to chemical composition of morphineSlight changes to chemical composition of morphine E.g. heroinE.g. heroin

Synthetic Narcotics Synthetic Narcotics Not related to morphine, but produce opiate like responsesNot related to morphine, but produce opiate like responses

Classification of OpiatesClassification of Opiates

Opium, morphine, heroin, thebaine & Opium, morphine, heroin, thebaine & codeine referred to as opiatescodeine referred to as opiates

Synthetic Narcotics referred to a synthetic Synthetic Narcotics referred to a synthetic opiates or synthetic opiate-like drugsopiates or synthetic opiate-like drugs

History of OpiumHistory of Opium

Native to Middle East in areas bordering Native to Middle East in areas bordering MediterraneanMediterranean

Also Laos, Thailand, Afghanistan, Mexico & Also Laos, Thailand, Afghanistan, Mexico & ColumbiaColumbia

Use dates back 6000 years to SummariansUse dates back 6000 years to Summarians Egyptians used it medically 3500 years agoEgyptians used it medically 3500 years ago

Excavation of ceramic opium pipe in CypresExcavation of ceramic opium pipe in Cypres Common use among Islamic peoples for medical Common use among Islamic peoples for medical

& recreational purposes& recreational purposes not forbidden in Koran as were alcohol & many other not forbidden in Koran as were alcohol & many other

drugsdrugs

History of OpiumHistory of Opium Arab traders took to India & ChinaArab traders took to India & China

Also, western Europe learned about it from Also, western Europe learned about it from Arabs during crusades Arabs during crusades

1520 Paracelsus & laudanum1520 Paracelsus & laudanum 1680 Thomas Sydenham & his version of 1680 Thomas Sydenham & his version of

laudanumlaudanum Next 200 yrs primary consumption of opium Next 200 yrs primary consumption of opium

is as drinkis as drink

China & OpiumChina & Opium

Up to 1700’s Chinese use limited to Up to 1700’s Chinese use limited to “painkiller”“painkiller”

1818thth century development of opium smoking century development of opium smoking China first laws against Opium use in 1729China first laws against Opium use in 1729

dependence problem recognizeddependence problem recognized

British traded for tea with ChineseBritish traded for tea with Chinese 1773 Brits control of India-begin to supply 1773 Brits control of India-begin to supply

opium to China opium to China basis for Opium wars between China & Britishbasis for Opium wars between China & British

China & OpiumChina & Opium

China tried to control drug problemChina tried to control drug problem 1839 Defiance of European power1839 Defiance of European power

Confiscation of large quantities of opiumConfiscation of large quantities of opium Burned it in CantonBurned it in Canton Start of opium warStart of opium war

Opium WarsOpium Wars

First WarFirst War 1839-1842 Hong Kong ceded to British (‘til 1839-1842 Hong Kong ceded to British (‘til

1997), Canton & Shanghai opened for trade1997), Canton & Shanghai opened for trade

Second WarSecond War 1858-1860 British joined by French & 1858-1860 British joined by French &

American forcesAmerican forces 20 mill. pounds sterling, opening of 20 mill. pounds sterling, opening of

remaining ports, legalization & regulation of remaining ports, legalization & regulation of opium trade (ended 1906)opium trade (ended 1906)

Difference in Opium UseDifference in Opium Use

Major difference between opium use in China & Major difference between opium use in China & West was method of consumptionWest was method of consumption laudanum laudanum

Identified with Victorian Era Identified with Victorian Era Opening of “respectable parlors”Opening of “respectable parlors”

Chinese smoked it Chinese smoked it Identified with Opium DensIdentified with Opium Dens Ideal of “lazy” ChineseIdeal of “lazy” ChineseSeen as degrading & dirty vice Seen as degrading & dirty vice

Opium & the WestOpium & the West

Western societiesWestern societies Used opium as aspirinUsed opium as aspirin Cheaper than liquorCheaper than liquor No negative public opinionNo negative public opinion No real problem with copsNo real problem with cops Used to sooth infants & childrenUsed to sooth infants & children

Teething, colic or to keep them quiteTeething, colic or to keep them quite Women used it more than maleWomen used it more than male

Greater # addictionGreater # addiction

Problems in the WestProblems in the West

Collision of culturesCollision of cultures Chinese building railroadChinese building railroad 1875 San Francisco outlawed opium dens 1875 San Francisco outlawed opium dens

& opium smoking & opium smoking Laws targeted not at opium (laudanum legal), Laws targeted not at opium (laudanum legal),

but at Chinesebut at Chinese

Federal laws prohibiting opium smoking Federal laws prohibiting opium smoking followed followed

Morphine & the WestMorphine & the West

1803 Sertürner separated morphine from 1803 Sertürner separated morphine from opiumopium Increased dependence potentialIncreased dependence potential Morphine 10 X opium potencyMorphine 10 X opium potency Morpheus; Greek God of dreamsMorpheus; Greek God of dreams

1856 development of hypodermic needle1856 development of hypodermic needle Use became widespreadUse became widespread Doctors began injecting opium solutions (thought Doctors began injecting opium solutions (thought

sidestep addiction-thought purer & safer )sidestep addiction-thought purer & safer ) Used during Civil War for injuries (dependency known Used during Civil War for injuries (dependency known

as “soldier’s disease”)as “soldier’s disease”)

Heroin: From Bad to WorstHeroin: From Bad to Worst

In 1874 British chemist altered morphineIn 1874 British chemist altered morphine but unnoticed until rediscovered in 1898 but unnoticed until rediscovered in 1898 1898 German Heinrich Dreser1898 German Heinrich Dreser

Heroin-altered form of morphine Heroin-altered form of morphine 3X-4 X more potent than morphine 3X-4 X more potent than morphine Thought to be safer than morphineThought to be safer than morphine

Sold by Bayer beginning in lieu of codeine as Sold by Bayer beginning in lieu of codeine as medicine for coughs, bronchitis, tuberculosismedicine for coughs, bronchitis, tuberculosis

Heroin also began to replace morphine in addicted Heroin also began to replace morphine in addicted individuals individuals

Opiates in the USOpiates in the US

By 1900 250, 000 “opium dependent By 1900 250, 000 “opium dependent people” in USpeople” in US

By 1913, 400,000 lbs of opium imported By 1913, 400,000 lbs of opium imported into U.S. for consumption by U.S. into U.S. for consumption by U.S. population of 90 mill. peoplepopulation of 90 mill. people

Laws began cropping up around this Laws began cropping up around this time and formed the cornerstone of time and formed the cornerstone of American drug laws todayAmerican drug laws today

Opiates in US Early 1900’sOpiates in US Early 1900’s

Harrison Act of 1914Harrison Act of 1914 No ban on opiates, but doctors had to No ban on opiates, but doctors had to

register with IRSregister with IRS Decreased prescriptionsDecreased prescriptions

Users not seen as victims but weakUsers not seen as victims but weak heroin drug of choice in black marketheroin drug of choice in black market

Shift of users not women, but white urban adult Shift of users not women, but white urban adult malesmales

Opiates Use in 1960’sOpiates Use in 1960’s

3 Major Social Developments3 Major Social Developments Crackdown cause shortage of heroin & Crackdown cause shortage of heroin &

increased smuggling & price increased smuggling & price Increased levels of crimeIncreased levels of crime Increased used by urban minoritiesIncreased used by urban minorities

Peace movement, hippies & drug culturePeace movement, hippies & drug culture Vietnam WarVietnam War

Opiates Use in 1980, 90’sOpiates Use in 1980, 90’s ““Golden Triangle”Golden Triangle”

Laos, Burma & ThailandLaos, Burma & Thailand Afghanistan, Pakistan, Iran & MexicoAfghanistan, Pakistan, Iran & Mexico Dominate heroin supply routeDominate heroin supply route Shift from Turkey as main supplierShift from Turkey as main supplier Opened a large vacuumOpened a large vacuum

Fentanyl “China White” used as surgical Fentanyl “China White” used as surgical anesthetic & prescription painkiller anesthetic & prescription painkiller

10 to 10,000 X stronger than heroin10 to 10,000 X stronger than heroin Sometimes found itself on black marketSometimes found itself on black market

Opiates in 20Opiates in 20thth century US century US Morphine is schedule IIMorphine is schedule II

Heroin schedule I Heroin schedule I In Britain comparably seems as “Schedule II”In Britain comparably seems as “Schedule II”

Schedule I = no accepted medical useSchedule I = no accepted medical use Schedule V = has medical use, not too Schedule V = has medical use, not too

addictiveaddictive most legally used opioids are either most legally used opioids are either

semisynthetic or syntheticsemisynthetic or synthetic no legal U.S. use for heroin - purely illicit drug no legal U.S. use for heroin - purely illicit drug

(in the US) with large worldwide market today (in the US) with large worldwide market today

Opiates in 20Opiates in 20thth century US century US

about 4-5000 metric tons opium produced about 4-5000 metric tons opium produced in 1990 (2,200 lbs)in 1990 (2,200 lbs)

compared to 200-225,000 metric tons compared to 200-225,000 metric tons coca in same yearcoca in same year

Business of OpiatesBusiness of Opiates

opium grown in 2 primary regions of world using opium grown in 2 primary regions of world using simple farming techniquessimple farming techniques

poppies grown, petals fall, small incisions, liquid poppies grown, petals fall, small incisions, liquid oozes out - opiumoozes out - opium

opium - 10% morphine 0.5% codeineopium - 10% morphine 0.5% codeine morphine refined in growing areas then morphine refined in growing areas then

transported or processedtransported or processed heroin - equal amount - then diluted to 1-10%heroin - equal amount - then diluted to 1-10%

Business of OpiatesBusiness of Opiates

extremely profitable as a businessextremely profitable as a business kg morphine in Italy $12,500 - heroin in kg morphine in Italy $12,500 - heroin in

U.S. 1.7 millionU.S. 1.7 million 10 kg opium $300 in production region10 kg opium $300 in production region heroin in New Delhi $10,000heroin in New Delhi $10,000 in U.S. 1.5 millionin U.S. 1.5 million

Absorption, Distribution, Absorption, Distribution, Metabolism & ExcretionMetabolism & Excretion

Most opiates poorly absorbed through GI Most opiates poorly absorbed through GI tract (except codeine)tract (except codeine) Effective nasally and through lungsEffective nasally and through lungs Opium frequently smoked, heroin snortedOpium frequently smoked, heroin snorted Most effective i.v. (heroin 100 times more Most effective i.v. (heroin 100 times more

potent i.v. than orally) potent i.v. than orally)

Absorption, distribution & Absorption, distribution & excretionexcretion

In bloodstream distributed throughout In bloodstream distributed throughout bodybody accumulating in kidney, lung, liver, spleen, accumulating in kidney, lung, liver, spleen,

muscle & brainmuscle & brain

Opiates and blood brain barrier Opiates and blood brain barrier Morphine does not cross BBB wellMorphine does not cross BBB well

only 20% of circulating enters brainonly 20% of circulating enters brain 30-60 min to reach significant brain concentrations30-60 min to reach significant brain concentrations


Heroin more lipid soluble so penetrates Heroin more lipid soluble so penetrates BBB betterBBB better

Both morphine & heroin cross placentaBoth morphine & heroin cross placenta heroin converted to morphine once it cross the heroin converted to morphine once it cross the

BBBBBB once crossed BBB codeine 10% converted to once crossed BBB codeine 10% converted to

morphinemorphine


Most opiates rapidly metabolized in liver Most opiates rapidly metabolized in liver and excreted by kidneyand excreted by kidney

Half-life about 2.5-3 hrsHalf-life about 2.5-3 hrs Duration of effect 4-5 hrsDuration of effect 4-5 hrs 5-15 mg optimal analgesic dose for 5-15 mg optimal analgesic dose for

morphine - addicts 2 g Hmorphine - addicts 2 g H

Opiates Opiates Opium, morphine, codeine Opium, morphine, codeine Derivatives or semisynthetic (minor modification Derivatives or semisynthetic (minor modification

in structure)in structure) heroin, nalorphine, and hydromorphoneheroin, nalorphine, and hydromorphone

Synthesized—have different structures, but Synthesized—have different structures, but similar propertiessimilar properties Meperidine (Demerol)Meperidine (Demerol) Fentanyl (Sublimaze)Fentanyl (Sublimaze)

Proxyphene (Darvon, Darvocet) Proxyphene (Darvon, Darvocet) – lousy analgesic– lousy analgesic

Methadone (Dolophine)Methadone (Dolophine)

Absorption, distribution & excretionAbsorption, distribution & excretion

Have somewhat different pharmacological Have somewhat different pharmacological effectseffects

Differ in potency, duration of action & oral Differ in potency, duration of action & oral effectivenesseffectiveness

Because of differences in pharmacokineticsBecause of differences in pharmacokinetics Heroin more potent than morphine when Heroin more potent than morphine when

injected, but same when taken orally.injected, but same when taken orally. slight modification of heroin from morphine slight modification of heroin from morphine

allows it to cross BBB better—What would this allows it to cross BBB better—What would this do?do?

Absorption, distribution & excretionAbsorption, distribution & excretion

Metabolized into morphine in brainMetabolized into morphine in brain because it gets there quicker, more rapid intense effects.because it gets there quicker, more rapid intense effects. Codeine- 12x less potent that morphine when injectedCodeine- 12x less potent that morphine when injected better absorbed orally (morphine\heroin weak alkaloids)better absorbed orally (morphine\heroin weak alkaloids) Endogenous opiates more potent than heroinEndogenous opiates more potent than heroin But inactivated quicklyBut inactivated quickly Fentanyl-50 times more powerful than heroin (IM)Fentanyl-50 times more powerful than heroin (IM) Used for surgery, but easy for addicts to ODUsed for surgery, but easy for addicts to OD

Medical UseMedical Use

• analgesiaanalgesia

• sedation-markedly differs between sedation-markedly differs between individualsindividuals

poor sedative in generalpoor sedative in general

• anti-diarrhea agentsanti-diarrhea agents extremely effective for dysentery (1800's)extremely effective for dysentery (1800's) were the only effective agents in that timewere the only effective agents in that time

Mechanism of Action Mechanism of Action

act via the endogenous opiate systemact via the endogenous opiate system 1960's discovery of the opiate antagonist 1960's discovery of the opiate antagonist

naloxone (Narcannaloxone (Narcan77)) implication of common receptor site for opiates implication of common receptor site for opiates

actionsactions 1973 Pert and Snyder discovery of "opiate 1973 Pert and Snyder discovery of "opiate

receptors"receptors" led to discovery of several endorphins in 1975led to discovery of several endorphins in 1975

beta-endorphinbeta-endorphin enkephalinenkephalin dynorphindynorphin

Pharmacological ActionsPharmacological Actions

Primary effect of narcotics is sedative-Primary effect of narcotics is sedative-hypnotichypnotic Some cause stimulation immediate after Some cause stimulation immediate after

injectioninjection Cats and some humans are the only mammals that Cats and some humans are the only mammals that

show stimulationshow stimulation


Primary sites of action - Primary sites of action - CNS and GI tractCNS and GI tract For both medicine and abuse, opiate use due to For both medicine and abuse, opiate use due to

3 actions3 actions AnalgesiaAnalgesia (best for dull continuous, not sharp) (best for dull continuous, not sharp)

still feel sensations, can remain alertstill feel sensations, can remain alert vision, hearing, touch okayvision, hearing, touch okay

EuphoriaEuphoria (dream like state with intense visions) (dream like state with intense visions) ConstipationConstipation (used for diarrhea and dysentery) (used for diarrhea and dysentery)


Natural pain relief systemNatural pain relief system Used for chronic, not sharp, acute painsUsed for chronic, not sharp, acute pains

childbirth, battlefield injuries, strenuous exercise, childbirth, battlefield injuries, strenuous exercise, acupunctureacupuncture

addiction to exercise related to endorphin releaseaddiction to exercise related to endorphin release

can you be addicted to an endogenous can you be addicted to an endogenous substance?substance?


Opiates also relieve psychological painOpiates also relieve psychological pain anxieties, feelings of inadequacy, hostility & anxieties, feelings of inadequacy, hostility &

aggressionaggression produce extremely pleasant mood states - produce extremely pleasant mood states -

euphoriaeuphoria pain relief due to central effect - no effect on pain relief due to central effect - no effect on

sensory nerve transmissionsensory nerve transmission begins at spinal cord & continues throughout begins at spinal cord & continues throughout

CNSCNS

Abuse PotentialAbuse Potential

Abuse is related to euphoriant actions (CNS Abuse is related to euphoriant actions (CNS action)action)

2 main groupings2 main groupings visual illusions-dream like statesvisual illusions-dream like states clarity of thought and alleviation of clarity of thought and alleviation of

psychological painpsychological pain

Abuse PotentialAbuse Potential

Trance-like state - visual illusionsTrance-like state - visual illusions dream-like images - great deal of claritydream-like images - great deal of clarity doesn't influence sensory inputdoesn't influence sensory input the only perceptual effect is on painthe only perceptual effect is on pain

can alleviate physical paincan alleviate physical pain can alleviate psychological paincan alleviate psychological pain

strong emotionally pleasant feelingsstrong emotionally pleasant feelings

Side EffectsSide Effects

vomitingvomiting very common with first dosevery common with first dose chance-may be due to effect on the chance-may be due to effect on the

vestibular apparatusvestibular apparatus respiratory depressionrespiratory depression

decrease sensitivity to COdecrease sensitivity to CO22

occurs at low doses-those common for occurs at low doses-those common for analgesiaanalgesia

increase dose-increase depressionincrease dose-increase depression most common cause of death in overdosemost common cause of death in overdose


Body temperatureBody temperature resetting of body temperature thermostatresetting of body temperature thermostat

with limited use-lowers temperature by about 1 with limited use-lowers temperature by about 1 degreedegree can persist for a monthscan persist for a months

Sex hormonesSex hormones inhibitedinhibited

males-decreased testosterone levels-males-decreased testosterone levels-decreased sex drivedecreased sex drive

females-decreased estrogen females-decreased estrogen


Cardiovascular effectsCardiovascular effects increased skin blood flow-gives them a warm increased skin blood flow-gives them a warm

feelingfeeling blood pressure decrease upon standing -faintblood pressure decrease upon standing -faint

Pinpoint pupilsPinpoint pupils signs of overdosesigns of overdose seizuresseizures

Catatonia (only at very high doses)Catatonia (only at very high doses)

RECEPTOR TYPES MEDIATING RECEPTOR TYPES MEDIATING OPIOID EFFECTS OPIOID EFFECTS

11

spinal & supraspinal analgesiaspinal & supraspinal analgesia

22

respiratory depressionrespiratory depression GI motilityGI motility nauseanausea euphoriaeuphoria physical dependence (withdrawal symptoms)physical dependence (withdrawal symptoms) pupillary contractionpupillary contraction

RECEPTOR TYPES MEDIATING RECEPTOR TYPES MEDIATING OPIOID EFFECTS OPIOID EFFECTS

(kappa)(kappa)

spinal & supraspinal analgesiaspinal & supraspinal analgesia sedationsedation pupil contractionpupil contraction dysphoria, psychotomimetic dysphoria, psychotomimetic

(delta)(delta)

spinal & supraspinal analgesiaspinal & supraspinal analgesia positive reinforcing effectspositive reinforcing effects modulate activity of modulate activity of receptors receptors

Receptor LocationReceptor Location

receptors - pain modulating regions of receptors - pain modulating regions of brainbrain dorsal horn of spinal corddorsal horn of spinal cord brain stembrain stem PAGPAG thalamusthalamus hypothalamushypothalamus striatumstriatum


receptors - broad distributionreceptors - broad distribution deep layers of cerebral cortexdeep layers of cerebral cortex limbic systemlimbic system hypothalamus hypothalamus

receptors - emotional response regions receptors - emotional response regions of brainof brain limbic system (amygdala)limbic system (amygdala) frontal cortexfrontal cortex nucleus accumbensnucleus accumbens


opioid induced euphoria not well understoodopioid induced euphoria not well understood seems to involve seems to involve 22 receptors & also receptors & also definitely not definitely not

opioids act as modulators and inhibit release of opioids act as modulators and inhibit release of excitatory amino acid neurotransmittersexcitatory amino acid neurotransmitters all act via second messenger systemsall act via second messenger systems found on presynaptic nerve terminalsfound on presynaptic nerve terminals also found to serve as cotransmitters (released with also found to serve as cotransmitters (released with

NE NE

Tolerance & DependenceTolerance & Dependence

develop with repeated usedevelop with repeated use More rapidly and to greater degree as potency More rapidly and to greater degree as potency

increasesincreases Heroin & methadone develop different patterns Heroin & methadone develop different patterns

for withdrawalfor withdrawal Heroin withdrawal begins 4-5 hrs after last doseHeroin withdrawal begins 4-5 hrs after last dose

strong flu like symptomsstrong flu like symptoms greatest magnitude of symptoms between 24-72 hrsgreatest magnitude of symptoms between 24-72 hrs pretty much done in a couple of weekspretty much done in a couple of weeks


Methadone withdrawal 24-48 hrs after last doseMethadone withdrawal 24-48 hrs after last dose withdrawal symptoms reported to be less intensewithdrawal symptoms reported to be less intense however, much greater durationhowever, much greater duration can take months to clear all withdrawal symptomscan take months to clear all withdrawal symptoms

Methadone admin subcu for analgesiaMethadone admin subcu for analgesia Same potency as morphine, half potency as heroinSame potency as morphine, half potency as heroin

More effective orally than bothMore effective orally than both Suppresses opiate withdrawalsSuppresses opiate withdrawals actions 3 to 4 time longer than morphineactions 3 to 4 time longer than morphine


Why do we pay for people to be maintained on Why do we pay for people to be maintained on methadone?methadone?

1) effective orally - limits needle use1) effective orally - limits needle use

2) long duration action2) long duration action

3) effective dose remains stable3) effective dose remains stable

4) cheap4) cheap

5) does not produce euphoria as well 5) does not produce euphoria as well actually blocks to heroinactually blocks to heroin

6) prevents opiate withdrawal6) prevents opiate withdrawal

TreatmentTreatment

Therapeutic groups (Synanon & Daylop)Therapeutic groups (Synanon & Daylop) In West Berlin- 15% abstained compared to 4%In West Berlin- 15% abstained compared to 4%

Elimin of cond craving (to drug related stim) through Elimin of cond craving (to drug related stim) through extinction & class condextinction & class cond

Mostly blocking narcotic effectsMostly blocking narcotic effects Antagonist break up drug taking from reinforcementAntagonist break up drug taking from reinforcement Naloxone (NarcanNaloxone (Narcan77)-not too effective)-not too effective Naltrexen (TrexenNaltrexen (Trexen77 or ReVia or ReVia77) block up to 3 days) block up to 3 days What may be a problem with antagonist?What may be a problem with antagonist?

TreatmentTreatment

Substituting narcotics w/less disruptive Substituting narcotics w/less disruptive (Methadone)(Methadone) Developed by Nazis in WWIIDeveloped by Nazis in WWII

Dole and Nyswander (1976)—narcotic addicitionsDole and Nyswander (1976)—narcotic addicitions

Gave large levels of methadoneGave large levels of methadone Despite addiction went back to school, got jobs Despite addiction went back to school, got jobs

etc.,etc.,

TreatmentTreatment

Withdrawal symptoms in addicts with Withdrawal symptoms in addicts with naloxone adminnaloxone admin

Administer both heroin & naloxone Administer both heroin & naloxone repeatedly togetherrepeatedly together no tolerance or dependence developsno tolerance or dependence develops interesting way to see what receptor type interesting way to see what receptor type

mediates what responsesmediates what responses

the major opiates most common used drug for relief of pain only true narcotics (stupor, sleep,...

Documents

opium use

china opium china

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opium wars

major opiates opium

history of opium native

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