Drugs for the Treatment of Heroin Addiction Karina Garrett CHEM 5398 April 6, 2006.

Drugs for the Treatment Drugs for the Treatment of Heroin Addictionof Heroin Addiction

Karina GarrettKarina Garrett

CHEM 5398CHEM 5398

April 6, 2006April 6, 2006

What is heroin?What is heroin?

Heroin is an opioid, derived from the opium Heroin is an opioid, derived from the opium poppypoppy

Chemical name: diacetylmorphineChemical name: diacetylmorphine Morphine, the active ingredient in opium, is Morphine, the active ingredient in opium, is

substituted with two acetyl unitssubstituted with two acetyl units

morphine diacetylmorphine

Effects of heroinEffects of heroin ““Positive” effectsPositive” effects

Heroin's main effect is a sense of euphoriaHeroin's main effect is a sense of euphoria Also, flushing of the skin and heavy extremitiesAlso, flushing of the skin and heavy extremities

The onset of these effects differs based on the method of The onset of these effects differs based on the method of administrationadministration

Smoked/snorted = 10-15 minSmoked/snorted = 10-15 min Injected = 7-10 secondsInjected = 7-10 seconds

The sense of euphoria lasts for several hoursThe sense of euphoria lasts for several hours Negative effectsNegative effects

Drowsiness and mental cloudinessDrowsiness and mental cloudiness Nausea and vomittingNausea and vomitting Itchy skinItchy skin Slowed breathing and cardiac functionSlowed breathing and cardiac function

History of heroinHistory of heroin

Originally created by the Bayer company in 1895 as Originally created by the Bayer company in 1895 as an alternative to morphinean alternative to morphine It had the same effects as morphine without the negative It had the same effects as morphine without the negative

side effects of morphine, and was thought to be much saferside effects of morphine, and was thought to be much safer It was used as a step-down drug for morphine addictsIt was used as a step-down drug for morphine addicts

By 1905, heroin addiction had risen to alarming ratesBy 1905, heroin addiction had risen to alarming rates In 1923, it became illegal to sell narcoticsIn 1923, it became illegal to sell narcotics The Heroin Act was passed in 1924, making it illegal The Heroin Act was passed in 1924, making it illegal

to manufacture or produce herointo manufacture or produce heroin

How heroin worksHow heroin works

Because of the two acetyl groups, heroin is Because of the two acetyl groups, heroin is less polar than morphineless polar than morphine

This allows heroin to cross the blood-brain This allows heroin to cross the blood-brain barrier with much greater effeciencybarrier with much greater effeciency

Once in the brain, heroin is converted to Once in the brain, heroin is converted to morphine, and becomes “trapped” by the morphine, and becomes “trapped” by the barrierbarrier

The morphine interacts with receptors and The morphine interacts with receptors and causes the effects. causes the effects.

How heroin worksHow heroin works Three analgesic receptors where morphine interacts (as an Three analgesic receptors where morphine interacts (as an

agonist)agonist) µµ-receptor-receptor κκ-receptor-receptor δδ-receptor-receptor

Receptors located non-uniformly throughout Central Nervous Receptors located non-uniformly throughout Central Nervous SystemSystem Cerebral cortex has mostCerebral cortex has most Spinal cord has significantly lessSpinal cord has significantly less

Morphine reacts differently at each receptor siteMorphine reacts differently at each receptor site At At µµ-receptor, morphine binds most strongly – causes euphoria and -receptor, morphine binds most strongly – causes euphoria and

negative side effects – causes addiction!negative side effects – causes addiction! At At κκ-receptor, morphine binds less strongly – cause sedation and -receptor, morphine binds less strongly – cause sedation and

analgesic effect without negative side effectsanalgesic effect without negative side effects At At δδ-receptor, morphine binds strongly – causes analgesic effect -receptor, morphine binds strongly – causes analgesic effect

ReceptorsReceptors

µµ-receptor - changes shape -receptor - changes shape after morphine after morphine

binds, opens up a binds, opens up a K+ ion channelK+ ion channel

ReceptorsReceptors

κκ-receptor – -receptor –

changes shape after morphine binds, changes shape after morphine binds, closes Ca2+ ion channelcloses Ca2+ ion channel

ReceptorsReceptors

δδ-receptor – -receptor –

G-protein-linked – G-protein-linked – when morphine when morphine binds, causes binds, causes fragmentation of G-fragmentation of G-protein, no cAMP protein, no cAMP produced (necessary produced (necessary for pain for pain transmission)transmission)

How users become addictedHow users become addicted

The body cannot completely eradicate drugs. The body cannot completely eradicate drugs. It metabolizes them, and the metabolites get It metabolizes them, and the metabolites get stored in fatty tissue. When the fatty tissue is stored in fatty tissue. When the fatty tissue is broken down, the metabolites are released and broken down, the metabolites are released and act on the brain again, causing a craving.act on the brain again, causing a craving.

Drugs used in the United StatesDrugs used in the United States

MethadoneMethadone Levo-alpha-acetyl-methadol (LAAM)Levo-alpha-acetyl-methadol (LAAM) buprenorphinebuprenorphine naltrexonenaltrexone

MethadoneMethadone

HistoryHistory Created during World War II in Germany as a Created during World War II in Germany as a

morphine substitutemorphine substitute In 1960’s Dr.’s Nyswander and Cole carried out In 1960’s Dr.’s Nyswander and Cole carried out

clinical trials for methadone treatment for heroin clinical trials for methadone treatment for heroin addictionaddiction

Ten years of studies showed that methadone Ten years of studies showed that methadone eliminated withdrawal symptoms and cravingseliminated withdrawal symptoms and cravings

Approved by the FDA for heroin addiction Approved by the FDA for heroin addiction maitenance treatment in 1972maitenance treatment in 1972

MethadoneMethadone

How it worksHow it works Methadone is broken down in the liver and storedMethadone is broken down in the liver and stored When the brain opiate receptors are ready, When the brain opiate receptors are ready,

methadone is mobilized and fills the receptorsmethadone is mobilized and fills the receptors Methadone is an agonist, so it works similar to Methadone is an agonist, so it works similar to

heroin, but does not produce the extreme highs and heroin, but does not produce the extreme highs and lowslows

If patients are on blockade doses (70 mg), they can If patients are on blockade doses (70 mg), they can go 2 days between dosesgo 2 days between doses

MethadoneMethadone

Methadone is folded to Methadone is folded to

fit into the opioid receptorfit into the opioid receptor

Controls cravings by keeping receptors active without Controls cravings by keeping receptors active without producing euphoriaproducing euphoria


MethadoneMethadone Levo-alpha-acetyl-methadol (LAAM)Levo-alpha-acetyl-methadol (LAAM) buprenorphinebuprenorphine naltrexonenaltrexone

Levo-alpha-acetyl-methadolLevo-alpha-acetyl-methadol

Similar to methadoneSimilar to methadone AgonistAgonist Controls cravings without producing a sense of Controls cravings without producing a sense of

euphoriaeuphoria Long-lastingLong-lasting

Methadone =24-48 hoursMethadone =24-48 hours LAAM = 72 hoursLAAM = 72 hours


HistoryHistory First produced in 1948 as an analgesicFirst produced in 1948 as an analgesic Studies from 1952 showed it was effective at suppressing Studies from 1952 showed it was effective at suppressing

opiate withdrawal symptomsopiate withdrawal symptoms Studies from the 70’s showed that LAAM is safe and Studies from the 70’s showed that LAAM is safe and

effective for heroin addiction treatmenteffective for heroin addiction treatment After a decade of little research, the NIDA submitted for After a decade of little research, the NIDA submitted for

FDA approvalFDA approval After one final study, in addition to the studies from the After one final study, in addition to the studies from the

70’s, LAAM was approved by the FDA in 199370’s, LAAM was approved by the FDA in 1993

How it worksHow it works Metabolized in liver to nor-LAAM and dinor-Metabolized in liver to nor-LAAM and dinor-

LAAMLAAM Both have slower metabolism times than LAAMBoth have slower metabolism times than LAAM Causes the long-lasting effectCauses the long-lasting effect

Acts using the same mechanism as methadoneActs using the same mechanism as methadone


Problems and questionsProblems and questions No travel dosage is allowedNo travel dosage is allowed

Methadone is given for emergency travelMethadone is given for emergency travel Not enough information on the effect of using Not enough information on the effect of using

LAAM during pregnancyLAAM during pregnancy Currently, the FDA suggests pregnant women switch to Currently, the FDA suggests pregnant women switch to

methadonemethadone


MethadoneMethadone Levo-alpha-acetyl-methadol (LAAM)Levo-alpha-acetyl-methadol (LAAM) BuprenorphineBuprenorphine NaltrexoneNaltrexone

BuprenorphineBuprenorphine

Partial agonistPartial agonist Controls cravingsControls cravings

Still some sense of euphoriaStill some sense of euphoria Safer than heroinSafer than heroin

Not as addictive, little risk of overdoseNot as addictive, little risk of overdose Longer-lasting than methadone, not as long as LAAMLonger-lasting than methadone, not as long as LAAM

24-60 hours24-60 hours Lowest category drug for treatment of heroin Lowest category drug for treatment of heroin

addiction (cat. III)addiction (cat. III) Easier than methadone to escape dependencyEasier than methadone to escape dependency


HistoryHistory In 1978, Dr. Donald Jasinski first suggested the possibility In 1978, Dr. Donald Jasinski first suggested the possibility

of buprenorphine as a treatment for opiate addictionof buprenorphine as a treatment for opiate addiction Several studies over the next 15 years were conductedSeveral studies over the next 15 years were conducted A treatment plan was approved by the FDA in 2003A treatment plan was approved by the FDA in 2003

It included a buprenorphine pill during the initial tolerance phaseIt included a buprenorphine pill during the initial tolerance phase The maintenance phase uses a different pill, containing The maintenance phase uses a different pill, containing

buprenorphine and naloxonebuprenorphine and naloxone

**Not all buprenorphine is approved for heroin addiction treatment! **Not all buprenorphine is approved for heroin addiction treatment! Buprenorphine is not safe in an unsupervised setting!Buprenorphine is not safe in an unsupervised setting!


How it worksHow it works It is partial agonist, meaning it uses the same It is partial agonist, meaning it uses the same

mechanism as heroin, methadone, and LAAMmechanism as heroin, methadone, and LAAM Metabolized in the liver to metabolites that are Metabolized in the liver to metabolites that are

more effectivemore effective The effects increase linearly, but only to a certain The effects increase linearly, but only to a certain

dosage – after that, the effects plateau (the “ceiling dosage – after that, the effects plateau (the “ceiling effect”)effect”)

Prevents overdosePrevents overdose Helps lower addictiveness – not as high of a highHelps lower addictiveness – not as high of a high


Problems and QuestionsProblems and Questions There is little information on the effect of There is little information on the effect of

buprenorphine on pregnant womenbuprenorphine on pregnant women A few cases have showed no problemsA few cases have showed no problems

The withdrawal effects are not completely masked The withdrawal effects are not completely masked by buprenorphineby buprenorphine

They are much milderThey are much milder


MethadoneMethadone Levo-alpha-acetyl-methadol (LAAM)Levo-alpha-acetyl-methadol (LAAM) BuprenorphineBuprenorphine NaltrexoneNaltrexone

NaltrexoneNaltrexone

Used mainly for alcoholism treatmentUsed mainly for alcoholism treatment New method in other countries, currently New method in other countries, currently

being researched in the United Statesbeing researched in the United States Opioid antagonist – blocks effect of opioids by Opioid antagonist – blocks effect of opioids by

blocking receptorsblocking receptors Non-addictiveNon-addictive


HistoryHistory Approved by the FDA in 1984 for opioid treatmentApproved by the FDA in 1984 for opioid treatment Approved by the FDA in the last five years for Approved by the FDA in the last five years for

alcoholism treatmentalcoholism treatment


How it worksHow it works Naltrexone is attached to the opioid receptors, Naltrexone is attached to the opioid receptors,

competitively inhibiting the attachment of opioids competitively inhibiting the attachment of opioids to the receptorsto the receptors

Completely blocks euphoria feeling, but some still Completely blocks euphoria feeling, but some still feel nauseousfeel nauseous


Problems and QuestionsProblems and Questions Not used in pregnant womenNot used in pregnant women

Why not?Why not? No evidence showing harm to either mother or fetusNo evidence showing harm to either mother or fetus

Studies have shown that patients taking naltrexone Studies have shown that patients taking naltrexone rarely maintain the dosage prescribed by their rarely maintain the dosage prescribed by their doctordoctor

High relapse numbersHigh relapse numbers Australia researchAustralia research


The Australian Medical Procedures Research The Australian Medical Procedures Research Foundation has started a new and Foundation has started a new and revolutionary treatment planrevolutionary treatment plan Starts with rapid de-toxStarts with rapid de-tox Naltrexone implants to maintain steady levelNaltrexone implants to maintain steady level

Rapid de-toxRapid de-tox

Rapid de-tox is a relatively new procedure Rapid de-tox is a relatively new procedure (began in 1997)(began in 1997)

Patient is given some anesthesia and a drug Patient is given some anesthesia and a drug cocktail to rapidly remove all drugs from the cocktail to rapidly remove all drugs from the systemsystem Drugs include:Drugs include:

Narcan – removes all opioids from receptorsNarcan – removes all opioids from receptors Naltrexone – blocks receptorsNaltrexone – blocks receptors

Naltrexone implantsNaltrexone implants

Done to maintain natrexone levels over an Done to maintain natrexone levels over an extended period of timeextended period of time

Naltrexone tablets are stacked in a Naltrexone tablets are stacked in a biodegradable tubebiodegradable tube

Inserted into the abdominal wallInserted into the abdominal wall Tablets dissolve slowly, exposing tablet Tablets dissolve slowly, exposing tablet

underneathunderneath Usually three implants, which will last 12-18 Usually three implants, which will last 12-18

monthsmonths

ResultsResults

The clinic statistics show that 95% of patients The clinic statistics show that 95% of patients remain opioid-free at the 6 month mark after remain opioid-free at the 6 month mark after the treatmentthe treatment

This is significantly higher than with oral This is significantly higher than with oral naltrexonenaltrexone

Pregnancy is not an issue, and has been Pregnancy is not an issue, and has been showed to have many positive effects on the showed to have many positive effects on the babybaby No withdrawal post-natalNo withdrawal post-natal

ReferencesReferenceswww.opioids.com

www.drugabuse.gov

www.health.org

buprenorphine.samhsa.gov

www.drugs.com

Drugs for the Treatment of Heroin Addiction Karina Garrett CHEM 5398 April 6, 2006.

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