Drugs for the Treatment of Heroin AddictionKarina GarrettCHEM 5398April 6, 2006

What is heroin?Heroin is an opioid, derived from the opium poppyChemical name: diacetylmorphineMorphine, the active ingredient in opium, is substituted with two acetyl units

Effects of heroinPositive effectsHeroin's main effect is a sense of euphoriaAlso, flushing of the skin and heavy extremitiesThe onset of these effects differs based on the method of administrationSmoked/snorted = 10-15 minInjected = 7-10 secondsThe sense of euphoria lasts for several hoursNegative effectsDrowsiness and mental cloudinessNausea and vomittingItchy skinSlowed breathing and cardiac function

History of heroinOriginally created by the Bayer company in 1895 as an alternative to morphineIt had the same effects as morphine without the negative side effects of morphine, and was thought to be much saferIt was used as a step-down drug for morphine addictsBy 1905, heroin addiction had risen to alarming ratesIn 1923, it became illegal to sell narcoticsThe Heroin Act was passed in 1924, making it illegal to manufacture or produce heroin

How heroin worksBecause of the two acetyl groups, heroin is less polar than morphineThis allows heroin to cross the blood-brain barrier with much greater effeciencyOnce in the brain, heroin is converted to morphine, and becomes trapped by the barrierThe morphine interacts with receptors and causes the effects.

How heroin worksThree analgesic receptors where morphine interacts (as an agonist)-receptor-receptor-receptorReceptors located non-uniformly throughout Central Nervous SystemCerebral cortex has mostSpinal cord has significantly lessMorphine reacts differently at each receptor siteAt -receptor, morphine binds most strongly causes euphoria and negative side effects causes addiction!At -receptor, morphine binds less strongly cause sedation and analgesic effect without negative side effectsAt -receptor, morphine binds strongly causes analgesic effect

Receptors-receptor - changes shape after morphine binds, opens up a K+ ion channel

Receptors-receptor changes shape after morphine binds, closes Ca2+ ion channel

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

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

Drugs used in the United StatesMethadoneLevo-alpha-acetyl-methadol (LAAM)buprenorphinenaltrexone

MethadoneHistoryCreated during World War II in Germany as a morphine substituteIn 1960s Dr.s Nyswander and Cole carried out clinical trials for methadone treatment for heroin addictionTen years of studies showed that methadone eliminated withdrawal symptoms and cravingsApproved by the FDA for heroin addiction maitenance treatment in 1972

MethadoneHow it worksMethadone is broken down in the liver and storedWhen the brain opiate receptors are ready, methadone is mobilized and fills the receptorsMethadone is an agonist, so it works similar to heroin, but does not produce the extreme highs and lowsIf patients are on blockade doses (70 mg), they can go 2 days between doses

MethadoneMethadone is folded to fit into the opioid receptor

Controls cravings by keeping receptors active without producing euphoria

Drugs used in the United StatesMethadoneLevo-alpha-acetyl-methadol (LAAM)buprenorphinenaltrexone

Levo-alpha-acetyl-methadolSimilar to methadoneAgonistControls cravings without producing a sense of euphoriaLong-lastingMethadone =24-48 hoursLAAM = 72 hours

Levo-alpha-acetyl-methadolHistoryFirst produced in 1948 as an analgesicStudies from 1952 showed it was effective at suppressing opiate withdrawal symptomsStudies from the 70s showed that LAAM is safe and effective for heroin addiction treatmentAfter a decade of little research, the NIDA submitted for FDA approvalAfter one final study, in addition to the studies from the 70s, LAAM was approved by the FDA in 1993

How it worksMetabolized in liver to nor-LAAM and dinor-LAAMBoth have slower metabolism times than LAAMCauses the long-lasting effectActs using the same mechanism as methadone

Levo-alpha-acetyl-methadolProblems and questionsNo travel dosage is allowedMethadone is given for emergency travelNot enough information on the effect of using LAAM during pregnancyCurrently, the FDA suggests pregnant women switch to methadone

Drugs used in the United StatesMethadoneLevo-alpha-acetyl-methadol (LAAM)BuprenorphineNaltrexone

BuprenorphinePartial agonistControls cravingsStill some sense of euphoriaSafer than heroinNot as addictive, little risk of overdoseLonger-lasting than methadone, not as long as LAAM24-60 hoursLowest category drug for treatment of heroin addiction (cat. III)Easier than methadone to escape dependency

BuprenorphineHistoryIn 1978, Dr. Donald Jasinski first suggested the possibility of buprenorphine as a treatment for opiate addictionSeveral studies over the next 15 years were conductedA treatment plan was approved by the FDA in 2003It included a buprenorphine pill during the initial tolerance phaseThe maintenance phase uses a different pill, containing buprenorphine and naloxone**Not all buprenorphine is approved for heroin addiction treatment! Buprenorphine is not safe in an unsupervised setting!

BuprenorphineHow it worksIt is partial agonist, meaning it uses the same mechanism as heroin, methadone, and LAAMMetabolized in the liver to metabolites that are more effectiveThe effects increase linearly, but only to a certain dosage after that, the effects plateau (the ceiling effect)Prevents overdoseHelps lower addictiveness not as high of a high

BuprenorphineProblems and QuestionsThere is little information on the effect of buprenorphine on pregnant womenA few cases have showed no problemsThe withdrawal effects are not completely masked by buprenorphineThey are much milder

Drugs used in the United StatesMethadoneLevo-alpha-acetyl-methadol (LAAM)BuprenorphineNaltrexone

NaltrexoneUsed mainly for alcoholism treatmentNew method in other countries, currently being researched in the United StatesOpioid antagonist blocks effect of opioids by blocking receptorsNon-addictive

NaltrexoneHistoryApproved by the FDA in 1984 for opioid treatmentApproved by the FDA in the last five years for alcoholism treatment

NaltrexoneHow it worksNaltrexone is attached to the opioid receptors, competitively inhibiting the attachment of opioids to the receptorsCompletely blocks euphoria feeling, but some still feel nauseous

NaltrexoneProblems and QuestionsNot used in pregnant womenWhy not?No evidence showing harm to either mother or fetusStudies have shown that patients taking naltrexone rarely maintain the dosage prescribed by their doctorHigh relapse numbersAustralia research

NaltrexoneThe Australian Medical Procedures Research Foundation has started a new and revolutionary treatment planStarts with rapid de-toxNaltrexone implants to maintain steady level

Rapid de-toxRapid de-tox is a relatively new procedure (began in 1997)Patient is given some anesthesia and a drug cocktail to rapidly remove all drugs from the systemDrugs include:Narcan removes all opioids from receptorsNaltrexone blocks receptors

Naltrexone implantsDone to maintain natrexone levels over an extended period of timeNaltrexone tablets are stacked in a biodegradable tubeInserted into the abdominal wallTablets dissolve slowly, exposing tablet underneathUsually three implants, which will last 12-18 months

ResultsThe clinic statistics show that 95% of patients remain opioid-free at the 6 month mark after the treatmentThis is significantly higher than with oral naltrexonePregnancy is not an issue, and has been showed to have many positive effects on the babyNo withdrawal post-natal

Referenceswww.opioids.comwww.drugabuse.govwww.health.orgbuprenorphine.samhsa.govwww.drugs.com