Drugs for the Treatment

of Heroin Addiction
Karina Garrett
CHEM 5398
April 6, 2006
 What is heroin?
 Heroin is an opioid, derived from the opium
poppy
 Chemical name: diacetylmorphine
 Morphine, the active ingredient in opium, is
substituted with two acetyl units

morphine diacetylmorphine
 Effects of heroin
 “Positive” effects
 Heroin's main effect is a sense of euphoria
 Also, flushing of the skin and heavy extremities
 The onset of these effects differs based on the method of
administration
 Smoked/snorted = 10-15 min
 Injected = 7-10 seconds
 The sense of euphoria lasts for several hours
 Negative effects
 Drowsiness and mental cloudiness
 Nausea and vomitting
 Itchy skin
 Slowed breathing and cardiac function
 History of heroin
 Originally created by the Bayer company in 1895 as
an alternative to morphine
 It had the same effects as morphine without the negative
side effects of morphine, and was thought to be much safer
 It was used as a step-down drug for morphine addicts
 By 1905, heroin addiction had risen to alarming rates
 In 1923, it became illegal to sell narcotics
 The Heroin Act was passed in 1924, making it illegal
to manufacture or produce heroin
 How heroin works
 Because of the two acetyl groups, heroin is
less polar than morphine
 This allows heroin to cross the blood-brain
barrier with much greater effeciency
 Once in the brain, heroin is converted to
morphine, and becomes “trapped” by the
barrier
 The morphine interacts with receptors and
causes the effects.
 How heroin works
 Three analgesic receptors where morphine interacts (as an
agonist)
 µ-receptor
 κ-receptor
 δ-receptor
 Receptors located non-uniformly throughout Central Nervous
System
 Cerebral cortex has most
 Spinal cord has significantly less
 Morphine reacts differently at each receptor site
 At µ-receptor, morphine binds most strongly – causes euphoria and
negative side effects – causes addiction!
 At κ-receptor, morphine binds less strongly – cause sedation and
analgesic effect without negative side effects
 At δ-receptor, morphine binds strongly – causes analgesic effect
 Receptors
 µ-receptor - changes shape
after morphine
binds, opens up a
K+ ion channel
 Receptors

 κ-receptor –
changes shape after morphine binds,
closes Ca2+ ion channel
 Receptors
 δ-receptor –
G-protein-linked –
when morphine
binds, causes
fragmentation of G-
protein, no cAMP
produced (necessary
for pain
transmission)
 How users become addicted
 The 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 States
 Methadone
 Levo-alpha-acetyl-methadol (LAAM)
 buprenorphine
 naltrexone
 Methadone
 History
 Created during World War II in Germany as a
morphine substitute
 In 1960’s Dr.’s Nyswander and Cole carried out
clinical trials for methadone treatment for heroin
addiction
 Ten years of studies showed that methadone
eliminated withdrawal symptoms and cravings
 Approved by the FDA for heroin addiction
maitenance treatment in 1972
 Methadone
 How it works
 Methadone is broken down in the liver and stored
 When the brain opiate receptors are ready,
methadone is mobilized and fills the receptors
 Methadone is an agonist, so it works similar to
heroin, but does not produce the extreme highs and
lows
 If patients are on blockade doses (70 mg), they can
go 2 days between doses
 Methadone
 Methadone is folded to
fit into the opioid receptor

 Controls cravings by keeping receptors active without

producing euphoria
 Drugs used in the United States
 Methadone
 Levo-alpha-acetyl-methadol (LAAM)
 buprenorphine
 naltrexone
 Levo-alpha-acetyl-methadol
 Similar to methadone
 Agonist
 Controls cravings without producing a sense of
euphoria
 Long-lasting
 Methadone =24-48 hours
 LAAM = 72 hours
 Levo-alpha-acetyl-methadol
 History
 First produced in 1948 as an analgesic
 Studies from 1952 showed it was effective at suppressing
opiate withdrawal symptoms
 Studies from the 70’s showed that LAAM is safe and
effective for heroin addiction treatment
 After a decade of little research, the NIDA submitted for
FDA approval
 After one final study, in addition to the studies from the
70’s, LAAM was approved by the FDA in 1993
 How it works
 Metabolized in liver to nor-LAAM and dinor-
LAAM
 Both have slower metabolism times than LAAM
 Causes the long-lasting effect
 Acts using the same mechanism as methadone
 Levo-alpha-acetyl-methadol
 Problems and questions
 No travel dosage is allowed
 Methadone is given for emergency travel
 Not enough information on the effect of using
LAAM during pregnancy
 Currently, the FDA suggests pregnant women switch to
methadone
 Drugs used in the United States
 Methadone
 Levo-alpha-acetyl-methadol (LAAM)
 Buprenorphine
 Naltrexone
 Buprenorphine
 Partial agonist
 Controls cravings
 Still some sense of euphoria
 Safer than heroin
 Not as addictive, little risk of overdose
 Longer-lasting than methadone, not as long as LAAM
 24-60 hours
 Lowest category drug for treatment of heroin
addiction (cat. III)
 Easier than methadone to escape dependency
 Buprenorphine
 History
 In 1978, Dr. Donald Jasinski first suggested the possibility
of buprenorphine as a treatment for opiate addiction
 Several studies over the next 15 years were conducted
 A treatment plan was approved by the FDA in 2003
 It included a buprenorphine pill during the initial tolerance phase
 The 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!
 Buprenorphine
 How it works
 It is partial agonist, meaning it uses the same
mechanism as heroin, methadone, and LAAM
 Metabolized in the liver to metabolites that are
more effective
 The effects increase linearly, but only to a certain
dosage – after that, the effects plateau (the “ceiling
effect”)
 Prevents overdose
 Helps lower addictiveness – not as high of a high
 Buprenorphine
 Problems and Questions
 There is little information on the effect of
buprenorphine on pregnant women
 A few cases have showed no problems
 The withdrawal effects are not completely masked
by buprenorphine
 They are much milder
 Drugs used in the United States
 Methadone
 Levo-alpha-acetyl-methadol (LAAM)
 Buprenorphine
 Naltrexone
 Naltrexone
 Used mainly for alcoholism treatment
 New method in other countries, currently
being researched in the United States
 Opioid antagonist – blocks effect of opioids by
blocking receptors
 Non-addictive
 Naltrexone
 History
 Approved by the FDA in 1984 for opioid treatment
 Approved by the FDA in the last five years for
alcoholism treatment
 Naltrexone
 How it works
 Naltrexone is attached to the opioid receptors,
competitively inhibiting the attachment of opioids
to the receptors
 Completely blocks euphoria feeling, but some still
feel nauseous
 Naltrexone
 Problems and Questions
 Not used in pregnant women
 Why not?
 No evidence showing harm to either mother or fetus
 Studies have shown that patients taking naltrexone
rarely maintain the dosage prescribed by their
doctor
 High relapse numbers
 Australia research
 Naltrexone
 The Australian Medical Procedures Research
Foundation has started a new and
revolutionary treatment plan
 Starts with rapid de-tox
 Naltrexone implants to maintain steady level
 Rapid de-tox
 Rapid 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
system
 Drugs include:
 Narcan – removes all opioids from receptors
 Naltrexone – blocks receptors
 Naltrexone implants
 Done to maintain natrexone levels over an
extended period of time
 Naltrexone tablets are stacked in a
biodegradable tube
 Inserted into the abdominal wall
 Tablets dissolve slowly, exposing tablet
underneath
 Usually three implants, which will last 12-18
months
 Results
 The clinic statistics show that 95% of patients
remain opioid-free at the 6 month mark after
the treatment
 This is significantly higher than with oral
naltrexone
 Pregnancy is not an issue, and has been
showed to have many positive effects on the
baby
 No withdrawal post-natal
 References
www.opioids.com
www.drugabuse.gov
www.health.org
buprenorphine.samhsa.gov
www.drugs.com