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Opiates
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Opiates

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  • http://www.rehab-international.org/wp-content/uploads/2008/01/opium.thumbnail.jpg
  • Should we change it to carbonyl, etc??
  • Fix citation
  • Fix citation
  • Diamond yellow = dopamine, Blue = dopamine receptor, red uptake pump removes, Endorphin = works as neuromodulator, efftects signal within postsynaptic cell
  • Morphine binds to G prot receptor  shape change  interacts w/ G protein  expels its GDP molecule and picks up GTP  G protein breaks in two pieces  here ½ binds to adenylyl cyclase and inhibits formation of Other times activated G prot change activity of ion channel/enzyme GTP breaks down  GDP  returns to resting conformation
  • Dopamine = BLUE, dopamine receptors = purple
  • Binding of opiates inhibits GABA release  decreased inhibition of dopaminergic neurons  more dopamine  HIGH At mu receptor, acts as stronger agonist
  • Red = reward pathway, green = areas where opiates bind
  • Fix citation
  • Fix citation
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  • CITE???
  • Transcript

    • 1. OPIATES Nina Bellio, Frank Chung, Emily Flynn, and Jane Qu
    • 2. The Human Face of Opiate Addiction http://www.youtube.com/watch?v=KGYjcNOOhKw&NR=1
    • 3. What are Opiates? <ul><li>Narcotics that originate from the poppy plant </li></ul><ul><li>Used to alleviate pain, suppress coughing, and treat diarrhea </li></ul>http://www.lib.fit.edu/pubs/librarydisplays/arts/poppy.jpg
    • 4. History <ul><li>Humans have used poppies for medicinal and recreational purposes since early civilizations </li></ul><ul><li>Traded throughout western Europe, Mediterranean, Middle East, and Asia minor </li></ul><ul><ul><li>Used as currency </li></ul></ul><ul><li>“ Opium” comes from the Greek opos (juice), and “morphine” from the Greek god of dreams, Morpheus </li></ul>
    • 5. Opium Wars <ul><li>In the 1800’s, British merchants began trading contraband opium for more valuable Chinese products (tea, silk, etc.) </li></ul><ul><li>Commissioner Lin, a Chinese diplomat, sent a letter to Queen Victoria asking her to stop the trade </li></ul><ul><li>Requests ignored  Opium Wars </li></ul>http://www.emsc.nysed.gov/ciai/socst/ghgonline/turnpoint/images/content/tp45/hong.jpg
    • 6. Where Opiates Come From <ul><li>When the poppy loses its petals, the bulb is ready to be cut </li></ul><ul><li>The liquid leaking out of the bulb is opium gum </li></ul><ul><li>The gum is boiled and strained, resulting in blocks of morphine </li></ul>http://www.rehab-international.org/wp-content/uploads/2008/01/opium.thumbnail.jpg
    • 7. Creation: Heroin <ul><li>Made with a variety of chemicals </li></ul><ul><ul><li>acetic anhydride, sodium carbonate, activated charcoal, chloroform, ethyl alcohol, ether, and acetone </li></ul></ul><ul><li>Original purity of 90% </li></ul><ul><li>Dealers dilute drugs with caffeine, baking soda, baby powder, etc. </li></ul><ul><li>Usually <40% pure by the time it gets to a user </li></ul>http://www.justthinktwice.com/images/pic_heroine3.jpg
    • 8. How Opiates Feel <ul><li>One to two minute rush </li></ul><ul><ul><li>euphoria, relief of tension </li></ul></ul><ul><li>Four to five hour high </li></ul><ul><ul><li>warmth, drowsiness, satisfaction, mild dizziness, apathy </li></ul></ul><ul><li>First time: causes nausea/vomiting, often unpleasant </li></ul><ul><ul><li>effects decrease over time </li></ul></ul>
    • 9. Morphine <ul><li>Triple carbon ring </li></ul><ul><li>One ring with N-CH 3 on it </li></ul>http://z.about.com/d/chemistry/1/7/f/e/morphine.jpg http://www.drugs-forum.com/opiate-chemistry.html http://www.thetoadband.com/Toad/Toad/Images/Morphine_sulfate2.jpg
    • 10. Heroin <ul><li>Similar to morphine (opiate alkaloids) </li></ul><ul><li>Some differences, highlighted by the orange boxes </li></ul><ul><li>Carbonyl instead of hydroxyl groups </li></ul>http://img.freebase.com/api/trans/image_thumb/wikipedia/images/commons_id/1017373?maxheight=510&mode=fit&maxwidth=510 http://www.drugs-forum.com/opiate-chemistry.html
    • 11. Codeine <ul><li>Difference from morphine is shown in the orange box </li></ul><ul><li>Has H 3 CO instead of hydroxyl group </li></ul>http://upload.wikimedia.org/wikipedia/commons/e/ed/Codeine.png http://www.drugs-forum.com/opiate-chemistry.html
    • 12. Vicodin (Hydrocodone) <ul><li>Different conformation </li></ul><ul><li>Methyl instead of OH </li></ul><ul><li>Single bond and C=O instead of double bond and OH </li></ul>http://upload.wikimedia.org/wikipedia/commons/c/cc/Hydrocodone.svg http://media.canada.com/8975269b-0529-4353-a446-596d133824d2/cnsphoto-strachan-house.jpg
    • 13. Prescription Opiates <ul><li>Prescribed for pain relief </li></ul><ul><li>Generic names: hydrocodone, oxycodone, morphine sulfate, dihydromorphine </li></ul><ul><li>Brand names: Demerol, Lorcet, Vicodin, Norco, Lortab, Percocet/Percodan, Oxycontin, RMS/MS Contin, Dilaudid/Palladone </li></ul><ul><li>Often acetominophen added to decrease addictive properties, but increases risk of overdose resulting in liver problems </li></ul>http://babydollsandbeerbottles.files.wordpress.com/2009/08/pill_bottle_and_pills1.jpg http://erstories.net/wp-content/uploads/2008/06/pills-red-and-blue.jpg
    • 14. What should the doctor do? <ul><li>Read the scenario </li></ul><ul><li>Discuss with your group </li></ul><ul><li>Answer the question: how should the patient be given morphine? </li></ul><ul><li>Be prepared to justify your answer </li></ul><ul><li>Why do the different methods of drug administration have different effects? </li></ul>Source: “Understanding Neurobiology through the study of Addiction.” NIH.
    • 15. What should the doctor do? <ul><li>Inhalant or injection </li></ul><ul><li>Goal: quick relief of pain so fracture can set </li></ul><ul><li>Disadvantage of inhalants: amount of drug that enters blood more variable (some exhaled) </li></ul><ul><li>With injection, all of the drug enters the bloodstream </li></ul>Source: “Understanding Neurobiology through the study of Addiction.” NIH.
    • 16. How Opiates Work <ul><li>Attach to endorphin (a.k.a. opiate) receptors </li></ul><ul><li>Two kinds of opiates </li></ul><ul><ul><li>Agonists: activate receptors </li></ul></ul><ul><ul><li>Antagonists: block receptors, prevent action of agonists </li></ul></ul><ul><li>Concentrated in reward pathway and pain pathway </li></ul>
    • 17. Opiates And Endorphins <ul><li>Opiates have similar structures to endorphins, enkephalins, and dynorphins </li></ul><ul><li>All are peptides </li></ul>http://theoncologist.alphamedpress.org/cgi/content/full/9/6/717/F1
    • 18. Opiate Receptors <ul><li>Three kinds: mu, delta, and kappa receptors </li></ul><ul><ul><li>Morphine acts as a strong agonist at the mu subtype and as a weak agonist at the delta and kappa subtypes </li></ul></ul><ul><li>All G-protein coupled receptors </li></ul>http://www.nida.nih.gov/pubs/teaching/largegifs/slide-5.gif
    • 19. G protein Cascade http://theoncologist.alphamedpress.org/content/vol9/issue6/images/large/717_fig2.jpeg
    • 20. Mu Opiate Receptors <ul><li>Primary target for opiates </li></ul><ul><li>Highly concentrated in the thalamus, cerebral cortex, visual cortex, and basal ganglia </li></ul><ul><ul><li>Number of receptors varies between individuals (genetic) </li></ul></ul><ul><ul><li>More receptors  more pain tolerance </li></ul></ul><ul><li>Also, highly concentrated in nucleus accumbens (in reward pathway) </li></ul><ul><ul><ul><li>Mice lacking mu receptors are more sensitive to pain and do not become morphine dependent </li></ul></ul></ul>https://www.scientificamerican.com/article.cfm?id=personal-pain
    • 21. Pain Pathway <ul><li>Nociceptors (pain-sensing neurons) perceive pain  reflex and message sent to brain </li></ul><ul><li>Neurons in pain pathway synthesize endorphins </li></ul><ul><li>Endorphins suppress glutamate release in pre-synaptic neurons and hyperpolarize post-synaptic neurons </li></ul><ul><ul><li>Prevent the passage of nociceptive signals </li></ul></ul><ul><li>Opiates work like endorphins </li></ul><ul><ul><li>Only stronger because self-administered and we can control how much we receive </li></ul></ul>http://www.dana.org/uploadedImages/Images/Spotlight_Images/DanaGuide_CH09B05_P167a_spot.jpg
    • 22. Reward Pathway <ul><li>Stimulated normally by food, sex, water, etc. </li></ul><ul><li>VTA (ventral tegmental area) connects to the nucleus accumbens and prefrontal cortex </li></ul><ul><li>Neurons in VTA contain dopamine, which is released in the nucleus accumbens and prefrontal cortex in response to the rewarding stimulus </li></ul>http://www.drugabuse.gov/pubs/teaching/Teaching2/largegifs/slide11.gif
    • 23. Dopamine Release <ul><li>Gluatamte (excitatory) usually causes neighboring neurons to release GABA (inhibitory)  dopamine neuron blocked </li></ul><ul><ul><li>Prevents over-excitation </li></ul></ul><ul><li>Endorphins and opiate agonists disrupt these inhibitory mechanisms </li></ul><ul><ul><li>Block GABA response </li></ul></ul><ul><ul><li>Dopamine release  sensation of pleasure </li></ul></ul>http://www.drugabuse.gov/pubs/teaching/Teaching2/Teaching4.html
    • 24. Dopamine Release http://www.cnsforum.com/content/pictures/imagebank/hirespng/moa_heroin_delta_kappa.png
    • 25. Action of Opiate Agonists <ul><li>Binding to endorphin receptors in pain pathway (thalamus, brain stem, spinal cord)  analgesia </li></ul><ul><li>Binding to receptors in reward pathway  dopamine released  person feels good </li></ul>http://www.drugabuse.gov/pubs/teaching/Teaching2/Teaching4.html
    • 26. Effect on the Rest of the Body <ul><li>Vomiting center in brain (causes stomach muscles to contract) </li></ul><ul><ul><li>First uses  vomiting/nausea </li></ul></ul><ul><ul><li>Effect dulls over time </li></ul></ul><ul><li>Respiratory center in brain (regulates breathing) </li></ul><ul><ul><li>Inhibits  decreased frequency and depth of breathing </li></ul></ul><ul><ul><li>Overdose  stop breathing </li></ul></ul>http://mayoclinic.com/images/image_popup/r7_respiratory.jpg
    • 27. Effect on the Rest of the Body <ul><li>Endocrine System </li></ul><ul><ul><li>Slightly lowers body temperature, cortisol, and testosterone production </li></ul></ul><ul><ul><li>With tolerance, effect dulls </li></ul></ul><ul><li>Pupils contract (miosis) </li></ul><ul><li>Histamine released  widened veins, flushed appearance, itching, sweating </li></ul><ul><li>Intestines (also have opiate receptors) </li></ul><ul><ul><li>Inhibit intestinal peristalsis  constipation </li></ul></ul>
    • 28. Negative Effects <ul><li>Can cause circulatory collapse, coma, cardiac arrest, depressed appetite and sex drive </li></ul><ul><li>Related dangers (injection): HIV, Hepatitis B and Hepatitis C </li></ul><ul><li>Relatively few long-term health effects (not like alcohol/smoking) </li></ul><ul><li>Very easy to overdose </li></ul><ul><li>Worst “side” effect: addiction </li></ul>http://www.waukeshafp.org/images/residents_faculty/injection.jpg
    • 29. Who is the Addict? <ul><li>Read about Pat and Chris </li></ul><ul><li>Discuss with your group: who is the addict? </li></ul><ul><li>Be prepared to justify your answer </li></ul>Source: “Understanding Neurobiology through the study of Addiction.” NIH.
    • 30. Who is the Addict? <ul><li>What did your group decide: who is the addict? Why? </li></ul><ul><li>What are the differences in why and how Chris and Pat take morphine? </li></ul><ul><li>How does this affect whether or not they are are addicted? </li></ul>Source: “Understanding Neurobiology through the study of Addiction.” NIH.
    • 31. Who is the Addict? <ul><li>Difference in reason for taking drugs </li></ul><ul><ul><li>Pat took to escape problems, also expected high </li></ul></ul><ul><ul><li>Chris took to reduce pain, without motivation for getting high </li></ul></ul><ul><li>Pain patients are actually at a low risk for becoming addicted </li></ul>Source: “Understanding Neurobiology through the study of Addiction.” NIH.
    • 32. Tolerance and Dependence <ul><li>Tolerance </li></ul><ul><ul><li>Develops quickly to pain-relieving effects of opiates </li></ul></ul><ul><ul><li>Morphine binds to receptors  enzyme that causes cell to continue impulse firing inhibited </li></ul></ul><ul><ul><li>Frequent use  adaptation  no longer causes enzyme change </li></ul></ul><ul><ul><li>Need increasing amounts to relieve pain </li></ul></ul><ul><li>Dependence </li></ul><ul><ul><li>Drug needed to function normally </li></ul></ul><ul><ul><li>Very uncomfortable withdrawal (nausea, muscle spasms, cramps, anxiety, fever, diarrhea) </li></ul></ul>
    • 33. Addiction <ul><li>Can be dependent but not addicted </li></ul><ul><ul><li>Reward pathway underlies addiction, pain pathway underlies dependence </li></ul></ul><ul><li>Myth: therapeutic painkillers produce high rate of addiction </li></ul><ul><ul><li>Patients managing pain can experience withdrawal </li></ul></ul><ul><ul><li>Not addicted because do not want it after taken off </li></ul></ul><ul><li>Addiction to one opiate is often treated by another </li></ul>http://www.drugabuse.gov/pubs/teaching/Teaching2/Teaching4.html
    • 34. House http://www.youtube.com/watch?v=gQmlsmOZl6c
    • 35. Drug Addiction Treatment <ul><ul><li>Addiction is a chronic disease </li></ul></ul><ul><ul><ul><li>Often thought of as self-inflicted </li></ul></ul></ul><ul><ul><ul><li>Initial choice to use, but afterwards compulsive </li></ul></ul></ul><ul><li>Similar to other chronic diseases (ex. hypertension, diabetes) </li></ul><ul><ul><li>Voluntary choices also contribute to severity of other chronic diseases </li></ul></ul><ul><ul><li>Treatment requires medical compliance </li></ul></ul><ul><ul><ul><li>Adherence to a doctor’s treatment plan </li></ul></ul></ul>
    • 36. Treatment <ul><li>Which disease has the highest rate of medical compliance? </li></ul><ul><li>Medical compliance is following a physician’s treatment orders </li></ul>Disease Medical Compliance Heroin Addiction ? Hypertension ? Diabetes ?
    • 37. Treatment <ul><li>Heroin treatment has a higher rate of medical compliance than other chronic diseases </li></ul><ul><li>As a result, treatment is often more successful than treatment for other chronic diseases </li></ul><ul><li>Successful treatment usually uses a combination of behavioral and pharmacological treatments </li></ul>Source: “Understanding Neurobiology through the study of Addiction.” NIH. Disease Medical Compliance Heroin Addiction 60% Hypertension <30% Diabetes <50%
    • 38. Behavioral Treatment <ul><li>In conjunction with pharmacological treatments </li></ul><ul><li>Addicts learn to deal with the environmental factors that could trigger drug use </li></ul><ul><li>Counseling individually or as a group </li></ul><ul><li>Relapse </li></ul><ul><ul><li>Does occur </li></ul></ul><ul><ul><li>Is considered a part of treatment process </li></ul></ul>
    • 39. Pharmacological Treatments <ul><li>Opiate receptor agonist </li></ul><ul><ul><li>Binds to opiate receptor </li></ul></ul><ul><ul><li>Therefore prevents other agonists from binding (competes with them) </li></ul></ul><ul><ul><li>Example: Methadone </li></ul></ul><ul><li>Opiate receptor antagonist </li></ul><ul><ul><li>Entirely blocks other agonists from binding to receptor </li></ul></ul><ul><ul><li>Example: Naxolone </li></ul></ul>Source: “Understanding Neurobiology through the study of Addiction.” NIH.
    • 40. Treatment: Methadone <ul><li>Opiate receptor agonist </li></ul><ul><li>Treats heroin addicts </li></ul><ul><ul><li>Because heroin causes release of extra dopamine, addicts need an opiate to occupy the receptor </li></ul></ul><ul><li>Methadone is used to occupy the receptor </li></ul><ul><ul><li>Can be taken orally in liquid or pill form </li></ul></ul><ul><ul><li>Withdrawal suppressed for 24-36 hrs </li></ul></ul><ul><ul><li>Does not produce a euphoric high </li></ul></ul><ul><li>Methadone withdrawal is slower </li></ul>http://www.drugscope-dworld.org.uk/wip/24/images/methadone.JPG
    • 41. Methadone problems <ul><li>Highly addictive </li></ul><ul><li>Sold in large quantities on the black market </li></ul><ul><li>High risk of overdose </li></ul><ul><li>Use needs to be supervised by drug counselors or medical personnel </li></ul>http://content.answers.com/main/content/img/oxford/Oxford_Chemistry/0192801015.methadone.1.jpg
    • 42. Treatment: Naxolone <ul><li>Opiate receptor antagonist </li></ul><ul><li>Used in cases of overdose </li></ul><ul><li>Causes effect only after opiate use </li></ul><ul><li>No narcotic effect  cravings still persist </li></ul>http://opioids.com/naloxone/naloxone.jpg
    • 43. Treatment: Buprenorphine <ul><li>Partial agonist </li></ul><ul><li>Agonist properties: can’t get high because activation does not occur fully </li></ul><ul><li>Not nearly as addictive as methadone so is better for treatment </li></ul><ul><ul><li>No withdrawal symptoms or high </li></ul></ul>http://www.drugs.com/pro/images/23aa1bb3-cecf-4e62-29bb-48488bb66fc3/xen-0327-1.jpg
    • 44. How Buprenorphine Works http://www.naabt.org/education/images/Receptors_HiRes.jpg
    • 45. How Buprenorphine Works http://www.naabt.org/education/images/Receptors_HiRes.jpg
    • 46. How Buprenorphine Works http://www.naabt.org/education/images/Receptors_HiRes.jpg
    • 47. How Buprenorphine Works http://www.naabt.org/education/images/Receptors_HiRes.jpg
    • 48. In the Words of an Ex-Addict <ul><li>“ It was the first habit I had ever kicked in my long life of addiction outside of jail. The drug may have spared my life and a few banks at the same time. Buprenorphine was a miracle drug…It helped me clear my habit, and it can’t be abused.” Dannie Martin, ex-heroin addict and bank robber </li></ul>
    • 49. Social Implications <ul><li>Addicts seek alternate sources of income, often turning to criminal activity to pay for drugs </li></ul><ul><li>Negative impact on family and friends </li></ul><ul><li>Difficulties in school and work </li></ul>
    • 50. Economic Implications <ul><li>High costs to legal and healthcare systems </li></ul><ul><li>Opiate abuse and addiction costs Americans over $484 billion annually </li></ul><ul><li>Opium accounted for 53% of Afghanistan’s GDP in 2007, according to the UNODC </li></ul>
    • 51. Bibliography <ul><li>Advanced Treatment of Opiate Dependency. Opiates and Opiate Side Effects. </li></ul><ul><li><http://www.opiates.com/opiates/opiate-side-effects.html>. 18 October 2009. </li></ul><ul><li>  </li></ul><ul><li>Bear, Mark F., Barry W. Connors, and Michael A. Paradiso. Neuroscience: Exploring the Brain . </li></ul><ul><li>Baltimore: Lippincott Williams & Wilkins, 2001. </li></ul><ul><li>  </li></ul><ul><li>BBC News: World Edition. Heroin. 8 February 2003. </li></ul><ul><li><http://news.bbc.co.uk/2/hi/health/medical_notes/85691.stm>. 5 October 2009. </li></ul><ul><li>  </li></ul><ul><li>Chudler, Eric H. Heroin. 2008. <http://faculty.washington.edu/chudler/hero.html>. 16 October </li></ul><ul><li>2009. </li></ul><ul><li>  </li></ul><ul><li>Clear Haven Center. Signs of Opiate Addiction and Abuse. <http://www.clearhavencenter.com/ </li></ul><ul><li>substance-abuse-treatment-resources/signs-of-Opiate-use.php>. 18 October 2009. </li></ul><ul><li>DrugTexT Web Lab. The Opiates . 1995. <http://www.drugtext.org/sub/opiat1.html>. 14 October </li></ul><ul><li>2009. </li></ul><ul><li>  </li></ul>
    • 52. Bibliography <ul><li>Erickson, Carlton. The Science of Addiction . W.W. New York: Norton and Company, 2007. </li></ul><ul><li>  </li></ul><ul><li>European College of Neuropsychopharmacology. “How Does The Opioid System Control Pain, </li></ul><ul><li>Reward And Addictive Behavior?” ScienceDaily 15 October 2007. 18 October 2009. <http://www.sciencedaily.com­/releases/2007/10/071014163647.htm>. </li></ul><ul><li>  </li></ul><ul><li>Executive Office of the President Office of National Drug Control Policy. Methadone. April </li></ul><ul><li>2000.<http://www.whitehousedrugpolicy.gov/publications/factsht/methadone/index.html>. 4 October 2009. </li></ul><ul><li>  </li></ul><ul><li>Fields, Howard. “The Psychology of Pain”. Scientific American Mind September 2009: 42-50. </li></ul><ul><li>  </li></ul><ul><li>Gahlinger, Paul. Illegal Drugs . New York: Penguin Group, 2005. </li></ul><ul><li>  </li></ul><ul><li>Goldstein, Avram. Addiction: From Biology to Drug Policy . New York: Oxford University </li></ul><ul><li>Press, 2001. </li></ul><ul><li>  </li></ul><ul><li>Hodgson, Barbara. Opium: A Portrait of the Heavenly Dream . Toronto: Greystone Books, 1999. </li></ul><ul><li>  </li></ul>
    • 53. Bibliography <ul><li>Hoffman, John and Susan Froemke. Addiction . New York: Rodale, 2007. </li></ul><ul><li>  </li></ul><ul><li>House: Broken Intro. <http://www.youtube.com/watch?v=gQmlsmOZl6c> . 15 October 2009. </li></ul><ul><li>  </li></ul><ul><li>Kallen, Stuart, ed. Heroin: At Issue . New York: Greenhaven Press, 2006. </li></ul><ul><li>  </li></ul><ul><li>Leutwyler, Kristin. “Personal Pain.” Scientific American Mind July 26 1999: Scientific American </li></ul><ul><li>Mind Online. <http://www.scientificamerican.com/sciammind > 14 October 2009. </li></ul><ul><li>  </li></ul><ul><li>Mission Enabled. Opium Addiction Facts. 2009. <http://www.drug-addiction- </li></ul><ul><li>support.org/Opiate-Addiction-Facts.html>. 10 October 2009. </li></ul><ul><li>  </li></ul><ul><li>National Institute of Health. Understanding Neurobiology through the Study of Addiction. 2000. </li></ul><ul><li><http://science-education.nih.gov/supplements/nih2/addiction/default.htm>. 8 October 2009. </li></ul><ul><li>  </li></ul><ul><li>NIDA. The National Institute on Drug Abuse . 27 July 2009. </li></ul><ul><li><http://www.drugabuse.gov/pubs/teaching/default.html>. 13 October 2009. </li></ul><ul><li>  </li></ul>
    • 54. Bibliography <ul><li>Opiates and cannabinoids in pain-relief. </li></ul><ul><li>< http://www.biotopics.co.uk/newgcse/opiatesandcannabinoidsplus.html>. 13 October 2009. </li></ul><ul><li>  </li></ul><ul><li>PBS and WGBH/Frontline. The Opium Kings. 1998. </li></ul><ul><li><http://www.pbs.org/wgbh/pages/frontline/shows/heroin/brain/>. 8 October 2009. </li></ul><ul><li>  </li></ul><ul><li>Poppies International Inc. From Flowers to Heroin. 2006. </li></ul><ul><li><http://www.poppiesinternational.com/opium_poppy/opium_poppy.html>. 5 October 2009. </li></ul><ul><li>  </li></ul><ul><li>Porreca, Frank and Theodore Price. “When Pain Lingers”. Scientific American Mind September </li></ul><ul><li>2009: 34-42. </li></ul><ul><li>  </li></ul><ul><li>Raehal, Kristen M., and Laura M. Bohn. “Mu Opioid Receptor Regulation And Opiate </li></ul><ul><li>Responsiveness.” AAPS Journal 2005. 18 October 2009. <http://www.aapsj.org/view.asp?art=aapsj070360>. </li></ul><ul><li>  </li></ul><ul><li>RxList Inc. Narcan. 2009. <http://www.rxlist.com/narcan-drug.htm>. 5 October 2009. </li></ul><ul><li>  </li></ul>
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    • 56. Bibliography <ul><li>  Wickelgren, Ingrid. “I do not feel your pain”. Scientific American Mind September 2009: 50-58. </li></ul><ul><li>Young Face of Heroin Addiction. </li></ul><ul><li><http://www.youtube.com/watch?v=KGYjcNOOhKw&NR=1>. 15 October 2009. </li></ul>

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