Elizabeth Liu Duy Tran BINF705

Should patients in chronic pain be allowed whatever pain remediation possible including the use of the strongest opioids such as heroin? (Algology) Elizabeth Liu Duy Tran BINF705

Definition of Chronic Pain • Originally defined as pain that has lasted 6 months or longer. • Pain that persists longer than the temporal course of natural healing that is associated with a particular type of injury or disease process • An unpleasant sensory and affective experience induced by the exposure to noxious stimuli i.e. injury incipient or substantive in nature. (The International Association for the Study of pain)

Management • It is rare to completely achieve absolute and sustained relief of pain. Thus, the clinical goal is pain management. Pain management covers the spectrum of medications, injections, infusions as well as neuroablative procedures. Therefore, pain management is often multidisciplinary in nature. • Medications • Opioids and non opioids • Antidepressants and Antiepileptic Drugs • Injection, Neuromodulation and Neuroablative Therapy • Rehabilitation

Medication • The drugs used in pain management may be broadly categorized as opioid and nonopioid medications. • Opioids are derived from opium, modestly effective analgesics in chronic pain management. However, they are associated with adverse effects, especially during the commencement or change in dosing and administration. • When opioids are used for prolonged periods drug tolerance, chemical dependency and addiction may occur. • The other major group of analgesics are nonsteroidal anti-inflammatory drugs. This class of medications has limited benefit in chronic pain disorders and with long term use is associated with significant adverse effects • OxyContin and Medical Marijuana are the two interventions for pain have been in the news recently

Controlled Substances Act (CSA) • Enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. • The CSA is the legal basis by which the manufacture, importation, possession, and distribution of certain drugs are regulated by the federal government of the United States. The Act also served as the national implementing legislation for the Single Convention on Narcotic Drugs. • The legislation created five Schedules (classifications), with varying qualifications for a drug to be included in each. • Two federal departments, the Department of Justice and the Department of Health and Human Services (which includes the Food and Drug Administration) determine which drugs are added or removed from the various schedules, though the statute passed by Congress created the initial listing. Classification decisions are required to be made on the criteria of potential for abuse, accepted medical use in the United States, and potential for addiction. • The Department of Justice is also the executive agency in charge of federal law enforcement. State governments also regulate certain drugs not controlled at the federal level.

Schedule I Drugs • Findings required: • (A) The drug or other substance has a high potential for abuse. • (B) The drug or other substance has no currently accepted medical use in treatment in the United States. • (C) There is a lack of accepted safety for use of the drug or other substance under medical supervision. • No prescriptions may be written for Schedule I substances, and such substances are subject to production quotas by the DEA.

Schedule I Drugs Include • GHB (Gamma-hydroxybutyrate), which has been used as a general anesthetic with minimal side-effects and controlled action but a limited safe dosage range. It was placed in Schedule I in March 2000 after widespread recreational use • 12-Methoxyibogamine (Ibogaine) • Cannabis (includes tetrahydrocannibinols found in marijuana, hashish, and hashish oil). Cannabis has legal medical uses in some countries and the U.S. Consequently, extreme controversy exists about its placement in Schedule I. Main article: Cannabis rescheduling in the United States. • Dimethyltryptamine (DMT) • Heroin (Diacetylmorphine), which is used in much of Europe as a potent pain reliever in terminal cancer patients. (It is about twice as potent, by weight, as morphine.) • MDMA (3,4-methylenedioxymethamphetamine,Ecstasy), which continues to be used medically, notably in the treatment of post-traumatic stress disorder (PTSD).The medical community originally agreed upon placing it as a Schedule 3 substance. The government denied this suggestion from the medical community, without any discussion. The FDA approved this PTSD use in 2001. • Psilocybin, the active ingredient in psychedelic mushrooms

Schedule I Drugs Include Cont. • 5-MeO-DIPT (Foxy / Foxy Methoxy / 5-methoxy-n,n-diisopropyltryptamine) • Lysergic acid diethylamide (LSD / Acid), which has historically been used to treat alcoholism and other addictions, helped to stop cluster headaches, and has been shown to be useful in treating schizophrenia, bi-polar, and other psychological disorders. • Peyote, one of the few plants specifically scheduled, which has a narrow exception to its illegal status for religious use by members of the Native American Church; • Mescaline, the main psychoactive ingredients of the peyote cactus; • Methaqualone (Quaalude, Sopor, Mandrax); It was previously used for similar purposes as used for barbiturates, until it was scheduled up. • 2,5-dimethoxy-4-methylamphetamine (STP / DOM) • 2C-T-7 (Blue Mystic / T7) • 2C-B (Nexus / Bees / Venus / Bromo Mescaline) • Cathinone (β-ketoamphetamine) is a monoamine alkaloid found in the shrub Catha edulis (Khat). • AMT (alpha-methyltryptamine)

Schedule II Drugs • Findings required: • (A) The drug or other substance has a high potential for abuse. • (B) The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions. • (C) Abuse of the drug or other substances may lead to severe psychological or physical dependence. • These drugs are only available by prescription, and distribution is carefully controlled and monitored by the DEA. Oral prescriptions are allowed, except that the prescription is limited to 30 doses, although exceptions are made for cancer patients, burn victims, etc. No refills are allowed. Also, Schedule II drugs are subject to production quotas set by the DEA.

Schedule II Drugs Include • Cocaine (used as a topical anesthetic) • Methylphenidate (Ritalin) • Morphine • Phencyclidine (PCP) • Most pure opioid agonists: meperidine, fentanyl, hydromorphone, opium, oxycodone (main ingredient in Percocet and OxyContin), or oxymorphone • Short-acting barbiturates, such as secobarbital • Amphetamines were originally placed in Schedule III, but was moved to Schedule II in 1971. Injectable methamphetamine has always been in Schedule II

Schedule III Drugs • Findings required: • (A) The drug or other substance has a potential for abuse less than the drugs or other substances in schedules I and II. • (B) The drug or other substance has a currently accepted medical use in treatment in the United States. • (C) Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence. • These drugs are available only by prescription, though control of wholesale distribution is somewhat less stringent than Schedule II drugs. Prescriptions for Schedule III drugs may be refilled up to five times within a six month period.

Schedule III Drugs Include • Anabolic steroids (including prohormones such as androstenedione and androstenediol) • Intermediate-acting barbiturates, such as talbutal or butalbital • Buprenorphine • Dradorn • Ketamine, a drug originally developed as a milder substitute for PCP (mainly to use as a human anesthetic) but has since become popular as a veterinary anesthetic • Xyrem, a preparation of GHB used to treat narcolepsy. Xyrem is in Schedule III but with a restricted distribution system • Hydrocodone / codeine, when compounded with an NSAID (e.g. Vicoprofen, when compounded with ibuprofen) or with acetaminophen (paracetamol) (e.g. Vicodin / Tylenol 3) • Marinol, a synthetic form of Tetrahydrocannabinol (THC) used to treat nausea and vomiting caused by chemotherapy, as well as appetite loss caused by AIDS • Paregoric • Phloemate

Schedule IV Drugs • Findings required: • (A) The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule III. • (B) The drug or other substance has a currently accepted medical use in treatment in the United States. • (C) Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III. • Control measures are similar to Schedule III. Prescriptions for Schedule IV drugs may be refilled up to five times within a six month period.

Schedule IV Drugs Include • Benzodiazepines, such as alprazolam (Xanax), chlordiazepoxide (Librium), diazepam (Valium), flunitrazepam (Rohypnol) (Note that Rohypnol is not used medically in the United States, and some states have placed it in Schedule I under state law.) • Zolpidem (sold in the U.S. as Ambien) • Dextropropoxyphene (sold in the U.S. as Darvocet) • Long-acting barbiturates such as phenobarbital; • Some partial agonist opioid analgesics, such as pentazocine (Talwin); • Certain non-amphetamine stimulants, including pemoline and the pseudostimulant modafinil.

Schedule V Drugs • Findings required: • (A) The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule IV. • (B) The drug or other substance has a currently accepted medical use in treatment in the United States. • (C) Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule IV. • Schedule V drugs are sometimes available without a prescription.

Schedule V drugs Include • Cough suppressants containing small amounts of codeine • Preparations containing small amounts of opium or diphenoxylate (used to treat diarrhea); • Pregabalin, an anticonvulsant and pain modulator.

Opioid • The main use is for pain relief. These agents work by binding to opioid receptors, which are found principally in the central nervous system and the gastrointestinal tract. The receptors in these two organ systems mediate both the beneficial effects, and the undesirable side effects. • There are four broad classes of opioids: • endogenous opioid peptides (opioids produced naturally in the body); • opium alkaloids, such as morphine and codeine; • semi-synthetic opioids, such as heroin and oxycodone; • Fully synthetic opioids, such as pethidine and methadone.

History of Opioids • 1817, Friedrich Wilhelm Adam Sertürner reported the isolation of pure morphine from opium after at least thirteen years of research and a nearly disastrous trial on himself and three boys. • Morphine was the first pharmaceutical isolated from a natural product, and this success encouraged the isolation of other alkaloids • 1820, isolations of narcotine, strychnine, veratrine, colchicine, caffeine, and quinine were reported. • Morphine sales began in 1827, by Heinrich Emanuel Merck of Darmstadt, and helped him expand his family pharmacy into the massive Merck KGaA pharmaceutical company. • Codeine was isolated in 1832 by Robiquet. • Heroin, the first semi-synthetic opiate, was first synthesized in 1874, but was not pursued until its rediscovery in 1897 by Felix Hoffmann at the Bayer pharmaceutical company in Elberfeld, Germany.

History of OpioidsCont. • From 1898 through to 1910 heroin was marketed as a non-addictive morphine substitute and cough medicine for children. • By 1902, sales made up 5% of the company's profits, and "heroinism" had attracted media attention. • Oxycodone, a thebaine derivative similar to codeine, was introduced by Bayer in 1916 and promoted as a less-addictive analgesic. Preparations of the drug such as Percocet and Oxycontin remain popular to this day. • A range of synthetic opioids such as methadone (1937), pethidine (1939), fentanyl (late 1950s), and derivatives have been introduced, and each is preferred for certain specialized applications. • No drug has yet been found that can match the painkilling effect of opium without also duplicating much of its addictive potential.

Heroin • A semi-synthetic opioid. • It mimics endorphins and creates a sense of well-being upon entering the bloodstream It is thus used both as a pain-killer and a recreational drug. • The body responds to heroin in the brain by reducing (and sometimes stopping) production of the endogenous opioids when heroin is present. Endorphins are regularly released in the brain and nerves and attenuate pain. Their other functions are still obscure, but are probably related to the effects produced by heroin besides analgesia • Internationally, heroin is controlled under Schedules I and IV of the Single Convention on Narcotic Drugs. • It is illegal to manufacture, possess, or sell heroin in the United States; however, under the name diamorphine, heroin is a legal prescription drug in the United Kingdom

Diamorphine (Heroin) • The UK Department of Health's Rolleston Committee report in 1926 established the British approach to heroin prescription to users, which was maintained for the next forty years: dealers were prosecuted, but doctors could prescribe heroin to users when withdrawing it would cause harm or severe distress to the patient. • This "policing and prescribing" policy effectively controlled the perceived heroin problem in the UK until the 1960s. • 1964 only specialized clinics and selected approved doctors were allowed to prescribe heroin to users. • By 1970s, the emphasis shifted to abstinence and the prescription of methadone, until now only a small number of users in the UK are prescribed heroin.

Oxycodone • Oxycodone is a semi-synthetic opioid derived from the alkaloid thebaine, unlike most early opium-derived drugs which instead used the morphine or codeine alkaloids also found in the plant. • Oxycodone was first synthesized in a German laboratory in 1916, a few years after the German pharmaceutical company Bayer had stopped the mass production of heroin due to addiction and abuse by both patients and physicians. It was hoped that a thebaine-derived drug would retain the analgesic effects of morphine and heroin with less of the euphoric effect which led to addiction and over-use. • To some extent this was achieved, as oxycodone does not "hit" the central nervous system with the same immediate punch as heroin or morphine do and it does not last as long. The subjective experience of a "high" was still reported for oxycodone, however, and it made its way into medical usage in small increments in most Western countries until the introduction of the OxyContin preparation radically boosted oxycodone use.

OxyContin • OxyContin is a medically prescribed pill that contains Oxycodone, • A synthetic opioid with analgesic properties similar to opium-derived painkillers like morphine or codeine. • OxyContin is a Schedule II drug under the Controlled Substances Act (CSA), which includes legal drugs that are subject to the maximum amount of government control and regulation. The FDA approved OxyContin in 1995 and Purdue Pharma introduced the drug in 1996. • Unlike Percocet, whose potential for abuse is limited by the presence of paracetamol, OxyContin contains only oxycodone and inert filler

OxyContin Cont. • In 2001, OxyContin was the number one opioid painkiller sold and in 2000 over 6.5 million prescriptions were written. • OxyContin is prescribed for patients with moderate or severe pain who need extended relief from treatment of terminal cancer and severe injuries. • Addiction to OxyContin is rare for those who use the drug as recommended, however, due to pharmacy break-ins, growing levels of recreational use, and increased media reports of Oxycontin abuse, the DEA heavily regulates prescriptions. • Some pharmacies now no longer stock the drug and many doctors are afraid to prescribe OxyContin and other legitimate pain medications out of fear of government sanctions. • This stigmatizes patients in need of pain medication and makes it more difficult for them to obtain relief.

The Need For Pain Management • Natural opiate and synthetic derivatives have been lauded as excellent painkillers, while at the same time criticized as highly addictive substances. • Over the last two decades, the medical community has been more attentive to pain and pain management. As a result, the use of opioid medicine has increased, especially among cancer patients who were previously under treated. • According to the American Medical Association (AMA) and the National Institutes of Health (NIH), approximately 17 million Americans suffer from unyielding pain. A 1997 report by the AMA stated that a major problem in American medicine was inadequate treatment of pain. In addition, The American Pain Foundation estimates that 50 million U.S. citizens suffer from significant pain daily.

What To Do About OxyContin • The National Foundation for the Treatment of Pain has concluded that OxyContin abuse is a minor problem compared to the millions of untreated, under treated, mistreated, and abandoned patients. • The FDA has stated that, "Although abuse, misuse, and diversion are potential problems for all opioids, including OxyContin, opioids are a very important part of the medical armamentarium for the management of pain when used appropriately under the careful supervision of a physician." The agencies will "help to ensure that these important drugs remain available to appropriate patients."

Medical Marijuana (Medical Cannabis) • Medical cannabis refers to the use of the drug Cannabis as a physician recommended herbal therapy, most notably as an antiemetic. • Cannabis has been used for medicinal purposes for over 4,800 years. • Surviving texts from Ancient India confirm that its psychoactive properties were recognized, and doctors used it for a variety of illnesses and ailments. (gastrointestinal disorders, insomnia, headaches and as a pain reliever) • Cannabis as a medicine was common throughout most of the world in the 1800s, It was used as the primary pain reliever until the invention of aspirin. • The term medical marijuana post-dates the U.S. Marijuana Tax Act of 1937, the effect of which made cannabis prescriptions illegal in the United States. • Later in the century, researchers investigating methods of detecting cannabis intoxication discovered that smoking the drug reduced intraocular pressure. (High intraocular pressure causes blindness in glaucoma patients) • In the 1970s, a synthetic version of THC, the primary active ingredient in cannabis, was synthesized to make the drug Marinol. • Users reported several problems with Marinol, however, that led many to abandon the pill and resume smoking the plant. • Patients complained that the violent nausea associated with chemotherapy made swallowing pills difficult. The effects of smoked cannabis are felt almost immediately, and is therefore easily dosed. • Marinol (Dronibanol), like ingested cannabis, is very psychoactive, and is harder to titrate than smoked cannabis. • Marinol has also consistently been more expensive than herbal cannabis. Some studies have indicated that other chemicals in the plant may have a synergistic effect with THC.

Medical Marijuana • Marijuana is the most commonly abused illicit drug in the United States. A dry, shredded green/brown mix of flowers, stems, seeds, and leaves of the plant Cannabis sativa, it usually is smoked as a cigarette (joint, nail), or in a pipe (bong). It also is smoked in blunts, which are cigars that have been emptied of tobacco and refilled with marijuana, often in combination with another drug. It might also be mixed in food or brewed as a tea. As a more concentrated, resinous form it is called hashish and, as a sticky black liquid, hash oil. Marijuana smoke has a pungent and distinctive, usually sweet-and-sour odor. • Marijuana is a Schedule I substance under the Controlled Substances Act (CSA). Schedule I drugs are classified as having a high potential for abuse, no currently accepted medical use in treatment in the United States, and a lack of accepted safety for use of the drug or other substance under medical supervision.

Medical Marijuana • It is illegal to possess cannabis under federal law in all fifty states. • While federal law does trump state law, most law enforcement regarding cannabis is handled at the state and local law enforcement level. • Currently, there are twelve states with effective medical marijuana laws on the books: Alaska, California, Colorado, Hawaii, Maine, Maryland, Montana, Nevada, Oregon, Rhode Island, Vermont, and Washington. It should be noted that Maryland's law does not legalize possession of medical cannabis, but rather makes it unobtainable legally, the offense of which is a maximum penalty of a $100 fine. • Twenty Additional US States have resolutions on their books affirming the medicinal value of marijuana. (Alabama, Arizona, Arkansas, Connecticut, Georgia, Illinois, Louisiana, Michigan, Minnesota, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and Massachusetts. Florida and Ohio formerly had medicinal marijuana resolutions that have since been repealed) • Eighteen US States do not recognize the medicinal value of marijuana.(Delaware, Florida, Idaho, Indiana, Iowa, Kansas, Kentucky, Mississippi, Missouri, Nebraska, North Dakota, Ohio, Pennsylvania, South Dakota, Utah, West Virginia, Wisconsin, and Wyoming. )

Facts On Medical Marijuana • University of Mississippi has grown marijuana since 1968 funded by Nature Institution on Drug Abuse (NIDA), then later by National Institution Health (NIH). Grow 1.5 to 6.5 acres of marijuana. • Every state residence voted for medical marijuana except South Dakota which is 48% to 52% • According to the US government marijuana alone has never cause a death from overdose. • The British Lung Foundation reports that 3-4 marijuana cigarettes a day are as dangerous to the lungs as 20 or more tobacco cigarettes a day. • A UCLA study found no association between marijuana and lung cancer. • In 1978 the U.S. government started the Compassionate Investigational New Drug (IND) program, which supplies about 300 marijuana cigarettes per month to seriously ill patients approved for the program. The program was shut down in 1991, but seven of those patients (as of 7/31/06), continue to receive the free government marijuana. • Marijuana extracts were one of the top three most prescribed medicines in the United States each year from 1842 until the 1890s.

Drugs that contain chemical taken directly from the Marijuana Plat (1) Four Categories of Pharmaceutical Drugs Based on Marijuana

Four Categories of Pharmaceutical Drugs Based on Marijuana • Drugs that contain synthetic versions of chemicals naturally found in marijuana (2)

Four Categories of Pharmaceutical Drugs Based on Marijuana • Drugs that contain chemicals similar to those in marijuana but not found in the plant (6)

Four Categories of Pharmaceutical Drugs Based on Marijuana • Drugs that do not work like marijuana but use the same brain pathways (4)

Pros of Medical Marijuana • Overwhelming that marijuana can relieve certain types of pain, nausea, vomiting and other symptoms caused by such illnesses as multiple sclerosis, cancer and AIDS. Compared with cigarettes and alcohol, the health risks and societal costs associated with even chronic marijuana use are mild. Yet we don't ban those items, while we deny marijuana to seriously ill people who could get a lot of relief from it. This is misguided and cruel. • Prohibition of marijuana doesn't work. It has only spawned an enormous black market, eroded our civil rights and corrupted our justice system. • No one overdoses on marijuana because it has a negligible therapeutic ratio; that is, you don't have to use much to get the desired effect. • Prohibition of marijuana over the past decades has not diminished the demand in the US

Cons of Medical Marijuana • The government has an obligation to protect public health • The 'Gateway' Thesis: Pot smokers are much more likely than non-users to graduate to harder drugs like cocaine and heroin • No hardcore evidence that prove marijuana is a effective drug as medicine, 20 year research have produce no reliable scientific proof • Legalization of drug, crime will increase due to a higher increase of pot users which will eventually become addicts and will steal or kill in order to get their drugs

Case 1 • Woman Denied Right to Use Marijuana as Life-saving Medication • Angel Raich, 41yr old mother from Oakland California, suffer from inoperable brain tumour, a weight-loss disorder, seizures, chronic nausea and scoliosis. Doctor has claim that marijuana is the only drug keeping her alive. She takes marijuana every few hours, under her doctor’s advice to control pain and give her an appetite otherwise she would “starve to death”.

Case 1 Cont. • Raich v. Ashcroft, 2003 U.S.Summary: The Ninth Circuit held that the federal Department of Justice should be temporarily enjoined from enforcing the Controlled Substances Act with respect to medical marijuana users in California pending trial of the case. The plaintiffs, a patient and two unnamed growers who supply her with the drug and another patient who grows her own marijuana, filed suit after a series of DEA raids against medical marijuana patients and suppliers in California, which allows medical marijuana use. The plaintiffs argued that because the medical use of marijuana by California residents does not cross state lines and is not commerce, Congress is without power to regulate it under the Commerce Clause. The three-judge panel of the Ninth Circuit found that the plaintiffs’ argument that the federal law is unconstitutional as applied to them was likely to succeed. The court found that “the appellants’ class of activities - the intrastate, noncommercial cultivation, possession and use of marijuana for personal medical purposes on the advice of a physician - is, in fact, different in kind from drug trafficking.” The appellate panel remanded the case to the district judge and ordered him to enjoin raids by federal officials pending trial of the case. The ruling may be appealed by the Justice Department to a larger panel of the circuit court or to the U.S. Supreme Court.

Case 2 • Jenks v. State, Fla. Dist1991Summary: Jenks and his wife, who both suffered from AIDS, were convicted of manufacturing cannabis which they used to control nausea. This opinion acquits appellants, noting that they met the elements of the medical necessity defense and that marijuana’s presence on Schedule I did not preclude the use of that defense because these drugs are subject to limited medical uses.

Case 3 • Seeley v. State Wash.1997Summary: This challenge to a Washington law, which names marijuana as a Schedule I controlled substance, was brought by a patient with terminal bone cancer who claimed therapeutic benefits from smoking marijuana. The Washington Supreme Court held that the law did not violate the Washington Constitution and that the right to smoke marijuana also fails federal equal protection analysis because it is not a fundamental right and is not within a zone of privacy.

Case 4 • Allen v. Purdue Pharma L.P. (Stamford, CT 2002) • Plaintiff alleges that Mrs. Allen took OxyContin and, as a direct and proximate cause there from suffered addiction to the drug and other related damages, which caused her to inject the pill in her vein, which resulted in her death. • Judge Rowe's ruled when you ignore safety warnings and take an otherwise safe and effective product in an irresponsible and illegal manner, no personal injury lawyer will be able to help you cash in on your own misconduct by suing the product's maker.

Case 5 • Doctor Guilty in OxyContin case (FL, 2002) • Dr. James Graves ,Florida's top OxyContin prescriber, was convicted of manslaughter for prescribing the drug to 4 patients who overdosed and died. He was making $500,000 a year from his pain management practice.

References • http://www.soyouwanna.com/site/pros_cons/pot/pot.html • http://www.painandthelaw.org/palliative/marijuana_cases.php • http://www.medicalmarijuanaprocon.org/pop/cannabisdrugs.htm • http://www.medicalmarijuanaprocon.org/pop/testing.htm • http://www.nida.nih.gov/about/organization/nacda/marijuanastatement.html • http://www.usdoj.gov/dea/pubs/csa.html • http://www.law.cornell.edu/uscode/21/usc_sec_21_00000812----000-.html • http://www.wikipedia.com • http://stopthedrugwar.org/chronicle/467/support_for_marijuana_legalization_low_in_europe • http://www.ninds.nih.gov/disorders/chronic_pain/chronic_pain.htm#What_is • http://www.ampainsoc.org/advocacy/opioids.htm • http://www.medscape.com/viewarticle/549294 • http://www.painreliefnetwork.org/prn/how-expert-testimony-distorts-the-standard-preemptive-analgesia-ethics-an-underlying-principle.php • http://www.jhu.edu/~jhumag/0699web/pain.html • http://jama.ama-assn.org/cgi/content/full/292/11/1394 • http://en.wikipedia.org/wiki/Controlled_Substances_Act • http://www.medicalmarijuanaprocon.org/ • http://www.sptimes.com/2002/02/20/State/Doctor_guilty_in_OxyC.shtml

Thank You

Elizabeth Liu Duy Tran BINF705