Opiates : History and Treatment Options

1. Opiates: History and Treatment Options West Virginia UniversitySchool of Medicine Ehab S. Abdallah M.D

3. General Terms • Narcotics – A general term technically referring to an opiate - related or opiate -derived drugs. It is often mistakenly used to include several other illicit drug categories as well. • Opium – An analgesic and euphoriant drug acquired from the dried juice of the opium poppy. • Opiates – Any ingredients of opium or chemical derivatives of these ingredients. Opiate generally refer to opium, morphine, codeine, thebaine and Heroin.

4. Synthetic opiates – Synthetic drugs unrelated to morphine that produce opiate like effects. • Codeine – One of the three active ingredients in opium, used primarily to treat coughing. • Morphine – One of the three major active ingredients in opium. • Thebaine – One of the three major active ingredients in opium. • Heroin – A chemical derivative of morphine. It is approximately three times as potent as morphine and a major drug of abuse

5. Opium Opiates Morphine Codeine Thebaine Opiate Derivatives Heroin Hydromor- phone (Dilaudid) Oxymorphine (Numorphan) Oxycodone (Percondan) Etorphine Synthetic Opiates Methadone Meperidine (Demerol) Propoxy- phene (Darvon) LAAM (Orlaam)

6. Opium in History • The source is the opium poppy. Known by its potential name as papaver somniferum (literally “the poppy that brings sleep.”) • Opium is harvested by a small shallow incision in the capsules allowing a milky white juice to ooze out. • Opium was first described in specific detail in the third century B.C. but we can be fairly sure that it was used for at least a thousand years before that.

8. Egyptians were knowledgeable about the medicinal value of opium evidence of this was found in the Ebers Papyrus writings. • In the second century A.D., Claudius Galen, the famous Greek physician and surgeon to Roman gladiators recommended opium for everything. • Western Europe was introduced to opium in the eleventh and twelfth centuries from returning crusaders who learned of it from the Arabs. • In 1520, a physician named Paracelsus introduced a medicinal drink containing opium, wine and an assortment of spices. He called the mixture Laudanum (Derived from Latin meaning “something to be praised”) .

9. In 1680, the English physician Thomas Sydenham, considered the father of clinical medicine, introduced a highly popular version of an opium drink called Syndenham’s Laudanum. • For the next 200 years or so, the acceptable form of taking opium among Europeans and Americans would be in the form of a drink, either Sydenham’s recipe or variations.

11. The Opium War • Sometime in the eighteenth century, China invented a novel form of opium use, opium smoking, which eventually became synonymous in the Western mind with China itself. • In the eighteenth century the British people had fallen in love with Chinese tea. • British merchants wanted to buy tea and send it home, but what could they sell to the Chinese in exchange? • The problem was that there were few, if any, commodities that China really wanted from the outside. • In Chinese eyes, the rest of the world was populated by “barbarians” with inferior cultures offering nothing or little the Chinese people needed. • The answer was the opium. In 1773 British forces has conquered Bengal province in India and suddenly had a monopoly on raw opium. • It was now easy to introduce opium to China as a major item of trade

12. Opium was successfully smuggled into China through local British and Portuguese merchants, allowing the British government and its official trade representative, the East India Company, to carry off the public image of not being directly involved in opium trade. • Opium, flooding into the country from its southern part of Canton, found a ready market, opium dependence soon became a major Chinese problem. • Despite repeated efforts by the Chinese emperor to reduce the use of opium within China or to cut the supply line from India, the monster flourished. • By 1839, the tension had reached a peak. In a historic act of defiance against the European powers, including Britain, an imperial commissioner appointed by the Chinese emperor to deal with the opium problem once and for all confiscated a huge quantity of opium and burned it publicly in Canton. • Events escalated shortly after this until open fighting between Chinese and British soldiers broke out. The opium war had begun.

14. By 1842, British artillery and warships had overwhelmed a nation unprepared to deal with European firepower. In a humiliating treaty, China was forced to sign over to Britain the island of Hong Kong and its harbor (until the distant year of 1997), granting to British merchants exclusive trading rights in major Chinese ports, and pay a large amount of money to the British losses during the war. • Despite these agreements, fighting broke out again between 1858 and 1860; this time British soldiers were joined by the French and Americans. • Finally in a treaty signed in 1860, China was required to legalize opium within its borders. • The opium war had succeeded in opening up the gates of China, much against its will, to the rest of the world. (The Opium War from the Chinese perspective.)

16. Opium in Britain • The acceptable form of opium use in Victorian England was opium drinking in the form of laudanum. • The Oriental practice of opium smoking was identified by the British with vice and degradation and associated with the very lowest fringes of society. • Opium in the mid-1800s was the aspirin of its day. There was no negative public opinion and seldom any trouble with the police.

17. Any opium addict, as long as there were no signs of opium smoking, was considered no worse than a drunkard. • Dozens of laudanum based medicines, with appealing names like • A penny worth of peace • Mrs. Winslow’s Soothing Syrup, Were used to dull teething pain or colic, or to keep children quiet. • In 1821, Thomas DeQuincey published his book, Confessions of an English Opium Eater, that created a new cultural phenomenon for recreational opium use.

18. Opium in the United States • Opium consumption in the U.S. paralleled its widespread use in Britain. • Opium poppies were cultivated in Vermont and New Hampshire, in Florida and Louisiana, and later in California and Arizona. • Women outnumbered men in opium use during the 1800s by as much as three to one. • Alcohol drinking was not an acceptable behavior for females but laudanum was. The consequence was that “husbands drank alcohol in the saloons; wives took opium at home.”

19. Opium was advertised as a treatment of alcohol addiction, “white star secret liquor cure” was designed to be added to a gentlemen’s after-dinner coffee. • 1850s-1860s • Thousands of Chinese men and boys were brought to the West to build the railroads. • Most of the Chinese workers were recruited from the Canton area where opium traffic was particularly intense. • The practice of opium smoking was well known to them.

20. In 1875 San Francisco outlawed opium smoking, a federal law forbidding opium smoking soon followed. • The Harrison Act of 1914 required that physicians registered with the Internal Revenue Service the opiate drugs that were being prescribed to their patients and pay a small fee for the right to prescribe such drugs. • In the 1920s, the U.S. Supreme Court interpreted the Harrison Act more widely. Under the Court’s new interpretation of the Harrison Act, no physician was permitted to prescribe opiate drugs for “non-medical” use.

21. In 1803, a German clerk named Friedrick Serturner First isolated a yellowish-white substance in raw opium turned to be its primary active ingredient. He called it morphium, later changed to morphine, in honor of Morpheus, the Greek god of dreams. • In 1898, heroin was introduced into the market by the Bayer Company in Germany as a new pain killer. It is the same company that had been successful in the development of aspirin.

22. Administering Lowered body temperature Decreased blood pressure Skin flushed and warm Papillary constriction Constipation Respiratory depression Decreased sex drive Muscular relaxation Nodding, stupor Analgesia Euphoria Withdrawing Elevated body temperature Increased blood pressure Piloerection (gooseflesh) Tearing, runny nose Diarrhea Yawning, panting, sneezing Spontaneous ejaculations and orgasms Restlessness, involuntary twitching and kicking movements Insomnia Pain and irritability Depression and anxiety Symptoms of administering heroin and of withdrawing heroin

23. Type of Narcotic Morphine White heroin Brown heroin (from Mexico) Heroin combined with amphetamines Heroin combined with cocaine Heroin combined with marijuana Heroin combined with cocaine and marijuana Heroin combined with cocaine and morphine Codeine combined with Doriden (a nonbarbiturate sedative-hypnotic) Street Name Big M, Miss Emma, white stuff, M, dope, hocus, unkie, stuff, morpho Junk,smack, horse, scag, H, hard stuff, dope, boy, boot, blow, jolt, spike, slam Black tar, tootsie roll, chapapote (Spanish for “tar”), Mexican mud, peanut butter, poison, black jack Bombitas Dynamite, speedball, whizbang, goofball Atom bomb, A-bomb Frisco special, Frisco speedball Cotton brothers Loads, four doors, hits Street names for narcotic drugs

24. Generic Name Morphine Heroin Codeine Methadone Meperidine Butorphanol Hydromorphone Nalbuphine Propoxyphene Oxycodone Oxycodone/Acetaminophen Acetaminophen/Hydrocodone Oxycodone/Aspirin Trade Name(s) Astromorph, PF, Duramorph, Epimorph, Kadian, Infumorph 200&500, morphitec, M.O.S., MS Contin, MSIR, OMS Concentrate, Oramorph SR, RMS, Roxanol, Rescudose, Ultraject -------- Codeine Dolophine, Methadose Demerol, Pathadol, Pethidine Stadol Dilaudid Nubain Darvon, Dolene, Novapropoxyn OxyContin, Oxyfast, Roxicodone, Supeudol Percocet, Endocet, Oxycocet, Roxicet, Roxilox, Tylox, OxylR Vicodin, Lorcet, Anexsia, Lortab Percodan, Endodan, Oxycodan, Percodan-Demi, Roxiprin Common Opiate Agents of Abuse

25. Exogenous opiate drugs act on opiate receptors in the brain. Researchers theorize that these opiate receptors exist in order to facilitate the action of the body’s endogenous opiate like substances known as endorphine and enkaphalin (natural morphine). • Exogenous opiate drugs function as agonist to the brain opiate receptors, turning on the natural analgesic pathway in the brain and producing the characteristic analgesia and euphoria sensation that in susceptible individuals reinforces drugs and propels the addiction. • Habitual opiate use, while turning on the pain-suppression pathway, causes the normal endogenous opiate system to decrease the production of endorphin and enkephalin.

26. Repetitive use of exogenous opiates also produces adaptation of the opiate receptors, rendering them less sensitive to agonist actions. • This “Down-Regulation” of the receptors requires larger amounts of the drug to produce similar effects, a phenomena called tolerance, and produces withdrawal symptoms when the receptors are not under agonist effect.

27. Treatment Options • Methadone • Clonidine (Alpha-adrenergic receptor agonist) • Ultra rapid detox • Methadone maintenance • LAMM (Levo-alpha-acetylmethadol).

28. Rapid Detox • Substance abuse and dependency is a major public health concern in the United States because of the economic and human costs. • Current drug abuse treatment approaches, developed primarily during the 1960’s and 1970’s, have changed very little since their inception. The changes that have occurred in treatment in the last decade have been primarily structural and have been propelled by the tide of managed care reforms rather than the emergency of treatment models.

29. Managed care and cost-containment polices have affected substance abuse treatment by decreasing the type and intensity of services, shifting treatment from in-patient and residential care to out-patient settings. • Eighty-seven percent of patients are now treated in out-patient programs (substance abuse and Mental Health Services Administration, 1996).

30. The Development of New Models of Treatment • Substantive advancements have occurred in our understanding of the genetic and biochemical basis of substance abuse and addiction in the last 10 years. Yet little of this information has been translated into alternative treatment models for the addicted patient. • Abstinence remains the goal of traditional addiction treatment. • Sudden cessation of opioid use causes predictable cascade of symptoms collectively referred as withdrawal symptoms as previously mentioned.

31. Medically supervised detoxification treatment has traditionally been seen as the golden standard and as the logical starting point of treatment. • Traditional detox has involved treatment with prescription medications, which produces similar physiological responses, less psycho-activation, and which can be more precisely regulated and tapered as the patient’s metabolism readjusts to functioning without the addictive drugs. • Traditional detox takes an average of 3 to 15 days, depending on the abused drug. • Medical detox controls but does not eliminate subjectively uncomfortable withdrawal symptoms.

32. Universally accepted addiction treatment approaches are beginning to be challenged by the emergence of innovative treatment approaches based on the new understanding of the neurochemistry of addiction. • Rapid detox has emerged as an alternative that is gaining in both acceptance and popularity, evidence by recent showcasing in television episodes of E.R. • Rapid detox is an umbrella term that has come to represent new treatment approaches specifically designed to detox patients addicted to natural and synthetic opiate drugs within hours rather than the traditional days and to almost completely eliminate the subject of discomfort of withdrawal symptoms. • Started in Europe in the late 1980’s and brought to the United States in late 1996.

33. Common trade names for rapid detox treatment programs • Rapid detox (RO) • Neuroregulated detox • Neuro-adaptation treatment • OADUSA (opioid antagonist agent detox under sedation or anesthesia) • IND (intensive narcotic detox) • UROD (Ultra-rapid opiate detox) • RAND (rapidly accelerated narcotic detox) • KIYSR (kick in your sleep rapid relief)

34. Rapid Detox • Rapid detox procedures has been done by employing two novel approaches. • First, general anesthesia is to ensure no subjective distress is felt. • Second, use of large dosages of opiate antagonist in order to rapidly and completely remove the exogenous opiate drugs from the opiate receptors in the brain. • Because patient can not feel no subjective distress from withdrawal, detox can be completed within few hours (4-6) rather than 3 to 15 days with traditional detox.

35. It is important to differentiate between: • Rapid detox, similar to traditional detox strategies, but patient receives more sedation than usual during the withdrawal .sedation is accomplished through the use of benzodiazepines and can decrease the time of withdrawal by a day or two. The sedation is done to minimize the subjective distress of withdrawal symptoms allowing detox to progress more rapidly. • Ultra-rapid detox. An approach using general anesthesia to induce complete unconsciousness, thus ensure complete comfort during detox.

36. Procedures • Rapid detox programs require either overnight monitoring or one day program where individuals checks-in early in the morning and leaves at the same day. • All programs require pre-evaluation entails drug history, psychological evaluation, medical history and current health status evaluation. • Start I.V. and induce general anesthesia.

37. Ultra-rapid detox (UROD) has become potent protected treatment name however literature still refer to it as rapid detox.

38. Most programs offering rapid detox require an anesthesiologist to be present to monitor the anesthesia and perform the procedure in the location (hospital) where emergency services are quickly available should complication arise. • Once general anesthesia has been induced and no subjective withdrawal discomfort felt by the patient. opiate receptor blockade is accomplished with the use of opiate antagonist agents. • Three common opiate antagonists exist: Naltrexone, naloxone and nalmefene. By far naltrexone is the most widely used opiate antagonist during rapid detox.

39. Comparison of Opiate Antagonist Agents

40. The opiate antagonists have competitive binding at opiate receptor level, washing out any exogenous opiates and assisting the receptors to begin to reestablish normal sensitivity. • The amount of opiate antagonist required and therefore the length of time anesthesia must be maintained depends on patient weights and the duration and intensity of their addictions. • Procedure average time 4-6 hours. • A short recovery period should follow, including mild nausea and diarrhea. • The patient is continued on the opiate antagonist agent, usually Naltrexone, as once a day oral dosage for 6 to 12 months.

41. Treatment Indications • Addiction to opiate agents • Motivated for treatment • No co-morbid health condition • Failure of past traditional detox programs • Normal liver function lab values • Normal thyroid function lab values • Limited cardiovascular risk factors.

42. Treatment contraindications • Poly-substance abuse to primarily non-opiates • Little internal motivation • Medically compromised or unstable • No attempts at detox • Liver disease • Thyroid disease • Cardiovascular disease.

43. Advantages of ultra-rapid detox • Minimizing the very clinical significant, subjectively distressing withdrawal symptoms of opiate addiction. • Rapid detox occurs at the neuroreceptor level and affords the patient an opportunity to start intensive follow up immediately while feeling physically capable to engage in ongoing treatment.

44. Confidentiality can be facilitated when patients do not require protracted hospitalization, making treatment more acceptable to some. • Continuous use of opiate antagonists post detox affords the patient a measure of protection against relapse and decreases cravings and increases the likelihood of successful treatment.

45. Intensive follow up counseling is required after the rapid detox to address needed lifestyle changes, psychological factors and continued abstinence.

46. Disadvantages of ultra-rapid detox • Risks related to general anesthesia use the risk of death associated with general anesthesia is 1 in 250,000 and risk of adverse events rises to 1 in 10,000. • Rapid detox accomplishes medical detox or removal of the physiological effects of the opiate. It does little to affect the physiological withdrawal syndrome, and substantial psychological support and counseling are required for the patient to maintain a drug-free lifestyle.

47. Because rapid detox is considered experimental, insurance companies do not cover the cost. • Lack of reliable and valid empirical studies regarding the efficacy of the treatment.