Opiates
(Ch. 15)
  1. OPIUM: A HISTORICAL PERSPECTIVE
  1. Opium comes from the plant Papaver somniferum
  2. Opium is produced and available for collection for only a few days of the plant's life, between the time the petals drop and before the seed pod matures. Today, as before, opium harvesters move through the fields in the early evening and use a sharp clawed tool to make shallow cuts into the unripe seed pod. During the night a white substance oozes from the cuts, oxidizes to a gummy, red-brown colored resinous substance. In the morning this substance is carefully scraped from the pod and collected in small balls. This raw opium forms the basis for the opium medicines used throughout history and is the substance from which morphine is extracted and then heroin is derived
  3. Early Egyptians and Greeks (1500 BC) are believed to have used opium, socially and medicinally
  4. In Arabia, opium use was common because the Koran forbade alcohol use
  5. Opium and hashish became the primary social drug wherever the Islamic culture moved
  6. Opium was later introduced into India, China and Europe
  7. The English writer Thomas De Quincey glorified opium in the early 1800ís
  1. THE OPIUM WARS
  1. One reason opium smoking was popularized in China was because of the ban on tobacco smoking in 1644. At first, opium was mixed with tobacco and took the edge off of the craving for tobacco - the amount of tobacco used was gradually reduced and then omitted altogether
  2. In 1729, opium smoking for nonmedical purposes was outlawed, giving rise to illegal smuggling from India
  3. Eventually the British smuggled in opium for profit through the British East India Company
  4. When the emperor of China attempted to suppress the opium smuggling, the Opium War broke out in 1839 between England and China. Basically, the British went to war in order to continue bringing opium into China against the wishes of the Chinese national government. The war lasted for two years
  5. In 1906, Parliament supported and passed a bill that eventually ended the opium trade by 1913
  1. THE DEVELOPMENT OF OPIUM DERIVATIVES
  1. Morphine was developed in 1806 by Frederich Serturner. The active agent was ten times as potent as opium.
  2. By 1832 codeine was developed.
  3. The major increase in the use of morphine came as a result of two nondrug developments:  1) the development of the hyperdermic syringe in 1853, and 2) war - The American Civil War (1861-1865); the Prussian-Austrian War (1866); and the Franco-Prussian War (1870). Prussia is a former state in N. Europe; it bacame the foundation for the German empire in the 1870s. Morphine given by injection worked rapidly and well for the reduction of pain and relief from dysentary
  4. Heroin was developed in the late 1874 by adding two acetyl groups to the morphine molecule, yeilding diacetylmorphine, which was eventually given the brand name Heroin and placed on the market in 1898 by Bayer Laboratories
  5. Heroin is three times as potent as morphine. The pharmacology of heroin and morphine is identical except that the two acetyl groups increase the lipid solubility of the heroin molecule, and thus the molecule enters the brain more rapidly. The additional groups are then dettached, yielding morphine. Therefore, the effects of morphine and heroin are identical except that heroin is more potent and acts faster
  1. NARCOTIC ADDICTION
  1. Addiction increased as a result of opiates in patent medicines (for self-medication), development of the hypodermic needle, importation of Chinese laborers, and use during the Civil War
  2. Medical concern developed over the number of peole who were addicted to opiates, and this concern was a part of the motivation that led to the passage of the 1906 Pure Food and Drug Act
  3. Physicians dispensed opiates a great deal in their practice and this contributed to high rates of opiate addiction (~1% of the population at the turn of the century).
  4. There is plenty of support for the thesis that between the period 1806-1914, when drugs were widely used - it was because they met the needs of that culture
  5. The 1914 Harrison Act curtailed legal use of narcotics by addicts by limiting access and eventually eliminating access to addicts
  6. After the Harrison Act, addicts were viewed as degenerate, vile individuals rather than as poor people worthy of sympathy. By 1922, the only source of opiates available for the nonhospitalized addict was an illegal dealer. Because heroin was the most potent opiate available, it was the easiest to conceal and therefore became the illegal dealer's choice. The cost through this source was 30-50 times the price of the same drug through legitimate sources, which no longer were available to the addict
  7. After World War II, heroine use increased in slum areas of large cities; gradually prices increased, and quality decreased
  8. In 1961 a critical shortage of heroin developed and prices tripled - it was this event that that disrupted the previous social cohesiveness among addicts, increased the amount of crime, and contributed to the general social disorganzation of the ghettos, where most addicts lived
  9. During the Vietnam conflict early reports (1971) estimated that 10-15% of the American troops were addicted to heroin. Many of these were thought to be addicts. A follow-up study released in September 1971 showed that most of the Vietnam heroin users did not continue heroin use in this country. Only 1-2% were using narcotics 8-12 months after returning from Vietnam and being released from the service, approximately the same percentage of individuals found to be using narcotics when examined for induction into the service.
  10. Different groups of researchers estimated the number of heroin addicts from 1970 to the mid-1980s, and the estimates mostly ranged between 400,000 and 500,000 addicts
  11. Today, over half of the heroin supply comes from Southeast Asia (56%), followed by Southwest Asia and Mexico (~22% each)
  12. Since the mid-1970s the quality (purity) of heroin has increased drastically
  1. PHARMACOLOGY OF NARCOTICS
  1. Heroin is capable of penetrating the blood-brain barrier more easily than morphine, thus making heroin 2-3 times more potent
  2. Medicinal chemists have worked hard to produce compounds that would be effective painkillers, trying to separate the analgesic effect of theopiates from their depence-producing effects. Althugh the two efects could not be separated, the research has resulted in synthetic opiates that are sold as pain releivers.
  3. Sympathetic narcotics such as fentanyl and sufentanyl are vastly more potent
  4. Narcotic antagonists such as naloxone and naltrexone block the action of narcotics. They may save a person's life by reversing the depressed respiration resulting from a narcotic overdose
  5. Enkephalins and endorphins are morphine-like substances many times more potent which are naturally present in the brain. Both of these substances are contained within neurons and released from terminals to act as neurotransmitters or as modulators of neural activity.
  6. These substances,as well as th natural and synthetic opiate drugs have actions on at least three different types of opiate receptors, the structures of which were discovered in the early-1990s. One of the most important sites of action may be the midbrain central gray are, a region known to be involved with pain perception. However there are many sites of interaction between these systems and areas that relate to pain; and pain is a complex psychological and neurological phenomenon - so we cannot say that we understand completely how the opiates act to reduce pain. In addition, we know that large amounts of endorphins are relaeased from the pituitary gland in response to stress. Also, enkephalins are released from the adrenal gland. The function of these peptides circulating through the blood as hormones are not understood at this point
  1. BENEFITS AND DRAWBACKS OF NARCOTICS
  1. The major benefit of narcotics is that they reduce the emotional response to pain. The effect of narcotics is relatively specific to pain.
  2. Relief of diarrhea (decreasing the number of peristaltic contractions) and suppression of coughing (decreasing activity in the cough control center in the medulla) are also achieved by narcotics
  3. Tolerance to narcotics occurs although some of the tolerance may be learned (in anticipation of receiving a dose)
  4. Physical and psychological dependency results from prolonged narcotic use
    1. positive reinforcement - a behavior is reliably followed by the presentation of a stimulus, leading to an increase in the probability of the behavior and its eventual maintenance at a higher rate than before
    2. negative reinforcement - an (taking a drug) is followed by the removal of withdrawal symptoms, leading toi further strengthening of the habit.
  5. Some narcotic users are so-called needle freaks who simply like the rush derived from injecting
  6. Narcotics depress the respiratory centers in the brain and death can follow if enough narcotics are used
  7. Unsterile needles represent another danger, since hepatitis and HIV can be contracted
  8. If they survive, addicts may stop using the drugs because they "mature out"
  9. Withdrawal symptoms are not the excruciating experience the media portrays them to be
  10. New derivatives are constantly being developed, many with worse consequences than the present drugs
  1. THERAPEUTIC APPROACHES TO NARCOTIC ADDICTION
  1. Early in the 1930s, as an answer to prison overpopulation, the US government established treatment facilities at Lexington, Kentucky, and Fort Worth, Texas
  2. Narcotic antagonists such as naltrexon block the effects of narcotics
  3. Methadone & L-apha-acetyl methadol (LAAM) maintenance programs substitute methadone or LAAM (approved for use in 1993) for heroin, preventing withdrawal symptoms from occurring for up to 24 hours or longer. The theory behind the use of methadone to help rehabilitate addicts is that the long-lasting effects of methadone prevent withdrawal symptoms and block the pleasurable effects of opiates. This could be done in a more controlled environment.
  4. In Britain addicts may receive heroin or cocaine or methadone from a specially licensed physician if the addict is registered as such