MORPHINE

1. Part One MORPHINE OPIUM ALKALOIDS

2. OPIUM When the unripe seed capsule of the opium poppy (Papaver somniferum) is cut, a viscous milky liquid exudes. This is collected. On exposure to air the exudate dries and hardens, giving a hard but slightly sticky mass known as “opium”. Many alkaloids (> 40) are present in opium; the major one is morphine. MAJOR OPIUM ALKALOIDS (% of total alkaloids) morphine 10-20% noscapine 4-8% (also called narcotine) codeine 0.2-0.8% papaverine 0.5-1.5% thebaine 0.2-1.0% laudanosine < 0.1%

3. WORLDWIDE DISTRIBUTION Opium poppies are native to Asia Minor and SE Asia. However, now they are cultivated in third world countries worldwide and by drug cartels in South America. Before the war opium was a major income source for for the Taliban, and still supports local tribal leaders in Afghanistan. It is a major item of illicit commerce, along with cocaine, in Columbia. Opium is converted to Heroin in drug labs. Heroin is more potent than morphine.

4. CALIFORNIA POPPIES Papaver spp Do not contain morphine or codeine, but like all poppies have papaverine (the “poppy alkaloid”).

5. OPIUM POPPY Papaver somniferum

6. Collecting Opium

7. HARDENED OPIUM MASS OPIUM, MORPHINE AND HEROIN

8. MORPHINE PHARMACOLOGY Powerful analgesic and sedative - modifies the perception of pain rather than eliminates it - 10-15 mg of morphine take effect in 15 min - produces sleep and analgesia lasting 6 hr Unpleasant side effects - physiolgically addicting - constipating - respiratory depresssant overdoses cause death due to respiratory failure and severe anaphylaxis (shock) Lethal dose: 10 mg children, 0.5-2 g for adults, addicts can tolerate up to 7 g per day

9. MORPHINE - SOME HISTORY Morphine was the first pure alkaloid (vegetable base) to be isolated. Serturner 1805 is usually credited with being first. (with claims by Derosne 1803, Sequin 1804) (codeine in 1833 by Robiquet) He named it after Morpheus (Greek god of dreams) It required more than 150 years (1805 - 1956) to completely determine the structure of morphine. Many research groups contributed to the effort.

10. CLASSICAL TIMES Homer (The Odyssey) called poppy juice “nepenthe”. Poppy seeds and capsules have been found in neolithic dwellings (3000 B.C.) in Switzerland. Minoan cultures venerated the poppy and made goddess figures with poppy seedpod crowns. MIDDLE AGES Opium was brought from Turkey, China and India along the caravan routes in the middle ages.

11. OPIUM WARS British East India Company (starting in 1773) used it as an item of trade for chinese silk and tea. They grew the opium in Bengal and Burma. In China it was smoked in “opium dens”. In the nineteenth century China recognized opium smoking was becoming a serious societal problem. In 1820 the Chinese outlawed importation of opium, which started a vigorous black market, fueled by the British. In 1839 the Chinese destroyed 20,000 cases of opium starting the “Opium Wars” with England, which they lost in 1842, signing the Treaty of Nanking, which opened several ports to the trade. In 1858 opium was once again legalized by the Chinese.

12. NINETEENTH CENTURY EUROPE AND AMERICA In the nineteenth century, opium became a recreational drug in Europe and the United States. Hector Berlioz is said to have written his “Sinfonie fantastique” and Edgar Allen Poe is said to have written stories and poems under its influence. “Laudanum” and opium extracts were available in drugstores and on the field of battle at the time of the Civil War. Many injured soldiers became addicted. Many tonics sold in stores and by travelling salesmen of the time contained both alcoholANDopium. PURE FOOD AND DRUG ACT The Pure Food and Drug Act stopped all this in 1906. This was truly a landmark piece of American legislation.

13. OPIUM WARS OPIUM DEN

14. HEROIN Morphine is easily acetylated to diacetylmorphine using acetic anhydride. morphine HEROIN diacetylmorphine Originally introduced by drug companies as the “heroic” new drug, with “ all properties of morphine except the addiction tendency” ….. this was soon proved to be false! Heroin is more potent than morphine (it takes less for the same effect), lasts longer, and is more addicting. Addiction to heroin is a serious social problem today.

15. CODEINE Codeine can be produced by methylation of morphine morphine CODEINE OH- monomethylmorphine Codeine is a powerful antitussive - it blocks the cough reflex.

16. ASSIGNMENTS Read: Hesse Alkaloids - Nature’s Cure or Curse, Wiley-VCH (2000) 11.5 “Opium”, pp 338-350 Chapter 10 “Historical Aspects of Alkaloid Chemistry” pp 313-323