The use of certain species of the poppy to produce analgesia and euphoria goes back at least as far as recorded history. A Sumerian tablet from about 4500 BC not only refers to the poppy as hul gil — the “plant of joy” — but also tells how to cultivate it, harvest the sap, and prepare it as a drink. Medical texts from ancient Egypt prescribe use of poppy juice to relieve severe pain. The Greek philosopher and botanist Theophrastus (c. 371-c. 287 BC) observed that this product was “both blessedly beneficial and occasionally lethal.” The Greeks called the sap opium and meconium.
That ancient medicine had learned how to harness the therapeutic powers of Papaver somniferum was something of a miracle, as Thomas Dormandy, MD, noted in his fascinating new book Opium: Reality's Dark Dream. The plant is relatively easy to grow, but processing the sap is neither straightforward nor intuitive.
Dr. Dormandy describes how a thin cloudy white liquid seeps out when the plant's pod is incised, a complex chemical brew containing water, sugar, protein, wax, gum, acids and alkaloids. It has little pharmacological activity, however, and becomes dark and sticky when exposed to air. Most importantly, the alkaloids are oxidized and transformed into active opiates such as morphine and codeine.
It is easy to make a mistake when producing opium. The incision that liberates opium must be careful and precise. If the cut is too deep, the thin liquid runs out quickly, dripping uselessly to the ground before it can be harvested. If the cut is too shallow, the sap quickly coagulates, sealing the pod before much opium is produced. The ideal incision is said to be 1.0-1.5 mm deep, but judging this is a matter of skill and experience, as is determining the ideal time of day to tap the pods.
Paracelsus (1493-1541), the father of toxicology, is best known for his maxim: “All things are poison, and nothing is without poison; only the dose permits something not to be poisonous.” He was also the first to formulate laudanum, a tincture of opium that was palatable when taken orally and would have profound effects on history and literature over the next several centuries. Dr. Dormandy cites one of Paracelsus's recipes: “Take of Thebaic opium one ounce, of orange and lemon juice six ounces, of cinnamon and cariophilli each half an ounce. Pound those ingredients together, mix them well, and place them in a glass vessel with its covering. Let them be digested in the sun or in dung for a month. Then press out the mixture and place them in another vessel with the following: half a scruple of must and half a scruple each of corals and of a magistery of true pearls. Mix those, and after digesting all for a month, add a scruple and a half of the quintessence of gold.”
A century later, the English physician Thomas Sydenham had a simpler but no less intriguing formula for preparing laudanum: “[O]ne pint of sherry wine, two ounces of good quality Indian or Egyptian opium, one of saffron, a cinnamon stick and a clove, both powdered. Mix and simmer over a vapour bath for two or three days until the tincture has the proper slightly viscid but still easily poured consistence.”
Dr. Dormandy reports that Sydenham dispensed his elixir to treat everything from cholera to bunions. It also unlocked the imagination, judging from the list of authors who used the drug. Many of the romantic poets — Keats, Francis Thompson, and George Crabbe, among them — fueled their creativity with hefty doses of laudanum. Samuel Taylor Coleridge, whose poem “Kubla Khan” is a detailed description of an opium dream, was reported to consume a quart of laudanum per week. Coleridge cursed laudanum as “this free-agency-annihilating Poison,” despite this intake, or perhaps because of it.
Use of laudanum had spread from the literati to the hoi polloi by the mid-1800s. Patients could readily obtain laudanum-based patent medications over-the-counter from chemist's shops in England. Pediatric formulations were also available under such trade names as Mrs. Winslow's Soothing Syrup, Street's Infant Quietener, and Atkinson's Baby Preservative. These were said to be good for colic or, really, for anything that would make an infant cry.
Recent advances in science by this time were quickly making commerce in laudanum and opium itself obsolete. A young pharmacist's apprentice in Germany named Friedrich Serturner had succeeded in isolating the most active alkaloid in opium, a compound he called “morphine” that, gram for gram, was 10 times more potent than opium itself. The French chemist Pierre Robiquet isolated a second alkaloid, codeine, in 1832, and the 1841 invention of a hypodermic syringe that attached to a sharp hollow needle enabled precise amounts of morphine to be administered subcutaneously, intramuscularly, or intravenously.
The last major step in the evolution of opium took place toward the end of the 19th century. Researchers at the Bayer pharmaceutical company in Germany — already working on acetylating salicylic acid to make it more effective — subjected morphine to a similar reaction and succeeded in synthesizing diacetylmorphine. They found that taking the substance made them feel like heroes, and they called the new drug heroin, initially marketing it as a safe, nonaddicting narcotic.
Dr. Dormandy, a retired pathologist, tells this history with skill and abundant detail, although the narrative does drag some in the last third of the book which concentrates on politics and attempts to control the distribution and use of narcotics. The extensive annotated bibliography will prove invaluable to anyone researching the history of narcotics.
Some mistakes should have been caught before publication. Coleridge did not live into his mid-70s but died at 61. It was Truman Capote, not Allen Ginsberg, who said of Jack Kerouac's novel On the Road: “That's not writing; that's typing.” And opiates were certainly not the drugs most associated with the flower-power culture.
Nevertheless, Opium: Reality's Dark Dream should be on the short list for any toxicologist or pharmacologist with an interest in medical history.
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* Opium: Reality's Dark Dream by Thomas Dormandy, MD, was published by Yale University Press (366 pp; $40).
* Visit Dr. Gussow's blog at www.thepoisonreview.com.
* Read all of Dr. Gussow's past columns at http://bit.ly/GussowToxRounds.
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