A HISTORY OF MORPHINE
Addictiveness of drug long used to ease pain makes it a double- edged sword
Famed Harvard Medical School professor and writer Oliver Wendell Holmes opined in the 1800s that if all medicinal drugs used at the time could be sunk to the bottom of the sea, “it would be all the better for mankind and all the worse for the fishes.”
He was, however, careful to make an exception for opium, the resinous latex that exudes from the seed pod of the opium poppy. The use of opium predates written history with remains of poppy pods having been found in caves that are known to have been occupied by humans as early as 10,000 BC. Of course exactly what role the poppies played in the cavemen’s lives is not known, but it is possible that by trial and error they chanced upon the calming and pain- relieving properties of poppy juice. By 3500 BC, the Sumerians who occupied Mesopotamia, now western Iraq, were trading opium with other civilizations implying widespread awareness of the effects of consuming opium. Ancient Roman and Greek physicians prescribed opium for melancholy, pain, coughing and diarrhea, conditions for which opium does provide relief.
“Take opium, mandragora and henbane in equal parts and mix with water,” a 12th- century treatise advised doctors. “When, you want to saw or cut a man,” it continued, “dip a rag in this, put it to his nostrils and he will sleep so deep that you may do what you wish.” The problem was that sometimes the sleep became permanent. In the 16th century, Swiss- German physician and alchemist Paracelsus, perhaps best known for his dictum, “only the dose makes the poison,” discovered that opium was more soluble in alcohol than water and recommended a solution he called “laudanum” for relieving pain. The name came from the Latin “laudare,” meaning “to praise,” but laudanum wasn’t always praiseworthy. Determining appropriate dosage was difficult because solutions varied greatly in concentration of active ingredients and physicians also began to notice that stopping the drug after long- term use led to “great and intolerable distresses, anxieties and depression of the spirit,” essentially the first reports of addiction and withdrawal.
Laudanum became the Victorian era’s most popular medicine. It was of course used for pain, but many looked to it for its euphoriainducing effect. These were well described in Thomas De Quincey’s classic work Confessions of an English Opium- Eater. De Quincey had been introduced to laudanum in 1804 as a treatment for trigeminal neuralgia, a disease of the trigeminal nerve that runs down the face. Even mild stimulation such as brushing the teeth or exposure to the wind can trigger a jolt of excruciating pain. Little wonder that De Quincey sang the praises of laudanum: “Here was a panacea for all human woes, here was the secret of happiness.” Samuel Taylor Coleridge was also keen on laudanum. His famous poem Kubla Khan about the 13thcentury Chinese emperor was based on a dream he had while in a laudanum- induced stupor. For those of you interested in trivia, Mary Todd Lincoln was a laudanum addict, and so was Mattie Blaylock, common law wife of Wyatt Earp. In Uncle Tom’s Cabin, Cassy kills one of her children with laudanum to prevent him from growing up in slavery and Bram Stoker’s Dracula puts Lucy’s maids to sleep with laudanum before sinking his teeth into her neck.
In the early 19th century, German pharmacist Friedrich Wilhelm Serturner became the first person to ever isolate an active ingredient from a medicinal plant, naming the compound he managed to purify from an opium extract “morphine” after Morpheus, the Greek god of dreams. After experimenting on mice and stray dogs, he took it himself and enlisted friends to ingest the substance to determine an appropriate dosage for humans. Serturner noted that 30 mgs induced a happy, light- headed sensation, a second dose caused drowsiness and fatigue, and a third dose caused a deep sleep with nausea and headaches upon awakening. After this, his friends refused to continue the experiment. The introduction of the hypodermic syringe made appropriate dosages easier to administer, but also facilitated abuse. Morphine, as the drug was called in English, was used extensively during the Civil War for pain of battle wounds with thousands of survivors becoming addicted to the drug.
It wasn’t until the 1970s that the mechanism of morphine’s activity was understood in detail. The molecule binds to receptors in the central nervous system interfering with the transmission of pain signals. But there was the question as to why such receptors exist. After all, the human body did not evolve to respond to extracts of a poppy that grows in the Orient. As it turns out, morphine’s molecular structure happens to mimic natural pain relievers produced by the body that appropriately were termed endorphins from endogenous and morphine.
Over the years, attempts were made to separate morphine’s medicinal properties from its addictive ones by modifying its molecular structure. Diacetylmorphine was introduced by the Bayer company in 1894 as “Heroin” because in clinical trial subjects experienced a “heroic” feeling. It was believed to be more potent and less addictive than morphine and was actually used to treat morphine addiction. That didn’t work.
Diacetylmorphine was introduced by the Bayer company in 1894 as ‘ Heroin’.
Actually, heroin is more fat soluble than morphine, allowing it to move easily across the blood brain barrier into the brain where it converts to morphine. This means a greater supply of morphine to the brain than is achieved by administering morphine, and a more powerful effect along with a greater potential for addiction. By the 1920s, heroin was banned giving rise to an illicit industry to convert morphine to heroin, an industry that is 10 times greater than the production of medicinal morphine. There are no viable synthetic methods to produce morphine, so the drug is still extracted from the poppy, although preliminary experiments have indicated a possibility of production using genetically engineered yeast.
Morphine is the proverbial double- edged sword. It can be a pain- alleviating angel or an addiction- causing devil.