The Opium Story
Part One: The History of Opium
by Bruce Thomson, Thomson Therapy Center PC
Humans have been harvesting the opium poppy for at least 7000 years! The opium poppy is native to the Southern and Western Mediterranean in Europe, where it was first domesticated. Opium appears to have spread from West to East, then back to the West again. Evidence of harvest and use has been found in Late Stone Age settlements in Swiss Lake Villages near the headwaters of the Rhine, the Rhone, the Po and the Danube rivers, at Lake Bracciano in Italy and in Germany, dating to 5700 BC. In Bronze Age Spain (4200 BC) opium poppy capsules were placed with burial items in woven grass bags in the Cueva de los Murcialagos (‘Bat Cave’) near Granada. By 3400 BC the Sumerians in Mesopotamia were referring to opium as Gil, ‘happiness’, and the opium poppy as Hul Gil, the ‘plant of joy’. Perhaps in a bit of subtle revenge, they passed their knowledge, and the addictive plant, on to the Assyrians and the Babylonians who conquered them.
Egyptians of the Bronze Age grew opium poppies (Opium Thebacium) in famous fields near Thebes by 1500 BC, and traded it with the Phoenicians, Minoans, Greeks and Carthaginians. The trade spread to Crete (1300 BC) and Cyprus (1100 BC), where the “Peoples of the Sea” created high quality knives used specifically for the harvest of opium. The ancient Greeks knew opium, and in fact the name is derived from the Greek opos, ‘juice’, and opion, ‘poppy juice’. Homer refers to it in both the Iliad and the Odyssey around 850 BC. Greek and Egyptian physicians of the Bronze Age used opium to ease pain and the authorities mixed it with hemlock to insure quick, painless death for criminals. Hippocrates, “the father of medicine” stated its usefulness as a narcotic (from the Greek for “benumbing or deadening”) in 460 BC. The Latin name, Papaver somniferum, actually means sleep-bringing poppy. Many physicians used opium for pain relief, yet they were very concerned about causing accidental death due to uncertain dosages. And from the very start people were becoming addicted to the drug.
Around 330 BC Alexander the Great probably introduced opium to Persia and India during his campaigns of conquest. Opium was used in Arabic medicine from the first century onward, then used recreationally in Islamic societies. The Roman Emperor, Marcus Aurelius, was reputed to have died from an overdose of opium, which he took regularly to control the pain of his wounds and stiff joints. He was considered the last of the “Five Good Emperors” of Rome and his death led to the dissolution of the Pax Romana. If Opium addiction played a part, then it could be said to have hastened the fall of Rome! Even 2000 years ago opiates were taking a heavy toll on society.
Opium use spread to China with Arab traders by 400 AD, and use was heavy in Turkey, Iran, India and China. Ironically, use in Europe was largely forgotten due to unavailability and the Church’s condemnation of anything from Arabia. Somewhere between the tenth and thirteenth century opium made its way back from Asia Minor to Europe. In the early 1500’s Portuguese sailors trading in the East China Sea began the practice of smoking Opium. The results were an immediate and dramatic increase in reaction to the drug. The Chinese at first rejected the practice and outlawed it, only to later run into considerable domestic use and conflict with European nations profiting from the trade.
In 1527, a Swiss-German alchemist named Paracelsus described the mix of opium, ethanol and other ingredients, as a painkiller in European medical literature. He named it Laudanum after the Latin verb laudare, to praise. Laudanum came in many strengths and mixtures over the years. It is typically 10% powdered opium, 18-45% ethyl alcohol, and a variety of non-active additions including saffron, cinnamon, cloves, honey, musk, amber and even crushed pearls.
Even as the Portuguese were sending opium into China in the 1600’s, English ships chartered by Elizabeth I were bringing Indian opium to Britain at her command. Laudanum use became widespread for treating a variety of conditions – coughing, diarrhea and especially pain. One famous preparation by Thomas Sydenham included opium, sherry and herbs. In addition to treating medical concerns like cholera, dysentery, consumption and rheumatism, laudanum was in demand for military use. By 1841 the U.S. Army was using 2.8 million ounces of opium tincture (Laudanum) and 500,000 opium pills each year. And one portion of the population in particular demanded laudanum – women. Estimates are that three fourths of those who became addicted to laudanum were women taking the medication to treat menstrual cramps.
During the 1700’s the Dutch and then the British, began importing vast amounts of opium from India into China. The Dutch reintroduced the Chinese to smoking opium and it took hold. As the British gained control of India, they also controlled its opium production and began sending as much as 2000 chests of opium per year to China. The Chinese emperors responded by making illegal the smoking of opium in 1729, then opium itself in 1799. The British refused to stop the vastly profitable trade and in 1839 began the First Opium War with China. The Chinese lost the war, gave in to the opium trade, and even ceded Hong Kong to the British. Many wealthy Americans, including Charles Cabot, John Cushing and Jacob Astor began to trade in opium to China as well, finding the profits irresistible. In the 1850’s the British arrived in Burma and began massive imports of opium there as well. The Second Opium War, pitting Britain and France against China in 1856, solidified the legal sale of opium in China.
The British also firmed up their position on the supply side. In addition to India, they monopolized the purchase of Turkish opium, sending it exclusively to England and the U.S. Western use continued to soar at this time. By 1830, England was importing 22,000 pounds of opium per year, and by 1840 the U.S. was importing 24,000 pounds. However the writing was on the wall. Addiction rates in Western nations were soaring with estimates ranging from 250,000 to 1,000,000 addicts in the U.S. by 1900. The government would soon be forced to take action.
In 1875 San Francisco banned opium dens. In 1890 the U.S. Congress imposed a tax on opium and morphine. In 1891 California required warning labels on narcotics (any psychoactive compound that produces the morphine-like effect of relieving pain and inducing deep sleep. Psychoactive drugs, also known as psychotropic drugs, are chemical substances that cross the blood-brain barrier and act upon the central nervous system to change perception, mood, consciousness, cognition and behavior). By 1907 opiates required a prescription and by 1909 opium itself was illegal in the U.S. In 1914, 34 nations signed the Harrison Narcotics Act and agreed to control narcotics. By 1924, 62 nations had joined the Opium Commission.
While moving to fight the importation and use of Opium at home, the British continued to supply India and China with the drug. It was not until 1910 that the British agreed to dismantle the India-China opium trade, after 150 years of efforts by the Chinese leaders to reject it.
Opium actually began to fade as a drug of choice in the early 1800s. In 1805, Freidrich Serturner, an uneducated, 21-year-old German pharmacist’s assistant, isolated an organic alkaloid compound from opium. He found it to be 5-10 times as powerful as opium! He eventually named the substance morphine, after Morpheus, the Greek god of dreams. His work was slow to gain recognition, but by 1818 he was internationally renowned, and in 1827 Merck & Company of Darmstadt, Germany began the commercial manufacturing of morphine. They were the first to build a huge pharmaceutical company around opioids, but as you will soon see, they were far from the last.
Morphine quickly became a medical mainstay, used to treat a wide variety of illnesses. It had the usual opioid treatment characteristics: it was an analgesic (pain reliever); an antitussive (cough suppressant); an anti-diarrheal and helped with shortness of breath. When Dr. Alexander Wood developed the hypodermic syringe using a hollow needle to pierce the skin, morphine became injectable. The effects were instantaneous and three times as powerful as oral morphine. Sadly the trail of misery that so often follows relief with opioids was not slow to make an appearance. A woman named Mrs. Wood soon became the first recorded fatality from an injection overdose when she died from self-administered morphine! Accounts disagree on whether she was Dr. Wood’s wife or another relative, but agree on the fact of her death.
Once morphine had been isolated as the first alkaloid, (naturally occurring chemical compounds containing mostly nitrogen atoms, which are purified from raw extracts often through the use of acid), it was only a matter of time before others were found. In 1832, a French chemist named Pierre Robiquet was able to isolate codeine, the second alkaloid of opium, and the Merck chemical works immediately began to manufacture and market it alongside morphine. Along with the third alkaloid, thebaine, these 3 “natural opiates” would be accompanied by a host of further synthesized and lab-created “opioids”, including such familiar names as hydrocodone (in Vicodin), oxycodone (in Oxycontin), methadone and heroin.
This article courtesy of Bruce Thomson, M.S., M.S.W., all rights reserved.
Bruce is a Psychotherapist in Private Practice in Ann Arbor. He is the Chair of the Addiction and Recovery Special Interest Group for the NASW, MI, and he lectures on the brain chemistry of addiction for the University of Michigan, the NASW, and in schools throughout the state.
The Opium Story
Part Two: The Family of Opium Compounds
by Bruce Thomson, Thomson Therapy Center PC
The opium poppy is an annual herb that grows up to 3-5 feet tall. In addition to its lovely flowers, it packs a very powerful narcotic punch. The seed pods of the poppy produce a large amount of a latex-like liquid, and this liquid is loaded with the alkaloids that make opium so effective. Opium is harvested by scoring immature seed pods. The milky latex inside leaks out and is scraped off. This liquid dries to a sticky brown mass called opium.
In Part One of the Opium Story we saw how that opium has impacted civilization for the past 7700 years! By the early 1800’s a new factor was in play. Chemists had begun to isolate pure, natural alkaloids from the opium. These alkaloids were often more powerful than the original opium. There are over 50 alkaloids contained in the opium poppy but three of them are the most significant. Their narcotic effects earn them the title of the “natural opiates”. They are morphine, codeine, and thebaine.
Morphine is the most prevalent alkaloid in opium (10-16%). It causes most of the harm such as pulmonary edema, respiratory depression, coma, cardiac arrest, etc. 120-250 mg is lethal (about 2 grams of opium). Morphine is not very efficient when taken orally. It breaks down in the intestinal walls and is metabolized in the liver. Its full effect became felt when the injectable syringe appeared around 1850. With direct access to the blood plasma, morphine became 3-4 times more powerful, and deadly! Morphine is 3-10 times as powerful as opium, 10 times as powerful as codeine and 360 times as powerful as aspirin. Oral morphine is the pain relief standard other opioids are compared to. Heroin (Diacetylmorphine) is an opioid derived from morphine and is 2-4 times as strong.
Codeine is the second most predominant alkaloid in opium at 1-3%. From morphine, the alkaloid codeine is isolated (codeine can also be extracted directly from opium but this is less efficient). Codeine is the most widely used opiate in the world and perhaps the most widely used drug. It is 8-12% as strong as morphine and acts as an analgesic (pain suppressant), antitussive (cough suppressant), and anti-diarrheal. It is very effective when taken orally and has less physical dependency. The semi-synthetic opioids dyhydrocodeine , hydrocodone, ethylmorphine and benzylmorphine are derived from codeine.
Thebaine is the third opium alkaloid. It is a stimulant rather than a depressant. It is poisonous and is primarily used to synthesize opioids such as hydrocodone, oxycodone, oxymorphone, nalbuphine, naloxone, naltrexone, buprenorphine and etorphine . These last two are derived from a metabolite, (a metabolite is the product of metabolism), of thebaine called oripavine (as strong as morphine but very toxic so only used to produce other drugs).
Papaverine. This fourth component of opium is an example of the many non-opiate alkaloids because it is not a narcotic. It is used to treat heart and brain spasms, visceral spasms, and erectile dysfunction.
Opioids are chemicals that work by binding to specific opioid receptors in the central nervous system and gastrointestinal tract. Opioids include the natural alkaloids of opium, called opiates; semi-synthetic opioids created from natural opiates; fully synthetic opioids created chemically, and endogenous opioid peptides (internally produced short polymers created from linking amino acids – our brains natural opioids).
Opioids are useful for treating cough, diarrhea, shortness of breath, and pain. They do carry the risk of multiple adverse side-effects. These include nausea, vomiting, drowsiness, itching, dry mouth, constipation, confusion, dizziness, headache, urinary retention, muscle rigidity, flushing, hypothermia, hallucination, delirium, respiratory depression, hypotension, and tachycardia. They can compromise immune system function, lower testosterone levels, decrease muscle strength and cause osteoporosis.
Tolerance to opioids develops through receptor desensitization. Opioid dependence means painful withdrawal symptoms if use is stopped. These symptoms include dysphoria (sadness), insomnia, sweating, nausea, depression, fatigue, vomiting and pain.
The semi-synthetic opioids derived from natural opiates include:
Benzylmorphine. About 1/11 as strong as oral morphine.
Dihydrocodeine (Paramol). 1/7 to 1/10 as strong as morphine. Developed to treat tuberculosis, pertussis, and pneumonia.
Ethylmorphine . 1/5 as strong as morphine. Developed in 1884 by Merck. Used primarily to treat dry coughing and to remove inflammation products from the eyes.
Hydrocodone (Vicodin). 1/2 as strong as morphine. Derived from codeine or thebaine. Often combined with other analgesics. Vicodin is hydrocodone combined with acetaminophen. This can lead to liver problems due to Vicodin overuse which implies a deluge of acetaminophen. Problems are exacerbated by using alcohol concurrently. Any use of alcohol, benzodiazepines, cocaine, barbiturates, or amphetamines, while taking Vicodin, can cause heart failure, respiratory failure, liver/kidney failure, jaundice, amnesia, blackouts, seizures and coma.
Oxycodone (Oxycontin). 1.5-2 times as strong as morphine. Synthesized from Thebaine in 1926. Severe withdrawal symptoms require gradual withdrawal. Oxycontin is a time-release oxycodone. The manufacturer, Purdue Pharma has been sued for advertising practices. Lots of abuse due to high drug concentration, resale, crushing.
Percocet (Deplagos in Italy) . Oxycodone with acetaminophen.
Percodan. Oxycodone with aspirin (325mg).
Nicomorphine (Vilan). 2-3 times as strong as morphine. Synthesized from morphine in 1904. Used primarily in Germany.
Diacetylmorphine (Heroin). Heroin is 2-4 times as potent as morphine. Heroin was first synthesized from morphine in 1874. In 1897 a chemist at Bayer was trying to produce codeine from morphine and instead came up with Diacetylmorphine and Bayer Heroin was born. That’s right, before there was Bayer Aspirin, there was Bayer Heroin. Bayer was to become the second pharmaceutical company to make a fortune off of opium, following in Merck’s footsteps. From 1898 to 1910 heroin was marketed by Bayer as non-addictive. Then it was found to be a quicker acting form of morphine and completely addictive. For the complete story of heroin see the link below.
Hydromorphone (Dilauded). 5 times as strong as morphine. Derived from a ketone (carbon atom compounds) of Morphine. It is a very strong antitussive and is used in place of morphine. Synthesized in 1924. Brief but intense withdrawal.
Oxymorphone (Opana). 7 times as strong as morphine. Developed in Germany in 1914
Desomorphine (Permonid). 8-10 times as strong as morphine. Derived from morphine in 1932 in the U.S. When homemade it results in the deadly designer drug “crocodile” created by combining it with gasoline or paint thinner, iodine, hydrochloric acid and red phosphorous from match heads. This drug is being used by as many as 1 million Russians today.
Buprenorphine (Subutex, Suboxone). 40 times as strong as morphine. Used for pain control and to treat opiate addiction. When combined with Naloxone it is called Suboxone.
Etorphine. 1000-3000 times as strong as morphine. Primarily used on large animals such as elephants!
The Fully Synthetic Opioids created in a lab include:
Dextropropoxyphene (Darvocet, Darvon). A weak analgesic about 1/40 strength of morphine. Due to increasing dosage to chase effects, lots of potential liver damage from the acetaminophen added in.
Pethidine (Demerol). 1/3 as strong as morphine. This first synthetic was created in 1932. Very toxic.
Levorphanol (Levo-Dromoran). 4-8 times as strong as morphine. Developed in Germany in 1948. Used for chronic pain due to long duration of effect.Methadone . 3-7 times as strong as morphine depending on length of use. Developed in 1937 in Germany due to a morphine shortage. Long lasting and inexpensive. Used to treat opioid dependence.
Fentanyl (Sublimaze). 50-100 times as strong as morphine. Created in 1959 in US.
Sufentanil (Sufenta). 500-1000 times as strong as morphine. Synthesized at Janssen in 1974. Used mainly in operating rooms.
Carfentanil. 10,000-100,000 times as strong as morphine. Synthesized at Janssen in 1974. Used only for animals.
Endogenous (substances that originate from within an organism, tissue, or cell) opioid peptides (short polymers of amino acids linked by peptide bonds . They have the same chemical structure as proteins , but only shorter in length) . Our bodies produce these “human opioids”:
Endorphins (“endogenous morphine”). Produced in the pituitary gland and the hypothalamus. They are generated by exercise, excitement, pain, spicy food and orgasm. They are natural pain relievers. They are picked up by opioid receptors.
Enkaphalins . A pentapeptide (peptide consisting of five amino acids) that helps regulate the coding and processing of noxious stimuli. Discovered in 1975. Also picked up by opioid receptors.
Dynorphins. Produced in the hypothalamus, hippocampus and spinal cord. Affects appetite, electrical activity, etc. 6-10 times as effective at pain relief as morphine.
Endomorphins. There are two of these peptides that may help regulate arousal and sedative behaviors.
Part Three: Opioids and the brain – the brain chemistry of addiction.
Part Four: The scope of today’s problem, the local crisis and famous opioid addicts.
Part Five: Treatment of opioid addiction – Medical and Psychosocial. What really works.
Part Six: Education and prevention. Dealing with shame, pain, trauma and greed.