Something with Poison in it …. Poppies.

Source: Image: By NEUROtiker (Own work) [Public domain], via Wikimedia Commons

“Something with poison in it … attractive to the eye and soothing to the smell, poppies, poppies …. Now they’ll sleep.” (Wicked Witch of the West, “The Wizzard of Oz”, 1939)

When the Wicked Witch of the West was trying to stop Dorothy from getting to the Emerald City, she used poppies. Dorothy, Toto, and the Cowardly Lion were all put to sleep and the Tin Man froze up due to tear-induced rusting. Only the Straw Man was left standing and it seemed that all might be lost. The witch’s plan failed, however, thwarted by Glenda. I, and I am sure many others, still remember this scene vividly from childhood and it has clearly had an impact in cinematic history. The Wizard of Oz is one of the most popular and beloved movies of all time. The band Nirvana even used imagery reminiscent of Oz’s poppy fields in their controversial 1993 music video “Heart Shaped Box”.

At the time this celebrated movie was released, what would become the global Drug War was already 25 years old. It had started with the passage of the Harrison Narcotics Act in 1914. This act targeted the use of cocaine and heroin, which were freely available in patent medicines and were used by women to control menstrual pain, by old soldiers to alleviate pain from wounds obtained in the Civil War, and in popular products like Coca Cola. Of course, most of the enforcement of this new drug law was to fall on minority groups, like African Americans who were said by some to take cocaine and commit terrible crimes and Chinese workers who were said to spend hours lying about in opium dens instead of doing their jobs. A powerful force behind the criminalization of psychoactive drugs was Harry Anslinger, who was the first commissioner of the Federal Bureau of Narcotics. He hounded Blues singer Billy Holiday until her death because of her use of heroin, while at the same time making sure that Judy Garland (Dorothy) was able to deal with her heroin addiction without legal difficulty (Hari, 2015). It seems ironic that after he retired he began taking daily doses of morphine to treat the pain of angina, something he had tirelessly worked to keep others from being able to do (Hari, 2015).

For thousands of years, the poppy has given relief to those suffering the deepest pains experienced by humans. And for nearly as long there have been those who found its allure so great that they gave up nearly everything else in life to use it. In HBO’s fictional Game of Thrones, “milk of the poppy” is frequently mentioned. This reflects the reality of the use of opium during medieval times. When little else could be done, the “milk of the poppy” (opium) could help ease the pain of wounds and injuries and help bring restful sleep.

Morphine (chemical structure shown above) was found to be the active ingredient in opium, which is the latex of the opium poppy seedpod. It was named for the Greek god Morpheus, the god of dreams. The effects of this powerful pain killer on the world of dreams was clear, as it tended to induce a dreamy sleep. Morphine relaxes the body and eases the suffering of physical injury, while it slows the breath and digestive system. It can help a person slip into a dreamy sleep, or, if enough is taken or mixed with other drugs, such as alcohol, gently into death. Many terminal patients over the years have undoubtedly been helped in their passage into death by the mental and physical effects of this remarkable drug.

After morphine was understood chemically, it was only a matter of time until more powerful drugs would be patterned on it. Heroin was developed to give greater pain relief and is about twice as potent as morphine. More recent drugs are much more powerful. Fentanyl is about one hundred times more powerful than morphine, and the even more powerful drug W-18 may have recently appeared in some street drug markets, although there is controversy about this.

Morphine-like drugs (opiods) bind to the mu-, delta-, and kappa-opiod receptors and block pain signals (Stahl, 2013). They also induce euphoria at, and above, doses needed to relieve pain (Stahl, 2013). Opioids have effects on the respiratory centers of the brain. Codeine cough syrups can help quiet a serious cough and help bring on sleep. They also tend to slow gut motility and can help control diarrhea. Some of us may remember being given paregoric, tincture of opium, as children, for this purpose or to help with tooth or other troubling pain and to help bring sleep.

The benefits of opioids, when taken to an extreme, also can become the greatest problems. The intense euphoria that they can induce is highly reinforcing and is the basis of the development of addiction. Their ability to control diarrhea can also lead to severe constipation. Given the current heavy use of these medications for pain management, there is now medicine specifically designated to help with the severe constipation that can occur with chronic use of these drugs. You may remember the controversial Super Bowl add for this product at Super Bowl 50.

With regard to sleep, the opiates do have some uses. They can be prescribed for the control of severe restless legs symptoms in patients without a history of addiction (Montplaisir, Allen, Walters, & Ferini-Strambi, 2011). They can be used to induce sleep, but this would not typically be an appropriate use for these drugs (Epstein, 2007) except as an additional benefit perhaps when a person is dealing with severe pain as when recovering from surgery. Caution is required because the side effects of depressed breathing, lowered blood pressure, dizziness, next day sedation, constipation, nausea, vomiting, and risk of addiction, make them too risky to use when other, less problematic, medications are available (Epstein, 2007). Their action at the mu- and delta-receptors affects the respiratory centers of the brain and can result in respiratory depression, which can be, at higher doses, severe enough to be life threatening (Schweitzer, 2011).

These powerful drugs are therefore rarely used in sleep medicine. But they have become incredibly popular, and have been frequently prescribed not only for cancer pain but also for the treatment of chronic, non-cancer-related pain (Van Ryswyk, 2016). Because of the way opioids affect the respiratory centers of the brain, sensitivity to the build up of carbon dioxide in the blood is changed and this can lead to prolonged breathing pauses in sleep that are known as central apneas (Schweitzer, 2011). Indeed, it is now known that a majority of patients being chronically treated with opioid medications have sleep disordered breathing (Van Ryswyk, 2016). Just as with the above-mentioned opioid-induced constipation, there is also continuing research on the best method of treating opioid induced central sleep apnea (Van Ryswyk, 2016). A method of pressurizing the upper air way and controlling non-obstructive (central) breathing pauses that shows considerable promise is known as adaptive servo-ventilation (ASV) (Van Ryswyk, 2016).

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Therapies such as ASV may help patients who must be on long-term opioid therapy sleep better and more safely. The story of how these drugs have gone, over the last 20 years or so, from being outlawed and dangerous substances associated with the American underclass to being the outlawed and dangerous substances of the American working class is in itself a fascinating story (Quinones, 2015).

The story is told by Quinones (2015) and I will try to briefly summarize what is an extremely complex and still not fully understood history that I watched develop over the decades. I was involved professionally in the management of chronic pain during the 1980s, 1990s, and 2000s, and as a result, I have been concerned about the rapid growth of the use of opioids for chronic, non-cancer pain. I now see patients in my sleep practice that are dealing with the effects of opioid-induced sleep disordered breathing. The story has numerous subplots but began with the slow hollowing out of the working and middle classes as the economic policies adopted in the last 35 years pushed for maximum profit for companies and minimum pay for workers. These policies pushed companies to move work to other countries with cheaper labor. At the same time automation greatly reduced the need for labor. There were fewer good paying factory jobs and whole communities have been left behind. Meanwhile a revolution in pain management was occurring. One aspect of this was to recognize the importance of identifying and treating pain. While this was a generally positive development, some in the pharmaceutical industry exploited it by pushing for greater prescription of opioid medication.

These trends came together when people found themselves in poor paying, demanding jobs with little prospect of finding work following a lay-off or other type of job loss. Many people, who may have had to tolerate a pain problem, now saw that getting onto disability might be the only way to survive. Getting diagnosed with and put on disability for illnesses related to chronic pain conditions opened these patients to treatment with a new, high-potency medication, OxyContin. As the years went on and the public, regulatory bodies, and physicians became more concerned about problems of addiction and a growing number of fatalities, many patients were rapidly weaned off or even simply cut off from the medications on which they had become dependent. Entrepreneurial families in certain areas of Mexico developed new and highly effective marketing and distribution systems for black tar heroin. When patients run out of money or are cut off by their doctors, many will find a connection for a cheaper and more powerful black market fix.

As we say goodbye to 2016, a year that many have found to be especially disturbing and dispiriting, the opioid epidemic continues to claim lives and remains a challenge to all health providers. According to the Department of Health and Human Services, 78 people die every day from overdoses due to legal and illegal opioids. Godlee (2016), in an editorial for the BMJ (British Medical journal), declared that the effort to control drug use with laws has failed, and health care providers should support approaches that emphasize treatment over punishment. In that spirit I am hoping for a brighter 2017, with successful renewed efforts to improve sleep and provide better care for patients.

Epstein, L. J. (2007). The Harvard Medical School Guide to A Good Night’s Sleep. New York: McGraw Hill.

Godlee, F. (2016). The war on drugs has failed: doctors should lead calls for drug policy reform. BMJ, 355:i6067 doi: 10.1136/bmj.i6067.

Hari, J. (2015). Chasing the Scream: The First and Last Days of the War on Drugs. New York: Bloomsbury.

Montplaisir, J. Allen, R.P., Walters, A., Ferini-Strambi, L., (2011). Restless legs syndrome and periodic limb movements during sleep, in Kryger, M.H., Roth, T., & Dement, W.C. (Eds), (2011). Principles & Practice of Sleep Medicine, 5th Ed. St. Louis: Elsevier Saunders.

Quinones, S. (2015). Dreamland. New York: Bloomsbury Press.

Schweitzer, P.K., (2011). Drugs that disturb sleep & wakefulness, in Kryger, M.H., Roth, T., & Dement, W.C. (Eds), (2011). Principles & Practice of Sleep Medicine, 5th Ed. St. Louis: Elsevier Saunders.

Stahl, S. M., (2013). Stahl’s Essential Psychopharmacology, 4th Ed. Cambridge: Cambridge University Press.

Van Ryswyk, E. (2016). Opioids and sleep-disordered breathing. Chest, 150 (4), p. 934 – 942.

Source: "Yin and Yang" by Klem - This vector image was created with Inkscape by Klem, and then manually edited by Mnmazur.. Licensed under Public Domain via Wikimedia Commons -