Opioids Part l

By Frank G. Vice, DVM, BS Pharm

Opioids There are several varieties of Papaver, the poppy flower, but only Papaver   somniferum   contains opium, a milky extract collected from its seed pods.  Papaver somniferum is probably the oldest medicinal plant and opium is the first medicinal used in the ancient world. The earliest references related to opium growth and use were found in writings by the Sumerians who lived around 3400 BC. Poppies can be found growing in the hot dry Middle Eastern area of the lower Mesopotamia Valley near the Tigris and Euphrates Rivers, which is the likely site for its early cultivation. As cultures in the region changed, the demand for opium increased for both medicinal and recreational use. The knowledge and technique of cultivated growth and opium harvesting soon expanded along the Silk Road, throughout the Mediterranean and Asia, and finally into China. Early cultures, principally those in northern India, realized the opium poppy is an annual herb. It grows with an erect stem and a single flower requiring rich moist soil and abundant sun to mature its seed pods.  All parts of the plant produce opium, a white latex material, but it is the seed pod that is the focus of most of the opium collection. Early planters realized that opium is produced and is available for collection for just a few days during late May and early June. Collection of opium occurs during the early morning  hours with family members cutting the seed pod capsules and using iron scoops to scrap the white poppy juice as it oozes from the incised capsules. This raw white opium will oxidize to a thick reddish brown material, which is the basic form of the medicinal substance. Raw opium, when harvested fresh, has a mixture of several chemicals known as alkaloids. These naturally occurring chemical compounds are produced by a number of microscopic organisms, as well as various plant varieties. It is the chemical structure of an alkaloid that enables it to exert its pharmaceutical and physio-chemical activity.

The popularity of opium, both as a medicinal and as a recreational drug, continued through the ages influencing all cultures throughout Asia, the Middle East, and Europe. There is strong evidence the Romans used opium throughout the empire as a part of the Greek influence on medicine. Knowledge of medicinal opium was nearly lost as the Roman Empire fell into decline, ultimately having little influence on the world’s opium use for the next 1000 years. However, it was during this Dark Age of Europe that opium use gained strength throughout the early Arabian culture. It became a product of trade between China, India and the Arabian world.

As time progressed, exploration and trade into new lands continued. Arab traders and Portuguese sailors smoked opium and advanced the knowledge of opium’s medicinal and recreational use to the Chinese, who began mixing it with tobacco, to smoke in specialized pipes.   In 1527, Paracelsus, a physician born in Switzerland, began using raw opium mixed with alcohol for a variety of maladies. This preparation was possibly the early form of laudanum.  However, the addictive properties would not be understood until years later.  During the close of the Dark Ages and the dawn of the Renaissance, Europe began to recover from its difficult past. It was during this time that England became a dominant force in colonial expansion. The British East India Company was formed as a private company to share in the Indian spice trade, but ultimately evolved to shipping opium to China in exchange for Chinese tea. British opium shipments created a Chinese demand for more recreational opium. This increasing desire by the Chinese to smoke opium, worried their government until, eventually, they refused all additional shipments. As a part of this refusal, they attempted, but failed, to confiscate and destroy a large shipment of British opium. Finally, in the mid 1800’s, the Chinese government ultimately was powerless in their resistance to control opium smuggling and elected to fight the British in a series of opium wars.

The loss of the first opium war in 1842 and the second opium war in 1860 resulted in a Chinese loss of territories which included Hong Kong Harbor.  It was opium’s increase availability and recreational use which left many Chinese citizens hopelessly addicted.

As opium’s use and influence continued to expand, early European chemists began experimenting, attempting to isolate its active chemical ingredients.  In 1805, while living in Paderborn, Germany, Friedrich Serturner, a young apothecary assistant, chemically, isolated opium’s primary active alkaloid ingredient and named it “Morphium”, later to be called Morphine.  This new pain killer was added to a mixture of flavoring agents and alcohol and sold in grocery stores.  This flavored alcohol based tincture was sold with the patent name “laudanum” and was frequently used on children to stop teething pain, control cough, or simply to sedate a child to stop it from crying. Since the addictive properties of this wonder drug were not understood, many children would experience withdrawal symptoms following repeated use. The medical world slowly understanding the value and implications of morphine as a pure isolated chemical. It was after the development of the hypodermic syringe in 1853 by Dr. Alexander Wood that Morphine made its rapid entrance into medical and recreational use. Using a syringe made it possible to rapidly administer morphine directly into the blood, with nearly instant pain relief. The addictive concerns continued to be misunderstood, since the current thought was morphine would be eliminated from the body faster through injection.

The soldiers in wars around the world began to appreciate the rapid pain relief from morphine injection. Early military physicians had little to offer a severely wounded soldier except pain relief and therefore large doses were given. Following the American Civil War, so many soldiers were addicted to morphine that a new group of addictive symptoms developed called “Soldiers Disease”.  Eventually, late in the 19th century, several forms of opiate addiction were emerging, beginning with oral and inhalant opium addiction, a result of smoking opium, a patent medicine addiction, due to an unregulated patent medicine industry selling products laced with opium or morphine, and the addiction of returning Civil War soldiers.

The ability to inject morphine was critical for pain management but socially destructive, as it destroyed the lives of those who developed an addiction. It is has been suggested that the Americans began their addiction to opiates around the turn of the 19th century, with rapid addiction development and only brief periods of addiction decline. Early medical and social recognition of addiction was considered “a bad habit” or “a health misfortune”, not as a criminal concern.  Addiction was pitied as an unfortunate turn of events. Opium smoking was mostly an ethnic indulgence and did not directly affect larger society groups. Most people thought very little about drug addiction until the newspaper articles suggested and discussed all of the “evil” activity associated with smoking in opium dens. In fact, these reports were mostly false, manufactured to sell newspapers. Other addictive concerns should have focused on Civil War soldiers using injectable morphine, and later heroin. However, by all accounts, it was patent medicines that proved to be the most dangerous addictive influence. This early unregulated industry supplied health care medication to a needy public without offering complete knowledge or sympathy to the potential for addiction. Their use of homemade elixirs laced with alcohol and opium along with flavoring agent was an extremely profitable business that took advantage of an uninformed and naïve public. There was no legal recourse, no defense for harm, and no government oversight to protect the public from addiction or death. Without oversight, these “snake oil salesmen” took advantage of every town, grocery, and pharmacy selling and spreading their contaminated elixirs to trusting families with children.

A patent medicine was simply a homemade tonic created by individuals who wanted to sell products to sick patients, convincing them they would feel better and get well.  Health care and education were so poor during the 19th century that many patent medicine users trusted in the tonics because, for a short time, they did feel better. There were no legitimate medications available, nor was there any depth of medical knowledge, compared to the sophistication of health care in the 21st century. Patent medication grew in popularity and use, in large part, due to the general need for some type of health care. Diseased and addicted Civil War veterans were suffering and self-medication with products that made them feel better was too tempting. These tonics were inexpensive and most were socially acceptable by a public that lacked medical sophistication due to poor education.  Users of patent medication were gullible and trusting due to painted advertising, catchy songs, and testimonials of previous users. Even local physicians used and recommended these products to families. At that time, dispensed medications were not regulated by any agency. This unregulated pharmaceutical use allowed the patent medication industry to flourish. Labeling of ingredients incorporated into these patent mixtures was not required, therefore, the users were completely unaware of the potential danger awaiting them as they used the medication. Finally, following years of patent medicine use, the federal government, during the President Theodore Roosevelt’s administration, recognized the seriousness of the problem. They recognized labeling requirements and oversight regulations were needed for this industry. Therefore, in 1906, passage of The Pure Food and Drug Act occurred. This congressional act initiated the beginning of federal control over all products purchased and used by the public.

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