In an evolutionary blink of the eye, the Agricultural Revolution changed the course of world history. It not only catapulted the homo sapien population, but also propelled a few plants into becoming the most successful species in the history of the earth. Wheat, maize, rice, and potatoes went from being wild, uncultivated crops to accounting for sixty percent of the world’s calorie intake. The ten-thousand year relationship between homo sapiens and these crops has essentially transformed into an obligate symbiosis, as each is dependent on the other for its survival. Whereas the above-mentioned plants multipied due to their energy content, Papaver somniferum (opium poppy) tapped into its psychoactive properties to catalyze its spread from Europe into Asia and now throughout the world. Its use dates back to the earliest agricultural period 7500 years ago when societies cultivated it for food, oil, medicine, and shamanic journeying. To ensure its continued cultivation and survival, P. somniferum, adapted itself to serve humankind’s strongest drive – the urge to seek pleasure.
The Sumerians referred to poppies as hul gil, “joy plant” and documented the process of gathering opium in tablets.The seed of the poppy by itself is a non-psychoactive food. However, when the seed capsule is scratched, a milky latex-like material emerges and as it hardens, it turns a dark brown. This material is raw opium. Opium in its various forms has been in the physician’s arsenal since at least 1600 B.C. An Egyptian medical treatise from that period recommended opium for a range of conditions ranging from a colicky child to snakebites. By 6th century BC, poppies were grown in Persia and opium was known as theriac. To the Greco-Romans, the poppy was known as the “destroyer of grief.” Hippocrates and Aristotle both discussed the hypnotic and medicinal properties of opium. The Roman emperor Marcus Aurelius consumed regular doses of opium prepared by the preeminent Roman physician of the time – Galen. However, as the Roman Empire collapsed and the trade routes collapsed, Europe descended into the Dark Ages and the poppy was soon forgotten in the West.
In contrast, the Arab empire took the helm from the Eastern Roman Empire and expanded into Northern Africa and Asia. As the Arabs controlled and secured the old Asian and African trade routes, Baghdad became the capital of the scientific and intellectual world. Silk, spices, and technologies such as paper making and the Indian numbers system were imported to the Mediterranean and poppies introduced to the East. As with sugar, wherever the Arabs went, so too did the poppy plant. Poppies became a major crop in South Asia and Indian opium became a major product in the proceeding centuries. The writings of classical physicians such as Galen and Hippocrates were translated into Arabic and used as starting point for experimentation and the development of novel therapeutics. Physicians in the Islamic world prescribed opium to aid in several medical procedures as sedatives and anesthetics. The distinguished Persian polymath, Avicenna, wrote an essay on opium, calling it the “most powerful of narcotics.” Ironically, as an avid user, Avicenna is rumored to have died of opium overdose.
Thereafter, the crusades (re)introduced the Europeans to Islamic delicacies like sugar, saffron, jasmine, and coffee. It also reintroduced them to Greek and Roman polymaths and it reinvigorated medieval medicine by adding drugs such as camphor, aloes, and laudanum (tincture of opium). Paracelsus – the ‘father’ of modern chemotherapy – effectively marketed laudanum as a panacea and the drug inspired generations of entrepreneurs to offer their own formulations. Within a century, opium was used both as medicine and food in Europe. Pharmacies sold laudanum formulations that claimed to cure melancholy, increase sexual vigor, and alleviate pain. For most of history, opium was not smoked but rather the black sticky resin was dissolved into wine or tea and imbibed. The ancient Greeks drank a poppy head tea called mekonion. However, the introduction of smoking intoxicants from the New World led to a booming market for opium, as smoking facilitated a quicker onset of action and bypassed fist pass liver detoxification. With increased supply and more effective methods of ingestion, the potential for abuse only increased.
The next step in the history of opium occurred in the early 19th century when the most powerful alkaloid in opium was discovered and named by a German pharmacist. Morpheus(ine) – the Greek god of dreams – is not only more potent but also more addictive than raw opium. However, since morphine was more expensive than opium, it remained markedly less popular. Subsequently, the invention of the hypodermic syringe enabled subcutaneous and standardized administration of morphine. The syringe arrived just in time to inject morphine into soldiers of the brutal wars of the mid and late 19th century. Thereafter, morphine was readily available and used throughout Europe and the United States. Other less potent alkaloids such as codeine and noscapine were soon isolated. Codeine is currently the most widely used opiate in the world. All of these isolates caused addiction and tolerance and chemists began searching for a non-addictive alternative to morphine.
In pursuit of that goal, chemists progressed from isolating active alkaloids to creating entirely novel substances. The breakthrough occurred when Bayer pharmaceuticals synthesized diacetylmorphine in 1897. Experimental reports claimed that the drug made its users feel “heroisch” and Bayer introduced its newest wonder drug, heroin. Heroin was presented as a children’s cough suppressant and was also marketed as a cure for morphine addiction. It was available in many forms including as cough lozenges, tablets, and an elixir. The American Medical Association approved heroin for medical use in 1906, however, it was abundantly clear that heroin did not curb morphine addiction, but was also two times as powerful as morphine. The acetyl groups in heroin provide heroin with an improved ability to penetrate the blood-brain barrier. It produces an intense rush of euphoria and a physical sensation that has been described as having an orgasm throughout your body. After the synthesis of heroin, it was only a matter of time before more powerful synthetic and semi-synthetic opioids such as hydromorphone, oxymorphone, hydrocodone, naloxone, and fentanyl entered the market. The analgesic potency of fentanyl is 470 times that of morphine.
Humans have enjoyed the pain relief and been addicted to the pleasures of the opium poppy at least since the Agricultural Revolution and probably even beforehand. The plant ensured its survival and propagation by tapping into the human brain’s ‘wanting and liking’ pathways. However, like most chronic diseases, the epidemic of opiate addiction is the direct result of uninhibited and even incentivized consumption on an industrialized scale. In my next post, I will attempt to explore the interplay of drug policy, human biology, and pharmaceutical impetus that has caused overdose related death of 300,000 Americans in the last 20 years.