by Barrett McBride

The opium poppy is one of the most controversial and influential plants of all time. This unassuming garden flower’s potent alkaloids have the power to erase pain, cause ecstasy or inflict a dark addiction. One of the most important plants economically and culturally throughout the ages, the poppy has cured the pain of cancer, war, and plague as well as been the source of suffering, war and death. Although synthetic pain medications exist and new drugs are on the horizon, the alkaloids of the poppy continue to influence our economy, culture and play a vital role in modern pharmacology. The plant can be found in the Mecklenburg Square Garden. The seeds begin to germinate in early spring with buds and flowers emerging in mid to late summer.

Illustration by Prof. Dr. Otto Wilhelm Thomé Flora von Deutschland, Österreich und der Schweiz 1885, Gera, Germany. Via Wikimedia commons

Introduction

Papaver somniferum, commonly known as the opium poppy, is a hardy annual herb believed to be native to southern Europe or Asia Minor. It is a tall, erect plant with a glaucous colour and can grow up to 100 cm in height. The leaves are simple and serrated with a cabbage-like appearance at its base. The stem is nearly smooth with white bristles below the flower. The flowers have radial symmetry with four petals and are typically white, blue-purple or red with dark bases and range in diameter from 30-100 mm. (Mifsud, 2003; Harris, 2019; Duke, 1983)

Opium pod cut to demonstrate fluid extraction Source: KGM007 [Public domain], via Wikimedia Commons

Once the flower has bloomed and the petals fall off, an ovular blue-green fruit pod (capsule) emerges which consists of the seeds and sap. The sap, a milky-white latex substance known as opium, can contain between 50 and 80 alkaloids, including the potent painkillers- morphine, codeine and thebaine. The numerous seeds are tiny, grey-blue and kidney shaped and will fall from the fruit pod if allowed to dry naturally. (Dittbrenner, Mock, Borner, et al., 2009; Hilton, 2002)’

Distribution and varieties

Today, P. somniferum is globally naturalized with three suggested subspecies and 52 botanical varieties reported until 1981 (Hammer, 1981). It is cultivated widely by both hobby gardeners and farmers (Dittbrenner, Mock, Borner, et al., 2009). Gardeners have grown poppies for ornamental purposes recorded as early as 1750 in the Americas (Mahr, 2017). The purpose of its production as an agricultural crop is for poppy seeds for consumption (humans and cattle), which uses cultivars with a very low content of alkaloids. Others are used for the illicit production of opium and for manufacturing legal pharmaceuticals.

The dual purpose in breeding has resulted in distinctly different alkaloid levels between varieties.For example, gardeners have selectively bred species for appearance and seed production while pharmaceutical companies and illicit opium producers have selected (and even modified) for high alkaloid levels (Mahr, 2017; Meos, Saks & Raal, 2017). To illustrate this point, researchers showed a common garden cultivar, “Marianne”, to contain only 14% morphinan alkaloid content as relative to total alkaloids. Conversely, an ‘elite’ variety, selectively developed by the drug industry contained opium with up to 91% morphinan alkaloid levels. Note, it is difficult to establish visual characteristics that can be consistently correlated with morphinan alkaloid levels. (Meos, Saks & Raal, 2017; Dittbrenner, Mock, Borner, et al., 2009)

Papaver somniferum ( 3 images)
Source: the author

Etymology

The name Papaver somniferum has many understood meanings and tells the story of its early use. The species name, somniferum, is of Latin origin and means ‘sleep’ or ‘sleep-inducing’. However, less certainty exists surrounding the origin of the genus name, Papaver. A common belief is that the root word, papa is from Latin, meaning “of the children” or relatedly the Celtic word “papapap”, a reference to porridge given to infant children. The porridge is said to have contained juice from the petals or leaves of the plant and induced sleep (Verschoor, n.d.; Cameron, 1900). Another reference dates back to the Assyrian name for the poppy, “aratpa-pal”, a word most likely derived from the Sumerian name which means “joy plant”.

History and Traditional Use

The opium poppy is potentially one of the oldest and longest used medicinal plants. It has been grown and processed for its narcotic properties since at least the Neolithic period. The earliest known reference being a set of Sumerian clay tablets (ca. 3000 B.C.E) discovered in modern-day Iraq. The tablets describe the cultivation, harvest and consumption of opium from the poppy plant. Records show opium was also used throughout ancient Egypt and in some religious ceremonies. One story describes that the god Isis used it to cure the headache of Ra. (Schiff, 2002; Wink, 1998)

Mentions of opium in Greek and Roman literature are prolific. Homer, Hippocrates and Pliny all celebrate opium as an intoxicant, sedative, painkiller and even poison when given with hemlock. The Greek-turned-Roman physician, botanist, and pharmacologist Dioscorides, author of the iconic pharmacopoeia De Materia Medica, described the benefits and risks of its use around 50 C.E. (Schiff, 2002; Wink, 1998).

As humans spread throughout the earth, so did opium. By the 8th century Arab merchants had brought opium to both China and India. In China, opium was initially taken as medicine for dysentery by the upper classes. However, by the 17th century nearly 25% of the population smoked opium as an intoxicant. Despite being banned by the Chinese emperor, the British government along with American smugglers persisted by pushing the product through routes in India. This led to a series of events that culminated in the mid-19th century Opium Wars. The conflict, began by the British fully for economic gain, resulted in British victory and the opium trade being restored in China by force (Schiff, 2002; Brownstein, 1993; Ratsch, 2005). The historical consequences of the opium war have impacted on Chinese – British relations for over a century.

Modern Use

At that time, opium and its alkaloids made a widespread comeback in Europe in a series of formulated medicines. The first of which was Laudanum, a commercially sold tincture of opium. English physician Thomas Sydenham initially introduced it as an over-the-counter remedy for the plague. Later it became a general household tonic for pain and cough and subsequently as an inebriant to deal with the harsh realities of life in the 19th century.

Next was morphine, isolated in 1804 by the German chemist, Sertürner, and named after the Greek god of dreams, Morpheus. Pharmaceutical company Merck popularized morphine in 1827 as a painkiller but later it was used for a broader range of therapy including as premedication with anaesthesia. Unfortunately, these products fell to the same pattern of abuse as opium had overtime. Finally, in the late 19th century, Heroin was debuted by the pharmaceutical company Bayer as a “non-addictive morphine substitute” in what was a failed attempt to introduce a compound with less potential for abuse. (Schiff, 2002; Brownstein, 1993)

Bayer heroin bottle, originally containing 5 grams of Heroin substance. Source: Mpv_51 [Public domain]

Active constituents of opium alkaloids – Phytochemistry

Alkaloids are secondary-metabolites found in virtually all parts of a plant including the leaves, stems, fruits and seeds. Structurally they are defined as a nitrogen-containing ringed molecule. They exist, not as part of a plant’s primary life-cycle, but as mechanisms of self-defence and attraction.

The opium poppy, specifically the sap of the plant, contains numerous alkaloids of the benzylisoquinoline class, many of which have a narcotic effects when ingested by humans. The most important with respect to therapeutic effect are morphine, codeine, thebaine, papaverine and noscapine.

Although alkaloid levels vary by variety and plant, the most predominant alkaloid is morphine. Morphine is a potent naturally-occurring analgesic and considered the prototype opiate- the standard for which the capacity of other molecules to exhibit pain relief is measured. It has been used for thousands of years yet still remains one of the best performing drugs in its class (Facchini, Hagel, Liscombe, et al., 2007; Frick, Kramell, Schmidt, et al., 2005; Dittbrenner, Mock, Borner, et al., 2009).

Codeine and noscapine are also pharmaceutically important but exhibit less analgesic effects and are often used as an antitussive. Papervine is used as a smooth muscle relaxant for ischemic conditions and in some surgeries. Thebaine is important as the basis for production of semi-synthetic painkillers such as oxycodone and buprenorphine (Dittbrenner, Mock, Borner, et al., 2009).

How does it work? – Pharmacology

Opium alkaloids work by directly acting on the central nervous system (CNS) to block pain signals traveling to the brain. The structural chemistry of the molecules make it possible to bind directly to opioid receptors located within nerve cells throughout the inner spine and brain. These receptors exist as part of an endogenous system of messenger peptides and naturally occurring receptors collectively referred to as endorphins (endogenous + morphine) (Schiff, 2002).

Although most people can self-attest to the efficacy of opioids, studies in the early part of the 20th century began to describe the existence of the opioid receptor system. In the 1970s, using a series of ligand binding assays, researchers showed that opioid compounds did in fact bind with receptors. Three separate studies in 1973 showed that selectively labelled opioids could displace radiolabeled ligands and established three classes of receptors: mu, delta, and kappa. (Kieffer & Evans, 2009; Snyder & Pasternak, 2003)

In the 1990s advances in molecular biology and DNA science enabled researchers to clone the first opioid receptors. This was seen as a vital step in discovering the full range and complexity of the opioid receptor system. Understanding the way opioid receptors function selectively has served as the basis for application in pharmacology and drug development. Currently, new classes of drugs are being developed that can selectively target opioid receptors with the goal of developing less addictive drugs that can effectively treat specific types of pain or even emotional dysfunction and stress. (Kieffer & Evans, 2009; Snyder & Pasternak, 2003)

Safety and contemporary medicinal preparations

Modern drug formulations of the poppy’s alkaloids mostly used pure morphine and codeine as well as semisynthetic derivatives hydrocodone, oxycodone, oxymorphone and full synthetic analogues fentanyl and methadone (Schiff, 2002). Despite the fact that they are not available over-the-counter (with the exception of low dose codeine) many of the above drugs listed above (along with heroin) have been the source of modern epidemics in opioid addiction.

Their highly effective action at the opioid receptor sites make them very effective at generating pleasurable effects and thus a high potential for addiction. Those suffering from opioid addiction can experience physical withdrawal symptoms if use is halted. Increasing tolerance is also a major concern since opioids can cause respiratory depression and even death if taken improperly. Unfortunately many people have become addicted after being treated for chronic pain. (W H O, 2018)

Conclusion

The opium poppy is a powerful plant with a long history of use. Its alkaloids, in various forms, have been used as painkillers, cough suppressants and for the treatment of diarrhoea for thousands of years. The botanical drugs and medicines derived from this species have provided countless millions of patients comfort from pain and even saved lives in its role in advancing the widespread use of anaesthesia in surgery. Today many synthetic and semi-synthetic pain relieving drugs have been developed that are based on or still manufactured from parts of the plant. Whether synthetic or naturally derived the opioid alkaloids are extremely effective yet strongly addicting. History has proven that this plant can truly be a gift or a curse.

The Author

Barrett McBride MSc (2019-20) Medicinal Natural Products and Phytochemistry at UCL School of Pharmacy, Research Cluster Drug Discovery And Therapeutic Target Identification. Barrett is interested in researching psychedelic plant compounds for mental health care and their potential as a previously overlooked source for drug discovery. His MSc project (2019) investigates Anadenanthera spp., the active ingredient of an ancient entheogenic snuff called Yopo.

Disclaimer

In this essay we do not advise or recommend herbs for medicinal or health use. This information is intended for educational purposes only and should not be considered as a recommendation or endorsement of any particular medical or health treatment. The use of any such product should be based on the appropriate advice of a healthcare professional or based on the information available in the patient information leaflets.