Peter R. Martin: Historical Dictionary of Addiction

Opium

According to the latest electronic version of the Oxford English Dictionary (OED), the noun opium originated from the Hellenistic Greek ὄπιον (poppy juice, opium), which in turn, was from the ancient Greek ὀπός (vegetable juice) in combination with the diminutive suffix -ιον.   Ancient Greek writings from the 9^th century B.C. mention what might well be opium in Homer’s Odyssey (Brownstein 1993): “Presently she [Helen] cast a drug into the wine of which they drank to lull all pain and anger and bring forgetfulness of every sorrow.” 

The first documented use of the word was a description by Caius Plinius Secundus (AD 23/24 –79), or Pliny the Elder, the Roman> author, naturalist and natural philosopher, in his Naturalis Historia (Plinius Secundus 1866).  Subsequently the noun opium has related forms in French (opium in 13^th century in Old French; opion in 15^th century in Middle French), Italian (oppio alsoopio in 14^th century) and Spanish (opio, 1555).  The primary definition in OED is: “A reddish-brown strongly scented addictive drug prepared from the thickened dried latex of the unripe capsules of the opium poppy, Papaver somniferum, used illicitly as a narcotic, and occasionally medicinally as a sedative and analgesic.”

As the opium poppy extracts began to be formulated into medicinal preparations, a related term, the noun/adjective opiate began to be used, originally defined as: “any medicinal preparation containing opium, used chiefly to induce sleep or relieve pain.”  This definition was later modified: “specifically any drug derived from opium, especially morphine and codeine; any of a group of narcotic drugs structurally related to morphine or having physiological effects similar to those of morphine.”  Finally, the noun/adjective opioid came into use as pharmacognosy progressed and allowed the synthesis of molecules with similar actions to those extracted from the poppy, defined as: “any synthetic narcotic drug derived from or having properties similar to those of morphine.” Eventually, the terms opioid and opiate came to be used almost interchangeably. 

The first use of the word opium in the English language according to OED was in about 1398 by the Cornish scholar John Trevisian who translated the Bartholomaeus Anglicus (Bartholomew the Englishman) compilation of the encyclopedia De proprietatibus rerum (“On the properties of things”), the most widely circulated medieval encyclopedia (Bartholomaeus 2010): “Popy hatte papauer…Ther of comeþ Ius þat phisicians clepeþ opium oþer opion.” The first use in English of the term opiate was in translation of Chirugia Magna (de Chauliac 1659) of the French physician and surgeon Guy de Chauliac (c. 1300–1368): “Solaced or conforted with croco or mirra storacus, as castorio, as in philoneo & in opiatez [L. filonio et opiatis] & suppositoriez.”  The term opioid was introduced in the 1950s (Gross and Schiffrin 1955): “Acheson has suggested that the morphinans and other synthetic morphine substitutes should be called opioids.”

The earliest quotes suggested the significant role of extracts from the opium poppy in the physician’s armamentarium.  A mention of the uses of opium and opiates for analgesia in surgery is found in the translation of the book Noble Experyence Vertuous Handy Warke of Surgeri (Brunschwig 1539) written by the German surgeon, alchemist and botanist Hieronymus von Brunschwig (c.1450–c.1512): “Whan the payne is grete, then it is nedefull to put therto a lytell Opium.”).  Also, medical uses for various complaints are noted in the first illustrated herbal produced in English Grete Herball (Treveris 1529): “Agaynst payne of the heed called mygreyne or cephale gyve some hote opiate.”). 

Laudatory quotations from eminent physicians have continued through history, including one widely attributed to Sir Thomas Sydenham (1624–1689) who has been referred to as the English Hippocrates: “Among the remedies which it has pleased almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium.”  Sir William Osler (1849–1919), the esteemed Canadian physician of the Victorian era, analogously proclaimed that opium was, “God's own medicine.”

While the role of opium in medicine was being explored, it soon became apparent that problems were associated with repeated use of poppy extracts and not all about opiates was positive, especially recognition of potential toxicity and addiction.  For example, the writer and traveler George Sandys alluded to out-of-control use of opium (1615): “The Turkes are also incredible takers of Opium”;  the English satirist Edward Ward (1699) referred to a potential for loss of temper and possibility of violence related to taking opium: “Offer violence to your most pretious Lives, by taking…Opium”; and the disturbing consequences of discontinuing chronic opioid use were commented upon by the author, politician and arts patron Horace Walpole (1846):  “Lady Stafford used to say to her sister, ‘Well, child, I have come without my wit to-day;’ that is, she had not taken her opium.” 

The physician Robert Godfrey wrote in his treatise Various Injuries and abuses in chymical and galenical Physick committed by Physicians and Apothecaries (1674): “Instances… of such who with Opiates slept to Death.”  This quotation presaged by three centuries the current notion that physician prescribing was the basis for overdose deaths in the “opioid epidemic” of our day (Baumblatt, Wiedeman, Dunn et al. 2014).  Horatio Curtis Wood, the American physician, succinctly wrote (1874): “Death occurs from opium, in the great majority of cases, by failure of the respiration.” Wood’s observation resonates with present-day reports of declining life expectancy fueled by opioid overdose deaths (Hedegaard, Miniño and Warner 2018); such an unexpected decline has not been documented in the U.S. in the past century since a four-year period which simultaneously included World War I and a flu pandemic.

Opium has been used by mankind for thousands of years (Rudgley 1999).  Its use in prehistoric times preceded even that of alcohol with which it was subsequently combined, predominantly to relieve pain (see above) as well as to enhance religious rituals and spiritual enlightenment by altered sensory experiences. The opioid poppy has been domesticated by farmers in the northeastern part of the Mediterranean since 6000 B.C.  Cultivation of the poppy spread westward during the Neolithic period with records of the seed found in Switzerland, Germany and then extending northward to the British Isles and Poland.  Sumerians, in what today is Iraq, started using opium extracts derived from the seed capsules of the poppy at the end of the 3^rd century B.C.  Arab traders brought opium to India and China between the 10^th and 13^th centuries and subsequently opium made its way from Asia Minor to all parts of Europe. 

Friedrich Sertürner, a German pharmacist, is credited with isolating the active ingredient from opium extracts at the beginning of the 19^th century (Serturner 1806).  Sertürner called the isolate morphium after Morpheus, the Greek god of dreams, as in his experimentation the compound highly effectively induced sleep.  The French chemist J.L. Gay-Lussac is known for popularizing Sertürner’s discovery and eventually changing the name to morphine (Brook, Bennett and Desai 2017).  

Morphine was first listed in the London Pharmacopeia in 1836, but it was the creation of the hypodermic needle (Rynd 1845) which fueled the meteoric rise in use of morphine (Brook, Bennett and Desai 2017). The combination of high potency and the ability to inject the solution directly into the bloodstream to provide rapid pain relief on the battlefield led to morphine supplanting opium except in patent medicines.  Toxicity, especially addiction to opiates, became more apparent as potency rose.  Consequently, a great deal of energy was spent trying to develop a safer, more efficacious, opiate that did not cause addiction.  

Diacetylmorphine, or morphine diacetate, was first synthesized in 1874 by C. R. Alder Wright, an English chemist, but became popular only after it was independently re-synthesized 23 years later by another chemist, Felix Hoffmann, working at Bayer Pharmaceutical.  Bayer’s management reputedly coined the drug’s name, “heroin” based on the German heroisch, which means “heroic, strong” and pronounced the drug to be more potent than morphine and free from abuse liability. This was the first of several such claims for novel opiates throughout the 20^th century that go on to the present (Van Zee 2009).  

Another strategy to contain opiate addiction has been legislation to diminish supply, e.g., the International Opium Convention signed in 1912 by the United States and many other countries.  The Harrison Narcotics Tax Act became United States federal law on December 17, 1914, for regulation and taxation of the production, importation, and distribution of opiates and coca products; this law is considered an important first step in the eventual criminalization of opioid users (Anonymous 1915).

 The British organic chemist Sir Robert Robinson discovered the molecular structure of morphine (Gulland and Robinson 1923) for which he was awarded the Nobel Prize in Chemistry in 1947 (Bentley 1987).  In 1939, meperidine, the first drug with a structure altogether different from that of morphine but with very similar pharmacological properties was discovered by serendipity.  Meperidine has found use predominantly as an analgesic.  In 1946, methadone, another structurally unrelated compound with similar pharmacological profile to morphine was synthesized.  Methadone is widely used in the treatment of opioid use disorder due to its pharmacokinetic characteristic of a very slow elimination from the body and reduction of both craving (“narcotic hunger”) and the withdrawal syndrome from opioids with higher abuse liability like morphine or heroin (Dole and Nyswander 1965).  Both of these compounds are considered opioids, a point succinctly made by Martin (1967): “We have adopted the term opioid, which was proposed by Professor George H. Acheson, to designate those analgesics whose pattern of pharmacological and agonistic effects is similar to that of morphine and… have called this pattern of effects the opioid syndrome.” 

The final chapter in understanding the compelling history of the opium poppy and man, beyond opiates derived from the opium poppy, those chemically modified to alter their effects and various opioids synthesized de novo in the pharmaceutical laboratory, is the discovery of the site of action of the opioid molecule within the central nervous system at stereospecific binding sites (Pert and Snyder 1973) and the discovery that these physiologically active receptors bind endogenously produced molecules (Goldstein, Lowney and Pal 1971; Hughes, Smith, Kosterlitz et al. 1975).  This work would not have ultimately been possible without the synthesis by Weijlard and Erikson (1942) of nalorphine (N-allylnormorphine), the first opiate antagonist (Unna 1943), which could reverse many actions of opioids, including the respiratory depression produced by morphine or methadone (Fraser, Wikler, Eisenman and Isbell 1952).  Interestingly nalorphine had analgesic properties but also caused anxiety and dysphoria because it was a mixed agonist-antagonist. Nevertheless, nalorphine led to the first discovered pure antagonist devoid of agonistic activity and that was a competitive antagonist at several opioid receptors (Martin 1967).

It should not escape the reader, that the word opium has extended meanings beyond physiology and medicine.  These definitions of the word have significant social and historical implications as defined in OED: “Something which soothes or dulls the senses; a stupefying agent; or something regarded as inducing a false sense of contentment amongst the general populace, especially whilst diverting attention from more important matters or pursuits (originally and especially with reference to religion).”  This meaning appeared in English quickly after the original (e.g., Bishop Thomas Morton [1608]): “Stupified with that Opium of implicit faith and blinde deuotion.”) and plays a special role in 20^th century political philosophy (e.g., H.J. Stenning’s translation of Karl Marx (1926): “Religion is the moan of the oppressed creature, the sentiment of a heartless world, as it is the spirit of spiritless conditions. It is the opium of the people.”).

Finally, the tremendous role in medical practice, the economy and the geopolitics of opium per se and subsequently, synthetic opioids should not be forgotten.  First, there is a strong belief that the current opioid epidemic in the United States (and possibly globally) has been substantially influenced by the opioid prescribing of physicians manipulated by sophisticated marketing by the pharmaceutical industry with the tacit acquiescence of regulating government agencies (Keefe 2021).  Additionally, there is little doubt that the western world literally destroyed China’s sovereignty, society and its economy in the mid-19^th century via the opium trade (Bradley 2015).  As William Atherton DuPuy wrote (1916): “The smuggling of opium and of Chinamen was known to go hand in hand.”  Prior to the Opioid Wars China had ranked first in the world for many centuries in gross domestic product (GDP) before it tumbled precipitously during the 20^th century (Maddison 2013).  China now seems to be returning the favor as the United States is now struggling with its own Opioid Crisis fueled in part by synthetic opioids manufactured in China and distributed illicitly (Wee and Hernández 2017).

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December 9, 2021