The real Theriac - panacea, poisonous drug or quackery?

ETHNOPHARMACOLOGICAL RELEVANCE: Theriac is considered the most popular cure-all multi-ingredient medicine and has been used for more than two millennia. It has also been used as one of the most important anti-epidemic drugs up to the 19th c., treated as an emergency medicine in case of e.g. bubonic plague. AIM OF THE STUDY: Until now, no reliable information regarding the pharmacological effect of the treacle was available, including its possible toxic or narcotic properties. In order to change the state of knowledge in this matter we have selected the Theriac recipe that had been actually used for producing the treacle in 1630, which was confirmed by the official municipal documents of the time. METHODS: The recipe was written in Latin, with the use of pre-Linnean nomenclature and then apothecary common names, which required translation into the modern scientific language in order to get reliable pharmacological conclusions. The information from historical sources has been compiled with the pharmacological data concerning the most potent compounds, which for the first time made it possible to calculate the amounts of active compounds in the doses taken by then patients. RESULTS: Only two species included in Theriac can be harmful in humans: poppy and sea squill, but in both cases the calculated quantity of morphine and cardiac glycosides, respectively, were below toxic level. There are no indications, both from the historical and pharmacological point of view, for Theriac being toxic or narcotic in patients, when used as prescribed. CONCLUSIONS: As for now, the most probable is that the treacle owed its postulated efficacy in the main indications to the placebo effect. Still, the results should be further confirmed by reconstructing the actual Theriac and subjecting it to modern tests and analyses.

Testing Drugs and Trying Cures: Experiment and Medicine in Medieval and Early Modern Europe.

This article examines traditions of testing drugs (as substances) and trying cures (on patients) in medieval and early modern Europe. It argues that the history of drug testing needs to be a more central story to overall histories of scientific experiment. The practice of conducting thoughtful-and sometimes contrived-tests on drugs has a rich and varied tradition dating back to antiquity, which expanded in the Middle Ages and early modern period. Learned physicians paired text-based knowledge (reason) with hands-on testing (experience or experiment) in order to make claims about drugs' properties or effects on humans. Lay practitioners similarly used hands-on testing to gain knowledge of pharmaceutical effects. Although drug testing practices expanded in scale, actors, and sites, therpublished a work extolling the virtues of drugs froe was significant continuity from the Middle Ages to the eighteenth century.

The Live Chicken Treatment for Buboes: Trying a Plague Cure in Medieval and Early Modern Europe.

This article traces a seven-hundred-year history of one puzzling treatment for plague buboes that used the rumps of chickens to draw out the bubo's poisons. It traces the origin of the recipe to Avicenna's Canon and explores how medieval and early modern physicians altered the treatment and explained its workings up to the early eighteenth century. Much of the analysis focuses on the variants of the recipe that German physicians created as they adapted or elaborated on older recipes. This article argues that most variations of the treatment likely resulted from physicians trying ideas on paper, rather than in practice, as they attempted to unlock the mysteries of the plague's underlying poisons. Starting in the sixteenth century, however, evidence suggests that practice began to play an important role in the adaptation and interpretation of the "live chicken" recipes.

On Anecdote and Antidotes: Poison Trials in Sixteenth-Century Europe.

This article describes the use of poison trials, in which an animal or a condemned criminal was poisoned, to test antidotes in sixteenth-century Europe. In contrast to most drug testing in medieval and early modern Europe, which was gathered in the normal course of therapeutic experience, the poison trial was a contrived, deliberate event. I argue that poison trials had an important function in both medical testing and medical writing in the period between 1524-1580. While poison trials dated back to antiquity, they tended to be described in medieval texts as theoretical possibilities rather than empirical tests that had already occurred. In contrast, early modern physicians conducted poison trials and described them as anecdotes in medical texts. Although physicians did not explicitly separate poison trials from evidence gathered in the course of regular therapeutic experience, they did imbue the outcome of poison trials with considerable epistemological weight.

Natural Inhibitors of Snake Venom Metalloendopeptidases: History and Current Challenges.

The research on natural snake venom metalloendopeptidase inhibitors (SVMPIs) began in the 18th century with the pioneering work of Fontana on the resistance that vipers exhibited to their own venom. During the past 40 years, SVMPIs have been isolated mainly from the sera of resistant animals, and characterized to different extents. They are acidic oligomeric glycoproteins that remain biologically active over a wide range of pH and temperature values. Based on primary structure determination, mammalian plasmatic SVMPIs are classified as members of the immunoglobulin (Ig) supergene protein family, while the one isolated from muscle belongs to the ficolin/opsonin P35 family. On the other hand, SVMPIs from snake plasma have been placed in the cystatin superfamily. These natural antitoxins constitute the first line of defense against snake venoms, inhibiting the catalytic activities of snake venom metalloendopeptidases through the establishment of high-affinity, non-covalent interactions. This review presents a historical account of the field of natural resistance, summarizing its main discoveries and current challenges, which are mostly related to the limitations that preclude three-dimensional structural determinations of these inhibitors using "gold-standard" methods; perspectives on how to circumvent such limitations are presented. Potential applications of these SVMPIs in medicine are also highlighted.

[Moyse Charas, a typical master apothecary and physician for his time (1619-1698)].

The life of Moyse Charas has been very stormy, especially after 1680. One can consider three main periods in his carrier : a first one from his birth in Uzès (France), in 1619, to 1680 ; his exile from 1680 to 1689 in various European countries ; and finally, his return to Paris in 1690 until his death in 1698. He decided his return to Paris and confirmed his conversion to Catholicism the 1st of July 1691, being received by Louis XIV and elected as a member of the French Academy of Sciences in 1692. Charas dictated his one's will the 12th of January 1698, a few days before his death. All along his very active life, Charas was noteworthy by two major achievements : his interest and works on viper and, as a consequence, on theriac ; and his book that became a reference for all apothecaries and physicians at the time, the Pharmacopée Royale galénique et chimique (the Galenic and Chemical Royal Pharmacopoeia). The present study examines specifically the influence of Charas' pharmacopoeia to the Universal Pharmacopeia of Lémery, and the conceptual visible differences between the two authors. He decided his return to Paris and confirmed his conversion to Catholicism the 1st of July 1691, being received by Louis XIV and elected as a member of the French Academy of Sciences in 1692. Charas dictated his one's will the 12th of January 1698, a few days before his death. All along his very active life, Charas was noteworthy by two major achievements : his interest and works on viper and, as a consequence, on theriac ; and his book that became a reference for all apothecaries and physicians at the time, the Pharmacopée Royale galénique et chimique (the Galenic and Chemical Royal Pharmacopoeia). The present study examines specifically the influence of Charas' pharmacopoeia to the Universal Pharmacopeia of Lémery, and the conceptual visible differences between the two authors.

Ethnopharmacological approach to the herbal medicines of the "Antidotes" in Nikolaos Myrepsos׳ Dynameron.

ETHNOPHARMACOLOGICAL RELEVANCE: This paper focuses on the plants quoted in the recipes of the first chapter entitled "About the Antidotes" belonging to the first and largest section "Element Alpha" of Nikolaos Myrepsos׳ Dynameron, a medieval medical manuscript. Nikolaos Myrepsos was a Byzantine physician at the court of John III Doukas Vatatzes at Nicaea (13th century). He wrote in Greek a rich collection of 2667 recipes, the richest number known in late Byzantine era, conventionally known as Dynameron and divided into 24 sections, the "Elements". The only existing translation of this work is in Latin, released in 1549 in Basel by Leonhart Fuchs. Since no other translation has ever been made in any language, this work still remains poorly known. MATERIALS AND METHODS: Our primary source material was the codex written in 1339 and kept in the National Library of France (in Paris) under the number grec. 2243. For comparison, all the other codices, which contain the entire manuscript, have also been studied, namely the codices EBE 1478 (National Library of Greece, Athens), grec. 2237 and grec. 2238 (both in Paris), Lavra Ε 192 (Mont Athos, Monastery of Megisti Lavra), Barocci 171 (Oxford) and Revilla 83 (Escorial). RESULTS: The exhaustive study of the "About the Antidotes" led us to the interpretation of 293 plant names among which we recognized 39 medicinal plants listed by the European Medicines Agency, (Herbal Medicines, www.ema.eu); the therapeutic indications of some of them provided by Myrepsos were similar or related to their current ones, as given in their monographs. The plants belong to various families of which the most frequent are: Apiaceae 10.6%; Lamiaceae 9.2%; Asteraceae 8.9%; Fabaceae 6.8% and Rosaceae 5.1%. The most frequently mentioned plants even under several different names are the following: Apium graveolens L., Crocus sativus L., Nardostachys jatamansi (D. Don) DC., Zingiber officinale Roscoe, Rosa centifolia L., Syzygium aromaticum (L.) Merr. & L.M. Perry, Papaver somniferum L., Costus sp., Petroselinum crispum (Mill.) Fuss, Anethum graveolens L., Foeniculum vulgare Mill., Daucus carota L. CONCLUSIONS: This research led us to the conclusion that the content of "About the Antidotes" is a valuable source for the study of recipes based mainly on medicinal plants, most of them inherited from classic ancient Greek and Hellenistic periods.

The bezoar stone: a princely antidote, the Távora Sequeira Pinto Collection-Oporto.

Bezoar stones, once used as universal antidotes and panaceas, but currently regarded as costly and useless medicines of the past, are a major milestone in the history of toxicology. Arabic physicians had been using bezoars in medicine from the 8th century onwards. In the 16th century, the Portuguese controlled bezoar trade from India, and the Portuguese doctors Garcia de Orta, Amatus Lusitanus, and Cristobal Acosta introduced the medicinal use of Oriental bezoars to European medical literature. Some criticism aside, leading European doctors prescribed bezoars mainly as powerful antidotes. Five bezoars that now adorn the Távora Sequeira Pinto Collection in Oporto testify to the allure and glory of bezoars at the height of their golden age, when they equalled the splendour of gems and noble minerals that dominated the Eastern and Western lithotherapy.The end of the 18th century marked the end of ancient panaceas. This article focuses on the therapeutic and apotropaic use of bezoars.