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Year : 2021  |  Volume : 35  |  Issue : 3  |  Page : 103-116

The Literary Works of Miguel de Cervantes from the Perspective of Psychopharmacology: The Four Aspects of Phármakon

Faculty of Health Sciences, University Camilo José Cela; Hospital 12 de Octubre Research Institute (i+12), Madrid, Spain; Portucalense Institute of Neuropsychology and Cognitive and Behavioural Neurosciences (INPP), Portucalense University, Porto, Portugal

Date of Submission03-Jun-2021
Date of Decision30-Jun-2021
Date of Acceptance01-Jul-2021
Date of Web Publication24-Sep-2021

Correspondence Address:
Francisco Lopez-Munoz
C/ Castillo de Alarcón 49, 28692 Villanueva de la Cañada, Madrid

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/TPSY.TPSY_23_21

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Background: Miguel de Cervantes (1547–1617) was a Spanish writer, who has often been considered as the greatest writer in the Spanish language and one of the world's outstanding novelists. His novel Don Quixote, is a work often cited as both the first modern novel and one of the best works of world literature. The life of Cervantes has been full of fascinations, imaginations, attracting the attention from all walks of people, including psychiatrists. Methods: With career interest in psychopharmacology, the author in this review intends to focus on Cervantes's notions in his works on the use of psychotropic agents. The author also categorized psychotropic agents into four different scenarios of use – therapeutic remedies, toxic and poisonous agents (love philters, poisonous potions), antidotes as well as drugs of abuse (witches' ointments). Results: Cervantes' works were found that Cervantes made references to those preparations in Don Quixote, The Galatea, Journey to Parnassus, The Spanish English Lady, The Lawyer of Glass, The Jealous Old Man from Extremadura, The Dialogue of the Dogs, Pedro de Urdemalas and The Diversion. The main agents cited by Cervantes in the context analyzed included henbane, tobacco, rhubarb, rosemary, vervain, and in a masked way, opium. Cervantes did not identify the ingredients of other preparations with psychotropic properties, although, in the sense of the symptoms described by the author, they could be plants of the Solanaceae family, such as the henbane, nightshade, jimson weed, belladonna, or mandrake. Conclusion: Cervantes' texts, although by no means scientific treatises, give us with a correct description of the uses (and effects) of psychotropic substances in late Renaissance Spain, and explain how a group of drugs could have four archetypal qualities – remedy, poison, antidote, and drug of abuse.

Keywords: antidotes, drugs of abuse, poisons, psychotropic agents

How to cite this article:
Lopez-Munoz F. The Literary Works of Miguel de Cervantes from the Perspective of Psychopharmacology: The Four Aspects of Phármakon. Taiwan J Psychiatry 2021;35:103-16

How to cite this URL:
Lopez-Munoz F. The Literary Works of Miguel de Cervantes from the Perspective of Psychopharmacology: The Four Aspects of Phármakon. Taiwan J Psychiatry [serial online] 2021 [cited 2023 May 29];35:103-16. Available from: http://www.e-tjp.org/text.asp?2021/35/3/103/326573

  Introduction Top

Psychopharmacology is nowadays considered a well-established scientific discipline, with its own distinct character within the framework of pharmacology. But it would be completely wrong to apply the scientific parameters governing this discipline to historical analyses in general and that of late Renaissance European society in particular, with regard to pharmacological aspects specifically, and the concept of mental illness or substance-related disorders.

Etymologically, the Spanish word “fármaco” (pharmaceutical/drug) comes from the Greek phármakon (Φάρμακον), a meaning that appears in The Iliad and is an archetype or exemplary model from which other ideas and concepts are derived, including four interesting concepts – “remedy,” “poison,” “antidote,” and “drug of abuse” [1]. Therefore, in keeping with its original definition, a drug would encompass not only those substances used in the treatment and prevention of diseases but also those that could cause harmful effects when administered accidentally or intentionally and those used to neutralize such effects. Finally, this umbrella would also include all substances consumed socially for the purpose of mood modification and even those consumed at events with a magical or heterodox orientation. Nevertheless, the boundaries between these four qualities of pharmakon are still not fully defined today, meaning that the difference between drugs and poisons lies in the dose administered, individual susceptibility or the differential organic accumulation process. In this respect, we should remember the words of Paracelsus (Theophrastus Phillippus Aureolus Bombastus von Hohenheim) (1493–1541) in his work Defensiones (1537–1538): “Alle Dinge sind ein Gift… Allein die Dosis macht, daß ein Ding kein Gift ist” (“All things are poison... The dosage alone makes it so a thing is not a poison”) [2].

The medical aspects of the Renaissance brought about a real change of mentality in the way of understanding human beings, their behavior, and their ailments. In addition, the introduction of the printing press made it possible for scientific knowledge in general, and medical knowledge in particular, to be widely disseminated. Finally, the discovery of the New World and commercial expansion toward the East made it possible to broaden the therapeutic armamentarium available to European physicians [3]. But during this period, even in its later stages, beliefs and behaviors typical of earlier times survived, framed in the irrationality of magic, witchcraft and the presence of evil, and many substances with toxic properties were also used for extra-therapeutic purposes [1].

All these uses of psychotropic agents and poisons that affect sanity, and the use of toxic products by marginal groups can be seen in the literary works of the most international of Spanish writers, Miguel de Cervantes (1547–1616) [Figure 1], which undoubtedly provide a wonderful reflection of the social fabric, uses and customs of late Renaissance Spain. Indeed, one of the constants in Cervantes' writings is the constant appearance of marginal and marginalized characters, including madmen, in the author's desire to make a sharp and shrewd critique of the society in which he lived. The most obvious evidence of this can be found in the numerous characters portrayed in his Novelas Ejemplares (Exemplary Novels, 1613), possibly Cervantes' most important and best-known work after Don Quixote (El Ingenioso Hidalgo Don Quijote de La Mancha, 1605) [Figure 2]. It features witches and sorceresses throughout, closely related to the heterodox practice of medicine and closely linked, in the Spanish imagination of the time, to individuals of Moorish or Jewish origin [4].
Figure 1: Oil portrait of Miguel de Cervantes, dated 1600 and attributed to Juan de Jáuregui y Aguilar (1583–1641).

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Figure 2: Frontispieces of the princeps editions of Don Quixote (1605), dedicated to the Duke of Béjar, and the Exemplary Novels (1613), both published by the Juan de la Cuesta press, located in Atocha street in Madrid.

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  Life and Work of Miguel de Cervantes Top

Descended from a family of health workers, Cervantes was born on September 29, 1547, in Alcalá de Henares, a university town near Madrid, and spent his childhood in various cities (Pisuerga, Valladolid, Madrid, Cordoba, Cabra, and Seville), following his father's family's job postings. At the age of 21 years, he moved to Rome, possibly fleeing from the law, to enter the service of Cardinal Giulio Acquaviva d'Aragona (1546–1574) as a waiter. It is thought that Cervantes could have fought a duel with court painter Antonio de Sigura (d. 1605), who would later become intendant of the royal buildings. Fate was at work in this case, as Cervantes was sentenced in absentia to a 10-year banishment and the public amputation of his right hand. Whatever the reason, his flight spared the hand that would go on to write some of the most memorable pages in world literature.

While in Italy, Cervantes joined the army of Philip II (1527–1598) between 1569 and 1571, specifically in the Tercios of Naples, whose Captain-General was Álvaro de Bazán (1526–1588), Marquis of Santa Cruz, who later went on to fight the Turks in the Mediterranean. He took part in the unsuccessful relief of Cyprus and later, at the age of 24 years, in the famous battle of Lepanto (1571), where the Holy League completely defeated the Ottoman Navy. Although he was ill with a fever, Cervantes' performance during the battle can be considered truly heroic, defending the position of the skiff of the galley to which he was attached. Cervantes received three arquebus wounds in this battle, two in the chest and one in the left hand, leaving it useless for the rest of his life.

On his return to Spain in 1575, with a reputation for heroism acquired at Lepanto, the galley in which he made the crossing was seized near the Catalan coast by Algerian corsairs and he was taken to Algiers, where he was held captive for more than five years. His period of captivity was characterized by continuous escape plans, with four attempts, all of them unsuccessful. Finally, Trinitarian friars were able to rescue him on October 24, 1580. This period of captivity in Africa made a deep impression on the writer and is a theme of autobiographical inspiration in many of his works.

Cervantes was discharged from the militia in 1584, the year in which he married Catalina de Salazar y Palacios (1565–1626) in the town of Esquivias (Toledo), but his links to the Navy continued from 1587 to 1590, working for the Royal Treasury and other state administrations, as a tax collector and commissioner of supplies of wheat and oil for the Great Armada that Philip II planned to send against England. To this end, he traveled the roads of La Mancha and Andalusia to requisition supplies and was briefly imprisoned due to accusations made by his adversaries and for abuses of his assistants. In 1594, he went back to work as a tax collector for the kingdom of Granada, and when the collections office in Seville went bankrupt, he was once again imprisoned in the Royal Jail in Seville for several months. During this stay there, it is thought that he might have developed the outline of his masterpiece, Don Quixote, and some of the stories in the Exemplary Novels, thanks to his close contact with the Seville underworld.

In 1608, Cervantes settled in Madrid, seat of the Court, and began a feverish period of literary activity, and took an interest in religious life, joining the strict Congregation of the Slaves of the Blessed Sacrament in 1609 and the Third Order of St. Francis in 1613. Miguel de Cervantes died on April 22, 1616, in a situation of poverty and family disagreements, possibly from complications due to diabetes.

Cervantes was a restless man who lived in a time of great uncertainty, and there are many biographical works about him. Examples include Astrana [5], Mayans y Siscar [6], Fitzmaurice-Kelly [7], Canavaggio [8],[9], Rey and Sevilla [10], Eisenberg [11], Alvar [12], Fernández Alvárez [13], Sliwa [14], etc.

It is clear that Miguel de Cervantes Saavedra can be considered one of the great figures in the history of world literature, even though his literary production is not extensive [Table 1]. His literary output was published in a historical period of transition between the Renaissance and the Baroque, a period which is often considered to have begun, in Spain, with the death of Philip II in 1598.

Apart from a few poetic compositions which he wrote throughout his life, Cervantes' first works are two plays published in 1582, El trato de Argel (The Trade of Algiers), inspired by his memories of captivity in Algiers, and Numancia (The Siege of Numantia), as well as the pastoral novel La Galatea (The Galatea, 1585). In early 1605, the first part of his masterpiece, Don Quixote, came off the presses of Juan de la Cuesta in Madrid. It quickly became a huge success, both in Spain and abroad, with many editions in Portuguese, French and English. In 1613, a set of 12 works, written at different times, came out of the same printing house in Madrid. These were to make up the Exemplary Novels, some of them written during the period of his Andalusian commissions and incarceration, such as Rinconete y Cortadillo (Rinconete and Cortadillo) and El celoso extremeño (The Jealous Old Man from Extremadura). This work was even more successful than Don Quixote, with 4 editions in 10 months, and another 23 editions during the 17th century, as well as 8 reprints in France, where it was used to learn Spanish.

The following year saw the publication of the scholarly work Viaje del Parnaso (Journey to Parnassus, 1614) and in 1615 a compilation of plays entitled Ocho comedias y ocho entremeses nuevos (Eight Comedies and Eight New Interludes). That same year, in response to the publication of the “false” Quixote written under the pseudonym Alonso Fernández de Avellaneda, Cervantes published the Segunda Parte del Ingenioso Cavallero Don Quixote de la Mancha (Don Quixote, Part II, 1615). During the last months of his life, Cervantes devoted his efforts to finishing a work he had begun many years earlier, the Byzantine novel Los trabajos de Persiles y Sigismunda (The Trials of Persiles and Sigismunda), which was completed four days before his death and published posthumously in January 1617.

The great international recognition of Cervantes' work is due, to a large extent, to Don Quixote. The cultural significance of this novel is attested to by a survey carried out a few years ago by the Nobel Institute and the Norwegian Book Club. A sample of 100 writers from 54 countries was asked about the best literary work of all time. Don Quixote was the most popular choice, with 50% more votes than the runner-up, In Search of Lost Time (1913), by Marcel Proust (1871–1922) [15].

  Cervantes' Hypothetical Knowledge of Therapy Top

It should be borne in mind that Cervantes, as the son of a surgeon-healer, the brother of a nurse and great-grandson of a medical graduate, had some knowledge of the art of medicine, the knowledge that he may have brought to his literary creations. Similarly, his closest friendships also included doctors. Some authors have even postulated that the author of Don Quixote may have studied some medical subjects specifically [16]. Cervantes also lived during a period that saw great advances in Spanish medicine [17],[18],[19], including authors who worked on the medicine of the mind, such as Oliva Sabuco de Nantes Barrera (1562 - c.1646), Antonio Gómez Pereira (1500–1558), Juan Luís Vives (1492–1540) and Juan Huarte de San Juan (1529–1588), the most internationally renowned Spanish scientific author of his time, whose only work Examen de ingenios para las ciencias (The Examination of Men's Wits, 1575) is thought to have had a direct influence on the conception of Don Quixote [19],[20],[21]. Cervantes may also have obtained first-hand clinical and therapeutic information relating specifically to the mentally ill from his direct contact with patients in the Psychiatric Hospital in Seville [22]. Finally, many well-known medical treatises of the time have been identified in Cervantes' private library [23], among them, the aforementioned The Examination of Men's Wits, and, more importantly for the subject that concerns us, a Salamancan edition of Dioscorides, annotated and illustrated by Andrés Laguna (1494–1560) [Figure 3], possibly a family heirloom.
Figure 3: Portrait of Andrés Laguna (1499–1560) from an engraving for Dioscorides (Acerca de la materia medicinal y de los venenos mortíferos), translated and annotated by this author, corresponding to the 1563 edition, printed in Salamanca by Mathías Gast (ca. 1523–1577), and frontispiece of this edition of Dioscorides.

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The Segovian physician Andrés Laguna, whom we shall discuss later, can be considered a prototype humanist physician of the Renaissance, and although he was the son of a doctor who was a Jewish convert, he achieved fame during his lifetime as one of the most brilliant figures of European culture of the time, becoming the personal physician of Emperor Charles V (1500–1558), Pope Julius III (1487–1555) and King Philip II [24],[25],[26]. Although he wrote more than 30 works on various subjects, including philosophical, historical, political and literary works, and strictly medical ones, Laguna's best known work is the annotated translation of Dioscorides' De Materia Medica (1555).

Cervantes was also fond of mentioning, commenting on and even criticizing many of the books and manuscripts in his private library in his literary works [23], and, in line with this argument, Dioscorides is the only work of a scientific-medical nature that the novelist cites in his entire literary production, specifically in Don Quixote: “For all that, answered Don Quixote, I would rather have just now a quarter of bread, or a loaf and a couple of pilchards' heads, than all the herbs described by Dioscorides, even with Doctor Laguna's notes” (Part I, Chapter XVIII) [27]. Moreover, according to some authors [28], it should be borne in mind that Laguna wrote his comments on Dioscorides in a universal discourse in the Spanish language, so that they could be used and understood not only by medical professionals of the time but also by lay people with therapeutic expertise, as he avoided resorting to the technification of vulgar language [29]. In this regard, we found that Cervantes' descriptions of the effect of certain plants match those given by Laguna to a large extent, as we shall see later. All these data have allowed us to hypothesize that reading the Dioscorides edition annotated by Laguna may have provided Cervantes with a documentary source for his therapeutic and toxicological passages [30],[31].

Whether he read other pharmacological texts, although probable, is certainly more difficult to prove, such as the famous work by Nicolás Monardes (1507–1588), Historia Medicinal de las cosas que se traen de nuestras Indias Occidentales que sirven en Medicina (Medical Study of the Products Imported from our West Indian Possessions, 1565) [Figure 4], despite the fact that Cervantes cites plants and remedies described by this Sevillian doctor in his works that are not included, or only very briefly, in Laguna's work, such as the tobacco plant or bezoar stones [1]. Whatever the case, there is no doubt that Cervantes' medical and therapeutic knowledge was by no means superficial [32],[33],[34],[35].
Figure 4: Portrait of Nicolás Monardes (1493–1588) and cover of the Seville edition of 1574 of his work Historia Medicinal de las Cosas que se Traen de Nuestras Indias Occidentales que sirven en medicina (National Library of Madrid).

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The first quality of phármakon: remedy

The Renaissance understanding of madness differed little from the medieval conceptualization. As such, many manifestations of mental illness continued to be regarded as a sign of diabolical intervention, in part due to the nefarious influences of the religious wars that ravaged Europe at the time [36], although from the 16th century onwards many physicians gradually began to develop a process of de-spiritualizing or de-satanizing mental illness [37]. Cervantes' works clearly show us these dichotomies, revealing the perception of mad or alienated people in Spanish society at the turn of the century [21],[38]. In fact, mad characters are a constant in many of Cervantes' works [Figure 5] (Don Quixote, Cardenio, Anselmo, Basilio, the Lawyer of Glass, the jealous from Extremadura, the madmen of Seville and Cordoba, etc.) [21],[22],[38],[39]. But it should be borne in mind that Cervantes may have used the device of madness as a literary strategy to avoid the crudeness of his vision of a society that he found inaccessible and to engage in a veiled critique of it.
Figure 5: Engraving by Gustave Doré (1832-1883), entitled Don Quixote reading chivalric books, intended to illustrate the Prologue to the French edition of Don Quixote of 1863.

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In therapeutics, the remedies used at this time were few and of an eminently nonspecific nature, such as purgatives and evacuants [3]. When treating the sick, the aim was to counteract the production of materia infirmitatis (matter causing the illness) with various drugs, mainly of herbal origin [40], such as hellebore (Helleborus niger or Veratrum album), a the emetic effect of which was used to divert or eliminate excess bile and acidic humours [41]. In this way, vomiting would allow the recovery of eukrasía, i.e., the correct mixture of humours on which health is based [36]. Other substances of plant origin that were part of the therapeutic arsenal of medicine for mental illnesses were henbane (Hyoscyamus albus and niger), belladonna (Atropa belladona), mandrake (Mandragora officinarum), jimson weed (Datura stramonium), valerian (Valeriana officinalis) and opium (Papaver somniferum). It should also be noted that the entire pharmacotherapeutic arsenal available at this time was increasing with new drugs and remedies from botanical species brought from the Nuevo Mundo, such as extracts from cinchona bark, used as a tonic for patients classified as “asthenic,” and tobacco (Nicotiana tabacum), used as a stimulant and “brain decongestant” [42].

Cervantes was familiar with many of the different apothecary preparations and the pharmacopoeia of the time, based mainly on the application of oils, ointments, balms, preserves, roots, barks, and syrups [35]. Some of these preparations, whether fictional or of real use, are reflected in the works of the Spanish writer. Examples include the famous balm of Fierabras, rhubarb powder (root of Rheum officinale (Chinese rhubarab), and Rumex alpinus (monk's rhubarb)) [43], white ointment and “oleum magistrale” [33]. We have identified 10 plants mentioned in Cervantes' texts for their hypothetical therapeutic, recreational, or health-promoting properties: chicory (Cichorium intybus), oleander (Nerium oleander), henbane, opium, rosemary (Rosmarinus officinalis), rhubarb, tobacco, tamarisk (Tamarix gallica), caper spurge (Euphorbia lathyris) and vervain (Verbena officinalis) [31]. Of these, 6 are mentioned for their psychotropic properties [Table 2] [Figure 6]. However, a detailed medical reading of Cervantes' works shows that he does not usually consider the use of agents with a primary psychopharmacological action, but resorts to the use of different apothecary preparations with secondary or delayed psychopharmacological effects, such as certain balms, purgatives, or emetics.
Figure 6: Botanical illustrations of the works of Laguna and Monardes corresponding to the plants cited in the Cervantes texts in relation to the matter addressed in this work. §Andrés Laguna. Acerca de la materia medicinal y de los venenos mortíferos (Salamanca, 1563). †Nicolás Monardes. Historia medicinal de las cosas que se traen de nuestras Indias Occidentales que Sirven en Medicina (Sevilla, 1580). A, Henbane (Hyoscyamus)§; B, Papaver (Papaver Pithitis)§; C, Rosemary (Rosmarinus Coronarium)§; D, Rhubarb (Oxylaphatum)§; E, Tobacco (Tabacum); F, Vervain (Verbenaca)§.

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In Don Quixote, the therapeutic remedies par excellence are balms, drugs made with aromatic substances and those intended to cure wounds and sores, which, due to the continuous and successful references to their use, include “balm of Fierabras,” a kind of therapeutic panacea for Don Quixote that belongs to the group of magical remedies which abound in the literature of medieval chivalry [44]. Salutary and effective balms, in this case, administered orally with the ability to cure any type of illness, would have been prepared using oil, wine, salt and rosemary, following a common procedure in pharmacy practice at the time, namely the mixing of several simple medicines (three of vegetable origin and one mineral) to obtain a compound, in the style of the famous theriacs [44],[45]. The preparation of the balm [Figure 7] is described by Don Quixote; the four natural ingredients must be put over a fire in a pot and boiled for a long time, and finally, the compound is poured into a tin basin. It is possible that the recipe described by Cervantes was based on real formulations available at the time [44]. In fact, the Portuguese physician Petrus Hispanus (1215–1277), the future Pope John XXI, is credited with writing a book in about 1272 entitled Thesaurus pauperum, which contains a very similar formula, cooking rosemary in olive oil, for the same purpose: to obtain “a very precious and virtuous ointment” [44],[46].
Figure 7: Engraving by Ricardo de los Ríos (1846–1929) on an original drawing by Jules Worms (1832–1924), entitled Don Quixote prepares the Balm of Fierabras, and intended for the French translation of Don Quixote by Cesar Oudin and Francois de Rosset (L'Histoire de Don Quichotte de la Mancha, Paris, Librairie des Bibliophiles, 1884).

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The effects of the balm of Fierabras are also described by Cervantes: initially, it brings on intense vomiting, followed by heavy sweating and fatigue, and then a deep sleep. When he awoke three hours later, the restorative effect was so marked that the hidalgo thought he was completely cured. It is possible that the true psychopharmacological effect of the preparation lies in its ability to induce a deep sleep, which is responsible for the subsequent restorative effect [47]. In fact, since the 19th century, it has been scientifically documented that psychiatric patients, particularly manic and psychotic patients, have shown great improvement and are more relaxed in the days following adequate rest.

Of the ingredients in the balm of Fierabras, rosemary stands out as an agent to which abundant therapeutic properties have been attributed [Table 2]. Rosemary is a known choleretic, a characteristic that has been partially confirmed in animal experiments, as well as a diuretic. It has also been suggested that it may have spasmolytic activity, due to one of its constituents, borneol. Its properties as a stimulant are also well known [48]. During the 16th century, rosemary became part of the composition of a number of medicinal preparations, such as the balm of Opodeldoc, the balm of Porras, the balm of Aparicio or the soothing balm [46]. In his adaptation of Dioscorides, Andrés Laguna wrote of rosemary: “the eating of its flower in a preserve comforts the brain, the heart and the stomach; sharpens understanding, restores lost memory, awakens the mind, and in sum, is a healthy remedy for all kinds of cold ailments of the head and the stomach” [49].

Purgatives are also mentioned in Cervantes' principal work, Don Quixote, in the sense that these agents were used at the time in the context of mental health, i.e., as substances capable of eliminating morbid humors, allowing for spiritual purification. The priest at the place Cervantes did not want to remember commented, in relation to the hidalgo: “he stands in need of a little rhubarb to purge his excess of bile” (Part I, Chapter VI) [27]. The rhizome of monks' rhubarb (Rumex alpinus and Rumex patientia), a plant that grows in northern Spain, which is rich in tannic and chrysophanic acids, has purgative and tonic properties as mentioned above [Table 2], and was used to purge choleric and phlegmatic humors [43]. This species of rhubarb was usually cultivated in the cloisters of monasteries for the monastic apothecary's shop. The other rhubarb (Rheum spp.), popularly known as “Chinese rhubarb,” also has the same laxative properties [50], although its exotic origin (far East) made its popular use in 16th century Spain practically impossible. In the Iberian Peninsula, on the other hand, there is abundant growth of common sorrel (Rumex acetosa), a plant commonly known as dock weed, the rhizome of which is also rich in chrysophanic acid. In relation to the root of this plant, Laguna commented that “knowing of its valuable laxative properties, doctors ordinarily administer it instead of rhubarb, to purge the excess of bile, which is why many wise doctors consider it as true rhubarb” [49]. It is possible that Cervantes' commentary on rhubarb refers to any of these plants of the genus Rumex, which would further strengthen the hypothesis that Cervantes had read Dioscorides.

The second quality of phármakon: poison

Until the Renaissance, poisonous substances and toxic agents originating exclusively from nature were relatively rare. Most of them were of vegetable origin and many shared a therapeutic use, with certain exceptions such as hemlock (Conium maculatum) and aconite (Aconitum napellus). A considerably smaller number consisted of minerals, notably arsenic, and the rest came from the animal kingdom, which was particularly feared (e.g., snake and scorpion venom) [51].

The great interest in poisons during the Renaissance was partly fuelled by the development of alchemical disciplines through the influential work of Paracelsus, by the introduction of new poisons and toxic substances from the New World [3] and by new editions of the main classical sources, such as the treatises on toxicology written in Greek verse by Nicander of Colophon (second century B.C.) (Theriaca and Alexipharmaca). In addition, knowledge of the properties of poisons became of great importance due to their potential criminal, political and military uses [1],[52]. The high level of virtuosity that the “art of poisoning” acquired for political purposes in this period needs to be remembered, as illustrated by the papal court of the Spanish Borgia family (1455–1503) and the Florentine cardinals [53]. To this must be added the proliferation of characters linked to magical practices that were commonly perceived as being associated with the religious minorities of the time, basically the Jews, and engaged in casting spells, incantations or love philters [54]. These practices came to be an inseparable part of the European collective imagination during the 16th century, as reflected in the literary works of a large number of authors [1].

The literary significance of some of these preparations is such that they constitute the core narrative of several of Cervantes' Exemplary Novels [55]. Nevertheless, Cervantes makes frequent use of the generic term “poison” (and its synonyms) in his works, although he usually does so in a symbolic or metaphorical way. For example, it is used seven times in Don Quixote but only once is there as an explicit reference to the role of these substances: “All that certain silly women and quacks do is to turn men mad with potions and poisons” (Part I, Chapter XXII) [27].

Within the literary framework of intoxications based on love, Cervantes resorts to the use of poisons for homicidal and criminal purposes [54] in La española inglesa (The Spanish English Lady, 1613), one of his Exemplary Novels. In this novel, the Protestant chambermaid decides to poison Isabela out of spite for having spurned the amorous advances of her son, Count Arnesto [Figure 8]: “And she was determined to kill Isabela with poison; ... that same afternoon she poisoned Isabela in a conserva (preserve) that she gave her, obliging her to take it on the grounds that it was good for the anxiety she felt in her heart... Isabela's tongue and throat began to swell up, her lips to turn black and her voice to go hoarse; her eyes glazed over and her chest was tight: all well-known signs of having been poisoned” [27]. Note that, the poison was administered in a “preserve,” i.e., in a medication with a soft consistency, consisting of a vegetable substance and sugar, so that the therapeutic active ingredient was preserved, making it easier to administer.
Figure 8: Illustration of the novel The Spanish English Lady attributed to Josef Ximeno (1757–1807) for the edition of the Exemplar Novels by Antonio Sancha (Madrid, 1783), where the effects of the poisoning of the protagonist are shown.

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The Spanish term “tósigo” (poison/venom) comes from the Latin “toxicum” and is referred to in Dioscorides as a poison that inflames the tongue and lips and induces madness [51]. Laguna describes the toxic effects induced by henbane in much the same way: “those who took hyoscyamus albus were overcome by great looseness of the joints, abscesses on the tongue, swelling of the mouth, inflammation of the eyes and clouding of the vision, shortness of breath, deafness and dizziness, discomfort in the gums, and in the whole body” [49]. However, other toxic substances could also cause the symptomatology described by Cervantes. Indeed, in the chapter on “toxico,” a poison that “inflames the tongue and lips,” Laguna discusses the nature of this substance mentioned by Dioscorides, which he says was used by the barbarians to poison their arrows. For this reason, the possibility that black hellebore, known in Castile as “crossbowmen herb,” or aconite, which was known as “napelo” and also used by the Arabs for this purpose, could both cause similar symptoms, has been postulated [49].

In another of the Exemplary Novels, The Jealous Old Man from Extremadura, there is a curious quotation about opium, the prototypical sedative agent, when the young wife Leonora [Figure 9] applies a narcotic preparation, the composition of which is not revealed, to her elderly husband Carrizales: “an ointment of such virtue that, on applying it to his pulses and his temples, caused a deep sleep, from which nobody could rouse him in two days, unless it were by washing all the anointed parts with vinegar... and likewise she anointed the windows of his nose... It took little time for the alopiado (opiate) unguent to show signs of its virtues, because the old man soon began to snore loudly... The ointment with which her husband was smeared had such virtues that, without actually taking his life, left a man as though dead” [27]. In this passage, Cervantes uses an Italianised adjective (“alopiado”) to indicate that the ointment applied by the wife is made with opium [Table 2]. This word derives from the Italian “alloppiato,” which had been used in Italy since the 14th century to designate beverages containing opiate derivatives. The description of the effects of the “alopiado” (opiated) ointment is also consistent with the descriptions made by Laguna in his annotated version of Dioscorides. In relation to papaver hortense, particularly the subspecies papaver pithitis and papaver nigrum, Laguna notes that: “an ounce of this seed given to a man of slight build will send him to sleep in aeternum... The juice of the seed... seriously puts a person to sleep...” [49].
Figure 9: Illustration from the novel The Jealous Old Man from Extremadura by Claude-Louis Desrais (1746–1816) for a French edition of the Exemplary Novels (Nouvelles espagnoles de Michel de Cervantès, Chez Defer Demaisonneuve Libraire, Paris, 1775).

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As far as plants with narcotic properties are concerned, the only one mentioned in Cervantes' works is henbane [Table 2], which is mentioned in The Galatea, with specific reference to its hypnotic effects: “You have taken the strength from henbane, / with which ungrateful love/drowsed my painful virtue” [27]. A brief reference to the properties of this plant also appears in Journey to Parnassus: “Morpheus, the god of slumber, came to view/As if by magic; on his head was worn/A wreath of henbane leaves, of saintly hue” [27]. Henbane, popularly known as “black henbane” and “stinking nightshade,” is a plant rich in alkaloids with high sedative activity like other Solanaceae, such as hyoscyamine and scopolamine [48]. In fact, a popular Spanish proverb says that “al que come beleño, no le faltará sueño,” literally “he who eats henbane will not lack sleep,” and the verb “embeleñar” comes to mean to lull to sleep or even poison. Of the flowers of this plant, which Laguna calls hyoscyamus, Dioscorides says that “they give rise to very troublesome dreams” [49]. However, extra-medicinal toxic uses were more common historically. Since the Middle Ages, henbane has been used as an ingredient in potions prepared by sorcerers and witches for its hallucinogenic effects [4],[56], as we shall discuss later. In the treatise Occult Botany attributed to him, Paracelsus commented on how “evil sorcerers take advantage of the evil properties of black henbane to produce madness and sometimes death” [57].

The preparation of potions and “love philters” using herbal remedies, generally also consisting of different Solanaceae, such as jimson weed, solanum, henbane or mandrake, capable of modifying the feelings and will of those who consume them, within the framework of popular lore related to sorcery [58], is also described in some of Cervantes' works [59], for example in El licenciado Vidriera (The Lawyer of Glass, 1613), one of his Exemplary Novels [Figure 10]: “So, on the advice of a Morisca woman, she took a Toledan quince, and in that fruit she gave him one of those contrivances called charms, thinking that she was thereby forcing him to love her; as if there were, in this world, herbs, enchantments, or words of power, sufficient to enchain the free-will of any creature. These things are called charms, but they are in fact poisons: and those who administer them are actual poisoners, as has been proved by sundry experiences” [27]. The traditional dedication of the Moorish community to medicine, still evident during Cervantes' lifetime [60], and their extensive knowledge of herbs and plants make the choice of this sorceress a very plausible representation of the environment of the connoisseurs of common or popular botany in 16th century Spain.
Figure 10: Detail of the engraving by Jacob Folkema (1692–1767) intended to illustrate the novel The Lawyer of Glass, in the edition of the Exemplary Novels produced by J. Neaulme (The Hague, 1739).

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Cervantes also describes the toxic effects of these herbal preparations: “In an unhappy moment Rodaja ate the quince, but had scarcely done so when he began to tremble from head to foot as if struck by apoplexy, remaining many hours before he could be brought to himself. At the end of that time, he partially recovered but appeared to have become almost an idiot. He complained, with a stammering tongue and feeble voice, that a quince which he had eaten had poisoned him, and also found means to intimate by whom it had been given, when justice at once began to move in quest of the criminal; but she, perceiving the failure of her attempt, took care to hide herself, and never appeared again... Six months did Thomas remain confined to his bed; and during that time he not only became reduced to a skeleton but seemed also to have lost the use of his faculties. Every remedy that could be thought of was tried in his behalf; but although the physicians succeeded in curing the physical malady, they could not remove that of the mind; so that when he was at last pronounced cured, he was still afflicted with the strangest madness that was ever heard of among the many kinds by which humanity has been assailed. The unhappy man imagined that he was entirely made of glass” [27]. We are therefore presented with an initial picture of dreamlike mental confusion which is clearly of toxic origin, which could well be caused by mandrake or jimson weed. Of mandrake, which is also known as “Devil's testicle” or “Satan's apple,” one of the toxic effects of which is inducing convulsive crises due to its richness in atropine [61], Laguna says that “it primarily affects the brain, the temple and the dwelling place of the soul... inasmuch as it makes causes drunkenness, headaches, dims the eyesight and gives rise to cold sweats, the precursors of death, now approaching and close at hand...” [49]. All this is consistent with the effects of the “veneficio” (sorcery) administered to the Lawyer of Glass. However, the effects on Thomas could also be attributed to jimson weed, also known as “fig of hell,” “crazy weed,” “devil's trumpet,” “angel's trumpet,” “devil's weed,” “thorn apple,” and “stinkweed,” a solanaceous plant whose most active alkaloid is daturin [48]. This plant is widely used to make philters to change the behavior of poisoned people [56]. After it has been administered, a period of great nervous excitement ensues, with tremors, convulsions and delirium, followed by a dulling of the senses, a weakening pulse and breathing and progressive paralysis, leading to a loss of consciousness and the possibility of falling into a coma [61].

The third quality of phármakon: antidote

The use of general antidotes or panaceas for treating poisoning was also common practice in the Renaissance period [51]. Some of them were remedies of a simple nature and generally of mineral origin (Lemnian earth, deer heart bone, ivory or precious stones, primarily hyacinth, pearls and emerald), while others were considered compound medicines, such as mithridate (mithridaticus antidotus), which, in its different variants, had as many as 54 ingredients. This preparation would later evolve into the famous theriac (Theriaca) [53]. But the two most famous universal antidotes from antiquity to the Cervantine era were undoubtedly unicorn horn and bezoar stones [53].

The latter (Lapis bezoardicus) are stones the size of a chestnut, which form in a certain area of the stomach or gall bladder of some animal species and more frequently in deer and goats, particularly in the Capra aegagrus [62], and in the American vicuña. Monardes dedicated a medical treatise to its virtues, stating that “it is the principal remedy for all kinds of poison that we now know of…” [63]. In fact, the set of alexipharmic agents were also called bezoartic medicines. Like unicorn horn, bezoar stones were considered a luxury good, and were even polished and set in gold and silver jewelry, for which they fetched a very high price [64]. It is in this sense that Cervantes mentions them in his comedy La entretenida (The Diversion, 1615), when Muñoz gives instructions to Cardenio so that he add to his pretense of being an influential Indian: “But do not fail to bring/some bezoar stones,/and strings of pearls/y and parrots that talk” [27].

In the case of the criminal poisoning in the exemplary novel The Spanish English Lady, mentioned previously, Cervantes also mentions the unicorn as an antidote, when he relates that Isabela, the Queen “ordered large quantities of unicorn horn powder, together with other antidotes that great princes tend to have to hand for such needs” [27]. This passage also hints that the writer might have read Laguna's work. According to the Segovian physicist, “of all the medicines that preserve against pestilence and poison, unicorn horn has pride of place... The conciliator's preferred remedy, above all others, is emerald powder, of which two drams are prescribed. But this cure can only be administered to Pontiffs and Emperors” [49]. Framed in medieval mythology, the unicorn was initially likened to the rhinoceros, as evidenced in Isidore of Seville's Etymologiae (627–30) (c. 556–636). But during the Middle Ages, legends eventually depicted it as a stylized white horse, with antelope legs and a goat's beard, with a long, straight, spiral horn on its forehead [Figure 11] [65]. This appendage, known as the alicorn, administered in the form of scrapings, would be the most highly prized anti-venom known. Meanwhile, key people also used it to make cups and glasses, on the contents of which no poison could exert its effect [66].
Figure 11: One of the six engravings in the Unicorn series made by Jean Duvet (1485–1562) between 1545 and 1560, which shows the popular belief that this animal was capable of purifying poisoned waters with its horn (National Gallery of Art, Washington, Rosenwald Collection).

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Many plants were also used as specific antidotes against certain poisons, such as the herb scorzonera (Scorzonera hispanica), to which Monardes devoted a special treatise in his Medical Study, together with vervain. In his theatrical comedy Pedro de Urdemalas (1615), Cervantes mentions vervain, a plant with magical properties [Table 2], even during the early baroque period: “Here we have vervain,/full of rare virtues” [27]. Vervain is a plant commonly known at the time as the “holy herb,” because of its use as a bouquet in religious ceremonies in ancient times, or the “spellcraft herb,” underlining its magical nature. In fact, it was harvested on the night of St. John's Eve and its flowers were widely used to make love philters [46]. An ancient grimoire attributed to a 13th century Dominican known as Albert the Great (possibly St Albert the Great) reads: “by rubbing your hands with the juice of vervain and then touching the person you want to fall in love with, you will awaken an irresistible love in the object of your desire” [67]. Laguna commented that “they call it a holy herb because it is useful for purging the house of misfortunes, by hanging on to it,” and it has many different uses, including as an antidote to poisons.

The fourth quality of phármakon: drug of abuse

From the 12th century, the proliferation of witches throughout Europe imbued popular culture with a whole host of legends [68], which eventually became a genuine “reality,” fiercely resisted by ecclesiastical and civil authorities, particularly after the Fourth Lateran Council (1215–1216) [4]. The Inquisition (Inquisitio Haereticae Pravitatis Sanctum Officium) was set up in 1184 under the Ad abolendam papal bull of Pope Lucius III (1097–1185). This institution was charged with harshly prosecuting any possibility of deviation from Catholic orthodoxy, including, of course, the practices of witchcraft [1].

The heresy trials for witchcraft initiated by the Tribunal of the Inquisition reached their peak during Cervantes' lifetime, turning Europe into a permanent bonfire between 1550 and 1650 as a result of the so-called “witch-hunt,” although to a much lesser extent in the Mediterranean countries [1]. The inquisitorial trials confirmed the use of potions and ointments, especially by witches themselves, usually made from hallucinogenic plants such as bittersweet or black nightshade (Solanum nigrum), mandrake, henbane, belladonna and jimson weed, which were boiled in their famous cauldrons together with fats and many other substances [69].

These ointments were applied to the genital region and their effects were almost immediate, as the active hallucinogenic ingredients were rapidly absorbed through the vaginal mucosa [56]. The ingredients of these ointments produced hallucinations while awake (sensation of being transported through the air, sexual fantasies, visions of strange beings, etc.). This was followed by a deep sleep, in which the dream was confused with reality upon awakening. For example, among the effects of henbane is that of inducing a strange sensation of lightness and weightlessness, which may explain the vivid certainty of flying, as in the case of witches flying on their brooms [Figure 12} [46]. In fact, Laguna may have been the first scientist to demonstrate the correlation between the consumption of psychotropic substances contained in plants of the Solanaceae family and the practice of witchcraft [70]. In his notes on Dioscorides, Laguna describes its pleasant effects and sensations, but he was also able to demonstrate them experimentally by applying these witches' ointments to normal subjects, such as the wife of a municipal executioner suffering from insomnia, concluding that these drugs (“roots which engender madness”) cause an increase in suggestibility, inducing a kind of transient mental disorder [49].
Figure 12: Linda maestra (1799), engraving number 68 of the Caprichos by Francisco de Goya (1746–1828).

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Cervantes describes the effects of witches' ointments in detail in the exemplary novel El coloquio de los perros (The Dialogue of the Dogs, 1613) [Figure 13] [71],[72], when the dog Berganza comments on the activities of one of his masters, an old woman known as Cañizares, a member of a well-known community of witches, of true origin, in the Cordovan town of Montilla, who confesses to practising acts of witchcraft and using ointments specific to these practices: “This unguent that we witches put on ourselves is made up of the juices of herbs that are cold in the extreme, … and I tell you they are so cold that they deprive us of all senses when we spread them on ourselves, and we lie stretched out and naked on the ground, and then they say that in fantasy everything occurs to us that appears to happen in reality… After applying the ointment, it seems to us that we change our form, becoming roosters, owls or crows, and we go to the place where our master awaits us, and there we take on our original form and enjoy the delights of which I didn't tell you... my ointments give me some good times... and the delight is much greater imagined than actually experienced...” [27].
Figure 13: Illustration of the novel The Dialogue of the Dogs attributed to Josef Ximeno (1757–1807) for the edition of the Exemplary Novels of Antonio Sancha (Madrid, 1783).

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Cervantes returns to this theme in The Trials of Persiles and Sigismunda, when he comments on the activities of Cenotia, a Moorish sorceress who is an expert in making ointments from diabolical herbs and is able to fly through the air [27],[73]. However, Cervantes limits himself to glossing over the properties of these herbal preparations, without going into their hypothetical composition. This may not be due to ignorance on the part of the author, who as we have said was no stranger to medical and therapeutic matters, but rather, as several authors suggest, to an excess of zeal toward the authorities of the Inquisition. We must not forget the particular vulnerability of the writer at this time, who, having been questioned as an old Christian, had to leave his blood purity permanently unblemished [59],[71],[72].

In the chapter on solanum that gives rise to madness (“that which unhinges reason” and “deprives of understanding and sense”, in the words of Laguna) and “black nightshade,” a solanaceous plant with significant hallucinogenic effects [46], Laguna comments on its consumption as follows: “…produces vain images, but very pleasant ones, which should be understood between dreams. This, then, must be (as I see it) the virtue of these ointments that witches tend to spread over themselves, the extreme coldness of which sends them to sleep in such a way that the resulting prolonged and very deep slumber floods their brains with such fancies and fantasies that on waking they confess to what they never actually did” [49]. These toxicological notes shed new light on the social view of witches and sorceresses, who began to cease to be seen as possessed and to be evaluated from the perspective of alienated and intoxicated subjects. In fact, on many occasions, the ointments were prepared for recreational and playful purposes, without the excuse of ritual or satanic purposes.

As can be seen, there is an enormous similarity between Laguna's writings, discussed above, and those of Cervantes, who masterfully describes the psychotropic effects of the mixtures of hallucinogenic agents administered topically (out-of-body travel, visual hallucinations, pleasurable sensations, etc.) in his work, which seems to confirm the literary writer's use of the scientist's annotations [30],[31],[59]. However, Cervantes may also have been inspired by the well-known work of Pedro Ciruelo (1470–1548), professor of Thomist theology at the University of Alcalá, entitled Reprobación de las supersticiones y hechicerías (Reprobation of Superstition and Witchcraft), which was first published in Alcalá de Henares in 1530 but reprinted up to nine times before the first edition of the Exemplary Novels. In relation to witches' ointments, Ciruelo comments: “... As soon as they finish smearing and saying those words, others fall to the ground as if they were dead, cold and without any feeling... And after two or three hours they get up very gently and talk a lot about other lands and places where they say they have gone… And none of it is true, even if they think that everything is as they have dreamed it to be...” [74].

In relation to substances intended for recreational use, in his poetic work Journey to Parnassus, Cervantes also mentions the use of tobacco. This plant, like many other American botanical species, had only just been introduced into Spain at the time Cervantes published his works. The tobacco plant, initially known by various names such as the “devil's weed,” the “comforting weed” and the “herb of all evils,” was considered a great therapeutic remedy [Table 2] [75]. In fact, Monardes recommended it for up to 36 different ailments in his work, including joint problems, swellings, colds, toothache, chilblains, strokes, bites, and old sores [76]. It was also traditionally used as a potent (but dangerous) laxative in the form of leaf enemas [46]. Interestingly, Monardes also recommended tobacco in the treatment of poisoning: “Our tobacco is excellent for poisons and poisonous wounds. This has been known for some time now.” [63].

In another section of his work entitled Modo como los sacerdotes de los indios usaban el tabaco (The Way the Priests of the Indians Use Tobacco), Monardes refers to a toxic quality of this plant, mirroring the quality highlighted by Cervantes in his poetic text, i.e., tobacco's capacity to stimulate the brain and the imagination, especially in cases of intellectual fatigue [46]. Monardes notes: “The Indians in our West Indies use tobacco to relieve fatigue and to take relief from work” [63]. It is precisely this psycho-stimulant property that Cervantes is referring to, to criticize poets of little talent, when he mentions this plant in Journey to Parnassus: “That which is harvested is tobacco/which for those who are disturbed serves as a head/of some feeble-brained poet” [27]. Six years later, in the first specific therapeutic work on the plant, Historia de las virtudes i propiedades del Tabaco, i de los modos de tomarle para las partes intrínsecas i de aplicarle a las extrínsecas (History of the Virtues and Properties of Tobacco, 1620), written by the Cordovan apothecary Juan de Castro Medinilla y Pabón (b. 1594), he specifies that tobacco “sharpens your wits,… increases memory and gives alacrity to the tongue in speaking” [77].

  Conclusion Top

Miguel de Cervantes shows in his works that he had extensive knowledge of medicine, possibly from his family and friends, and from reading and working with various treatises on the subject, some of which were part of his private library, such as the edition of Dioscorides annotated by Andrés Laguna. We hypothesize that this work may have served as a documentary source for the pharmacological and toxicological passages in Cervantes' works [1],[30],[31],[55],[59]. Cervantes also discusses the use of psychotropic substances in the context of the practice of witchcraft and related magical phenomena [73],[78], which may be a mere extrapolation of the popular and literary interest in these subjects during the Spanish Golden Age [79], and he describes the toxic effects of these substances and preparations in detail. This allows us to speculate what the ingredients of these preparations might have been from a pharmacological point of view: henbane, solanum and belladonna in The Dialogue of the Dogs, mandrake and datura in The Lawyer of Glass, henbane in The Spanish English Lady, and, of course, opium in The Jealous Old Man from Extremadura.

In this way, Cervantes' texts, although by no means scientific treatises, give us with an accurate approximation of the uses (and effects) of psychotropic substances in late Renaissance Spain and explain how a group of drugs could have four archetypal qualities: remedy, poison, antidote and drug of abuse.

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Francisco López-Muñoz, a member of international advisory board of the Taiwanese Journal of Psychiatry, had no rôle in the peer review process or decision to publish this editorial.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13]

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