Brahman priests and scholars were the medical leaders in the earliest recorded histories, three of which are of primary importance:

The Susruta detailed more than 700 medicinal plants, the most common of which were condiments such as sugar, cinnamon, pepper, and various other spices. Included among them were descriptions of the depressant effects of Hyoscyamus and Cannabis indica. The eponymously named text (Susruta, c. 700–600 bce) described Susruta’s use of wine to the point of inebriation as well as fumitory cannabis in preparation for surgical procedures. Part of the difficulty with so many drugs was that they were not well codified and were prescribed in casual ways by numerous practitioners, who relied on (clinical) observation of effects [6].

Agriculture developed in the area between the Tigris and Euphrates rivers, and a sophisticated cultivation of plant materials useful for the alleviation of symptomatic disease was not only practiced, but also recorded. Nearly 30,000 clay tablets from the era of Ashurbanipal of Assyria (568–626 bce) were discovered in the mid-nineteenth century near the site of Nineveh, capital of the neo-Assyrian Empire, with numerous references to plant remedies. Beers were especially well developed in ancient Babylon. Cannabis indica was known for producing intoxication, ecstasy, and hallucinations, when reinforced with hemp. This was all under the supervision of the priesthood. In addition, hallucinogenic mushrooms were employed in ancient Sumeria. Poppies were used mainly as a condiment in Sumerian life. Although there is no drug activity in the poppy leaves, fruit, or root, if the unripe seed capsule is opened, the white juice resulting from that is (raw) opium, the dried “latex” of which forms alkaloids as it dries. However, opium was not described (as far as we know) in the Ashurbanipal tablets.

Jewish medicine received significant contributions from the Babylonians during the Babylonian captivity (597–538 bce) as well as from the Egyptians during the Egyptian Captivity (a date which is much less clear, based on 430 years of captivity prior to the Exodus, accepted as 1313 bce in rabbinic literature [7]). Jewish potions were prepared by the priesthood for pain relief and the imparting of sleep during surgical procedures, venesection, and leeching; Samme de shinda was probably a hemp potion, but probably not an opium derivative [8].

The major influence on the emerging Greek world of medicine came from Egypt. Our knowledge of their codification is relatively robust because of the medical papyri, most of which were hieratic (hieroglyphics or ideographs), compiled from around 2000–1200 bce (Table 1.1). They themselves were probably copied from older originals, as evidenced by the use of archaic terminology within the medical papyri, more characteristic of language from around 3,000 bce.

It is ironic, and somewhat puzzling, that despite the richness of ancient documentation from the aforementioned artifacts, there is a paucity of information about narcotics and sedatives in ancient Egypt. Most of the suggestions about the use of such medications are by inference. For example, Ebers 782 cites “shepnen of shepen” (poppy seeds of poppy) to settle crying children. Interestingly, the poppy seed contains relatively little morphine; it is the latex produced from the incision of the seed pod that actually contains the active ingredient. Another suggestion, by inference, is that base ring juglets were used to import opium from Cyprus in about 1500 bce, because of the resemblance of these juglets, when inverted, to a poppy head [9] (Fig. 1.2) and the reported finding of morphine in an Egyptian juglet from the tomb of Kha (19th Dynasty), although this has been disputed [10]. Cannabis (C. sativa) was prescribed by mouth, rectum, vagina, and delivered transdermally and by fumigation, yet central nervous system effects were not described. The London and Ebers papyri refer to mantraguru, an obvious common origin with mandrake, or Mandragora. Some species of lotus (Nymphaea caerulea and N. lotos) are native to Egypt and contain several narcotic alkaloids that can be extracted in alcohol, leading to a logical hypothesis that lotus-containing wine might have additional narcotic effects. Ebers 209 and 479 both refer to preparations for the relief of right-sided abdominal pain and jaundice (respectively) containing lotus flower as an ingredient, but directing that the lotus flower has to “spend the night” with wine and beer—conditions that would likely permit alkaloid extraction. It is therefore interesting that depictions of the lotus flower being sniffed are the only artifactual suggestion of the possible medical use of lotus (Fig. 1.3).

All over the world, indigenous people have learned the medicinal properties of plants in their environments and have applied them to medical use. The remarkable acquisition of a sufficient amount of experience to provide the basis for a systematic analysis and an accumulated fund of knowledge, probably transmitted initially through oral tradition and along specific lines of professional authority (physicians, priesthood, specialized castes of drug-gatherers and preparers), undoubtedly took a long time. It is extraordinary, moreover, for its survival and consistency through the ages, laying the groundwork for Classical civilization and beyond.

In 640 ce, the Saracens conquered Alexandria, Egypt’s seat of ancient Greek culture, and by 711 ce they were patrons of learning, collecting medical knowledge along the way. Unlike the Christians, who believed that one must suffer as part of the cure, the Saracens tried to ease the discomfort of the sick. They flavored bitter drugs with orange peels and sweets, coated unpleasant pills with sugar, and studied the lore of Hippocrates and Galen. Persian physicians became the major medical teachers after the rise of the Baghdad Caliphate around 749 ce, with some even penetrating as far east as India and China. By 887 there was a medical training center with a hospital in Kairouan in Northern Africa.

The most prominent of the Arab writers on medicine and pharmacy were Rhazes (865–925 ce) and Avicenna (930–1036 ce), whose main work was A Canon on Medicine. The significance of this thread of ancient medical philosophy was that during the eleventh and twelfth centuries this preserved knowledge was transmitted back to Christian Europe during the Crusades. Avicenna noted the special analgesic and soporific properties of opium, henbane, and mandrake [17] (Fig. 1.5).

The first Christian early medieval reference to anesthesia is found in the fourth century in the writings of Hilary, the bishop of Poitiers [18]. In his treatise on the Trinity, Hilary distinguished between anesthesia due to disease and “intentional” anesthesia resulting from drugs. While St. Hilary does not describe the drugs that lulled the soul to sleep, at this time (and for the following few centuries) the emphasis remained on mandragora.

From 500 to 1400 ce, the church was the dominant institution in all walks of life, and medicine, like other learned disciplines, survived in Western Europe between the seventh or eighth and eleventh centuries mainly in a clerical environment. However, monks did not copy or read medical books merely as an academic exercise; Cassiodorus (c. 485 ce–c. 585 ce), in his efforts to bring Greek learning to Latin readers and preserve sacred and secular texts, recommended books by Hippocrates, Galen, and Dioscorides while linking the purpose of medical reading with charity care and help.

Conventional Greco-Roman drug tradition, organized and preserved by the Muslims, returned to Europe chiefly through Salerno, an important trade center on the southwest coast of Italy in the mid 900s. One of the more impressive practices documented at Salerno was intentional surgical anesthesia, described in Practica Chirugiae in 1170 by the surgeon Roger Frugardi (Roger of Salerno, 1140–1195), in which he mentions a sponge soaked in “narcotics” and held to the patient’s nose. Hugh of Lucca (ca. 1160–1252) prepared such a sleeping sponge according to a prescription later described by Theodoric of Cervia (ca. 1205–1296). As an added precaution, Theodoric bound his patients prior to incision. The description of the soporific sponge of Theodoric survived through the Renaissance largely because of Guy de Chauliac’s (1300–1367) The Grand Surgery and the clinical practices of Hans von Gersdorff (c. 1519) and Giambattista della Porta (1535–1615), who used essentially the same formula of opium, unripe mulberry, hyoscyamus, hemlock, mandragora, wood-ivy, forest mulberry, seeds of lettuce, and water hemlock (Fig. 1.6).