Lethal Lullabies: A History of Opium Use in Infants.

Poppy extract accompanied the human infant for more than 3 millenia. Motives for its use included excessive crying, suspected pain, and diarrhea. In antiquity, infantile sleeplessness was regarded as a disease. When treatment with opium was recommended by Galen, Rhazes, and Avicenna, baby sedation made its way into early medical treatises and pediatric instructions. Dabbing maternal nipples with bitter substances and drugging the infant with opium were used to hasten weaning. A freerider of gum lancing, opiates joined the treatment of difficult teething in the 17th century. Foundling hospitals and wet-nurses used them extensively. With industrialization, private use was rampant among the working class. In German-speaking countries, poppy extracts were administered in soups and pacifiers. In English-speaking countries, proprietary drugs containing opium were marketed under names such as soothers, nostrums, anodynes, cordials, preservatives, and specifics and sold at the doorstep or in grocery stores. Opium's toxicity for infants was common knowledge; thousands of cases of lethal intoxication had been reported from antiquity. What is remarkable is that the willingness to use it in infants persisted and that physicians continued to prescribe it for babies. Unregulated trade, and even that protected by governments, led to greatly increased private use of opiates during the 19th century. Intoxication became a significant factor in infant mortality. As late as 1912, the International Hague Convention forced governments to implement legislation that effectively curtailed access to opium and broke the dangerous habit of sedating infants.

The pharmacology of medieval sedatives: the "Great Rest" of the Antidotarium Nicolai.

ETHNOPHARMACOLOGICAL RELEVANCE: Past practices of compound drugs from different plant ingredients enjoyed remarkable longevity over centuries yet are largely dismissed by modern science as subtherapeutic, lethal or fanciful. AIM OF THE STUDY: To examine the phytochemical content of a popular medieval opiate drug called the "Great Rest" and gauge the bioavailability and combined effects of its alkaloid compounds (morphine, codeine, hyoscyamine, scopolamine) on the human body according to modern pharmacokinetic and pharmacodynamic parameters established for these compounds. CALCULATIONS AND THEORY: We reviewed the most recent studies on the pharmacodynamics of morphine, codeine, hyoscyamine and scopolamine to ascertain plasma concentrations required for different physiological effects and applied these findings to dosage of the Great Rest. RESULTS: Given the proportional quantities of the alkaloid rich plants, we calculate the optimal dose of Great Rest to be 3.1±0.1-5.3±0.76 g and reveal that the lethal dose of Great Rest is double the therapeutic concentration where all three alkaloid compounds are biologically active. CONCLUSION: This study helps establish the effective dose (ED50), toxic dose (TD50) and lethal dose (LD50) rates for the ingestion of raw opium, henbane and mandrake, and describes their probable combined effects, which may be applied to similar types of pre-modern pharmaceuticals to reveal the empirical logic behind past practices.