The idea that the history of modern, essentially experimental, pharmacology began in the early years of the 19th century is widely shared by scholars. The emblematic milestone of that view is the isolation of morphine by Friedrich Sertürner in 1805. Morphine was, thus, the first plant alkali (alkaloid), and also the first organic substance identified. In addition to allegedly exerting large influence on the understanding of the composition and behaviour of matter, as well as inducing a major transformation within the field of pharmacology, the notion of “alkaloid” as active principle of plant matter contributed to both, the development of organic chemistry, and to the disciplinary autonomy of the plant sciences. Therefore, the notion of “alkaloid” is at the very centre of the modern process of specialisation of science, which was based on the dissolution of the traditional links among the three kingdoms of nature that hereafter were reconfigured on the grounds of other models as, e.g., the cycle of matter. Nevertheless, a closer look into 18th century pharmacology shows that contemporary scholars were utterly persuaded that there were principles of activity in matter, and that they could be isolated in the laboratory. In the present study, we discuss the quest for the active principle of opium by two highly influential 18th century scholars. Charles Alston (1683-1760), the famous Edinburgh professor of materia medica, published in Medical Essays and Observations, in 1752, a monograph entitled Dissertation on Opium, which was widely read and deeply informed the contemporary ideas on the operation of opium. Also from Edinburgh, John Murray’s (d. 1820) Elements of Materia Medica and Pharmacy (1802) exhibits one of the earliest applications of the novel conception on the “chemical elements” to the knowledge on the composition and action of drugs. By addressing the ideas of Alston and Murray we are granted a glimpse to the more widely spread ideas on the activity of matter on the very eve of Sertürner’s discovery. [Support: FAPESP No.2011/14040-9]