Tuesday, 28 April 2015

The pharmacology of medieval sedatives: The “Great Rest” of the Antidotarium Nicolai

Volume 155, Issue 1, 8 August 2014, Pages 443–449

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.


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.


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.

Graphical abstract

Full-size image (26 K)

Chemical compounds studied in this article

  • Morphine (Pubichem CID: 5288826);
  • Codeine (PubChem CID: 5284371);
  • l-hyoscyamine (PubChem CID: 154417);
  • Scopolamine (PubChem CID: 5184)


  • Medieval medicine;
  • Sedatives;
  • Alkaloids;
  • Dosage;
  • Opium

Corresponding author. Tel.: +1 647 988 8370; fax: +1 416 9784810.
Tel.: +1 416 305 3897; fax: +1 16 978 6395.