Opiates found in 17th c. patients of Milan hospital

Analysis of the bones and preserved brain tissue of nine 17th century patients of the main hospital in Milan has revealed the presence of codeine, morphine, noscapine and papaverine, all derivates of the opium poppy. This is the first time the presence of Papaver somniferum has been detected in historical and archaeological human remains.

The Ospedale Maggiore, also known as Ca’ Granda, was founded in the mid-15th century by Francesco Sforza, duke of Milan, to provide free health care for the poor. By the 16th century it was the city’s main hospital and held in high esteem throughout Europe for its innovative medical care, hygiene practices and treatment by specialized doctors. Some of those practices like the daily change of bed linens are givens today, but were revolutionary in the 1600s.

The hospital’s archives have been preserved from its founding in 1456 until it was closed in the 20th century. They provide a rich record of centuries of hospital administration and medical practices, including the medicines in its pharmacopeia. The records of the medications are incredibly detailed, listing plant and animal ingredients, how they were made and type of preparation.

Researchers seeking to verify the usage of drugs as described in the historical archives turned to another extraordinary record, this one archaeological: the hospital’s crypt. The Ospedale Maggiore had a dedicated burial crypt that was constantly expanded and used throughout the 17th century. An estimated 2.9 million bones lie in its 14 chambers today, the remains of more than 10,000 people who died at the hospital.

Bone and brain tissue trap traces of medicine that were in the body at time of death, so the research team took biological samples from the bones in the crypt and from brain tissue preserved by natural saponification (a process that converts organs into adipocere, in insoluble soap). Out of the nine samples of preserved brain tissue and eight cranial samples, toxicological analysis found alkaloids from different derivatives of the opium poppy in six of them, four from the brain tissue, two from the crania.

Specifically, noscapine, papaverine, and codeine (active principles of Papaver somniferum) were noted in preserved brain tissue, whereas in addition to these molecules, morphine was also detected in bone samples. The skeletons with traces of Papaver somniferum belonged to three females (including two young adults), one male, and one subadult of 11–12 years (for whom sex estimation could not be performed). In one case with positive toxicological findings, signs of ante-mortem trauma were seen on the left parietal bone with loss of bone tissue and possible trepanation. This could have been responsible for chronic inflammation and pain which may have been treated with the use of the Papaver somniferum plant at the hospital. […]

Papaver somniferum is present in the Ca’ Granda pharmacopoeia archives, showing not only that it was present in the pharmacy, but that it was also actively used as a medical treatment. Opium was listed in the apothecary’s archives as early as 1558 in form of laudanum or black poppy seeds; in the inventory list of 1604 the presence of white poppy seeds, black poppy seeds, poppy syrup and thebaic opium is reported, while in 1617 the hospital also introduced laudanum patches39. Additionally, according to the registries preserved at the former hospital, the doctors of the Modern Age, and in particular at the Ca’ Granda, used opium reduced to dried or juice pill (Capsulae sicca et succus capsularum inmaturarum) and as tincture of opium (Laudanum), as a narcotic, analgesic, astringent, coagulant, spasmolytic and antitussive. The findings presented in this research therefore confirm the archival data and implement our knowledge of the history of medicine in Milan.

The results of the study have been published in the journal Scientific Reports and can be read here.