Psychoactive Plant Extracts

A history of flower power, Part II

Posted Oct 24, 2020

In the first posting of this two-part blog, we described how plants and animals engaged in a coevolutionary process, in which each developed defensive measures against the other, in a cyclic manner (1).  One type of defensive response was for plants to generate 'chemical thorns'. These were often alkaloids or other substances with unpleasant taste, or which were toxic or otherwise lowered the predator’s ability to protect itself due to sedation or intoxication (2). In prehistoric times many of these substances were incorporated into religious ceremonies or the practice of magic, continuing into the age of classical Greece.

In this posting, we will describe how the notion of medicines (particularly psychoactive agents) came to be dissociated from a religious/magical context, and began to be studied as physical substances that influence physiological processes. Then we will trace the growing understanding of psychoactive plant extracts into modern times.

Dr. Otto Wilhelm Thome, in Wikimedia Commons/Public Domain
Hellebore, in the buttercup family, was used in ancient Greece for melancholy.
Source: Dr. Otto Wilhelm Thome, in Wikimedia Commons/Public Domain

The first step in removing medicines from a religious context came with Hippocrates of Kos (c460-c370 BC), sometimes thought of as the ‘father of medicine’, who argued that disease was not retribution from on high but rather came about from disorders of bodily processes. Similarly, he believed that medicines did not possess supernatural powers but rather had understandable interactions with the body.

More specifically, Hippocrates taught that opium did not have magical properties but recognized it as useful as a hypnotic, for pain, and for what he thought were uterine disorders. Spearmint (Mentha spicata) was believed to be helpful as a diuretic, as well as for nausea and anxiety.

Ultimately a large pharmacologic tradition was developed. Mandrake (Mandragora) was widely used in Greek and Roman medicine, and the dream-like state and partial amnesia it produced were recommended for those undergoing surgery. Extracts of hellebore from the buttercup family, which, like mandrake, could be very toxic, were given in ancient Greece as a treatment for melancholy.

Although some physicians persevered in thinking of medicines in this new light, the Romans and their successors often continued to interweave them with religion and magic. This persisted into the Middle Ages, when the practice of witchcraft often involved giving draughts or ointments, which were thought to produce otherworldly, and sometimes erotic, experiences, as well as philters, or love potions. Self-styled witches and sorcerers dispensed medicines such as opiates and belladonna-related substances from solanaceous plants for healing purposes. At one point, their administration of medicines was considered to be among their crimes by the Inquisition.

Others persisted in studying drugs in a non-magical, non-religious context. One source of knowledge was the returning Crusaders, who described the practices of Arab physicians, who often dispensed psychoactive substances. For those who wished to study and administer medicines, it was crucial to avoid the clutches of the Inquisition by separating their activities from those of magicians. To this end, many moved to the newly formed universities, which developed, for instance, in Bologna (1088), Paris (1150), and Oxford (1167). The packaging of the medicines was altered so that they were dissimilar from those used in magic—pills and tinctures, for instance, sometimes replaced ointments.

Beginning in the 1500s, new ways of understanding medicines began to appear, in the form of the Medical Renaissance. A leader in the new movement was Paracelsus (1493-1541), who, though he taught briefly at the University of Basel, spent most of his career working as a traveling physician. He rejected the knowledge of the ancients as interpreted in academe and instead believed that there was much to be learned from the practical experience of apothecaries, barber-surgeons, and even sorcerers.

Instead of looking for panaceas that could cure all ills, he focused on finding medicines for specific diseases. He emphasized the importance of dose, which he thought crucial in separating medicines from poisons. In the course of the next two centuries the Medical Renaissance, with its emphasis on observation and experimentation, blossomed with the work of Ambrose Paré (1510-1590), a French physician who improved surgical methods and wound care; the Flemish anatomist Andreas Vesalius (1514-1564), whose drawings advanced the understanding of human anatomy; and the English physician William Harvey (1578-1657), who clarified the process of blood circulation. This new spirit provided the backdrop for the later discovery of new medicines.

The spirit set in motion during the Medical Renaissance ultimately resulted in a greater understanding of the pharmacological actions of the then-known drugs, as well as the appearance of synthetic compounds three centuries later. Notably among these in the nineteenth century were methylene blue, the first synthetic drug, which was used for malaria, and chloral hydrate, the first synthetic hypnotic. Even today, though, about one quarter of marketed drugs are still plant-derived.

Active substances from plants, then, have interacted with humans since the earliest time, and over the centuries, our understanding of them has evolved with our views of our place in the world (2). Turning to alkaloids in particular, the important thing to remember is that there are several thousand of them, with an incredible diversity of properties. Some, for instance strychnine, are lethally toxic and have no medicinal value. At another extreme are ones that continue to be used as effective treatments, such as ephedrine, given during surgical anesthesia to reduce excessive secretions; colchicine, for gout; physostigmine, for post-anesthesia care and as an antidote for overdoses of anticholinergics; and alkaloids from the Pacific yew, which are used in chemotherapy.

Psilocybin, a Drug Enforcement Administration class I scheduled drug and a hallucinogen closely related to ayahuasca (1) and DMT, has been granted "breakthrough therapy" status by the FDA for study in treatment-resistant depression (3). Indeed, for the last few years, there has been a movement to reconsider a possible role of psychedelic drugs, both natural (psilocybin, ayahuasca) and synthetic (such as MDMA) for a variety of conditions, also including anxiety disorders, addictive disorders, PTSD and end-of-life care (4).

Perhaps the best stance is awareness of the diversity of alkaloids and related substances, recognition that claims about them need to be studied carefully, and respect for their potential for both harm and good.

This article is adapted from the book Nepenthe's Children: The history of the discoveries of medicines for sleep and anesthesia.

References

1.   Mendelson, W.B.: Psychoactive plant extracts: A history of flower power, Part I. Psychology Today, September 16, 2020. https://www.psychologytoday.com/nz/blog/psychiatry-history/202009/psychoactive-plant-extracts

2. Mendelson, W.B.: Nepenthe’s Children: The history of the discoveries of medicines for sleep and anesthesia. Pythagoras Press, New York, 2020. https://www.goodreads.com/book/show/55230099-nepenthe-s-children

3.  Haridy, R.: Psychedelic psilocybin therapy for depression granted breakthrough therapy status by FDA. NewAtlas, October 24, 2018. https://newatlas.com/psilocybin-magic-mushrooms-depression-fda-breakthrough-therapy/56928/

4. Reiff, C.M. et al.: Psychedelics and psychedelic-assisted psychotherapy. Am. J. Psychiat. 177: 391-410, 2020. https://pubmed.ncbi.nlm.nih.gov/32098487/https://pubmed.ncbi.nlm.nih.gov/32098487/