Psychoactive Plant Extracts

Ayahuasca brewing.

Source: 'Apollo' in Wikimedia Commons/Public Domain

Potent plant extracts have been in the news in recent days. In one case, Axios reported that President Trump expressed enthusiasm after an Oval Office presentation on oleandrin as a treatment for COVID-19 (1). In another, The New York Times described a resort-like setting in Costa Rica to which sufferers from PTSD travel to seek relief by taking the hallucinogenic substance ayahuasca (2). Both substances are unproven, and not FDA-sanctioned as treatments. Oleandrin, a cardiac glycoside derived from the oleander plant (Nerium oleander) is very toxic, and can be lethal in very small amounts. Ayahuasca is made from a combination of the Banisteriopsis caapi vine and the Psychotria viridis bush, and has been imbibed for centuries as a spiritual medicine among indigenous peoples in the Amazon rainforests. Its active ingredient is related to the psychedelic plant alkaloid N,N-Dimethyltryptamine (DMT). While the substances we have described here sound fairly exotic, there are many alkaloids with which we are much more familiar, including caffeine, nicotine, morphine, and cocaine.

To give perspective on news articles about plant derivatives proposed as medicines or known to us as substances of abuse, it might be worthwhile to look back at where they come from, emphasizing those which are psychoactive. In this first post in a two-part series, we will look at how they affected, and were understood, by humans from their earliest days through the classical period in Greece. In the next post we will see how these ideas evolved from then until the present day, and the renewed interest in psychedelic substances in psychiatry.

The origins of alkaloids spring from the history of how plants and the species which prey upon them, including bacteria, insects or animals, evolved together. Typically, this happened by one developing protective measures, then the other forming countermeasures, followed by a new protective adaptation in the first one, in an ongoing cycle. In this process by which two interacting species produce genetic change in each other, known as coevolution, a plant might defend itself, for instance, by growing thorns. If animals find ways of dealing with them, another plant response can be producing alkaloids, nitrogen-containing compounds with various physiologic functions including acting as ‘chemical thorns,’ with unpleasant smell or taste, or which produce toxicity. Alternatively, in responding to mammals, plants may fabricate chemicals which lower the ability for vigilance or defense due to intoxication or sedation.

Our ancestors, then, were faced with a number of alkaloids and other substances produced by plants or fungi, which could affect them in many ways. Hemp was described in China by 4000 BC. The poppy appeared in Lower Mesopotamia (Southwest Asia), and Sumerians referred to it as early as 3400 BC as Hul Gil, the ‘joy plant.’ Solanaceous plants from the nightshade family, containing potent alkaloids such as henbane, mandrake, and datura were recognized in the Middle and Far East as well as Europe.

Many of these substances were incorporated into the practice of primitive religions. In hunter-gatherer societies, affirmation of membership in a group was reinforced by ingesting plant products supplied by a shaman, in which inebriation resulted in experiences which seemed to give knowledge of one’s place in the world. Diseases were looked upon as punishments or signs of impurity, and one way of responding was to transfer them to a sacrificial person or animal.

Some historians have suggested that the use of drugs as well became entwined with the practice of sacrifice. The Greek word phármakon, from which we derive the words ‘pharmacy’ and ‘pharmacology' resembles pharmakós, referring to the practice of transferring guilt to a scapegoat figure. In a festival of Apollo in ancient Greece honoring the first fruits and wheat crop of the year, an exceptionally ugly or deformed person was selected as the pharmakoi. They were first fed well, then thrashed with vegetation (thus shifting any uncleanliness in the crop to them), including ritualistically whipping the genitals seven times with fig branches. They were then run out of town, or worse. Even beyond the association of sacrifice, we still see the origins involving magic in our words for medicines and pharmacists. The Greek word phármakon suggests not only to a drug and sacrifice, but also charms, philters, or enchantment, and a pharmakeus was “a preparer of drugs, a poisoner, a sorcerer." (3)

In Greece during the Age of Pericles (495-429 BC), healing, magic, and medicines remained interconnected (3). In the temples of Asclepius, supplicants were bathed and purified, then ingested substances, presumably hallucinogens, which caused them to fall into a state of ‘temple sleep.’ They would then experience healing dreams, in which Asclepius or his daughters would advise them on how to get better. The oracle at the Temple of Apollo at Delphi would breathe vapors from underground, and chew on oleander leaves containing conessine, a steroid histamine antagonist, as well as oleandrin. In the resultant trance-like condition, the oracle would make prophecies, which rulers from all of Greece valued greatly.

The association of alkaloids with witchcraft was seen In Homer’s Odyssey, in which the goddess/sorceress Circe transformed Odysseus’ men into swine after drinking derivatives of mandrake and datura. She also poisoned the water in which a romantic rival bathed, metamorphosing her into a very unlovely shape, not to mention changing Picus, an Italian king who was immune to her charms, into a woodpecker. She had a reputation as a polypharmakos, one who knows many drugs, and all in all, a person not to be trifled with.

It was during this time that the first steps toward extricating the notions of disease and medicines from magic began. As we will see in the next post, it started with the physician Hippocrates of Kos, who argued that diseases were not punishments from on high, and that medicines could be understood by their physical properties and how they interacted with bodily processes.

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