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.
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.
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 article 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 part 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.