Plant hallucinogens as magical medicines

"Were such things here as we do speak about?
Or have we eaten on the insane root
That takes the reason prisoner?"

Shakespeare, Macbeth I.iii

Thus wonders Banquo, who witnessed, together with Macbeth, the witches’ sabbath and the first foretelling of their future at the beginning of Shakespeare’s play. The apparitions were either true – or a hallucination. By giving these two options in 1606, at the height of the witch-hunt in Europe, Shakespeare not only provides a reasonable interpretation of the state of bewitchment, i.e. of delirious dreams, but also points to a possible cause of this insanity. There are poisonous plants that, upon contact or ingestion, cloud our mind and make us experience unreal sensations. As the deplorable persecution of witches tells us, most Europeans unfortunately lacked such botanical knowledge at that time

Plants of the family Solanaceae

The “insane root” may well have been mandrake (Mandragora officinarum), the most famous magic plant of the Mediterranean, sold at high prices in markets north of the Alps. Since the root can resemble a human body, mandrake was believed to contain a spirit that brings fortune and guards against evil those who own or carry the root. However, it was a dangerous business to dig up the plant, as it would issue a deadly shriek when taken from the earth. For this purpose, people were advised to fasten a dog to the half-exposed root and let the animal draw the plant out, a ritual that is often depicted in medieval books (left). Hundreds of years later, Goethe’s Mephistopheles makes fun of this superstition: “Da stehen sie umher und staunen, vertrauen nicht dem hohen Fund; der eine faselt von Alraunen, der andre von dem Schwarzen Hund.” (‘There they stand and marvel, not believing in the precious find; one drivels of mandrake, the other of the Black Dog.’ Goethe, Faust II, Act I).

Mandrake and other plants of the nightshade family (Solanaceae) contain alkaloids that block nerve impulses, which may lead to hallucinations. Although the cellular and molecular mechanism of action was only explained at the end of the 20th century, the pharmacological effects of these plants were already described by the Greco-Roman physicians Dioscurides (1st century AD) and Galenus (circa 129-199) and, from the 16th century onwards, by authors of herbal medicine books in local languages. The plants deadly nightshade (Atropa belladonna) and henbane (Hyoscyamus niger; below) are indigenous to middle and northern Europe and were therefore readily available for medicinal use or narcotic and poisonous abuse.

The physician Leonhart Fuchs explains in his New Kreüterbuch (printed in 1543) how to apply parts of these plants as sleeping agents and painkillers. In addition, he warns of their narcotic and toxic effects (see box). He also groups the plant thorn-apple (Datura stramonium; below), which had recently been brought to Europe by travellers from India or Mexico, botanically correctly with the nightshades, but admits his ignorance of its medicinal usage.

Witch ointments

If ever there were women experimenting with poisonous plants, and if ever they did anything other than use their knowledge to heal sick people who could not afford to (or maybe wisely choose not to) see a doctor, they may have used black or deadly nightshade and henbane as powerful ingredients in their medicines. Unfortunately, there are no direct sources for the recipes of witches’ concoctions. As is known from the literature condemning magic rituals, so-called ‘witch ointments’ were used to anoint a broomstick or a chair as a prerequisite for riding through the air and dancing at the witches’ sabbath (see box, image left). Such an ointment was reputedly given to the accused directly by the Devil or by an older woman who was already a member of the witches’ circle.

 

 

 

 

The recipes that have survived were written down by physicians. For example, Johannes Hartlieb, explaining the seven magic arts to the duke Johann of Brandenburg-Kulmbach in 1456, names six plants for the preparation of unguentum pharelis (see box). Although the plants were believed to possess magic powers, they are relatively harmless. Hartlieb had studied both theology and medicine, as was usual at the time, and the purpose of his writing is to prove that all witchcraft and magic is a lie. He therefore may have left out any narcotic ingredients on purpose.

Other physicians, however, most of them writing centuries later, name the plants of the family of nightshades along with the highly toxic wolfs-bane (Aconitum napellus), hemlock (Conium maculatum), and the sleep-inducing opium poppy (Papaver somniferum) as ingredients for witches’ medicines. They seem to have put together everything that was poisonous, and ethnologists of the 19th century, recreating witches’ ointments and applying them to their skin, indeed experienced disturbing hallucinations with all the side effects on the nervous system that a contemporary pharmacologist would expect.

Witches probably did not read the medical literature of their time, but we can safely assume that they knew of the hallucinogenic effects of the plants that grew in their neighbourhood. Henbane was already used by Germanic tribes to increase the intoxicating action of their ale. It was banned as an ingredient of beer in 1507/1516 in Bavaria, and after that its use in narcotic drinks was, at least in southern Germany, illegal. Deadly nightshade was also widely known. Its common name, ‘belladonna’, alludes to the practice of Italian Renaissance women who dilated their pupils with eye drops to make them look sexually attractive. If these women also ingested deadly nightshade, they would have experienced euphoria due to a stimulation of the central nervous system.

The pharmacology of nightshade plants

Today the action of deadly nightshade, henbane, and thorn-apple is understood in molecular detail. They all contain the alkaloids atropine and scopolamine, two closely related substances which interfere with the parasympathetic nervous system. Under parasympathetic stimulation, the heart-beat slows, smooth muscles (the involuntary muscles of inner organs) contract, digestion juices flow, and glands produce watery fluids (saliva, tears, bronchial mucous; Table 1). The neurotransmitter acetylcholine couples these nerve signals to the effector cells by activating muscarinic receptors, which in turn trigger changes within the cell that are related to the physiological response of the organ. For example, the intracellular Ca²⁺ concentration increases, which is necessary for muscle contraction and secretion.

Atropine and scopolamine chemically resemble the neurotransmitter acetylcholine. They also bind to muscarinic receptors but fail to stimulate the cell (i.e., act as antagonists). Thus, nerve transmission is blocked. Since acetylcholine is an important neurotransmitter in the brain as well, antagonism of muscarinic receptors also causes central effects. At low doses (0.5-1 mg), atropine leads to mild excitation, whereas scopolamine is responsible for drowsiness, fatigue, dreamless sleep and euphoria. The ingestion of higher doses causes restlessness and hallucinations. Poisoning with about 10 mg of atropine (less for children) leads to central depression of life functions, which may progress to coma, circulatory collapse and respiratory failure (Table 1).

Medical use of atropine and related drugs

Atropine, scopolamine and synthetic analogues are still used as medicines, mainly to inhibit the effects of the parasympathetic nervous system. In order to prevent disturbing side effects, either the substances are applied locally (eye drops for the examination of the retina, inhalation for respiratory diseases), or specific receptor blockers are developed (tablets blocking gastric acid secretion to treat peptic and duodenal ulcers; see box).

Blocking the action of acetylcholine also improves the motion disorder Parkinsons' disease. However, since the introduction of more specific drugs acting on dopamine pathways, atropine derivatives are used only to treat early symptoms or as additional therapy.

The most important use of atropine today is as an antidote for poisoning by the alkaloid muscarine (present in certain mushrooms) or by organophosphate insecticides. Both substances overstimulate the parasympathetic system. To antagonise toxic effects, atropine is injected for up to 48 hours. The doctor monitors the patient closely, giving a new injection as soon as muscarinic symptoms reappear, but not too early so as to prevent atropine toxicity.

Conclusion

Today, we have difficulties understanding the deep, sincere belief in witchcraft and in the reality of magic that governed Europe for centuries. It is even more puzzling to realise that the heyday of witch-hunting happened in the 16th and 17th centuries, a time when the Sun was put in the centre of the universe and Renaissance artists drew muscular, naked human bodies right in the heart of the Vatican. Unfortunately, most of our scientist colleagues of 500 years ago did not speak up and solve the mysteries of night flights on broomsticks, although they – like Shakespeare – were almost certainly familiar with the hallucinogenic effects of some plants. But why did the ‘witches’ themselves not explain where their dreams came from? I suspect that very few of those who were accused, tortured and burnt had actually experienced hallucinations caused by toxic plants – or indeed by anything else. In the face of the estimated 60,000 victims in Europe, one could believe that the Devil himself had had a hand in it.