by Autumn Roberts

Atropa belladonna L. has a long and fascinating history as a medicine, a poison, and even a component of magic spells. A subshrub that grows across the world, it is counted as one of the most poisonous plants known in the 21^st century. Due to its high toxicity it is not, presumably, a desirable inhabitant of a garden but as A. belladonna will grow naturally in open areas it may be found unexpectedly. For decades it has been used by poisoners, by witches, and even by women seeking to enhance their appearance. Despite its deadly reputation, and rightly so, A. belladonna has also demonstrated therapeutic properties due to the alkaloids present within, demonstrating effective in treating asthma and skin wounds. These implications hold great promise for future study of this plant with such a devious past.

Atropa belladonna

Atropa belladonna L. is a member of the Solanaceae, a branching herbaceous perennial plant that is native to North and Western Africa, Turkey, Europe, and Iran (Kwakye, et al., 2018). Common names for the plant include deadly nightshade, devil’s berries, and beautiful death (Lackovic, 2017).

A. belladonna grows as a subshrub with thin and brittle leaves of light- to olive-green colour. The bell-shaped flowers consist of five small, purple, reflexed lobes, and its berries ripen to a shiny black (Herbal Medicines Compendium, 2014).  In Britain A. belladonna is commonly found growing on calcareous soils, disturbed ground, hedgerows, along paths and banks, and open woodland (Woodland Trust, 2016). In the Bloomsbury area it can be found in wastelands, open spaces, and on grids around trees along the roads.

Members of the Solanaceae are known to produce a myriad of alkaloids, and A. belladonna is no exception. It produces tropane alkaloids such as atropine, hyoscyamine, and scopolamine that function as a chemical defence when the plant is under stress. These and up to twenty different tropane alkaloids are present throughout the entire plant and hold therapeutic significance – treating motion sickness, gastrointestinal disturbances, and Parkinson’s disease (Kwakye, et al., 2018). However, because of these alkaloids A. belladonna is one of the most toxic plants in the Eastern Hemisphere, with the ability to poison at very small doses (Kohnen-Johannsen & Kayser, 2019).

A wicked past – the history and legends of Atropa

The initial discovery of A. belladonna is difficult to pin down, as it can be traced to over 2000 years ago. Many records detail its use in the Ancient Greek, Byzantine, and Medieval periods primarily as a potent poison, but also as a hallucinogenic, sedative, and pain-reliever (Mann, 1994; Muller, 1998; Ramoutsaki, et al., 2002). Some sources detail its use as far back as the Mesopotamian era, yet with such a broad timeline there is little available that narrows this period down (Carod-Artal, 2013).

Regardless of this uncertainty, most historical mentions of Atropa relate to its use as a potent poison. Emperors Augustus and Claudius of Rome were both supposedly felled on instruction of their wives by concoctions of the plant (Wink, 1998). King Duncan I of Scotland arranged for the Norwegian King Sueno and his troops to be poisoned with A. belladonna through infused wine and ale (Buchanan, 1733). It was only from the 16^th century that British apothecaries began to study deadly nightshade outside of this purpose (Kwakye, et al., 2018).

However, according to folk lore and historical accounts some had already discovered another use for Atropa belladonna. Witches would use the plant alongside henbane, opium, and other poisonous plants to concoct an ointment that would allow them to fly and gather with others of their ilk (Muller, 1998). This ointment was considered to be dark magic, no likely helped in reputation by its hallucinogenic effects, and yet constituted a means of entertainment and enjoyment for poorer individuals. After use one was said to experience festivities, flights through the air, dancing, even transformation into an animal. These hallucinations would be so vivid that when a person awoke they would be fully convinced their experience was real. In Magia Naturalis the use of Atropa belladonna is described to induce delirium at banquets for similar entertainment (Mann, 1994). However, with the wide variation in historic accounts of witchcraft it remains unclear how much of this can be substantiated in some detail, and how much may be derived from the inquisition’s claims against alleged witches.

During the Renaissance (14^th to 17^th century) another use for A. belladonna was employed in Italy. Women would apply the juice of the berries to their eyes, causing a dilation of the pupils to appear attractive (Ulbricht, et al., 2004). This effect is due to the alkaloids within the berries acting as muscarinic antagonists, blocking receptors in the muscles of the eyes and causing the pupils to expand. Unfortunately, this also led to an inability to focus on nearby objects, visual distortions, and eventual blindness. While the practice flared up again in Paris during the late 19^th and early 20^th century, due to these effects it eventually died out (Hardman, et al., 2011).

The species name belladonna is most commonly accepted to have originated from this use – belladonna meaning “beautiful lady”. However, other old legends state that the name refers to the way in which the plant takes on the form of an enchantress whom it is dangerous to look upon. Some scholars have suggested that the name is derived from Bellona, the Roman goddess of war, as priests may have drunk an infusion of the plant before invoking her (Campbell, 2005).

The full name Atropa belladonna was first given to the plant by Carl Linnaeus (1707-1778), a Swedish botanist who published Species Plantarum in 1753.  “Atropa” takes from the Greek mythos of the Fates, or Moirai, who controlled the threads of life of each person – Clotho spinds the threas, Lachesis measures and allots the length of life, and Atropos severs the thread.

During the 19^th century the plant was eventually incorporated into non-FDA approved, over-the-counter drugs as its therapeutic capabilities came to light.Nightshade was employed for numerous ailments: as a component of cough-cold products, a sedative for whooping cough, and an analgesic in motion sickness and Parkinson’s (Lee, 2007).

The chemistry and toxicology

Alkaloids are the primary constituents of A. belladonna L., characterised by their basic nitrogen atom content. They are organic esters formed from tropic acid and an organic base (Hodgson, 2012), and function as the plant’s chemical defense in conditions of stress. While all parts of the plant contain alkaloids, the highest content is within the ripe fruit and green leaves. The leaves reach a maximum content of alkaloids when the plant is budding and flowering.

The effects of deadly nightshade are mainly attributed to three different alkaloids – hyoscyamine, scopolamine, and atropine. Atropine is a mixture of d-hyoscyamine and l-hyoscyamine, referring to the chirality of the molecules (Wink, 1998). Its isolation from A. belladonna and its chemical properties were published by P. L. Geiger and O. Hesse in 1833. All three alkaloids are antimuscarinic agents – they competitively inhibit muscarinic acetylcholine receptors (mAChRs) by binding to them and blocking the ability of acetylcholine (Ach) to do the same (Kohnen-Johannsen & Kayser, 2019). mAChRs belong to a class of metabotropic receptor that use G proteins as a signalling mechanism. Their competitive inhibition prevents the formation of G protein-coupled receptor complexes that activate internal signal transduction pathways, thus inhibiting cellular responses across both the central nervous system and autonomic nervous system (Bousta, et al., 2001). In the parasympathetic system this can affect smooth and cardiac muscle, exocrine glands, and intramural neurons.

Because of this effect, atropine, hyoscyamine, and scopolamine are anticholinergics. Their action can induce multiple effects in the body; they act as hallucinogenics, amnestics, sedatives, and anti-emetics to name a few effects (Beyer, et al., 2009). Compared to scopolamine, atropine has a more prolonged effect on the heart, intestine, and bronchial muscles due to its possession of a tertiary amine. Being non-ionised, it enables easy passage across the blood-brain barrier (BBB) allowing for a more profound effect (Ulbricht, et al., 2004). The GI tract and salivary glands are also affected by these alkaloids, undergoing a decrease in sympathetic effects.

It is this antimuscarinic and anticholinergic activity that make A. belladonna incredibly toxic. With ingestion greater than 1.5mg, toxicity usually occurs between 30 – 60 minutes. Overdose causes a myriad of effects. In the central nervous system, those poisoned may experience memory distortion, hallucinations, cardiovascular and respiratory failure. Peripheral effects include flushed skin, dryness of mouth, fever, hypertension, and mydriasis (Beyer, et al., 2009).

As children especially may be attracted to the blue berries of the plant, it is vital to take extra precautions around such areas that may have deadly nightshade present. Because this plant is incredibly toxic it is critical that those who have accidentally ingested any amount seek the proper medical attention. If you or someone you know has ingested A. belladonna call emergency services immediately on 999 (UK only; for other countries call your local emergency services number).

Mystical medicine – the modern applications of A. belladonna

As historical use can attest, there is a potential use for the therapeutic application of deadly nightshade despite its high toxicity. At low doses the plant has been studied in the context of treating several ailments.

Skin wound healing involves multiple types of white blood cell, several of which have been proven to possess muscarinic receptors (Kurzen, et al., 2004). Due to this, A. belladonna has been studied for wound healing properties in male rats (Gal, et al., 2009). Differentiation, proliferation, and cell survival of keratinocytes and fibroblasts were measured after application of an A. belladonna extract. Wounds with an aqueous extract applied demonstrated reduced inflammation and accelerated collagen formation (Gal, et al., 2009), replicated by Udupa et al. (2015).

It has also proven effective in the treatment of dengue infection, a mosquito-borne viral disease that can cause vomiting, headaches, skin rashes, as well as potentially serious haemorrhages. A low dose of A. belladonna applied in vivo can alleviate redness, pain, and the headaches associated with dengue (Bousta, et al., 2001), and has also shown to decrease other flaviviral infections (Saxena, et al., 2017).

Atropa belladonna is considered a key herb in the treatment of asthma due to its atropine content (Graham & Blaiss, 2000). This draws on its a history of treating respiratory conditions in the early 20^th century, through inhalation of the fumes from burnt plants (Ziment, 1996). In vivo studies have demonstrated the ability of atropine to reverse bronchoconstrictrion, however this is dependent on the route of administration – inhalation being the most effective (Moulton & Fryer, 2010).

Atropine is also the mainstay in treatment of acute organophosphorus (OP) poisoning, as the toxicity is due to the over-activation of cholinergic receptors throughout the body (through excess ACh). Atropine antagonises the parasympathetic effects of ACh and reverses life-threatening features includeing bronchospasm, hypotension, and central respiratory depression (Paudyal, 2007).

Final thoughts

The ever-increasing knowledge on A. belladonna has allowed us to devise many important therapeutic treatments for multiple medical conditions, and this well of value may continue to grow. Its fascinating and deadly history in both myth and medicine has made it one of the most well known poisonous plants across the globe, and while this title is certain to remain it may also be one day known as a vital source of valuable medicinal traits. However, its reputation must always be remembered and cautioned given how quick it can be to poison, as it is truly a species of nightshade worthy of the title ‘deadly’.

Disclaimer:
This essay in no way serves as guidance for the use of Atropa belladonna. This information is intended for educational purposes only and should not be considered as a recommendation or an endorsement of any particular medical or health treatment. The use of any such product should be based on the appropriate advice and prescription of health care professionals, or based on the information available for THR products.

© 2019 Autumn Roberts. All rights reserved.

About the Author:

Autumn Roberts is an MSc student in Medicinal Natural Products and Phytochemistry at the UCL School of Pharmacy, University of London (2018-2019)

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