Hoary thorn-apple

Datura metel is itself a crude antimuscarinic drug: its flower contains scopolamine, hyoscyamine and atropine, and the Hong Kong Hospital Authority puts the toxic dose at about 1 g of dried flower, a quarter of a fruit, or two seeds - against a medicinal flower dose of 0.3-0.6 g. Any co-prescribed antimuscarinic adds directly to that blockade and can convert a therapeutic dose into anticholinergic delirium, hyperthermia, urinary retention, ileus, tachyarrhythmia, seizure, coma or death. Mass poisonings from Datura-contaminated food and from ingestion of the plant are well documented, including fatalities confirmed by detection of atropine and scopolamine at autopsy.

Tricyclics, sedating antihistamines and the low-potency antipsychotics carry substantial intrinsic muscarinic antagonism. Adding the tropane alkaloids of Datura metel raises the total anticholinergic burden multiplicatively rather than additively at the level of clinical effect, because central muscarinic blockade produces delirium as a threshold phenomenon. Emergency series of Datura anticholinergic poisoning describe exactly this presentation from the plant alone; the elderly and those on polypharmacy are at greatest risk.

Cholinesterase inhibitors raise synaptic acetylcholine and so oppose the muscarinic blockade of scopolamine, hyoscyamine and atropine. In a patient taking donepezil for dementia or pyridostigmine for myasthenia gravis, Datura metel blunts or reverses the therapeutic effect and can precipitate a myasthenic crisis or an abrupt cognitive decline. The relationship runs the other way too: physostigmine, a tertiary-amine cholinesterase inhibitor that crosses the blood-brain barrier, is the specific antidote for the central anticholinergic delirium these alkaloids cause, and has been used in outbreak management of Datura poisoning.

Scopolamine is centrally sedating and amnestic in its own right, which is why the classical Chinese use of this flower was as a surgical anaesthetic taken with hot wine - an explicitly potentiated combination. Modern co-administration reproduces that: alcohol, benzodiazepines and opioids deepen the obtundation while the tropane alkaloids add delirium, hyperthermia and tachycardia, and the antimuscarinic slowing of gastric emptying can delay and then prolong absorption of the co-ingested drug. Recreational use of Datura, often with alcohol or cannabis, is a recurring cause of emergency presentations.

Datura metel has a long documented use as a smoked or inhaled drug for asthma and chronic bronchitis in both Chinese and Ayurvedic practice, and it is that antimuscarinic bronchodilation which the inhaled ipratropium and tiotropium class reproduces in a measured dose. Smoking or inhaling the plant delivers scopolamine and hyoscyamine systemically with no control of dose per puff, no standardisation of alkaloid content between plants or plant parts, and rapid onset, so anticholinergic delirium and tachycardia occur readily; the route is a recognised means of recreational abuse for exactly that reason. Layering it on a prescribed inhaled antimuscarinic compounds the systemic exposure.

The dried flowers of Datura metel and the non-toxic flowers of Campsis grandiflora resemble each other and are confused in the herbal trade. Review of Hong Kong pharmacovigilance data for 1989-2012 found that erroneous substitution accounted for roughly 41-42% of all herbal-medicine anticholinergic poisonings, with substitution of Flos Campsis by Flos Daturae Metelis the predominant single cause; the author concluded that preventing that one substitution would remove about 40% of such poisonings. Fatal cases have occurred.

In the same Hong Kong series, contamination of non-toxic herbs by tropane alkaloids - Rhizoma Atractylodis in particular, at 50% of cases in the 1989-2005 period - was the other predominant cause of herbal anticholinergic poisoning, alongside erroneous substitution. Datura seed and plant debris entering the supply chain at harvest or storage is the presumed source, mirroring the contaminated-food outbreaks documented for the genus, and it means a patient can receive a toxic tropane dose from a formula that contains no Datura on its label.