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Datura stramonium intake: a report on three cases.

Datura stramonium is a flowering plant with hallucinogenic properties belonging to the Solanaceae family (Angiospermae Dicotiledoni). The Solanaceae family is of great economic importance because many of its species originating from the Americas have been highly cultivated over the years (Mino et al. 2005). Other plants with psychoactive properties of the same family are mandrake (Mandrogora officinarum), belladonna (Atropa belladonna), henbane (Hyoscyamus niger), and tobacco (Nicotiana tabacum). The family also includes such common edible plants as the tomato (Lycopersicon esculentum), pepper (Capsicum annuum) and potato (Solanum tuberosum). In particular, the potato is one of over 900 cultivated species belonging to the genus Solanum, which also contains the eggplant (Solanum melogena) (Friedman 2005). The Datura genus also includes Datura inoxia, Datura metel, Datura arborea and Datura stramonium, which are generally referred to as D. stramoniun. In Italy the latter is commonly known as erba del diavolo (devil's grass), erba delle streghe (witch's grass), noce spinosa (prickly nut), erba maga (magic grass), erba dei ladri (thief's grass), or erba metella (metel grass). In the U.S. and Europe the D. stramonium plant is known as jimson weed, loco weed, angel's trumpet, devil's trumpet, witch's thimble, devil 's apple, thorn apple, stinkweed, mad apple, devil 's weed, malpitte and green dragon (Beno, Osterhoudt & Meaney 2004; Shervette et al. 1979). The most common name is jimson weed, a shortened version of "Jamestown weed." It was named after the first recorded accidental ingestion, which occurred in Jamestown, Virginia (USA), in 1676 (Beno et al. 2004; Shervette et al. 1979). There is evidence to suggest that the plant commonly known as moonflower is instead Datura inoxia, based on the patient's description and clinical presentation (DeFrates et al. 2005). D. stramonium grows in temperate and subtropical regions and can be found throughout Asia, Europe, and the Americas. Its origin is uncertain and its properties were already well known to the natives ofboth the Old and the New Worlds. This species can now be found all over Italy, from the plains to the submountainous areas where it grows sporadically on wasteland, remaining close to ruins and the edges of roads. In our local area, around Naples, the plant is known to farmers by the name cardone. D. stramonium is an annual herbaceous plant with a fusiform tap root, an upright stem with ramose bifurcations and a height that can sometimes exceed one meter. Its leaves are ovate, with an oval plate and jagged-toothed margin. Its blossom is white or purple, singular, 8-10 cm long with a pungent odor. Its cup, which is slightly swollen underneath, is divided into five lanceolatus pointed lobes (Figure 1A). Its fruit is a large, prickly, four-celled ovate capsule. The seed capsules are typically the size of a walnut and are covered in thorns (hence the name "thorny nut"); it contains numerous black and reniform seeds, about 3 mm in length (Figure 1B). The flowering season occurs between July and October; its flowers remain closed during the day and then open completely at night, giving off an intense and penetrating scent that attracts night butterflies; in fact, pollination is entomogama (via pronubial insects). The names "devil's grass" or "witchgrass" refer to its narcotic, sedative and hallucinogenic properties that have been used for therapeutic purposes or in rituals by spiritual shamans of many Indian tribes, and by the Druids and Europeans in the past (Haas 1995). The generic name Datura is taken from tatorha, an ancient Arabic word, while the name of the species Stramonium may originate from the Greek word strychnos = nightshade and manikos = mad, recalling the toxicity of the plant on the central nervous system (CNS).

[FIGURE 1 OMITTED]

D. stramonium, similar to the other species D. inoxia and D. metel, is a highly poisonous plant due to a high concentration of potent and toxic alkaloids such as hyoscine (also called scopolamine), hyoscyamine and atropine, commonly known as "daturines" (Figure 2). These alkaloids are present in varying concentrations in all plant tissues, mainly in the seeds (Patterson & O'Hagan 2002; Miraldi et al. 200 I). The variation in concentration of alkaloids depends on the stage of development of the plant and the environmental conditions in which it has grown. There is a drop in alkaloid concentration during the day and an increase at night, as well as a drop following a rainy period as opposed to clear weather (Miraldi et al. 200 I). D. stramonium also contains malic acid, tannin, rubber, fats, calcium and potassium salts (Patterson & O'Hagan 2002). The plant is used in the pharmaceutical industry for its anti-inflammatory, antiasthmatic, antispasmodic and antihelmintic properties (Mino et al. 2005). Furthermore, it has been shown that D. stramonium plant extracts are efficacious against dyspnea, nervous cough, pertussis, asthma, enuresis, epilepsy and neuralgia. In addition, it has hypnotic, antidandruff, midriatic, narcotic, analgesic and anaesthetic properties. A common chemical property of D. stramonium alkaloids is a methylated nitrogen atom N-CH3 atone end of the molecule (Figure 2). This chemical structure is also found in acetylcholine, which is the main neurotransmitter projecting impulses from the brain to neuromuscular junctions. Therefore, the properties of D. stramonium could be due to interference with acetylcholine receptors, perhaps by competing with them at the synaptic junctions, thus blocking or inhibiting neurotransmission. As previously mentioned, all parts of D. stramonium are poisonous. Both fresh and dried leaves and seeds are highly toxic and sometimes lethal. Indeed, depending on the amount consumed, several D. stramonium alkaloids may have synergistic effects resulting in memory loss, stupor, amnesia, euphoria, hallucinations, and coma (Boumba et al. 2004). The most popular way to ingest this plant is to chew the seeds. However, other methods of consumption include brews prepared by boiling fresh or dried leaves or the smoking of homemade cigarettes. The effects of D. stramonium intake include elation, narcosis and perceptive distortion and even the complete loss of any sense of reality. Hallucinations may appear so real that a person may see and interact with imaginary objects or persons. Such effects usually appear 30 to 45 minutes after oral consumption and last from five hours to several days. Other symptoms of intoxication include mydriasis, cycloplegia, hot flashes, warm and dry skin, dry mouth, urinary retention, tachycardia, hyper or hypotension, delirium, jerky and/or myoclonic movements, choreoathetosis, hyperthermia, coma, respiratory arrest, CNS stimulation followed by depression and in rare cases even seizures. The onset of symptoms occurs within 30 to 60 minutes after smoking leaves or drinking a brew and one to four hours after ingesting plant material or seeds. Initial symptoms include first a dry mouth and then pupil dilatation. These symptoms typically last between 24 to 48 hours because of delayed gastrointestinal motility; however symptoms have been reported to last for up to one to two weeks. Although poisoning may lead to fatal medullary paralysis, arrhythmias and cardiovascular collapse, deaths relating to jimson weed are mainly the result of impaired judgment and coordination resulting in risky behavior associated with accidental death.

[FIGURE 2 OMITTED]

Between 5% and 8% of those trying D. stramonium (depending on the ingested dose), some of whom are simply curious consumers who want to experience the effects it can generate, have died simply by using a cheap infusion made with leaves of D. stramonium (Parissis et al. 2003). This is mainly due to the narrow range between the active and lethal dose of D. stramonium and the consequent high risk of serious toxic effects after consumption (DeFrates et al. 2005).

CASE REPORTS

This article describes three cases of D. stramonium intake, which took place in a residential substance abuse treatment center in a rural location. We have given the three male subjects imaginary names in order to protect their identity and privacy.

The first one, Max, 32 years old, had been an addict for 16 years and had a history of multiple drug abuse: heroin, cocaine, and especially high doses of benzodiazepines (self-administration of lormetazepam iv). During the early part of his addiction he lived with his family, but subsequently left home and went to live on the streets with no fixed abode. For about 15 consecutive months, he lived in a residential substance abuse treatment center, although he had previously spent periods of his addict life in other residential substance abuse treatment centers. There, during the 15 months, he was detoxified from his primary addiction to heroin and benzodiazepines (BDZ) and stayed drug-free for one year. Max had never taken D. stramonium previously.

The second patient, Luke, 24 years old, had been an addict for six years, during which time he lived with his family. He was a habitual heroin consumer and occasionally used cocaine. Luke has been living in a residential substance abuse treatment center for about six months, where he has been detoxified from his primary addiction to heroin. He has been drug-free for four months. Luke had never taken D. stramonium previously.

The third patient, Mario, 33 years old, has been a heroin, cocaine and BDZ iv addict for 15 years. He spent about three years in a residential substance abuse treatment center, alternating with periods of imprisonment. Mario had also been detoxified from his primary addiction to heroin and has been drug-free for three years. Unlike the other two patients, Mario had already taken D. stramonium several times (seed and leaf infusions of the plant).

In all three cases, Max, Luke and Mario took D. stramonium on two nonconsecutive days. On the first day, they ingested considerable quantities of seeds in one single swallow. No symptoms were noted, apart from Max, who met a physician by chance; the physician noticed a suspicious dilation of the pupils and requested a toxicological examination for the detection of urine metabolites of cocaine, amphetamines, [[DELTA].sup.9]-tetrahydrocannabinol and benzodiazepine. However, the drug test produced negative results. On the second day, the patients took D. stramonium seeds in two separate administrations, one late morning and the other in the evening. Mario was the only one who was already familiar with the substance and so he took the lowest dose, while Luke and Max took a considerable amount of seeds. After two hours, Max and Luke reported a sudden surge in strength and energy, with some aggressive compulsions towards their peers. The symptoms became apparent initially in one of the men and then 30 minutes later in the other. They subsequently appeared to be confused and showed signs of organized and poorly structured delirium. Furthermore, they appeared temporospatially disoriented; elation and nonharmonized perceptive phenomena were noted. Moreover, Max showed the most serious psychiatric symptoms. A physician was contacted, who rushed to the site and examined the two patients who had peripheral anticholinergic symptoms, such as dilated and lazy pupils, dried mucous membranes, redness, tachycardia and CNS symptoms such as agitation, confusion, disorientation and hallucinations. Vital signs were taken and Luke's body temperature was 37.2[degrees]C, his blood pressure was 130/70 mmHg and he had a pulse rate of 106 beats/min. Max's vital signs were: body temperature of 37.4[degrees]C, blood pressure of 135/75 mmHg and a pulse rate of 109 beats/min. In both men dry mucous membranes, dry and flushed skin, decreased bowel sounds, urinary retention, mydriasis and cycloplegia were noted. They were treated with a slow iv infusion of 1 mg/min diazepam (10 mg/ in 10 ml of saline in 10 min) since the rapid injection of 10 mg of diazepam or the use of veins with too small a lumen carries certain risks. Indeed it is important that iv injection should be directly into a large lumen vessel, such as an antecubital vein and the ampul solution should be administered slowly (a dose of 5 mg/min is recommended). Within a few minutes, the sedative effect of BDZ became evident. During the following night, (after about six hours) diazepam administration was repeated (an oral dose of 5 mg) and the morning after, only a moderate disperceptive state remained. The central and peripheral symptoms disappeared without leaving any consequences after 10pm. However, there have been cases in which symptoms have lasted for several days. This pharmacokinetic difference could be related both to the dose and individual characteristics of the addict.

The following morning, blood samples were taken from the two patients (Max and Luke). These exams showed a certain level of putative liver toxicity. A few days later, it was discovered that Mario had also taken D. stramonium and, unlike the other two men, he had not shown any apparent symptoms. Indeed, since Mario was a more expert user of D. stramonium, he had taken a lower dose of the drug and was therefore able to mask his disperceptive state with greater self-control, as he reported during the interview that took place three days later. A blood sample from Mario was also analyzed but no pathological changes were found in this case. Evidence exists of acute toxic hepatitis cases (Ertekin, Selimoglu & Altinkaynak 2005), probably induced by tannic acid contained in the plant.

DISCUSSION

Datura stramonium is a hallucinogenic plant that causes serious poisoning, as already reported (Arnett 1995). To date, there is a growing trend among the younger generations to experiment with this plant through recreational drug abuse. Young people are particularly susceptible to D. stramonium abuse because, unlike many other illicit drugs, it is readily available and costs nothing to obtain. For this reason, emergency physicians need to be aware of the potential sources of plant hallucinogens and the spectrum of its toxic effects such as headache, dry throat, mydriasis, loss of motor control, blurred vision, increased heart rate and body temperature. Paralysis and respiratory blockade can result in death. All parts of the D. stramonium are toxic as they contain the belladonna alkaloids: atropine, L-hyoscyamine and L-scopolamine. Atropine and scopolamine are chemically similar to acetylcholine. Therefore they also bind to muscarinic receptors but fail to stimulate these receptors and act as antagonists by blocking these receptors to acetylcholine. Nerve transmission is therefore blocked. Since acetylcholine is also an important neurotransmitter in the brain, antagonism of muscarinic receptors also causes CNS effects. At low doses (0.5-1 mg), atropine leads to mild excitation, whereas scopolamine leads to drowsiness, fatigue, dreamless sleep and euphoria. The ingestion of higher doses causes restlessness and hallucinations. Poisoning with about I 0 mg of atropine (less for children) leads to CNS depression of vital functions, which may progress to coma, circulatory collapse and respiratory failure. The highest concentration of alkaloids is found in the D. stramonium seed (equivalent to 0.1 mg of atropine per seed). Chewing the seeds releases the alkaloids from their protective coating (Ellenhorn 1997).

Cases demonstrating the hallucinogenic properties of D. stramonium have frequently been described. Its effects at high doses can include incoherent speech, disorientation, delusions, dreamlike frenzy, often followed by depression and amnesia during the period of intoxication. In southern Canada and the United States, most reports of D. stramonium abuse involve cases occurring over a prolonged period (Spina & Taddei 2007; Forrester 2006). There is evidence of epidemic outbreaks of plant ingestion, where several patients present with D. stramonium symptoms within a short period of time, such as one series of 11 teenagers who came to a particular emergency room over a four-hour period (Tiongson & Salen 1998). In France, the number of hospitalizations for acute D. stramonioum poisoning has increased rapidly, as indicated by the statistics of the Bordeaux Poison Center (14 hospitalizations for voluntary poisonings with D. stramonium in 2002, compared with five in 200 1; Arouko et al. 2003). More recently, other cases of adolescents admitted to hospitals (de Germond-Burquier, Narring & Broers 2008; Montcriol et al. 2007) after voluntary D. stramonium intoxication have been reported. In Italy, there have been some significant cases of D. stramonium poisoning. In one particular case in Lucca (Italy), six minors were treated in hospital for serious poisoning after taking a herbal infusion of D. stramonium. In another incident more recently in Livorno (Italy), a boy risked his life because of a D. stramonium infusion (Pichini 201 0). The boy, who had just turned eighteen, was admitted to the hospital emergency room. He was not making any sense and before leaving his friends in a rush said that he had "drunk an infusion." Doctors had to fight to save his life. He did not seem to be prey to the usual drugs, even the best-known chemical ones. He was admitted to the department of emergency medicine; physicians contacted the Poison Center of the Niguarda Hospital and on the basis of his symptoms they were able to diagnose D. stramonium intoxication. Six years ago, in Viareggio, two boys risked death after taking an infusion of D. stramonium seeds (Pichini 2010). A survey has been carried out recently in Campania (Italy) and it has been found D. stramonium intake is becoming much more popular among local consumers (Pichini 2010).

D. stramonium intake follows a particular ritual; it is usually taken as a group, where it is agreed that some members of the group (two or three) should not take the plant in order to remain lucid and to watch the other members of the group who take the plant extracts. This proves that the phenomenon is probably more widespread than one might imagine.

In conclusion the absence of any legislation contributes to open D. stramonium abuse and makes this plant a tempting choice for those who abuse psychoactive substances. Consequently, it is extremely important to be able to recognize the effects and symptoms related to the intake of D. stramonium early on in order to help diagnose intoxication correctly (Robot et al. 1995). Indeed, the plant can be extremely dangerous because of its wide availability (Arouko et al. 2003; Oberndorfer et al. 2002). It would therefore be useful to know how to deal with such an emergency.

http://dx.doi.org/10.1080/02791072.2010.10400713

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Parissis, D.; Mellidis, C.; Boutis, A.; Apostolidis, K.; Ignatiadis, M.; Kiosses, V. & Milonas, I. 2003. Neurological findings in a case of coma secondary to Datura stramonium poisoning. European Journal of Neurology 10: 745-46.

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Luigi Stella, M.D., Ph.D. *; Maria Redenta Vitelli, M.D., Ph.D. **; Enza Palazzo, Ph.D. **; Patrizia Oliva, M.D., Ph.D. ***; Vito De Novellis, M.D., Ph.D. *; Annalisa Capuano, M.D. *; Maria Antonietta Scafuro, M.D. *; Liberato Berrino, M.D. *; Francesco Rossi, M.D. * & Sabatino Maione, M.D., Ph.D. *

([dagger]) Written informed consent was obtained from the patients for publication of these case reports. The authors would like to thank the psychologist, Dr. A. Mautone, and nurse, Miss C. Manzo, without whose selfless contributions of time and energy this work could not have been accomplished. We are also grateful to Dr. Siobhan Marie Nott for proofreading the paper.

* Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Faculty of Medicine and Surgery, Second University of Naples; Public Service of Addiction of A.S.L. NA 3 Sud Castellammare di Stabia, Naples, Italy.

** Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Faculty of Medicine and Surgery, Second University of Naples, Naples, Italy.

*** Public Service of Addiction of A.S.L. SA Salerno, Italy.

Please address correspondence and reprint requests to Enza Palazzo, Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Faculty of Medicine and Surgery, Second University of Naples, Via Costantinopoli, 16-80138 Naples, Italy. Phone: +39 081-5665880; fax: +39 081-5667503; email: enza.palazzo@unina2.it
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Author:Stella, Luigi; Vitelli, Maria Redenta; Palazzo, Enza; Oliva, Patrizia; De Novellis, Vito; Capuano, A
Publication:Journal of Psychoactive Drugs
Date:Dec 1, 2010
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