See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/278283549

Anticholinergic intoxication due to Mandragora officinarum

Article  in  Clinical Toxicology · June 2008

CITATIONS READS

0 488

6 authors, including:

Panagiota D Nikolaou Ioannis Papoutsis

National and Kapodistrian University of Athens National and Kapodistrian University of Athens
58 PUBLICATIONS   651 CITATIONS    78 PUBLICATIONS   771 CITATIONS   

SEE PROFILE SEE PROFILE

Constantinos Pistos Sotiris Athanaselis

National and Kapodistrian University of Athens National and Kapodistrian University of Athens
58 PUBLICATIONS   1,291 CITATIONS    133 PUBLICATIONS   1,613 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Forensic clininal examination in Greece View project

Quantitative determination of steroid hormones and their metabolites in the systemic circulation of women with benign and malignant breast diseases and healthy
individuals, with current analytical techniques View project

All content following this page was uploaded by Maria Stefanidou on 01 October 2018.

The user has requested enhancement of the downloaded file.

 The Journal of Emergency Medicine, Vol. 42, No. 6, pp. 662–665, 2012
Copyright Ó 2012 Elsevier Inc.
Printed in the USA. All rights reserved
0736-4679/$ - see front matter

doi:10.1016/j.jemermed.2011.03.023

Selected Topics:
Toxicology

ACCIDENTAL POISONING AFTER INGESTION OF ‘‘APHRODISIAC’’ BERRIES:

DIAGNOSIS BY ANALYTICAL TOXICOLOGY

Panagiota Nikolaou, PHD, Ioannis Papoutsis, PHD, Maria Stefanidou, PHD, Artemis Dona, PHD,
Constantinos Maravelias, PHD, Chara Spiliopoulou, PHD, and Sotirios Athanaselis, PHD,
Department of Forensic Medicine and Toxicology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Reprint Address: Panagiota Nikolaou, PHD, Department of Forensic Medicine and Toxicology, School of Medicine, National and Kapodistrian
University of Athens, 75 Mikras Asias, Athens 115 27, Greece

, Abstract—Background: A large number of plants, INTRODUCTION

seeds, and berries have been used for medicinal, psycho-
tropic, or aphrodisiac purposes for a thousand years.
Mandragora officinarum belongs to the family of Solana-
ceae and is traditionally known as an aphrodisiac and is
closely associated with witchcraft. Objectives: In this study
we report a case of an accidental poisoning after ingestion of
some ‘‘aphrodisiac’’ berries and the contribution of the tox-
icological analysis in the case investigation. Case Report: A
35-year-old man was admitted to the hospital with clinical
signs and symptoms of an anticholinergic syndrome. The di-
agnosis of the poisoning was made by the toxicological anal-
ysis of the patient’s urine. The cause of the poisoning was
revealed by his girlfriend’s disclosure that the patient had
intentionally consumed some ‘‘aphrodisiac’’ berries to en-
hance his sexual performance. Subsequently, berries similar
to the ones consumed were sent to the laboratory. The anal-
ysis of the urine and the berries revealed the presence of
hyoscyamine and scopolamine; the berries were identified
as Mandragora officinarum berries. Decontamination and
symptomatic treatment were proven effective for the control
of this poisoning. The patient recovered completely after
hospitalization for 4 days. Conclusion: This case report indi-
cates the importance of analytical toxicology in diagnosis
of intoxications after the consumption of unknown plants
or plant products and presents the clinical aspects of
Mandragora intoxication. Ó 2012 Elsevier Inc.
, Keywords—Mandragora officinarum; poisoning; hyo-
scyamine; scopolamine
Mandragora officinarum is a solanaceous plant that
grows wild in Mediterranean countries and is widespread
in the countryside of Greece (1). It is a perennial herb with
oblong ovate leaves, blue violet flowers (Figure 1A), and
yellow berries (Figure 1B) (2). The alkaloid mandragor-
ine was initially thought to be its active substance, but
later it was found to be a mixture of hyoscyamine and sco-
polamine. All parts of Mandragora species (leaves, seeds,
berries, and roots) are poisonous, as they all contain tro-
pane alkaloids, basically hyoscyamine and scopolamine
(3,4). Mandrake is the common name for different
Mandragora species belonging to the family of
Solanaceae (1,3). This plant dates back thousands of
years and it was used in medicine as a narcotic before
surgery, but also as an emetic and as antidote for
snakebites (5). Due to the ‘‘human body’’ shape of Man-
drake’s root (Figure 1C) and its narcotic and poisonous ef-
fects, it was also known as magic, aphrodisiac,
hallucinogenic, and is closely associated with witchcraft
under the name of ‘‘Devil’s herb’’ (2,3). The concept of
this strange plant is surrounded with various myths and
legends and recalls something mysterious, gloomy, and
even horrible (6). The berries of the plant are also called
love apples because they were believed to increase fertil-
ity (3). As mentioned above, Mandragora plants can

RECEIVED: 6 July 2010; FINAL SUBMISSION RECEIVED: 8 September 2010;

ACCEPTED: 20 March 2011

662
Toxic ‘‘Aphrodisiac’’ Berries
Figure 1. Mandragora officinarum plant (A), berries (B), and root (C).
easily be found in Greece, but the consumption of its
berries is not at all a common practice.
CASE REPORT
A 35-year-old man was admitted to the hospital with an
intense anticholinergic syndrome, comprising central
and peripheral signs and symptoms. All symptoms ap-
peared approximately 1 h after the ingestion of approxi-
mately five berries of a plant unknown to him, that he
had picked up in the countryside after the recommenda-
tion of a friend, to enhance his sexual performance. The
patient initially experienced nausea, vomiting, abdominal
pain, agitation, aggression, and hallucinations. During his
admission to the hospital, 4 h after the consumption of the
berries, the patient showed mydriasis, dry mouth and
skin, hyperthermia (body temperature 38.1 C), tachycar-
dia (heart rate 110 beats/min), and increased blood pres-
sure (155/95 mm Hg). The patient’s electrocardiogram
was otherwise normal, and there were no pathological
findings on a brain computed tomography scan. The pa-
tient showed urinary retention and suffered from increas-
ing abdominal pain, so a catheter was required. The
diagnosis of this poisoning was based on the clinical signs
and symptoms of the anticholinergic syndrome, as well as
on the results of the toxicological analysis of the biolog-
ical fluids of the patient. A urine sample collected right
after hospital admission as well as a blood sample and
berries similar to the ones consumed were sent for analy-
sis to the Toxicology Laboratory. After the results of urine
toxicological analysis, the patient’s girlfriend (and not the
patient himself) revealed that he had consumed five
berries to enhance his sexual performance after her rec-
ommendation.
Treatment of the patient included gastric decontami-
nation with oral administration of a single dose of 75 g ac-
tivated charcoal (1 g/kg) in combination with magnesium
663
sulfate as cathartic and one administration of antidotal
treatment with physostigmine (2 mg in 10 mL glucose
5%, slow intravenous). Physostigmine was administered
after the identification of tropane alkaloids in the patient’s
urine, about 2 h after his admission. After treatment, an-
ticholinergic symptoms resolved. The patient fully recov-
ered without obvious adverse systemic effects and was
discharged after 4 days of hospitalization.
LABORATORY ANALYSIS
The method used for the analysis of biological fluids and
the relative evidential materials involved in this intoxica-
tion was based on routine protocols of the laboratory and
the relative literature (7,8).
Biological Samples
In 1 mL blood or urine, 50 mL of internal standard solu-
tion (methaqualone, 10 mg/L) and 0.5 mL of phosphate
buffer (Na2HPO4) pH = 9 were added. The tubes were
vortex mixed for 1 min. Then the samples were liquid-
liquid extracted with 6 mL dichloromethane: isopropanol
(9:1, v/v), by intensive vortexing for 5 min. After centri-
fuging at 3000 rpm for 10 min, the organic supernatant
phase was transferred into a clean test tube and evapo-
rated to dryness under a gentle stream of N2 at 40 C. In
each dried sample, 50 mL of ethyl acetate was added to
reconstitute the analytes.
Evidential Materials
An appropriate quantity of Mandragora berries was
weighed (1.0 g) and segmented. Then 2 mL of water were
added to the sample and the pH was adjusted to 12 by addi-
tion of NaOH 1N. The sample remained for 24 h at 37 C.
Afterwards, the pH of the sample was adjusted to 9 and
664 P. Nikolaou et al.

the sample was centrifuged at 3000 rpm for 10 min. The su-
pernatant was liquid-liquid extracted as described above.
Chromatographic separations were performed with
a GC/EI–MS (gas chromatography/electron impact-
mass spectrometry) system (Shimadzu QP 5000;
Shimadzu Scientific Instruments, Columbia, MD) equip-
ped with an Agilent HP-5 MS capillary column (Agilent
Technologies Inc., Santa Clara, CA) (30 m  0.25 mm in-
side diameter, film thickness: 0.25 mm) under the follow-
ing conditions: the injector and detector temperatures
were 200 C and 300 C, respectively, helium carrier gas
flow rate was 1.0 mL/min, and the column temperature
was programmed from 100 C (hold for 1 min) to 295 C
Figure 2. Chromatogram of patient urine sample: 539.8 mg/L
(hold for 3 min) at a rate of 20 C/min. The mass spec- hyoscyamine and 32.7 mg/L scopolamine.
trometer was operated in electron impact ionization
mode and the mass range was 50–600 amu for the screen-
ing of the samples. For the quantitation of hyoscyamine about 2 to 4 h, and both substances are excreted to urine
and scopolamine, selective ion monitoring mode was (>80%) in 24 h (9).
used. The mass spectra of hyoscyamine, scopolamine,
and methaqualone have a base peak of m/z 124, 94, and CONCLUSIONS
235, respectively. The retention times of hyoscyamine,
scopolamine, and methaqualone were 10.05, 10.60, and This case report focuses on the problems that arise after
9.83 min, respectively, and the total chromatographic the consumption of unknown plants or plant products
run time was <13 min. that may be life threatening. History is always extremely
important for the investigation of a poisoning, especially
with plant products. An emergency toxicological analysis
DISCUSSION
of biological fluids obtained from the patient, as close to
the incident as possible, has to be performed in the frame-
The Toxicology Laboratory carried out the analysis of bi-
work of the differential diagnosis. In similar cases that
ological samples (blood and urine) and berries similar to
were previously published, the diagnosis set was based
the ones consumed, to determine the diagnosis. In the
exclusively on history, and the symptoms appeared with-
urine sample, which was collected right after the patient’s
out toxicological analysis results (4,10). In intoxication
hospital admission, hyoscyamine and scopolamine were
cases where unknown plants have been consumed, it is
identified at concentrations of 539.8 and 32.7 mg/L, re-
an absolute necessity that the responsible plants be sent
spectively, and the blood sample was negative for pres-
to a Toxicology Laboratory for further investigation. A
ence of tropane alkaloids. The blood sample and the
thorough laboratory investigation of these cases always
berries similar to the ones consumed were sent to the Lab-
contributes significantly to the differential diagnosis
oratory after the results of urine toxicological analysis.
and to the effective treatment of poisoning.
No other toxic substances were identified in the biologi-
cal samples of the patient. The berries were identified
as Mandragora berries by a botanically experienced cli-
nician after their GC/MS analysis had already revealed REFERENCES
the presence of tropane alkaloids, hyoscyamine and sco-
polamine, at concentrations of 25.6 and 0.7 mg/g, respec- 1. Vlachos P, Poulos L. A case of Mandrake poisoning. Clin Toxicol
tively. A chromatogram of the urine sample is presented 1982;19:521–2.
in Figure 2. The limit of detection of the method (recov- 2. Piccillo GA, Miele L, Mondati E, et al. Anticholinergic syndrome
due to ‘‘Devil’s herb’’: when risks come from the ancient time. Int
ery $ 85%) used for blood and urine analysis, for both J Clin Pract 2006;60:492–4.
hyoscyamine and scopolamine in blood, was 5.0 mg/L. 3. Hanus LO, Rezanka T, Spizek J, et al. Substances isolated from
The negative result for presence of tropane alkaloids Mandragora species. Phytochemistry 2005;66:2408–17.
4. Piccillo GA, Mondati EGM, Moro PA. Six clinical cases of Man-
in blood probably was due to the pharmacokinetic dragora autumnalis poisoning: diagnosis and treatment. Eur
characteristics of hyoscyamine and scopolamine, in com- J Emerg Med 2002;9:342–7.
bination with the time elapsed (6 h ) between the con- 5. Ramoutsaki IA, Dimitriou H, Kalmanti M. Management of child-
hood diseases in the Byzantine period: I—Analgesia. Pediatrics
sumption of the berries and the blood collection. Int 2002;44:335–7.
Plasma half-life of hyoscyamine and scopolamine is 6. Carter AJ. Myths and mandrakes. J R Soc Med 2003;96:144–7.
Toxic ‘‘Aphrodisiac’’ Berries
7. Namera A, Yashiki M, Hirose Y, et al. Quantitative analysis of tro-
pane alkaloids in biological materials by gas chromatography-mass
spectrometry. Forensic Sci Int 2002;130:34–43.
8. Miraldi E, Masti A, Ferri S, et al. Distribution of hyoscyamine
and scopolamine in Datura stramonium. Fitoterapia 2001;72:
644–8.
View publication stats
665
9. Moffat AC, Jackson JV, Moss MS, et al. Clarke’s isolation and iden-
tification of drugs. 2nd edn. London: The Pharmaceutical Press;
1986:363–4, 674–6.
10. Tsiligianni IG, Vasilopoulos TK, Papadokostakis PK, et al. A two
cases clinical report of Mandragora poisoning in primary care in
Crete, Greece: two case report. Cases J 2009;2:9331.