SUMMARY: We report two patients who developed a prolonged featureless headache, they think after a drink was ‘spiked’. We speculate that each was exposed to scopolamine, resulting in enhanced trigeminal release of vasodilator neuropeptides, including Calcitonin Gene-Related Peptide (CGRP), and thus the headache

Carlos M Villalón

Richard Peatfield

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Peatfield and Villalón SpringerPlus 2013, 2:39
http://www.springerplus.com/content/2/1/39CASE STUDY Open AccessHeadache after exposure to ‘date-rape’ drugs
Richard Peatfield1* and Carlos M Villalón2Abstract
Summary: We report two patients who developed a prolonged featureless headache, they think after a drink was
‘spiked’. We speculate that each was exposed to scopolamine, resulting in enhanced trigeminal release of
vasodilator neuropeptides, including Calcitonin Gene-Related Peptide (CGRP), and thus the headache.Introduction
Many hypnotic and tranquillising drugs can also induce
amnesia, an effect exploited by anaesthetists when per-
forming potentially distressing medical procedures such
as endoscopies in anxious patients. Unfortunately, many
of the drugs have also found a place in criminal youth
culture, enabling the unscrupulous to render victims po-
werless to resist sexual assault or even theft. As a result
some of these agents, including flunitrazepam (Rohypnol)
have been withdrawn from sale. Many are benzodiaze-
pines, and are sedative, which is often useful in legitimate
clinical practice, but (it may be assumed) less so when
such drugs are used for criminal purposes.
The muscarinic receptor antagonist scopolamine
(l-hyoscine), derived from Henbane in Europe, has been
used as an anaesthetic premedication for many years, as it
simultaneously inhibits vagal reflexes, dries oral secretions
and impairs memory, without suppressing respiration.
Unfortunately, it can also induce restlessness, excitement,
hallucinations and euphoria. Indeed, its affinity for sub-
types of the muscarinic acetylcholine receptor seems little
different from the closely related drug atropine, but due to
its higher lipid solubility it penetrates the central nervous
system much better (Bonner et al. 1987). It is found in lar-
ger quantities in a number of South American plants,
most notably the Borrachera tree, yielding Burundanga
“the terror of Colombia”. When taken orally, Burundanga
(pronounced boor-oon-DAN-ga) induces a hypnosis-like
state, and it is becoming the assault-chemical of choice
there, due to its disinhibitory and amnesic effects.
In the present study, we report two young women
who each behaved in an uncharacteristic manner after* Correspondence: r.peatfield@imperial.ac.uk
1Princess Margaret Migraine Clinic, Charing Cross Hospital, London W6 8RF,
UK
Full list of author information is available at the end of the article
© 2013 Peatfield and Villalón; licensee Springer
Commons Attribution License (http://creativeco
reproduction in any medium, provided the origan evening out in London, and who then developed a
chronic, relatively featureless headache, and speculate
that this might have been a result of exposure to
scopolamine.
Case 1
A 24 year old woman, who works as a travel manager
for a theatre management company; said that she often
goes to social occasions as part of her work. She had
had migraines since her menarche at the age of 12. The
attacks were first infrequent, but recently they had been
occurring every six to seven weeks, lasting a day. It was
a bifrontal throbbing headache with a little nausea (but
no vomiting), and with photophobia but no other focal
symptoms. The pain usually responded to Zolmitriptan.
Her mother, maternal grandmother, aunt and older bro-
ther were similarly affected.
She developed a chronic headache in September 2009.
This had started the night after a work dinner, at which
she emphasises that she only had one alcoholic drink.
Towards the end of the evening, she suddenly started
slurring her speech, and a senior colleague persuaded
her to go home. She has absolutely no memory of her
journey back to (she presumes) Charing Cross station,
perhaps a 5 minute walk. She seems to have brought a
train ticket as judged by her own credit card account
(even though she holds a season ticket to Dartford), and
found herself in Dover at 3 am with no intervening
memory. She got a taxi home, but then had to be looked
after by a friend as her parents were abroad. She was
quite unable to move for a full day. It is of great interest
that several of her colleagues (who had never hitherto
been interested in her welfare) phoned her at home to
ensure that she had got home safely.
She had a generalised headache from then, like a
“squeezing pain” right through her head. This failed to. This is an Open Access article distributed under the terms of the Creative
mmons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
inal work is properly cited.
Peatfield and Villalón SpringerPlus 2013, 2:39 Page 2 of 3
http://www.springerplus.com/content/2/1/39respond first to Zolmitriptan, and then to Co-codamol,
and more recently she has taken amitriptyline (25 mg
daily), which has improved her sleeping pattern, but not
the headache, though it does vary in severity. She discon-
tinued the contraceptive pill (Microgynon) in late August
2009 because of weight gain. She still sleeps poorly, with
insomnia for up to two to three hours, but no early wa-
king. There were no significant abnormalities on exami-
nation. The dose of amitriptyline was increased and the
codeine discontinued, depending as best she can on anti-
inflammatory drugs.
Case 2
This 18 year old woman works as a sales assistant in a
jewellery shop. There was no past or family history of
headache. She thinks a drink was spiked “by the barman”
in a night club in March 2009. Her mother's account is
that she was “put outside” the night club where she col-
lapsed, and her mother came to fetch her. She was found
to be drowsy and crying with her eyes wide open. She
could not see her mother, but recognised her voice. She
was taken to the local hospital emergency department,
but treated as a “drunken teenager” and allowed to sleep
it off in a cubicle. She was clearly difficult to rouse du-
ring this time. She was completely amnesic until waking
up in hospital, perhaps five hours after she took the
drink.
For the next eighteen months she had a chronic,
though variable, right hemicranial headache. There was
some nausea, and occasional vomiting when the pain
was bad. She was not pregnant. She had taken Microgy-
non 30 since the age of 13, and she had used dothiepin
at a dose of 75 mg daily for the headache without much
benefit. The pain had not responded to paracetamol, co-
codamol or tramadol.
There was a slight drift of the right hand on examin-
ation, but no other abnormalities. An MRI scan showed
no abnormality in the brain substance, though there was
a glomus vagale paraganglioma, which was considered
asymptomatic, and is being monitored with regular
scans. A trial of indomethacin was unsuccessful, as was
topiramate up to 100 mg daily. She discontinued this in
September 2010, and the pain has gradually improved
since then. By June 2011 she was having a 4-day attack
every 2–3 months.
Discussion
There seems to be at least circumstantial evidence these
women's drinks were 'spiked', though identification of
the drug administered is necessarily speculative. We
have no direct evidence at all, though the relative lack of
sedation does suggest Burundanga.
Burundanga is a kind of voodoo powder obtained from
a Colombian local plant of the nightshade family, ashrub called borrachera, or “drunken binge”. Used for
hundreds of years by native South Americans in reli-
gious ceremonies, the powder when ingested causes vic-
tims to lose their will and memory, sometimes for days.
When refined, the powder yields scopolamine, a well-
known drug with legitimate uses as a sedative and to
combat motion sickness. But in Colombia the drug’s
most avid users are street criminals. Crooks mix the
powder with sedatives and feed the Burundanga cocktail
to unsuspecting victims whom they then proceed to rob -
or worse. Doctors there estimate that Colombian hustlers
slip the odourless, colourless and soluble Burundanga
in food or drink to about 500 unwitting victims in the
city each month. About half of the city’s total emergency
room admissions for poison are Burundanga victims
(De Cordoba 1995).
Cases of headache induced by scopolamine have been
recorded. Gordon (Gordon et al. 1991) reported a naval
airman who developed chronic headaches after five
months’ continuous treatment with scopolamine, and
Ikeda et al. (Ikeda et al. 2009) noted that 54 out of 1919
subjects premedicated with 20 mg scopolamine for‚ gastro-
intestinal X-ray examination’ developed headaches - all
had a past history of migraine, and only one of the 1865
non-migraineurs had a headache, and this was mild. The
headaches lasted several hours. The headache seems unre-
lated to the suppression of muscarinic parasympathetic
vasodilatation in the cerebral circulation, as scopolamine
does not affect this, at least in the rat (Kowacs et al. 2004).
The therapeutic benefit of acetylcholinesterase inhibitor
drugs such as donepezil in migraine (Ikeda et al. 2009;
Nicolodi et al. 2002) suggests that cholinergic pathways
may suppress migrainous attacks and, thus, muscarinic
cholinergic receptor antagonists might lead to the deve-
lopment of headache.
Animal studies suggest that M2 muscarinic receptor
subtypes are presynaptically located on cholinergic nerve
terminals, where they can act as autoreceptors to de-
crease acetylcholine release (by negative feed-back me-
chanisms). Interestingly, blockade of these sites (with
atropine, scopolamine or more selective M2 receptor an-
tagonists) facilitates acetylcholine release and learning in
rats (Vazquez & Baghdoyan 2003). Although we did not
directly measure CGRP concentrations in the jugular
venous blood of these women, we wonder if prejunc-
tional muscarinic blockade (by scopolamine) may have
led to an increase in CGRP release. This would follow
from the fact that muscarinic M2 and M4 receptors (for
which scopolamine displays a high affinity) are coupled
to Gi proteins; upon activation, this would lead to a de-
crease in intraneuronal cAMP levels, a decrease in Ca2+
conductance and an increase in K + conductance. These
are signal transduction systems usually associated with
inhibition of neurotransmitters release.
Peatfield and Villalón SpringerPlus 2013, 2:39 Page 3 of 3
http://www.springerplus.com/content/2/1/39If this were the case, then blockade of these receptors
by scopolamine could result in an increase in CGRP re-
lease, cranial vasodilatation and, consequently, headache,
or even migraine! The actions of scopolamine are longer
lasting than those of atropine, though clearly some long-
lasting adaptive mechanism is required to account for a
headache that lasts for several months.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
RP saw the patients and drafted the clinical details, and CMV provided the
pharmacological commentary. Both authors read and approved the final
manuscript.
Author details
1Princess Margaret Migraine Clinic, Charing Cross Hospital, London W6 8RF,
UK. 2Departamento de Farmacobiología, Cinvestav-Coapa, Deleg. Tlalpan
14330, México D.F, Mexico.
Received: 7 September 2012 Accepted: 17 December 2012
Published: 8 February 2013
References
Bonner TI, Buckley NJ, Young AC, Brann MR (1987) Identification of a family of
muscarinic acetylcholine receptor genes. Science 237:527–532
De Cordoba J (1995) Drugged in Columbia: street thugs dope unwitting victims.
The Wall Street Journal p A1
Gordon CR, Mankuta D, Shupak A, Spitzer O, Doweck I (1991) Recurrent classic
migraine attacks following transdermal scopolamine intoxication. Headache
31:172–4
Ikeda K, Kawase Y, Takazawa T et al (2009) Scopolamine-induced Migraine Like
Headache. Inter Med 48:681–685
Kowacs F, Williamson DJ, Goadsby PJ (2004) Neurogenic vasodilation of dural
blood vessels is not mediated by cholinergic transmission in the
anaesthetized rat. Eur J Pharmacol 493:133–137
Nicolodi M, Galeotti N, Ghelardini C, Bartolini A, Sicuteri F (2002) Central
cholinergic challenging of migraine by testing second generation
anticholinesterase drugs. Headache 42:596–602
Vazquez J, Baghdoyan H (2003) Muscarinic and GABAA receptors modulate
acetylcholine release in feline basal forebrain. Eur J Neurosci 17:249–259
doi:10.1186/2193-1801-2-39
Cite this article as: Peatfield and Villalón: Headache after exposure to
‘date-rape’ drugs. SpringerPlus 2013 2:39.Submit your manuscript to a 
journal and beneﬁ t from:
7 Convenient online submission
7 Rigorous peer review
7 Immediate publication on acceptance
7 Open access: articles freely available online
7 High visibility within the ﬁ eld
7 Retaining the copyright to your article
    Submit your next manuscript at 7 springeropen.com


Headache after exposure to ‘date-rape’ drugs

Crossref

a SpringerOpen JournalPeatfield and Villalón SpringerPlus 2013, 2:39http://www.springerplus.com/content/2/1/39CASE STUDY Open AccessHeadache after exposure to ‘date-rape’ drugsRichard Peatfield1* and Carlos M Villalón2AbstractSummary: We report two patients who developed a prolonged featureless headache, they think after a drink was‘spiked’. We speculate that each was exposed to scopolamine, resulting in enhanced trigeminal release ofvasodilator neuropeptides, including Calcitonin Gene-Related Peptide (CGRP), and thus the headache.IntroductionMany hypnotic and tranquillising drugs can also induceamnesia, an effect exploited by anaesthetists when per-forming potentially distressing medical procedures suchas endoscopies in anxious patients. Unfortunately, manyof the drugs have also found a place in criminal youthculture, enabling the unscrupulous to render victims po-werless to resist sexual assault or even theft. As a resultsome of these agents, including flunitrazepam (Rohypnol)have been withdrawn from sale. Many are benzodiaze-pines, and are sedative, which is often useful in legitimateclinical practice, but (it may be assumed) less so whensuch drugs are used for criminal purposes.The muscarinic receptor antagonist scopolamine(l-hyoscine), derived from Henbane in Europe, has beenused as an anaesthetic premedication for many years, as itsimultaneously inhibits vagal reflexes, dries oral secretionsand impairs memory, without suppressing respiration.Unfortunately, it can also induce restlessness, excitement,hallucinations and euphoria. Indeed, its affinity for sub-types of the muscarinic acetylcholine receptor seems littledifferent from the closely related drug atropine, but due toits higher lipid solubility it penetrates the central nervoussystem much better (Bonner et al. 1987). It is found in lar-ger quantities in a number of South American plants,most notably the Borrachera tree, yielding Burundanga“the terror of Colombia”. When taken orally, Burundanga(pronounced boor-oon-DAN-ga) induces a hypnosis-likestate, and it is becoming the assault-chemical of choicethere, due to its disinhibitory and amnesic effects.In the present study, we report two young womenwho each behaved in an uncharacteristic manner after* Correspondence: r.peatfield@imperial.ac.uk1Princess Margaret Migraine Clinic, Charing Cross Hospital, London W6 8RF,UKFull list of author information is available at the end of the article© 2013 Peatfield and Villalón; licensee SpringerCommons Attribution License (http://creativecoreproduction in any medium, provided the origan evening out in London, and who then developed achronic, relatively featureless headache, and speculatethat this might have been a result of exposure toscopolamine.Case 1A 24 year old woman, who works as a travel managerfor a theatre management company; said that she oftengoes to social occasions as part of her work. She hadhad migraines since her menarche at the age of 12. Theattacks were first infrequent, but recently they had beenoccurring every six to seven weeks, lasting a day. It wasa bifrontal throbbing headache with a little nausea (butno vomiting), and with photophobia but no other focalsymptoms. The pain usually responded to Zolmitriptan.Her mother, maternal grandmother, aunt and older bro-ther were similarly affected.She developed a chronic headache in September 2009.This had started the night after a work dinner, at whichshe emphasises that she only had one alcoholic drink.Towards the end of the evening, she suddenly startedslurring her speech, and a senior colleague persuadedher to go home. She has absolutely no memory of herjourney back to (she presumes) Charing Cross station,perhaps a 5 minute walk. She seems to have brought atrain ticket as judged by her own credit card account(even though she holds a season ticket to Dartford), andfound herself in Dover at 3 am with no interveningmemory. She got a taxi home, but then had to be lookedafter by a friend as her parents were abroad. She wasquite unable to move for a full day. It is of great interestthat several of her colleagues (who had never hithertobeen interested in her welfare) phoned her at home toensure that she had got home safely.She had a generalised headache from then, like a“squeezing pain” right through her head. This failed to. This is an Open Access article distributed under the terms of the Creativemmons.org/licenses/by/2.0), which permits unrestricted use, distribution, andinal work is properly cited.Peatfield and Villalón SpringerPlus 2013, 2:39 Page 2 of 3http://www.springerplus.com/content/2/1/39respond first to Zolmitriptan, and then to Co-codamol,and more recently she has taken amitriptyline (25 mgdaily), which has improved her sleeping pattern, but notthe headache, though it does vary in severity. She discon-tinued the contraceptive pill (Microgynon) in late August2009 because of weight gain. She still sleeps poorly, withinsomnia for up to two to three hours, but no early wa-king. There were no significant abnormalities on exami-nation. The dose of amitriptyline was increased and thecodeine discontinued, depending as best she can on anti-inflammatory drugs.Case 2This 18 year old woman works as a sales assistant in ajewellery shop. There was no past or family history ofheadache. She thinks a drink was spiked “by the barman”in a night club in March 2009. Her mother's account isthat she was “put outside” the night club where she col-lapsed, and her mother came to fetch her. She was foundto be drowsy and crying with her eyes wide open. Shecould not see her mother, but recognised her voice. Shewas taken to the local hospital emergency department,but treated as a “drunken teenager” and allowed to sleepit off in a cubicle. She was clearly difficult to rouse du-ring this time. She was completely amnesic until wakingup in hospital, perhaps five hours after she took thedrink.For the next eighteen months she had a chronic,though variable, right hemicranial headache. There wassome nausea, and occasional vomiting when the painwas bad. She was not pregnant. She had taken Microgy-non 30 since the age of 13, and she had used dothiepinat a dose of 75 mg daily for the headache without muchbenefit. The pain had not responded to paracetamol, co-codamol or tramadol.There was a slight drift of the right hand on examin-ation, but no other abnormalities. An MRI scan showedno abnormality in the brain substance, though there wasa glomus vagale paraganglioma, which was consideredasymptomatic, and is being monitored with regularscans. A trial of indomethacin was unsuccessful, as wastopiramate up to 100 mg daily. She discontinued this inSeptember 2010, and the pain has gradually improvedsince then. By June 2011 she was having a 4-day attackevery 2–3 months.DiscussionThere seems to be at least circumstantial evidence thesewomen's drinks were 'spiked', though identification ofthe drug administered is necessarily speculative. Wehave no direct evidence at all, though the relative lack ofsedation does suggest Burundanga.Burundanga is a kind of voodoo powder obtained froma Colombian local plant of the nightshade family, ashrub called borrachera, or “drunken binge”. Used forhundreds of years by native South Americans in reli-gious ceremonies, the powder when ingested causes vic-tims to lose their will and memory, sometimes for days.When refined, the powder yields scopolamine, a well-known drug with legitimate uses as a sedative and tocombat motion sickness. But in Colombia the drug’smost avid users are street criminals. Crooks mix thepowder with sedatives and feed the Burundanga cocktailto unsuspecting victims whom they then proceed to rob -or worse. Doctors there estimate that Colombian hustlersslip the odourless, colourless and soluble Burundangain food or drink to about 500 unwitting victims in thecity each month. About half of the city’s total emergencyroom admissions for poison are Burundanga victims(De Cordoba 1995).Cases of headache induced by scopolamine have beenrecorded. Gordon (Gordon et al. 1991) reported a navalairman who developed chronic headaches after fivemonths’ continuous treatment with scopolamine, andIkeda et al. (Ikeda et al. 2009) noted that 54 out of 1919subjects premedicated with 20 mg scopolamine for‚ gastro-intestinal X-ray examination’ developed headaches - allhad a past history of migraine, and only one of the 1865non-migraineurs had a headache, and this was mild. Theheadaches lasted several hours. The headache seems unre-lated to the suppression of muscarinic parasympatheticvasodilatation in the cerebral circulation, as scopolaminedoes not affect this, at least in the rat (Kowacs et al. 2004).The therapeutic benefit of acetylcholinesterase inhibitordrugs such as donepezil in migraine (Ikeda et al. 2009;Nicolodi et al. 2002) suggests that cholinergic pathwaysmay suppress migrainous attacks and, thus, muscariniccholinergic receptor antagonists might lead to the deve-lopment of headache.Animal studies suggest that M2 muscarinic receptorsubtypes are presynaptically located on cholinergic nerveterminals, where they can act as autoreceptors to de-crease acetylcholine release (by negative feed-back me-chanisms). Interestingly, blockade of these sites (withatropine, scopolamine or more selective M2 receptor an-tagonists) facilitates acetylcholine release and learning inrats (Vazquez & Baghdoyan 2003). Although we did notdirectly measure CGRP concentrations in the jugularvenous blood of these women, we wonder if prejunc-tional muscarinic blockade (by scopolamine) may haveled to an increase in CGRP release. This would followfrom the fact that muscarinic M2 and M4 receptors (forwhich scopolamine displays a high affinity) are coupledto Gi proteins; upon activation, this would lead to a de-crease in intraneuronal cAMP levels, a decrease in Ca2+conductance and an increase in K + conductance. Theseare signal transduction systems usually associated withinhibition of neurotransmitters release.Peatfield and Villalón SpringerPlus 2013, 2:39 Page 3 of 3http://www.springerplus.com/content/2/1/39If this were the case, then blockade of these receptorsby scopolamine could result in an increase in CGRP re-lease, cranial vasodilatation and, consequently, headache,or even migraine! The actions of scopolamine are longerlasting than those of atropine, though clearly some long-lasting adaptive mechanism is required to account for aheadache that lasts for several months.Competing interestsThe authors declare that they have no competing interests.Authors’ contributionsRP saw the patients and drafted the clinical details, and CMV provided thepharmacological commentary. Both authors read and approved the finalmanuscript.Author details1Princess Margaret Migraine Clinic, Charing Cross Hospital, London W6 8RF,UK. 2Departamento de Farmacobiología, Cinvestav-Coapa, Deleg. Tlalpan14330, México D.F, Mexico.Received: 7 September 2012 Accepted: 17 December 2012Published: 8 February 2013ReferencesBonner TI, Buckley NJ, Young AC, Brann MR (1987) Identification of a family ofmuscarinic acetylcholine receptor genes. Science 237:527–532De Cordoba J (1995) Drugged in Columbia: street thugs dope unwitting victims.The Wall Street Journal p A1Gordon CR, Mankuta D, Shupak A, Spitzer O, Doweck I (1991) Recurrent classicmigraine attacks following transdermal scopolamine intoxication. Headache31:172–4Ikeda K, Kawase Y, Takazawa T et al (2009) Scopolamine-induced Migraine LikeHeadache. Inter Med 48:681–685Kowacs F, Williamson DJ, Goadsby PJ (2004) Neurogenic vasodilation of duralblood vessels is not mediated by cholinergic transmission in theanaesthetized rat. Eur J Pharmacol 493:133–137Nicolodi M, Galeotti N, Ghelardini C, Bartolini A, Sicuteri F (2002) Centralcholinergic challenging of migraine by testing second generationanticholinesterase drugs. Headache 42:596–602Vazquez J, Baghdoyan H (2003) Muscarinic and GABAA receptors modulateacetylcholine release in feline basal forebrain. Eur J Neurosci 17:249–259doi:10.1186/2193-1801-2-39Cite this article as: Peatfield and Villalón: Headache after exposure to‘date-rape’ drugs. SpringerPlus 2013 2:39.Submit your manuscript to a journal and beneﬁ t from:7 Convenient online submission7 Rigorous peer review7 Immediate publication on acceptance7 Open access: articles freely available online7 High visibility within the ﬁ eld7 Retaining the copyright to your article    Submit your next manuscript at 7 springeropen.com

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