354 Short report
First case report of recreational use of 2,5-dimethoxy-4chloroamphetamine confirmed by toxicological screening
Hanna Ovaskaa, Adie Viljoenb, Malgorzata Puchnarewiczc, Jenny Buttonc,
John Ramseyd, David W. Holte, Paul I. Dargana and David M. Wooda
Routine toxicological screening is generally not undertaken
in patients with recreational drug toxicity. We report here
the benefits of toxicological screening in confirming drugs
that have been ingested and potentially detecting drugs
that have not previously been reported in the medical
literature. In this case, the patient was reported to have
ingested a combination of 2,5-dimethoxy-4iodoamphetamine and methylenedioxymetamphetamine
and developed sympathomimetic toxicity, but on extended
toxicological screening he was shown to have actually
ingested 2,5-dimethoxy-4-chloroamphetamine and
methylenedioxymetamphetamine. As 2,5-dimethoxy-4chloroamphetamine is a substituted amphetamine, it is
covered under the generic Misuse of Drugs act (1971) in
the UK; although in the majority of the EU it remains
uncontrolled, as there is no similar generic drug legislation.
We believe that discrepancies in the legal status of
recreational drugs in the EU limit the effectiveness of drug
enforcement policies and that EU drug legislation should
Introduction
The use of recreational drugs is common throughout the
EU, although there are differences in individual drug
use between countries [1]. Many recreational drugs,
such as amphetamines, methylenedioxymetamphetamine
(MDMA; ‘ecstasy’) and cocaine, are controlled under
drug legislation such as the Misuse of Drugs Act (1971) in
the UK. More recently other drugs such as g-hydroxybutyrate have been classified under these regulations,
when it was realized that there were problems associate
with their use. However, new synthetic compounds such
as 1-benzylpiperazine, other piperazines and hallucinogenic amphetamines continue to be developed and/or
marketed [2–6].
2,5-Dimethoxy-4-chloroamphetamine (DOC), and related
analogues 2,5-dimethoxy-4-iodoamphetamine (DOI) and
2,5-dimethoxy-4-bromoamphetamine (DOB), are synthetic, ring-substituted phenethylamine amphetamine
derivatives, and their methods of synthesis are easily
available on the internet ([7], http://www.erowid.org/
archive/rhodium/chemistry/doc.synth.html). DOC has
rarely been reported as a recreational drug of abuse on
user websites, although there are no reports in the medical
literature of confirmed toxicological detection in humans
after its recreational use (http://www.erowid.org/chemicals/
doc/doc_article1.shtml). We report here a patient who
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0969-9546 be harmonized to ensure consistency. European Journal of
c 2008 Wolters Kluwer
Emergency Medicine 15:354–356 Health | Lippincott Williams & Wilkins.
European Journal of Emergency Medicine 2008, 15:354–356
Keywords: 2, 5-dimethoxy-4-bromoamphetamine, 2, 5-dimethoxy-4chloroamphetamine, 2, 5-dimethoxy-4-iodoamphetamine, drug legislation,
recreational drugs, toxicological screening
a
Department of Clinical Toxicology, Guy’s and St Thomas’ Poisons Unit, Guy’s
and St Thomas’ NHS Foundation Trust, London, bDepartment of Chemical
Pathology, Lister Hospital, Stevenage, Departments of cForensic Toxicology
Service, dBioanalytics, Analytical Unit and e TICTAC Communications Ltd,
St George’s University of London, London, UK
Correspondence to Dr Hanna Ovaska, MD, Specialist Registrar in General
Medicine and Clinical Pharmacology and Therapeutics, Guy’s and St Thomas’
Poisons Unit, Avonley Road, London SE14 5ER, UK
Tel: + 44 207 771 5315; fax: + 44 207 771 5306;
e-mail: Hanna.Ovaska@gstt.nhs.uk
Received 13 December 2007 Accepted 9 February 2008
consumed a variety of recreational drugs, including DOC,
and developed seizures and rhabdomyolysis requiring
intensive care unit (ICU) admission; toxicological analysis
confirmed the ingestion of DOC in addition to other
recreational drugs of abuse.
Case report
A 20-year-old man with no significant past medical history
collapsed having tonic-clonic seizures at a rave party. As a
result of his reduced level of consciousness at the scene,
endotracheal intubation was performed by the ambulance
crew for airway protection. The patient was reported by
friends to have ingested DOI earlier that evening. Paper
tabs similar to those used for lysergic acid diethylamide
(LSD), but impregnated with DOC were recovered from
other attendees at the same event. History of ingestion of
ethanol and other recreational drugs of abuse, including
MDMA, was also reported.
On arrival at the Emergency Department (ED), he had a
Glasgow Coma Scale of 3/15. He had a sinus tachycardia
with a heart rate of 152 beats/min and blood pressure
of 144/57 mmHg. He had a temperature of 36.81C. Both
of his pupils were dilated (6 mm) and were nonreactive to
light; apart from this, neurological examination was
normal and, in particular, there was normal tone and
reflexes and no evidence of clonus. His initial ECG
DOI: 10.1097/MEJ.0b013e3282fc765b
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Recreational use of DOC Ovaska et al. 355
confirmed sinus tachycardia, with normal QRS duration
and corrected QT interval. He had metabolic acidosis
(pH 7.29, bicarbonate 17 mmol/l and base excess – 21).
Initial biochemistry and haematological investigations
were normal, apart from elevated random blood glucose
of 9.6 mmol/l, neutrophilia of 10.5 106/l and a low serum
albumin of 30 g/l (reference range 35–50 g/l). In addition,
there was biochemical evidence of rhabdomyolysis, with
an initial creatinine kinase of 1314 IU/l and a normal
troponin I. In view of his reduced level of consciousness
and seizures, a computed tomography scan of his brain
was performed, which was normal.
After initial stabilization in the ED, he was admitted to
the ICU for ongoing management. Later that night, he
developed a low-grade pyrexia (37.61C), and became
cardiovascularly unstable with a systolic blood pressure
of 98 mmHg and a heart rate of 92 beats/min. His blood
pressure improved with intravenous fluid resuscitation
[500 ml colloid (Voluven; Fresenius Kabi, Bad Homburg,
Germany) and 500 ml crystalloid (Hartmans solution)]
and he did not require any inotropic support. In view of
his initial reduced level of consciousness, he was
commenced on broad-spectrum intravenous cefuroxime
and metronidazole for possible aspiration pneumonia.
The patient remained heamodynamically stable during
the rest of the ICU admission. His creatinine kinase
concentration peaked at 4924 IU/l and there was no
associated renal dysfunction. The initial metabolic
acidosis was corrected with intravenous fluid resuscitation, and was thought to be because of his tonic-clonic
seizures before admission to the ED. He was extubated
22 h after admission to the ED and was discharged from
hospital with no long-term sequelae. During his admission he confirmed that, earlier to his collapse at the rave
party, he had ingested MDMA and a recreational drug,
which he believed contained DOI.
Toxicological screening
Serum and urine samples were sent to the Forensic
Toxicology Services at St George’s, University of London,
UK. Routine toxicological analysis of both specimens
using full scan electron ionization gas chromatography–
mass spectrometry after liquid/liquid extraction identified the presence of DOC, MDMA at a concentration of
0.57 mg/l and 3,4-methylenedioxyafetamine at a concentration below 0.05 mg/l. DOC quantification could not be
performed owing to the absence of a pure reference
standard. However, qualitative confirmation was undertaken using a product previously identified to contain
DOC using nuclear magnetic resonance spectroscopy and
liquid chromatography–mass spectrometry, supplied by
TICTAC Communications (St George’s, University of
London, London, UK). No other recreational drugs were
detected using a broad toxicology screen. The only other
drugs detected were laudanosine (an atracurium meta-
bolite), metronidazole and lidocaine, all related to
treatment given in the ICU.
Discussion
In this study, we have described a case of polydrug use,
including DOC, with toxicological screening that confirmed the presence of both DOC and MDMA in plasma
and urine samples. We were unable to quantify the
concentration of DOC, hence it is not possible to
determine what proportion of the clinical features
observed in this patient were because of DOC or MDMA.
No reports of confirmed DOC use are available in the
medical literature, although there have been previous
user website reports concerning its use and the potential
adverse effects (http://www.erowid.org/chemicals/doc/
doc_article1.shtml).
Routine toxicological screening is generally not undertaken in patients with recreational drug toxicity, as it will
usually have no immediate impact on the clinical
management of individual patients. This case report
demonstrates that when toxicological screening is undertaken, with the appropriate expertise, novel drugs may be
detected. This patient believed that he had ingested
DOI, but toxicological screening confirmed that he had,
in fact, ingested DOC. We have previously reported
similar discrepancies in patient self-reported recreational
drug ingestion in relation to toxicology screening results
[2]. In our view, there is a need for a systematic
toxicology screening in centres treating large numbers
of patients with recreational drug toxicity together with a
toxicology laboratory with sufficient expertise to detect
novel agents. This view is supported by other published
reports which have suggested that this may help to
determine evolving epidemiological trends in recreational
drug availability, use and toxicity [2,3].
DOC and its related analogues DOI and DOB are
substituted amphetamine derivatives and so they are
controlled by the generic Misuse of Drugs Act (1971) in
the UK, and possession and/or supply carry the same
penalties as for other amphetamines. DOC and DOI were
controlled as Schedule I substances in Denmark in April
2007 and DOC is listed in Analge I (list 1) in Germany.
However, in all other European countries that do not have
generic drug classification systems, DOC, DOB and DOI
are not covered under current drug legislation, so
possession and supply remain legal. These discrepancies
in the legal status of drugs such as DOC in the EU limit
the effectiveness of drug enforcement policies and, in our
view, drug legislation in the EU should be harmonized so
that there is consistency.
Acknowledgements
Competing interests: D.W. and P.D. have worked as
scientific advisors to the UK Advisory Council on the
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356
European Journal of Emergency Medicine 2008, Vol 15 No 6
Missuse of Drugs and the European Monitoring Centre
for Drugs and Drug Abuse.
References
1
2
United Nations Office on Drugs and Crime. World Drug Report 2007. http://
www.unodc.org/pdf/research/wdr07/WDR_2007.pdf (last accessed 13
December 2007).
Wood DM, Dargan PI, Button J, Holt DW, Ovaska H, Ramsey J, et al.
Collapse, reported seizure–and an unexpected pill. Lancet 2007; 369:1490.
3
4
5
6
7
Staack RF. Piperazine designer drugs of abuse. Lancet 2007; 369:
1411–1413.
Muller AA. New drugs of abuse update: foxy methoxy. J Emerg Nurs 2004;
30:507–508.
Wilson JM, McGeorge F, Smolinske S, Meatherall R. A foxy intoxication.
Forensic Sci Int 2005; 148:31–36.
Babu K, Boyer E, Hernon C, Brush D. Emerging drugs of abuse. Clin Pediatr
Emerg Med 2005; 6:81–84.
Coutts RT, Malicky JL. The synthesis of some analogs of the hallucinogen
1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). Can J Chem
1973; 51:1402–1409.
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