Ethylphenidate (EPH)

Critical Review Report

Agenda Item 4.7

Expert Committee on Drug Dependence

Thirty-eighth Meeting
Geneva, 14-18 November 2016
38th ECDD (2016) Agenda item 4.7 EPH

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Contents
Acknowledgements .......................................................................................................................... 5
Summary .......................................................................................................................................... 6
1. Substance identification .................................................................................................... 7
A. International Nonproprietary Name (INN) ........................................................................ 7
B. Chemical Abstract Service (CAS) Registry Number .......................................................... 7
C. Other Chemical Names ...................................................................................................... 7
D. Trade Names ...................................................................................................................... 7
E. Street Names ...................................................................................................................... 7
F. Physical Appearance.......................................................................................................... 7
G. WHO Review History ......................................................................................................... 7
2. Chemistry ........................................................................................................................... 8
A. Chemical Name .................................................................................................................. 8
B. Chemical Structure ............................................................................................................ 8
C. Stereoisomers ..................................................................................................................... 8
D. Methods and Ease of Illicit Manufacturing ....................................................................... 8
E. Chemical Properties .......................................................................................................... 8
F. Identification and Analysis................................................................................................. 9
3. Ease of Convertibility Into Controlled Substances .......................................................... 9

4. General Pharmacology ..................................................................................................... 9

A. Routes of administration and dosage ................................................................................. 9
B. Pharmacokinetics ............................................................................................................... 9
C. Pharmacodynamics .......................................................................................................... 10
5. Toxicology ....................................................................................................................... 10

6. Adverse Reactions in Humans ........................................................................................ 10

7. Dependence Potential...................................................................................................... 11
A. Animal Studies .................................................................................................................. 11
B. Human Studies ................................................................................................................. 11
8. Abuse Potential................................................................................................................ 12
A. Animal Studies .................................................................................................................. 12
B. Human Studies ................................................................................................................. 12
9. Therapeutic Applications and Extent of Therapeutic Use and Epidemiology of Medical
Use ................................................................................................................................... 12

10. Listing on the WHO Model List of Essential Medicines ............................................... 12

11. Marketing Authorizations (as a Medicinal Product) ..................................................... 12

12. Industrial Use .................................................................................................................. 12

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13. Non-Medical Use, Abuse and Dependence .................................................................... 12

14. Nature and Magnitude of Public Health Problems Related to Misuse, Abuse and
Dependence ..................................................................................................................... 13

15. Licit Production, Consumption and International Trade ............................................. 13

16. Illicit Manufacture and Traffic and Related Information ............................................ 13

17. Current International Controls and Their Impact ........................................................ 14

18. Current and Past National Controls............................................................................... 14

19. Other Medical and Scientific Matters Relevant for a Recommendation on the
Scheduling of the Substance ........................................................................................... 14

References ...................................................................................................................................... 15
Annex 1: Report on WHO Questionnaire for Review of Psychoactive Substances for the 38th
ECDD: Evaluation of Ethylphenidate ......................................................................................... 17

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Acknowledgements

This report has been drafted under the responsibility of the WHO Secretariat, Essential Medicines
and Health Products, Policy Access and Use team. The WHO Secretariat would like to thank the
following people for their contribution in producing this critical review report: Prof. Jason White,
Australia (literature search, review and drafting) and Dr. Stephanie Kershaw, Geneva, Switzerland
(editing and questionnaire report drafting).

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Summary

Ethylphenidate is a structural analogue of methylphenidate, which is controlled as a Schedule II

substance under the U.N. 1971 Convention on Psychotropic Substances. Ethylphenidate is also
produced in vivo as a metabolite when methylphenidate and ethanol are ingested together.

Ethylphenidate acts as a dopamine and noradrenaline reuptake inhibitor in vitro, and can be
distinguished from methylphenidate by its greater dopaminergic selectivity relative to
noradrenergic actions. Ethylphenidate demonstrates effects typical of amphetamine-like
stimulants, including tachycardia, hypertension, dilated pupils, agitation and fever. Users on
internet forums report tolerance to its effects, leading to a higher drug dose to achieve the same
effect and also describe a strong urge to redose.

It has no known approved medical or industrial applications.

Ethylphenidate is being used for nonmedical purposes, although the prevalence cannot be
accurately determined. It was first reported to the European Union in 2011 by the United Kingdom
and has been seized in a number of European countries and placed under domestic control in
several countries. It is currently being sold as a ‘legal’ product and is readily available online.
Ethylphenidate use has been associated with a number intoxications and fatalities, including one
death attributable solely to use of the drug.

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1. Substance identification
A. International Nonproprietary Name (INN)
None

B. Chemical Abstract Service (CAS) Registry Number

57413-43-1 (base) [1]
19716-79-1 (Hydrochloride) [2]

C. Other Chemical Names

Ethylphenidate
Ethyl-2-phenyl-2-(piperidin-2-yl)acetate
(RS) - ethyl 2-phenyl-2-(piperidin-2-yl)acetate
dl-ethylphenidate
EPH

D. Trade Names
None

E. Street Names
Nopaine, gogaine, ching, burst, blue, magic crystals, psyclone [3-5]

F. Physical Appearance
Coarse white, off-white, or yellowish crystalline powder [6]

G. WHO Review History

Ethylphenidate has not been previously pre-reviewed or critically reviewed. The
current review is based on information that ethylphenidate is clandestinely
manufactured, poses a public health risk and has no therapeutic use. There is
existing published literature that ethylphenidate may cause harm.

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2. Chemistry
A. Chemical Name
IUPAC Name: ethyl 2-phenyl-2-piperidin-2-ylacetate [1]
CA Index Name: Not available

B. Chemical Structure

Free base:
Molecular Formula: C15H21NO2
Molecular Weight: 247.3327 g/mol

C. Stereoisomers
Ethylphenidate is a chiral compound and is mainly found as the racemate dl-
ethylphenidate [7]

D. Methods and Ease of Illicit Manufacturing

Ethylphenidate can be produced by hydrolysing methylphenidate with
hydrochloric acid (HCl) to ritalinic acid, which in turn, can subsequently be
esterified to ethylphenidate with ethanolic HCl (refer to figure below). [8, 9]

E. Chemical Properties
Melting point: Unknown
Boiling point: Unknown
Solubility: Unknown

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F. Identification and Analysis
Several non-enantioselective [10-12] and enantiospecific [13] liquid
chromatography-tandem mass spectrometry (LC-MS/MS) assays have been
reported for the analysis of ethylphenidate in human plasma. Other analytical
techniques and assessments of ethylphenidate include Infrared Spectroscopy
(FTIR), Gas Chromatography/Mass Spectrometry (GC/MS), Nuclear Magnetic
Resonance Imaging (NMR), Proton-Transfer-Reaction Mass Spectrometry (PTR-
MS), UFLC-MS/MS. [8, 14-16]

3. Ease of Convertibility Into Controlled Substances

Ethylphenidate can be converted into methylphenidate and vice versa. Methylphenidate is
controlled as a Schedule II substance under the U.N. 1971 Convention on Psychotropic
Substances.

Ethylphenidate can be produced from methylphenidate as described in Section D.

Ethylphenidate is also produced as a metabolite from the co-ingestion of methylphenidate
and alcohol (ethanol).[3] This has been confirmed in studies where healthy volunteers
received a single oral dose of methylphenidate (20mg) followed by consumption of ethanol
[10, 11]. It has been suggested that the formation of ethylphenidate in vivo and its
subsequent effects may contribute to the co-abuse of methylphenidate and ethanol. [10]

Ethylphenidate can be relatively easily converted into methylphenidate using methanol and
other readily available chemicals. [9]

4. General Pharmacology
A. Routes of administration and dosage
According to internet forums, the most common route of use is by nasal insufflation. [6,
17] Other routes include oral, anal, vapour inhalation and intravenous injection. [6]

B. Pharmacokinetics
There are no controlled human studies of the pharmacokinetics of ethylphenidate. User
reports suggest that following its administration the mean onset time is approximately 13
minutes (ranging from 0-35 minutes) for nasal insufflation and 23 minutes (5-31 minutes)
for oral administration. The mean duration of effects is relatively short at approximately 2
hours. [17]

The metabolism of ethylphenidate has been investigated in vitro using human liver
microsomes and cytosol. Ethylphenidate first undergoes hydroxylation forming two
primary mono-hydroxylated metabolites and then secondary metabolites result from
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dehydration and ring opening with an additional hydroxylation. The involvement of
different human cytochrome P450 (CYP) enzymes was also investigated using a panel of
human recombinant CYPs. The results suggested that CYP2C19 is the most important
enzyme in ethylphenidate metabolism, with involvement in the formation of all seven
detected ethylphenidate metabolites; however, other CYPs also play some role.[18]

C. Pharmacodynamics
Two early studies suggested that ethylphenidate was pharmacodynamically similar to
methylphenidate, but less potent. Portoghese and Malspeis [19] reported that
ethylphenidate was 80% as active as methylphenidate in inducing locomotor activity in
mice. Schweri et al. [20] found that ethylphenidate exhibits approximately 50% of the
potency of methylphenidate in the inhibition of [3H]methylphenidate binding to rat
synaptosomes.

More recent research has indicated that ethylphenidate is a selective and potent dopamine
uptake inhibitor and that this activity resides almost solely in the d enantiomer. [7, 21, 22];
d-ethylphenidate shows greater potency than cocaine in dopamine uptake inhibition and,
compared to cocaine and methylphenidate, it is more selective for the dopamine transporter
relative to the noradrenergic and serotonergic transporters. d-ethylphenidate increases
locomotor activity and, at high doses, induces stereotypy. For locomotor activity, it is
slightly less potent than d-methylphenidate, possibly due to its relatively low noradrenergic
activity.

There are no human studies of ethylphenidate pharmacodynamics.

5. Toxicology
There appear to be no published controlled studies on the safety of ethylphenidate in animals
or in humans. Adverse reactions determined from case studies and user internet forums are
detailed in the section below.

6. Adverse Reactions in Humans

Three cases of ethylphenidate acute toxicity requiring hospitalization have been reported in
the UK [23]. These cases were associated with signs and symptoms similar to other
amphetamine-type stimulants, including tachycardia, hypertension, dilated pupils,
palpitations, fever, anxiety, agitation, paranoia and tremor.

In a review of reports on user internet forums, ethylphenidate was described as producing a

range of adverse effects similar to other amphetamine-like stimulants. These included
increased heart rate, sweating, muscle tension (sometimes manifested as jaw clenching, teeth
grinding or tremor), decreased appetite, insomnia, agitation and restlessness, anxiety,
paranoia, hallucinations and impaired thinking. [6]
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Ethylphenidate was first associated with a death in Germany in 2014, but its role in the
fatality is unclear. [16] The autopsy indicated death due to mitral valve endocarditis in
combination with pneumonia, and it was likely that the endocarditis had persisted for a
period before death. It was suggested that the cardiovascular actions of ethylphenidate may
have contributed to death, but the concentration in femoral blood (0.1 mg/L) post-mortem
was in the lower range found in fatalities.

Ethylphenidate was subsequently identified in a case series of 19 deaths that occurred

between July 2013 and December 2014. [3] The majority of individuals were male (n=14)
and from the East of Scotland (n=16). Current or previous heroin abuse was a common
factor in 16 cases, with injection identified as the common route of administration. The
concentration of ethylphenidate in post-mortem femoral blood ranged from 0.008 mg/L to
over 2 mg/L. Other drugs commonly detected were benzodiazepines (n=15), methadone
(n=8) and other opioids (n=11). Ethylphenidate was specifically mentioned in the cause of
death for 5 cases, but there were no cases in which ethylphenidate was the sole cause of
death.

The most recent report is of a case series of 7 documented deaths that occurred between
February 2013 and January 2015 in the UK in which the presence of ethylphenidate was
analytically confirmed. [2] The causes of death were hanging (2 cases), mixed drug toxicity
(4 cases) and ethylphenidate toxicity (1 case). The concentrations of ethylphenidate in post-
mortem femoral blood ranged from 0.026 mg/L to 2.18 mg/L. In the one case in which
ethylphenidate was present as the sole drug and was the apparent cause of death, the
concentration was 2.18 mg/L.

7. Dependence Potential
A. Animal Studies
There are no published animal models of ethylphenidate effects.

B. Human Studies
There are no published reports with ethylphenidate under controlled conditions reporting
physical dependence associated with administration of ethylphenidate.

There is one very brief published case study describing a 24 year old French male who
developed dependence on ethylphenidate purchased from the internet. The subject had
previously been dependent on cannabis, heroin/morphine and had occasionally used
stimulants. [24]

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In the review of user reports [6], there was a strong theme of risk of addiction from
ethylphenidate use. Users described persistent impulses to redose, urges to prolong the
effects, an inability to control craving for the drug and failed attempts to restrain use.

8. Abuse Potential
A. Animal Studies
There are currently no published animal models of ethylphenidate abuse liability using
drug discrimination, conditioned place preference or self-administration.

B. Human Studies
There were no published reports of controlled studies evaluating abuse-liability procedures
such as self-administration, drug discrimination, or using drug liking inventories.

However, the assessment of user reports [6] described a number of desirable effects of the
drug. Users reported an immediate and intense rush of pleasurable stimulation, which was
characterized by alertness and a general mood lift. Other effects included increased self-
confidence, improved ability to focus and concentrate, and enhanced social interaction and
social skills. The pro-social effects appear similar to those reported by users of MDMA.

9. Therapeutic Applications and Extent of Therapeutic Use and

Epidemiology of Medical Use
There are currently no known therapeutic applications for ethylphenidate.

10. Listing on the WHO Model List of Essential Medicines

Ethylphenidate is not listed on the WHO Model List of Essential Medicines (19th List).

11. Marketing Authorizations (as a Medicinal Product)

None

12. Industrial Use

Ethylphenidate has no current legitimate industrial, cosmetic, agrochemical, cosmetic,
human or animal use. It may be used as a reference standard in a forensic laboratories.

13. Non-Medical Use, Abuse and Dependence

Ethylphenidate use has been associated with deaths due to mixed drug toxicity, and in one
documented instance, the drug alone. [2, 3] It has been identified in confiscated material e.g.
[25], sold over the internet [24, 26] and discussed on drug-user websites. [27-29] Its use has
been noted in a number of countries. An internet snapshot survey in 2015 identified 83

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websites selling ethylphenidate, with 61% of these based in the UK and the remainder in
Europe, Asia and North America. [17] In the UK, it first appeared as a new psychoactive
substance (NPS) in 2011 and is now one of the most commonly encountered stimulant NPS.
[30]

Also refer to Annex 1: Report on WHO questionnaire for review of psychoactive substances.

14. Nature and Magnitude of Public Health Problems Related to Misuse,

Abuse and Dependence
Problems documented to date in relation to the use of ethylphenidate are consistent with the
actions and effects of an amphetamine-like stimulant. Based on this, as well as user reports
and documented cases of toxicity, it would be expected that use of ethylphenidate will be
particularly associated with adverse effects on mental health (including paranoia, psychotic
effects, anxiety, depression) and risk of potentially fatal cardiovascular disorders.

Some problems have been noted in relation to the route of administration used. The most
common route of use is by nasal insufflation and it has been reported that this can be
associated with intense pain, nosebleeds and tears [2, 17]. In addition, ethylphenidate
injections have been associated with severe soft tissue infections in a series of 9 cases in the
UK. However, there were a number of confounding factors, including the presence of other
drugs and substances (e.g. citric acid) in the injection solution, contamination and poor
injection technique, which make it difficult to assign a role to ethylphenidate itself. [4]

Concern has also been raised over existing drug injectors, particularly heroin injectors,
moving to administration of NPS such as ethylphenidate. A survey conducted in the UK
suggests that a change to ethylphenidate administration leads to significant adverse effects
on physical and mental health along with an increase in risky behavior (e.g. sharing
equipment, infection transmission), with a resultant increased demand on health services.
[31]

Also refer to Annex 1: Report on WHO questionnaire for review of psychoactive substances.

15. Licit Production, Consumption and International Trade

None

16. Illicit Manufacture and Traffic and Related Information

Ethylphenidate, in tablets and powder form, has been seized in a number of countries
including France [32], Germany [16], UK [5, 30] and Italy [25].

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Also refer to Annex 1: Report on WHO questionnaire for review of psychoactive substances.

17. Current International Controls and Their Impact

Ethylphenidate is not controlled under the 1961, 1971 or 1988 United Nation Conventions.
Structurally, ethylphenidate is a homologue of methylphenidate, a stimulant used in the
treatment of attention deficit hyperactivity disorder (ADHD) which is controlled as a
Schedule II substance under the U.N. 1971 Convention on Psychotropic Substances.

18. Current and Past National Controls

Ethylphenidate is under control in the following countries [23]: United Kingdom (2015),
Germany (2013), Denmark (2013), Poland (2015), China (2015), Austria (2012) and
Sweden. It is also covered by analogue legislation in a number of countries due to its
similarity to methylphenidate.

Also refer to Annex 1: Report on WHO questionnaire for review of psychoactive substances.

19. Other Medical and Scientific Matters Relevant for a Recommendation on

the Scheduling of the Substance
None

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References

1. UNODC. Ethylphenidate. Laboratory and Scientific Section Portal 2016 15/08/2016];

Available from: https://www.unodc.org/LSS/Substance/Details/216e8a35-f131-4834-874e-
d237e4e603c3.
2. Maskell, P.D., et al., Seven fatalities associated with ethylphenidate. Forensic Science
International, 2016. 265: p. 70-74.
3. Parks, C., D. McKeown, and H.J. Torrance, A review of ethylphenidate in deaths in east
and west Scotland. Forensic Science International, 2015. 257: p. 203-208.
4. Yong, L.Y., et al., Injected novel legal highs associated with severe soft tissue infection: A
regional hand unit's experience. The Surgeon.
5. Santacroce, R., et al., Psyclones: a roller coaster of life? Hidden synthetic cannabinoids
and stimulants in apparently harmless products. Hum Psychopharmacol, 2015. 30(4): p.
265-71.
6. Soussan, C. and A. Kjellgren, "Chasing the high" - experiences of ethylphenidate as
described on international internet forums. Subst Abuse, 2015. 9: p. 9-16.
7. Patrick, K.S., et al., Synthesis and pharmacology of ethylphenidate enantiomers: the
human transesterification metabolite of methylphenidate and ethanol. J Med Chem, 2005.
48(8): p. 2876-81.
8. Casale, J.F. and P.A. Hays, Ethylphenidate: An analytical profile. Microgram J, 2011. 8(2):
p. 58-61.
9. Markowitz, J.S. and K.S. Patrick, Ethylphenidate: From biomarker to designer drug.
Mental Health Clinician, 2013. 3(6): p. 318-320.
10. Markowitz, J.S., et al., Ethylphenidate formation in human subjects after the
administration of a single dose of methylphenidate and ethanol. Drug Metab Dispos, 2000.
28(6): p. 620-4.
11. Koehm, M., G.F. Kauert, and S.W. Toennes, Influence of ethanol on the pharmacokinetics
of methylphenidate's metabolites ritalinic acid and ethylphenidate. Arzneimittelforschung,
2010. 60(5): p. 238-44.
12. Lalande, M., D.L. Wilson, and I.J. McGilveray, HPLC Determination of Methylphenidate
in Human Plasma. Journal of Liquid Chromatography, 1987. 10(10): p. 2257-2264.
13. Zhu, H.-J., K.S. Patrick, and S. Markowitz, Enantiospecific determination of dl-
methylphenidate and dl-ethylphenidate in plasma by liquid chromatography-tandem mass
spectrometry: Application to human ethanol interactions. Journal of chromatography. B,
Analytical technologies in the biomedical and life sciences, 2011. 879(0): p. 783-788.
14. Zhang, C., et al., Development and validation of an UFLC-MS/MS method for
enantioselectivity determination of d,l-thero-methylphenidate, d,l-thero-ethylphenidate and
d,l-thero-ritalinic acid in rat plasma and its application to pharmacokinetic study. J
Chromatogr B Analyt Technol Biomed Life Sci, 2016. 1011: p. 45-52.
15. Sulzer, P., et al., Designer Drugs and Trace Explosives Detection with the Help of Very
Recent Advancements in Proton-Transfer-Reaction Mass Spectrometry (PTR-MS), in
Future Security: 7th Security Research Conference, Future Security 2012, Bonn, Germany,
September 4-6, 2012. Proceedings, N. Aschenbruck, et al., Editors. 2012, Springer Berlin
Heidelberg: Berlin, Heidelberg. p. 366-375.
16. Krueger, J., et al., First detection of ethylphenidate in human fatalities after ethylphenidate
intake. Forensic Science International, 2014. 243: p. 126-129.

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17. Ho, J.H., et al., Ethylphenidate: availability, patterns of use, and acute effects of this novel
psychoactive substance. Eur J Clin Pharmacol, 2015. 71(10): p. 1185-96.
18. Negreira, N., et al., Identification of in vitro metabolites of ethylphenidate by liquid
chromatography coupled to quadrupole time-of-flight mass spectrometry. J Pharm Biomed
Anal, 2016. 117: p. 474-84.
19. Portoghese, P.S. and L. Malspeis, Relative hydrolytic rates of certain alkyl (b) dl-alpha-(2-
piperidyl)-phenylacetates. J Pharm Sci, 1961. 50: p. 494-501.
20. Schweri, M.M., et al., [3H]Threo-(+/-)-methylphenidate binding to 3,4-
dihydroxyphenylethylamine uptake sites in corpus striatum: correlation with the stimulant
properties of ritalinic acid esters. J Neurochem, 1985. 45(4): p. 1062-70.
21. Patrick, K.S., T.R. Corbin, and C.E. Murphy, Ethylphenidate as a selective dopaminergic
agonist and methylphenidate-ethanol transesterification biomarker. J Pharm Sci, 2014.
103(12): p. 3834-42.
22. Williard, R.L., et al., Methylphenidate and its ethanol transesterification metabolite
ethylphenidate: brain disposition, monoamine transporters and motor activity. Behav
Pharmacol, 2007. 18(1): p. 39-51.
23. Bailey, G.P., et al., Nopaine no gain: recreational ethylphenidate toxicity. Clin Toxicol
(Phila), 2015. 53(5): p. 498-9.
24. Pignon, B., et al., Dependence on Internet-Purchased Ethylphenidate. J Clin
Psychopharmacol, 2015. 35(4): p. 472-3.
25. Odoardi, S., F.S. Romolo, and S. Strano-Rossi, A snapshot on NPS in Italy: Distribution of
drugs in seized materials analysed in an Italian forensic laboratory in the period 2013–
2015. Forensic Science International, 2016. 265: p. 116-120.
26. Bertol, E., et al., A mixed MDPV and benzodiazepine intoxication in a chronic drug
abuser: Determination of MDPV metabolites by LC–HRMS and discussion of the case.
Forensic Science International, 2014. 243: p. 149-155.
27. Erowid. Ethylphenidate. [cited 2016; Available from:
https://erowid.org/chemicals/ethylphenidate/ethylphenidate.shtml.
28. Bluelight. Ethylphenidate. [cited 2016; Available from:
http://www.bluelight.org/vb/threads/603365-The-Ethylphenidate-(Ethyl-phenyl(piperidin-
2-yl)acetate)-Megathread-V1.
29. TripSit. Ethylphenidate. [cited 2016; Available from:
http://drugs.tripsit.me/Ethylphenidate.
30. Ford, L.T. and J.D. Berg, Analysis of legal high materials by ultra-performance liquid
chromatography with time of flight mass spectrometry as part of a toxicology vigilance
system: what are the most popular novel psychoactive substances in the UK? Ann Clin
Biochem, 2016.
31. Lafferty, C., et al., The experience of an increase in the injection of ethylphenidate in
Lothian April 2014-March 2015. Scott Med J, 2016.
32. Roussel, O., et al. The development of new psychoactive substances in France. in 53rd
Annual Meeting of The International Association of Forensic Toxicologists. 2015.
Florence.

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Annex 1: Report on WHO Questionnaire for Review of Psychoactive

Substances for the 38th ECDD: Evaluation of Ethylphenidate
Data was obtained from 47 Member States (6 AFR, 2 EMR, 26 EUR, 7 PAH, 1 SEAR and 5
WPR).

A total of 44 Member States (4 AFR, 2 EMR, 24 EUR, 7 PAH, 1 SEAR and 6 WPR) answered the
questionnaire for Ethylphenidate (EPH). Of these, 21 respondents (16 EUR, 2 PAH and 3 WPR)
had information on this substance.

LEGITIMATE USE

There were 20 countries that reported no approved medical products containing EPH for human or
veterinarian indications. There was also no reported industrial use in 16 countries.

EPH is currently being used in medical or scientific research in one country for metabolism and
abuse potential research. Importation is the origin/source of EPH when used for legitimate non-
medical/non-scientific use.

EPH was not reported to be used for any cultural, religious or ceremonial purposes in 18 countries.

EPIDEMIOLOGY OF NON-MEDICAL/NON-SCIENTIFIC USE – USE FOR

PSYCHOACTIVE PURPOSES OR RECREATIONAL DRUG USE

There were 16 countries that reported EPH as being misused for its psychoactive properties (as a
recreational drug). Common routes of administration for non-medical/non-scientific purposes are
oral (8 countries), sniffing (6 countries), injection (4 countries), inhalation (3 countries) and
smoking (3 country). The main route of administration for EPH was reported as oral (3 countries),
sniffing (2 countries), smoking (1 country) and injection (1 country). One country commented that
it was “through the nose”.

The most common formulation reported for non-medical/non-scientific purposes was powder (13
countries), followed by tablets (5 countries), liquid or solution for oral administration/use (3
countries) and injectable (2 countries) formulations. Other formulations reported were EPH
impregnated plant material (2 countries) and tobacco (1 country).

There were 12 countries which reported that the source of EPH for non-medical/non-scientific use
was smuggling.

Party settings (1 country) and former/current injectors of heroin (1 country) were specified as
subpopulations known to misuse EPH.

The level of negative health-impact originating from this substance's non-medical consumption
was reported as either negligible (1 country), substantial (4 countries) or serious (5 countries). For
the countries that indicated a substantial or serious level of negative health-impact, they specified
that it was due to the association of EPH with adverse effects (including intoxications,
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transmission of communicable diseases through injection drug use for example large number of
soft tissue infections which can result in prolonged hospital admissions and extensive surgical
interventions) and fatalities. It was also commented that EPH has mild amphetamine-like side
effects and is related to methylphenidate which has been reported as addictive.

Three countries reported emergency room/department visits related to the non-medical use of
EPH. A combined total of 2 cases in 2012 and 19 cases (no further information or time frame)
were provided.

The adverse effects which presented for EPH at the emergency room/department included
hypertension, pupil dilation, mouth dryness, high pulse, elevated body temperature, restlessness,
hallucinations, seizures, palpitations, chest pain, fever, drowsiness, anxiety, paranoia, visual
disturbance, agitation, bilateral intention tremor and paresthesis. Increased urea and creatine kinase
were also listed.

In regards to the mortality rate, data was provided by 4 countries. The rate which included
involvement of other substances was reported to be 26 cases in 2013, 9 cases in 2014 (in 7 cases
EPH was not reported as cause of death), 9 cases in 2015 and 2 cases in 2016 to date. Finally the
rate, where it was unknown if other substances were involved was 19 cases in 2015 and 6 cases in
2016 to date. Another country commented that there may be a higher number of cases because in
their country there is no reporting obligation by hospitals, poison centers etc.

STATUS OF NATIONAL CONTROL AND POTENTIAL IMPACT OF

INTERNATIONAL CONTROL

There were 17 countries reported that EPH was under national control. The legislation the control
is based upon included Medicines Act (2 countries), Controlled Substances Act (11 countries),
Criminal Law Act (1 country), Analog Act (1 country) and other specific legislation (2 countries
stated that it was specific legislation for new psychoactive substances). In one country, the control
is a temporary provision, ending in June 2017 and it was commented that it will likely become
permanently controlled following that. There were no challenges to implementing controls for
EPH reported.

The scope of the controls includes production (14 countries), manufacturing (15 countries),
exporting (15 countries), importing (17 countries), distribution (16 countries), use (12 countries)
and possession (14 countries).

Reported illicit activities involving EPH include manufacture of the substance by chemical
synthesis (1 country), trafficking (9 countries), smuggling (1 country), diversion (1 country),
domestic internet sales (1 country), internet sales from abroad (7 countries), internet sales from
unknown locations (4 countries) and finally sales to people who use this substance (5 countries).

There were 13 countries which completed the section on the number of seizures. The combined
number of seizures was 584 (2014), 670 (2015) and 80 (2016 to date). One country stated that
EPH has been seized since 2012. Also, one country commented that they had noticed a decline of
cases as soon as the substance was placed under control by national legislation.

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38th ECDD (2016) Agenda item 4.7 EPH
If EPH was placed under international control, 20 countries responded that they would have the
capacity to enforce the control at the national level. There were 20 countries, which responded that
they would have the forensic laboratory capacity to analyse the substance.

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