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Drug residues in syringes and other injecting paraphernalia in Hungary

Article  in  Drug Testing and Analysis · May 2017

DOI: 10.1002/dta.2217

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DOI: 10.1002/dta.2217

SHORT COMMUNICATION

Drug residues in syringes and other injecting paraphernalia in

Hungary
Anna Péterfi1,2 | József Csorba3 | Tamás Figeczki3 | József Kiss3 |

Katalin Medgyesi‐Frank3 | János Posta4 | V. Anna Gyarmathy5,6

1
Hungarian National Focal Point (REITOX),
Budapest, Hungary
2
Eötvös Loránd University, Doctoral School of
Psychology, Budapest, Hungary
3
Hungarian Interchurch Aid, Hungary
4
University of Debrecen, Debrecen, Hungary
5
Johns Hopkins Bloomberg School of Public
Health, Baltimore, Maryland, USA
6
Semmelweis University, Budapest, Hungary
Correspondence
Anna Péterfi, Hungarian National Focal Point
(REITOX), 1 Lorántffy Zs. út, 1022 Budapest,
Hungary.
Email: peterfi@gmail.com
Funding information
European Union, Grant/Award Number:
JUST/2013/ISEC/DRUGS/AG/6418
The appearance and spread of new psychoactive substances (NPS) is a phenomenon seen
throughout Europe since 2008. Synthetic cathinones, a group of NPS, have been self‐reported
as the drug injected by the vast majority of people who inject drugs (PWID) in Hungary. This
study aims at updating our knowledge of what exactly are the compounds injected by PWID.
This multi‐site study analysed residues from used injecting drug paraphernalia collected from
PWID via low‐threshold services and from public places in Budapest, Debrecen, Miskolc, Szeged,
Békéscsaba and Pécs between March 2015 and February 2016. The paper describes the results
of the chemical analysis of 2985 analytical samples created out of the 22 005 objects collected in
this period. Active agents and their occurrences (compound cases) were identified using GC–MS.
The study detected 161 different compounds, mostly synthetic cathinones (29%), non‐psychoac-
tive compounds (14%), amines (12%), non‐psychoactive medications (12%) and other substances
(32%). Of the 12 762 compound cases, 50% were cathinones, 18% substitution medications, 9%
non‐controlled psychoactive substances and 24% other substances. Among compound cases, the
most frequent cathinones were pentedrone (21%) and α‐PHP (12%). Among substitution medica-
tions, most were methadone (93%), and non‐controlled psychoactive substances were caffeine
(74%) and nicotine (21%). Overall, the most prevalent substances were methadone (16%),
pentedrone (10%) and caffeine (7%) with considerable variation detected among participating
cities.
Our results are consistent with previous self‐reported data showing a high prevalence of syn-
thetic cathinone injection among PWID in Hungary. We also detected a large‐scale misuse of
methadone by PWID.

KEY W ORDS

GC–MS, injecting paraphernalia, methadone misuse, new psychoactive substances, people who
inject drugs

1 | I N T RO D U CT I O N tripled among people who inject drugs (PWID) in Hungary between

Europe has experienced the growth and dispersion of new psychoac-
tive substances (NPS) since 2008. Seizures of NPS increased seven‐
fold between 2008 and 2013 in Europe: a total of 482 new substances
were reported to the European Monitoring Centre for Drugs and Drug
Addiction (EMCDDA) Early Warning System1 in this period. However,
the scale of the phenomenon in terms of spatial diffusion, prevalence
and affected populations varies across Europe. Data from police sei-
zures, needle and syringe programmes, and research studies suggest
NPS use is increasing in Hungary.2-9 National data collected by the
REITOX Hungarian National Focal Point (HNFP) indicate NPS injection
2011 and 2015, from 26 to 80%.5 HNFP collects self‐reported data
annually among registered clients at needle and syringe programmes
in Hungary assessing the primary drug injected. The first synthetic can-
nabinoids and cathinones emerged in street seizures in 2009.8 By
2013, the number of NPS seizures outnumbered those of ‘traditional’
substances in the national seizures statistics.4 The consumption of
NPS has been reported in problem drug users3-9 and recreational drug
users10 as well. However, the prevalence of lifetime NPS use among
16‐year‐old pupils (10.7% lifetime prevalence – LTP – of ‘designer
drug’ use)11 and among 18‐ to 34‐year‐old adults (4.2% LTP of syn-
thetic cannabinoid use, 2.7% LTP of ‘new stimulant’ use)12 in Hungary

Drug Test Anal. 2017;1–8. wileyonlinelibrary.com/journal/dta Copyright © 2017 John Wiley & Sons, Ltd. 1
2 PÉTERFI
is lower than in most European countries. At the same time cathinones
are self‐reported as preferred among PWID.3,5,6,9 Because of the rap-
idly evolving market of NPS and the fast emergence of new com-
pounds, little is known about the actual compounds injected by
PWID. The chemical analysis of residual content in injecting parapher-
nalia is a novel method 13,14
for identifying actual compounds injected
in Hungary. Self‐reported data from needle and syringe programmes
suggest that the injection of NPS is widespread among PWID in
Hungary.
The study reported here utilized a screening approach also applied
in a previous Swiss study to include as many substances in the analysis
as possible.14 While the Hungarian Institute for Forensic Sciences also
examines the content of injecting paraphernalia acquired via seizures,
this study applied a more inclusive method of sample collection in
order to provide a more comprehensive picture of the substances
injected. The study was first proposed within ‘Breaking the drug cycle’
of the Hungarian Interchurch Aid (ISEC project ID: 6418) with the aim
of providing analytically confirmed real‐time information on sub-
stances injected in six Hungarian cities in 2015 and 2016. Here we
present the results of the first 12 months of the 20‐month project.
2 | METHODS
2.1 | Collection of used injecting paraphernalia
Used and discarded injection‐related paraphernalia (needles and syrin-
ges and other paraphernalia typically used for drug injecting) were col-
lected between March 2015 and February 2016 at seven locations in
Hungary: Budapest districts 7 and 23, Debrecen, Miskolc, Szeged,
Békéscsaba and Pécs. Used paraphernalia were submitted directly by
PWID to the needle and syringe programmes among partner organiza-
tions and also collected from the streets in the neighbourhoods of the
partner organisations. At one location injecting paraphernalia was
obtained from syringe vending machines as well. Samples were also
collected from the streets and syringe vending machines in addition
to low‐threshold programmes to ensure that injecting equipment from
a diverse population of PWID was included.
2.2 | Sample preparation and chemical analysis
Altogether, 22 005 objects (injection‐related paraphernalia) were col-
lected during the 12‐month study period. These items were converted
into 3261 composite samples by grouping the objects on the basis of
location, month of submission, packaging and visual similarities (e.g.
type and colour of syringes). Each composite sample consisted of
between 1 and 25 objects (mean 4.65; mode 3) (e.g. a syringe and a
spoon or four syringes).
For preparation, syringe needles were removed from the syringes
using a high‐frequency oscillating knife. Paraphernalia were then
rinsed 5–10 times with 100–150 μL of high‐purity water (ca 37°C).
Extracts of the residues found on objects belonging to the same com-
posite sample were analysed together as one analytical sample. After
the water evaporated, 20–40 μL of chloroform–ethanol solution was
added to the recovered sample. The active agents of the substance
residues were identified using a gas chromatography method with
ET AL.
mass spectrometry detection (Agilent 7890A GC system, 7693
Autosampler, 5975C MSD; MSD ChemStation E.02.02.1431 software
from Agilent Technologies, Santa Clara, CA, USA) at the Toxicology
Laboratory of the Institute of Forensic Medicine of the University of
Debrecen. The analysis had the following parameters: capillary column,
J&W DB‐35MS UI, 30 m × 0.25 mm × 0.25 μm; injection volume, 1 μL;
injector temperature, 250°C. Sampling settings were the following:
split ratio, 20:1; oven temperature programme, 80°C (1 min), heating
15°C/min up to 300°C, 21 min hold times; interface, 280°C; MS
source, 230°C; ionization, EI; detection mode, SCAN. This study
followed a screening approach to identify all possible active agents
instead of confirming the presence of a list of substances. Therefore
the identification of the compounds was carried out by means of ana-
lytical standards or with the help of international mass spectral libraries
(Table 1) (Cayman Spectral Library v.05202016, SWGDRUG MS
Library v.2.4, PMW Tox3 Library, NIST08 Mass Spectral Library v2.0,
SUDMED 2288 Library, EMCDDA EDND database). Chromatograms
were analysed using Enhanced Chemstation. The identified com-
pounds were grouped into one of ten categories, based on a combina-
tion of legal and chemical status, as follows. (A) Controlled substances:
1, cathinones; 2, amines (including phenethylamines, indolalkylamines,
arylalkylamines, arylcyclohexylamines); 3, cannabinoids (including nat-
ural and synthetic cannabinoids); 4, opioids; 5, cocaine; (B) diverted
medications: 6, substitution medications; 7, other psychoactive medi-
cations; 8, non‐psychoactive medications; and (C) other: 9, other
non‐controlled psychoactive substances; 10, other non‐psychoactive
compounds.
2.3 | Data management and analysis
As this analysis focused on assessing the substances injected, only data
related to the composite samples that held at least one of the following
types of objects were included: (1) needle, (2) syringe, (3) bottom of tin
can, (4) metal cap, (5) heating tin, (6) metal container, (7) metal spoon.
These objects were associated with injecting route of administration
while composite samples that failed to comply with this inclusion crite-
rion were excluded.
During the 12‐month study, consolidation of collected drug para-
phernalia resulted in 3261 composite samples each representing an
independent unit of analysis (analytical sample). The chemical analysis
detected at least one active agent in 3132 cases (96%), with 129 ana-
lytical samples containing no active agents. Among the 3132 compos-
ite samples with at least one active agent, 2985 contained objects that
were directly linked to injecting. Only these 2985 injection‐related
samples were included in the final statistical analysis. Analytical sam-
ples held between one and 18 active agents. Each of these active
agents was registered as a ‘compound case’ regardless of the number
of active agents identified in the same analytical sample. Overall the
2985 analytical samples contained 13 936 compound cases.
Among the active agents detected in the analytical samples, 7
compounds were unknown/unidentified making up 86 of the com-
pound cases. These unknown compounds were excluded from the
analysis. In addition, there were 20 substances (metabolites and syn-
thesis markers) which were categorized as the parent compound. As
such, 1088 compound cases were removed to avoid the duplication
PÉTERFI ET AL. 3

TABLE 1 Reference of chemical identification of the most frequent substances in each category
Detection was based on analytical
Category Substance Source of analytical standard libraries

Synthetic cathinones Penredrone HIFSa

α‐PHP HIFSa
Mephedrone Lipomed AGb
Isopentedrone ×
α‐PVP Lipomed AGb
α‐pep HIFSa
TV‐PVP HIFSa
4‐CMC HIFSa
Isomephedrone ×
Substitution medications Methadone Sigmac
Buprenorphine Lipomed AGb
Naloxone Purchased as licensed
medication Nexodald
Other non‐controlled psychoactive compounds Caffeine Lipomed AGb
Nicotine Reanale
Opioids Morphine Lipomed AGb
Codeine Lipomed AGb
Heroin Lipomed AGb
Meconin ×
Amines Amphetamine Lipomed AGb
DPIA ×
N‐acetylamphetamine ×
a
2‐MPA HIFS
Metamphetamine Lipomed AGb
MDMA Lipomed AGb
Other non‐psychoactive compounds Benzoic acid Sigmac
Acetylthebaol ×
Non‐psychoactive medications Acetaminophen Sigmac
Papaverine Sigmac
Griseofulvin ×
Other psychoactive medications Alprazolam Lipomed AGb
Ethylphenidate ×
Phenobarbital Lipomed AGb
Levamizol ×
a
Provided by the Hungarian Institute for Forensic Sciences, Budapest, Hungary.
b
Lipomed AG, Arlesheim, Switzerland.
c
Sigma‐Aldrich Kft., Budapest, Hungary.
d
OrPha Devel Handels und Vertriebs, Purkersdorf, Austria.
e
Reanal Zrt., Budapest, Hungary.

of the same active agent in the same analytical sample. Consequently,
the final analysis database contained 12 762 compound cases
(Figure 1).
All data management and analysis were performed in SAS V9.2.
3 | RESULTS
About half of the compound cases were detected in injecting para-
phernalia from Budapest district 7 (n = 7567), and the rest from Szeged
(n = 2831), Miskolc (n = 2419), Debrecen (n = 406), Budapest district
23 (n = 365), Békéscsaba (n = 249) and Pécs (n = 13).
Altogether, 161 unique compounds were detected. Most of the
identified compounds belonged to the group of synthetic cathinones
(29%), other non‐psychoactive compounds (14%), amines (12%) and
non‐psychoactive medications (12%) (Figure 2A). Of the 12 762 com-
pound cases, most were cathinones (6323; 50%) and substitution med-
ications (2279; 18%), followed by other non‐controlled psychoactive
substances (1152; 9%) (Figure 2B). Opioids (843; 7%), amines (686;
5%) and cocaine (19; 0%) were less common.
The 10 most frequently occurring substances in each category
are shown in Figure 3. Importantly, pentedrone and α‐PHP made
up 21% (1309 occurrences) and 12% (780 occurrences), respectively,
among all cathinone cases; methadone was 93% (2126 occurrences)
of all substitution medication cases; and caffeine (852; 74%) and
nicotine (244; 21%) were the top non‐controlled psychoactive
substances.
Ranking substances by frequency showed methadone (2126; 16%)
to be most common followed by pentedrone (1309; 10%) and caffeine
(852; 7%) (Figure 4). The substances traditionally associated with
injecting drug use were detected with a relatively low frequency:
amphetamine in 3% (367 occurrences), heroin in 2% (217 occurrences)
and cocaine in 0% (19 occurrences) of all compound cases. There was
considerable variation among the participating cities. The most fre-
quently occurring active agents were methadone (41; 17%) followed
by caffeine (29; 12%) in Békéscsaba, pentedrone (950; 13%) and
isopentedrone (630; 9%) in district 7 of Budapest, methadone (108;
36%) and caffeine (40; 13%) in district 23 of Budapest, caffeine (71;
17%) and α‐PHP (60; 15%) in Debrecen, methadone (581; 26%) and
pentedrone (207; 9%) in Miskolc, and methadone (757; 34%) followed
4 PÉTERFI
FIGURE 1 Methodological overview [Colour figure can be viewed at wileyonlinelibrary.com]
by mephedrone (395; 18%) in Szeged (Pécs was excluded here due to
the low number of collected samples).
Heroin was detected at three out of the seven locations with a fre-
quency between 3 and 0% at the individual study locations (Budapest
district 7: 206 occurrences, 3%; Budapest district 23: 8 occurrences,
3%; Miskolc: 3 occurrences, 0%; Békéscsaba, Debrecen, Pécs and
Szeged: 0 occurrences, 0%). Amphetamine was detected in Debrecen
in 16% (46 occurrences) and at other locations between 4 and 1%
(Békéscsaba: 6 occurrences, 2%; Budapest district 7: 263 occurrences,
4%; Budapest district 23: 4 occurrences, 1%; Miskolc: 17 occurrences,
1%; Pécs: 1 occurrences, 1%; Szeged: 30 occurrences, 1%).
4 | D I S C U S S I O N A N D CO N C L U SI O N S
Our study identified a large variety of substances within injecting par-
aphernalia throughout the 12 months of the study, including psychoac-
tive and non‐psychoactive agents. Out of the 161 different
compounds detected, cathinones greatly outnumbered every other
category with 47 different substances belonging to this group. Seizures
data show that some of these substances remain on the market for
2
years, but most rapidly cycle through the Hungarian drug market.
Our study found that synthetic cathinones were the most
commonly injected substances by Hungarian PWID. The findings are
consistent with both seizures data and self‐reported data from needle
and syringe programmes.2-8 Widespread use of NPS in the PWID com-
munities was also reported in Romania; however, the injection of NPS
has been detected in several other European countries as a sporadic
15
pattern or associated with specific user groups (e.g. MSM in Ireland).
A recent study identified injection of NPS in eight additional countries
(Austria, France, Finland, Ireland, Latvia, Slovenia, Sweden, UK).16 The
ET AL.
predominance of injecting synthetic cathinones among PWID in
Hungary is temporally associated with the recent heroin drought and
low purity of amphetamine.3,4,6 Heroin drought was experienced by a
number of European countries in 2010 and 201117 but in most of them
the availability of the substance has been increasing since then.18 In
Hungary the availability of heroin (assessed by the number of seizures)
shows a slight increase since 2011; nevertheless it was still relatively
low in 2014.18 Police investigation suggests Hungary is not a destina-
tion but a transit country for the larger European heroin market.19 The
continued low availability of heroin may be attributable to NPS filling
the market gap in Hungary after the heroin shortage of 2010 and
2011, providing a cheaper, semi‐legal alternative for the classical
substances. However, the cross‐sectional nature of our data limits
the ability to directly assess changes in the heroin and NPS market
over time and it remains unclear why this market reorganization was
not detectable in other European countries.
The long‐term health consequences of injecting these new syn-
thetic stimulants are still unknown, but some alarming trends have
been reported. Among them is the elevated risk of transmission of
HCV and HIV infection associated with the injection of NPS in
Hungary which is attributable to high‐risk behaviours such as syringe
sharing, daily injection, imprisonment and homelessness in the past
year, relative to primary opioid and amphetamine injectors.5,9,20
Since route of administration impacts the risk assessment of NPS,
the study results have been shared with the National Centre for Addic-
tions that is responsible for the risk assessment of emerging drugs in
Hungary.
A novel finding of our study is the relatively high (16%) prevalence
of methadone among the compound cases. Methadone injecting and
its diversion from therapeutic use is a common problem in connection
with opiate substitution therapy.13,21-23 However, no other studies in
PÉTERFI ET AL.
FIGURE 2 (A) number of individual
compounds identified. (B) Total number of
compound cases by substance group [Colour
figure can be viewed at wileyonlinelibrary.
com]
Hungary have shown such a high prevalence of methadone injection as
suggested by our results. As a matter of fact, methadone is almost
4
invisible in data reported by needle and syringe programmes' clients.
A possible explanation of the high consumption of methadone is the
aforementioned heroin drought.6,17,19 Before 2010, heroin was the
drug most frequently injected in Hungary, but it has virtually
disappeared from the illicit drug market in the past six years.4 Although
clients of needle and syringe programmes reported shifting to stimu-
lants (mostly cathinones) as a primary drug, the preference would
probably still be opioids if available. Due to the lack of availability of
heroin in Hungary, methadone is a viable replacement option.
Although the injection of methadone is not a novel phenomenon, it
presumably became prevalent due to these market changes in the
availability of heroin. As data collection in needle and syringe
programmes is limited to the primary substance injected, this may
explain the low prevalence detected by Rácz et al.3 and by the HNFP
report.4 Additionally sampling bias may limit the generalizability of
our study as five out of the seven study locations provided opiate
substitution treatment; therefore evidence of methadone diversion is
5
more likely within drug‐related litter collected by these services and
within their neighbourhoods and may over‐represent methadone
diversion among PWID not engaged with a needle and syringe
programme.
Caffeine was among the most frequently occurring substances. It
is not a surprising outcome as caffeine is a popular adulterant for
amphetamine, cocaine and heroin.4,24
Nicotine was also relatively prevalent in the samples. Based on the
chemical analysis it was not possible to determine if nicotine was used
as a cutting agent or injected on purpose. The reason for its presence
in injecting paraphernalia requires further investigation.
In a few cases, the study detected synthetic cannabinoids in
injecting paraphernalia. It can be assumed that these cases are due to
the unintended purchase and injection of synthetic cannabinoids as
needle and syringe programme service providers did not report the
injecting administration of these substances in their clientele and also
because the content of the powders can mingle at some point in the
supply chain (personal communication with the Hungarian Institute
for Forensic Sciences).
6 PÉTERFI
FIGURE 3 Breakdown of the most frequently occurring compounds by substance group [Colour figure can be viewed at wileyonlinelibrary.com]
The detection of metabolites in injecting paraphernalia is most
probably due to the fact that analysed syringes commonly contained
blood as a result of registering (when a small amount of blood is
withdrawn into the paraphernalia prior to injecting).
It is also noteworthy that in 129 analytical samples no active agents
could be detected by the chemical analysis. The absence of active
14
agents in injecting paraphernalia was also reported by Lefrançois et al.
The study detected marked geographical differences in the sub-
stances injected. There is no available study on the factors determining
local patterns in the country. However, the differences of the supply
side characteristics of the local drug market (structure, distribution sys-
tem, pricing), the composition of users (e.g. social conditions, price elas-
ticity of demand, attitude to NPS) and the availability of treatment
services (such as opiate substitution treatment) might have a determin-
25
ing role.
Based on the outcomes of this study it can be concluded that the
analysis of used and disposed injecting paraphernalia is a useful
approach for drug monitoring. It has the ability to (a) detect the
injecting use of emerging substances enabling risk assessment; (b)
detect phenomena, such as methadone injecting, that are invisible to
other data sources and indicators; and (c) be used to cross‐validate
trends observed in established indicators such as the injecting of
NPS in self‐reported and police seizures data.
ET AL.
5 | LIMITATIONS
Several limitations are noteworthy. The analytical strategy of the study
was to utilize international mass spectral libraries beside the available
analytical standards in order to detect a large variety of substances. Com-
posite samples represented a unique challenge. The detection of several
compounds in one composite/analytical sample may mean the following:
(1) several objects were collected together and each object contained dif-
ferent or various compounds; (2) one compound is the main component
and the other components are adulterants; (3) one injecting parapherna-
lia was used several times to inject several different drugs.14,15 If one
sample consisted of objects that were used in multiple injections injecting
different drug purchases, overlapping compounds were reported only
once, resulting in underreporting of that particular compound. In addi-
tion, the statistical analysis included all compounds linked to a sample,
not only the so‐called ‘main components’. Since objects were pooled in
a composite sample, it was not possible to disentangle which compound
was the main versus additional components within objects that were
parts of the composite sample. Another limitation is that the unit of anal-
ysis was the composite sample and frequency or number within a com-
posite sample cannot be distinguished. However, since the goal of the
analysis was to provide a cross‐section of the substances injected during
12 months in the participating cities in Hungary, it is irrelevant if the
PÉTERFI ET AL.
FIGURE 4 Geographical differences: Most frequent compounds detected. (Pécs was excluded from this analysis due to low sample size) [Colour
figure can be viewed at wileyonlinelibrary.com]
compound was a main or a non‐main compound and whether it was an
additive or a residue.
In order to reduce the effect of the bias caused by the grouping of
the injecting paraphernalia based on location, date of collection, pack-
aging and visual similarities, the calculations in this study were based
on compound cases.
Another limitation is that with the applied method of chemical
analysis it was not possible to identify 7 unique compounds (Unknown
(58,100), Unknown (109,252), Unknown (120), Unknown (126),
Unknown (129,145), Unknown (135), Unknown (196)) detected in a
total of 86 analytical samples. The reason for this is that due to the
sampling method, the amount of material available for extraction of
compounds was miniscule – enough to identify known compounds
but not enough to classify unknown compounds. It is possible that
these 7 unique compounds were NPS that have been unknown so
7
far, but they may also have been other known compounds. Given these
7 unique compounds are less than 5% of the total, it is unlikely that this
error would have significantly altered our findings.
ACKNOWLEDGEMENTS
This study was supported by the European Union (JUST/2013/ISEC/
DRUGS/AG/6418) and coordinated by the Hungarian Interchurch Aid.
The authors would like to thank the MÖSZ Debreceni Szociális és
Fejlesztő Központ, the MÖSZ Soroksári Addiktológiai Centrum, the
ArtÉra Alapítvány, the Dr Farkasinszky Terézia Ifjúsági Drogcentrum,
the Mi‐Értünk Prevenciós és Segítő Egyesület, the Drogambulancia
Alapítvány and the INDIT Közalapítvány for the collection of the
samples and the Toxicology Laboratory of the Institute of Forensic
Medicine of the University of Debrecen for the chemical analysis of
the collected objects.
8 PÉTERFI
The views expressed in this report are those of the authors and
not necessarily those of the Hungarian Interchurch Aid or other
organizations with which the authors are affiliated.
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How to cite this article: Péterfi A, Csorba J, Figeczki T, et al.
Drug residues in syringes and other injecting paraphernalia in
Hungary. Drug Test Anal. 2017;1‐8. https://doi.org/10.1002/
dta.2217