EMCDDA Initial Report 3 CMC Advance Release

INITIAL REPORTS 11
ISSN 2600-0954
0000-0000
3-CMC
Utminusamasfsitibusa
volupta EMCDDA aut
EMCDDA initial report on the new psychoactive
substance 1-(3-chlorophenyl)-2-(methylamino)
Ernam sequiatet omnis sundige neceprem cus
propan-1-one (3-chloromethcathinone, 3-CMC)
dic te dolum est, custiat asperis quia sectae
consequis dem landandae eveliqu iatusap
isciunti officiis corest, comniet ommodio
In accordance with Article 5b of Regulation (EC) No 1920/2006
(as amended)
About this series

publication
EMCDDA
Nisitat quationse
initial reports
numque arevoluptas
drawn up assunt
on one or several similar new
quam, eat aliquos
psychoactive substances
nis ant fuga.
that may
Ur alit
pose health or social risks at European
qui veliqui
Union level.netur? Iquas ipsusa verchil
magnimusam, tem fugias
Initial reports provide atemodi
scientific num lit
evidence to the Commission in order to allow
vera uis nonsequiam, siminus mi, nonem
it to make an informed decision regarding whether or not there is a need to
eaqui tende
request a riskvoluptate
assessmentnum.on a new psychoactive substance.
INITIAL REPORT I 3-CMC
Contents
Acknowledgments ................................................................................................................... 3
1. Introduction ......................................................................................................................... 4
2. Information collection process ............................................................................................ 5
3. Methodological note ............................................................................................................ 7
4. Information required by Article 5b(2) of the Regulation ...................................................... 8
4.1. Nature, number and scale of incidents showing health and social problems in which the
new psychoactive substance may potentially be involved, and the patterns of use of the new
psychoactive substance (Article 5b(2a)) ................................................................................. 8
4.2. Chemical and physical description of the new psychoactive substance and the methods
and precursors used for its manufacture or extraction (Article 5b2(b)) ................................. 13
4.3. Pharmacological and toxicological description of the new psychoactive substance
(Article 5b2(c)) ...................................................................................................................... 22
4.4. Involvement of criminal groups in the manufacture or distribution of the new
psychoactive substance (Article 5b2(d)) ............................................................................... 23
4.5. Information on the human and veterinary medical use of the new psychoactive
substance, including as an active substance in a medicinal product for human use or in a
veterinary medicinal product ................................................................................................. 25
4.6. Information on the commercial and industrial use of the new psychoactive substance,the
extent of such use, as well as its use for scientific research and development purposes .... 25
4.7. Information on whether the new psychoactive substance is subject to any restrictive
measures in the Member States ........................................................................................... 26
4.8. Information on whether the new psychoactive substance is currently or has been under
assessment within the system established by the 1961 Single Convention on Narcotic
Drugs, as amended by the 1972 Protocol, and the 1971 Convention on Psychotropic
Substances ........................................................................................................................... 28
4.9. Other relevant information ............................................................................................. 28
5. Analysis and assessment ................................................................................................. 29
6. References........................................................................................................................ 32
2
Acknowledgments
The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) would like to
thank the following for their contribution in producing this publication:
 the Early Warning System (EWS) correspondents of the Reitox national focal points
(NFPs) and experts from their national EWS networks;
 the Europol national units (ENUs) and Europol Project Synergy;
 the national competent authorities responsible for human and veterinary medicinal
products in the Member States, Norway, Iceland and Liechtenstein;
 the European Medicines Agency (EMA);
 the European Chemicals Agency (ECHA), the European Centre for Disease
Prevention and Control (ECDC), the European Food Safety Authority (EFSA) and the
European Commission; and
 the World Health Organization (WHO).
Project team: Rachel Christie, Paulete Duque, Michael Evans-Brown, Ana Gallegos,
Rita Jorge, Joanna De Morais, Gregorio Planchuelo and Roumen Sedefov.
Project leaders: Michael Evans-Brown, Ana Gallegos and Roumen Sedefov.
3
1. Introduction
1-(3-Chlorophenyl)-2-(methylamino)propan-1-one (3-chloromethcathinone, 3-CMC) is a

synthetic cathinone stimulant. It is a ring-substituted cathinone, which is structurally related
to methcathinone ( 1) and 4-chloromethcathinone (4-CMC) ( 2).
In Europe, 3-CMC is monitored by the EMCDDA as a new psychoactive substance ( 3)

through the European Union Early Warning System (EWS) in accordance with Article 5a of
Regulation (EC) No 1920/2006 (as amended) ( 4) ( 5).
3-CMC was formally notified as a new psychoactive substance ( 6) ( 7) by the EMCDDA on

behalf of Sweden on 14 October 2014. The notification was based on the identification of the
substance in a police seizure of 0.72 grams of powder made on 22 September 2014 in
Norrköping.
Since the formal notification, information on 3-CMC has been exchanged between the
EMCDDA and the European Union EWS Network (EMCDDA, Europol, Reitox national focal
points, and the Commission); the EMA have been kept duly informed.
The EMCDDA is currently monitoring 161 synthetic cathinones through the European Union
Early Warning System (EU EWS).
While the quantities of cathinone powders seized in Europe have been decreasing since
they peaked in 2015 and 2016, at around 1 800 kg per year, and falling to 750 kg by 2019,
during 2020 there was a significant increase, with approximately 3 300 kg of powders
seized. It appears, that at least in part, this increase has been driven by 3-CMC which
accounted for almost a quarter of the quantity of powders seized during 2020. In addition, 3-
methylmethcathinone (3-MMC), which is also currently the subject of an initial report
following its emergence in Europe, accounted for a similar quantity.
While information reported to the EMCDDA through the Early Warning System suggests that
some synthetic cathinones seized in Europe have originated from China, recently, there
have been an increasing number of reports of seizures that have originated from India,
including those relating to seizures of 3-CMC and 3-MMC. In addition, there has also been a
recent increase in the number of laboratories producing cathinones, including 3-CMC and 3-
MMC, seized in Europe.
(1) Listed in Schedule I of the 1971 United Nations Single Convention on Psychotropic Substances.
(2) Listed in Schedule II of the 1971 United Nations Single Convention on Psychotropic Substances.
(3) As defined in point 4 of Article 1 of Council Framework Decision 2004/757/JHA of 25 October 2004 laying down minimum
provisions on the constituent elements of criminal acts and penalties in the field of illicit drug trafficking (OJ L 335,
11.11.2004, p. 8).
(4) Regulation (EC) No 1920/2006 of the European Parliament and of the Council of 12 December 2006 on the European
Monitoring Centre for Drugs and Drug Addiction (recast) (O J L 376, 27.12.2006, p.1-13).
(5) Regulation (EU) 2017/2101 of the European Parliament and of the Council of 15 November 2017 amending Regulation
(EC) No 1920/2006 as regards information exchange on, and an early warning system and risk assessment procedure
for, new psychoactive substances (O J L 305, 21.11.2017, p.1-7).
(6) EMCDDA (2020), EMCDDA operating guidelines for the European Union Early Warning System on new psychoactive
substances. p. 15–6. http://www.emcdda.europa.eu/publications/guidelines/operating-guidelines-for-the-european-union-
early-warning-system-on-new-psychoactive-substances_en
substances. Guidance note 2. Formal notification of a new psychoactive substance.
https://www.emcdda.europa.eu/system/files/publications/12213/downloads/Guidance %20Note %202- %20Formal %20n
otification %20of %20a %20new %20psychoactive %20substance.pdf
4
Article 5b of Regulation (EC) No 1920/2006 (as amended) requires that ‘Where the Centre,
the Commission or a majority of the Member States considers that information shared on a
new psychoactive substance collected pursuant to Article 5a in one or more Member States
gives rise to concerns that the new psychoactive substance may pose health or social risks
at Union level, the Centre shall draw up an initial report on the new psychoactive substance’.
The initial report is submitted to the Commission and the Member States. The purpose of the
initial report is to provide scientific evidence to the Commission to allow it to make an
informed decision regarding whether or not there is a need to request a risk assessment on
a new psychoactive substance as set out in Article 5c of Regulation (EC) No 1920/2006 (as
amended).
Based on the information reported by the Network, on 9 September 2021, the EMCDDA
assessed the existing information ( 8) ( 9) on 3-CMC, based on the following criteria:
 reports of health problems;
 reports of social problems;
 reports of seized material;
 pharmacological and toxicological properties and analogy with better-studied

substances; and,
 potential for further spread.
The EMCDDA concluded that the assessment gave rise to concerns that 3-CMC may pose
health or social risks at Union level, and, consequently, determined that an initial report
should be produced.
2. Information collection process
In accordance with the requirements of Article 5b of the Regulation, on 13 September 2021,

the EMCDDA launched a procedure for the collection of additional information on 3-CMC in
order to support the production of the initial report.
The EMCDDA collected information through:
 a structured reporting form to the Reitox national focal points in the Member States,
Turkey, and Norway (Article 5b(4));
 routine monitoring of open source information;
 a search of open source information conducted specifically for the production of the
initial report which included: scientific and medical literature, official reports, grey
substances, Publications Office of the European Union, Luxembourg.
http://www.emcdda.europa.eu/publications/guidelines/operating-guidelines-for-the-european-union-early-warning-system-
on-new-psychoactive-substances_en
(9) This included information reported to the EMCDDA through the Early Warning System, including case reports and
aggregated datasets.
5
literature, internet drug discussion forums and related websites (hereafter, ‘user
websites’), and online vendors.
In addition, the EMCDDA also submitted requests to:
 The World Health Organization (WHO) in order to determine if 3-CMC is under

assessment or has been under assessment within the system established by the
1961 Single Convention on Narcotic Drugs, as amended by the 1972 Protocol, and
the 1971 Convention on Psychotropic Substances (‘United Nations system’).
 The European Medicines Agency (EMA) in order to determine if 3-CMC is used as

an active substance in a medicinal product for human or veterinary use at Union or
national level (Article 5b(5)). Specifically, the EMA was asked if 3-CMC is an active
substance in:
a. a medicinal product for human use or in a veterinary medicinal product that

has obtained a marketing authorisation in accordance with Directive 2001/83/
EC of the European Parliament and of the Council ( 10), Directive 2001/82/EC
of the European Parliament and of the Council ( 11) or Regulation (EC)
No 726/2004 of the European Parliament and of the Council ( 12);
b. a medicinal product for human use or in a veterinary medicinal product that is

the subject of an application for a marketing authorisation;
c. a medicinal product for human use or in a veterinary medicinal product whose

marketing authorisation has been suspended by the competent authority;
d. an unauthorised medicinal product for human use in accordance with Article 5

of Directive 2001/83/EC or in a veterinary medicinal product prepared
extemporaneously by a person authorised to do so under national law in
accordance with point (c) of Article 10(1) of Directive 2001/82/EC;
e. an investigational medicinal product as defined in point (d) of Article 2 of

Directive 2001/20/EC of the European Parliament and of the Council ( 13).
 Europol in order to provide information on the involvement of criminal groups in the

manufacture, distribution and distribution methods, and trafficking of 3-CMC, and in
any use of 3-CMC (Article 5b(6)).
(10) Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code
relating to medicinal products for human use (OJ L 311, 28.11.2001, p. 67).
(11) Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code
relating to veterinary medicinal products (OJ L 311, 28.11.2001, p. 1).
(12) Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community
procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a
European Medicines Agency (OJ L 136, 30.4.2004, p. 1).
(13) Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws,
regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in
the conduct of clinical trials on medicinal products for human use (OJ L 121, 1.5.2001, p. 34).
6
 The European Chemicals Agency (ECHA), the European Centre for Disease
Prevention and Control (ECDC) and the European Food Safety Authority (EFSA) in
order to provide the information and data at their disposal on 3-CMC (Article 5b(7)).
The information collection process was concluded on 8 October 2021. The EMCDDA
received responses from all 27 Member States, Turkey, and Norway. In addition, the
EMCDDA received responses from WHO, EMA, Europol, ECHA, ECDC, and EFSA.
3. Methodological note
3-CMC has been available on the drug market since 2014. Although 3-CMC is screened for
in many forensic and toxicology laboratories in Europe, it cannot be excluded that some
cases of 3-CMC are undetected or unreported, in particular in serious adverse events.
3-CMC has two positional isomers, whose discrimination poses analytical challenges. Due to
differences in reporting practices across Europe, the discrimination of 3-CMC from its
positional isomers is done in many, but not all, forensic and toxicology laboratories. For the
purposes of preparing this report, all detections where the positional isomer of 3-CMC has
not been specified to the EMCDDA have been excluded from the data analysis of physical
and biological samples. However, due to different reporting practices across Europe, it
remains possible that some detections reported as 3-CMC but that are actually a different
positional isomer, have been included.
For serious adverse events (SAEs), cases reported to the EMCDDA where the positional
isomer has not been specifically denoted have been included in the data analysis. However,
these cases are classified in the text as cases of ‘suspected exposure’ and not as
analytically confirmed cases. Certainty of exposure according to the Drug Exposure
Classification System (DECS) follows the same classification employed for SAEs.
Complementary data sources have been used in the preparation of the Initial Report:
 For the period comprised between 1 January 2014 and 31 December 2020, annual
aggregated seizure data which is systematically reported to the EMCDDA has been
used.
 For the period comprised between 1 January and 30 September 2021, event-based
data reported spontaneously to the EMCDDA, as well as data reported through
targeted requests for information (a structured reporting form sent to the Reitox
national focal points and responses to ad hoc information requests) have been used.
The bulk of this data, which is partial for the year 2021 and subject to change, has
been collected in two weeks and is not comparable to aggregated seizure data.
 Open source information identified through routine monitoring has also been used
throughout the report, when confirmed by Reitox national focal points.
Information on seizures reported by police and customs agencies is analysed separately. In

some cases, the seizure was either reported by the laboratory that analysed the sample,
without specifying whether the seizure was made by police or customs, the identity of the
reporting authority was either not specified by the reporting country or not clear from the
reports submitted to the EMCDDA. These cases are referred to as ‘Other seizures’.
7
4. Information required by Article 5b(2) of the Regulation
The order and titles of subsections 4.1 to 4.9, below, are as they appear in Article 5b(2) of
Regulation (EC) No 1920/2006 (as amended); sections 4.1 to 4.4 are cross-referenced with
the headings of Article 5b(2a) to Article 5b(2d) of the Regulation.
4.1. Nature, number and scale of incidents showing health and social problems
in which the new psychoactive substance may potentially be involved, and the
patterns of use of the new psychoactive substance (Article 5b(2a))
4.1.1. Information from seizures, collected samples and biological samples
The available evidence suggests that 3-CMC has been present on the European drugs
market since at least September 2014. The substance has been detected across a total of
23 Member States, and Norway. These detections relate to 9 607 seizures, 67 collected
samples and 213 biological samples.
Most reports related to the first identification of 3-CMC in a country occurred between 2014
and 2016 (n=16; 67 %), around the first identification in Europe.
Information from seizures
In total, 9 607 seizures, amounting to 2.7 tonnes of material (in all physical forms) were
reported by 23 countries. Of these, 1.1 tonnes were reported in the period of 2014 to 2020.
The remaining 1.6 tonnes were reported in 2021.
The large majority of the cases reported (9 375; 98 %) were seizures of powders, amounting
to 2.7 tonnes (Figure 1). To a much lesser extent, seizures of tablets and capsules (196
cases), other or unknown physical forms (21), herbal material (7), liquids (7), blotters (1),
were also reported. For this reason, the following analysis is focused on seizures of
powders.
A total of 9 375 seizures of powders were reported. The majority of cases comprise police
seizures (6 702 cases; 71 %). There were 533 cases reported by customs (6 %) and 2 140
other seizures (23 %) for which the seizing authority is either not reported or not known.
The majority of cases were reported by Poland (7 663 cases; 82 %). The country reporting
the largest quantities of seized powders was the Netherlands (2.1 tonnes; 78 %). Of these,
697 kg were seized in 2020, and 1.4 tonnes in 2021, by Dutch customs.
A summary of the information reported is provided below.
8
FIGURE 1
Quantity of 3-chloromethcathinone (3-CMC) powder seized in kg – Europe, 1 January
2012– 30 September 2021
Customs Police Other
1800
1350
900
450
0
2014 2015 2016 2017 2018 2019 2020 2021
Customs seizures
Since 2014, customs authorities have reported 533 seizures of 3-CMC amounting to 2.2
tonnes of powders. Of these, 165 seizures (1.4 tonnes; 65 %) occurred in 2021. While most
seizures were reported by Sweden (199 cases; 37 %), the largest quantities of powders
were seized in the Netherlands (2.1 tonnes; 94 % of customs seizures).
Customs seizures were typically larger in quantity than those reported by police and provide
some evidence of attempts to import large amounts of 3-CMC powders to Europe.
The largest single seizure was also reported by Dutch customs and occurred in 2021. The
seizure comprised of 400 kg of 3-CMC powders, also containing iso-3-CMC, which may
have been leftover impurity of synthesis. An additional 4 seizures, weighing a total of 1 tonne
of 3-CMC powders were also reported by Dutch customs in 2021.
For the majority of customs seizures, the origin of the consignment was not reported (520
cases; 1.5 tonnes). For the 13 cases where the origin of the consignment is known, the
largest quantity of powders originated in India (6 seizures pure powder amounting to 695 kg,
seized in the Netherlands, in 2020). In addition, 2 seizures were reported in 2015 which
originated in China and amounted to 5.9 kg. Whenever European countries were mentioned
as the country of origin (n=5), the consignments were typically small (less than 5 grams).
Belgium and the Netherlands were the only countries of origin mentioned in those cases.
The purity of 3-CMC detected was rarely reported. In the seizures that originated in India, 3-
CMC consisted of pure white powders. Sometimes, they were reported as ‘crystals’ or
‘rocks’. When reported, labels referred to ‘3-CMC’ or ‘Clophedrone’.
9
For the very few cases were other substances were reported, the powders typically
contained other stimulants such as other cathinones (including 3-MMC) and, amphetamine
(in 8 cases). One noteworthy exception was the seizure mentioned above where iso-3-CMC
was detected in 3-CMC powders. Adulterants and diluents reported included caffeine,
benzocaine, menthol and mannitol.
Police seizures
Since 2014, police authorities have reported 6 702 seizures of powders containing 3-CMC,
amounting to 322 kg (Figure 2).
Poland, Germany and Sweden reported 99 % of the powders seized (6624 seizures
amounting to 318 kg). Poland reported 94 % of all Police seizures (6329 cases) and half of
the quantity of powders seized by police (160 kg); German Police reported 28 seizures
(102 kg); and Swedish police reported 267 seizures (57 kg powders) all of which occurred in
2021. The remaining countries reported considerably smaller amounts.
FIGURE 2
Quantity of 3-chloromethcathinone (3-CMC) powder seized by police in kg – Europe,
1 January 2012– 30 September 2021
175
140
105
70
35
0
2014 2015 2016 2017 2018 2019 2020 2021
The largest single seizure of 3-CMC by police occurred in 2020 in Germany, in Bavaria. The
seizure consisted of 80 kg of powders contained in barrels labelled ‘Clophedron’. No other
substances were detected.
In reports of police seizures, quantification of the purity of the powders is typically not
provided. In the 12 cases where quantitative information on purity was provided (reported by
Germany) powders ranged from 79.5 % to 98.1 % purity. The purest powders were reported
as the hydrochloride salt of 3-CMC and the less pure were reported as the base form.
10
Other substances detected in police seizures (not quantified) included other cathinones
(including 4-CMC, 191 cases) and to a lesser extent illicit substances (such as
amphetamine, MDMA, and cocaine) as well as ketamine. Adulterants and diluents reported
included caffeine, benzocaine, lidocaine, paracetamol, caffeine, alanine and citric acid.
Powders were often described from as crystals, ranging from ‘colourless crystals’ to white, or
‘light-yellow’ crystalline material.
Other seizures
In 2 140 cases, the reporting authority was not reported or unknown. These cases amounted
to 157 kg of powders. Of these, 116 kg (74 %) were seized in 2021 by Poland, in 624 cases.
In these cases, other cathinones (including 3-MMC and 4-CMC), and illicit drugs (MDMA
and amphetamine) were also detected.
Information from collected samples
A total of 67 collected samples were reported to the EMCDDA, between 2015 and 2021, by
7 Member States: Austria (6), Czechia (1), France (2), Poland (55), Portugal (1), Slovenia
(1), and Spain (1). Of these, 66 samples were in powder form.
Samples were collected by drug-checking services (10 cases) or in the context of pilot drug
checking projects (4). A total of 48 collected samples were also reported by the Polish
Central Customs and Tax Laboratory in 2019.
3-CMC was the only substance detected in 50 cases. In 17 cases, it was detected in
combination with other cathinones: 4-CMC (6 cases); 4-CMC and 4-CEC (4); 4-CMC, 4-FPD
and 4-CEC (2), 4-CEC (1), methcathinone (1), N-methyl-N,N-dimethylcathinone (1), and 3-
MMC (1). In the latter case, the sample was reported to contain 38.7 % of the hydrochloride
salt of 3-CMC. In one case it was detected in combination with caffeine (1).
3-CMC was sold as other cathinones in 3 cases – as 3-MMC in 1 case, and as 4-MMC in 2
cases, where it was detected in combination with 4-CMC. In view of this, it is possible that
some users might consume the substance inadvertently when purchasing other cathinones.
Information on where the samples were purchased, packaging and pricing is mostly
unreported. When reported, the substance was bought online (3 cases).
The scientific literature has limited information regarding collected samples of 3-CMC. There
is only one recorded instance where other substances were mis-sold as 3-CMC – a sample
bought as 3-CMC which contained 4-CMC (Grifell et al. 2017).
Information from biological samples
A total of 213 detections where 3-CMC was analytically confirmed in biological samples
were reported by 4 Member States: Sweden (182), Hungary (18), Poland (12) and Spain (1).
Serious adverse events with confirmed exposure to 3-CMC from biological samples – 1
acute poisoning reported by Spain and 10 deaths reported by Poland (7) and Sweden (3) –
are discussed in Section 4.1.2.
11
In addition to these, 202 detections of 3-CMC in biological samples were reported by

Sweden (179), Hungary (18) and Poland (5). The biological samples were reported between
2015 and 2021 as follows: 2015 (18 samples), 2016 (1), 2017 (48), 2018 (13), 2019 (17),
2020 (36), 2021 (69). Detections included:
 4 samples associated with deaths, reported by Sweden ( 14);
 2 samples associated with non-fatal poisonings, reported by Hungary ( 15);
 27 samples associated with petty drug offences, reported by Sweden;
 21 cases of persons suspected of driving under the influence of drugs, reported by

Sweden (16), Poland (3) and Hungary (2);
 15 samples analysed for criminal justice purposes, reported by Hungary (14) and
Poland (1);
 15 samples associated with abuse cases, reported by Sweden;
 6 samples analysed for drug treatment purposes, reported by Sweden; and
 112 samples reported as aggregated data associated with forensic case work
(details not specified), reported by Sweden (111) and Poland (1).
4.1.2. Health problems
Acute poisonings
One acute non-fatal poisoning with confirmed exposure to 3-CMC was reported by Spain
and was related to chemsex ( 16). Other substances were identified in biological samples,
including 3-MMC, GHB/GBL, cocaine, sildenafil, and methamphetamine.
In addition, France and Sweden reported cases of serious adverse events without analytical
confirmation from biological samples. These include one case of drug dependence reported
by France and 47 acute poisonings with suspected exposure to 3-CMC reported to the
Swedish Poisons Information Centre between 2015 and 2021: 2015 (7 cases), 2016 (4),
2017 (8), 2018 (8), 2019 (6), 2020 (7), and 2021 (7). These cases are not discussed further
in this report.
Deaths
A total of 10 deaths with confirmed exposure to 3-CMC were reported by Poland (7) and
Sweden (3). The cases occurred between November 2019 and June 2021 (one case in
2019; three cases in 2020; six cases in 2021). Of the deaths, eight were male and two were
(14) These samples were reported in aggregated datasets, and there is no correspondence between the number of samples
and number of serious adverse events (SAEs), as more than one sample may have been taken from the same patient.
SAEs reported in aggregated datasets may or may not overlap with event-based SAEs discussed in Section 4.1.2.
(15) These samples were reported in aggregated datasets, and there is no correspondence between the number of samples
and number of serious adverse events (SAEs), as more than one sample may have been taken from the same patient.
SAEs reported in aggregated datasets may or may not overlap with event-based SAEs discussed in Section 4.1.2.
(16) Chemsex is a term used to describe an intentional sex under the influence of psychoactive drugs, mostly among men
who have sex with men.
12
female. Where reported, the males were aged between 17 and 47 (mean: 30.5; median:
39.5).
In six of the cases, other substances were identified, including central nervous system
depressants (such as alcohol, opioids, synthetic cannabinoids and benzodiazepines) and
central nervous system stimulants (such as amphetamine and other synthetic cathinones).
Of note is that in two of the cases where other substances where identified, the only
additional finding was alcohol. In at least three of the cases, the individuals were found
dead. A cause of death was reported in nine cases. In five cases, 3-CMC was the cause of
death or contributed to the death; in the remaining cases, the reported causes of death were
multi-organ trauma as a result of a traffic accident (in two cases), intoxication with
oxycodone and benzodiazepines (in one case), and gunshot wound to the chest (in one
case).
ECDC reported that currently they do not have any information on 3-CMC.
4.1.3. Social problems
While there is limited data on the social risks related to the use of 3-CMC, it is possible that
they share some similarities with those associated with other synthetic cathinones like 4-
MMC. Depending on the user group, these might include changes in the social and
economic conditions of the individual, impact their family structure and employment
situation, as well as confer increased vulnerability (Brookman et al. 2016).
4.1.4. Patterns of use
The limited information suggests that 3-CMC is sold and sought after as a stimulant drug in
its own right, but it may also be mis-sold as other drugs. Similar to other cathinones, such as
4-CMC, it is likely that 3-CMC is typically administered by insufflation (snorting), orally, and
in some cases by intravenous injection. It is expected that the substance is used by existing
stimulant users, such as those who use cocaine, amphetamines, ecstasy, and other
cathinones, who either add it to their existing repertoire or use it as a replacement
substance. This likely includes recreational use, and, in some cases high risk use, such as
injecting. Although specific information is lacking, similar to other cathinones, it is likely that
3-CMC is used in private spaces (such as homes and domestic parties) as well as
recreational settings (such as nightclubs, bars/pubs, music festivals).
4.2. Chemical and physical description of the new psychoactive substance and
the methods and precursors used for its manufacture or extraction (Article
5b2(b))
4.2.1. Chemical description and names
3-CMC is a synthetic derivative of the naturally occurring substance cathinone, which is

internationally controlled ( 17), and one of the psychoactive principles in khat (Catha edulis
(17) Listed in Schedule I of the 1971 United Nations Convention on Psychotropic Substances.
13
Forsk). 3-CMC was described in the scientific literature in the months prior to its first
detection on the drug market in Europe in September 2014 (Blough et al., 2014).
As with many other synthetic cathinone derivatives monitored by EMCDDA through the EU
Early Warning System, 3-CMC is an N-alkylated and ring-substituted cathinone.
The common name 3-CMC is derived from 3-chloromethcathinone ( 18). 3-CMC is the 3-
chloro derivative of methcathinone ( 19) and a positional isomer ( 20) of 4-CMC (4-
chloromethcathinone) ( 21), which are both internationally controlled. 3-CMC is structurally
related to 3-MMC (3-methylmethcathinone) ( 22), differing on the substituent present at the 3-
position of the phenyl ring. Higher and lower homologues of 3-CMC monitored by the
EMCDDA are: 3-CEC (3-chloroethcathinone) ( 23) and 3-chlorocathinone ( 24), respectively.
The molecular structure, molecular formula and molecular mass of 3-CMC are provided in
Figure 3.
FIGURE 3
Molecular structure, molecular formula, and molecular mass of 3-CMC
3-CMC 4-CMC Methcathinone 3-MMC

(clophedrone) (clephedrone)
Molecular C10H12CINO C10H12CINO C10H13NO C11H15NO

formula
Molecular mass 197.66 197.66 163.22 177.24
Note: Information on 4-CMC, methcathinone and 3-MMC is provided for comparison.
(18) The origin for the abbreviated common name is indicated by underlining the relevant letters in the common name.
(19) 2-(methylamino)-1-phenyl-propan-1-one; listed in Schedule I of the 1971 United Nations Single Convention on Psychotropic
Substances.
(20) Positional isomers (also known as regioisomers) have the same molecular formula and molecular weight, differing only in
the position of a functional group or substituent.
(21) 1-(4-Chlorophenyl)-2-(methylamino)propan-1-one; formally notified by the EMCDDA in August 2014; and listed in Schedule
II of the 1971 United Nations Single Convention on Psychotropic Substances.
(22) 2-(Methylamino)-1-(3-methylphenyl)propan-1-one; formally notified by the EMCDDA in September 2012.
(23) 1-(3-Chlorophenyl)-2-(ethylamino)propan-1-one; formally notified by the EMCDDA in March 2016.
(24) 2-Amino-1-(3-chlorophenyl)propan-1-one; formally notified by the EMCDDA in November 2020.
14
Common name(s):
3-CMC
3-Chloromethcathinone
Systematic (IUPAC) name:
1-(3-Chlorophenyl)-2-(methylamino)propan-1-one
(RS)-1-(3-chlorophenyl)-2-(methylamino)propan-1-one
Other chemical names:
1-(3-Chlorophenyl)-2-(methylamino)-1-propanone
1-(3-Chloro-phenyl)-2-methylamino-propan-1-one
3′-Chloro-2-methylaminopropiophenone
2-(Methylamino)-1-(3’-chlorophenyl)-1-oxopropane
Other names:
3-Chloro-methcathinone
3-Cl-methcathinone
3-Cl-MCAT
Clophedrone
Metaclephedrone
Meta-chloro-N-methyl-cathinone
Meta-chloromethcathinone
PAL-434
Chemical Abstracts Service (CAS) registry numbers:
1049677-59-9 (base)
1607439-32-6 (hydrochloride salt)
2291021-63-9 (R-isomer)
2107425-89-6 (S-isomer)
IUPAC International Chemical Identifier Key (InCHI Key):
VOEFELLSAAJCHJ-UHFFFAOYSA-N (base)
15
QXEPSICDXPPHTO-UHFFFAOYSA-N (hydrochloride salt)
VOEFELLSAAJCHJ-SSDOTTSWSA-N (R–isomer)
VOEFELLSAAJCHJ-ZETCQYMHSA-N (S–iomer)
IUPAC International Chemical Identifier String (InchI string):
InChI=1S/C10H12ClNO/c1-7(12-2)10(13)8-4-3-5-9(11)6-8/h3-7,12H,1-2H3 (base)
InChI=1S/C10H12ClNO.ClH/c1-7(12-2)10(13)8-4-3-5-9(11)6-8;/h3-7,12H,1-2H3;1H
(hydrochloride salt)
InChI=1S/C10H12ClNO/c1-7(12-2)10(13)8-4-3-5-9(11)6-8/h3-7,12H,1-2H3/t7-/m1/s1
(R-isomer)
InChI=1S/C10H12ClNO/c1-7(12-2)10(13)8-4-3-5-9(11)6-8/h3-7,12H,1-2H3/t7-/m0/s1
(S-isomer)
Simplified Molecular-Input Line-Entry System (SMILES):
O=C(c1cc(Cl)ccc1)C(C)NC (base)
Cl.CNC(C)C(=O)c1cccc(Cl)c1 (hydrochloride salt)
CN[C@H](C)C(=O)c1cccc(Cl)c1 (R-isomer)
CN[C@@H](C)C(=O)c1cccc(Cl)c1 (S-isomer)
4.2.2. Physical description
There is limited information available on the solubility, lipophilicity, melting and boiling points
or other physico-chemical properties of 3-CMC.
The hydrochloride salt of 3-CMC has been described in the literature as a grey solid
(Blough, 2014), a white solid (Shalabi et al., 2017) and a white powder (SWGDRUG, 2017;
RESPONSE, 2015), with melting points of 181 – 183 °C (Blough et al., 2014) and 193 °C
(Shalabi et al., 2017) reported. Shalabi et al., noted that due to the 10 °C discrepancy in the
melting point they obtained relative to the literature, the hydrochloride salt was submitted for
microanalysis (Shalabi et al., 2017).
Due to its similarity to 4-CMC, 3-CMC is expected to be soluble in organic solvents such as
dimethyl formamide (DMF) and dimethyl sulfoxide (DMSO) or solvents such as ethanol
(ECDD, 2019; Cayman Chemical, 2014).
To date, seizures and collected samples containing 3-CMC reported to the EMCDDA have
been mostly in powder form and, to a lesser extent, in tablet, capsule and liquid form. 3-
CMC has also been identified in herbal material and found in trace amounts in a syringe.
16
3-CMC has been identified in combination with other cathinones, including but not limited to:
2-MMC ( 25), 3-MMC, 3-CEC ( 26), 4-CEC ( 27), 4-CMC, 4-MEC ( 28), α-PVT ( 29), eutylone ( 30),
mexedrone ( 31) and N-ethylhexedrone ( 32). 3-CMC has also been identified in combination
with a variety of other categories of substances including synthetic cannabinoids such as 4F-
MDMB-BINACA (4F-MDMB-BUTINACA) ( 33) and internationally controlled substances such
as cocaine, MDMA, amphetamine and metamphetamine.
In at least some of the detections, the hydrochloride salt form of 3-CMC was identified.
A more detailed description of seizures and collected samples can be found in section 4.1.1.
4.2.3. Methods and chemical precursors used for the manufacture or extraction
Limited information is available about the chemical precursors or manufacturing methods

used to make the 3-CMC which has been identified within Europe. General methods for the
synthesis of cathinones, including 3-CMC are described below.
General methods for the synthesis of cathinones, including 3-CMC
Cathinones may be prepared using several synthetic approaches. For ring-substituted

cathinones, such as 3-CMC and 3-MMC, the simplest approach involves a 2-step
bromination-amination procedure which is a relatively straightforward process, using
equipment and knowledge similar to those required for the synthesis of other synthetic drugs
such as MDMA and amphetamine (EMCDDA, 2011).
The first step of the process consists in the α-bromination of a suitable arylketone
(commonly called a ‘propiophenone’), to produce an α-bromoketone under acidic or basic
conditions. The bromine for this step can be commercially obtained as a liquid or prepared
from a bromide salt (e.g. KBr), an acid (e.g. H2SO4), and an oxidizer (e.g. H2O2). Importantly,
bromine is toxic by inhalation, accelerates the burning of combustible material, is very
corrosive to tissue and to metals and dangerous for the environment.
After the preparation of the α-bromoketone, the product is reacted with an amine (for ring
substituted cathinones the amine is typically methylamine hydrochloride and triethylamine in
an acidic scavenger). This step promotes the nucleophilic substitution of the bromine to
obtain a free cathinone base (IV) (EMCDDA, 2011; Wrzesień, 2018). Due to the instability of
the free base, the product is converted into suitable salts (hydrochlorides or hydrobromides)
which are then recrystallised (EMCDDA, 2011; Wrzesień, 2018). Unless steps are taken to
resolve the reaction products, the synthesis produces racemic mixtures. In case the starting
arylketone precursor is unavailable or controlled, it can be easily prepared by a standard
Friedler-Crafts reaction, mixing the appropriate aryl derivative with propionyl chloride in the
(25) 2-(Methylamino)-1-(2-methylphenyl)propan-1-one
(26) 1-(3-Chlorophenyl)-2-(ethylamino)propan-1-one
(27) 1-(4-Chlorophenyl)-2-(ethylamino)propan-1-one
(28) 2-(Ethylamino)-1-(4-methylphenyl)propan-1-one
(29) 2-(Pyrrolidin-1-yl)-1-(thiophen-2-yl)pentan-1-one
(30) 1-(1,3-Benzodioxol-5-yl)-2-(ethylamino)butan-1-one
(31) 3-Methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one
(32) 2-(Ethylamino)-1-phenylhexan-1-one
(33) Methyl 2-(1-(4-fluorobutyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate
17
presence of aluminium chloride (Wrzesień, 2018). A standard Grignard reaction with the
corresponding ring-substituted benzene is also possible.
The preparation of cathinones using this method is an ‘industrially efficient’ process.

Intermediate can be produced on a large scale, sub-divided into lots and each lot reacted
with a different amine to produce a number of different cathinones (Collins, 2016).
Numerous alternative synthetic methods exist. One of the most relevant ones is the so-
called ‘permanganate process’, which involves the direct oxidation of a suitable ephedrine
analogue with a strong oxidant (potassium permanganate (VII) or potassium dichromate in
diluted sulfuric acid) to yield the desired cathinone. If is obtained in a specific enantiomeric
form, the synthesis is stereoselective and the resulting cathinone will be enantiopure, which
may be of interest one of the forms is more active than the other. Although this method can
yield stereoselective products, it presents important disadvantages in that manganese
impurities can contaminate the end products, unless careful and thorough purification steps
are taken. Cathinone products contaminated with manganese may cause serious poisoning
in consumers (EMCDDA, 2011).
A general synthesis scheme for methcathinone derivatives, including 3-CMC, has been
described by Blough et al., (Blough et al., 2019). Two specific methods for the synthesis of
the hydrochloride salt of 3-CMC have been described in the literature by Blough et al.,
(compound 9) and by Shalabi et al., (compound 6) (Blough et al., 2014; Shalabi, 2017).
For 3-CMC, Blough et al., treated 3-chloropropiophenone with bromine to yield 2-bromo-1-
(3’-chlorophenyl)-1-oxopropane, which was then reacted with N-benzylmethylamine to
produce 2-(N-benzyl-N-methylamino)-1-(3’-chlorophenyl)-1-oxopropane. This was then
mixed with 1-chloroethyl chloroformate in dichloroethane to afford 3-CMC hydrochloride as a
grey solid (Blough et al., 2014). Shalabi et al., reacted 2-bromo-1-(3-chlorophenyl)propan-1-
one with methylamine, in the presence of ethanol to yield 3-CMC hydrochloride as a white
solid (Shalabi et al., 2017).
Designer Precursors
Other than standard organic synthesis methods using known precursors, cathinones can be
prepared using so-called ‘designer precursors’. These are ‘purpose-made, close chemical
relatives of controlled precursors and can easily be converted into a controlled precursor and
usually have no legitimate use.’ (CND, 2020). They can be, for example, stable chemical
intermediates, masked derivatives of controlled precursors, or masked derivatives of
controlled drugs. (CND, 2020). Amine compounds, including cathinones, are especially
suited for the latter approach, in that ‘masking’ or ‘protecting’ groups (such as acetyl
protecting groups, ‘Boc’ groups, CBZ groups and/or ‘Tosyl’ groups for example) can be
easily introduced into the molecule (making it a different chemical entity) and then easily
cleaved off, often in quantitative yields to produce the controlled amine of choice.
Illicit production of 3-CMC
Information on the synthetic pathways used to produce the 3-CMC seized in Europe can
come from impurity profiling of seized/collected samples, from seizures of cathinone
precursors and from law enforcement intelligence collected in seizures of illicit cathinone
production sites.
18
Limited information exists on the synthetic impurities present in 3-CMC samples.

Approximately 400 kg of 3-CMC powders, also containing iso-3-CMC, were seized by Dutch
Customs in 2021. Isocathinones such as iso-3-CMC, can be by-products of cathinone
synthesis (Westphal et al.; 2012; Wrzesień, 2018), occurring when the amino moiety and the
keto group change place in the molecule. Their occurrence is attributed to the first synthetic
pathway (bromination/amination), which, as already explained above, is the most ‘industrially
efficient’ method to fabricate these compounds.
Seizures of precursors reported to the European Commission do not contain information on

specific chemicals needed for the synthesis of 3-CMC. Most of the reports consisted of
precursors for 4-MMC and 4-CMC, which can nonetheless be taken as indicative of the
processes used for their positional isomers. The majority of cathinone precursors seized
between 2015 and 2019 were chemicals needed for amination step in the
bromination/amination. This suggests that cathinone labs in Europe may be using the
pathway in question but and that they may be focused on the final stages of cathinones
production (‘finishing labs’).
Law enforcement information reported to the EMCDDA by law enforcement authorities

indicates that at least 55 cathinone illicit laboratories have been dismantled in Europe since
2011. Close to 50 % of the laboratories were seized between 2019 and 2021, suggesting
that there has been an increase in the interest in producing cathinones in Europe.
Of the 55 laboratories seized, 3 sites were involved in the production of 3-CMC: one seized
in Slovakia in 2017, and 2 seized in Poland in 2020.
4.2.4. Detection and analysis
Methods documented in the literature for the identification of 3-CMC in physical samples and
biological samples are referenced in Table 1.
TABLE 1
Methods documented in the literature for the identification of 3-CMC in physical
samples and biological samples
Physical samples
Method References
Gas chromatography–mass spectrometry (GC-MS) Blough et al., 2014

SWGDRUG, 2017
Cayman Chemical, 2015
RESPONSE, 2015
Fourier transform infrared spectroscopy (FTIR) SWGDRUG, 2017

RESPONSE, 2015
Piorunska-Sedlak et al., 2020
High-performance liquid chromatography-ultraviolet Hägele et al., 2020

(HPLC-UV) Kadkhodaei et al., 2018
Kadkhodaei et al., 2020
19
Raman spectroscopy Kranenburg et al., 2021
Chiral capillary electrophoresis (CEC) Hägele et al., 2019

1H nuclear magnetic resonance spectroscopy (NMR) Blough et al., 2014
SWGDRUG, 2017
RESPONSE, 2015
13C NMR RESPONSE 2015
Biological samples
Method References
HPLC and supercritical fluid chromatography tandem Lajtai et al., 2020

mass spectrometry (SFC-MS/MS)
Gas chromatography tandem mass spectrometry (GC- Woźniak et al., 2020

MS/MS)
Quantification of 3-CMC in physical samples can be carried out according to the general
procedure described by the UNODC (UNODC, 2020). Due to its structural similarity to 4-
CMC, quantification of 3-CMC in blood samples could be carried out according to the
procedure described by Wiergowski et al., using UPLC–MS/MS (Wiergowski et al., 2017).
Discrimination of 3-CMC from its positional isomers
3-CMC has two positional isomers, 2-CMC ( 34) and 4-CMC, differing only in the position of
the chlorine atom on the phenyl ring. Reference standards of the hydrochloride salt of 3-
CMC (Cayman Chemical, 2015), 2-CMC (Cayman Chemical, 2017), and 4-CMC (Cayman
Chemical, 2014) are commercially available. Reference standards are also commercially
available for the base form and the S-isomer of 3-CMC (Aurora Fine Chemicals, 2021a;
Aurora Fine Chemicals, 2021b).
Positional and structural isomers have the same molecular formula and molecular mass,
therefore the discrimination of these isomers of 3-CMC poses analytical challenges, as
techniques solely relying on mass will not allow an unequivocal identification. The positional
isomers of 3-CMC, 2-CMC and 4-CMC, can be discriminated for in many, but not all,
forensic and toxicology laboratories in Europe. The discrimination of positional isomers can
be achieved through the use of analytical reference standards, access to reference spectra
for the positional isomers and/or analytical methods in addition to GC-MS, such as FTIR or
NMR. The discrimination of these isomers is described in further detail below.
Analysis by GC-MS will result in very similar mass spectrometry fragmentation patterns.
Hägele et al. highlighted that discrimination by GC-MS is particularly challenging when using
common achiral columns (Hägele et al., 2019; Hägele et al., 2020). The ability to distinguish
between these isomers requires the use of analytical reference standards, access to
(34) 1-(2-Chlorophenyl)-2-(methylamino)-1-propanone
20
reference spectra for both substances, and/or additional analytical methods, such as FTIR or
NMR.
Hägele et al. demonstrated that positional isomers can be discriminated by use of capillary
electrochromatography (CEC), providing the example of the discrimination of three different
fluorinated methcathinone derivatives, 2-FMC ( 35), 3-FMC ( 36) and 4-FMC ( 37), with
carboxymethyl-β-CD as the chiral selector (Hägele et al., 2019). Kadkhodaei et al., also
demonstrated that using an isocratic HPLC method with a specific CSP could discriminate
between the three positional isomers of mephedrone (2-MMC, 3-MMC and 4-MMC)
(Kadkhodaei et al., 2020). It could be expected that the discrimination of 2-CMC, 3-CMC and
4-CMC is possible using these methods.
Piorunska-Sedlak et al., demonstrated that 3-CMC could be discriminated from 4-CMC using
ATR-IR, as the spectra are sufficiently different (Piorunska-Sedlak et al., 2020). 2-CMC was
not included in the analysis as it was not identified in the 45 samples studied (Piorunska-
Sedlak et al., 2020).
A validated GC–MS/MS method for the determination of NPS in blood samples from forensic
cases has been described by Woźniak et al. (Woźniak et al., 2020). The authors explained
that while 3-CMC and 4-CMC had close retention times and shared the same multiple
reaction monitoring (MRM) transitions, the identification of these compounds was facilitated
by the use of internal standards and by calculation of their relative retention times. It was
highlighted by the authors that the method is limited to screening, with quantification only
possible when only one of these analytes is present in a sample (Woźniak et al., 2020).
3-CMC is also a structural isomer of iso-3-CMC ( 38). Iso-3-CMC is not currently monitored by
the EMCDDA but other iso-cathinones monitored by the EMCDDA are: 3-fluoro-
isomethcathinone (3-FiMC) ( 39) iso-pentedrone ( 40) and iso-ethcathinone ( 41). Iso-3-CMC has
been recently identified, alongside 3-CMC, in two significant seizures reported by Customs
in the Netherlands, amounting to 400 kilograms of powder, that occurred in the first half of
2021. The presence of iso-3-CMC in these seizures could be as a result of dimerisation due
to the reaction of the alpha-haloketone and the amine. The detection of iso-cathinones in
seized samples has been discussed in the literature (McDermott et al. 2011). Based on the
authors hypotheses in their study of iso-mephedrone and iso-ethcathinone, the detection of
iso-3-CMC could be due to the starting material for 3-CMC having been contaminated with
the starting material for the iso-3-CMC, or from the use of liquid amine rather than amine in
solution during synthesis, or possibly as a result of rearrangement of 3-CMC directly to iso-
3-CMC through an imino-amine intermediate (McDermott et al. 2011). The authors
suggested that, based on their findings, the use of liquid amine was the likely factor in the
presence of the iso-cathinone compounds identified in seized samples and as these were
not commonly identified in samples this ‘could be used to compare batches of material and
suggest a common origin’ (McDermott et al. 2011).
(35) 1-(2-Fluorophenyl)-2-(methylamino)propan-1-one
(38) 1-(3-Chlorophenyl)-1-(methylamino)propan-2-one
(39) 1-(3-Fluorophenyl)-1-(methylamino)propan-2-one; formally notified by the EMCDDA in February 2012.
(40) 1-(Methylamino)-1-phenylpentan-2-one; formally notified by the EMCDDA in September 2011.
(41) 1-(Ethylamino)-1-phenylpropan-2-one; formally notified by the EMCDDA in June 2010.
21
Differentiation of enantiomers
Cathinones such as 3-CMC contain a stereogenic centre thus allowing for the existence of a
pair of enantiomers, (R)- and (S)-3-CMC. There is no information on the enantiomeric
composition of the samples of 3-CMC detected within the European Union, which in part
may reflect the fact that stereochemical analysis is not routinely undertaken in forensic
laboratories.
Differentiation of enantiomers is possible using the following techniques: chiral

chromatography, vibrational circular dichroism (VCD) spectroscopy and/or electronic circular
dichroism (ECD) spectroscopy.
Hägele et al., reported the use of an isocratic HPLC method with a specific chiral stationary
phase (CSP), developed for the enantioresolution of synthetic chiral drugs, to successfully
separate enantiomers of a range of new psychoactive substances, including 3-CMC (Hägele
et al., 2020). Kadkhodaei et al., also demonstrated the separation of a range of NPS
enantiomers using an isocratic HPLC method with a specific CSP (Kadkhodaei et al., 2018).
The authors highlighted that in general ‘for a successful chiral separation, the position and
the atomic mass of halogen substituents play a crucial role’, with substitution in the ortho
position considered to produce less satisfactory results than in the para position. This was
demonstrated by the successful chiral separation of 3-CMC and 4-CMC compared with 2-
CMC (Kadkhodaei et al., 2018).
4.3. Pharmacological and toxicological description of the new psychoactive

substance (Article 5b2(c))
3-CMC is a ring-substituted synthetic cathinone. Similar to closely related cathinones such

as 4-chloromethcathinone (clephedrone, 4-CMC), 3-CMC has been shown to interact with
the monoamine transporter system in a number of in vitro studies, which suggest that 3-
CMC acts as a psychostimulant. For example, 3-CMC was reported to act as a monoamine
(dopamine, noradrenaline and serotonin) transporter substrate that induces release in rat
brain synaptosomes (Kohut et al. 2013, Blough et al. 2014, Shalabi et al. 2017, Blough et al.
2019, Walther et al. 2019). This mechanistic principle is also found in other closely related
ring-substituted synthetic cathinones such as 4-MMC, methcathinone, and 4-CMC (Walther
et al. 2019). 3-CMC was also observed to produce sustained and selective decreases in
cocaine self-administration in rhesus monkeys and produced fewer side effects than
methcathinone (Kohut et al. 2013). 3-CMC was also 3–8 fold less potent than cocaine or
methcathinone in eliciting cocaine-like discriminative stimulus effects in rhesus monkeys
(Kohut et al. 2013). Consistent with a locomotor stimulant profile, 3-CMC was observed to
increase spontaneous horizontal locomotor activity in mice in a dose-dependent manner
(Wojcieszak et al. 2020). Taken together, these results suggest that 3-CMC is likely to act as
a stimulant in humans and might also show abuse liability. Acute effects of synthetic
cathinones include stimulant effects such elevated mood, euphoria, and increased energy
but undesired effects reflecting a sympathomimetic toxidrome are known to include
hyperthermia, tachycardia, hypertension, and psychosis (Baumann et al. 2018).
The acute effects of 3-CMC are likely to share some similarities with other substituted
cathinones such as 4-CMC. These might include general stimulation, euphoria, sociability,
22
increased heart rate and elevated blood pressure (Abdulrahim and Bowden-Jones, 2015;
Soares et al., 2021). Synthetic cathinones also have an abuse liability and dependence
potential (Bajaj et al., 2010; Batisse, et al., 2014; Dolengevich-Segal et al., 2016).
There is limited information on the acute toxicity of 3-CMC. Based on the available
information, the clinical features of poisoning are likely to be similar to those observed with
other synthetic cathinones. Adverse effects from overdosing 3-CMC might include
neurological (e.g. hallucination, seizures, agitation, anxiety, psychosis, reduced
consciousness), cardiovascular (e.g. tachycardia, hypertension, chest pain, cardiac arrest)
and respiratory (e.g. bradypnea, dyspnoea) clinical features (Abdulrahim and Bowden-
Jones, 2015; Soares et al., 2021).
Similar to other stimulant cathinones, the use of 3-CMC with other central nervous system
stimulants, including cocaine, amphetamine, methamphetamine or MDMA, is likely to
produce synergistic effects which can increase the risk of an acute intoxication.
While there is limited information for 3-CMC, the chronic health risks might share some
similarities to those seen with other synthetic cathinones such as 4-CMC. This may include
dependence.
ECHA reported to the EMCDDA that according to the Classification and Labelling (C&L)
Inventory, 3-CMC hydrochloride salt is classified as an eye irritant category 2. EFSA
reported to the EMCDDA that they do not currently have any information on 3-CMC.
4.4. Involvement of criminal groups in the manufacture or distribution of the

new psychoactive substance (Article 5b2(d))
Europol received replies from 13 Member States (Austria, Bulgaria, Croatia, Cyprus,
Denmark, Finland, France, Germany, Greece, Luxembourg, Poland, Slovakia and Slovenia)
and Norway.
Replies were also received from Iceland ( 42), the United Kingdom (UK) ( 43) and the United
States Drug Enforcement Administration (DEA) ( 44).
Involvement of criminal groups in the manufacture or distribution of 3-CMC
Poland reported the seizure of two clandestine laboratories producing 3-CMC, in the last
year. They reported that they do not currently have accurate data on the involvement of
(42) Iceland reported that no information was available on 3-CMC.

(43) The UK reported that according to records from the Border Force on the INCB IONICS system, there were ten incidents
involving 3-CMC so far in 2021. The UK was the destination country for seven of the ten shipments, while Poland (2) and
Ukraine (1) were the other destinations. The Netherlands was the origin country for all ten shipments. In the case of the
shipment destined for the Ukraine, it appears to have transited through the UK, where it was seized. In total, they
reported that there have been 82 incidents worldwide associated with 3-CMC, which have been recorded in the system
since March 2015.
(44) The DEA reported that information on seizures of 3-CMC have been provided by the DEA laboratory information
management system (LIMS) since it became the official record in October 2014. Information on other detections from
forensic laboratories other than the DEA system has also been provided by the Diversion Control Division’s NFLIS
database. The DEA reported that it is not aware of any domestic synthesis of 3-CMC and the substance is often
purchased via the surface or dark web and then shipped to the US. They noted that some of the seizures appeared to be
labelled as research chemicals, which they believe could have been purchased from chemical supply companies. A total
of three detections of 3-CMC were identified in the DEA LIMS in 2016, in crystalline, rock and powder form, ranging in
quantity from 0.96 to 54.463 grams. In one case, the hydrochloride salt form of 3-CMC was identified and, in the other
two cases, 3-CMC was identified with alpha-PVP and an unidentified substance. A total of 16 detections of 3-CMC were
registered in the Diversion Control Division’s NFLIS database, recorded between 2015 and 2019.
23
criminal groups in the manufacture, distribution and distribution methods, and trafficking of 3-
CMC.
Slovakia reported a significant decrease in the activities of foreign criminal groups, dealing
with the production of 3-CMC, according to information from the police. This decrease is
considered to be a result of Covid-19 restrictions.
No other information was received on the involvement of criminal groups in the manufacture
or distribution of 3-CMC.
Information on seizures of 3-CMC
In general, seizures of 3-CMC reported to Europol occurred between 2015 and 2021.
 Austria reported a slight increase in cases involving 3-CMC in recent years. 3-CMC
has been seized as a white powder, and as a brown liquid which was also found to
contain cocaine and/or 4-MMC.
 Denmark reported that most seizures of 3-CMC, approximately ten, were of small
quantities associated with personal consumption, seized in postal packages
originating from countries within the EU.
 Finland reported minor and infrequent seizures of 3-CMC, by police and customs,
also reported to the EMCDDA.
 France reported that 3-CMC has been identified in detections since 2014 and
according to information available to French police and OFDT ( 45) is available to
purchase online, at a reported price of 14 to 18 euro per gram. Information from
analysis by OFDT indicates that 3-CMC has been identified in products sold online
as 3-MMC. They also reported that while some seizures of 3-MMC have been
reported by French law enforcement services, no 3-CMC seizures have been
reported.
 Germany reported that all information has been sent to the EMCDDA by the
DBDD ( 46).
 Greece reported generally on 3-CMC, in the context of more specific information

provided on 3-MMC.Norway reported that 3-CMC was seized for the first time in
Norway in 2015, with tens of seizures reported between 2015 and 2017, followed by
a decrease in seizures from 2017. From 2020, an increase in seizures was observed
with more than 15 seizures of 3-CMC in crystal form reported; the largest individual
seizure during this timeframe was 2.5 kilograms.
 Slovakia reported two seizures of 3-CMC made by the police during four raids in
2019 (148.2 grams; and 0.76 grams also containing 3-CEC (3-chloroethcatinone).
 Slovenia reported that a total of 30 grams of 3-CMC was identified in seizures in

2019, from individuals who mostly purchased the substance online.
(45) The French Observatory for Drugs and Drug Addiction (OFDT).
(46) The German Monitoring Centre for Drugs and Drug Addiction (DBDD).
24
Austria, Bulgaria, Denmark and Greece reported information on the national control
measures applied to 3-CMC and/or 4-CMC. Croatia, Cyprus and Luxembourg reported that
no information is available.
4.5. Information on the human and veterinary medical use of the new
psychoactive substance, including as an active substance in a medicinal
product for human use or in a veterinary medicinal product
Based on the reported information from the EMA ( 47), it appears that 3-CMC is not an active
substance in:
a. a medicinal product for human use or in a veterinary medicinal product that has
obtained a marketing authorisation in accordance with Directive 2001/83/ EC of the
European Parliament and of the Council, Directive 2001/82/EC of the European
Parliament and of the Council or Regulation (EC) No 726/2004 of the European
Parliament and of the Council;
b. a medicinal product for human use or in a veterinary medicinal product that is the
subject of an application for a marketing authorisation;
c. a medicinal product for human use or in a veterinary medicinal product whose

marketing authorisation has been suspended by the competent authority.
In addition, it appears that 3-CMC is not an active substance in the following, although the
information, especially in relation to use in extemporaneously prepared products, is unknown
in some cases:
d. an unauthorised medicinal product for human use in accordance with Article 5 of

Directive 2001/83/ EC or in a veterinary medicinal product prepared
extemporaneously by a person authorised to do so under national law in
accordance with point (c) of Article 10(1) of Directive 2001/82/EC;
e. an investigational medicinal product as defined in point (d) of Article 2 of Directive

2001/20/EC of the European Parliament and of the Council.
4.6. Information on the commercial and industrial use of the new psychoactive
substance, the extent of such use, as well as its use for scientific research and
development purposes
3-CMC is available as an analytical reference material in clinical and forensic case work and
is used scientific research. There is currently no information that suggests 3-CMC is used for
other legitimate purposes.
(47) 26 Member States, as well as Norway and Iceland provided a response to the EMA’s request regarding human and/or
veterinary medicinal products.
25
ECHA reported that there are no registrations or classification and labelling (C&L)
notifications for 3-CMC in the C&L Inventory database ( 48).
ECHA reported a C&L notification for the hydrochloride salt of 3-CMC that classifies the
substance as an eye irritant category 2, and labels it with hazard statement H319 (‘causes
serious eye irritation’) (ECHA). The identity of C&L notifiers is not published on the ECHA
dissemination website, due to the sensitivity of this information.
EFSA holds no information on 3-CMC and has not assessed this substance in any context.
4.7. Information on whether the new psychoactive substance is subject to any

restrictive measures in the Member States
Six Member States (Bulgaria, Greece, Luxembourg, the Netherlands, Romania, and Spain)
reported that 3-CMC is not subject to restrictive measures at national level.
When reporting whether 3-CMC is subjected to restrictive measures, 11 Member States

(Austria, Belgium, Croatia, Denmark, France, Germany, Hungary, Ireland, Latvia, Lithuania,
and Malta) and Turkey mentioned that this substance is covered by the generic definition of
cathinones.
Drug control legislation
Thirteen Member States (Croatia, Czechia, Denmark, Estonia, France, Italy, Ireland, Latvia,
Poland, Portugal, Slovenia, Slovakia, and Sweden), Turkey and Norway reported that 3-
CMC is controlled under drug control legislation.
 Croatia reported that 3-CMC is controlled by generic definition since 2014;
 Czechia reported that 3-CMC is controlled since 2017;
 Denmark reported that 3-CMC is covered by generic cathinone classification since

2012;
 Estonia reported that 3-CMC is controlled under the Act on Narcotic Drugs and
Psychotropic Substances and Precursors thereof, List VI, since 2016;
 France reported that 3-CMC is controlled by a generic approach since 2012;
 Ireland reported that 3-CMC is covered by the generic cathinone definition under
Statutory Instrument 551/2011, in force since November 2011;
 Italy reported that 3-CMC was included in the list of new psychoactive substances in
the update of 6 August 2021 of the decree of the President of the Republic n. 309;
(48) ECHA’s C&L Inventory database contains classification and labelling information on notified and registered substances
received from manufacturers and importers. It also includes the list of harmonised classifications. The information
included in the preparation of this report is public.
26
 Latvia reported that 3-CMC is covered by generic definition in the law On the
Procedures for the Coming into Force and Application of the Criminal Law;
 Poland reported that 3-CMC is controlled by a regulation of the Minister of Health

since 2018;
 Portugal reported that 3-CMC is included in Law No 25/2021 of 11 May which

amends for the twentieth-seventh time the Decree-Law No 15/93 of 22th January, as
of 11 May 2021.
 Slovenia reported that 3-CMC is controlled by the Regulation on the Classification of

Illicit Drugs since 2016;
 Slovakia reported that 3-CMC is controlled by Act No 139/1998 Coll. on Narcotics

and Psychotropic Substances and Preparations since 1 January 2020;
 Sweden reported that 3-CMC was regulated as goods dangerous to health as of 18

August 2015 and was re-scheduled as a narcotic drug in 2019;
 Turkey reported that 3-CMC was controlled by generic legislation in the context of
Law on Control of Drugs numbered 2313, since 2016;
 Norway reported that 3-CMC is classified as a narcotic in Norway and is listed in

Narcotics legislation. Private import by mail is not permitted and companies need
licenses to import, export, or manufacture 3-CMC. 3-CMC is also classified as a
‘forbidden’ narcotic, meaning even stricter regulations regarding licenses for
import/export/manufacture.
New psychoactive substance legislation
Seven Member States (Austria, Belgium, Cyprus, Germany, Finland, Hungary, and Malta)
reported that 3-CMC is controlled under new psychoactive substance legislation.
 Austria reported that 3-CMC is covered by generic definition by the Austrian Act on
New Psychoactive Substances of 2012;
 Belgium reported that 3-CMC is covered by generic definition;
 Cyprus reported that 3-CMC is controlled since 2011;
 Germany reported that 3-CMC is covered by the New Psychoactive Substances Act
since 2016;
 Finland reported that 3-CMC is banned by a government decree on psychoactive

substances since 2015;
 Hungary reported that 3-CMC is covered by the definition of cathinones in Annex I of

Decree no. 55/2014 of the Ministry of Human Capacities, Substances since 2012.
27
 Malta reported that 3-CMC is not explicitly mentioned in their laws. Police prosecutes
the substance, as it is considered a derivative of cathinone and a new psychoactive
substance.
Medicines legislation
Lithuania reported that 3-CMC is controlled under medicines legislation (included in the
group of cathinone derivatives) since 10 March 2015.
Other information
3-CMC is controlled in China since October 2015.
4.8. Information on whether the new psychoactive substance is currently or

has been under assessment within the system established by the 1961 Single
Convention on Narcotic Drugs, as amended by the 1972 Protocol, and the 1971
Convention on Psychotropic Substances
The World Health Organization is the specialised United Nations agency designated for the
evaluation of the medical, scientific, and public health aspects of psychoactive substances
under the Single Convention on Narcotic Drugs, 1961, and the Convention on Psychotropic
Substances, 1971.
On 17 September 2021, the World Health Organization informed the EMCDDA that 3-CMC
is not currently under assessment nor has it been under assessment by the United Nations
system.
4.9. Other relevant information
Austria
In Austria, the drug checking service CheckIt reported two samples containing 3-CMC and
4-CMC in January 2020. Both samples were submitted as mephedrone (CheckIt, 2021).
Switzerland
In Switzerland, the drug checking service SaferParty reported 8 samples containing 3-CMC
between May 2019 and October 2021. In all cases 3-CMC was sold as other substance: 3-
MMC (in 4 cases) ( 49), MDMA (2), methamphetamine (1), and mephedrone (1). Three
samples contained other substances such as MDMA, 4-CEC, 3-MMC, 4-MMC, and
ketamine (SaferParty, 2021).
(49) In one of these cases, the sample was sold as ‘5-MMC’, which would be equivalent to 3-MMC.
28
5. Analysis and assessment
1-(3-Chlorophenyl)-2-(methylamino)propan-1-one (3-chloromethcathinone, 3-CMC) is a

synthetic cathinone with stimulant effects that is monitored as a new psychoactive substance
by the EMCDDA in accordance with Regulation (EC) No 1920/2006. The substance is an N-
alkylated and ring-substituted cathinone and contains a chiral centre so two enantiomers
may exist: (R)-3-CMC and (S)-3-CMC. It is a derivative of cathinone, the naturally occurring
stimulant and main psychoactive substance in the khat plant Catha edulis. 3-CMC is also
closely related to and shares similar stimulant effects with methcathinone (ephedrone) and
4-chloromethcathinone (4-CMC; clephedrone). Cathinone, methcathinone, and 4-CMC are
controlled under the 1971 United Nations Convention on Psychotropic Substances because
of the public health and social risks that they pose.
3-CMC was first identified in Europe in September 2014 based on a police seizure made in
Sweden. Despite appearing on the drug market at around the same time as 4-CMC, until
2020, the detection of 3-CMC in law enforcement seizures remained relatively low in
comparison to 4-CMC. However, during 2020 and 2021 there has been a large increase in
seizures of 3-CMC. Although the reasons for this are unclear, it does coincide with the
recent control of 4-CMC under the United Nations system in 2020. At least in part, it appears
that 3-CMC is being used as a ‘legal’ replacement to 4-CMC.
The limited information suggests that 3-CMC is sold and sought after as a stimulant drug in
its own right, but it may also be mis-sold as other drugs. Similar to other cathinones, such as
4-CMC, it is likely that 3-CMC is typically administered by insufflation (snorting), orally, and
in some cases by intravenous injection. It is expected that the substance is used by existing
stimulant users, such as those who use cocaine, amphetamines, ecstasy, and other
cathinones, who either add it to their existing repertoire or use it as a replacement
substance. This likely includes recreational use, and, in some cases high risk use, such as
injecting. Although specific information is lacking, similar to other cathinones, it is likely that
3-CMC is used in private spaces (such as homes and domestic parties) as well as
recreational settings (such as nightclubs, bars/pubs, music festivals).
Since 2014, 3-CMC has been identified in 23 Member States and Norway. In total,
approximately 2 720 kg of 3-CMC powder has been seized, including at least 2240 kg by
customs and 320 kg by police. However, of this, approximately 2 500 kg (92 %) was seized
between 2020 and 2021. During 2021, 3-CMC continues to be imported, distributed, and
used in parts of Europe; this includes the seizure of a total of 1 400 kg of powder at the
external EU border.
The available information suggests that 3-CMC is currently imported into Europe in bulk
quantities mainly from India, with approximately 700 kg of pure powders that originated from
the country seized in 2020. It is then processed, packaged, and then distributed in wholesale
and retail amounts in Europe either online or by street dealers. In addition, three illicit
laboratories producing 3-CMC have been seized in Europe, with the two most recent
laboratories seized in 2020.
Of particular note, is that while the quantities of cathinone powders seized in Europe have
been decreasing since they peaked in 2015 and 2016, at around 1 800 kg per year, and
falling to 750 kg by 2019, during 2020 there was a significant increase, with approximately 3
29
300 kg of powders seized. It appears, that at least in part, this increase has been driven by
3-CMC which accounted for just over a quarter of the quantity of powders seized during
2020. In addition, 3-methylmethcathinone (3-MMC), which is also currently the subject of an
initial report following its re-emergence in Europe, accounted for a similar quantity.
One acute non-fatal poisoning with confirmed exposure to 3-CMC has been reported by one
Member State: Spain. Other substances were identified.
A total of 10 deaths with confirmed exposure to 3-CMC have been reported by two Member
States: Poland and Sweden. In six cases, other substances were identified. The cases
occurred between November 2019 and June 2021; three of the deaths occurred in 2020 and
six in 2021. In five cases, 3-CMC was the cause of death or contributed to the death.
Currently, there is limited information on the involvement of criminal groups in the

manufacture, trafficking, and distribution of 3-CMC within Europe. However, based on
information reported to the EMCDDA, there is evidence of criminal acts, such as trafficking,
illicit production, and supply offences, involving 3-CMC.
The effect of the ongoing COVID-19 pandemic on the manufacture, trafficking, distribution
and use of 3-CMC is currently unknown. However, seizures of more than of 2 170 kg of bulk
powders by customs agencies during the pandemic suggest that 3-CMC continues to be
imported and distributed in Europe. It is possible that, in case of a reduced availability of
controlled stimulants (such as 4-CMC and MDMA) in Europe, criminal groups, as well as
drug users, may use a range of replacement substances, including 3-CMC.
Based on the available information, it appears that 3-CMC is not an active substance in a
medicinal product for human use or in a veterinary medicinal product in Europe. However,
the use of 3-CMC as an active substance in medicinal products prepared extemporaneously
or in investigational medicinal products cannot be excluded in some Member States due to a
lack of information. Aside from limited use as an analytical reference standard and in
scientific research, there is currently no information that suggests that 3-CMC is used for
other legitimate purposes.
3-CMC is subject to restrictive measures in 21 Member States, Turkey, and Norway. 3-CMC
is controlled in China. It is unknown if 3-CMC is controlled in India, from where bulk
quantities of pure powder have originated and recently been seized by customs agencies in
Europe.
3-CMC has not been subject to assessment nor is it currently under assessment by the
United Nations system.
The EMCDDA will continue to intensively monitor 3-CMC to ensure that new information is
provided to the Member States, Europol, the Commission and the EMA through the
European Union Early Warning System in a timely manner, to strengthen situational
awareness as well as to continue to inform preparedness and response measures at both
national and EU levels to protect public health.
Based on the analysis of the available information, especially the signals suggesting the
recent emergence of 3-CMC, the EMCDDA considers that there are indications that 3-CMC
may pose health or social risks at Union level. We conclude that the potential health and
30
social risks posed by the use, manufacture, distribution and involvement of criminal groups
could be thoroughly assessed through a risk assessment procedure in accordance with
Article 5c of Regulation (EC) No 1920/2006.
31
6. References
Abdulrahim, D. and Bowden-Jones, O., on behalf of the NEPTUNE Expert Group (2015),
‘Guidance on the management of acute and chronic harms of club drugs and novel
psychoactive substances’, Novel Psychoactive Treatment UK Network (NEPTUNE).
http://neptune-clinical-guidance.co.uk/clinical-guidance-2/
Aurora Fine Chemicals (2021a), ‘1-(3-chlorophenyl)-2-methylaminopropan-1-one ‘,

https://online.aurorafinechemicals.com/info?ID=182.971.435
Aurora Fine Chemicals (2021b), ‘1-(3-chlorophenyl)-2-methylaminopropan-1-one ‘,

https://online.aurorafinechemicals.com/info?ID=126.354.181
Bajaj, N., Mullen, D., Wylie, S. (2010), ‘Dependence and psychosis with 4-
methylmethcathinone (mephedrone) use’, BMJ case reports, 2010, bcr0220102780.
https://doi.org/10.1136/bcr.02.2010.2780
Batisse, A., Fortias, M., Bourgogne, E., Grégoire, M., Sec, I., Djezzar, S. (2014), ‘Case
series of 21 synthetic cathinones abuse’, Journal of Clinical Psychopharmacology, 34(3),
pp. 411–413. https://doi.org/10.1097/JCP.0000000000000116
Baumann, M. H., Walters, H. M., Niello, M. and Sitte, H. H. (2018), ‘Neuropharmacology of

synthetic cathinones’, Handbook of Experimental Pharmacology, 252(113-142.
https://doi.org/10.1007/164_2018_178
Blough, B. E., Landavazo, A., Partilla, J. S., Baumann, M. H., Decker, A. M., Page, K. M.
and Rothman, R. B., (2014), ‘Hybrid dopamine uptake blocker–serotonin releaser ligands: a
new twist on transporter-focused therapeutics’, ACS Medicinal Chemistry Letters, 5(6),
pp. 623–627. Available at: https://doi.org/10.1021/ml500113s
Blough, B. E., Decker, A. M., Landavazo, A., Namjoshi, O. A., Partilla, J. S., Baumann, M. H.
and Rothman, R. B., (2019), ‘The dopamine, serotonin and norepinephrine releasing
activities of a series of methcathinone analogs in male rat brain synaptosomes’,
Psychopharmacology, 236(3), pp. 915–924. Available at: https://doi.org/10.1007/s00213-
018-5063-9
Brookman, F., Bennett, T.H., Hills, R. (2016), ‘The pleasures and pains of mephedrone use:
Perceptions of users and practitioners’, Drugs: Education, Prevention and Policy.
http://dx.doi.org/10.1080/09687637.2016.1192106
Cayman Chemical (2014), Product information: 4-Chloromethcathinone (hydrochloride)’,

https://www.caymanchem.com/product/16436/4-2hloromethcathinone-(hydrochloride)

https://www.caymanchem.com/product/17394/3-chloromethcathinone-(hydrochloride)

https://www.caymanchem.com/product/17744/2-chloromethcathinone-(hydrochloride)
CheckIt. Warnungen. https://checkit.wien/warnungen/
Collins M, Doddridge A, Salouros H. (2016), ‘Cathinones: Isotopic profiling as an aid to

linking seizures’, Drug Testing and Analysis, 8(9):903-9.
32
CND (Commission on Narcotic Drugs) 2020, Commission on Narcotic Drugs Sixty-third

session, 2–6 March 2020; Conference room paper submitted by the International Narcotics
Control Board, titled: ‘Options to address the proliferation of non-scheduled chemicals,
including designer precursors – contribution to a wider policy dialogue’;
E/CN.7/2020/CRP.13; 21 February 2020 link:
https://www.unodc.org/documents/commissions/CND/CND_Sessions/CND_63/CRPs/ECN7
2020_CRP13_e_V2001490.pdf
Dolengevich-Segal, H., Rodríguez-Salgado, B., Gómez-Arnau, J., Sánchez-Mateos, D.

(2016), ‘Severe psychosis, drug dependence, and hepatitis C related to slamming
mephedrone’, Case Reports in Psychiatry, 2016, 8379562.
https://doi.org/10.1155/2016/8379562
ECDD (2019), Expert Committee on Drug Dependence, Critical Review Report: 4-CMC (4-
CHLOROMETHCATHIONE). Forty-second Meeting, Geneva, 21-25 October 2019. Available
at: https://www.who.int/medicines/access/controlled-substances/Final_4-CMC.PDF?ua=1
ECHA, C&L Inventory database. Notified classification and labelling. 1-(3-chlorophenyl)-2-

(methylamino)propan-1-one. https://echa.europa.eu/information-on-chemicals/cl-inventory-
database/-/discli/details/256275
European Monitoring Centre for Drugs and Drug Addiction (2011), Report on the risk
assessment of mephedrone in the framework of the Council Decision on new psychoactive
substances, Risk Assessments, Publications Office of the European Union, Luxembourg.
Link: https://www.emcdda.europa.eu/risk-assessments/mephedrone_en
Grifell, M., Ventura, M., Carbón, X., Quintana, P., Galindo, L., Palma, A., Fornis, I., Gil, C.,
Farre, M., Torrens, M. (2017), ‘Patterns of use and toxicity of new para‐halogenated
substituted cathinones: 4‐CMC (clephedrone), 4‐CEC (4‐chloroethcatinone) and 4‐BMC
(brephedrone)’, Human Psychopharmacology: Clinical and Experimental, 32(3), e2621.
https://doi.org/10.1002/hup.2621
Hägele, J. S., Hubner, E. M. and Schmid, M. G., (2019), ‘Chiral separation of cathinone
derivatives using β‐cyclodextrin‐assisted capillary electrophoresis–Comparison of four
different β‐cyclodextrin derivatives used as chiral selectors’, Electrophoresis, 40(14),
pp. 1787–1794. Available at: https://doi.org/10.1002/elps.201900085
Hägele, J. S., Basrak, M. and Schmid, M. G., (2020), ‘Enantioselective separation of Novel
Psychoactive Substances using a Lux® AMP 3 μm column and HPLC-UV’, Journal of
Pharmaceutical and Biomedical Analysis, 179, 112967. Available at:
https://doi.org/10.1016/j.jpba.2019.112967
Heather E., Bortz A., Shimmon R., McDonagh A.M. (2017), ‘Organic impurity profiling of
methylone and intermediate compounds synthesized from catechol’, Drug Testing and
Analysis, 9(3):436-45.
Kadkhodaei, K., Forcher, L. and Schmid, M. G., (2018), ‘Separation of enantiomers of new
psychoactive substances by high‐performance liquid chromatography’, Journal of Separation
Science, 41(6), pp. 1274–1286. Available at: https://doi.org/10.1002/jssc.201701239
Kadkhodaei, K., Kadisch, M. and Schmid, M. G., (2020), ‘Successful use of a novel lux® i‐
Amylose‐1 chiral column for enantioseparation of ‘legal highs’ by HPLC’, Chirality, 32(1),
pp. 42–52. Available at: https://doi.org/10.1002/chir.23135
33
Kohut, S. J., Fivel, P. A., Blough, B. E., Rothman, R. B. and Mello, N. K. (2013), ‘Effects of
methcathinone and 3-Cl-methcathinone (PAL-434) in cocaine discrimination or self-
administration in rhesus monkeys’, International Journal of Neuropsychopharmacology,
16(9), pp. 1985-1998. https://doi.org/10.1017/S146114571300059X
Kranenburg, R. F., Verduin, J., de Ridder, R., Weesepoel, Y., Alewijn, M., Heerschop, M.,
Keizers, P.H.J., van Esch, A. and van Asten, A. C., (2021), ‘Performance evaluation of
handheld Raman spectroscopy for cocaine detection in forensic case samples’, Drug
Testing and Analysis, 13(5), pp. 1054–1067. Available at: https://doi.org/10.1002/dta.2993
Lajtai, A., Mayer, M., Lakatos, Á., Kuzma, M. and Miseta, A., (2020), ‘New psychoactive
versus conventional stimulants-a ten-year review of casework in Hungary’, Legal Medicine,
47, 101780. Available at: https://doi.org/10.1016/j.legalmed.2020.101780
McDermott, S. D., Power, J. D., Kavanagh, P. and O’Brien, J., (2011), ‘The analysis of
substituted cathinones. Part 2: an investigation into the phenylacetone based isomers of 4-
methylmethcathinone and N-ethylcathinone’, Forensic Science International, 212(1-3),
pp. 13–21. Available at: https://doi.org/10.1016/j.forsciint.2011.06.030
Piorunska-Sedlak, K. and Stypulkowska, K., (2020), ‘Strategy for identification of new

psychoactive substances in illicit samples using attenuated total reflectance infrared
spectroscopy’, Forensic Science International, 312, 110262. Available at:
https://doi.org/10.1016/j.forsciint.2020.110262
Saferparty. Warnungen. https://www.saferparty.ch/warnungen.html
Shalabi, A. R., Walther, D., Baumann, M. H. and Glennon, R. A., (2017), ‘Deconstructed
analogues of bupropion reveal structural requirements for transporter inhibition versus
substrate-induced neurotransmitter release’, ACS Chemical Neuroscience, 8(6), pp. 1397–
1403. Available at: https://doi.org/10.1021/acschemneuro.7b00055
Soares, J., Costa, V. M., Bastos, M. L., Carvalho, F., Capela, J. P. (2021), ‘An updated
review on synthetic cathinones’, Archives of Toxicology, 95(9), pp. 2895–2940.
https://doi.org/10.1007/s00204-021-03083-3
Slovenian National Forensic Laboratory, (2015), ‘Analytical report 3-CMC (C10H12ClNO) 1-

(3-chlorophenyl)-2-(methylamino)propan-1-one’, NPS and related compounds – analytical
reports. European project RESPONSE to challenges in forensic drugs analyses. Available
at: https://www.policija.si/apps/nfl_response_web/0_Analytical_Reports_final/3-CMC-ID-
1152-report_final.pdf
SWGDRUG (2017), ‘Monographs: 3-CMC’, https://www.swgdrug.org/Monographs/3-

Chloromethcathinone.pdf
Walther, D., Shalabi, A.R., Baumann, M. H., Glennon, R. A. (2019), ‘Systematic structure-
activity studies on selected 2-, 3-, and 4-monosubstituted synthetic methcathinone analogs
as monoamine transporter releasing agents’, ACS Chemical Neuroscience, 10(1), pp. 740–
745. https://doi.org/10.1021/acschemneuro.8b00524
Westphal F., Junge T., Girreser U., Greibl W., Doering C. (2012), ‘Mass, NMR and IR
spectroscopic characterization of pentedrone and pentylone and identification of their
isocathinone by-products’, Forensic Science International, 10; 217(1-3):157-67.
Wojcieszak, J., Kuczynska, K. and Zawilska, J. B. (2020), ‘Four synthetic cathinones: 3-

chloromethcathinone, 4-chloromethcathinone, 4-fluoro-α-pyrrolidinopentiophenone, and 4-
34
methoxy-α-pyrrolidinopentiophenone produce changes in the spontaneous locomotor activity

and motor performance in mice with varied profiles’, Neurotoxicity Research, 38(2), pp. 536-
551. https://doi.org/10.1007/s12640-020-00227-8
Woźniak, M. K., Banaszkiewicz, L., Wiergowski, M., Tomczak, E., Kata, M., Szpiech, B.,
Namieśnik, J. and Biziuk, M., (2020), ‘Development and validation of a GC–MS/MS method
for the determination of 11 amphetamines and 34 synthetic cathinones in whole blood’,
Forensic Toxicology, 38(1), pp. 42–58. Available at: https://doi.org/10.1007/s11419-019-
00485-y
Wrzesień, W., Stanaszek, R., Zuba, D., Byrska B. (2018), ‘Clandestine laboratory producing
mephedrone (4-MMC) and clephedrone (4-CMC) – substance identification and hazard
analysis’, Problems of Forensic Sciences, Vol. 115 (CXV) 287-309.
35
TD-AZ-22-002-EN-N
Recommended citation:
European Monitoring Centre for Drugs and Drug Addiction (2021), EMCDDA initial report on
the new psychoactive substance 1-(3-chlorophenyl)-2-(methylamino)propan-1-one (3-
chloromethcathinone, 3-CMC). In accordance with Article 5b of Regulation (EC) No
1920/2006 (as amended), Initial reports, Publications Office of the European Union,
Luxembourg.
About the EMCDDA
The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) is the central
source and confirmed authority on drug-related issues in Europe. For over 25 years, it has
been collecting, analysing and disseminating scientifically sound information on drugs and
drug addiction and their consequences, providing its audiences with an evidence-based
picture of the drug phenomenon at European level.
The EMCDDA’s publications are a prime source of information for a wide range of audiences
including: policymakers and their advisors; professionals and researchers working in the
drugs field; and, more broadly, the media and general public. Based in Lisbon, the EMCDDA
is one of the decentralised agencies of the European Union.
More information
More information about the work and main outputs of the EU Early Warning System on new
psychoactive substances:
I EMCDDA Early Warning System on NPS
I EMCDDA New psychoactive substances webpage
I EMCDDA operating guidelines for the European Union Early Warning System on new
psychoactive substances, 2019
Legal notice: Neither the EMCDDA nor any person acting on behalf of the EMCDDA is responsible
for the use that might be made of the following information.
Luxembourg: Publications Office of the European Union
doi:10.2810/464710 I ISBN 978-92-9497-705-2 I ISSN 2600-0954
© European Monitoring Centre for Drugs and Drug Addiction, 2022
Reproduction is authorised provided the source is acknowledged. This publication is only available in
electronic format.
EMCDDA, Praça Europa 1, Cais do Sodré, 1249-289 Lisbon, Portugal

Tel. (351) 211 21 02 00 I [email protected]
emcdda.europa.eu I twitter.com/emcdda I facebook.com/emcdda
36

EMCDDA Initial Report 3 CMC Advance Release

Uploaded by

Copyright:

Available Formats

EMCDDA Initial Report 3 CMC Advance Release

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

EMCDDA Initial Report 3 CMC Advance Release

Uploaded by

Copyright:

Available Formats

INITIAL REPORTS 11

About this series

Project leaders: Michael Evans-Brown, Ana Gallegos and Roumen Sedefov.

1-(3-Chlorophenyl)-2-(methylamino)propan-1-one (3-chloromethcathinone, 3-CMC) is a

In Europe, 3-CMC is monitored by the EMCDDA as a new psychoactive substance ( 3)

3-CMC was formally notified as a new psychoactive substance ( 6) ( 7) by the EMCDDA on

 reports of health problems;

 reports of social problems;

 reports of seized material;

 pharmacological and toxicological properties and analogy with better-studied

 potential for further spread.

2. Information collection process

In accordance with the requirements of Article 5b of the Regulation, on 13 September 2021,

The EMCDDA collected information through:

 routine monitoring of open source information;

In addition, the EMCDDA also submitted requests to:

 The World Health Organization (WHO) in order to determine if 3-CMC is under

 The European Medicines Agency (EMA) in order to determine if 3-CMC is used as

a. a medicinal product for human use or in a veterinary medicinal product that

b. a medicinal product for human use or in a veterinary medicinal product that is

c. a medicinal product for human use or in a veterinary medicinal product whose

d. an unauthorised medicinal product for human use in accordance with Article 5

e. an investigational medicinal product as defined in point (d) of Article 2 of

 Europol in order to provide information on the involvement of criminal groups in the

Information on seizures reported by police and customs agencies is analysed separately. In

4. Information required by Article 5b(2) of the Regulation

4.1.1. Information from seizures, collected samples and biological samples

Information from seizures

A summary of the information reported is provided below.

Customs Police Other

Information from collected samples

Information from biological samples

In addition to these, 202 detections of 3-CMC in biological samples were reported by

 4 samples associated with deaths, reported by Sweden ( 14);

 2 samples associated with non-fatal poisonings, reported by Hungary ( 15);

 27 samples associated with petty drug offences, reported by Sweden;

 21 cases of persons suspected of driving under the influence of drugs, reported by

 15 samples associated with abuse cases, reported by Sweden;

 6 samples analysed for drug treatment purposes, reported by Sweden; and

4.1.2. Health problems

4.1.3. Social problems

4.1.4. Patterns of use

4.2.1. Chemical description and names

3-CMC is a synthetic derivative of the naturally occurring substance cathinone, which is

3-CMC 4-CMC Methcathinone 3-MMC

Molecular C10H12CINO C10H12CINO C10H13NO C11H15NO

Molecular mass 197.66 197.66 163.22 177.24

Note: Information on 4-CMC, methcathinone and 3-MMC is provided for comparison.

Systematic (IUPAC) name:

Other chemical names:

Chemical Abstracts Service (CAS) registry numbers:

1607439-32-6 (hydrochloride salt)

IUPAC International Chemical Identifier Key (InCHI Key):

QXEPSICDXPPHTO-UHFFFAOYSA-N (hydrochloride salt)

IUPAC International Chemical Identifier String (InchI string):

Simplified Molecular-Input Line-Entry System (SMILES):

Cl.CNC(C)C(=O)c1cccc(Cl)c1 (hydrochloride salt)

4.2.2. Physical description

Limited information is available about the chemical precursors or manufacturing methods