Synthetic Cannabinoids in Europe: A Review

2021·1.8 MB·English

Synthetic cannabinoids
in Europe – a review
I Legal notice
This publication of the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) is protected by copyright.
The EMCDDA accepts no responsibility or liability for any consequences arising from the use of the data contained in
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any EU Member State or any agency or institution of the European Union.
Luxembourg: Publications Office of the European Union, 2021
PRINT ISBN 978-92-9497-646-8 doi:10.2810/4249 TD-02-21-819-EN-C
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© European Monitoring Centre for Drugs and Drug Addiction, 2021
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I
Contents
I
2 Methods and information sources
I
4 Executive summary
I
5 Background
I
5 History of the development of synthetic cannabinoids
I
5 Legitimate uses of synthetic cannabinoids
I
6 International control measures
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6 Synthetic cannabinoids in Europe
I
6 Emergence as new psychoactive substances
I
6 Availability and size of the market
I
9 Response to synthetic cannabinoids
I
10 Replacement
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10 Physical, chemical and pharmacological description
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10 Physical and chemical description
I
12 Physical and pharmaceutical form
I
14 Pharmacology
I
21 Health and social risks
I
21 Acute toxicity
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29 Chronic toxicity
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31 Psychological and behavioural effects
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31 Dependence and abuse potential
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32 Effects on ability to drive and operate machines
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32 Social risks
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32 Extent and patterns of use, availability and potential for diffusion
I
32 Prevalence of use
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33 Patterns of use
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34 Availability, supply and involvement of organised crime
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36 Conclusions
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37 References
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51 Annex 1. Profiles of selected synthetic cannabinoids
I
61 Annex 2. Synthetic cannabinoids monitored by the EMCDDA through the EU Early
Warning System on new psychoactive substances (as of 16 April 2021)
Synthetic cannabinoids in Europe – a review
I Methods and information sources
Authors
Volker Auwärter (*), Joanna de Morais (**), Ana In the context of this report, ‘synthetic cannabinoids’ are
Gallegos (**), Michael Evans-Brown (**), Rachel defined as new psychoactive substances that mimic the
Christie (**), Rita Jorge (**) and Roumen Sedefov (**) effects of tetrahydrocannabinol, the major psychoactive
substance in cannabis. Another common name for this
(*) Forensic Toxicology Department, Institute of Forensic Medicine,
Medical Center, University of Freiburg, Germany group of substances is ‘synthetic cannabinoid receptor
(**) European Monitoring Centre for Drugs and Drug Addiction agonists’.
(EMCDDA), Lisbon, Portugal
Funding The terms ‘synthetic cannabinoid receptor agonists’, ‘spice’
and ‘synthetic cannabinoid’ were searched in Medline,
Part of this work was supported by EMCDDA
Google Scholar and PubMed. Literature searches used
contracts CT.18.SAS.0085.1.0 with Dr Volker
both the chemical structure and text queries in online
Auwärter and CT.18.SAS.0089.1.0 with Dr Simon
databases; searches were conducted in August 2019. The
Brandt.
publications retrieved were then reviewed for additional
Acknowledgements relevant references (the snowball technique). Searches
of the websites of selected medical specialty societies
The EMCDDA would like to extend its sincere thanks
and international, national and local government agencies
and appreciation to the Early Warning System
were conducted to identify position statements and
correspondents of the Reitox national focal points
reports. Search strings were introduced in Google and
and experts from their national early warning
Google Scholar, and the first 100 hits were screened to
system networks, as well as the Europol national
find additional relevant content. Although the systematic
units. The authors would like to thank the Forensic
searches were conducted in 2018, information from
Toxicology Department (Institute of Forensic
thematic scientific papers and reports published in 2019
Medicine, Medical Center, University of Freiburg,
and 2020 was also included in this report.
Germany); the Italian National Institute of Health; the
Forensic Science Centre of Lithuania; and Dr Craig
English-language articles were selected from a search of
McKenzie (Leverhulme Research Centre for Forensic
PubMed (National Center for Biotechnology Information),
Science, University of Dundee, United Kingdom),
Web of Science (Thomson Reuters), Medline and
for the images used in this publication. The authors
Google Scholar. The search terms used were ‘synthetic
also thank Arianna Giorgetti, Sebastian Halter,
cannabinoid receptor agonists’, ‘spice’ and ‘synthetic
Belal Haschimi, Laura Huppertz and Lukas Mogler
cannabinoid’. Textual searches were also conducted in
(Institute of Forensic Medicine, Medical Center,
popular English-language drug forums.
University of Freiburg, Germany) for their support; Dr
Simon Brandt (School of Pharmacy and Biomolecular
In addition, exact chemical structure-based searches
Sciences, Liverpool John Moores University, United
were done in SciFinder (American Chemical Society,
Kingdom) for peer-reviewing this report; and Regina
Chemical Abstract Service) and Reaxys (Elsevier). As
Kühnl (IFT Institut für Therapieforschung München,
part of the report, the individual profiles of selected
German Monitoring Centre for Drugs and Drug
synthetic cannabinoids were developed. The substances
Addiction) for reviewing parts of this report.
were identified by the European Monitoring Centre for
Drugs and Drug Addiction (EMCDDA) based on reports
Statement on the United Kingdom
of high availability in Europe and/or reports of serious
The United Kingdom left the European Union on adverse events. Google and specific drug user discussion
1 February 2020. For the purpose of this report, the forums and related websites (such as Bluelight, Eve
United Kingdom is not included in the term ‘Member and Rave, and Erowid) were searched for the terms
States’. ‘CUMYL-PeGACLONE’, ‘AMB-FUBINACA’, ‘AB-FUBINACA’,
‘CUMYL-5F-P7AICA’ and ‘5F-MDMB-PICA’, alone or
in combination with ‘buy’, ‘shop’, ‘research chemical’,
‘synthetic cannabinoid’, ‘dosing’, ‘poisoning’, ‘kaufen’,
‘räuchermischung’, ‘powder’ or ‘synthesis’. In addition,
colleagues within the authors’ scientific networks were
contacted to obtain information.
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Synthetic cannabinoids in Europe – a review
Searches of open source information, including scientific
articles, official reports, grey literature, internet drug
discussion forums and related websites, were also
included.
Information from the European Union Early Warning
System on NPS (EWS), operated by the EMCDDA, has
been included, as relevant. The EWS is composed of a
multiagency and multidisciplinary network, which includes
the EMCDDA, 29 national early warning systems (27 EU
Member States, Turkey, and Norway), Europol and its law
enforcement networks, the European Medicines Agency
(EMA), the European Commission and other partners.
Information from United Nations agencies (the United
Nations Office on Drugs and Crime and the World Health
Organization) as well as from third countries such as
Canada, Russia, the United Kingdom, and the United
States has also been included, as relevant.
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Synthetic cannabinoids in Europe – a review
I Executive summary and act as full agonists at the cannabinoid receptors
(THC, in contrast, is a partial agonist). This means that,
Synthetic cannabinoids are functionally similar to ∆9- even at very small doses, synthetic cannabinoids can
tetrahydrocannabinol (∆9-THC), the major psychoactive activate the cannabinoid receptors much more strongly
substance in cannabis. They bind to the same cannabinoid than THC. Secondly, products containing synthetic
receptors in the brain and other organs as THC. They were cannabinoids often contain high doses of the substances.
originally developed by scientists to study the body’s The combination of these two factors makes it difficult
endocannabinoid system, as well as to provide insights for users to control the dose that they are exposed to.
into disease and to help develop new medicines. Around This can lead them to rapidly administer a toxic dose
the mid-2000s, they began to appear in Europe in products unintentionally. These factors are also responsible for
called ‘Spice’ that were sold as ‘legal’ replacements for the outbreaks of mass poisonings seen with synthetic
cannabis. In these products, synthetic cannabinoids were cannabinoids, which have ranged from a handful of people
mixed with plant material, which could then be smoked to hundreds, some of whom have died. While many of
as cigarettes (‘joints’). In recent years, alongside these the outbreaks reported so far have been in the United
smoking mixtures, new products, including e-liquids for States, they have also occurred in Russia, Canada and
vaping using electronic cigarettes and paper impregnated Europe. Outbreaks due to synthetic cannabinoids being
with synthetic cannabinoids, have been sold on the drug mis-sold or used to adulterate cannabis products, as well
market. Unknown to users, synthetic cannabinoids have as other illicit drugs, such as opioids, are increasingly
also been mis-sold or used to adulterate cannabidiol common. Such outbreaks can rapidly overwhelm
(CBD) and THC e-liquids, as well as other illicit drugs, the capacity of emergency responders and hospital
such as opioids. Another concerning development is the emergency departments, which is of particular concern
recent adulteration of cannabis products with synthetic given the ongoing COVID-19 pandemic and the additional
cannabinoids in Europe. Typically, these adulterated burden already placed on healthcare systems. There is
products are low-THC herbal material or resins. In terms no approved antidote to poisoning caused by synthetic
of look, smell and flavour, these adulterated products cannabinoids. The effects on health from the chronic
would be very difficult to distinguish from ‘genuine’ illicit use of synthetic cannabinoids are largely unknown;
cannabis products and, as a result, users may be unaware however, regular use has been linked to problems such as
that they are using synthetic cannabinoids. As synthetic dependence and withdrawal symptoms.
cannabinoids are highly potent substances, people who
use these products could be at high risk of poisoning. Synthetic cannabinoids are used by a range of people,
including those who use cannabis, those who are regularly
Synthetic cannabinoids activate the same cannabinoid subjected to drug-testing procedures (such as prisoners)
receptors in the body as THC. The behavioural and and people who experiment with a range of substances
physiological effects that have been reported with (so called ‘psychonauts’). Increasingly, synthetic
synthetic cannabinoids include relaxation, euphoria, cannabinoids are also used by some high-risk drug users
lethargy, depersonalisation, distorted perception of time, and other vulnerable groups (such as prisoners and
impaired motor performance, hallucinations, paranoia, people experiencing homelessness), as they have gained
confusion, fear, anxiety, dry mouth, bloodshot eyes, a reputation for causing profound intoxication, they can be
tachycardia, nausea, and vomiting. cheaper than other drugs and they are easy to smuggle.
Despite similarities, however, synthetic cannabinoids In Europe, synthetic cannabinoids are monitored as
can cause more profound intoxication than cannabis. new psychoactive substances by the European Union
Severe poisonings are also more common, and fatalities Early Warning System. They are the largest group of
linked to the consumption of these substances have substances monitored by the European Monitoring
been recorded. There have been case reports of serious Centre for Drugs and Drug Addiction (EMCDDA), with
cardiovascular toxicity (including sudden death), rapid 209 reported between 1 January 2008 and 31 December
loss of consciousness/coma, respiratory depression, 2020. Since 2015, there has been a decrease in the
seizures and convulsions, hyperemesis, delirium, agitation, number of synthetic cannabinoids appearing for the
psychosis, and aggressive and violent behaviour. It appears first time each year on the drug market and an overall
that, at least in part, these effects are due to the high decrease in seizures of synthetic cannabinoids by law
potency of synthetic cannabinoids and the unintentionally enforcement. In part, these changes appear to be related
high doses that users may be exposed to. Firstly, laboratory to a disruption in the ‘legal high’ trade, which for a period
studies have found that many of the cannabinoids sold saw new psychoactive substances being sold openly
on the drug market are much more potent than THC on the high street in many countries in Europe. More
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Synthetic cannabinoids in Europe – a review
generally, broader policy responses designed to restrict This report provides a technical review of the current
the availability of new psychoactive substances are also body of knowledge regarding synthetic cannabinoids
likely to have had an effect. Despite this, the market in that are monitored by the EMCDDA. The aim of this
synthetic cannabinoids, once the epitome of the ‘legal report is to strengthen situational awareness of synthetic
highs’ phenomenon, continues to evolve and pose a cannabinoids in Europe and to help stakeholders prepare
threat to health security. During 2020, signals related for and respond to public health and social threats caused
to two synthetic cannabinoids, MDMB-4en-PINACA and by such substances.
4F-MDMB-BICA, led the EMCDDA to launch initial reports
on the substances because of concerns of potential
public health and social threats to Europe. Both MDMB-
4en-PINACA and 4F-MDMB-BICA were formally risk I Background
assessed by the EMCDDA in December 2020. Based on
the risk assessment reports, in March 2021 the European
I
Commission proposed that MDMB-4en-PINACA and History of the development of synthetic
4F-MDMB-BICA be controlled in Europe. Since 2016, a cannabinoids
total of seven synthetic cannabinoids have been formally
risk assessed by the EMCDDA (i.e. MDMB-CHMICA (2016), The first synthetic analogues of ∆9-tetrahydrocannabinol
5F-MDMB-PINACA, AB-CHMINACA, ADB-CHMINACA, (∆9-THC; the major psychoactive substance in cannabis)
CUMYL-4CN-BINACA (2017), 4F-MDMB-BICA and MDMB- were synthesised by Mechoulam (Mechoulam and Carlini,
4en-PINACA (2020)). 1978) shortly after the first total synthesis of ∆9-THC was
published (Mechoulam and Gaoni, 1965). Their chemical
Despite measures intended to reduce the availability structure was similar to the structure of ∆9-THC (e.g.
of synthetic cannabinoids on the drug market, data nabilone and A-41988). After the identification and cloning
reported to the EMCDDA through the EU Early Warning of the CB and CB cannabinoid receptors (Matsuda et
1 2
System show that synthetic cannabinoids continue to be al., 1990; Munro et al., 1993), a variety of chemicals with
widely available across Europe. As noted, the relatively diverse structures were screened for the ability to bind
low cost, easy availability and high potency of synthetic to these receptors. This led to the discovery of several
cannabinoids appear to have resulted in increased use classes of substances that could bind to and activate
among marginalised groups such as people experiencing the cannabinoid receptors (Huffman and Padgett, 2005;
homelessness and prisoners. This development has been Makriyannis and Deng, 2007). Subsequently, a large
associated with an increase in reports of serious harms. body of literature on the subject emerged, focused on the
For example, in prisons, alongside the adverse health development of synthetic cannabinoids as medicines.
effects, the market in and use of synthetic cannabinoids Cannabis was recognised as potentially useful for the
has been linked to an increase in aggression, violence, treatment of conditions such as pain, anorexia, wasting
bullying and debt. In some cases, this has caused a syndrome, muscle spasms and glaucoma (Compton et
serious threat to the overall safety and security of the al.,1992; Melvin et al., 1984), and new drug candidates
prison environment. were developed, focusing on easy to synthesise synthetic
cannabinoids with fewer psychotropic side effects
In the future, it can be expected that synthetic than cannabis. Simultaneously, other groups were also
cannabinoids with high potency and that are easy to investigating the structure–activity relationships of this
synthesise will continue to be introduced into the market. new class of substances (Aung et al., 2000; Huffman et al.,
2005; Melvin et al., 1993; Wiley et al., 2014).
The ongoing COVID-19 pandemic and the related response
measures may affect the existing synthetic cannabinoid
drug markets in unpredictable ways. Such effects may I Legitimate uses of synthetic cannabinoids
extend to changes in use and patterns of use of synthetic
cannabinoids. Seizures of bulk powders by European Synthetic cannabinoids have been the subject of extensive
national customs agencies during the pandemic suggest pharmacological and toxicological research. Some were
that synthetic cannabinoids continue to be imported into developed as drug candidates. Nabilone (Cesamet), for
and distributed within Europe. It is possible that, in the example, is used as an orally administered medicine
case of a reduced availability of cannabis and other illicit for the treatment of nausea and vomiting induced by
drugs in Europe, criminal groups, as well as drug users, cancer chemotherapy in patients receiving a wide variety
may use a range of replacement substances, including of chemotherapy regimens, or to treat cachexia under
synthetic cannabinoids. HIV treatment for patients who have failed to respond
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Synthetic cannabinoids in Europe – a review
adequately to conventional antiemetic treatments. Owing synthetic cannabinoids mixed with plant (herbal) material,
to its side effects and potential for abuse, which are very which could then be smoked as cigarettes (‘joints’)
similar to those of THC, nabilone is not a first-choice (Auwärter et al., 2009; EMCDDA, 2009, 2017; Jack, 2009).
therapy. In addition, synthetic cannabinoids are widely Such smoking mixtures have been referred to by a variety
used in scientific research and in analytical reference of names, depending on the country, region, product type,
material in clinical and forensic case work. brand name and user group. Names associated with these
products include ‘smoking mixtures’, ‘herbal smoking
mixtures’, ‘herbal incense’, ‘synthetic cannabis’, ‘legal
I International control measures weed’ and ‘K2’. Common street names used include ‘magic
tobacco’ in Hungary, ‘chimique’ in France, ‘Bonsai’ in Turkey
The following synthetic cannabinoids are included in the and, in Birmingham (United Kingdom), ‘Black Mamba’ or
list of substances in Schedule II of the United Nations simply ‘Mamba’. ‘Legal high’ products containing synthetic
Convention on Psychotropic Substances of 1971 (INCB, cannabinoids have been subject to innovative marketing
2020): approaches and are widely and openly available on the
(cid:1) AM-2201 (JWH-2201) and JWH-018 (AM-678) (since web. During the first few years of the phenomenon, similar
2015), products were also available in some countries in bricks-
and-mortar (‘head’ and ‘smart’) shops.
(cid:1) 5F-AKB-48 (5F-APINACA), MDMB-CHMICA and XLR-11
(5F-UR-144) (since 2017), Owing to the number and variety of synthetic cannabinoids
emerging on the drug market, one of the challenges
(cid:1) AB-CHMINACA, AB-PINACA, 5F-MDMB-PINACA
associated with their appearance is their naming. As the
(5F-ADB), AM-2201 carboxylate analogue quinolinyl
structures of most synthetic cannabinoids can be broken
derivative (5F-PB-22) and UR-144 (since 2018),
down into four components – tail, core, linker and linked
(cid:1) ADB-FUBINACA, AMB-FUBINACA (FUB-AMB), CUMYL- group – the EMCDDA has introduced a semi-systematic
4CN-BINACA and ADB-CHMINACA (since 2019), approach to assigning common names to them (EMCDDA,
2017). Each component of the structure is assigned
(cid:1) AB-FUBINACA, 5F-AMB (5F-AMB-PINACA), 5F-MDMB-
a code name, and the ordered combination of code
PICA and 4F-MDMB-BINACA (since 2020).
names for the linked group, tail, core and linker allows the
chemical structure of the substance to be ciphered.
In 2020, MDMB-4en-PINACA (WHO, 2020a) and CUMYL-
PeGACLONE (WHO, 2020b) were assessed at the
43rd meeting of the WHO Expert Committee on Drug I Availability and size of the market
Dependence and were recommended to be included
in Schedule II of the 1971 Convention on Psychotropic Synthetic cannabinoids are the largest group of new
Substances (WHO, 2020c). psychoactive substances monitored by the EMCDDA
through the EU Early Warning System, with 209 identified
on the drug market over the 13 years between 1 January
2008 and 31 December 2020. This includes 11 that were
I Synthetic cannabinoids in Europe identified for the first time in 2020. An average of 27
cannabinoids appeared each year in Europe between 2011
and 2015, but since 2016 the annual number has dropped
I Emergence as new psychoactive substances to around 10 (Figure 1).
A product called ‘Spice’, containing synthetic cannabinoids, In 2019, over 18 700 seizures of synthetic cannabinoids
appears to have emerged around 2004 as a legal were reported to the EU Early Warning System, which
alternative to cannabis and started to gain popularity represents around 54 % of the total number of seizures
in European countries. By 2008, these products were reported during that year (29 % in the Member States).
gaining wider popularity and were associated with In the European Union, most synthetic cannabinoids
numerous poisonings. Towards the end of 2008, the active seized were in the form of herbal plant material (5 208
substances in these Spice products were identified as cases, 112 kg) or powders (684 cases, 78 kg) (Figure 2).
JWH-018 and CP-47,497-C8, two synthetic cannabinoids The number of seizures is unevenly distributed across
developed decades ago in the context of research on the Europe, with Turkey accounting for the large majority of
endocannabinoid system (Auwärter et al., 2009; Uchiyama the seizures of synthetic cannabinoids reported in 2019
et al., 2009). These products were found to contain (65 %).
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Synthetic cannabinoids in Europe – a review
FIGURE 1
Number of synthetic cannabinoids formally notified to the EU Early Warning System for the first time, 2008–2020
35
31
30
29
30
24
25 23
20
15
11 11 11 11
10
10 8
6
5
1
0
2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020
FIGURE 2
Seizures of synthetic cannabinoids reported to the EU Early Warning System: trends in (a) the number of seizures of
synthetic cannabinoids and (b) the quantity seized, in weight (kg), 2005–2019 (all forms including powders and herbal
smoking mixtures – EU-27 and EU-27 + 2)
(a) 40 000
35 000
30 000
25 000
20 000
15 000
10 000
5 000
0
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019
EU-27 + 2 EU-27
(b) 3 000
2 500
2 000
1 500
1 000
500
0
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019
EU-27 + 2 EU-27
7
Synthetic cannabinoids in Europe – a review
In recent years, there has been a marked decrease in both
Box 1. Responses in Germany
the number of new synthetic cannabinoids appearing on
the market for the first time and the quantity of powders
Legislation Impact on the market and herbal material containing synthetic cannabinoids
seized in the European Union (Figure 2). Overall, these
The first identification of synthetic cannabinoids in Shortly after the inclusion of recently emerged synthetic developments may in part reflect a decrease in large-scale
herbal blends in Germany was reported by Auwärter and cannabinoids in the annexes of the German Narcotics processing of synthetic cannabinoids into herbal smoking
colleagues in 2008 (Auwärter et al., 2009). The synthetic Act, new substances with structural modifications mixtures, particularly the ‘legal high’ products that typified
cannabinoids detected were JWH-018, CP-47,497 and appeared on the market, presumably as a response by a large part of the new psychoactive substances market in
CP-47,497-C8. In January 2009, JWH-018, CP-47,497 producers to the control measures. Common strategies Europe between 2008 and 2015. Nonetheless, relatively
and three of its homologues were scheduled under the were the substitution of a hydrogen atom by a fluorine large amounts of bulk powders sufficient to make many
German Narcotics Law because of their potential for atom at the terminal position of the side chain or hundreds of thousands of street doses continue to be
abuse and their widespread use. In the following years, modifications at the linked group. seized at Europe’s borders each year, including throughout
further synthetic cannabinoids emerged and were the COVID-19 pandemic.
subsequently scheduled. Owing to the time lag between In December 2016, Angerer et al. (2018a) test-purchased
the emergence of new substances and their scheduling, herbal smoking mixtures containing the synthetic
distributors of new, unscheduled synthetic cannabinoids cannabinoid CUMYL-PeGACLONE, which was not
were prosecuted using the German Medicines Law. covered by the NpSG at that time. Furthermore, other
However, an appeal to the German Federal Supreme synthetic cannabinoids with core structures not covered
Court led to the European Court of Justice reviewing the by the NpSG emerged on the German drug market,
classification of herbal products containing synthetic such as those containing 7-azaindole cores. CUMYL-
cannabinoids as medicines according to the Medicines PeGACLONE was added to the annex of the Narcotics
Law. The European Court of Justice announced its Law in July 2018 by an amendment. With the emergence
decision on 10 July 2014 and concluded that, owing of its fluorinated analogue (5F-Cumyl-PeGaClone), the
to the absence of therapeutic potential and the control measures in place were again circumvented.
associated harms, the products could not be regarded However, with the amendment to the NpSG of July 2019,
as medicinal products as defined in Article 1 No 2 of azaindoles and the γ-carbolinones are now included, the
Directive 2001/83/EC. The resulting regulatory gap latter by modifying the definition of the linker.
led to the German ‘Act to combat the distribution of
new psychoactive substances’ (NpSG) which became Following the introduction of the NpSG, some new
effective on 26 November 2016. In contrast to the synthetic cannabinoids that are not covered by
Narcotics Law, which controls single substances as the generic definitions have appeared on the drug
enumerated in the annexes of the law, the NpSG uses market. These gaps in the definitions can be closed by
a generic approach by defining groups of substances amendments to the NpSG.
based on their chemical structure. Particularly
dangerous substances continue to be placed under the In the future, as producers continue their attempts to
Narcotics Act and, if a substance falls under both laws, circumvent control measures in Europe and elsewhere, it is
the stricter Narcotics Act is applied. The definition of a unclear what new synthetic cannabinoids may be developed
synthetic cannabinoid according to the NpSG comprises and what risks they may pose to health, especially with
four structural elements: core structure, side chain, linker regard to the potential introduction of remote structural
and a linked group. In the original version of the NpSG candidates. It is important that early warning systems can
from November 2016, five core structural elements were detect such substances in a timely manner so that public
defined. On 13 July 2019, an amendment came into health agencies can respond through timely and effective
force in which further core structures that had emerged actions to prevent or reduce the risk of harm.
on the market since 2016 were added. In response to
the identification, shortly after, of cyclobutylmethyl side Figure 3 shows a heat map in which the relative
chains, which were not covered by the act, another positivity rate of 20 selected synthetic cannabinoids
amendment was prepared, which came into force in urine samples analysed in the Institute of Forensic
on 9 July 2020. Meanwhile, synthetic cannabinoids Medicine Freiburg (Germany) is presented for 2015 to
carrying bicyclic side chains have emerged, and a third 2019, including the five compounds described in detail
amendment is currently in preparation. in Annex 1 of this report (i.e. CUMYL-PeGACLONE,
CUMYL-5F-P7AICA/5F-CUMYL-P7AICA, AB-FUBINACA,
AMB-FUBINACA, and 5F-MDMB-PICA).
8