Download Recent developments on the detection of harms arising from the use

No conflict of interest
Recent developments in the detection
of harms arising from the use of
synthetic cathinones in Europe
Ana Gallegos
24 September 2015
Lisbon Addictions Conference 2015
Paper session 10 – New opportunities for harm reduction: behaviours
The EU Early Warning System on NPS – since 1997
Reporting - forensic analysis
Targeted research
Open source information
The EU Early Warning System on NPS
Total: 527 substances under monitoring; 60% of which since 2012
95 synthetic cathinones monitored by the EWS
31 new in 2014; 18 new in 2015
methylone
101
The EU Early Warning System on NPS
Under the terms of the Joint Action 97/396/JHA
Under the terms of the Council Decision 2005/387/JHA
1997 – 2005
> 30 ‘new synthetic drugs’ detected
9 risk assessments
6 substances controlled
1998
1999
4-MTA
MBDB
2000
2001
2005 – present
> 450 new psychoactive substances detected
10 risk assessments
8 substances controlled
2003
2007
2005
PMMA *
Ketamine *
GHB
Internationally controlled, 2015
* Reviewed 36th/37th ECDD meetings
2C-I
2C-T-2
2C-T-7
TMA-2
2010
2012
Mephedrone
BZP
2013
5-IT
4-MA
2014
2015
α-PVP *
Methoxetamine *
MDPV
25I-NBOMe
AH-7921
4,4’-DMAR *
MT-45 *
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NPS ‘phenomenon’
Consistent increase in
Substances notified
Seizures (number and weight)
Serious adverse events associated with NPS
5
Number of seizures of synthetic cathinones (NSz)
NSz and quantity seized (powders), 2005-2013
10 657 seizures amounting
to more than 1.1 tonnes in 2013
NSz and proportion of seizures by substance, 2013
Number of seizures of synthetic cathinones (NSz)
NSz and quantity seized (powders), 2005-2013
NSz and proportion of seizures by substance, 2013
Many of them are used as
replacements for stimulants.
Typically supplied as a powder;
but also in tablet, capsule and
liquid form.
They are soluble in water and the powder can be dissolved for oral
use or intravenous and subcutaneous injection.
Number of seizures by substance
NSz and proportion of seizures by substance, 2013
RA – 2010
4000
Mephedrone
2000
0
2008
2013
1000
MDPV
500
0
2013
2008
1000
α-PVP
500
0
2005
2007
2009
2011
2013
Chemistry
Cathinone
Amphetamine
Methcathinone
Khat
Catha edulis Forsk
9
Structural diversity
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Chemical structure
sufficiently different so they fall outside the cope of (inter)national drug laws
Internationally controlled – 1971 UN Convention
Cathinone
Pyrovalerone
Methcathinone
Schedule I
Schedule IV
Schedule I
alpha-pyrrolidinovalerophenone
α–PVP
EU joint report, 2015
Under review (2015)
3,4-methylenedioxypyrovalerone
MDPV
EU risk assessment, 2014
Schedule II (2015)
4-methylmethcathinone
4-MMC, mephedrone
EU risk assessment, 2010
Schedule II (2015)
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Pharmacology
considerable diversity of pharmacology within the group of cathinones
‘Methamphetamine-like’ cathinones
Cathinone
Methcathinone
Schedule I
Schedule I
Toxicity similar to amphetamine, including:
hypertension, hyperthermia, euphoria, locomotor activation, and
hallucinations following higher or repeated doses.
Liechti, M.E. Swiss Med Wkly. 2015;145:w14043
Pharmacology
considerable diversity of pharmacology within the group of cathinones
‘Cocaine/MDMA’ cathinones
4-methylmethcathinone
4-MMC, mephedrone
EU risk assessment, 2010
Schedule II (2015)
Empathogen/stimulant-type effects; dependence potential
Subjective effects similar to those of cocaine but also MDMA
It has been reported to produce ‘strong craving’ in humans and
to be ‘more addictive’ than cocaine.
Acute toxicity: sympathomimetic toxidrome, agitation,
vomiting, psychosis, chest pain, seizures, insomnia
Liechti, M.E. Swiss Med Wkly. 2015;145:w14043
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Pharmacology
considerable diversity of pharmacology within the group of cathinones
‘Pyrovalerone-like’ cathinones
alpha-pyrrolidinovalerophenone
α–PVP
EU joint report, 2015
Pyrovalerone
Schedule IV
3,4-methylenedioxypyrovalerone
MDPV
EU risk assessment, 2014
Schedule II (2015)
More potent than cocaine or methamphetamine
High lipophilicity – they cross readily the blood-brain barrier
Risks of sympathomimetic toxicity and of addiction in humans
Acute toxicity: sympathomimetic toxidrome, agitation, psychosis, hallucinations,
combative behaviour, chest pain, prolonged insomnia
Liechti, M.E. Swiss Med Wkly. 2015;145:w14043
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Mephedrone
4-methylmethcathinone
11.2007
Finland
1st occurrence
2007
08.2007
Australia
4 capsules submitted to
hospital (Neorganics)
03.2008
Finland
1st notification
2008
01-03.2009
first cases of acute
toxicity reported
2009
10.2008
UK
1st notification
07.2010
European
risk assessment
12.2010
Decision of control
at European level
2010
11.2009
Media hype
2011
2010
UK first toxicologically
confirmed fatalities and
large seizures
16.04.2010
controlled under the UK
Misuse of Drugs Act
2015
International
control
Sc II - 1971UN
Convention
Sample of mephedrone bought in Lisbon (2010)
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MDPV
• MDPV has potent cocaine-like stimulant properties.
• MDPV was reported in seizures in 27 MS, Norway and Turkey. In excess of
5 500 seizures were reported, with two countries reporting >1000 seizures
each (UK, FI). The total amount of powder seized was over 200 kg.
• EMCDDA monitoring of Internet suppliers and retailers selling MDPV
identified more than 20 companies that may be based within the
European Union and China, offering up to multi-kilogram quantities of the
substance.
• A total of 525 non-fatal intoxications associated with MDPV have been
reported by 8 MS.
• Key adverse effects associated with MDPV intoxication frequently
reported in clinical case reports include: paranoid psychosis, hypertension,
tachycardia, diaphoresis, severe agitation, auditory and visual
hallucinations, profound anxiety, hyperthermia, violent outbursts and
multiple organ dysfunction.
• There have been a total of 108 deaths associated with MDPV reported by
8 MS and Norway in which MDPV has been detected in biological
samples.
α- PVP
• α-PVP, similarly to MDPV, is a potent psychostimulant with abuse liability
and dependence potential.
• α-PVP has been available in the EU since at least February 2011 and has
been detected in 28 MS, Turkey and Norway. In excess of 5200 seizures
were reported with 8 countries reporting > 100 seizures each (UK, FI, SK, SE,
IE, HU & TK). The total amount of powder seized was over 750 kg.
• It has been seized as a powder, but other forms including tablets have been
detected. Multi-kilogram quantities of α-PVP have been seized at EU
borders which usually originate from China. This includes the seizure of
more than 280 kg in 2015. Illicit production and tableting sites have also
been seized. α-PVP is sold as a ‘research chemical’ online and is available in
wholesale and consumer amounts.
• 140 serious adverse events associated with α-PVP have been reported by 9
MS. This includes acute intoxications requiring hospitalisation and more
than 100 deaths; in at least 23 of these deaths α-PVP was the cause of
death or contributed to it.
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Conclusions
•
Synthetic cathinones have carved a space in the illicit
stimulants market.
•
The injection of synthetic cathinones by high risk drug users
has been reported in a number of countries in Europe.
•
Injecting cathinones carries public health risks of bacterial
infections and transmission of blood-borne viruses such as
human immunodeficiency virus, hepatitis C virus and
hepatitis B virus.
•
Data suggests that injection of these substances lead to
different treatment needs than illicit drugs (more frequent
injecting, sharing of injecting equipment and psychosis).
•
Research needed (pharmacological & toxicological studies).
19
Thank you
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