Recent developments in the detection

of harms arising from the use of

synthetic cathinones in Europe

Ana Gallegos24 September 2015

Lisbon Addictions Conference 2015

Paper session 10 – New opportunities for harm reduction: behaviours

No conflict of interest

The EU Early Warning System on NPS – since 1997

Reporting - forensic analysis

Open source informationTargeted research

The EU Early Warning System on NPS

101

Total: 527 substances under monitoring; 60% of whic h since 2012

methylone

95 synthetic cathinones monitored by the EWS

31 new in 2014; 18 new in 2015

4

MBDB

4-MTA

Ketamine *GHB

PMMA *

2C-I2C-T-22C-T-7TMA-2

1998 1999 2000 2001 2003

BZP

2007

Mephedrone

2010

4-MA

2012

5-IT

2013 2014

Methoxetamine *MDPV25I-NBOMeAH-79214,4’-DMAR *MT-45 *

Under the terms of the Council Decision 2005/387/JHAUnder the terms of the Joint Action 97/396/JHA

2005

1997 – 2005 > 30 ‘new synthetic drugs’ detected9 risk assessments6 substances controlled

2005 – present > 450 new psychoactive substances detected10 risk assessments8 substances controlled

Internationally controlled, 2015* Reviewed 36th/37th ECDD meetings

2015

α-PVP *

The EU Early Warning System on NPS

NPS ‘phenomenon’

5

Consistent increase in � Substances notified� Seizures (number and weight)� Serious adverse events associated with NPS

NSz and quantity seized (powders), 2005-2013 NSz and proportion of seizures by substance, 2013

10 657 seizures amounting

to more than 1.1 tonnes in 2013

Number of seizures of synthetic cathinones (NSz)

NSz and quantity seized (powders), 2005-2013 NSz and proportion of seizures by substance, 2013

Typically supplied as a powder; but also in tablet, capsule and liquid form.

Number of seizures of synthetic cathinones (NSz)

They are soluble in water and the powder can be dis solved for oral use or intravenous and subcutaneous injection.

Many of them are used as replacements for stimulants.

0

2000

4000

Mephedrone

0

500

1000

MDPV

α-PVP

0

500

1000

2005 2007 2009 2011 2013

NSz and proportion of seizures by substance, 2013

Number of seizures by substance

RA – 2010

2008

2008

2013

2013

Chemistry

9

KhatCatha edulis Forsk

MethcathinoneCathinone Amphetamine

Structural diversity

10

Chemical structuresufficiently different so they fall outside the cope of (inter)national drug laws

11

Internationally controlled – 1971 UN Convention

4-methylmethcathinone

4-MMC, mephedrone

Schedule I

Methcathinone

EU risk assessment, 2010

Cathinone

alpha-pyrrolidinovalerophenone

α–PVP

Pyrovalerone

Schedule I Schedule IV

3,4-methylenedioxypyrovaleroneMDPV

EU risk assessment, 2014EU joint report, 2015

Schedule II (2015)Schedule II (2015)Under review (2015)

Pharmacologyconsiderable diversity of pharmacology within the group of cathinones

‘Methamphetamine-like’ cathinones

Cathinone

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

Schedule I

Methcathinone

Pharmacologyconsiderable diversity of pharmacology within the group of cathinones

13

4-methylmethcathinone

4-MMC, mephedrone

EU risk assessment, 2010

Schedule II (2015)

Liechti, M.E. Swiss Med Wkly. 2015;145:w14043

‘Cocaine/MDMA’ cathinones

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

‘Pyrovalerone-like’ cathinones

Pharmacologyconsiderable diversity of pharmacology within the group of cathinones

14

alpha-pyrrolidinovalerophenone

α–PVP

Pyrovalerone

Schedule IV

3,4-methylenedioxypyrovaleroneMDPV

EU risk assessment, 2014

EU joint report, 2015 Schedule II (2015)

Liechti, M.E. Swiss Med Wkly. 2015;145:w14043

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

Mephedrone4-methylmethcathinone

2007 2008 20102009 2011

08.2007Australia4 capsules submitted to hospital (Neorganics)

03.2008Finland1st notification

10.2008UK1st notification

12.2010Decision of control at European level

07.2010European risk assessment

16.04.2010controlled under the UK Misuse of Drugs Act

11.2009Media hype

2010UK first toxicologically confirmed fatalities and large seizures

01-03.2009first cases of acute toxicity reported

11.2007Finland1st occurrence

2015International controlSc II - 1971UNConvention

Sample of mephedrone bought in Lisbon (2010)

16

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

18

• 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.

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

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Ana.Gallegos@emcdda.europa.eu

Thank you