No conflict of interest Recent developments in the detection of harms arising from the use of synthetic cathinonesin 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 101 methylone
The EU Early Warning System on NPS Internationally controlled, 2015 * Reviewed 36 th /37 th ECDD meetings Under the terms of the Joint Action 97/396/JHA 1997 2005 > 30 new synthetic drugs detected 9 risk assessments 6 substances controlled Under the terms of the Council Decision 2005/387/JHA 2005 present > 450 new psychoactive substances detected 10 risk assessments 8 substances controlled 1998 1999 2000 2001 2003 2007 2010 2012 2013 2014 2015 4-MTA PMMA * 2005 Mephedrone 5-IT α-pvp * MBDB Ketamine * GHB 2C-I 2C-T-2 2C-T-7 TMA-2 BZP 4-MA Methoxetamine * MDPV 25I-NBOMe AH-7921 4,4 -DMAR * MT-45 * 4
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 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 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 4000 Mephedrone RA 2010 2000 0 2008 2013 1000 MDPV 500 0 1000 α-pvp 2008 2013 500 0 2005 2007 2009 2011 2013
Chemistry Cathinone Amphetamine Methcathinone Khat Catha edulis Forsk 9
Structural diversity 10
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 3,4-methylenedioxypyrovalerone MDPV 4-methylmethcathinone 4-MMC, mephedrone EU joint report, 2015 Under review (2015) EU risk assessment, 2014 Schedule II (2015) EU risk assessment, 2010 Schedule II (2015) 11
Pharmacology considerable diversity of pharmacology within the group of cathinones Cathinone Methamphetamine-like cathinones 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 13
Pharmacology considerable diversity of pharmacology within the group of cathinones alpha-pyrrolidinovalerophenone α PVP Pyrovalerone-like cathinones Pyrovalerone 3,4-methylenedioxypyrovalerone MDPV EU risk assessment, 2014 EU joint report, 2015 Schedule IV 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 14
Mephedrone 4-methylmethcathinone 11.2007 Finland 1 st occurrence 03.2008 Finland 1 st notification 01-03.2009 first cases of acute toxicity reported 07.2010 European risk assessment 12.2010 Decision of control at European level 2007 2008 2009 2010 2011 08.2007 Australia 4 capsules submitted to hospital (Neorganics) 10.2008 UK 1 st notification 11.2009 Media hype 2010 UK first toxicologically confirmed fatalities and large seizures 2015 International control Sc II - 1971UN Convention 16.04.2010 controlled under the UK Misuse of Drugs Act
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 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. 18
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 Ana.Gallegos@emcdda.europa.eu emcdda.europa.eu twitter.com/emcdda facebook.com/emcdda youtube.com/emcddatube flickr.com/photos/emcdda