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Bibliotecasgc.bage.esEMCDDA–Europol Joint Report on a new psychoactive substance: MDPV (3,4-methylenedioxypyrovalerone) In accordance with Article 5 of Council Decision 2005/387/JHA on the information exchange, risk assessment and control of new psychoactive substances About this series
EMCDDA–Europol Joint Report publications examine the detailed information
provided by the EU Member States on individual new psychoactive substances.
Information is collected from the Reitox network, the Europol national units and the
national competent authorities of the European Medicines Agency.
Each Joint Report serves as the basis upon which the decision to conduct a risk
assessment of the new psychoactive substance is taken. It is part of the three-step
procedure involving information exchange, risk assessment and decision-making in the
framework of the Council Decision 2005/387/JHA.
EMCDDA–Europol joint publication I Contents
The EMCDDA would like to thank the following for their contribution in producing this publication:
I the Early-warning system (EWS) correspondents of the Reitox national focal points (NFPs) and experts from their national EWS networks; I the Europol national units (ENUs) and Europol Project Synergy; I the national competent authorities responsible for human and veterinary medicinal products in the Member States, Norway and Iceland; I the European Medicines Agency (EMA) and the European Commission; I the World Health Organization; I EMCDDA staff: Brendan Hughes, Isabelle Giraudon, Athanasios Stamos, Marta Rychert and Katarzyna Natoniewska.
Project team: Andrew Cunningham, Michael Evans-Brown, Ana Gallegos, Roumen Sedefov, Anabela Almeida (EMCDDA) and Daniel Dudek (Europol).
I 1. Introduction
Europol asked the Europol National Units to provide information on: Article 5.1 of Council Decision 2005/387/JHA (1) (hereinafter referred to as the ‘Decision') stipulates that ‘Where Europol n the level of production of MDPV in their country; and the EMCDDA, or the Council, acting by a majority of its n the level of distribution of MDPV in their country; members, consider that the information provided by the n the level of trafficking of MDPV in their country, both for Member State on a new psychoactive substance merits the internal, transit or export purposes; collection of further information, this information shall be n the number of seizures of MDPV in their country, the total collated and presented by Europol and the EMCDDA in the amount of the seizures, country of origin, details on the form of a Joint Report (hereinafter the "Joint Report").' The physical forms (including photos); Joint Report shall be submitted to the Council, the European n the role of organised crime, or criminal groups, in the Medicines Agency (EMA) and the Commission.
production, distribution and trafficking of MDPV in their country; and, At the end of September 2013, the European Monitoring n any known aspect of violence and/or money laundering Centre for Drugs and Drug Addiction (EMCDDA) and Europol relating to the production and trafficking of MDPV.
examined the available information on a new psychoactive substance 3,4-methylenedioxypyrovalerone, commonly known Europol received responses from 15 Member States.
by the abbreviation ‘MDPV', through a joint assessment based upon the following criteria: According to Article 5.3 of the Decision, the EMA asked the national competent authorities responsible for human and 1. the amount of the material seized; veterinary medicinal products in the Member States as well as 2. evidence of organised crime involvement; in Norway and Iceland to provide information on whether: 3. evidence of international trafficking;4. analogy with better-studied compounds; n the new psychoactive substance MDPV has obtained a 5. evidence of the potential for further (rapid) spread; and, marketing authorisation; 6. evidence of cases of serious intoxication or fatalities.
n the new psychoactive substance MDPV is the subject of an application for a marketing authorisation; and, The EMCDDA and Europol agreed that the information n a marketing authorisation that had been granted in respect collected on MDPV satisfied criteria 1, 2, 3, 4 and 6. The two of the new psychoactive substance MDPV has been organisations therefore concluded that sufficient information had been accumulated to merit the production of a Joint Report on MDPV as stipulated by Article 5.1 of the Decision.
Twenty-five Member States (2), Norway and Iceland replied to the EMA's request. The EMA also provided information as relevant to the central authorisation procedure.
Furthermore, in anticipation of Article 7.3 of the Decision in I 2. Information collection process
relation to the manufacturing of medicinal products in the European Union, the EMA also requested whether the new In compliance with the provisions of the Decision, on 7 psychoactive substance MDPV is used to manufacture a October 2013 the EMCDDA and Europol launched a medicinal product: procedure for the collection of information on MDPV, in order to prepare the Joint Report. The information was collected n which has been granted a marketing authorisation; mainly through the Reitox National Focal Points in the Member n for which an application has been made for a marketing States, Turkey and Norway as well as the Europol National authorisation; and, Units. In addition, the EMA collected information through the n for which a marketing authorisation has been suspended national competent authorities responsible for human and by a competent authority.
veterinary medicinal products in the Member States as well as in Norway and Iceland. The information collection process was largely concluded by 18 November 2013; additional information and clarifications from some countries were received up to four weeks after this date.
(2) Austria, Belgium, Croatia, Cyprus, the Czech Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Malta, the Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden (1) OJ L 127, 20.5.2005, p. 32.
and the United Kingdom.
JOINT REPORTS I MDPV Twenty-four Member States (3), Norway and Iceland replied to the EMA's request. The EMA also provided information as I 3.1. Chemical and physical description, including the
names under which the new psychoactive relevant to the central authorisation procedure.
substance is known — Article 5.2(a) of the Decision The EMCDDA collected data through: Chemical description and names 1. a structured questionnaire from the Reitox national focal points. The EMCDDA received replies from 28 Member MDPV is a synthetic derivative of the naturally occurring States as well as Norway and Turkey; substance cathinone, one of the psychoactive principles in 2. data previously provided to the EU early-warning system khat (Catha edulis Forsk). All monitored synthetic cathinone (EWS) in EMCDDA–Europol Reporting Forms, EWS derivatives are either N-alkylated or the nitrogen atom is part Progress and Final Reports; of a pyrrolidine ring, which is the case with MDPV. Most of the 3. a specific information request to the World Health cathinone derivatives are also ring-substituted and MDPV Organization on whether or not MDPV is under assessment contains the 3,4-methylenedioxy substitution pattern on the by the United Nations system (see section 3.5); and, phenyl ring that is observed in other illicit drugs such as 4. a structured search of the scientific literature and of relevant Internet sites.
Pyrrolidine derivatives, such as MDPV, can be regarded as a Thus, information included in sections 3.2.1 and 3.3 of the subset of cathinone derivatives sharing the same structural Joint Report was provided by Europol, while the EMCDDA skeleton as pyrovalerone (Figure 1). Other examples in this provided information included in sections 3.1, 3.2.2, 3.4, 3.5, group are 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP) and 3.6, 3.7, 3.8.1, 3.8.2 and 3.8.3 (in part). The information included in sections 3.8.3 (in part), 4.1, 4.2 and 4.3 was provided by the EMA. The conclusion of the Joint Report were MDPV is the common name for prepared and agreed by the two organisations responsible — 3,4-methylanedioxypyrovalerone. The systematic chemical the EMCDDA and Europol. Further details of the seizures and collected samples (including images where available) reported to the EMCDDA are provided in Annex 1. The details of deaths associated with MDPV that have been reported to the Additional chemical synonyms reported are: EMCDDA are provided in Annex 2.
I 3. Information required by Article 5.2 of 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-yl)pentan-1-one;
The order and titles of subsections 3.1 to 3.8 and section 4 below are as they appear in Article 5.2(a) to (h) and Article 5.3(a) to (c) of the Decision; all sections are cross-referenced with those set down in the Decision.
Common names or codenames that have also been reported are: MDPK and metyleenidioksipyrovaleroni (Finnish).
The following street names have also been reported: MDPK, Magic, Super Coke, Peevee, New Ivory Wave, Kannibaldrogen, Apdamm, Aakkoset (meaning alphabet in Finnish), Bath Salt, MP, MP4 and MP3.
(3) Austria, Belgium, Croatia, Cyprus, the Czech Republic, Denmark, Estonia, Finally, the following ‘legal high' product names have been Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Malta, the associated with MDPV: ‘Mojo', ‘Yellow Submarine', ‘Ivory Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and the United Kingdom.
Wave', ‘Vanilla Sky', ‘NRG-3', ‘Flower Magic', ‘Gumi Cucoriedka', JOINT REPORTS I MDPV FIGURE 1The molecular structure, weight and monoisotopic mass of MDPV. The molecular structure for pyrovalerone is provided for comparison (* denotes the chiral centre).
Molecular formula: C H NO Molecular weight: 275.3429Monoisotopic mass: 275.152 ‘Kamikadze', ‘Xtacy', ‘Ivory Wave', ‘Extreme Star Dust', Reports from seizures and collected samples have noted the ‘Hurricane Charlie', ‘Dogs Bollix', ‘Doves Red', ‘Doves Ultra', presence of MDPV in: powders, powder-filled capsules, ‘Sextasy', ‘Orange Orbits', ‘Stardust', ‘Blow', ‘Recharge', tablets, blotters (small paper doses for sublingual/buccal ‘Charge+', ‘Lucky', ‘Generation 2012', ‘EL PADRINO' administration), liquids and vegetable material, and in residues (translation: the Godfather), ‘Coco Jumbo', ‘Cherry Coco on injecting equipment.
Jumbo', ‘SUNRISE', ‘TECHNO', ‘Greenway Speedway', ‘DANA', ‘OLGA', ‘LENA', ‘EVA', ‘CLARA', ‘MARKETA' and ‘JANA'.
A more detailed description of MDPV seizures and collected samples encountered can be found in subsections 3.2.1 and Chemical Abstract Service registry numbers (CAS RN) 3.2.2 below.
hydrochloride salt I 3.2. Information on the frequency, circumstances
and/or quantities in which a new psychoactive substance is encountered, and information on R-enantiomer base the means and methods of manufacture of the new psychoactive substance — Article 5.2(b) of S-enantiomer base deuterated (D ) base 3.2.1. Information provided to Europol 1246820-09-6 deuterated (D ) hydrochloride salt Europol received replies from 15 Member States (Belgium, The REACH registered substances database hosted by the Bulgaria, Croatia, Cyprus, Denmark, Estonia, Finland, Hungary, European Chemicals Agency (ECHA) was searched using the Italy, Latvia, Lithuania, Luxembourg, Poland, Slovakia and CAS registry numbers listed above. The search returned no Slovenia). Of these, four countries had no data relating to MDPV (Cyprus, Latvia, Luxembourg and Slovenia). The remaining 11 countries (Belgium, Bulgaria, Croatia, Estonia, Finland, Germany, Hungary, Italy, Lithuania, Poland and Slovakia) reported the following information.
The free base form of MDPV has been described as a brown or yellow-green amorphous powder. The hydrochloride salt form The level of production, distribution and trafficking is described as a white-tan crystalline hygroscopic powder with a melting point of 238–239oC.
Belgium reported that in 2013 there were eight cases in total, where MDPV was sent from China and entered Belgium en JOINT REPORTS I MDPV route to third countries. The final destinations in these cases 2011 and March 2013. It focused on the distribution of new were: Italy (three cases), the Netherlands (three) and the psychoactive substances sold via the Internet as so-called United Kingdom (two). The seized MDPV destined for Italy ‘legal high' products. During house searches made in March ranged from 18 g to 510 g. On two occasions the substance 2013, a total of 5 524 products containing new psychoactive was labelled as ‘ULTRAVIOLET AB' (18 g and 510 g) and as substances (NPS) were seized. Moreover, during further mail ‘LITHOPHONE' (100 g) on the other occasion. The MDPV confiscation another 3 999 NPS products were seized. Among ordered by consumers in the Netherlands was labelled as these, the following products contained MDPV: ‘SODIUM ALGINATE', with the following quantities seized: 1 516 g, 1 521 g and 2 022 g. In one of the two cases when 10 packages (1 g each) of the ‘bath salt' labelled MDPV was destined for the United Kingdom market (which ‘Charlie Sheen'; weighed 260 g in each case), the seized substance was labelled as ‘HETASTARCH'.
11 packages (1 g each) of the ‘bath salt' labelled ‘Mojo'; Bulgaria reported that customs authorities had reported 12 20 capsules (0.5 g each).
seizures of MDPV between July 2010 and March 2012. All seizures took place at Sofia Airport, and the substance had Further analysis revealed that more than 4 000 customers been sent to Bulgaria (in the majority of cases) from China, from Germany and other countries had used this now- Spain, Portugal, the United Kingdom or the Netherlands. One disrupted network. The NPS products were ordered by case was reported that involved almost 5 000 small packages wholesalers in Belgium, the Netherlands, the Czech Republic, of MDPV being sent to Poland via Hungary. In these 12 Portugal and Belize.
seizures, 5 267 g and 300 tablets of MDPV were seized. In some cases MDPV powder was mixed with caffeine and The second German investigation involved online vendors who lidocaine. MDPV tablets were pink in colour, with an elliptic were involved in supplying MDPV and methoxetamine. In the shape and were packed in small packages (containing two framework of this investigation, 30 kg of different NPS tablets each) bearing the label: ‘DOVES RED'. MDPV in products were seized. Amongst others, the following seizures powder form was identified in small packages bearing of MDPV were identified: different labels, for example, ‘IVORY WAVE', ‘MOJO', ‘FLOWER MAGIC POWDER' and ‘LOAD'.
4 packages (1 g each) of the ‘bath salt' labelled ‘highway'; The Bulgarian authorities also reported that the Research Institute of Forensic Sciences and Criminology of the Ministry 6.29 g of a white powder labelled ‘4-FMP'; of the Interior has recorded 19 cases related to MDPV seizures. In some of these cases MDPV was destined for 13.58 g of a white powder labelled ‘MDPV'; ‘smart shops' located in nearby resorts on the Black Sea.
0.94 g of a white powder labelled ‘ECKO', mixed with Croatia reported that MDPV was detected in 10 cases (14 g in a total of 90 g of a white powder with various labelling: Estonia reported one seizure of MDPV (1.68 g), made by ‘MDPV', ‘methylone', ‘4-FA', with a purity of 73 %; customs authorities in incoming mail from the United Kingdom. In this case, MDPV was mixed with alpha-PVP and a total of 2.568 g of a white powder with various labelling: ‘MDMAI', ‘MPPP', ‘Dimethocaine', ‘Alpha PPP', with a purity of 81 %; Finland reported that the number of seizures of MDPV had been higher a few years ago. Since the substance was 1.431 g of a white and beige powder with various classified as a controlled substance, the number had declined. labelling: ‘Synthacain', ‘Charge+', ‘Dimethocaine', According to data provided by Finland, there were eight ‘R-MMC', ‘Dichloropan', and without labelling; with a incidents where MDPV was seized in powder form (63.5 g in total). There is also information that MDPV was identified in 11 blood samples (no further details were provided to Europol).
1 g of a white powder labelled ‘Alpha-PPP'; The German report to Europol mentioned two significant 14 g of a white powder labelled ‘Alpha-PVP'; investigations during which seizures of MDPV were recorded. The first investigation was conducted between September 30 g of a brown powder; JOINT REPORTS I MDPV 61 packages of the so-called ‘legal high' product to 9 579 g in 2010 and to 5 730 g in 2012. It has been noted named ‘Brutal Powder', mixed with caffeine and that in 2013 the seizures of MDPV (both tablets and in powder form) fell significantly.
10 grams of a white powder labelled ‘Dichloropan'; Italy reported a limited number of seizures of MDPV. Three seizures of MDPV (in total 307.6 g) were made in the 28 g of a white powder labelled ‘Dimethocaine'; provinces of Roma, Milano and Taranto (September–October 2013). Italian citizens were reported to be involved in these 24 g of green tablets, also containing caffeine; 78 g of green tablets ‘Benzo F', also containing caffeine; Lithuania reported four seizures of MDPV made in 2012, totalling 1.326 g.
6 g of a white powder labelled ‘Synthacain'; In Poland, MDPV was seized as powder in quantities ranging 20 packages of the ‘bath salt' named ‘Tony Montana' (4) from 0.11 g to 525 g. The largest seizure, in April 2013, when also containing caffeine and lidocaine.
the substance was sent from China (ordered via www.
sensearomatic.com) to Poland by shipping company FedEx.
Data provided by Germany concerning MDPV seizures were recorded from February 2011 and November 2013. There has Slovakia reported 24 cases where MDPV was seized as a been a huge number of seizures where MDPV was detected. powder (various colours). In a significant majority of cases, the Bearing in mind the number of seizures and level of substance was seized in small packages labelled with various distribution it can be concluded that the market for MDPV has names: ‘Long Play' (eight cases); ‘Beep Beep' (eight); ‘Speed been growing in recent years. German authorities assume that Way' (one); ‘Popeyes Sniff' (one) and ‘LP' (one). In almost all a high number of cases in relation to MDPV are unreported. In cases, MDPV was identified in a mixture with other new the majority of cases MDPV was identified in so-called ‘legal psychoactive substances, such as: 2-DPMP (5) and high' products, with different labelling: ‘Mojo', ‘Mitseez', ‘Buzz buphedrone (the majority), MABP, bk-MDMA and Powder', ‘Sweed', ‘Ivory Wave', ‘J White Powder Cleaner', ethcathinone. Seizures of MDPV weighed between 0.218 g ‘Wakup', ‘Yellow Submarine', ‘XXX', ‘Buty', ‘Lionheart', ‘Rush and 53.315 g.
Hour', ‘Let's Play Crack Inside', ‘Charlie Sheen', ‘All Day, All Night – What the fuck', ‘Highway', ‘ECKO', ‘Brutal Powder', The Slovakian Financial Administration reported a case ‘Sextacy', ‘Insomnia' and ‘Ultra Charge'.
focused on a ‘smart shop' (Euphoria Shop Ltd) that distributed goods called ‘Aromatic herbs and imitations of spa salts'. The In most of these cases, MDPV was identified as main active Forensic Institute revealed that the products contained MDPV. ingredient mixed with other new psychoactive substances The goods were distributed via branches in six cities in and/or adulterants such as: 4-MEC, flephedrone, butylone, Slovakia. In June 2012, during searches made in these MDPBP, TFMPP, 3-FMC, MXE, 2C-E, para-fluoramphetamine, branches and in the house of a suspect, a total amount of AM-2201, pentedrone and/or lidocaine, caffeine, starch, 19 562 packages containing MDPV were seized. In addition, taurine, mannitol and benzocaine.
five plastic bags with crystalline white powder (20 g, 80 g, 300 g, 800 g, 1 kg) and EUR 6 191 in cash were seized.
The seizures of MDPV ranged from 0.02 g (March 2012) to 1 kg (January 2013, made up of 2 x 500 g).
Slovakia also reported a seizure of 10 kg of MDPV powder by customs officers of the Airport Financial Administration (no In Hungary the increase in availability, use and distribution of other details provided).
MDPV led the Ministry of Justice to propose an amendment to the Act on Drugs that then placed MDPV as a Class A drug. According to Slovakian authorities, imports are ordered via the The Hungarian Europol Liaison Officer reported that MDPV Internet and then delivered from China to Slovakia by mail was seized in tablet and powder form in 2009 and 2010 order (DHL, TNT, FedEx, etc.).
respectively. Seizures of MDPV tablets increased from 551 tablets in 2009 (six cases) to 8 522 tablets in 2012 (nine No reports were received that indicated licit or illicit cases). Seizures of powder have increased from 133 g in 2010 production of MDPV in any of these countries.
(4) Tony Montana is the name of Al Pacino's character in the 1983 film Scarface, directed by Brian de Palma, which tells the story of a Cuban refugee who becomes a drug kingpin in the cocaine trade in Miami, USA.
JOINT REPORTS I MDPV 3.2.2. Information provided to the EMCDDA Several of these products carry names that are associated with or similar to street names used for cocaine, amphetamine According to reports to the EMCDDA, MDPV has been present or ‘ecstasy' (MDMA). Other substances found along with on the EU drugs market since 2008 and subsequently a large MDPV in the same preparation include a wide range of new volume of data has been collected during this period, of which psychoactive substances (predominantly cathinones, but also a summary is presented below.
phenethylamines, piperazines, synthetic cannabinoid receptor agonists and a range of other substances), adulterants such Twenty-seven Member States (all Member States with the as benzocaine, lidocaine and caffeine, and in a smaller exception of Luxembourg), Norway and Turkey reported number of cases with substances that are internationally detections of MDPV (6).
controlled or controlled at the EU level.
Where information has been provided, quantities of powder for single seizures ranged from 0.02 g (Germany and Poland) Twenty-seven Member States (all Member States with the to 5 kg (Czech Republic). Hungary reported a seizure of 300 exception of Luxembourg), Norway and Turkey reported yellow tablets bearing a heart logo and a separate seizure of seizures (7) of MDPV to the EMCDDA. In excess of 5 500 two white tablets bearing markings resembling the Louis seizures have been reported, with two countries reporting Vuitton ‘LV' logo (8). Norway reported a seizure of 98 purple more than 1 000 seizures each: the United Kingdom (1 704) tablets bearing a space ship/rocket logo. These tablet findings and Finland (1 340). A further four countries reported more may suggest that MDPV is being sold as 'ecstasy'. There were than 100 seizures: Hungary (599), Poland (401), Ireland (242) also unmarked tablets reported in a variety of colours, and Spain (176).
including white, grey, pink, reddish and green, although many of these were associated with ‘legal high' products. A MDPV has typically been seized in powder form (reported by selection of images is provided in Annex 1.
all countries where MDPV was detected). Some countries also reported seizures of tablets or powder-filled capsules (Finland, More than 4 500 individual cases of MDPV powder have been France, Germany, Hungary, Italy, Lithuania, the Netherlands, reported, amounting to an excess of 200 kg of seized MDPV. Norway, Poland, Portugal, Romania, Spain, Sweden and the The vast majority of these are small cases; however, 45 of United Kingdom). Six countries (Denmark, Finland, France, them (reported by the Czech Republic, Finland, France, Latvia, Sweden and the United Kingdom) have seized liquids Hungary, Latvia, the Netherlands, Spain and Sweden) were in containing MDPV. Finland and Poland each reported a single excess of 500 g, accounting for more than approximately seizure of paper doses (also known as a ‘blotters'), i.e. small one-third of the total weight of powder seized. In 2011, for pieces of paper impregnated with MDPV for sublingual/buccal example, customs authorities in Hungary made seven administration. The Polish blotters (four in total) had an image separate seizures of MDPV powder amounting to of Bugs Bunny on them and also contained 2-DPMP, approximately 14.5 kg. Belgium, the Czech Republic, Germany ethylphenidate and the nootropic substance piracetam. and Lithuania provided information that MDPV seized by Hungary also reported two cases where MDPV was present as customs authorities had been sent from China. No other ‘powder on herb' and Poland reported a seizure of a ‘legal non-EU countries were identified in the reports, although two high' product labelled as ‘Greenway Speedway', which Member States reported the interception of packages sent contained vegetable material with MDPV present. Indeed, from another Member State. Several countries reported MDPV MDPV has often been found as an ingredient in so-called in powders contained in ‘legal high' products with names such ‘legal high' products, often in combination with other as ‘Charlie Sheen', ‘Synthacaine' or ‘Speedway Pro' (a full list substances. Several countries have described these as ‘bath of names is provided in Section 3.1 above).
salts', a term frequently used to describe ‘legal high' products. There were over 500 cases involving MDPV tablets or (6) ‘Detections' is an all-encompassing term and may include seizures and/or capsules, containing approximately 30 000 tablets in total. collected and/or biological samples. Seizure means a substance available Several countries reported tablets containing MDPV in (seized) through law enforcement activities (police, customs, border guards, etc.). Collected samples are those that are actively collected by drug branded ‘legal high' products with names such as ‘Yellow monitoring systems (such as test purchases) for monitoring and research Submarine', ‘Doves Red' and ‘Mind Candy' (a full list of names purposes. Biological samples are those collected from human body fluids (urine, blood, etc.) and/or specimens (tissues, hair, etc.).
is provided in Section 3.1 above).
(7) Many ‘seizures' relate to individual case-level data. However, some data provided to the EMCDDA are aggregated at the country level. Some of the data from the United Kingdom are reported as ‘records', where several records may come from the same case. Data is drawn from the Joint Report questionnaires and data provided in the bi-annual data gathering (EWS (8) It is common to find markings on tablets sold as ‘ecstasy' that copy those of Progress and Final Reports) and from individual Reporting Forms submitted popular cultural and iconic brands that are associated with quality. Louis on an ad hoc basis.
Vuitton is a French fashion label.
JOINT REPORTS I MDPV sample), cocaine (three), synthetic cocaine (two), ‘moji' (one), 6-APB (10) (two), 5-APB (11) (one) and ‘meferon' (two).
Eleven countries reported detections of MDPV in biological samples, including: Poland reported 887 cases of branded products containing up to 500 mg of MDPV, mostly in powder form, as well as in n a total of 99 deaths: Finland (40 deaths), United Kingdom tablets and capsules. Other substances detected in these (32), Sweden (21), Poland (three), Austria (one), France samples were: other synthetic cathinones (naphyrone, (one) and Norway (one) – see section 3.4.1 and Annex 2 for methedrone, buphedrone, pentedrone methylone, 4-MEC, FMC, MDPBP, butylone, BMDP), phenethylamines (pFPP, n 107 analytically confirmed non-fatal intoxications: Sweden fluoroamphetamine, 2C-E), synthetic cannabinoids (RCS-4, (99 cases), France (three), Italy (three) and Belgium (two); JWH-122, JWH-081), TFMPP, 5-HTP, creatine, lidocaine and n detections related to cases of suspicion of driving under the influence of drugs (Finland: 514 in the period 2009–13; Poland: one); driving under the influence of drugs and other Slovakia reported a total of 304 collected samples; some of crimes (Norway: nine; United Kingdom: one); drug testing them were offered through online shops (i.e. www.
(Poland: one); and unspecified detections in biological euphoriashop.sk, www.hypnotic.sk) under a variety of names samples (Sweden: 842; Hungary: 387; United Kingdom: six; including ‘Beep Beep', ‘Long Play', ‘Popeyes Sniff', ‘Speed Norway: six).
Way', etc. Other substances often detected in the samples include the synthetic cathinones buphedrone, Collected samples N-ethylcathinone and methylone, 2-DPMP and piracetam.
In addition to the detections of MDPV in seizures and A small number of collected samples were reported by biological samples, ten Member States (Austria, Cyprus, Cyprus, Denmark, Italy and the United Kingdom. In 2010 Denmark, France, Ireland, Italy, the Netherlands, Poland, Cyprus reported MDPV in two samples of a product of 500 mg Slovakia and the United Kingdom) also reported collected labelled ‘Ivory Wave'. Denmark reported three samples of powder in 2013. Italy reported a sample of 0.5 g of white powder purchased from the Internet and labelled ‘Ivory Wave'. In Austria 32 samples of powder were collected and analysed On the label on the back of the package, ingredients listed as part of the ‘pill'-testing project run by ‘ChEckiT!' between were ‘water softening agents, Epsom salts, sodium 2010 and 2013. The samples were sold as mephedrone, bicarbonate, sodium chloride, amino acid blends, and naturally cocaine, MDPV and speed. In two cases, amphetamine and occurring trace elements and minerals'. No other substances caffeine or bk-MBDB (9) were also detected.
in addition to MDPV were detected. The United Kingdom reported a sample of 33 g of MDPV powder purchased from France reported nine samples of powder collected from an Internet retailer (www.chembay.co.uk) in December 2008.
different venues. Where quantitative information is available, the weight ranged from 0.1 g to 0.5 g. In two of the samples, Further details of these collected samples, including alpha-PVP and pentedrone were also detected; in the other information on the product labels, are provided in Annex 1.
sample alpha-PVP and caffeine were detected. In one of the cases the sample was sold as cocaine.
In Ireland MDPV was identified in products collected from I 3.3. Information on the involvement of organised
crime in the manufacture or trafficking of the head shops, branded ‘Hurricane Charlie', ‘Dogs Bollix', ‘Doves new psychoactive substance — Article 5.2(c) of Red', ‘Doves Ultra', ‘Ivory Wave', ‘Sextasy', ‘Orange Orbits' and According to German authorities there are no links to suggest In the Netherlands, the Drugs Information and Monitoring the involvement of organised crime groups in the production, System (DIMS) detected MDPV in 27 samples (11 in 2010; trafficking and/or distribution of MDPV. It should be borne in nine in 2012; seven in 2013). Where information is provided, mind that easy access to substances (which can be in large the samples were sold at consumer level as MDPV (one amounts) within and outside the European Union via Internet shops indicates at least a certain level of organisation. In addition, organised crime groups' interest and presence in the (9) 2-Methylamino-1-(3,4-methylenedioxyphenyl)butan-1-one, also known as JOINT REPORTS I MDPV phenomenon of new psychoactive substances can be easily pyrovalerone and cannabis were also detected in this case. In concluded from the substantial profits that can be obtained the second case, which was a ‘forced hospitalisation', from this type of activity.
paranoid psychosis and aggression were noted. The symptoms reported were tachycardia, mydriasis, Money laundering aspects hypertension, agitation, profuse sweating, trembling, scarification and rhabdomyolysis. In this case, the route of No information was received on money laundering in administration was nasal and oral and the MDPV had been connection with the production and/or trafficking of MDPV.
bought on the Internet. Methylone (4 400 ng/mL) was also detected in this case. In the third case, where the detection of Violence in connection with production, wholesale and MDPV was in a sample of hair, the patient had also bought MDPV via the Internet and the route of administration was nasal. Symptoms reported were mydriasis and paranoid No information was received on incidents of violence in psychosis. Cannabis and alcohol were also detected in this connection with the production, wholesale and/or trafficking I 3.4. A first indication of the risks associated with the Italy reported three analytically confirmed non-fatal
new psychoactive substance, including the intoxications. The first case was from August 2011 when a health and social risks, and of the characteristics 20-year-old male was admitted to hospital very agitated with of users — Article 5.2(d) of the Decision tachycardia (HR (12) 115 bpm). He reported having consumed cannabis, alcohol and three white capsules. MDPV was found in urine (14 mg/L) and butylone was also present 3.4.1. First indication of health risks (concentration not provided). The patient was treated with benzodiazepines and discharged two days later. The second Up to 107 non-fatal intoxications and 99 deaths, analytically case was from October 2012 and involved a 38-year-old male confirmed to be associated with MDPV, were reported by who presented at the emergency department with agitation, Austria, Belgium, Finland, France, Italy, Poland, Sweden, the mild tachycardia (HR 105 bpm), distress and psychotic United Kingdom and Norway. Germany, Greece, Hungary, symptoms. He also reported visual and auditory Ireland and Slovakia have also reported cases, which have not hallucinations. He reported that he had taken ecstasy and been described below due to their non-confirmed status.
synthetic drugs generally named as ‘mefre, crystal and energy' by nasal insufflation. MDPV was detected in blood (12 mg/L) and urine (17 mg/L). Urine screening was negative for Non-fatal intoxications ketamine, atropine, scopolamine, levamisole, mephedrone, butylone, 4-MEC, methoxetamine, APB (13) (isomers), 4-FA (14), and MDAI (15). The third case also occurred in October 2012 and involved a 27-year-old male who presented Belgium reported two analytically confirmed, linked non-fatal at the emergency department. His father had found him in a intoxications in which the patients presented were stimulated, state of agitation, confusion and anxiety. The patient reported hypertensive and tachycardic. Traces of cocaine and having taken MDPV by intravenous injection for the last three amphetamines were also detected in urine samples (not to four days, together with benzodiazepines to counteract the quantified). They both reported visual and auditory excitatory effect of MDPV. The MDPV had been purchased hallucinations, severe psychosis and paranoia, and were from the Internet as a ‘bath salt'. Analysis of the patient's urine aggressive. They were treated with antipsychotics and their revealed MDPV (55 µg/L), alprazolam (113.79 µg/L) and status returned to normal after three to four days.
hydroxyalprazolam (103.59 µg/L). Three days after admission, the patient returned to the hospital for a second urine analyses, as requested by sanitary authorities. The patient reported continuing his use of MDPV and this was confirmed France reported three analytically confirmed non-fatal by the detection of MDPV in urine at a concentration of intoxication cases. In one case, the police brought a man in to 35 µg/L. The analyses also found chlordiazepoxide the emergency department. In this case, delirium syndrome was reported, including hallucinations, as well as (12) Heart rate.
rhabdomyolysis, tachycardia, hypotension, agitation, logorrhoea and acute renal failure. The MDPV metabolite, JOINT REPORTS I MDPV (13.03 µg/L), nordiazepam (61.55 µg/L), oxazepam (114.99 µg/L), diazepam (1.26 µg/L), temazepam (169.90 µg/L), alprazolam (10.43 µg/L) and alpha- Finland reported 40 deaths, which occurred between September 2009 and August 2013. The cases were all analytically confirmed, and where the concentration of MDPV was reported (20 cases) it ranged from 20 mg/mL to 4 800 mg/mL in blood; in all but one case, up to seven other Sweden reported 459 non-fatal intoxications between 2007 substances were detected. In 14 cases, five or more and 2013 as follows: 2007 (one case), 2008 (four), 2009 (15), substances were detected in addition to MDPV. The most 2010 (47), 2011 (32), 2012 (194) and 2013 (166). Of these, frequently encountered other substances detected were between 86 and 99 cases are known to have been analytically diazepam (22 cases), amphetamine (14), buprenorphine (14), confirmed (16). Two literature sources that describe a total of temazepam (nine), alprazolam (eight), ethanol (seven), 99 non-fatal intoxications have been used for the purposes of morphine (three) and pregabalin (three). Causes of death describing the health risks. In the first report (Lindeman et al., reported were accidental poisoning (22 cases), suicidal 2013), cases of stimulant toxicity were studied from one poisoning (four), suicide resulting from crush injuries (two), hospital in Sweden covering April–May for three consecutive suicide by hanging (two), suicide by carbon monoxide years (2010 to 2012). In April–May 2012 the number of poisoning (one), unspecified intoxication (one), unspecified patients with stimulant toxicity was 45, and 17 of these cases death and cirrhosis of liver (one), accidental injury to thoracic were examined toxicologically. Thirteen of these tested aorta (one), accidental death due to multiple rib fractures positive for MDPV and 12 were classified as chronic drug (one), infective myocarditis disease (one) and homicide (one). users, with >60 % noted to be hepatitis C virus (HCV) positive. The cause of death had not yet been registered in three cases.
The second study (Bäckberg et al., 2013) focused on the results of the STRIDA project, which monitors trends in acute poisonings with novel recreational drugs in Sweden. The study summarises the results for the first nine months in 2012 when France reported one death, which occurred in October 2012. MDPV was detected in 86 of 321 samples. In 17 cases the The cause of death was drowning. MDPV was present at a symptoms were severe (Poisoning Severity Score — PSS 3 concentration of 106 µg/L (blood) and 760 µg/L (urine). Other (Persson et al, 1998)) and consisted of extreme agitation, drugs detected were: PVP (18) (blood 40 µg/L; urine psychosis, hyperthermia, tachycardia, hypertension, 295 µg/L); pentedrone (blood 33 µg/L; urine 110 µg/L); myocardial infarction, rhabdomyolysis and renal failure. A few hydroxyzine (blood 194 µg/L); nordiazepam (blood 47 µg/L); patients needed therapy with sedatives for several days due oxazepam (blood 8 µg/L); cannabinoic acid (blood 15.7 µg/L); to prolonged symptoms. It was noted by the authors that and ethanol (blood 0.3 g/L). No further details were provided.
among the people that have come to medical attention, the incidence of severe poisonings (PSS 3) was highest for MDPV.
Poland reported three deaths associated with MDPV. The first death was in September 2010 and the reported cause of death was ‘metabolic dysfunction' caused by MDPV. The There were 99 deaths associated with MDPV that were concentration of MDPV determined in blood was 430 ng/mL analytically confirmed. These were reported by Austria (one), and ephedrine was also detected at a concentration of Finland (40), France (one), Poland (three), Sweden (21), the 324 ng/mL. No further details were available. The second and United Kingdom (32) and Norway (one) (17).
third cases were reported from 2011. The second case involved a road traffic collision where one driver suffered severe injuries, resulting in his death. During the police investigation, packages of white powders, called ‘Ivory Speed' Austria reported one death, which occurred in January 2012. and ‘Exclusive Dust', were found (Adamowicz et al., 2013). The case involved a ‘young man' who died from butylone MDPV was detected in blood at a concentration of 38 ng/mL, (bk-MBDB) overdose in combination with MDPV, methylone and buphedrone was also detected at a concentration of and 4-MEC. No further details were provided.
127 ng/mL. The third case involved a man with a history of drug addiction who was found unresponsive after a night of partying. A witness reported that he had taken a product 16) There is a potential that there may be an overlap of some cases reported by Lindeman et al., 2013 and the cases reported by Bäckberg et al., 2013 called ‘Speedway' while at the party. The post-mortem (17) Hungary reported two indirect deaths, which occurred in November 2011. No further details were provided and it is not known if these cases are analytically confirmed.
(18) Pyrrolidinovalerophenone. JOINT REPORTS I MDPV examination showed emaciation, external hydrocephalus and Pharmacology and mode of action atherosclerosis. The man also suffered from human immunodeficiency virus (HIV) infection (Adamowicz et al., Work by Baumann et al. (2013a) provides a systematic 2013). MDPV was detected in blood at a concentration of evaluation of the pharmacology and mode of action of MDPV 17 ng/mL, and clonazepam (1.2 ng/mL) and using in vitro and in vivo studies in rodents (20). In vitro data 7-aminoclonazepam (96 ng/mL) were also detected.
shows that MDPV acts as a potent catecholamine-selective (dopamine and noradrenaline) transporter blocker (Table 1), sharing some similarities with the structurally related compound pyrovalerone. Compared to cocaine, MDPV is Sweden reported 21 deaths: three in 2010, three in 2011, nine 50-fold more potent at DAT (dopamine transporter), 10-fold in 2012 and six in 2013. Brief comments were reported as more potent at NET (norepinephrine transporter), and 10-fold follows: in 2010 the deaths were intoxications involving less potent at SERT (serotonin transporter) (Baumann et al., several substances (not further described); in 2011 none of 2013a). In addition, the data also showed that MDPV does not the three deaths related only to MDPV; in 2012 there were act as a transporter substrate. Consistent with the in vitro several accidents, death by hanging and intoxications with data, in vivo microdialysis studies in rats found that MPDV several drugs (not further described); and in 2013 there was increased extracellular concentrations of dopamine in the one car accident and intoxications with several drugs (not nucleus accumbens and was 10-fold more potent than further described).
cocaine; while in vivo locomotor activity testing (stereotypy and forward locomotion) and assessment of cardiovascular United Kingdom parameters (heart rate and blood pressure) found that MPDV is at least 10-fold more potent than cocaine in inducing The United Kingdom reported 32 deaths between January locomotor activation, tachycardia and hypertension. The 2010 and an unspecified date in 2013 (11 in 2010; eight in authors concluded that the ‘potent blockade of dopamine 2011; 12 in 2012; one in 2013).
uptake caused by MDPV predicts that the drug has a high risk for abuse, whereas the potent blockade of norepinephrine Where reported, the causes of death were noted to be hanging uptake portends dangerous cardiovascular stimulation' (seven cases), cardiac-related causes (19) (five), drug toxicity (Baumann et al., 2013a).
(four), drowning (two), carbon monoxide poisoning (two), asphyxia (one), multiple injuries (suicide) (two), hypovolemic Simmler et al. (2013), using a human in vitro model, assessed shock due to laceration of left forearm associated with partial the blood–brain permeability of MDPV. They reported that transection of cephalic vein (one). In the remaining cases the MDPV exhibited particularly high blood–brain barrier cause was either unascertained or not specified. In the cases permeability as compared to other synthetic cathinones (with of drug toxicity, MDPV was normally present with other drugs. the exception of mephedrone) as well as reference Where reported, the most common other substances present compounds such as MDMA and amphetamine. In addition, were mephedrone (nine cases), 4-fluoromethcathinone they reported that the data for MDPV was consistent with (seven), cocaine (four), amphetamine (four) and MDMA active transport across the blood–brain barrier. The authors (three), although a range of other controlled drugs and concluded that the potency of MDPV at the DAT and NET and medicines were also detected. MDPV was not the sole cause high blood–brain barrier permeability could ‘result in high noted in any of the cases, and was specifically implicated as a sympathomimetic toxicity and risk of addiction in humans'.
contributory factor in nine of the cases.
No studies were identified that have examined the pharmacology and mode of action of MDPV in humans.
Norway reported one death in 2012 in which MDPV was Meyer et al. (2010) and Strano-Rossi et al. (2010) provide data detected during the toxicological examination of blood. The on the possible metabolites and metabolic pathways for cause of death in this case was not reported and no further MDPV in vitro using rat and/or human urine and human liver information was provided.
(19) Specifically: heart attack (one case), cardiac arrest (one), cardiac failure (one), coronary artery disease (one) and ischaemic heart disease (one).
(20) See also Gregg and Rawls (2013), Huang et al. (2012).
JOINT REPORTS I MDPV TABLE 1Transporter-mediated inhibition of uptake and stimulation of release in rat brain synaptosomes. Values are given as nM ± S.E.M. for N=3–4 experiments per drug. E % refers to percentage of maximal release response. Key: ‘—' indicate that compounds failed to elicit >30 % of the maximal response and therefore compounds are considered inactive in the release assay. Modified from Baumann et al. (2013a, 2013b) EC (nM ± S.E.M.) EC (nM ± S.E.M.) EC (nM ± S.E.M.) ratio model of reinforcement, higher doses of MDPV produced the highest breakpoints (Aarde et al., 2013; Watterson et al., See ‘Pharmacology and mode of action' (above) for an 2012). In addition, dose-substitution studies suggested that overview of some of the in vitro and in vivo animal data that is MDPV possessed greater potency and efficacy than relevant to the toxicity of MDPV in humans.
methamphetamine, with escalation studies showing that MDPV increases drug intake at similar doses to those Simmler et al. (2013) examined the cytotoxicity of MDPV in observed with methamphetamine (Watterson et al., 2012). vitro using a cell membrane integrity assay, which measures Finally they note that studies in mice undertaken by the release of adenylate kinase from damaged cells. MDPV did Fantegrossi et al. (2013) found that MDPV discriminates from not show apparent cytotoxicity at concentrations of 10 µM and saline and fully substitutes for MDMA and methamphetamine.
100 µM after 4 hours of incubation at 37°C. No studies were identified that have examined the toxicity of MDPV in humans.
The findings reviewed by Gregg and Rawls (2013) are supported by the work of Baumann et al. (2013a), which is The clinical features of acute toxicity associated with MDPV discussed in the section on ‘Pharmacology and mode of action' use as reported by the Member States are provided in section (above). They note that, based on the ‘potent and efficacious 3.4.1 ‘Non-fatal intoxications' and ‘Deaths' and in Annex 2. actions of MDPV on extracellular dopamine and motor activity' These include a number of analytically confirmed cases. Case shown in their study, suggests that MDPV has a high potential reports/series of intoxications where MDPV was analytical for abuse. In addition, they suggest that, given that MDPV has a confirmed report similar findings (Spiller et al., 2011).
weak effect on SERT, this may further enhance the reinforcing effects of the drug, given that studies have shown that Methods for the toxicological screening of MDPV in urine have elevations in synaptic serotonin can dampen the stimulant been reported by Strano-Rossi et al. (2010) and in blood by effects mediated by dopamine (Baumann et al., 2011; Wee et Marinetti and Antonides (2013).
al., 2005). No studies were identified that have examined the dependence and abuse potential of MDPV in humans.
Dependence and abuse potential A review by Gregg and Rawls (2013) provides an overview of 3.4.2. Characteristics of users the in vivo animal behavioural pharmacology studies relevant to the possible abuse potential of MPDV in humans (21). They The section below includes a discussion of the characteristics note that in rats the administration of MDPV both lowered of users, which includes information from self-reported use intracranial self-stimulation thresholds and led to self- from Internet drug discussion forums and related websites administration across multiple doses; while in a progressive- (hereafter ‘user websites'). As such it is important to note that it is not possible to confirm the specific substance(s) used, nor (21) See also Watterson et al. (2013). the purity, dose, etc. Analyses of products containing new JOINT REPORTS I MDPV psychoactive substances that are sold on the drug market have the drug. He also reported taking MDMA and ‘cathinone' as shown that the composition can differ between that claimed by well. Other symptoms reported included reduced appetite and the retailer, as well as over different geographical areas and weight loss, insomnia, loss of focus, absences, paranoia, a time. Similar caveats apply to these types of information that sensation of cold and a sensation of electrical discharge in the have been provided in case reports/series unless biological and heels by patients who had taken MDPV intranasally. The drug collected samples were taken and subjected to toxicological had been bought on the Internet. A range of other effects were and forensic analysis. In addition, the information provided by also noted, such as insomnia, psychomotor agitation patients in case reports/series, and that provided on user (experienced for three days by an injecting user); anxiety, websites, should be regarded as illustrative only and not taken intellectual stimulation, obsession to consume MDPV, as representative of users of MDPV in general. Finally, withdrawal symptoms, fatigue, sleep disorder and pain at the information from seizures, collected samples and user websites site of injection; chest pain, accelerated heart rate and suggest that MDPV has been commonly sold as a ‘legal' sensation of warmth (injecting user); agitation, facial replacement for cocaine, amphetamine or ‘ecstasy' (MDMA). erythrosis, dryness of the mucous and anxiety for five days for There is also information to suggest that MDPV has been sold a patient with intranasal use. Two others reported sexual directly on the illicit drug market as cocaine, amphetamine and stimulation and increased sociability.
MDMA, as well as mephedrone. In these cases users may be unaware that they are consuming MDPV. Additional research is Two studies are available that report the injection of MDPV, required in order to examine to what extent the characteristics although its injection is documented in other countries, such of MDPV users reflect those who use other stimulant drugs.
as France, Romania and Finland. In the first study, 183 clients of a needle exchange programme in Hungary agreed to report Route of administration, dose and drug regimens their drug using habits (Csák et al., 2013). This study found that during 2011 changes occurred in the nature of primary Information provided by the Member States, and from case injected substances: amphetamine was cited as the primary reports/series and user websites, suggests that the routes of injected substance by 45.9 % of the respondents and MDPV administration for MDPV were mainly nasal (insufflation/ by 48.1 %. Almost half of the former amphetamine injectors sniffing), oral (swallowing) or intravenous injection. Two had switched to MDPV (64 people, 45.1 %) as had 10 (41.7 %) countries reported that MDPV was detected in paper blotters of the former heroin injectors and 11 (78.6 %) of those using and therefore buccal or sublingual administration may also other substances (cocaine and mephedrone). The second occur. Furthermore, two countries reported the presence of study (Lindeman et al., 2013), also mentioned in Section 3.4.1, MDPV in vegetable material, and this product would most was initiated due to a sharp increase in the number of probably be smoked. Information from user websites suggests enquiries to the Swedish Poisons Information Centre that rectal administration may also be a route that is used.
regarding intoxications with MDPV. Of particular note is that, of the patients with confirmed or suspected MDPV Information from case reports/series and user websites consumption, 95 % were classified as chronic drug users and suggests that a range of doses are used that may depend on the >60 % were reported as positive for HCV.
route of administration. The Erowid user website includes a range of tentative ‘common doses' for three routes of Information from user websites suggests that MDPV may be administration: insufflation 5–11 mg; oral 8–15 mg; rectal used on its own as well as in combination with other new 6–12 mg (Erowid, 2013a). One case report noted that MDPV psychoactive substances, controlled drugs and/or produces psychoactive effects with as little as 3 mg to 5 mg, prescription medication (Erowid, 2013b; Drugs Forum, 2013). depending on its route of administration, and the average dose In most of the cases of non-fatal intoxications and deaths is approximately 5 mg to 20 mg. This report goes on to say that reported by the Member States, other new psychoactive repeated dosing is common to avoid an unpleasant come-down, substances and/or controlled drugs were detected in as is described with large single doses (Ross et al., 2012).
biological samples (Section 3.4.1 and Annex 2).
France also reported cases identified on the basis of interviews with patients. For one of these cases, the patient reported suffering malaise, tetany, language disorders and No studies were identified that have examined the subjective respiratory distress after taking MDPV by injection. Another effects of MDPV in humans; information is largely limited to patient suffered abnormal movements, trismus, profuse that provided in case reports/series (see ‘non-fatal sweating, visual disorders, insomnia, anorexia, dysuria, vertigo intoxications' and section above) and self-reported and dysuria for 24 hours after he had injected the drug. He experiences from user websites. Table 2 provides an overview also reported having taken 4-MEC. Another patient suffered of the self-reported duration of effects when MDPV is taken by agitation, confusion and had attempted suicide after injecting the oral and insufflated routes as reported by Erowid (2013c). JOINT REPORTS I MDPV Table 3 provides an overview of subjective effects of MDPV as Availability, supply, price reported by Erowid (2013c). In both cases the information was collated from users, research and other resources. No further A search of google.com using the search string ‘buy "MDPV"' details were provided on the methodology used to collate this conducted by the EMCDDA in December 2013 for the Joint information. Information provided in case reports and case Report identified a number of online shops offering MDPV for series of non-fatal intoxications associated with MDPV appear sale in both retail and wholesale quantities. In the former case, to support some of these effects. The section on ‘non-fatal MDPV may be sold as a ‘research chemical'.
intoxications', above, provides an overview of the other adverse effects reported to be associated with MDPV.
Data from the National Drug and Alcohol Research Centre's deep web monitoring programme of the Silk Road marketplace (22,23) (Van Buskirk et al., 2013) identified seven Examples of self-reported duration of effects of MDPV per retailers in early February 2013 offering MDPV for sale. Details route of administration (tentative) as reported by Erowid of the specific quantities and prices were not provided. The (2013c). No information on the doses that were used was number of such retailers was relatively stable over the preceding four months of monitoring (24). It is important to Duration of effects for MDPV note that the study was conducted before Silk Road was seized and taken offline in October 2013 by the United States Federal Bureau of Investigation. No studies were identified that have examined the sale of MDPV since Silk Road has Seizure data and information from collected samples reported by the Member States suggest that MDPV is sold as a drug in its own right and directly on the illicit drug market as cocaine, Hangover/day after amphetamine, MDMA and mephedrone.
TABLE 3Examples of subjective effects of MDPV as reported by Erowid (2013a). No information on the doses that were used was provided I 3.5. Information on whether or not the new
substance is currently under assessment, or has been under assessment, by the UN system — Subjective effects of MDPV Article 5.2(e) of the Decision Stimulation (mental and physical)Euphoria, mood lift The World Health Organization is the specialised United Nations agency designated for the evaluation of the medical, Increased productivity and motivationIncreased mental clarity scientific and public health aspects of psychoactive Enhanced creativity substances under the Single Convention on Narcotic Drugs, Feelings of empathy 1961 and the Convention on Psychotropic Substances, 1971. On 10 October 2013, the World Health Organization informed Stimulation (mental and physical)Mild elevation in heart rate the EMCDDA that MDPV is currently under assessment and ‘the critical review report will be published only early next year (Likelihood of negative side effects increases with higher doses) (probably April)'.
Tightened jaw muscles, grinding teeth (trismus and bruxia)Reduced enjoyment of eating/loss of appetiteDisturbed sleep patternsInvoluntary body movements (twitching, lip-smacking, etc.)Confusion and/or scrambled thoughts (22) The National Drug and Alcohol Research Centre (NDARC) is based at the University of New South Wales, Sydney, Australia.
(23) Silk Road is an anonymous, international online marketplace that operates as Residual depressed mood a Tor hidden service. It uses the peer-to-peer payment network and digital Nystagmus/eye spasm currency Bitcoin for monetary transactions. The original Silk Road marketplace was seized and taken offline on 2 October 2013 by the United Harsh comedown effects States Federal Bureau of Investigation. Since then a new version of Silk Road, Fiending (re-dosing repeatedly without planning to do so) sometimes described as ‘Silk Road 2.0', has become operational. See Christin (2012) for an overview of the original Silk Road.
(24) Nine retailers were identified in late October 2012; 10 in mid-November Very elevated heart rate 2012; 10 in late November 2012; 10 in mid-December 2012; nine in early Hallucinations/psychotic behaviour (at high doses or with January 2013; and nine in mid-January 2013. See Christin (2012) for a discussion of some of the market characteristics and dynamics of the original Silk Road.
JOINT REPORTS I MDPV Article 7.1 of Council Decision states that ‘no risk assessment In Belgium it was added to the list of substances on 20 March shall be carried out in the absence of a Europol/EMCDDA 2013. In Bulgaria it has been controlled under the Narcotic Joint Report. Nor shall a risk assessment be carried out where Substances Control Law since February 2011. In Croatia it is the new psychoactive substance concerned is at an advanced included in the list of drugs, psychotropic substances, plants stage of assessment within the United Nations system, used to produce drugs and substances that can be used in the namely once the WHO expert committee on drug dependence production of drugs. In Cyprus it is controlled under the has published its critical review together with a written Narcotic Drugs and Psychotropic Substances Law of 1977 as recommendation, except where there is significant new a class B drug that is covered by the generic definition of information that is relevant in the framework of this Decision'.
cathinones. In the Czech Republic it has been included in the Act 167/1998 Coll. on Addictive Substances. In Denmark it is The Joint Report has been produced on the understanding covered by the Executive Order on Euphoriant Substances. In that MDPV is not at an advanced stage of assessment within Estonia it has been listed in the Regulation No.73 of the the United Nations system.
Minister of Social Affairs since 29 November 2010. In Finland it has been listed in the Narcotics Act 373 of 2008 since 28 June 2010. In France it was added to the controlled narcotic 3.6. The date of notification on the Reporting Form of substance list since 2 August 2012. In Germany it has been the new psychoactive substance to the included in the list covered by the Narcotic Substance Law EMCDDA or to Europol — Article 5.2(f) of the since 26 July 2012. In Hungary it is listed in Schedule A (psychotropic substances) of Act XXV of 1998 on human pharmaceuticals. In Ireland it has been covered by the Misuse The first official EMCDDA–Europol notification of MDPV dates of Drugs Acts since 11 May 2010. In Italy it has been from December 2008 from the Finnish National Focal Point. controlled generically, as it is a derivative of 2-amino-1-phenyl- The Reporting Form details a seizure of two quantities of white 1-propanone, under the Decree of the President of the powder (each of 1 g) intercepted by customs authorities on 24 Republic 309/90 since 29 December 2011. In Latvia it is November 2008 in incoming mail. The powders were in controlled according to Cabinet Regulation 847 ‘Regulations regarding narcotic substances, psychotropic substances and pyrrolidinyl-pentan-1-one, purity 99 +%, 1g'. Identification was precursors to be controlled in Latvia'. In Luxembourg it has based on the analytical technique of GC-MS (25).
been controlled by the drug control legislation since 30 July 2012. In Poland it is covered by the Act of 15 April 2011 MDPV was added to the list of new psychoactive substances amending the Act of Counteracting Drug Addiction. In Slovakia monitored by the EMCDDA and Europol through the European it is in the first schedule of psychotropic substances set by the Union early-warning system and a profile of the substance Act. No 139/1998 Coll. as amended by the Act. No 43/2011 was created in the EMCDDA European Database on New Coll., which came into force on 1 March 2011. In Slovenia it Drugs (EDND). Since then, analytical details, background was included by the Decree on amending the Decree on information and information relevant to public health have Classification of Illicit Drugs, Official Gazette of RS No. been exchanged between EMCDDA, Europol and the Member 62/2013. In Sweden it comes under the Narcotic Drugs States on an ad hoc basis. The Commission and the EMA were Control Act (SFS 1992-860) and the Narcotic Drugs Control kept duly informed.
Ordinance (SFS 1994-1554). In the United Kingdom it was included in the generic definition of substituted cathinone derivatives placed under the Misuse of Drugs Act 1971 in April 3.7. Information on whether or not the new 2010. In Turkey it is listed in the Law on Control of Narcotics psychoactive substance is already subject to no.2313. In Norway it has been included by generic scheduling control measures at national level in a Member since 14 February 2013.
State — Article 5.2(g) of the Decision Three Member States (Austria, Portugal and Romania) control Twenty Member States (Belgium, Bulgaria, Croatia, Cyprus, MDPV under legislation penalising unauthorised supply of the Czech Republic, Denmark, Estonia, France, Germany, defined or qualifying new psychoactive substances. In Austria Hungary, Ireland, Finland, Italy, Latvia, Luxembourg, Poland, it is controlled under the generic definition within the New Slovakia, Slovenia, Sweden, and the United Kingdom), as well Psychoactive Substances Act. In Portugal it is listed as as Turkey and Norway control MDPV under drug control controlled under Decree-Law 54/2013. In Romania, Law 194/2011 subjects to control any psychoactive substance that qualifies by conforming to certain criteria (all substances with psychoactive potential are subject to control until proven (25) Gas chromatography-mass spectrometry.
harmless by a special designated commission).
JOINT REPORTS I MDPV In the Netherlands, MDPV sold in consumer amounts is Settings of use treated as being a medicinal product and must comply with medicines legislation (and general product safety legislation).
One of the reports of deaths provided by Poland noted the use of MDPV in the context of recreational use (at a party). Greece, Lithuania and Malta have reported that MDPV is not Samples have been collected from dance venues in Austria subject to control measures at the national level.
and the Netherlands, where it was reported to have been sold as mephedrone, cocaine, MDPV and speed (Austria), and No information was provided regarding the control status of cocaine, synthetic cocaine, ‘moji', 6-APB, 5-APB, MDPV and MDPV in Spain.
‘meferon' (the Netherlands). France reported that MDPV was ‘generally used at home during sexual context' (not further described). Sweden reported that ‘MDPV was popular two I 3.8. Further information — Article 5.2(h) of the
years ago among stimulant users, age group 20–30 years; they used MDPV at parties or at home (private parties that lasted from Friday night [until] Sunday night) and at times not regularly; at the moment MDPV is not present, the users 3.8.1. The chemical precursors that are known to have stopped using it because of negative side effects, mostly been used for the manufacture of the substance depression and strong craving.' No information was reported by the Member States, Turkey or Norway about the chemical precursors or manufacturing methods used to make MDPV. Methods for the production of Six countries reported the price of MDPV. France reported MDPV are documented in the scientific literature.
that MDPV was sold at between EUR 2–15 per gram. Hungary reported a price of EUR 13.5 (quantity not specified). Italy reported that prices were from EUR 14.95 for 0.5 g to EUR 169 3.8.2. The mode and scope of the established or for 10 g (source: www.spicestore247.biz/mdpv-1). The expected use of the new substance Netherlands reported information from a forum discussion that included prices for MDPV of EUR 35 per gram and MDPV has been marketed and sold through online shops as a EUR 160 for 5 g. Romania reported a price of EUR 25 (quantity branded ‘legal high' product and as a ‘research chemical'. not specified). Spain reported that when MDPV was sold as MDPV was not declared as an ingredient of the products. This cocaine the price was EUR 50–60 per gram and when it was has been confirmed by Denmark, Slovakia and the United sold as MDPV the price was EUR 20 per gram. In 2011 the Kingdom, each of which reported finding MDPV in samples of EMCDDA conducted a study of Internet sites selling new branded ‘legal high' products purchased from the Internet. psychoactive substances (EMCDDA, 2012). MDPV was found Furthermore, both Ireland and Poland reported significant to be on sale in January 2011 and July 2011 in 25 and 32 numbers of branded ‘legal high' products collected from shops respectively and the price was reported to be EUR 115– bricks and mortar shops (Kelleher et al., 2011). It is also 239 for 10 g.
important to note that information from the Member States (such as seizures, collected samples and non-fatal intoxications) and also from user websites suggests that MDPV may be commonly sold as a ‘legal' replacement for cocaine, amphetamine or MDMA. It is also sold directly on the I 3.8.3. Other use of the new psychoactive substance
and the extent of such use, the risks associated with this use of the new illicit drug market as these drugs (26). The use of MDPV by psychoactive substance, including the health injecting drug users has also been noted (see below). As a result, the mode and scope of use of MDPV may, in part, overlap and/or reflect the mode and scope of use of other No information was provided by any Member State, Turkey or stimulants used in recreational settings and by problematic Norway that indicated that MDPV had any other use apart drug users, including those who inject. Additional research is from legitimate scientific research and as an analytical required in order to examine to what extent, if any, the mode reference standard.
and scope of MDPV use overlaps with and/or reflects those groups.
(26) Other NPS and adulterants such as caffeine and lidocaine have been found JOINT REPORTS I MDPV From the available information it does not appear that MDPV I 4.3. Suspended marketing authorisation
is used in the manufacture of a medicinal product in the European Union. However, the collection of information cannot Twenty-five Member States, Norway and Iceland responded to be considered exhaustive in the absence of a European Union the EMA's information request (see section 2) reported that database on the synthetic routes of all medicinal products (27).
there had been no cases of a suspended marketing authorisation that had been granted in respect of the new psychoactive substance MDPV (28). The EMA also reported that the new psychoactive substance MDPV is not the subject of a suspended marketing authorisation through the central 4. Information from the EMA as
requested by Article 5.3 of the
I 5. Conclusions
I 4.1. Marketing authorisation
MDPV is a synthetic cathinone derivative, which is closely The 25 Member States, Norway and Iceland responded to the related to pyrovalerone. MDPV has been present in the EU EMA's information request (see section 2) reported that the drug market since at least November 2008 and has been new psychoactive substance MDPV has not obtained a detected in up to 107 non-fatal intoxications and 99 deaths, marketing authorisation (28). The EMA also reported that the particularly in Finland and the United Kingdom. There are new psychoactive substance MDPV has not obtained a some indications that it has been sold as a ‘legal' or synthetic marketing authorisation through the central authorisation version of cocaine and it has also been found in tablets resembling ‘ecstasy'. Large seizures have been made at borders and police operations have targeted its supply. Powder seizures have been reported, including multi-kilogram I 4.2. Application for a marketing authorisation
quantities. Most, but not all the Member States have control measures at the national level that cover MDPV; however, it Twenty-five Member States, Norway and Iceland responded to continues to be available and this is concerning. We conclude the EMA's information request (see section 2) reported that that the health and social risks caused by the manufacture, the new psychoactive substance MDPV is not the subject of trafficking and use of MDPV, and in particular the involvement an application for a marketing authorisation (28). The EMA also of organised crime and possible consequences of EU-level reported that the new psychoactive substance MDPV is not control measures, could be thoroughly assessed through a the subject of an application for a marketing authorisation risk assessment procedure in accordance with Article 6 of through the central authorisation procedure.
Council Decision 2005/387/JHA.
(27) I.e. products that have been granted a marketing authorisation, or where an application for a marketing authorisation has been made, or where the marketing authorisation has been suspended.
(28) Austria, Belgium, Croatia, the Czech Republic, Denmark, Estonia, Germany, Greece, Hungary, Iceland, Ireland, the Netherlands, Norway, Portugal, Slovenia, Spain, Sweden and the United Kingdom provided responses in relation to both human and veterinary medicinal products. Cyprus, Italy, Lithuania, Malta, Romania and Slovakia provided responses in relation to human medicinal products. France, Latvia and Poland provided responses in relation to veterinary medicinal products. In addition, the EMA provided information in relation to both human and veterinary medicinal products in respect of the central authorisation procedure.
JOINT REPORTS I MDPV I Aarde, S. M., Huang, P. K., Creehan, K. M., Dickerson, T. J. and Taffe, M. A. (2013), ‘The novel
recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: self-administration and locomotor activity in rats', Neuropharmacology, 71, pp. 130–140.
I Adamowicz, P., Gil, D., Skulska, A. and Tokarczyk, B. (2013), ‘Analysis of MDPV in blood: determination
and interpretation', Journal of Analytical Toxicology, 37, pp. 308–312.
I Bäckberg, M., Westerbergh, J., Al-Saffar, Y., Lindeman, E. and Helander, A. (2013), ‘Trends in
intoxications of novel psychoactive substances in Sweden during 2012', Clinical Toxicology, 51, pp. 256–257.
I Baumann, M. H., Clark, R. D., Woolverton, W. L., Wee, S., Blough, B. E. and Rothman, R. B. (2011), ‘In
vivo effects of amphetamine analogs reveal evidence for serotonergic inhibition of mesolimbic dopamine transmission in the rat', Journal of Pharmacology and Experimental Therapeutics, 337, pp. 218–225.
I Baumann, M. H., Partilla, J. S., Lehner, K. R., Thorndike, E.B., Hoffman, A.F., Holy, M., Rothman, R.B.,
Goldberg, S.R., Lupica, C.R., Sitte, H.H., Brandt, S.D., Tella, S.R., Cozzi, N.V., Schindler, C.W. (2013a), ‘Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive "bath salts" products', Neuropsychopharmacology, 38, pp. 552–562.
I Baumann, M. H., Partilla, J. S.and Lehner, K. R. (2013b), ‘Psychoactive "bath salts": not so soothing',
European Journal of Pharmacology, 698, pp. 1–5.
I Christin, N. (2012), Traveling the Silk Road: A measurement analysis of a large anonymous online
I Csák, R., Demetrovics, Z. and Rácz, J. (2013), ‘Transition to injecting 3,4-methylene-dioxy-
pyrovalerone (MDPV) among needle exchange program participants in Hungary', Journal of Psychopharmacology, 27, pp. 559–563.
I Drugs Forum (2013). http://www.drugs-forum.com/forum/showthread.php?t=125796
I EMCDDA (2012), Online sales of new psychoactive substances / ‘legal highs': summary of results
from the 2011 multilingual snapshots, EMCDDA, Lisbon. http://www.emcdda.europa.eu/publications/scientific-studies/2011/snapshot I Erowid (2013a). http://www.erowid.org/chemicals/mdpv/mdpv_dose.shtml
I Erowid (2013b). http://www.erowid.org/experiences/subs/exp_MDPV_Combinations.shtml
I Erowid (2013c). http://www.erowid.org/chemicals/mdpv/mdpv_effects.shtml
I Fantegrossi, W. E., Gannon, B. M., Zimmerman, S. M. and Rice, K. C. (2013), ‘In vivo effects of abused
"bath salt" constituent 3,4-methylenedioxypyrovalerone (MDPV) in mice: drug discrimination, thermoregulation, and locomotor activity', Neuropsychopharmacology, 38, pp. 563–573.
I Gregg, R. A. and Rawls, S. M. (2013), ‘Behavioral pharmacology of designer cathinones: a review of
the preclinical literature', Life Science, doi: 10.1016/j.lfs.2013.10.033.
I Huang, P. K., Aarde, S. M., Angrish, D., Houseknecht, K. L., Dickerson, T. J., Taffe, M. A. (2012),
‘Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats', Drug and Alcohol Dependence, 126, pp. 168–75.
I Kelleher, C., Christie, R., Lalor, K., Fox, J., Bowden, M., O'Donnell, C. (2011), An Overview of New
Psychoactive Substances and the Outlets Supplying Them, National Advisory Committee on Drugs, Dublin.
I Lindeman, E., Hultén, P., Carlvik, B., Ström, S., Enlund, M., Al-Saffar, Y., Helander, A. (2013), ‘The
impact of an MDPV-epidemic on a medium sized Swedish city', Clinical Toxicology, 51, pp. 257.
I Marinetti, L. J. and Antonides, H. M. (2013), ‘Analysis of synthetic cathinones commonly found in bath
salts in human performance and postmortem toxicology: method development, drug distribution and interpretation of results', Journal of Analytical Toxicology, 37, pp. 135–146.
JOINT REPORTS I MDPV I Meyer, M. R., Du, P., Schuster, F. and Maurer, H. H. (2010), ‘Studies on the metabolism of the
α-pyrrolidinophenone designer drug methylenedioxy-pyrovalerone (MDPV) in rat and human urine and human liver microsomes using GC-MS and LC-high-resolution MS and its detectability in urine by GC-MS', Journal of Mass Spectrometry, 45, pp. 1426–1442.
I Persson, H. E., Sjöberg, G. K., Haines, J. A. and Pronczuk de Garbino, J. (1998), ‘Poisoning severity
score: grading of acute poisoning', Journal of Toxicology-Clinical Toxicology, 36, pp. 205–213.
I Ross, E. A., Reisfield, G. M., Watson, M. C., Chronister, C. W. and Goldberger, B. A. (2012),
‘Psychoactive "bath salts" intoxication with methylenedioxypyrovalerone', American Journal of Medicine, 125, pp. 854–858.
I Simmler, L. D., Buser, T. A., Donzelli, M., Schramm, Y., Dieu, L.H., Huwyler, J., Chaboz, S., Hoener, M.C.,
Liechti, M.E. (2013) ‘Pharmacological characterization of designer cathinones in vitro', British Journal of Pharmacology, 168, pp. 458–470.
I Spiller, H. A., Ryan, M. L., Weston, R. G. and Jansen, J. (2011), ‘Clinical experience with and analytical
confirmation of "bath salts" and "legal highs" (synthetic cathinones) in the United States', Clinical Toxicology, 49, pp. 499–505.
I Strano-Rossi, S., Cadwallader, A. B., de la Torre, X. and Botrè, F. (2010), ‘Toxicological determination
and in vitro metabolism of the designer drug methylenedioxypyrovalerone (MDPV) by gas chromatography/mass spectrometry and liquid chromatography/quadrupole time-of-flight mass spectrometry', Rapid Communications in Mass Spectrometry, 24, pp. 2706–2714.
I Van Buskirk, J., Roxburgh, A., Bruno, R. and Burns, L. (2013), Drugs and the Internet, Issue 1, August.
Sydney: National Drug and Alcohol Research Centre. http://ndarc.med.unsw.edu.au/sites/default/files/ndarc/resources/DrugsTheInternet_Newsletter%20FINAL%20with%20ISSN.pdf I Watterson, L. R., Kufahl, P. R., Nemirovsky, N. E., et al. (2012), ‘Potent rewarding and reinforcing
effects of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV)', Addiction Biology, doi: 10.1111/j.1369-1600.2012.00474.x.
I Watterson, L. R., Watterson, E. and Olive, M. F. (2013), ‘Abuse liability of novel "legal high" designer
stimulants: evidence from animal models', Behavioural Pharmacology, 24, pp. 341–355.
I Wee, S., Anderson, K. G., Baumann, M. H., Rothman, R. B., Blough, B. E. and Woolverton, W. L. (2005),
‘Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs', Journal of Pharmacology and Experimental Therapeutics, 313, pp. 848–854.
JOINT REPORTS I MDPV Images of MDPV from seizures and collected samples Seizure: November 2010 40.35 g white powder divided over 74 small bags, seized in Brussels.
Seizing authority: police Seizure: September 2010 1 kg of a white powder, seized in Feucht.
Seizing authority: police Seizure: July 2009 300 yellow tablets, seized in Budapest.
Seizing authority: police Seizure: April 2011 2 white tablets, seized in Pest county.
Contents: MDPV and 4-FMC.
Seizing authority: police Collected sample, analysed in March 2010 white/off-white powder (‘Hurricane Charlie', ‘Dogs Bollix', ‘Doves Red', ‘Doves Ultra', ‘Ivory Wave', ‘Sextasy', ‘Orange Orbits', ‘Stardust'), head shop JOINT REPORTS I MDPV Numerous seized samples (powders, agglomerated powders, tablets), seized in Treviso.
Contents: MDPV, 4-FA, cocaine and lidocaine or procaine.
Seizing authority: Police Department, Treviso Seizure: March 2011 30 packets containing white powder — 15 g in all. Seized in Attard (EUR 13.5 per gram).
Seizing authority: Police Drug Squad Collected sample, analysed in March 2010 310 mg deep blue powder, colourless capsule.
Contents: MDPV and mephedrone not quantified.
Collecting authority: National Drug Service of Bureau of Fight Against Organised Crime, Police Force Headquarters; analysis was completed by Institute of the Forensic Science of Police Force (IFS).
Collected sample, analysed in September 2010 310 mg white powder, colourless capsule.
Contents: MDPV and Butylone not quantified.
Collecting authority: National Drug Service of Bureau of Fight Against Organised Crime, Police Force Headquarters; analysis was completed by Institute of the Forensic Science of Police Force (IFS).
JOINT REPORTS I MDPV Non-fatal intoxications and deaths where MDPV has been analytically confirmed in biological samples Non-fatal intoxications Results for other substances First-time MDPV use. Drug taken orally. Symptoms included hallucinations and severe psychosis, paranoia, visual and auditory hallucinations, aggressiveness. Hypertension, tachycardia. Treated with antipsychotics. Status normal after 3–4 days.
First-time MDPV use. Drug taken orally. Symptoms included hallucinations and severe psychosis, paranoia, visual and auditory hallucinations, aggressiveness. Hypertension, tachycardia. Treated with antipsychotics. Status normal after 3–4 days.
This case is related to the case described above. Date not specified Pyrovalerone (+) Symptoms included delirium syndrome, hallucination, rhabdomyolysis, tachycardia, hypotension, agitation, logorrhoea, acute renal failure.
Man brought in to the emergency department by the police.
Date not specified Methylone (4400 ng/mL) Symptoms included tachycardia, mydriasis, hypertension, agitation, profuse sweating, trembling, scarification, rhabdomyolysis. Paranoid psychosis, aggressivity. Route of administration: inhaled and oral. 10 g. Bought on the Internet. In combination with methylone.
Date not specified Intranasal ingestion. Duration of action: 2 days.
Symptoms: mydriasis, paranoid psychosis.
On admission, the patient was very agitated with tachycardia (Fc 115 bpm). He reported having consumed cannabis, alcohol and 3 white capsules. He was treated with benzodiazepine and discharged 2 days later.
The patient was admitted to the emergency department and reported having consumed (sniffing) ecstasy and synthetic drugs generally named as ‘mefre, crystal and energy'.
Symptoms included agitation, mild tachycardia (Fc 105 bpm), distress, psychotic symptoms and visual and auditory hallucinations. During the first 24 hours the patient was treated with fluids, benzodiazepine and haloperidol and was transferred to a psychiatric ward.
Mephedrone (-)Butylone (-)4-methylethcathinone (-)Methoxetamine (-)APB (29) isomers (-)4-fluoroamphetamine (-)MDAI (30) (-) JOINT REPORTS I MDPV Results for other substances On arrival in the emergency department the patient reported having consumed 3,4-methylenedioxypyrovalerone (MDPV) intravenously for the last 3–4 days, together with benzodiazepine, to counteract the excitatory effect of MDPV. Symptoms included admission: 35 µg/L 3 days after admission: psychomotor agitation, confusion and anxiety. Anamnestic information from the patient revealed previous use of pentedrone and 3-methylmethcathinone abandoned due to decreased interest on these substances.
Oxazepam (114.99 µg/L) Three days after admission, the patient had a second urine analyses, and reported having Diazepam (1.26 µg/L) continued his use of MDPV.
MDPV was purchased via the Internet and marketed as ‘bath salt'.
Result for other substances was From a total of 86 cases, in 17 cases the symptoms were severe (Poisoning Severity Score positive for 15/17 cases with severe — PSS 3) and consisted of extreme agitation, psychosis, hyperthermia, tachycardia, hypertension, myocardial infarction, rhabdomyolysis and renal failure. A few patients needed Benzodiazepines (7) were the most therapy with sedatives for several days due to prolonged symptoms.
frequently identified substances.
See Bäckberg et al. (2013) for further details.
Medicines included buprenorphine, tramadol and fentanyl.
Twelve of the 13 cases described were classified as chronic drug users, with >60 % noted to be HCV positive.
See Lindeman et al. (2013) for further details.
JOINT REPORTS I MDPV Results of toxicological analysis for Biological sample Butylone (bk-MBDB) overdose in combination with methylone, 4-methylethcathinone and cocaine.
4-methylethcathinone (+)Cocaine (+) Accidental death, poisoning by narcotics.
Olanzapine (0.7 mg/L)Methadone (0.4 mg/L)Chlorprothixen (0.1 mg/L)Diazepam (0.03 mg/L)Amphetamine (8.4 mg/L) Ethanol (1.5 g/kg) Accidental death, poisoning by narcotics.
Buprenorphine (0.001 mg/L) Diazepam (0.1 mg/L) Accidental death, poisoning by drugs or medicaments.
Temazepam (0.3 mg/L)Morphine (0.6 mg/L)Amphetamine (0.88 mg/L)THC (31) (<LOQ) Accidental death, poisoning by drugs or medicaments.
Alprazolam (0.1 mg/L)Tramadol (1.4 mg/L)Methadone (0.2 mg/L)Diazepam (0.02 mg/L) Suicide, poisoning by drugs or medicaments.
(estimated value) Trimipramine (0.3 mg/L)Oxycodone (2.2 mg/L) Suicide, propranolol poisoning .
Zolpidem (0.4 mg/L)Citalopram (0.9 mg/L)Oxazepam (1.7 mg/L)Olanzapine (0.2 mg/L)Propranolol (2.1 mg/L) Homicide, multiple injuries to neck.
Morphine (0.08 mg/L)Amphetamine (1.6 mg/L) Temazepam (0.9 mg/L) Suicide, hanging.
Diazepam (0.4 mg/L)Amphetamine (7.3 mg/L) (31) D9-tetrahydrocannabinol, the main psychoactive substance in cannabis.
JOINT REPORTS I MDPV Results of toxicological analysis for Biological sample Methadone (1.3 mg/L) Accidental death, poisoning by drugs or medicaments.
Temazepam (0.3 mg/L)Diazepam (0.1 mg/L)Amphetamine (0.06 mg/L)Buprenorphine (0.0044 mg/L) Accidental death, poisoning by drugs or medicaments.
Tramadol (5.3 mg/L)Valproate (19 mg/L)THC (32) (0.0061 mg/L) Ethanol (0.22 g/kg) Accidental death, injury of thoracic aorta' Amphetamine (0.16 mg/L) Accidental death, poisoning by drugs or medicaments.
Diazepam (0.1 mg/L)Oxycodone (0.13 mg/L) Disease, infective myocarditis.
Ethanol (1.3 g/kg) Accidental death, poisoning by drugs or medicaments.
Venlafaxine (8.7 mg/l)Levomepromazine (0.4 mg/l)Mirtazapine (0.3 mg/l)Nordiazepam (0.05 mg/l)Codeine (0.53 mg/l)Buprenorphine (0.0032 mg/L) Ethanol (0.36 g/kg) Accidental death, poisoning by drugs or medicaments.
Venlafaxine (0.9 mg/l)Alprazolam (0.05 mg/l)Diazepam (0.34 mg/l)Buprenorphine (0.0076 mg/l) Oxazepam (0.46 mg/L) Accidental death, poisoning by drugs or medicaments.
Temazepam (0.096 mg/L)Nordiazepam (0.024 mg/L)Amphetamine (0.11 mg/L)Buprenorphine (0.70 mg/L) Suicide, hanging.
Ethanol (0.51 g/kg) (32) D9-tetrahydrocannabinol, the main psychoactive substance in cannabis.
JOINT REPORTS I MDPV Results of toxicological analysis for Biological sample Nordiazapam (0.12 mg/L) Accidental death, poisoning by narcotics.
Morphine (0.15 mg/L)Codeine (0.02 mg/L)Amphetamine (0.20 mg/L)Oxycodone (<LOQ)THC (33) (+) Methadone (0.3 mg/L) Accidental death, poisoning by narcotics.
Temazepam (0.13 mg/L)Oxazepam (0.15 mg/L)Nordiazepam (0.026 mg/L)Amphetamine (+) Diazepam (0.033 mg/L) Accidental death, poisoning by narcotics.
DPMP (34) (+)Methylone (+) Suicide, poisoning by drugs or medicaments.
Amitriptyline (4.3 mg/L)Hydroxyzine (1.1 mg/L)Citalopram (0.7 mg/L)Perfenazine (0.21 mg/L) Disease, other and unspecified cirrhosis of liver.
Alprazolam (0.018 mg/L)Methadone (0.4 mg/L)Diazepam (0.13 mg/L) Alprazolam (0.44 mg/L) Suicide, crushing injury of skull.
Accidental death, poisoning by drugs.
Temazepam (1.1 mg/L)Quetiapine (0.3 mg/L)Methadone (0.2 mg/L)Diazepam (0.029 mg/L) Accidental death, poisoning by drugs.
This case has a connection to case 25 — the two deceased were found together.
Methadone (+)Quetiapine (+) Nordiazepam (0.20 mg/L) Suicide, toxic effect of carbon monoxide (COHb (35) 71 %).
(33) D9-tetrahydrocannabinol, the main psychoactive substance in cannabis.
JOINT REPORTS I MDPV Results of toxicological analysis for Biological sample Diazepam (0.30 mg/L) Suicide, crushing injuries involving other combinations of body regions.
Buprenorphine (0.0037 mg/L)Alprazolam (+)Clonazepam (+) Methadone (0.6 mg/L) Accidental death, poisoning by drugs or medicaments.
Temazepam 0.22 mg/L)Diazepam (0.15 mg/L)Buprenorphine (0.0017 mg/L) Accidental death, poisoning by narcotics.
Amphetamine (1.8 mg/L) Methadone (1.1 mg/L) Accidental death, poisoning by drugs or medicaments.
Mirtazapine (0.07 mg/L)Oxazepam (0.077 mg/L)Amphetamine (0.24 mg/L)Pregabalin (3.7 mg/L) Buprenorphine (+) Accidental death, poisoning by narcotics.
Verapamil (+)Propofol (+)Diazepam (+) Fentanyl (0.0097 mg/L) Accidental death, poisoning by narcotics.
Clonazepam (0.005 mg/L) Olanzapine (0.3 mg/L) Accidental death, poisoning by narcotics.
Alprazolam (0.005 mg/L)GHB (37) (1 500 mg/L) Ethanol (0.23 g/kg) Accidental death, poisoning by narcotics.
590 mg/mL (blood) Accidental death, multiple fractures of ribs.
α-PVP (38) (0.60 mg/L)Amphetamine (1.6 mg/L) Disease, intoxication — psychoactive substances.
Diazepam (0.064 mg/L)Buprenorphine (0.00066 mg/L)Pregabalin (4.4 mg/L)Amphetamine (< LOQ) JOINT REPORTS I MDPV Results of toxicological analysis for Biological sample Doxepine (1.5 mg/L) Suicide, doxepin poisoning.
Citalopram (1.9 mg/L)Quetiapine (1.3 mg/L)α-PVP (0.070 mg/L)Buprenorphine (0.029 mg/L)Temazepam (<LOQ) Ethanol (1.6 g/kg) Cause of death not yet registered.
Alprazolam (0.005 g/l)Diazepam (0.45 g/l)Codeine (0.15 g/l)Buprenorphine (0.0006 g/L) Trimethoprim (1.6 mg/L) Cause of death not yet registered.
Alprazolam (0.044 mg/L) Cause of death not yet registered.
Diazepam (0.092 mg/L)THC (39) (0.0051 mg/L)Buprenorphine (0.0012 mg/L)Fentanyl (0.0082 mg/L)Pregabalin (4.0 mg/L) 106 µg/L (blood) Cause of death: drowning.
760 µg/L (urine) (40 µg/L in blood)(295 µg/L in urine) (33 µg/L in blood)(110 µg/L in urine) Hydroxyzine (194 µg/L in blood)Nordazepam (47 µg/L in blood)Oxazepam (8 µg/L in blood)Cannabinoic acid (15.7 µg/L in blood)Ethanol (0.3 g/L in blood) Cause of death not reported.
Ephedrine (324 ng/mL) Cause of death: ‘metabolic dysfunction' caused by MDPV.
Buphedrone (127 ng/mL) Indirect death: car accident. During inspection of the deceased driver, the police found packages of white powder, labelled ‘Ivory Speed' and ‘Exclusive Dust', and a note reading ‘collector's product for field stone rinsing'.
See Adamowicz et al. (2013) for further information.
Clonazepam (1.2 ng/mL) Death after a night of partying. A witness testified that the man had taken a product called ‘Speedway'.
The autopsy showed emaciation, external hydrocephalus and atherosclerosis. Deceased with a history of drug addiction, HIV+.
See Adamowicz et al. (2013) for further information.
(39) D9-tetrahydrocannabinol, the main psychoactive substance in cannabis.
JOINT REPORTS I MDPV Results of toxicological analysis for Biological sample The deaths were intoxications involving several substances (not further None of the 3 deaths related only to MDPV.
There were several accidents, death by hanging and intoxications with several drugs (not further described).
There was one car accident and intoxications with several drugs (not further Fluoromethcathinone (+) Case 1: hit by train.
Case 2: bag over head.
Olanzapine (+)Amphetamine (+) Case 1: hanging.
Case 2: no circumstances reported.
Case 3: found at home.
Fluoromethcathinone (+)MDMA (40) (+)Methylone (+)MDAI (41) (+)5-IAI (42) (+)Methoxetamine (+)AMT (43) (+) (40) Methylenedioxymethylamphetamine (commonly known as ‘ecstasy').
JOINT REPORTS I MDPV Results of toxicological analysis for Biological sample United Kingdom** Jan–Dec 2012 6 cases of hanging.
1 case murder victim.
1 case murder suspect.
2 cases found dead at home.
1 case found in a canal.
1 case found dead in a car (carbon monoxide poisoning).
(One of the cases is a duplicate, although it is not certain which one, hence this group is counted as 11 cases — see death 99) Morphine (+)Mirtazapine (+)Diazepam (+)Zopiclone (+)Codeine (+) Coronary artery disease in the presence of MDPV.
Coroner's verdict: open verdict/unascertained. Fentanyl toxicity implicated.
(24 ng/mL in blood) Coroner's verdict: open verdict/unascertained. (37 µg in gastric sample) Cause of hypovolaemic shock: laceration of left forearm associated with partial transection of cephalic vein.
(+ in gastric sample) Toxic effects of pyrovalerone and MDPV.
THC-acid (44) (+ in blood) Coroner's verdict accidental/misadventure.
Lignocaine (+ in antemortem blood)Amiodarone (+ blood, therapeutic use suspected) Mixed drug toxicity. Implicated: methedrone, GBL and methylone. Cause of death: non-dependent abuse of drugs.
Coroner's verdict: open verdict/unascertained.
Multiple injuries. Had taken a variety of substances and alcohol.
(63 mg/100mL in blood) Coroner's verdict: suicide. Implicated drugs alcohol, mephedrone and MDPV.
(118 mg/100mL in urine) (<LOD (46) in matrix unknown) cocaine (+ in urine)levamisole (+ in urine)quinine (+ in urine) (44) D9-tetrahydrocannabinolic acid, a breakdown product of D9-tetrahydrocannabinol, the main psychoactive substance in cannabis.
(46) Limit of detection — the lowest amount that can be detected by the method used.
JOINT REPORTS I MDPV Results of toxicological analysis for Biological sample Alcohol (175 mg/100mL) Carbon monoxide poisoning, alcoholic liver disease.
Citalopram (0.12 mg/L) Implicated: 4-fluoromethcathinone and mephedrone.
Diazepam (85 µg/L) Coroner's verdict: suicide. Temazepam (99 µg/L) Asphyxia. Implicated: 4-fluoromethcathinone and mephedrone.
(0.21 mg/L in blood) Coroner's verdict: accidental/misadventure.
(23.62 mg/mL in urine) (<0.05 mg/L in urine) Ibuprofen (+ blood) 0.41 mg/L (blood) Amphetamine (+ blood) Cardiac arrest caused by either multiple drug toxicity or excited delirium.
0.75 mg/L (urine) Coroner's verdict: accidental/misadventure.
(0.05 mg/L in blood)(0.05 mg/L in urine) (0.55 mg/L in blood)(6.51 mg/L in urine) Alcohol (57 mg/100 mL) Cause of death unascertained.
Coroner's verdict: open verdict/unascertained.
TFMPP (47) (1.9 mg/L)Lignocaine (+) (0.04 µg/mL in blood) Coroner's verdict: open verdict/unascertained.
(+ on nasal swab) Lignocaine (+ on nasal swab)Benzocaine (+ on nasal swab)Sertraline (+ in blood)Diazepam (+ in blood) Drowning and multiple drug overdose. Implicated: MDMA, cocaine and Cocaine (929 µg/L) Coroner's verdict: accidental/misadventure.
(48) Methylenedioxymethylamphetamine (commonly known as ‘ecstasy').
JOINT REPORTS I MDPV Results of toxicological analysis for Biological sample Cause of death: ischaemic heart disease and illicit use of cathinones. Implicated (1.55 mg/l in blood), drugs: mephedrone, MDPBP and pentylone.
(94.2 mg/l in urine) Coroner's verdict accidental/misadventure.
(0.34 mg/l in blood)(29.4 mg/l in urine) (+ in matrix unknown) Cocaine (+ in urine) MDMA, cocaine, MDPV and methylmethcathinone toxicity. Implicated: ecstasy, cocaine and cathinones.
Coroner's verdict: open verdict/unascertained.
MDPV and heart attack.
Coroner's verdict: open verdict/unascertained.
United Kingdom** Apr 2012 AMT (50) (0.89 mg/L) Cause of death: cardiac failure, MDPV and AMT drug toxicity plus left ventricular hypertrophy and obesity.
Coroners' verdict: accidental/misadventure.
In this table LOD is the limit of detection and LOQ is the limit of quantitation.
* All cases in Finland are from medico-legal source and include suspect and unnatural deaths, non-related to poisoning.
** The United Kingdom reported data on fatal intoxications from two separate sources, ROAR Forensics and the national programme for Substance Abuse Deaths (np-SAD). It should be noted that, based on case-specific details, case 99 is believed to be a duplicate of one of the cases reported in the aggregated data from 2012, and has been counted once only.
Recommended citation: European Monitoring Centre for Drugs and Drug Addiction (2014), EMCDDA–Europol Joint Report on a new psychoactive substance: MDPV (3,4-methylenedioxypyrovalerone), Joint Reports, Publications Office of the European Union, Luxembourg.
The European Monitoring Centre for Drugs and Drug Addiction is the hub of drug-related information in Europe. Its mission is to provide the European Union and its Member States with ‘factual, objective, reliable and comparable information' on drugs and drug addiction and their consequences. Established in 1993, it opened its doors in Lisbon in 1995, and is one of the European Union's decentralised agencies. The Centre offers policymakers the evidence base they need for drawing up drug laws and strategies. It also helps professionals and researchers pinpoint best practice and new areas for analysis.
Related publications and websites EMCDDA and EuropolI EMCDDA–Europol 2012 Annual Report on the implementation of Council Decision 2005/387/JHA (New drugs in Europe, 2012) I EMCDDA Action on new drugs: www.emcdda.europa.eu/drug-situation/new-drugs These and all other EMCDDA publications are available from www.emcdda.europa.eu/publications Legal notice: The contents of this publication do not necessarily reflect the official opinions of the EMCDDA's partners, the EU Member States or any institution or agency of the European Union. More information on the European Union is available on the Internet (europa.eu).
Luxembourg: Publications Office of the European Uniondoi: 10.2810/24085 I ISBN 978-92-9168-680-3 European Monitoring Centre for Drugs and Drug Addiction, 2014Reproduction is authorised provided the source is acknowledged.
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