- Email: [email protected]
The comeback of Ecstasy: New designs and increased MDMA content
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ARTICLE IN PRESS
TOXAC-144; No. of Pages 2
Toxicologie Analytique & Clinique (2016) xxx, xxx—xxx
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LETTER TO THE EDITOR The comeback of Ecstasy: New designs and increased MDMA content To the editor Ecstasy (XTC), the tablet form of 3,4-methylenedioxymethamphetamine (MDMA), was popular, regarding its wide use and abuse, in the 1990s in the clubs and discotheques and even more in the techno free parties and underground nightlife events. Indeed, recreational XTC use is historically highly linked to the underground techno subculture, which was born in UK in the late 1980s during the second ‘‘summer of love’’, to such an extent that this movement was called ‘‘Ecstasy Culture’’. In the 2000s, changes in laws and regulations have altered the organization of festive techno space and, subsequently, the use of psychoactive drugs within it [1]. In 2008, the Cambodian authorities launched a largescale operation to destroy many Sassafras cultivation. As the safrole, one of the main precursors for the MDMA synthesis, comes from this shrub, these destructions led to an international shortage of MDMA. Consequently, pills sold for ecstasy often contained other molecules which sometimes led to side adverse effects. More and more, XTC gets a bad reputation, considered as a scam, and his popularity decreased. The real XTC became rarer and after the shortage, MDMA ‘‘crystal/rock’’ forms emerged on the market and were preferred by users owing to assessments of their high-purity [2]. This period also coincides with the gradual emergence of new psychoactive substances (NPS). ‘‘Research chemicals’’, ‘‘bath salts’’, or ‘‘legal highs’’ are other terms used for NPS which are usually sold via Internet websites [3]. Marketed in many different ways and forms, NPS use can be observed among many different user groups. Today, the global market for NPS continues to expand and a growing number of NPS is reported each year throughout the world although significant differences between countries and regions [4,5]. Since 2011, XTC has made a comeback in festive settings [6]. Today, XTC has evolved in order to increase attractiveness for young people including 3D-shapes, bright colors, and updated logos (i.e. Nespresso, Bentley, Bugatti, Durex, Nintendo. . .). Moreover, increases of the masses of the tablet and the MDMA content per tablet have been reported [7]. For instance, since 2014, 41 % of the alert messages delivered by Eurotox in Belgium have been related to XTC. Among these data coming from Belgium, Netherlands, Spain and United Kingdom, 73 % reported a risk associated with high dosages
of MDMA and 27 % concerned tablets containing NPS instead of MDMA [5,8]. According to this evolution and to associated health risks, the French Monitoring Centre for Drugs and Drug Addiction (Observatoire franc ¸ais des drogues et toxicomanies [OFDT]) spearheaded a survey in order to evaluate the composition of XTC that is currently circulating in France. More than one hundred XTC were collected from users between December 2014 and May 2015. Twenty-one tablets have been received and analyzed in our laboratory. Each tablet was photographed, described, weighted and measured. After thin manual grinding using a mortar, one 10-mg-aliquot of each sample was solubilized in 1 mL of methanol, sonicated for 5 minutes, and, subsequently, 1:10,000 diluted in methanol: 100 L of the obtained solution were evaporated to dryness using nitrogen after internal standards addition (methyl-clonazepam and -OHethyltheophyllin). The obtained residue was reconstituted in 100 L of the mobile phase and then analyzed using liquid chromatography with high-resolution mass spectrometry detection (LC-HRMS) with a UPLC-Xevo G2 QTOF (Waters, Manchester, UK) system. The chromatographic separation was performed using an Acquity TM HSS C18 column (1.8 m, 2.1 × 150 mm) (Waters) with an oven temperature of 50 ◦ C and a mobile phase gradient consisting in ammonium formate buffer pH 3/acetonitrile in 0.1 % formic acid. Ionization and acquisition were performed in positive electrospray mode and using the MSE mode, respectively. The LC-HRMS device is controlled by MassLynxTM 4.1 software (Waters). Data process and quantitation were performed using ChromaLynxTM , TargetLynxTM associated softwares (Waters) using a homemade database of more than 1400 substances including MDMA [9]. The 21 XTC analyzed samples were visually high quality tablets with various shapes and bright colors. Logos can effectively be considered as attractive, including actual trademarks: Nespresso, Chupa Chups, UPS, Louis Vuitton, Rolls Royce, Superman, Mitsubishi, Spiderman. . . Seventeen tablets with an average weight of 321 mg (ranging from 196 to 514 mg) contained an average quantity of MDMA of 145 mg (ranging from 69 to 279 mg) what therefore means that the tablets contained 46 % of this substance (ranging from 22 to 72 %). No MDMA was found in 4 tablets: one contained meta-chlorophenylpiperazine (mCPP), two contained only acetaminophen, and no active substance was found in the last one.
http://dx.doi.org/10.1016/j.toxac.2016.09.003 2352-0078/© 2016 Soci´ et´ e Franc ¸aise de Toxicologie Analytique. Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Richeval C, et al. The comeback of Ecstasy: New designs and increased MDMA content. Toxicologie Analytique & Clinique (2016), http://dx.doi.org/10.1016/j.toxac.2016.09.003
+Model TOXAC-144; No. of Pages 2
ARTICLE IN PRESS
2
Letter to the editor
The analysis results of this sampling were in accordance with those obtained by the other laboratories involved in this survey and with the current observations made by the other European countries, in terms of marketing efforts and purity. Moreover, those results underlines the dramatically increase of the average amount of MDMA per tablet during the two past decades. In the 2000s, the value was around 50—60 mg per tablet, [10—12] whereas today it is more often around 145 mg and 125 mg per tablet respectively in the French and the European market. The increase of the MDMA amount is logically linked to the rise of the tablets weight but it has also been observed a slight increase of the concentrations since the beginning of the 21st century. Considering that there is a persistent number of tablets without MDMA or containing another substance as a NPS (4/21), this survey and the elements previously documented [5,13,14] show the great variability and the dynamism of the XTC market. By the way, they also interrogate how drug users adapt their habits considering those changes. Users often pretend that they can know the content and the purity of their tablets by comparing their macroscopic characteristics. That is why it is important to remind them that on the one hand, a batch of tablets has a short life on the market. On the other hand, ingredient proportions or cooking manners are likely to change from one production cycle to another. Even if two tablets are visually strongly similar, their compositions could be totally different. Their weight, the presence or not of scoring line are not reliable. The only way to know the ecstasy content is to analyze it. It is undoubtedly even more important to ease the access at such analyzing services during nightlife events, where users are likely to purchase and consume drugs.
Disclosure of interest The authors declare that they have no competing interest.
References [1] Bernard H. Drogues de synthèse, anciennes et nouvelles, utilisées aujourd’hui en milieux festifs. Thèse pour le diplôme d’état de Docteur en Pharmacie. Limoges; 2012. [2] Girard G, Boscher G. L’ecstasy, de l’engouement à la « ringardisation ». In: Coste JM, editor. Les usages de drogues illicites en France depuis 1999 vus au travers du dispositif TREND. Paris: OFDT; 2010. p. 96—105. [3] Welter-Luedeke J, Maurer HH. New psychoactive substances: chemistry, pharmacology, metabolism, and detectability of amphetamine derivatives with modified ring systems. Ther Drug Monit 2016;38:4—11.
[4] EMCDDA. New psychoactive substances in Europe. An update from the EU Early Warning System (March 2015). Luxembourg: European Union; 2015. [5] UNODC. World drug report 2015. New York: United Nations; 2015. [6] Cadet-Taïrou A, Gandilhon M, Lahaie E, Martinez M, Dambélé S, Saïd S. Marchés, substances, usagers : les tendances récentes (2011—2012). Observations au plan national du dispositif TREND en matière de psychotropes illicites ou détournés de leur usage. Tendances 2013;86:1—8. [7] Lahaie E, Martinez M, Cadet A. MDMA (poudre et comprimé) : composition et aspect. Note SINTES no 2013-03 du 6 novembre 2013. Saint-Denis: OFDT; 2013. [8] Consulted on website http://www.eurotox.org/alertes/ on February 2 2016. [9] Boumrah Y, Humbert L, Phanithavong M, Khimeche K, Dahmania A, Allorge D. In vitro characterization of potential CYP- and UGT-derived metabolites of the psychoactive drug 25B-NBOMe using LC-high resolution MS. Drug Test Anal 2016;8:248—526. [10] Giraudon I, Bello PY. Regards sur l’ecstasy et d’autres produits de synthèse en France. Paris: OFDT; 2003. [11] Giraudon I, Bello PY. Monitoring ecstasy content in France: results from the National Surveillance System 1999—2004. Subst Use Misuse 2007;42(10):1567—78. [12] Lahaie E. Enquête SINTES 2009 sur la composition des produits de synthèse. Saint-Denis: OFDT; 2011. [13] UNODC. Global synthetic drugs assessment. Amphetamine-type stimulants and new psychoactive substances. New York: United Nations; 2014. [14] UNODC. World drug report 2016. New York: United Nations; 2016.
Camille Richeval a,b , Luc Humbert a , Thomas Nefau c , Magali Martinez c , Delphine Allorge a,b , Jean-Michel Gaulier a,b,∗ a
CHU de Lille, Unité Fonctionnelle de Toxicologie, 59000 Lille, France b Université de Lille, EA 4483—IMPECS—IMPact de l’Environnement Chimique sur la Santé humaine, 59000 Lille, France c Observatoire Franc ¸ais des Drogues et des Toxicomanies (OFDT), 93218 Saint-Denis-La-Plaine, France ∗ Corresponding author. Laboratory of Toxicology, CHRU, boulevard du Professeur-Jules-Leclercq, CS 70001, 59037 Lille cedex, France.
E-mail address: [email protected] (J.-M. Gaulier) Received 5 August 2016; received in revised form 16 September 2016; accepted 17 September 2016
Please cite this article in press as: Richeval C, et al. The comeback of Ecstasy: New designs and increased MDMA content. Toxicologie Analytique & Clinique (2016), http://dx.doi.org/10.1016/j.toxac.2016.09.003
ARTICLE IN PRESS
TOXAC-144; No. of Pages 2
Toxicologie Analytique & Clinique (2016) xxx, xxx—xxx
Disponible en ligne sur
ScienceDirect www.sciencedirect.com
LETTER TO THE EDITOR The comeback of Ecstasy: New designs and increased MDMA content To the editor Ecstasy (XTC), the tablet form of 3,4-methylenedioxymethamphetamine (MDMA), was popular, regarding its wide use and abuse, in the 1990s in the clubs and discotheques and even more in the techno free parties and underground nightlife events. Indeed, recreational XTC use is historically highly linked to the underground techno subculture, which was born in UK in the late 1980s during the second ‘‘summer of love’’, to such an extent that this movement was called ‘‘Ecstasy Culture’’. In the 2000s, changes in laws and regulations have altered the organization of festive techno space and, subsequently, the use of psychoactive drugs within it [1]. In 2008, the Cambodian authorities launched a largescale operation to destroy many Sassafras cultivation. As the safrole, one of the main precursors for the MDMA synthesis, comes from this shrub, these destructions led to an international shortage of MDMA. Consequently, pills sold for ecstasy often contained other molecules which sometimes led to side adverse effects. More and more, XTC gets a bad reputation, considered as a scam, and his popularity decreased. The real XTC became rarer and after the shortage, MDMA ‘‘crystal/rock’’ forms emerged on the market and were preferred by users owing to assessments of their high-purity [2]. This period also coincides with the gradual emergence of new psychoactive substances (NPS). ‘‘Research chemicals’’, ‘‘bath salts’’, or ‘‘legal highs’’ are other terms used for NPS which are usually sold via Internet websites [3]. Marketed in many different ways and forms, NPS use can be observed among many different user groups. Today, the global market for NPS continues to expand and a growing number of NPS is reported each year throughout the world although significant differences between countries and regions [4,5]. Since 2011, XTC has made a comeback in festive settings [6]. Today, XTC has evolved in order to increase attractiveness for young people including 3D-shapes, bright colors, and updated logos (i.e. Nespresso, Bentley, Bugatti, Durex, Nintendo. . .). Moreover, increases of the masses of the tablet and the MDMA content per tablet have been reported [7]. For instance, since 2014, 41 % of the alert messages delivered by Eurotox in Belgium have been related to XTC. Among these data coming from Belgium, Netherlands, Spain and United Kingdom, 73 % reported a risk associated with high dosages
of MDMA and 27 % concerned tablets containing NPS instead of MDMA [5,8]. According to this evolution and to associated health risks, the French Monitoring Centre for Drugs and Drug Addiction (Observatoire franc ¸ais des drogues et toxicomanies [OFDT]) spearheaded a survey in order to evaluate the composition of XTC that is currently circulating in France. More than one hundred XTC were collected from users between December 2014 and May 2015. Twenty-one tablets have been received and analyzed in our laboratory. Each tablet was photographed, described, weighted and measured. After thin manual grinding using a mortar, one 10-mg-aliquot of each sample was solubilized in 1 mL of methanol, sonicated for 5 minutes, and, subsequently, 1:10,000 diluted in methanol: 100 L of the obtained solution were evaporated to dryness using nitrogen after internal standards addition (methyl-clonazepam and -OHethyltheophyllin). The obtained residue was reconstituted in 100 L of the mobile phase and then analyzed using liquid chromatography with high-resolution mass spectrometry detection (LC-HRMS) with a UPLC-Xevo G2 QTOF (Waters, Manchester, UK) system. The chromatographic separation was performed using an Acquity TM HSS C18 column (1.8 m, 2.1 × 150 mm) (Waters) with an oven temperature of 50 ◦ C and a mobile phase gradient consisting in ammonium formate buffer pH 3/acetonitrile in 0.1 % formic acid. Ionization and acquisition were performed in positive electrospray mode and using the MSE mode, respectively. The LC-HRMS device is controlled by MassLynxTM 4.1 software (Waters). Data process and quantitation were performed using ChromaLynxTM , TargetLynxTM associated softwares (Waters) using a homemade database of more than 1400 substances including MDMA [9]. The 21 XTC analyzed samples were visually high quality tablets with various shapes and bright colors. Logos can effectively be considered as attractive, including actual trademarks: Nespresso, Chupa Chups, UPS, Louis Vuitton, Rolls Royce, Superman, Mitsubishi, Spiderman. . . Seventeen tablets with an average weight of 321 mg (ranging from 196 to 514 mg) contained an average quantity of MDMA of 145 mg (ranging from 69 to 279 mg) what therefore means that the tablets contained 46 % of this substance (ranging from 22 to 72 %). No MDMA was found in 4 tablets: one contained meta-chlorophenylpiperazine (mCPP), two contained only acetaminophen, and no active substance was found in the last one.
http://dx.doi.org/10.1016/j.toxac.2016.09.003 2352-0078/© 2016 Soci´ et´ e Franc ¸aise de Toxicologie Analytique. Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Richeval C, et al. The comeback of Ecstasy: New designs and increased MDMA content. Toxicologie Analytique & Clinique (2016), http://dx.doi.org/10.1016/j.toxac.2016.09.003
+Model TOXAC-144; No. of Pages 2
ARTICLE IN PRESS
2
Letter to the editor
The analysis results of this sampling were in accordance with those obtained by the other laboratories involved in this survey and with the current observations made by the other European countries, in terms of marketing efforts and purity. Moreover, those results underlines the dramatically increase of the average amount of MDMA per tablet during the two past decades. In the 2000s, the value was around 50—60 mg per tablet, [10—12] whereas today it is more often around 145 mg and 125 mg per tablet respectively in the French and the European market. The increase of the MDMA amount is logically linked to the rise of the tablets weight but it has also been observed a slight increase of the concentrations since the beginning of the 21st century. Considering that there is a persistent number of tablets without MDMA or containing another substance as a NPS (4/21), this survey and the elements previously documented [5,13,14] show the great variability and the dynamism of the XTC market. By the way, they also interrogate how drug users adapt their habits considering those changes. Users often pretend that they can know the content and the purity of their tablets by comparing their macroscopic characteristics. That is why it is important to remind them that on the one hand, a batch of tablets has a short life on the market. On the other hand, ingredient proportions or cooking manners are likely to change from one production cycle to another. Even if two tablets are visually strongly similar, their compositions could be totally different. Their weight, the presence or not of scoring line are not reliable. The only way to know the ecstasy content is to analyze it. It is undoubtedly even more important to ease the access at such analyzing services during nightlife events, where users are likely to purchase and consume drugs.
Disclosure of interest The authors declare that they have no competing interest.
References [1] Bernard H. Drogues de synthèse, anciennes et nouvelles, utilisées aujourd’hui en milieux festifs. Thèse pour le diplôme d’état de Docteur en Pharmacie. Limoges; 2012. [2] Girard G, Boscher G. L’ecstasy, de l’engouement à la « ringardisation ». In: Coste JM, editor. Les usages de drogues illicites en France depuis 1999 vus au travers du dispositif TREND. Paris: OFDT; 2010. p. 96—105. [3] Welter-Luedeke J, Maurer HH. New psychoactive substances: chemistry, pharmacology, metabolism, and detectability of amphetamine derivatives with modified ring systems. Ther Drug Monit 2016;38:4—11.
[4] EMCDDA. New psychoactive substances in Europe. An update from the EU Early Warning System (March 2015). Luxembourg: European Union; 2015. [5] UNODC. World drug report 2015. New York: United Nations; 2015. [6] Cadet-Taïrou A, Gandilhon M, Lahaie E, Martinez M, Dambélé S, Saïd S. Marchés, substances, usagers : les tendances récentes (2011—2012). Observations au plan national du dispositif TREND en matière de psychotropes illicites ou détournés de leur usage. Tendances 2013;86:1—8. [7] Lahaie E, Martinez M, Cadet A. MDMA (poudre et comprimé) : composition et aspect. Note SINTES no 2013-03 du 6 novembre 2013. Saint-Denis: OFDT; 2013. [8] Consulted on website http://www.eurotox.org/alertes/ on February 2 2016. [9] Boumrah Y, Humbert L, Phanithavong M, Khimeche K, Dahmania A, Allorge D. In vitro characterization of potential CYP- and UGT-derived metabolites of the psychoactive drug 25B-NBOMe using LC-high resolution MS. Drug Test Anal 2016;8:248—526. [10] Giraudon I, Bello PY. Regards sur l’ecstasy et d’autres produits de synthèse en France. Paris: OFDT; 2003. [11] Giraudon I, Bello PY. Monitoring ecstasy content in France: results from the National Surveillance System 1999—2004. Subst Use Misuse 2007;42(10):1567—78. [12] Lahaie E. Enquête SINTES 2009 sur la composition des produits de synthèse. Saint-Denis: OFDT; 2011. [13] UNODC. Global synthetic drugs assessment. Amphetamine-type stimulants and new psychoactive substances. New York: United Nations; 2014. [14] UNODC. World drug report 2016. New York: United Nations; 2016.
Camille Richeval a,b , Luc Humbert a , Thomas Nefau c , Magali Martinez c , Delphine Allorge a,b , Jean-Michel Gaulier a,b,∗ a
CHU de Lille, Unité Fonctionnelle de Toxicologie, 59000 Lille, France b Université de Lille, EA 4483—IMPECS—IMPact de l’Environnement Chimique sur la Santé humaine, 59000 Lille, France c Observatoire Franc ¸ais des Drogues et des Toxicomanies (OFDT), 93218 Saint-Denis-La-Plaine, France ∗ Corresponding author. Laboratory of Toxicology, CHRU, boulevard du Professeur-Jules-Leclercq, CS 70001, 59037 Lille cedex, France.
E-mail address: [email protected] (J.-M. Gaulier) Received 5 August 2016; received in revised form 16 September 2016; accepted 17 September 2016
Please cite this article in press as: Richeval C, et al. The comeback of Ecstasy: New designs and increased MDMA content. Toxicologie Analytique & Clinique (2016), http://dx.doi.org/10.1016/j.toxac.2016.09.003