New Psychoactive Substances (NPS) – a Challenge for the Addiction Treatment Services

Abstract

Over the last few years, hundreds of new psychoactive substances (NPS) have been identified in Europe. Apart from some herbal compounds, NPS mainly include synthetic cannabinoids and a range of new synthetic stimulants (e. g., cathinones). Synthetic NPS are often developed whilst modifying the basic chemical (e. g., phenethylamine or tryptamine) structure. Although the pharmacology and toxicology of most NPS are hardly known, they are being offered, especially online, as “bath salts,” as “incense mixtures,” or under other misleading labels. In addition, NPS are advertised as “legal highs,” suggesting that, in contrast to substances regulated by the national laws, trading with NPS is legal. Although only little is known about the prevalence of NPS use, some of these molecules may be associated with a range of severe adverse reactions. Indeed, different from cannabis, synthetic cannabinoid users may present with epileptic seizures, loss of consciousness, and a range of persisting psychopathological disorders. Future studies should inform better-tailored management strategies.

Key words

new psychoactive substances - internet - cathinones - synthetic cannabinoids - narcotics law

• References

• 1 EMCDDA . Annual Report 2011: The state of the drugs problem in Europe. Lisbon: Publication Office of the European Union; 2011
• 2 EMCDDA . European Drug Report 2013: Trends and developments. Lisbon: Publication Office of the European Union; 2013
• 3 EMCDDA . European Drug Report 2014: Trends and developments. Lisbon: Publication Office of the European Union; 2014
• 4 EMCDDA . European Drug Report 2015: Trends and developments. Lisbon: Publication Office of the European Union; 2015
• 5 EMCDDA . European Drug Report 2016: Trends and developments. Lisbon: Publication Office of the European Union; 2016
• 6 Schifano F, Orsolini L, Duccio Papanti G. et al. Novel psychoactive substances of interest for psychiatry. World Psychiatry. 2015; 14: 15-26
• 7 Baumann MH, Solis E, Watterson LR. et al. Baths salts, spice and related designer drugs: the science behind the headlines. J Neurosci. 2014; 34: 15150-15158
• 8 EMCDDA . New psychoactive substances in Europe – an update from the EU Early Warning System. Lisbon: Publication Office of the European Union; 2015
• 9 Hohmann N, Mikus G, Czock D. Wirkungen und Risiken neuartiger psychoaktiver Substanzen. Dtsch Arzteblatt Int 2014; 111: 139-147
• 10 Scherbaum N, Schifano F, Siemann H. New psychotropic drugs – “legal highs”. Fortschr Neurol Psychiatr 2014; 82: 532-543
• 11 Shulgin A, Shulgin A. PIHKAL – A Chemical Love Story. Berkeley: Transform Press; 1991
• 12 Luke DP, Terhune DB. The induction of synaesthesia with chemical agents: a systematic review. Front Psychol 2013; 4: 753
• 13 Rätsch C. Enzyklopädie der psychoaktiven Pflanzen. 9th ed. Aarau: AT-Verlag; 2009
• 14 Hadlock GC, Webb KM, McFadden LM. et al. 4-Methylmethcathinone (mephedrone): neuropharmacological effects of a designer stimulant of abuse. J Pharmacol Exp Ther. 2011; 339: 530-536
• 15 Spiller HA, Ryan ML, Weston RG. et al. Clinical experience with and analytical confirmation of “bath salts” and “legal highs” (synthetic cathinones) in the United States. Clin Toxicol (Phila) 2011; 49: 499-505
• 16 Thornton SL, Gerona RR, Tomaszewski CA. Psychosis from a bath salt product containing flephedrone and MDPV with serum, urine, and product quantification. J Med Toxicol 2012; 8: 310-313
• 17 Froberg BA, Levine M, Beuhler MC. et al. Acute methylenedioxypyrovalerone toxicity. J Med Toxicol 2015; 11: 185-194
• 18 Antonowicz JL, Metzger AK, Ramanujam SL. Paranoid psychosis induced by consumption of methylenedioxypyrovalerone: two cases. Gen Hosp Psychiatry 2011; 33: 640.e5-e6
• 19 Mangold AR, Bravo TP, Traub SJ. et al. Flashback phenomenon and residual neurological deficits after the use of “bath salt” 3,4-methylendioxypyrovalerone. World J Emerg Med 2014; 5: 63-66
• 20 Rasimas JJ. “Bath Salts” and the return of serotonin syndrome. J Clin Psychiatry 2012; 73: 1125-1127
• 21 Schifano F, Corkery J, Ghodse AH. Suspected and confirmed fatalities associated with mephedrone (4-methylmethcathinone, “meow meow”) in the United Kingdom. J Clin Psychopharmacol 2012; 32: 710-714
• 22 Barrios L, Grison-Hernando H, Boels D. et al. Death following ingestion of methylone. Int J Legal Med. 2016; 130: 381-385
• 23 Namera A, Urabe S, Saito T. et al. A fatal case of 3,4-methylendioxypyrovalerone poisoning: coexistence of alpha-pyrrolidinobutiophenone and alpha-pyrrolidinovalerophenone in blood and/or hair. Forensic Toxicol 2013; 31: 338-343
• 24 Shulgin A, Shulgin A. TiHKAL – The Continuation. Berkeley: Transform Press; 1997
• 25 Corkery JM, Durkin E, Elliot S. et al. The recreational tryptamine 5-MeO-DALT (N,N-diallyl-5-methoxytryptamine): a brief review. Prog Neuropsychopharmacol Biol Psychiatry 2012; 39: 259-262
• 26 Schifano F, Papanti GD, Orsolini L. et al. Novel psychoactive substances: the pharmacology of stimulants and hallucinogens. Expert Rev Clin Pharmacol 2016; 9: 943-954
• 27 Bonnet U, Mahler H. Synthetic cannabinoids: spread, addiction biology & current perspective of personal health hazard. Fortschr Neurol Psychiatr 2015; 83: 221-231
• 28 Atwood BK, Huffman J, Straiker A. et al. JWH018, a common constituent of “Spice” herbal blends, is a potent and efficacious cannabinoids CB1 receptor agonist. Br J Pharmacol 2010; 10: 585-593
• 29 Werse B, Morgenstern C. The trend points towards pure substances – changes in the use of “legal highs”/new psychoactive substances (NPS) based on the results of 2 online surveys. Suchttherapie 2015; 16: 36-41
• 30 De Luca MA, Castelli MP, Porcu A. et al. Native CB1 receptor affinity, intrinsic activity, and accumbens shell dopamine stimulant properties of third generation Spice/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 AND STS-135. Neuropharmacology 2016; 105: 630-638
• 31 Mir A, Obafemi A, Young A. et al. Myocardial infarction associated with the synthetic cannabinoid K2. Pediatrics 2011; 128: e1622-e1627
• 32 Hermanns-Clausen M, Kneisel S, Szabo B. et al. Acute toxicity due to comfirmed consumption of synthetic cannabinoids: clinical and laboratory findings. Addiction 2012; 108: 534-544
• 33 Hurst D, Loeffler G, McLay R. Psychosis associated with synthetic cannabinoid agonists: a case series. Am J Psychiatry 2011; 168: 1119
• 34 Zimmermann US, Winkelmann PR, Pilhatsch M. et al. Withdrawal phenomena and dependence syndrome after the consumption of “Spice Gold.”. Dtsch Arztebl Int 2009; 106: 464-467
• 35 Niesink RJ, van Laar MW. Does cannabidiol protect against adverse psychological effects of THC?. Front Psychiatry 2013; 4: 130
• 36 Papanti GD, Orsolini L, Francesconi G. et al. “Noids” in a nutshell: everything you (don’t) want to know about synthetic cannabimimetics. Adv Dual Diagn 2014; 7: 137-148
• 37 Graziano S, Orsolini L, Rotolo MC et al. Herbal highs: review on psychoactive effects and neuropharmacology. Curr Neuropharmacol 2016, Oct 31 [Epub ahead of print]
• 38 Siemann H, Specka M, Schifano F. et al. Salvia Divinorum – Präsenz einer neuen Droge im Internet. Gesundheitswesen 2016; 68: 323-327
• 39 Corazza O, Schifano F, Farre M. et al. Designer drugs on the internet: a phenomenon out-of-control? The emergence of hallucinogenic drug Bromo-Dragonfly. Curr Clin Pharmacol 2011; 6: 125-129
• 40 Coppola M, Mondola R. A new stimulant of abuse: 5-(2-aminopropyl)-indole. Am J Psychiatry 2013; 170: 226
• 41 Sainsbury PD, Kicman AT, Archer RP. et al. Aminoindanes – the next wave of “legal highs”?. Drug Test Anal 2011; 3: 479-482
• 42 Linsen F, Koning RP, van Laar M. et al. 4-fluoroamphetamine in the Netherlands: more than a one-night stand. Addiction 2015; 110: 1138-1143
• 43 Ávila Escribano JJ, Sánchez Barba M, Álvarez Pedrero A. et al. Predictive capacity of Cloninger’s temperament and character inventory (TCI-R) in alcohol use disorder outcomes. Adicciones 2016; 28: 136-143
• 44 EMCDDA . New psychoactive substances in Europe. Lisbon: Publication Office of the European Union; 2016
• 45 EU Court. Judgment of the Court (Fourth Chamber) of 10 July 2014. Criminal proceedings against Markus D. (C-358/13) and G. (C-181/14). Available from: http://curia.europa.eu/juris/document/document.jsf?docid = 154827&doclang = EN
• 46 Neue-psychoaktive-Stoffe-Gesetz. https://www.bundesregierung.de
• 47 Psychoactive Substances Act. http://www.legislation.gov.uk
• 48 Gomes de Matos E, Atzendorf J, Kraus L. et al. Substanzkonsum in der Allgemeinbevölkerung in Deutschland. Sucht 2016; 62: 271-281
• 49 Pabst A, Kraus L, Gomes de Matos E. et al. Substanzkonsum und substanzbezogene Störungen im Jahr 2012. Sucht 2013; 59: 321-331
• 50 Orth B. Die Drogenaffinität Jugendlicher in der Bundesrepublik Deutschland 2015. Rauchen, Alkoholkonsum und Konsum illegaler Drogen: aktuelle Verbreitung und Trends. BZgA-Forschungsbericht. Köln: Bundeszentrale für gesundheitliche Aufklärung; 2016
• 51 Weaver MF, Schnoll SH. Hallucinogens and club drugs. In: Galanter M, Kleber HD. (eds.). Textbook of Substance Abuse Treatment. 4th ed. Arlington: American Psychiatric Publishing; 2008: 191-200
• 52 Dirks H, Esser S, Borgmann R. et al. Substance use and sexual risk behaviour among HIV-positive men who have sex with men in specialized out-patient clinics. HIV Med 2012; 13: 533-540
• 53 Härtel-Petri R. Illegale Drogen – “Crystal Meth”: Enormes Suchtpotenzial. Dtsch Arztebl Int 2014; 111: 638-640
• 54 Dart RC, Surratt HL, Cicero TJ. et al. Trends in opioid analgesic abuse and mortality in the United States. N Engl J Med 2015; 372: 241-248
• 55 Schubert I, Ihle P, Sabatowski R. Zunahme der Opioidverordnungen in Deutschland zwischen 2000 und 2010. Dtsch Arztebl Int 2013; 110: 45-51
• 56 Spina SP, Taddei A. Teenagers with Jimson weed (Datura stramonium) poisoning. CJEM 2007; 9: 467-468
• 57 Nutt D, King LA, Saulsbury W. et al. Development of a rational scale to assess the harm of drugs of potential misuse. Lancet 2007; 369: 1047-1053
• 58 Simonato P, Corazza O, Santonastaso P. et al. Novel psychoactive substances as a novel challenge for health professionals: results from an Italian survey. Hum Psychopharmacol 2013; 28: 324-331
• 59 Lieb M, Bader M, Palm U. et al. Ketamininduzierte Vesikopathie. Psychiatr Praxis 2012; 39: 43-45
• 60 Orsolini L, St John-Smith P, McQueen D et al. Evolutionary considerations on the emerging subculture of the e-psychonauts and the novel psychoactive substances: a comeback to the shamanism? Curr Neuropharmacol 2016, Nov 11 [Epub ahead of print]
• 61 EMCDDA. Drug profiles. http://www.emcdda.europa.eu/publications/drug-profiles
• 62 UNODC. Early warning advisory on new psychoactive substances. http://www.unodc.org
• 63 Drugcom. http://www.drugcom.de
• 64 NEPTUNE. Guidance on the clinical management of acute and chronic harms of club drugs and novel psychoactive substances. The Health Foundation. 2016; Available from: http://neptune-clinical-guidance.co.uk/wp-content/uploads/2015/03/NEPTUNE-Guidance-March-2015.pdf
• 65 Ninnemann AL, Lechner WV, Borges A. et al. Synthetic cannabinoids to avoid urine drug screens: implications for contingency management and other treatments for drug dependence. Addict Behav 2016; 63: 72-73
• 66 Dresen S, Ferreiros N, Pütz M. et al. Monitoring of herbal mixtures potentially containing synthetic cannabinoids as psychoactive compounds. J Mass Spectrom 2010; 45: 1186-1194
• 67 Borg D, Tverdovsky A, Stripp R. A fast and comprehensive analysis of 32 synthetic cannabinoids using agilent triple quadrupole LC-MS-MS. J Anal Toxicol 2017; 41: 6-16
• 68 Kyriakou C, Pellegrini M, García-Algar O et al. Recent trends in analytical methods to determine new psychoactive substances in hair. Curr Neuropharmacol 2016, Nov 11 [Epub ahead of print]
• 69 Regan L, Mitchelson M, MacDonald C. Mephedrone toxicity in a Scottish emergency department. Emerg Med J 2011; 28: 1055-1058
• 70 EMCDDA . Hospital emergency presentations and acute drug toxicity in Europe – update from the Euro-DEN Plus research group and the EMCDDA. Lisbon: Publications Office of the European Union; 2016