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Synthetic Cathinones: Neurotoxic Health Hazards and Potential for Abuse

  • Trevor Archer
  • Richard M. Kostrzewa
Chapter
First Online:
Part of the Current Topics in Neurotoxicity book series (Current Topics Neurotoxicity, volume 12)

Abstract

Synthetic cathinones (SCs) represent an alternative to the prevailing array of drugs of abuse, with this being attributable to a variety of factors pertaining to reward/reinforcement potency, apparent but not necessarily lower toxicity risk, and easy access in “alternative” marketplaces. SCs retain distinctive neuropharmacological profiles and the induction of a disparate behavioral spectrum relating to locomotor activity, learning effectiveness, anxiety, thermoregulation, and abuse liability.

Keywords

Synthetic cathinones Reward Self-administration Neurotoxicity Health hazards 
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References

  1. Aarde SM, Huang PK, Creehan KM et al (2013) The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: self-administration and locomotor activity in rats. Neuropharmacology 71:130–140.  https://doi.org/10.1016/j.neuropharm.2013.04.003CrossRefPubMedPubMedCentralGoogle Scholar
  2. Aarde SM, Taffe MA (2017) Predicting the abuse liability of entactogen-class, new and emerging psychoactive substances via preclinical models of drug self-administration. Curr Top Behav Neurosci 32:145–164.  https://doi.org/10.1007/7854_2016_54
  3. Adamowicz P, Zuba D, Byrska B (2014) Fatal intoxication with 3-methyl-N-methylcathinone (3-MMC) and 5-(2-aminopropyl)benzofuran (5-APB). Forensic Sci Int 245:126–132.  https://doi.org/10.1016/j.forsciint.2014.10.016CrossRefPubMedGoogle Scholar
  4. Alfaifi H, Abdelwahab SI, Mohan S et al (2017) Catha edulis Forsk. (Khat): evaluation of its antidepressant-like activity. Pharmacogn Mag 13(Suppl 2):S354–S358.  https://doi.org/10.4103/pm.pm_442_16
  5. Alvarez JC, Fabresse N, Larabi IA (2017) Prevalence and surveillance of synthetic cathinones use by hair analysis: an update review. Curr Pharm Des.  https://doi.org/10.2174/1381612823666170704124156CrossRefPubMedGoogle Scholar
  6. Angoa-Pérez M, Anneken JH, Kuhn DM (2017) Neurotoxicology of synthetic cathinone analogs. Curr Top Behav Neurosci 32:209–230.  https://doi.org/10.1007/7854_2016_21CrossRefPubMedGoogle Scholar
  7. Assi S, Gulyamova N, Ibrahim K et al (2017) Profile, effects, and toxicity of novel psychoactive substances: a systematic review of quantitative studies. Hum Psychopharmacol 32(3).  https://doi.org/10.1002/hup.2607CrossRefGoogle Scholar
  8. Awadalla NJ, Suwaydi HA (2017) Prevalence, determinants and impacts of khat chewing among professional drivers in Southwestern Saudi Arabia. East Mediterr Health J 23(3):189–197CrossRefGoogle Scholar
  9. Barrios L, Grison-Hernando H, Boels D et al (2016) Death following ingestion of methylone. Int J Legal Med 130(2):381–385.  https://doi.org/10.1007/s00414-015-1212-4CrossRefPubMedGoogle Scholar
  10. Baumann MH, Bukhari MO, Lehner KR et al (2017) Neuropharmacology of 3,4-methylenedioxypyrovalerone (MDPV), its metabolites, and related analogs. Curr Top Behav Neurosci 32:93–117.  https://doi.org/10.1007/7854_2016_53CrossRefPubMedPubMedCentralGoogle Scholar
  11. Byrska B, Stanaszek R, Zuba D (2017) Alpha-PVP as an active component of herbal highs in Poland between 2013 and 2015. Drug Test Anal 9(8):1267–1274.  https://doi.org/10.1002/dta.2151CrossRefPubMedGoogle Scholar
  12. Dolengevich-Segal H, Rodríguez-Salgado B, Gómez-Arnau J, Sánchez-Mateos D (2016) Severe psychosis, drug dependence, and hepatitis C related to slamming mephedrone. Case Rep Psychiatry 2016:8379562.  https://doi.org/10.1155/2016/8379562CrossRefPubMedPubMedCentralGoogle Scholar
  13. Drug Enforcement Administration, Department of Justice (2014a) Schedules of controlled substances: temporary placement of 10 synthetic cathinones into Schedule I, Final Order. Fed Regist 79:12938–12943Google Scholar
  14. Drug Enforcement Administration, Department of Justice (2014b) Schedules of controlled substances: extension of temporary placement of 10 synthetic cathinones into Schedule I of the Controlled Substances Act. Final order. Fed Regist 81:11429–11431Google Scholar
  15. Gannon BM, Galindo KI, Mesmin MP et al (2017a) Relative reinforcing effects of second-generation synthetic cathinones: acquisition of self-administration and fixed ratio dose-response curves in rats. Neuropharmacology. pii: S0028–3908(17)30385–4.  https://doi.org/10.1016/j.neuropharm.2017.08.018
  16. Gannon BM, Galindo KI, Rice KC, Collins GT (2017b) Individual differences in the relative reinforcing effects of 3,4-methylenedioxypyrovalerone under fixed and progressive ratio schedules of reinforcement in rats. J Pharmacol Exp Ther 361(1):181–189.  https://doi.org/10.1124/jpet.116.239376CrossRefPubMedPubMedCentralGoogle Scholar
  17. Giannotti G, Canazza I, Caffino L et al (2017) The cathinones MDPV and α-PVP elicit different behavioral and molecular effects following acute exposure. Neurotox Res.  https://doi.org/10.1007/s12640-017-9769-yCrossRefPubMedGoogle Scholar
  18. Glennon RA, Dukat M (2017) Structure-activity relationships of synthetic cathinones. Curr Top Behav Neurosci 32:19–47.  https://doi.org/10.1007/7854_2016_41CrossRefPubMedPubMedCentralGoogle Scholar
  19. Grapp M, Kaufmann C, Ebbecke M (2017) Toxicological investigation of forensic cases related to the designer drug 3,4-methylenedioxypyrovalerone (MDPV): detection, quantification and studies on human metabolism by GC-MS. Forensic Sci Int 273:1–9.  https://doi.org/10.1016/j.forsciint.2017.01.021CrossRefPubMedGoogle Scholar
  20. Gray R, Bressington D, Hughes E, Ivanecka A (2016) A systematic review of the effects of novel psychoactive substances ‘legal highs’ on people with severe mental illness. J Psychiatr Ment Health Nurs 23(5):267–281.  https://doi.org/10.1111/jpm.12297CrossRefPubMedGoogle Scholar
  21. Grecco GG, Kisor DF, Magura JS, Sprague JE (2017) Impact of common clandestine structural modifications on synthetic cathinone “bath salt” pharmacokinetics. Toxicol Appl Pharmacol 328:18–24.  https://doi.org/10.1016/j.taap.2017.05.010CrossRefPubMedGoogle Scholar
  22. Guirguis A, Corkery JM, Stair JL et al (2017) Intended and unintended use of cathinone mixtures. Hum Psychopharmacol 32(3).  https://doi.org/10.1002/hup.2598
  23. Hayashi K, Wakabayashi C, Ikushima Y, Tarui M (2017) High prevalence of quasi-legal psychoactive substance use among male patients in HIV care in Japan: a cross-sectional study. Subst Abuse Treat Prev Policy 12(1):11.  https://doi.org/10.1186/s13011-017-0097-2CrossRefPubMedPubMedCentralGoogle Scholar
  24. Huskinson SL, Naylor JE, Townsend EA et al (2017) Self-administration and behavioral economics of second-generation synthetic cathinones in male rats. Psychopharmacology 234(4):589–598.  https://doi.org/10.1007/s00213-016-4492-6CrossRefPubMedGoogle Scholar
  25. Katz DP, Bhattacharya D, Bhattacharya S et al (2014) Synthetic cathinones: “a khat and mouse game”. Toxicol Lett 229(2):349–356.  https://doi.org/10.1016/j.toxlet.2014.06.02CrossRefPubMedGoogle Scholar
  26. King HE, Riley AL (2017) The affective properties of synthetic cathinones: role of reward and aversion in their abuse. Curr Top Behav Neurosci 32:165–181.  https://doi.org/10.1007/7854_2016_32CrossRefPubMedGoogle Scholar
  27. Lantz SM, Rosas-Hernandez H, Cuevas E et al (2017) Monoaminergic toxicity induced by cathinone phthalimide: an in vitro study. Neurosci Lett 655:76–81.  https://doi.org/10.1016/j.neulet.2017.06.059CrossRefPubMedGoogle Scholar
  28. Matthews A, Sutherland R, Peacock A et al (2017) I like the old stuff better than the new stuff? Subjective experiences of new psychoactive substances. Int J Drug Policy 40:44–49.  https://doi.org/10.1016/j.drugpo.2016.11.004CrossRefPubMedGoogle Scholar
  29. Matsuta S, Shima N, Kamata H et al (2015) Metabolism of the designer drug α-pyrrolidinobutiophenone (α-PBP) in humans: identification and quantification of the phase I metabolites in urine. Forensic Sci Int 249:181–188.  https://doi.org/10.1016/j.forsciint.2015.02.004CrossRefPubMedGoogle Scholar
  30. Mekonen T, Fekadu W, Mekonnen TC, Workie SB (2017) Substance use as a strong predictor of poor academic achievement among university students. Psychiatry J. 2017:7517450.  https://doi.org/10.1155/2017/7517450CrossRefPubMedPubMedCentralGoogle Scholar
  31. Miller B, Kim J, Concheiro M (2017) Stability of synthetic cathinones in oral fluid samples. Forensic Sci Int 274:13–21.  https://doi.org/10.1016/j.forsciint.2016.11.034CrossRefPubMedGoogle Scholar
  32. Nakajima M, Molla K, Belachew B et al (2017) Khat use is associated with tobacco, alcohol, and illicit drug use: a cross-sectional examination in the United States. J Psychoactive Drugs 49(5):413–419.  https://doi.org/10.1080/02791072.2017.1342155CrossRefPubMedGoogle Scholar
  33. Naylor JE, Freeman KB, Blough BE et al (2015) Discriminative-stimulus effects of second generation synthetic cathinones in methamphetamine-trained rats. Drug Alcohol Depend 149:280–284.  https://doi.org/10.1016/j.drugalcdep.2015.02.002CrossRefPubMedPubMedCentralGoogle Scholar
  34. Nguyen JD, Aarde SM, Cole M et al (2016) Locomotor stimulant and rewarding effects of inhaling methamphetamine, MDPV, and mephedrone via electronic cigarette-type technology. Neuropsychopharmacology 41(11):2759–2771.  https://doi.org/10.1038/npp.2016.88CrossRefPubMedPubMedCentralGoogle Scholar
  35. Palamar JJ, Acosta P, Sherman S et al (2016) Self-reported use of novel psychoactive substances among attendees of electronic dance music venues. Am J Drug Alcohol Abuse 42(6):624–632.  https://doi.org/10.1080/00952990.2016.1181179CrossRefPubMedPubMedCentralGoogle Scholar
  36. Palamar JJ, Acosta P, Calderón FF et al (2017a) Assessing self-reported use of new psychoactive substances: the impact of gate questions. Am J Drug Alcohol Abuse 43(5):609–617.  https://doi.org/10.1080/00952990.2017.1322094CrossRefPubMedGoogle Scholar
  37. Palamar JJ, Acosta P, Cleland CM (2017b) Attitudes and beliefs about new psychoactive substance use among electronic dance music party attendees. Subst Use Misuse 1–10.  https://doi.org/10.1080/10826084.2017.1327980
  38. Palamar JJ, Salomone A, Gerace E et al (2017c) Hair testing to assess both known and unknown use of drugs amongst ecstasy users in the electronic dance music scene. Int J Drug Policy 48:91–98.  https://doi.org/10.1016/j.drugpo.2017.07.010CrossRefPubMedGoogle Scholar
  39. Papaseit E, Moltó J, Muga R et al (2017) Clinical pharmacology of the synthetic cathinone mephedrone. Curr Top Behav Neurosci 32:313–331.  https://doi.org/10.1007/7854_2016_61CrossRefPubMedGoogle Scholar
  40. Piacentino D, Kotzalidis GD, Longo L et al (2017) Body image and eating disorders are common among professional and amateur athletes using performance and image enhancing drugs: a cross-sectional study. J Psychoactive Drugs 49(5):373–384.  https://doi.org/10.1080/02791072.2017.1359708CrossRefPubMedGoogle Scholar
  41. Pourmand A, Mazer-Amirshahi M, Chistov S et al (2018) Designer drugs: review and implications for emergency management. Hum Exp Toxicol 37(1):94–101.  https://doi.org/10.1177/0960327117698542CrossRefPubMedGoogle Scholar
  42. Romanek K, Stenzel J, Schmoll S et al (2017) Synthetic cathinones in Southern Germany—characteristics of users, substance-patterns, co-ingestions, and complications. Clin Toxicol (Phila) 55(6):573–578.  https://doi.org/10.1080/15563650.2017.1301463CrossRefGoogle Scholar
  43. Salomone A, Palamar JJ, Gerace E et al (2017) Hair testing for drugs of abuse and new psychoactive substances in a high-risk population. J Anal Toxicol 41(5):376–381.  https://doi.org/10.1093/jat/bkx020CrossRefPubMedGoogle Scholar
  44. Schifano F, Orsolini L, Papanti D, Corkery J (2017) NPS: medical consequences associated with their intake. Curr Top Behav Neurosci 32:351–380.  https://doi.org/10.1007/7854_2016_15CrossRefPubMedGoogle Scholar
  45. Schifano F, Papanti GD, Orsolini L, Corkery JM (2016) Novel psychoactive substances: the pharmacology of stimulants and hallucinogens. Expert Rev Clin Pharmacol 9(7):943–954.  https://doi.org/10.1586/17512433.2016.1167597CrossRefPubMedGoogle Scholar
  46. Schmoll S, Romanek K, Stich R et al (2017) An internet-based survey of 96 German-speaking users of “bath salts”: frequent complications, risky sexual behavior, violence, and delinquency. Clin Toxicol (Phila).  https://doi.org/10.1080/15563650.2017.1353094CrossRefGoogle Scholar
  47. Simmler LD, Liechti ME (2017) Interactions of cathinone NPS with human transporters and receptors in transfected cells. Curr Top Behav Neurosci 32:49–72.  https://doi.org/10.1007/7854_2016_20CrossRefPubMedGoogle Scholar
  48. Simmler LD, Rickli A, Hoener MC, Liechti ME (2014) Monoamine transporter and receptor interaction profiles of a new series of designer cathinones. Neuropharmacology 152–160.  https://doi.org/10.1016/j.neuropharm.2013.11.008CrossRefGoogle Scholar
  49. Simmons SJ, Gregg RA, Tran FH et al (2016) Comparing rewarding and reinforcing properties between ‘bath salt’ 3,4-methylenedioxypyrovalerone (MDPV) and cocaine using ultrasonic vocalizations in rats. Addict Biol.  https://doi.org/10.1111/adb.12479CrossRefPubMedGoogle Scholar
  50. Smith KE, Bunting AM, Staton M et al (2017) Examination of synthetic cannabinoid and cathinone use among a drug-using offender sample, 2013–2015. J Psychoactive Drugs 49(5):436–445.  https://doi.org/10.1080/02791072.2017.1361560CrossRefPubMedGoogle Scholar
  51. Stanciu CN, Penders TM, Gnanasegaram SA et al (2017) The behavioral profile of methylenedioxypyrovalerone (MDPV) and α-pyrrolidinopentiophenone (PVP)—a systematic review. Curr Drug Abuse Rev.  https://doi.org/10.2174/1874473710666170321122226CrossRefPubMedGoogle Scholar
  52. Stogner JM, Miller BL (2013) Investigating the ‘bath salt’ panic: the rarity of synthetic cathinone use among students in the United States. Drug Alcohol Rev 32(5):545–549.  https://doi.org/10.1111/dar.12055CrossRefPubMedGoogle Scholar
  53. Styszko K, Dudarska A, Zuba D (2016) The presence of stimulant drugs in wastewater from Krakow (Poland): a snapshot. Bull Environ Contam Toxicol 97(3):310–315.  https://doi.org/10.1007/s00128-016-1869-5CrossRefPubMedPubMedCentralGoogle Scholar
  54. Sutherland R, Bruno R, Peacock A et al (2017) Motivations for new psychoactive substance use among regular psychostimulant users in Australia. Int J Drug Policy 43:23–32.  https://doi.org/10.1016/j.drugpo.2016.12.021CrossRefPubMedPubMedCentralGoogle Scholar
  55. Valente MJ, Araújo AM, Silva R et al (2016) 3,4-Methylenedioxypyrovalerone (MDPV): in vitro mechanisms of hepatotoxicity under normothermic and hyperthermic conditions. Arch Toxicol 90(8):1959–1973.  https://doi.org/10.1007/s00204-015-1653-zCrossRefPubMedGoogle Scholar
  56. Watterson LR, Olive MF (2017) Reinforcing effects of cathinone NPS in the intravenous drug self-administration paradigm. Curr Top Behav Neurosci 32:133–143.  https://doi.org/10.1007/7854_2016_33CrossRefPubMedGoogle Scholar
  57. Wojcieszak J, Andrzejczak D, Woldan-Tambor A, Zawilska JB (2016) Cytotoxic activity of pyrovalerone derivatives, an emerging group of psychostimulant designer cathinones. Neurotox Res 30(2):239–250.  https://doi.org/10.1007/s12640-016-9640-6CrossRefPubMedGoogle Scholar
  58. Xu P, Qiu Y, Zhang Y et al (2016) The effects of 4-methylethcathinone on conditioned place preference, locomotor sensitization, and anxiety-like behavior: a comparison with methamphetamine. Int J Neuropsychopharmacol 19(4). pii: pyv120.  https://doi.org/10.1093/ijnp/pyv120CrossRefGoogle Scholar
  59. Zona LC, Grecco GG, Sprague JE (2016) Cooling down the bath salts: carvedilol attenuation of methylone and mephedrone mediated hyperthermia. Toxicol Lett 263:11–15.  https://doi.org/10.1016/j.toxlet.2016.10.012CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PsychologyUniversity of GothenburgGothenburgSweden
  2. 2.Department of Biomedical SciencesQuillen College of Medicine, East Tennessee State UniversityJohnson CityUSA

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