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Khat and synthetic cathinones: a review

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Abstract

For centuries, ‘khat sessions’ have played a key role in the social and cultural traditions among several communities around Saudi Arabia and most East African countries. The identification of cathinone as the main psychoactive compound of khat leaves, exhibiting amphetamine-like pharmacological properties, resulted in the synthesis of several derivatives structurally similar to this so-called natural amphetamine. Synthetic cathinones were primarily developed for therapeutic purposes, but promptly started being misused and extensively abused for their euphoric effects. In the mid-2000’s, synthetic cathinones emerged in the recreational drug markets as legal alternatives (‘legal highs’) to amphetamine, ‘ecstasyʼ, or cocaine. Currently, they are sold as ‘bath salts’ or ‘plant foodʼ, under ambiguous labels lacking information about their true contents. Cathinone derivatives are conveniently available online or at ‘smartshops’ and are much more affordable than the traditional illicit drugs. Despite the scarcity of scientific data on these ‘legal highs’, synthetic cathinones use became an increasingly popular practice worldwide. Additionally, criminalization of these derivatives is often useless since for each specific substance that gets legally controlled, one or more structurally modified analogs are introduced into the legal market. Chemically, these substances are structurally related to amphetamine. For this reason, cathinone derivatives share with this drug both central nervous system stimulating and sympathomimetic features. Reports of intoxication and deaths related to the use of ‘bath salts’ have been frequently described over the last years, and several attempts to apply a legislative control on synthetic cathinones have been made. However, further research on their pharmacological and toxicological properties is fully required in order to access the actual potential harm of synthetic cathinones to general public health. The present work provides a review on khat and synthetic cathinones, concerning their historical background, prevalence, patterns of use, legal status, chemistry, pharmacokinetics, pharmacodynamics, and their physiological and toxicological effects on animals and humans.

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References

  • AAPCC (2013) American Association of Poison Control Centers: bath salts. Available in http://www.aapcc.org/alerts/bath-salts/

  • Aarde SM, Angrish D, Barlow DJ et al (2013a) Mephedrone (4-methylmethcathinone) supports intravenous self-administration in Sprague-Dawley and Wistar rats. Addict Biol 18(5):786–799. doi:10.1111/adb.12038

    Google Scholar 

  • Aarde SM, Huang PK, Creehan KM, Dickerson TJ, Taffe MA (2013b) The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: self-administration and locomotor activity in rats. Neuropharmacology 71:130–140. doi:10.1016/j.neuropharm.2013.04.003

    CAS  PubMed  Google Scholar 

  • Adebamiro A, Perazella MA (2012) Recurrent acute kidney injury following bath salts intoxication. Am J Kidney Dis Off J Natl Kidney Found 59(2):273–275. doi:10.1053/j.ajkd.2011.10.012

    Google Scholar 

  • Alem A, Kebede D, Kullgren G (1999) The prevalence and socio-demographic correlates of khat chewing in Butajira, Ethiopia. Acta Psychiatr Scand Suppl 397:84–91. doi:10.1111/j.1600-0447.1999.tb10699.x

    CAS  PubMed  Google Scholar 

  • Al-Habori M (2005) The potential adverse effects of habitual use of Catha edulis (khat). Expert Opin Drug Saf 4(6):1145–1154. doi:10.1517/14740338.4.6.1145

    PubMed  Google Scholar 

  • Ali WM, Zubaid M, Al-Motarreb A et al (2010) Association of khat chewing with increased risk of stroke and death in patients presenting with acute coronary syndrome. Mayo Clin Proc 85(11):974–980. doi:10.4065/mcp.2010.0398

    PubMed  Google Scholar 

  • Alkadi HO, Noman MA, Al-Thobhani AK, Al-Mekhlafi FS, Raja a YA (2002) Clinical and experimental evaluation of the effect of khat-induced myocardial infarction. Saudi Med J 23(10):1195–1198

    PubMed  Google Scholar 

  • Al-Motarreb A, Baker K, Broadley KJ (2002) Khat: pharmacological and medical aspects and its social use in Yemen. Phytother Res 16(5):403–413. doi:10.1002/ptr.1106

    CAS  PubMed  Google Scholar 

  • Al-Motarreb A, Briancon S, Al-Jaber N et al (2005) Khat chewing is a risk factor for acute myocardial infarction: a case-control study. Br J Clin Pharmacol 59(5):574–581. doi:10.1111/j.1365-2125.2005.02358.x

    CAS  PubMed  Google Scholar 

  • Al-Motarreb A, Al-Habori M, Broadley KJ (2010) Khat chewing, cardiovascular diseases and other internal medical problems: the current situation and directions for future research. J Ethnopharmacol 132(3):540–548. doi:10.1016/j.jep.2010.07.001

    CAS  PubMed  Google Scholar 

  • Al-Mugahed L (2008) Khat chewing in Yemen: turning over a new leaf. Bull World Health Organ 86(10):741

    PubMed  Google Scholar 

  • Angoa-Pérez M, Kane MJ, Francescutti DM et al (2012) Mephedrone, an abused psychoactive component of ‘bath salts’ and methamphetamine congener, does not cause neurotoxicity to dopamine nerve endings of the striatum. J Neurochem 120(6):1097–1107. doi:10.1111/j.1471-4159.2011.07632.x

    PubMed Central  PubMed  Google Scholar 

  • Angoa-Pérez M, Kane MJ, Briggs DI et al (2013) Mephedrone does not damage dopamine nerve endings of the striatum, but enhances the neurotoxicity of methamphetamine, amphetamine, and MDMA. J Neurochem 125(1):102–110. doi:10.1111/jnc.12114

    Google Scholar 

  • Antonowicz JL, Metzger AK, Ramanujam SL (2011) Paranoid psychosis induced by consumption of methylenedioxypyrovalerone: two cases. General Hosp Psychiatry 33(6):640 e5–640 e6. doi:10.1016/j.genhosppsych.2011.04.010

    Google Scholar 

  • Archer RP (2009) Fluoromethcathinone, a new substance of abuse. Forensic Sci Int 185(1–3):10–20. doi:10.1016/j.forsciint.2008.11.013

    CAS  PubMed  Google Scholar 

  • Arunotayanun W, Gibbons S (2012) Natural product ‘legal highs’. Nat Prod Rep 29(11):1304–1316. doi:10.1039/c2np20068f

    CAS  PubMed  Google Scholar 

  • Balint EE, Falkay G, Balint GA (2009) Khat—a controversial plant. Wien Klin Wochenschr 121(19–20):604–614. doi:10.1007/s00508-009-1259-7

    PubMed  Google Scholar 

  • Banjaw MY, Miczek K, Schmidt WJ (2006) Repeated Catha edulis oral administration enhances the baseline aggressive behavior in isolated rats. J Neural Transm 113(5):543–556. doi:10.1007/s00702-005-0356-7

    CAS  PubMed  Google Scholar 

  • Baumann MH, Ayestas MA Jr, Partilla JS et al (2012) The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 37(5):1192–1203. doi:10.1038/npp.2011.304

    CAS  Google Scholar 

  • Baumann MH, Partilla JS, Lehner KR (2013a) Psychoactive “bath salts”: not so soothing. Eur J Pharmacol 698(1–3):1–5. doi:10.1016/j.ejphar.2012.11.020

    CAS  PubMed  Google Scholar 

  • Baumann MH, Partilla JS, Lehner KR et al (2013b) Powerful cocaine-like actions of 3,4-Methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive ‘bath salts’ products. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 38(4):552–562. doi:10.1038/npp.2012.204

    CAS  Google Scholar 

  • Belhadj-Tahar H, Sadeg N (2005) Methcathinone: a new postindustrial drug. Forensic Sci Int 153(1):99–101. doi:10.1016/j.forsciint.2005.04.023

    CAS  PubMed  Google Scholar 

  • Bentur Y, Bloom-Krasik A, Raikhlin-Eisenkraft B (2008) Illicit cathinone (“Hagigat”) poisoning. Clin Toxicol 46(3):206–210. doi:10.1080/15563650701517574

    CAS  Google Scholar 

  • Borek HA, Holstege CP (2012) Hyperthermia and multiorgan failure after abuse of “bath salts” containing 3,4-methylenedioxypyrovalerone. Ann Emerg Med 60(1):103–105. doi:10.1016/j.annemergmed.2012.01.005

    PubMed  Google Scholar 

  • Bossong MG, Van Dijk JP, Niesink RJ (2005) Methylone and mCPP, two new drugs of abuse? Addict Biol 10(4):321–323. doi:10.1080/13556210500350794

    CAS  PubMed  Google Scholar 

  • Boulanger-Gobeil C, St-Onge M, Laliberte M, Auger PL (2012) Seizures and hyponatremia related to ethcathinone and methylone poisoning. J Med Toxicol Off J Am Coll Med Toxicol 8(1):59–61. doi:10.1007/s13181-011-0159-1

    Google Scholar 

  • Brandt SD, Sumnall HR, Measham F, Cole J (2010a) Analyses of second-generation ‘legal highs’ in the UK: initial findings. Drug Test Anal 2(8):377–382. doi:10.1002/dta.155

    CAS  PubMed  Google Scholar 

  • Brandt SD, Sumnall HR, Measham F, Cole J (2010b) Second generation mephedrone. The confusing case of NRG-1. Bmj 341:c3564. doi:10.1136/bmj.c3564

  • Brandt SD, Wootton RC, De Paoli G, Freeman S (2010c) The naphyrone story: the alpha or beta-naphthyl isomer? Drug Test Anal 2(10):496–502. doi:10.1002/dta.185

    CAS  PubMed  Google Scholar 

  • Brandt SD, Freeman S, Sumnall HR, Measham F, Cole J (2011) Analysis of NRG ‘legal highs’ in the UK: identification and formation of novel cathinones. Drug Test Anal 3(9):569–575. doi:10.1002/dta.204

    CAS  PubMed  Google Scholar 

  • Brenneisen R, Geisshusler S, Schorno X (1986) Metabolism of cathinone to (−)-norephedrine and (−)-norpseudoephedrine. The Journal of pharmacy and pharmacology 38(4):298–300. doi:10.1111/j.2042-7158.1986.tb04571.x

    CAS  PubMed  Google Scholar 

  • Brenneisen R, Fisch HU, Koelbing U, Geisshusler S, Kalix P (1990) Amphetamine-like effects in humans of the khat alkaloid cathinone. Br J Clin Pharmacol 30(6):825–828. doi:10.1111/j.1365-2125.1990.tb05447.x

    CAS  PubMed  Google Scholar 

  • Bretteville-Jensen A, Tuv S, Bilgrei O, Fjeld B, Bachs L (2013) Synthetic cannabinoids and cathinones: prevalence and markets. Forensic Sci Rev 25:7–26

    Google Scholar 

  • Bronstein AC, Spyker DA, Cantilena LR, Jr., Green JL, Rumack BH, Dart RC (2011) 2010 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 28th annual report. Clinical toxicology 49(10):910–41 doi:10.3109/15563650.2011.635149

  • Bruno R, Matthews AJ, Dunn M et al (2012) Emerging psychoactive substance use among regular ecstasy users in Australia. Drug Alcohol Depend 124(1–2):19–25. doi:10.1016/j.drugalcdep.2011.11.020

    PubMed  Google Scholar 

  • Brunt TM, Poortman A, Niesink RJ, van den Brink W (2011) Instability of the ecstasy market and a new kid on the block: mephedrone. J Psychopharmacol 25(11):1543–1547. doi:10.1177/0269881110378370

    CAS  PubMed  Google Scholar 

  • Cameron KN, Kolanos R, Solis E Jr, Glennon RA, De Felice LJ (2013) Bath salts components mephedrone and methylenedioxypyrovalerone (MDPV) act synergistically at the human dopamine transporter. Br J Pharmacol 168(7):1750–1757. doi:10.1111/bph.12061

    CAS  PubMed  Google Scholar 

  • Canning H, Goff D, Leach MJ, Miller AA, Tateson JE, Wheatley PL (1979) The involvement of dopamine in the central actions of bupropion, a new antidepressant [proceedings]. Br J Pharmacol 66(1):104P–105P

    CAS  PubMed  Google Scholar 

  • Carbone PN, Carbone DL, Carstairs SD, Luzi SA (2013) Sudden cardiac death associated with methylone use. Am J Forensic Med Pathol 34(1):26–28. doi:10.1097/PAF.0b013e31827ab5da

    PubMed  Google Scholar 

  • Carhart-Harris RL, King LA, Nutt DJ (2011) A web-based survey on mephedrone. Drug Alcohol Depend 118(1):19–22. doi:10.1016/j.drugalcdep.2011.02.011

    CAS  PubMed  Google Scholar 

  • Carvalho F (2003) The toxicological potential of khat. J Ethnopharmacol 87(1):1–2

    PubMed  Google Scholar 

  • Carvalho M, Carmo H, Costa VM et al (2012) Toxicity of amphetamines: an update. Arch Toxicol 86(8):1167–1231. doi:10.1007/s00204-012-0815-5

    CAS  PubMed  Google Scholar 

  • Cawrse BM, Levine B, Jufer RA et al (2012) Distribution of methylone in four postmortem cases. J Anal Toxicol 36(6):434–439. doi:10.1093/jat/bks046

    CAS  PubMed  Google Scholar 

  • Chapman MH, Kajihara M, Borges G et al (2010) Severe, acute liver injury and khat leaves. N Engl J Med 362(17):1642–1644. doi:10.1056/NEJMc0908038

    CAS  PubMed  Google Scholar 

  • Clein LJ, Benady DR (1962) Case of diethylpropion addiction. Br Med J 2(5302):456

    CAS  PubMed Central  PubMed  Google Scholar 

  • Colosimo C, Guidi M (2009) Parkinsonism due to ephedrone neurotoxicity: a case report. Eur J Neurol Off J Eur Fed Neurol Soc 16(6):e114–e115. doi:10.1111/j.1468-1331.2009.02606.x

    CAS  Google Scholar 

  • Colzato LS, Ruiz MJ, van den Wildenberg WP, Hommel B (2011) Khat use is associated with impaired working memory and cognitive flexibility. PLoS ONE 6(6):e20602

    CAS  PubMed Central  PubMed  Google Scholar 

  • Coppola M, Mondola R (2012) Synthetic cathinones: chemistry, pharmacology and toxicology of a new class of designer drugs of abuse marketed as “bath salts” or “plant food”. Toxicol Lett 211(2):144–149. doi:10.1016/j.toxlet.2012.03.009

    CAS  PubMed  Google Scholar 

  • Corkery JM, Schifano F, Oyefeso A et al (2011) ‘Bundle of fun’or’bunch of problems’? Case series of khat-related deaths in the UK. Drugs Educ Prev Policy 18(6):408–425. doi:10.3109/09687637.2010.504200

    Google Scholar 

  • Council E (2010) 2010/759/EU: council Decision of 2 December 2010 on submitting 4-methylmethcathinone (mephedrone) to control measures. Off J Eur Union L 322:44–45

    Google Scholar 

  • Cox G, Rampes H (2003) Adverse effects of khat: a review. Adv Psychiatr Treat 9:456–463. doi:10.1192/apt.9.6.456

    Google Scholar 

  • Cozzi NV, Sievert MK, Shulgin AT, Jacob P 3rd, Ruoho AE (1999) Inhibition of plasma membrane monoamine transporters by beta-ketoamphetamines. Eur J Pharmacol 381(1):63–69. doi:10.1016/S0014-2999(99)00538-5

    CAS  PubMed  Google Scholar 

  • Cunningham GL (1963) Diethylpropion in the treatment of obesity. J Coll General Pract 6:347–349

    CAS  Google Scholar 

  • Dal Cason TA (1997) The characterization of some 3, 4-methylenedioxycathinone (MDCATH) homologs. Forensic Sci Int 87(1):9–53. doi:10.1016/S0379-0738(97)02133-6

    CAS  Google Scholar 

  • Dal Cason TA, Young R, Glennon RA (1997) Cathinone: an investigation of several N-alkyl and methylenedioxy-substituted analogs. Pharmacol Biochem Behav 58:1109–1116. doi:10.1016/S0091-3057(97)00323-7

    CAS  PubMed  Google Scholar 

  • Dargan PI, Albert S, Wood DM (2010) Mephedrone use and associated adverse effects in school and college/university students before the UK legislation change. QJM Mon J Assoc Phys 103(11):875–879. doi:10.1093/qjmed/hcq134

    CAS  Google Scholar 

  • Dargan PI, Sedefov R, Gallegos A, Wood DM (2011) The pharmacology and toxicology of the synthetic cathinone mephedrone (4-methylmethcathinone). Drug Test Anal 3(7–8):454–463. doi:10.1002/dta.312

    CAS  PubMed  Google Scholar 

  • Davies S, Wood DM, Smith G et al (2010) Purchasing ‘legal highs’ on the Internet–is there consistency in what you get? QJM Mon J Assoc Phys 103(7):489–493. doi:10.1093/qjmed/hcq056

    CAS  Google Scholar 

  • de Bie RM, Gladstone RM, Strafella AP, Ko JH, Lang AE (2007) Manganese-induced Parkinsonism associated with methcathinone (Ephedrone) abuse. Arch Neurol 64(6):886–889. doi:10.1001/archneur.64.6.886

    PubMed  Google Scholar 

  • Deluca P, Schifano F, Davey Z, Corazza O, Di Furia L, Group PWMR (2009a) MDPV Report. Available at http://www.psychonautproject.eu/

  • Deluca P, Schifano F, Davey Z, Corazza O, Di Furia L, Group PWMR (2009b) Mephedrone report. Available at http://www.psychonautproject.eu/

  • den Hollander B, Rozov S, Linden AM, Uusi-Oukari M, Ojanpera I, Korpi ER (2013) Long-term cognitive and neurochemical effects of “bath salt” designer drugs methylone and mephedrone. Pharmacol Biochem Behav 103(3):501–509. doi:10.1016/j.pbb.2012.10.006

    Google Scholar 

  • Deniker P, Loo H, Cuche H, Roux JM (1975) Abuse of pyrovalerone by drug addicts. Ann Med Psychol 2(4):745–748

    CAS  Google Scholar 

  • Derungs A, Schietzel S, Meyer MR, Maurer HH, Krahenbuhl S, Liechti ME (2011) Sympathomimetic toxicity in a case of analytically confirmed recreational use of naphyrone (naphthylpyrovalerone). Clin Toxicol 49(7):691–693. doi:10.3109/15563650.2011.592838

    CAS  Google Scholar 

  • Dhaifalah I, Santavy J (2004) Khat habit and its health effect. A natural amphetamine. Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia 148(1):11–15

  • Drug Enforcement Administration DoJ (1993a) Schedules of controlled substances: placement of cathinone and 2,5-dimethoxy-4-ethylamphetamine into schedule I. Fed Reg 58(9):4316–4318

    Google Scholar 

  • Drug Enforcement Administration DoJ (1993b) Schedules of controlled substances: temporary placement of cathine ((+)-norpseudoephedrine), fencamfamine, fenproporex and mefenorex into schedule IV. Fed Reg 53(95):17459–17460

    Google Scholar 

  • Drug Enforcement Administration DoJ (2011) Schedules of controlled substances: temporary placement of three synthetic cathinones in Schedule I. Final order. Fed Reg 76(204):65371–65375

    Google Scholar 

  • Drug Enforcement Administration DoJ (2012) Schedules of controlled substances: extension of temporary placement of methylone into schedule I of the controlled substances Act. Final order. Fed Reg 77(202):64032–64033

    Google Scholar 

  • EMCDDA (2011) The EMCDDA annual report 2011: the state of the drugs problem in Europe. Euro Surveill. doi:10.2810/44330. Available at http://www.emcdda.europa.eu/

  • EMCDDA (2012) The EMCDDA annual report 2012: the state of the drugs problem in Europe. Euro Surveill. doi:10.2810/64775. Available at http://www.emcdda.europa.eu/

  • EMCDDA-Europol (2009) EMCDDA–Europol 2008 annual report on the implementation of council decision 2005/387/JHA. Available at http://www.emcdda.europa.eu/

  • EMCDDA-Europol (2010) EMCDDA–Europol 2009 annual report on the implementation of council decision 2005/387/JHA. Available at http://www.emcdda.europa.eu/

  • EMCDDA-Europol (2011) EMCDDA–Europol 2010 annual report on the implementation of council decision 2005/387/JHA. Available at http://www.emcdda.europa.eu/

  • Emerson TS, Cisek JE (1993) Methcathinone: a Russian designer amphetamine infiltrates the rural midwest. Ann Emerg Med 22(12):1897–1903. doi:10.1016/S0196-0644(05)80419-6

    CAS  PubMed  Google Scholar 

  • Europol–EMCDDA (2010) Europol–EMCDDA Joint Report on a new psychoactive substance: 4-methylmethcathinone (mephedrone). Available at http://www.emcdda.europa.eu/

  • Falgiani M, Desai B, Ryan M (2012) “Bath salts” intoxication: a case report. Case Rep Emerg Med 2012:976314. doi:10.1155/2012/976314

    PubMed Central  PubMed  Google Scholar 

  • Fantegrossi WE, Gannon BM, Zimmerman SM, Rice KC (2013) In vivo effects of abused ‘bath salt’ constituent 3,4-methylenedioxypyrovalerone (MDPV) in mice: drug discrimination, thermoregulation, and locomotor activity. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 38(4):563–573. doi:10.1038/npp.2012.233

    CAS  Google Scholar 

  • Fasanmade A, Kwok E, Newman L (2007) Oral squamous cell carcinoma associated with khat chewing. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104(1):e53–e55. doi:10.1016/j.tripleo.2007.01.010

    PubMed  Google Scholar 

  • Fass JA, Fass AD, Garcia AS (2012) Synthetic cathinones (bath salts): legal status and patterns of abuse. Ann Pharmacother 46(3):436–441. doi:10.1345/aph.1Q628

    PubMed  Google Scholar 

  • Fay V, Eitel J (2013) High on the designer drug naphyrone: a case report of “bath salt” toxicity. Internet J Adv Nurs Pract 12(1)

  • Feyissa AM, Kelly JP (2008) A review of the neuropharmacological properties of khat. Prog Neuropsychopharmacol Biol Psychiatry 32(5):1147–1166. doi:10.1016/j.pnpbp.2007.12.033

    CAS  PubMed  Google Scholar 

  • Fluckiger FA, Gerock JE (1887) Contribution to the knowledge of catha leaves. Pharm J Transvaal 18:221–224

    Google Scholar 

  • Fröhlich S, Lambe E, O’Dea J (2011) Acute liver failure following recreational use of psychotropic “head shop” compounds. Ir J Med Sci 180(1):263–264. doi:10.1007/s11845-010-0636-6

    PubMed  Google Scholar 

  • Gardos G, Cole JO (1971) Evaluation of pyrovalerone in chronically fatigued volunteers. Curr Ther Res Clin Exp 13(10):631–635

    CAS  PubMed  Google Scholar 

  • Garrett G, Sweeney M (2010) The serotonin syndrome as a result of mephedrone toxicity. BMJ Case Rep 2010:1–5. doi:10.1136/bcr.04.2010.2925

  • Gershman JA, Fass AD (2012) Synthetic cathinones (‘bath salts’): legal and health care challenges. P & T Peer Rev J formul Manag 37(10):571–595

    Google Scholar 

  • Gezon LL (2012) Drug crops and food security: the effects of khat on lives and livelihoods in northern madagascar. Cult Agric Food Environ 34(2):124–135. doi:10.1111/j.2153-9561.2012.01072.x

    Google Scholar 

  • Giannini JA, Castellani S (1982) A manic-like psychosis due to khat catha edulis Forsk. Clin Toxicol 19(5):455–459

    Google Scholar 

  • Gibbons S, Zloh M (2010) An analysis of the ‘legal high’ mephedrone. Bioorg Med Chem Lett 20(14):4135–4139. doi:10.1016/j.bmcl.2010.05.065

    CAS  PubMed  Google Scholar 

  • Goldberg J, Gardos G, Cole JO (1973) A controlled evaluation of pyrovalerone in chronically fatigued volunteers. Int Pharmacopsychiatry 8(1):60–69

    CAS  PubMed  Google Scholar 

  • Goldstone MS (1993) ‘Cat’: methcathinone–a new drug of abuse. JAMA, J Am Med Assoc 269(19):2508

    CAS  Google Scholar 

  • Gorgaslidze AG, Saifullaeva MA, Kuz’mina MM, Golitsina LS, Smetnev AS (1993) Cardiac arrhythmia and myocardial contraction in opium and ephedrone addiction. Kardiologiia 33(1):14–16

    CAS  PubMed  Google Scholar 

  • Gorun G, Dermengiu D, Curcă C, Hostiuc S, Ioan B, Luta V (2010) Toxicological drivers issues in “legal highs” use. Romanian J Legal Med 18(4):272

    Google Scholar 

  • Goshgarian AM, Benford DM, Caplan JP (2011) Bath salt abuse: neuropsychiatric effects of cathinone derivatives. Psychosomatics 52(6):593–594. doi:10.1016/j.psym.2011.03.003

    PubMed  Google Scholar 

  • Granek M, Shalev A, Weingarten AM (1988) Khat-induced hypnagogic hallucinations. Acta Psychiatr Scand 78(4):458–461

    CAS  PubMed  Google Scholar 

  • Griffith JD, Carranza J, Griffith C, Miller LL (1983) Bupropion: clinical assay for amphetamine-like abuse potential. J Clin Psychiatry 44(5 Pt 2):206–208

    CAS  PubMed  Google Scholar 

  • Griffiths P, Lopez D, Sedefov R et al (2010) Khat use and monitoring drug use in Europe: the current situation and issues for the future. J Ethnopharmacol 132(3):578–583. doi:10.1016/j.jep.2010.04.046

    PubMed  Google Scholar 

  • Guantai AN, Maitai CK (1983) Metabolism of cathinone to d-norpseudoephedrine in humans. J Pharm Sci 72(10):1217–1218

    CAS  PubMed  Google Scholar 

  • Gunderson EW, Kirkpatrick MG, Willing LM, Holstege CP (2013) Intranasal substituted cathinone “bath salts” psychosis potentially exacerbated by diphenhydramine. J Addict Med 7(3):163–168. doi:10.1097/ADM.0b013e31829084d5

    PubMed  Google Scholar 

  • Hadlock GC, Webb KM, McFadden LM et al (2011) 4-Methylmethcathinone (mephedrone): neuropharmacological effects of a designer stimulant of abuse. J Pharmacol Exp Ther 339(2):530–536. doi:10.1124/jpet.111.184119

    CAS  PubMed  Google Scholar 

  • Halbach H (1972) Medical aspects of the chewing of khat leaves. Bull World Health Organ 47(1):21–29

    CAS  PubMed Central  PubMed  Google Scholar 

  • Halket JM, Karasu Z, Murray-Lyon IM (1995) Plasma cathinone levels following chewing khat leaves (Catha edulis Forsk.). J Ethnopharmacol 49(2):111–113

    CAS  PubMed  Google Scholar 

  • Hansen P (2010) The ambiguity of khat in Somaliland. J Ethnopharmacol 132(3):590–599. doi:10.1016/j.jep.2010.02.028

    PubMed  Google Scholar 

  • Hill SL, Thomas SH (2011) Clinical toxicology of newer recreational drugs. Clin Toxicol 49(8):705–719. doi:10.3109/15563650.2011.615318

    CAS  Google Scholar 

  • Hyde J, Browning E, Adams R (1928) Synthetic homologs of d, l-ephedrine. J Am Chem Soc 50(8):2287–2292

    CAS  Google Scholar 

  • Iqbal M, Monaghan T, Redmond J (2012) Manganese toxicity with ephedrone abuse manifesting as Parkinsonism: a case report. J Med Case Rep 6(1):52. doi:10.1186/1752-1947-6-52

    PubMed Central  PubMed  Google Scholar 

  • James D, Adams RD, Spears R et al (2011) Clinical characteristics of mephedrone toxicity reported to the U.K. National Poisons Information Service. Emerg Med J EMJ 28(8):686–689. doi:10.1136/emj.2010.096636

    CAS  Google Scholar 

  • Jerry J, Collins G, Streem D (2012) Synthetic legal intoxicating drugs: the emerging ‘incense’ and ‘bath salt’ phenomenon. Clevel Clin J Med 79(4):258–264. doi:10.3949/ccjm.79a.11147

    Google Scholar 

  • Kalix P (1983) A comparison of the catecholamine releasing effect of the khat alkaloids (−)-cathinone and (+)-norpseudoephedrine. Drug Alcohol Depend 11(3–4):395–401

    CAS  PubMed  Google Scholar 

  • Kalix P (1984) Recent advances in khat research. Alcohol Alcohol 19(4):319–323

    CAS  PubMed  Google Scholar 

  • Kalix P (1991) The pharmacology of psychoactive alkaloids from ephedra and catha. J Ethnopharmacol 32(1–3):201–208. doi:10.1016/0378-8741(91)90119-X

    CAS  PubMed  Google Scholar 

  • Kalix P (1992) Cathinone, a natural amphetamine. Pharmacol Toxicol 70(2):77–86. doi:10.1111/j.1600-0773.1992.tb00434.x

    CAS  PubMed  Google Scholar 

  • Kalix P (1996) Catha edulis, a plant that has amphetamine effects. Pharm World Sci PWS 18(2):69–73

    CAS  Google Scholar 

  • Kalix P, Braenden O (1985) Pharmacological aspects of the chewing of khat leaves. Pharmacol Rev 37(2):149–164

    CAS  PubMed  Google Scholar 

  • Kalix P, Khan I (1984) Khat: an amphetamine-like plant material. Bull World Health Organ 62(5):681–686

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kamata HT, Shima N, Zaitsu K et al (2006) Metabolism of the recently encountered designer drug, methylone, in humans and rats. Xenobiotica Fate Foreign Compd Biol Syst 36(8):709–723. doi:10.1080/00498250600780191

    CAS  Google Scholar 

  • Karila L, Reynaud M (2011) GHB and synthetic cathinones: clinical effects and potential consequences. Drug Test Anal 3(9):552–559. doi:10.1002/dta.210

    CAS  PubMed  Google Scholar 

  • Kasick DP, McKnight CA, Klisovic E (2012) “Bath salt” ingestion leading to severe intoxication delirium: two cases and a brief review of the emergence of mephedrone use. Am Journal Drug Alcohol Abuse 38(2):176–180. doi:10.3109/00952990.2011.643999

    Google Scholar 

  • Kassie F, Darroudi F, Kundi M, Schulte-Hermann R, Knasmuller S (2001) Khat (Catha edulis) consumption causes genotoxic effects in humans. Int J Cancer 92(3):329–332

    CAS  PubMed  Google Scholar 

  • Kelly JP (2011) Cathinone derivatives: a review of their chemistry, pharmacology and toxicology. Drug Test Anal 3(7–8):439–453. doi:10.1002/dta.313

    CAS  PubMed  Google Scholar 

  • Khan S, Shaheen F, Sarwar H, Molina J, Mushtaq S (2013) “Bath salts”-induced psychosis in a young woman. Prim Care Companion CNS Disord 15(1):1–7. doi:10.4088/PCC.12l01417

  • Khreit OI, Grant MH, Zhang T, Henderson C, Watson DG, Sutcliffe OB (2013) Elucidation of the Phase I and Phase II metabolic pathways of (±)-4′-methylmethcathinone (4-MMC) and (±)-4′-(trifluoromethyl)methcathinone (4-TFMMC) in rat liver hepatocytes using LC-MS and LC-MS(2). J Pharm Biomed Anal 72:177–185. doi:10.1016/j.jpba.2012.08.015

    CAS  PubMed  Google Scholar 

  • Klein A, Beckerleg S, Hailu D (2009) Regulating khat—dilemmas and opportunities for the international drug control system. Int J Drug Policy 20(6):509–513

    PubMed  Google Scholar 

  • Klein A, Jelsma M, Metaal P (2012) Chewing over Khat prohibition. In: The globalisation of control and regulation of an ancient stimulant. Transnational Institute Series on Legislative Reform of Drug Policies No. 17. Transnational Institute, Amsterdam

  • Knoll J (1979) Studies on the central effects of (-)cathinone. NIDA Res Monogr 27:322–323

    CAS  PubMed  Google Scholar 

  • Kovacs K, Toth AR, Kereszty EM (2012) A new designer drug: methylone related death. Orv Hetil 153(7):271–276. doi:10.1556/OH.2012.29310

    PubMed  Google Scholar 

  • Kriikku P, Wilhelm L, Schwarz O, Rintatalo J (2011) New designer drug of abuse: 3,4-Methylenedioxypyrovalerone (MDPV). Findings from apprehended drivers in Finland. Forensic Sci Int 210(1–3):195–200. doi:10.1016/j.forsciint.2011.03.015

    CAS  PubMed  Google Scholar 

  • Kuenssberg E (1962) Diethylpropion. Br Med J 2(5306):729

    PubMed Central  Google Scholar 

  • Kyle PB, Iverson RB, Gajagowni RG, Spencer L (2011) Illicit bath salts: not for bathing. J Miss State Med Assoc 52(12):375–377

    PubMed  Google Scholar 

  • Lea T, Reynolds R, De Wit J (2011) Mephedrone use among same-sex attracted young people in Sydney, Australia. Drug Alcohol Rev 30(4):438–440. doi:10.1111/j.1465-3362.2011.00288.x

    PubMed  Google Scholar 

  • Levine M, Levitan R, Skolnik A (2013) Compartment syndrome after “bath salts” use: a case series. Ann Emerg Med 61(4):480–483. doi:10.1016/j.annemergmed.2012.11.021

    PubMed  Google Scholar 

  • Lindsay L, White ML (2012) Herbal marijuana alternatives and bath salts—“barely legal” toxic highs. Clin Pediatr Emerg Med 13(4):283–291. doi:10.1016/j.cpem.2012.09.001

    Google Scholar 

  • Lisek R, Xu W, Yuvasheva E et al (2012) Mephedrone (‘bath salt’) elicits conditioned place preference and dopamine-sensitive motor activation. Drug Alcohol Depend 126(1–2):257–262. doi:10.1016/j.drugalcdep.2012.04.021

    CAS  PubMed Central  PubMed  Google Scholar 

  • Locos O, Reynolds D (2012) The characterization of 3,4-dimethylmethcathinone (3,4-DMMC). J Forensic Sci 57(5):1303–1306. doi:10.1111/j.1556-4029.2012.02142.x

    CAS  PubMed  Google Scholar 

  • Lopez-Arnau R, Martinez-Clemente J, Pubill D, Escubedo E, Camarasa J (2012) Comparative neuropharmacology of three psychostimulant cathinone derivatives: butylone, mephedrone and methylone. Br J Pharmacol 167(2):407–420. doi:10.1111/j.1476-5381.2012.01998.x

    CAS  PubMed  Google Scholar 

  • Lopez-Arnau R, Martinez-Clemente J, Carbo M, Pubill D, Escubedo E, Camarasa J (2013) An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as “bath salts”. Progress Neuro Psychopharmacol Biol Psychiatry 45:64–72. doi:10.1016/j.pnpbp.2013.04.007

  • Lusthof KJ, Oosting R, Maes A, Verschraagen M, Dijkhuizen A, Sprong AG (2011) A case of extreme agitation and death after the use of mephedrone in The Netherlands. Forensic Sci Int 206(1–3):e93–e95. doi:10.1016/j.forsciint.2010.12.014

    PubMed  Google Scholar 

  • Maan ZN, D’Souza AR (2012) Spontaneous subcutaneous emphysema associated with mephedrone usage. Ann R Coll Surg Engl 94(1):e38–e40. doi:10.1308/003588412X13171221499108

    CAS  PubMed  Google Scholar 

  • Mackay K, Taylor M, Bajaj N (2011) The adverse consequences of mephedrone use: a case series. Psychiatrist 35(6):203–205. doi:10.1192/pb.bp.110.032433

    Google Scholar 

  • Maheux CR, Copeland CR (2012) Chemical analysis of two new designer drugs: buphedrone and pentedrone. Drug Test Anal 4(1):17–23. doi:10.1002/dta.385

    CAS  PubMed  Google Scholar 

  • Maheux CR, Copeland CR, Pollard MM (2010) Characterization of three methcathinone analogs: 4-methylmethcathinone, methylone, and bk-MBDB. Microgram J 7:42–49

    CAS  Google Scholar 

  • Manghi RA, Broers B, Khan R, Benguettat D, Khazaal Y, Zullino DF (2009) Khat use: lifestyle or addiction? J Psychoact Drugs 41(1):1–10. doi:10.1080/02791072.2009.10400669

    Google Scholar 

  • Marinetti LJ, Antonides HM (2013) Analysis of synthetic cathinones commonly found in bath salts in human performance and postmortem toxicology: method development, drug distribution and interpretation of results. J Anal Toxicol 37(3):135–146. doi:10.1093/jat/bks136

    CAS  PubMed  Google Scholar 

  • Markantonis SL, Kyroudis A, Beckett AH (1986) The stereoselective metabolism of dimethylpropion and monomethylpropion. Biochem Pharmacol 35(3):529–532

    CAS  PubMed  Google Scholar 

  • Martinez-Clemente J, Lopez-Arnau R, Carbo M, Pubill D, Camarasa J, Escubedo E (2013) Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics. Psychopharmacology 229(2):295–306. doi:10.1007/s00213-013-3108-7

    Google Scholar 

  • Marusich JA, Grant KR, Blough BE, Wiley JL (2012) Effects of synthetic cathinones contained in “bath salts” on motor behavior and a functional observational battery in mice. Neurotoxicology 33(5):1305–1313. doi:10.1016/j.neuro.2012.08.003

    CAS  PubMed Central  PubMed  Google Scholar 

  • Maskell PD, De Paoli G, Seneviratne C, Pounder DJ (2011) Mephedrone (4-methylmethcathinone)-related deaths. J Anal Toxicol 35(3):188–191. doi:10.1093/anatox/35.3.188

    CAS  PubMed  Google Scholar 

  • Mas-Morey P, Visser M, Winkelmolen L, Touw D (2012) Clinical toxicology and management of intoxications with synthetic cathinones (“bath salts”). J Pharm Pract 26(4):353–357. doi:10.1177/0897190012465949

    Google Scholar 

  • Mathys K, Brenneisen R (1992) Determination of (S)-(−)-cathinone and its metabolites (R, S)-(−)-norephedrine and (R, R)-(−)-norpseudoephedrine in urine by high-performance liquid chromatography with photodiode-array detection. J Chromatogr 593(1–2):79–85. doi:10.1016/0021-9673(92)80270-5

    CAS  PubMed  Google Scholar 

  • Maurer HH, Kraemer T, Springer D, Staack RF (2004) Chemistry, pharmacology, toxicology, and hepatic metabolism of designer drugs of the amphetamine (ecstasy), piperazine, and pyrrolidinophenone types: a synopsis. Ther Drug Monit 26(2):127–131

    CAS  PubMed  Google Scholar 

  • McClean JM, Anspikian A, Tsuang JW (2012) Bath salt use: a case report and review of the literature. J Dual Diagn 8(3):250–256. doi:10.1080/15504263.2012.697447

    Google Scholar 

  • McElrath K, O’Neill C (2011) Experiences with mephedrone pre- and post-legislative controls: perceptions of safety and sources of supply. Int J Drug Policy 22(2):120–127. doi:10.1016/j.drugpo.2010.11.001

    PubMed  Google Scholar 

  • McGraw M, McGraw L (2012) Bath salts: not as harmless as they sound. J Emerg Nurs 38(6):582–588. doi:10.1016/j.jen.2012.07.025

    Google Scholar 

  • McNamara S, Stokes S, Coleman N (2010) Head shop compound abuse amongst attendees of the Drug Treatment Centre Board. Ir Med J 103(5):134, 136–137

    Google Scholar 

  • Measham F, Moore K, Newcombe R (2010) Tweaking, bombing, dabbing and stockpiling: the emergence of mephedrone and the perversity of prohibition. Drugs Alcohol Today 10(1):14–21. doi:10.5042/daat.2010.0123

    Google Scholar 

  • Measham F, Wood DM, Dargan PI, Moore K (2011) The rise in legal highs: prevalence and patterns in the use of illegal drugs and first-and second-generation “legal highs” in South London gay dance clubs. J Subst Use 16(4):263–272. doi:10.3109/14659891.2011.594704

    Google Scholar 

  • Meng H, Cao J, Kang J et al (2012) Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat. Toxicol Lett 208(1):62–68. doi:10.1016/j.toxlet.2011.10.010

    CAS  PubMed  Google Scholar 

  • Meyer MR, Du P, Schuster F, Maurer HH (2010a) Studies on the metabolism of the alpha-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. J Mass Spectrom JMS 45(12):1426–1442. doi:10.1002/jms.1859

    CAS  Google Scholar 

  • Meyer MR, Wilhelm J, Peters FT, Maurer HH (2010b) Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography-mass spectrometry. Anal Bioanal Chem 397(3):1225–1233. doi:10.1007/s00216-010-3636-5

    CAS  PubMed  Google Scholar 

  • Meyer MR, Vollmar C, Schwaninger AE, Wolf E, Maurer HH (2012) New cathinone-derived designer drugs 3-bromomethcathinone and 3-fluoromethcathinone: studies on their metabolism in rat urine and human liver microsomes using GC-MS and LC-high-resolution MS and their detectability in urine. J Mass Spectrom JMS 47(2):253–262. doi:10.1002/jms.2960

    CAS  Google Scholar 

  • Meyer MR, Prosser D, Maurer HH (2013) Studies on the metabolism and detectability of the designer drug beta-naphyrone in rat urine using GC-MS and LC-HR-MS/MS. Drug Test Anal 5(4):259–265. doi:10.1002/dta.1443

    CAS  PubMed  Google Scholar 

  • Miller ML, Creehan KM, Angrish D et al (2013) Changes in ambient temperature differentially alter the thermoregulatory, cardiac and locomotor stimulant effects of 4-methylmethcathinone (mephedrone). Drug Alcohol Depend 127(1–3):248–253. doi:10.1016/j.drugalcdep.2012.07.003

    CAS  PubMed Central  PubMed  Google Scholar 

  • Morikawa K, Oshita M, Yamazaki M et al (1987) Pharmacological studies of the new centrally acting muscle relaxant 4′-ethyl-2-methyl-3-pyrrolidinopropiophenone hydrochloride. Arzneimittelforschung 37(3):331

    CAS  PubMed  Google Scholar 

  • Morris K (2010) UK places generic ban on mephedrone drug family. Lancet 375(9723):1333–1334. doi:10.1016/S0140-6736(10)60559-4

    PubMed  Google Scholar 

  • Motbey CP, Hunt GE, Bowen MT, Artiss S, McGregor IS (2012a) Mephedrone (4-methylmethcathinone, ‘meow’): acute behavioural effects and distribution of Fos expression in adolescent rats. Addict Biol 17(2):409–422. doi:10.1111/j.1369-1600.2011.00384.x

    CAS  PubMed  Google Scholar 

  • Motbey CP, Karanges E, Li KM et al (2012b) Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion. PLoS ONE 7(9):e45473. doi:10.1371/journal.pone.0045473

    CAS  PubMed Central  PubMed  Google Scholar 

  • Motbey CP, Clemens KJ, Apetz N et al (2013) High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: neural consequences and comparison with methamphetamine. J Psychopharmacol 27(9):823–836. doi:10.1177/0269881113490325

    Google Scholar 

  • Mugele J, Nanagas KA, Tormoehlen LM (2012) Serotonin syndrome associated with MDPV use: a case report. Ann Emerg Med 60(1):100–102. doi:10.1016/j.annemergmed.2011.11.033

    PubMed  Google Scholar 

  • Murray BL, Murphy CM, Beuhler MC (2012) Death following recreational use of designer drug “bath salts” containing 3,4-methylenedioxypyrovalerone (MDPV). J Med Toxicol Off J Am Coll Med Toxicol 8(1):69–75. doi:10.1007/s13181-011-0196-9

    Google Scholar 

  • Nencini P, Ahmed AM (1989) Khat consumption: a pharmacological review. Drug Alcohol Depend 23(1):19–29. doi:10.1016/0376-8716(89)90029-X

    CAS  PubMed  Google Scholar 

  • Nencini P, Amiconi G, Befani O, Abdullahi MA, Anania MC (1984) Possible involvement of amine oxidase inhibition in the sympathetic activation induced by khat (Catha edulis) chewing in humans. J Ethnopharmacol 11(1):79–86. doi:10.1016/0378-8741(84)90097-7

    CAS  PubMed  Google Scholar 

  • Nicholson PJ, Quinn MJ, Dodd JD (2010) Headshop heartache: acute mephedrone ‘meow’ myocarditis. Heart 96(24):2051–2052. doi:10.1136/hrt.2010.209338

    PubMed  Google Scholar 

  • Odenwald M (2007) Chronic khat use and psychotic disorders: a review of the literature and future prospects. SUCHT-Zeitschrift für Wissenschaft und Praxis/Journal of Addiction Research and Practice 53(1):9–22. doi:10.1024/2007.01.03

    Google Scholar 

  • Osorio-Olivares M, Rezende MC, Sepulveda-Boza S, Cassels BK, Fierro A (2004) MAO inhibition by arylisopropylamines: the effect of oxygen substituents at the beta-position. Bioorg Med Chem 12(15):4055–4066. doi:10.1016/j.bmc.2004.05.033

    CAS  PubMed  Google Scholar 

  • Patel SL, Murray R, Britain G (2005) Khat use among Somalis in four English cities. Home Office, London

  • Paul BD, Cole KA (2001) Cathinone (Khat) and methcathinone (CAT) in urine specimens: a gas chromatographic-mass spectrometric detection procedure. J Anal Toxicol 25(7):525–530. doi:10.1093/jat/25.7.525

    CAS  PubMed  Google Scholar 

  • Pawlik E, Plasser G, Mahler H, Daldrup T (2012) Studies on the phase I metabolism of the new designer drug 3-fluoromethcathinone using rabbit liver slices. Int J Legal Med 126(2):231–240. doi:10.1007/s00414-011-0601-6

    PubMed  Google Scholar 

  • Pearson JM, Hargraves TL, Hair LS et al (2012) Three fatal intoxications due to methylone. J Anal Toxicol 36(6):444–451. doi:10.1093/jat/bks043

    CAS  PubMed  Google Scholar 

  • Pedersen AJ, Reitzel LA, Johansen SS, Linnet K (2013) In vitro metabolism studies on mephedrone and analysis of forensic cases. Drug Test Anal 5(6):430–438. doi:10.1002/dta.1369

    Google Scholar 

  • Peevers CG, Moorghen M, Collins PL, Gordon FH, McCune CA (2010) Liver disease and cirrhosis because of khat chewing in UK Somali men: a case series. Liver Int 30(8):1242–1243. doi:10.1111/j.1478-3231.2010.02228.x

    PubMed  Google Scholar 

  • Penders TM, Gestring RE, Vilensky DA (2012) Excited delirium following use of synthetic cathinones (bath salts). Gen Hosp Psychiatry 34(6):647–650. doi:10.1016/j.genhosppsych.2012.06.005

    PubMed  Google Scholar 

  • Peters FT, Meyer MR, Fritschi G, Maurer HH (2005) Studies on the metabolism and toxicological detection of the new designer drug 4′-methyl-alpha-pyrrolidinobutyrophenone (MPBP) in rat urine using gas chromatography-mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 824(1–2):81–91. doi:10.1016/j.jchromb.2005.07.003

    CAS  Google Scholar 

  • Portuguese Government (2013) Decreto-Lei n.º 54/2013. Diário da República 75

  • Prosser JM, Nelson LS (2012) The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol Off J Am Coll Med Toxicol 8(1):33–42. doi:10.1007/s13181-011-0193-z

    Google Scholar 

  • Ramsey J, Dargan PI, Smyllie M et al (2010) Buying ‘legal’ recreational drugs does not mean that you are not breaking the law. QJM Month J Assoc Phys 103(10):777–783. doi:10.1093/qjmed/hcq132

    CAS  Google Scholar 

  • Regan L, Mitchelson M, Macdonald C (2011) Mephedrone toxicity in a Scottish emergency department. Emerg Med J EMJ 28(12):1055–1058. doi:10.1136/emj.2010.103093

    Google Scholar 

  • Regunath H, Ariyamuthu VK, Dalal P, Misra M (2012) Bath salt intoxication causing acute kidney injury requiring hemodialysis. Hemodial Int Int Sympos Home Hemodial 16(Suppl 1):S47–S49. doi:10.1111/j.1542-4758.2012.00750.x

    Google Scholar 

  • Roelandt P, George C, d’Heygere F et al (2011) Acute liver failure secondary to khat (< i > Catha edulis </i >)–induced necrotic hepatitis requiring liver transplantation: case report. Transpl Proc 43(9):3493–3495. doi:10.1016/j.transproceed.2011.09.032

    CAS  Google Scholar 

  • Rojek S, Klys M, Strona M, Maciow M, Kula K (2012) “Legal highs”–toxicity in the clinical and medico-legal aspect as exemplified by suicide with bk-MBDB administration. Forensic Sci Int 222(1–3):e1–e6. doi:10.1016/j.forsciint.2012.04.034

    PubMed  Google Scholar 

  • Russo R, Marks N, Morris K, King H, Gelvin A, Rooney R (2012) Life-threatening necrotizing fasciitis due to ‘bath salts’ injection. Orthopedics 35(1):e124–e127. doi:10.3928/01477447-20111122-36

    PubMed  Google Scholar 

  • Saem de Burnaga Sanchez J (1929) Sur un homologue de l’éphédrine [On an analogue of ephedrine]. Bulletin de la Societé Chimique de France 45:284–286

    Google Scholar 

  • Sakitama K, Ozawa Y, Aoto N, Nakamura K, Ishikawa M (1995) Pharmacological properties of NK433, a new centrally acting muscle relaxant. Eur J Pharmacol 273(1–2):47–56. doi:10.1016/0014-2999(94)00666-U

    CAS  PubMed  Google Scholar 

  • Sammler EM, Foley PL, Lauder GD, Wilson SJ, Goudie AR, O’Riordan JI (2010) A harmless high? Lancet 376(9742):742. doi:10.1016/S0140-6736(10)60891-4

    PubMed  Google Scholar 

  • Sanotsky Y, Lesyk R, Fedoryshyn L, Komnatska I, Matviyenko Y, Fahn S (2007) Manganic encephalopathy due to “ephedrone” abuse. Mov Disord Off J Mov Disord Soc 22(9):1337–1343. doi:10.1002/mds.21378

    Google Scholar 

  • Sauer C, Peters FT, Haas C, Meyer MR, Fritschi G, Maurer HH (2009) New designer drug alpha-pyrrolidinovalerophenone (PVP): studies on its metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric techniques. J Mass Spectrom JMS 44(6):952–964. doi:10.1002/jms.1571

    CAS  Google Scholar 

  • Schifano F, Albanese A, Fergus S et al (2011) Mephedrone (4-methylmethcathinone; ‘meow meow’): chemical, pharmacological and clinical issues. Psychopharmacology 214(3):593–602. doi:10.1007/s00213-010-2070-x

    CAS  PubMed  Google Scholar 

  • Seaton D, Duncan L, Rose K, Scott AM (1961) Diethylpropion in the treatment of “refractory” obesity. Br Med J 1(5231):1009

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sharma TR, Iskandar JW, Ali R, Shah UR (2012) Bath salts-induced delirium and brief psychotic episode in an otherwise healthy young man. Prim Care Companion CNS Disord 14(2):1–4. doi:10.4088/PCC.11l01224

  • Shima N, Katagi M, Tsuchihashi H (2009) Direct analysis of conjugate metabolites of methamphetamine, 3, 4-methylenedioxymethamphetamine, and their designer drugs in biological fluids. J Health Sci 55(4):495–502. doi:10.1248/jhs.55.495

    CAS  Google Scholar 

  • Shima N, Katagi M, Kamata H et al (2013) Urinary excretion and metabolism of the newly encountered designer drug 3, 4-dimethylmethcathinone in humans. Forensic Toxicol 31(1):101–112. doi:10.1007/s11419-012-0172-3

    CAS  Google Scholar 

  • Shimizu E, Watanabe H, Kojima T et al (2007) Combined intoxication with methylone and 5-MeO-MIPT. Prog Neuropsychopharmacol Biol Psychiatry 31(1):288–291. doi:10.1016/j.pnpbp.2006.06.012

    CAS  PubMed  Google Scholar 

  • Shortall SE, Macerola AE, Swaby RT et al (2013a) Behavioural and neurochemical comparison of chronic intermittent cathinone, mephedrone and MDMA administration to the rat. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol 23(9):1085–1095. doi:10.1016/j.euroneuro.2012.09.005

  • Shortall SE, Green AR, Swift KM, Fone KC, King MV (2013b) Differential effects of cathinone compounds and MDMA on body temperature in the rat, and pharmacological characterization of mephedrone-induced hypothermia. Br J Pharmacol 168(4):966–977. doi:10.1111/j.1476-5381.2012.02236.x

    CAS  PubMed  Google Scholar 

  • Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD (1999) Storage and release of catecholamines. In: Siegel GJ, Fisher SK, Uhler MD, Albers RW, Agranoff BW (eds) Basic neurochemistry: molecular, cellular and medical aspects, 6th edn. Lippincott Williams & Wilkins, Philadelphia

  • Simmler LD, Buser TA, Donzelli M et al (2013) Pharmacological characterization of designer cathinones in vitro. Br J Pharmacol 168(2):458–470. doi:10.1111/j.1476-5381.2012.02145.x

    CAS  PubMed  Google Scholar 

  • Smith K, Flatley J (2011) Drug misuse declared: findings from the 2010/11 British Crime Survey England and Wales. Home Office Statistical Bulletin 12(11)

  • Sogawa C, Sogawa N, Ohyama K et al (2011) Methylone and monoamine transporters: correlation with toxicity. Curr Neuropharmacol 9(1):58–62. doi:10.2174/157015911795017425

    CAS  PubMed  Google Scholar 

  • Soroko FE, Mehta NB, Maxwell RA, Ferris RM, Schroeder DH (1977) Bupropion hydrochloride ((±) alpha-t-butylamino-3-chloropropiophenone HCl): a novel antidepressant agent. J Pharm Pharmacol 29(12):767–770. doi:10.1111/j.2042-7158.1977.tb11460.x

    CAS  PubMed  Google Scholar 

  • Soufi HE, Kameswaran M, Malatani T (1991) Khat and oral cancer. J Laryngol Otol 105(8):643–645. doi:10.1017/S0022215100116913

    CAS  PubMed  Google Scholar 

  • Sparago M, Wlos J, Yuan J et al (1996) Neurotoxic and pharmacologic studies on enantiomers of the N-methylated analog of cathinone (methcathinone): a new drug of abuse. J Pharmacol Exp Ther 279(2):1043–1052

    CAS  PubMed  Google Scholar 

  • Spiller HA, Ryan ML, Weston RG, Jansen J (2011) Clinical experience with and analytical confirmation of “bath salts” and “legal highs” (synthetic cathinones) in the United States. Clin Toxicol 49(6):499–505. doi:10.3109/15563650.2011.590812

    CAS  Google Scholar 

  • Springer D, Peters FT, Fritschi G, Maurer HH (2002) Studies on the metabolism and toxicological detection of the new designer drug 4′-methyl-alpha-pyrrolidinopropiophenone in urine using gas chromatography-mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 773(1):25–33. doi:10.1016/S1570-0232(01)00578-5

    CAS  Google Scholar 

  • Springer D, Fritschi G, Maurer HH (2003a) Metabolism and toxicological detection of the new designer drug 3′,4′-methylenedioxy-alpha-pyrrolidinopropiophenone studied in urine using gas chromatography-mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 793(2):377–388. doi:10.1016/S1570-0232(03)00350-7

    CAS  Google Scholar 

  • Springer D, Fritschi G, Maurer HH (2003b) Metabolism and toxicological detection of the new designer drug 4′-methoxy-alpha-pyrrolidinopropiophenone studied in rat urine using gas chromatography-mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 793(2):331–342. doi:10.1016/S1570-0232(03)00334-9

    CAS  Google Scholar 

  • Springer D, Fritschi G, Maurer HH (2003c) Metabolism of the new designer drug alpha-pyrrolidinopropiophenone (PPP) and the toxicological detection of PPP and 4′-methyl-alpha-pyrrolidinopropiophenone (MPPP) studied in rat urine using gas chromatography-mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 796(2):253–266. doi:10.1016/j.jchromb.2003.07.008

    CAS  Google Scholar 

  • Springer D, Peters FT, Fritschi G, Maurer HH (2003d) New designer drug 4′-methyl-alpha-pyrrolidinohexanophenone: studies on its metabolism and toxicological detection in urine using gas chromatography-mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 789(1):79–91. doi:10.1016/S1570-0232(03)00043-6

    CAS  Google Scholar 

  • Springer D, Staack RF, Paul LD, Kraemer T, Maurer HH (2005) Identification of cytochrome P450 enzymes involved in the metabolism of 3′,4′-methylenedioxy-alpha-pyrrolidinopropiophenone (MDPPP), a designer drug, in human liver microsomes. Xenobiotica Fate Foreign Compd Biol Syst 35(3):227–237. doi:10.1080/00498250400028239

    CAS  Google Scholar 

  • Spyker DA, Thomas S, Bateman DN et al (2012) International trends in designer amphetamine abuse in UK and US, 2009–2012. Clin Toxicol 50(636):141

    Google Scholar 

  • Strano-Rossi S, Cadwallader AB, de la Torre X, Botre 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 Commun Mass spectrom RCM 24(18):2706–2714. doi:10.1002/rcm.4692

    CAS  Google Scholar 

  • Striebel JM, Pierre JM (2011) Acute psychotic sequelae of “bath salts”. Schizophr Res 133(1–3):259–260. doi:10.1016/j.schres.2011.09.001

    PubMed  Google Scholar 

  • Szendrei K (1980) The chemistry of khat. Bull Narc 32(3):5–35

    CAS  PubMed  Google Scholar 

  • Tariq M, Islam MW, al-Meshal IA, el-Feraly FS, Ageel AM (1989) Comparative study of cathinone and amphetamine on brown adipose thermogenesis. Life Sci 44(14):951–955. doi:10.1016/0024-3205(89)90494-3

    CAS  PubMed  Google Scholar 

  • Tesfaye F, Byass P, Wall S, Berhane Y, Bonita R (2008) Association of smoking and khat (Catha edulis Forsk) use with high blood pressure among adults in Addis Ababa, Ethiopia, 2006. Preventing Chronic Disease 5(3)

  • Thornton SL, Gerona RR, Tomaszewski CA (2012) Psychosis from a bath salt product containing flephedrone and MDPV with serum, urine, and product quantification. J Med Toxicol 8(3):310–313. doi:10.1007/s13181-012-0232-4

    PubMed Central  PubMed  Google Scholar 

  • Toennes SW, Kauert GF (2002) Excretion and detection of cathinone, cathine, and phenylpropanolamine in urine after kath chewing. Clin Chem 48(10):1715–1719

    CAS  PubMed  Google Scholar 

  • Toennes SW, Harder S, Schramm M, Niess C, Kauert GF (2003) Pharmacokinetics of cathinone, cathine and norephedrine after the chewing of khat leaves. Br J Clin Pharmacol 56(1):125–130. doi:10.1046/j.1365-2125.2003.01834.x

    CAS  PubMed  Google Scholar 

  • United Nations (1975) Etudes sur la composition chimique du khat: recherches sur la fraction phénylalkylamine. UN document MNAR/11/1975

  • Van Hout MC, Brennan R (2011) Plant food for thought: a qualitative study of mephedrone use in Ireland. Drugs Educ Prev Policy 18(5):371–381. doi:10.3109/09687637.2010.537713

    Google Scholar 

  • Vardakou I, Pistos C, Spiliopoulou C (2011) Drugs for youth via Internet and the example of mephedrone. Toxicol Lett 201(3):191–195. doi:10.1016/j.toxlet.2010.12.014

    CAS  PubMed  Google Scholar 

  • Vardakou I, Pistos C, Dona A, Spiliopoulou C, Athanaselis S (2012) Naphyrone: a “legal high” not legal any more. Drug Chem Toxicol 35(4):467–471. doi:10.3109/01480545.2011.642381

    CAS  PubMed  Google Scholar 

  • Varlibas F, Delipoyraz I, Yuksel G, Filiz G, Tireli H, Gecim NO (2009) Neurotoxicity following chronic intravenous use of “Russian cocktail”. Clin Toxicol 47(2):157–160. doi:10.1080/15563650802010388

    CAS  Google Scholar 

  • Varner KJ, Daigle K, Weed PF et al (2013) Comparison of the behavioral and cardiovascular effects of mephedrone with other drugs of abuse in rats. Psychopharmacology 225(3):675–685. doi:10.1007/s00213-012-2855-1

    CAS  PubMed  Google Scholar 

  • Vekariya RH (2012) Towards understanding the mechanism of action of abused cathinones. Virginia Commonwealth University, Richmond, VA

  • Volkow ND (2011) ‘Bath salts’–emerging and dangerous products. Natl Inst Drug Abuse. available at http://www.drugabuse.gov/about-nida/directors-page/messages-director/2011/02/bath-salts-emergingdangerous-products

  • Warrick BJ, Wilson J, Hedge M, Freeman S, Leonard K, Aaron C (2012) Lethal serotonin syndrome after methylone and butylone ingestion. J Med Toxicol Off J Am Coll Med Toxicol 8(1):65–68. doi:10.1007/s13181-011-0199-6

    Google Scholar 

  • Watterson L, Hood L, Sewalia K, Tomek S, Yahn S (2012a) The reinforcing and rewarding effects of methylone, a synthetic cathinone commonly found in “bath salts”. J Addict Res Ther S 9:2. doi:10.4172/2155-6105.S9-002

    Google Scholar 

  • Watterson LR, Kufahl PR, Nemirovsky NE et al (2012b) Potent rewarding and reinforcing effects of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV). Addict Biol 1–10. doi:10.1111/j.1369-1600.2012.00474.x

  • Westphal F, Junge T, Rosner P, Fritschi G, Klein B, Girreser U (2007) Mass spectral and NMR spectral data of two new designer drugs with an alpha-aminophenone structure: 4′-methyl-alpha-pyrrolidinohexanophenone and 4′-methyl-alpha-pyrrolidinobutyrophenone. Forensic Sci Int 169(1):32–42. doi:10.1016/j.forsciint.2006.07.024

    CAS  PubMed  Google Scholar 

  • Westphal F, Rosner P, Junge T (2010) Differentiation of regioisomeric ring-substituted fluorophenethylamines with product ion spectrometry. Forensic Sci Int 194(1–3):53–59. doi:10.1016/j.forsciint.2009.10.007

    CAS  PubMed  Google Scholar 

  • Widler P, Mathys K, Brenneisen R, Kalix P, Fisch HU (1994) Pharmacodynamics and pharmacokinetics of khat: a controlled study. Clin Pharmacol Ther 55(5):556–562. doi:10.1038/clpt.1994.69

    CAS  PubMed  Google Scholar 

  • Wikstrom M, Thelander G, Nystrom I, Kronstrand R (2010) Two fatal intoxications with the new designer drug methedrone (4-methoxymethcathinone). J Anal Toxicol 34(9):594–598. doi:10.1093/jat/34.9.594

    PubMed  Google Scholar 

  • Winder GS, Stern N, Hosanagar A (2013) Are “bath salts” the next generation of stimulant abuse? J Subst Abuse Treat 44(1):42–45. doi:10.1016/j.jsat.2012.02.003

    PubMed  Google Scholar 

  • Winstock AR, Mitcheson LR, Deluca P, Davey Z, Corazza O, Schifano F (2011) Mephedrone, new kid for the chop? Addiction 106(1):154–161. doi:10.1111/j.1360-0443.2010.03130.x

    PubMed  Google Scholar 

  • Wolfes O (1930) Über das Vorkommen von d-nor-iso-Ephedrin in Catha edulis. Arch Pharm 268(2):81–83

    CAS  Google Scholar 

  • Wood DM, Davies S, Greene SL et al (2010a) Case series of individuals with analytically confirmed acute mephedrone toxicity. Clin Toxicol 48(9):924–927. doi:10.3109/15563650.2010.531021

    CAS  Google Scholar 

  • Wood DM, Davies S, Puchnarewicz M et al (2010b) Recreational use of mephedrone (4-methylmethcathinone, 4-MMC) with associated sympathomimetic toxicity. J Med Toxicol Off J Am Coll Med Toxicol 6(3):327–330. doi:10.1007/s13181-010-0018-5

    Google Scholar 

  • Wood DM, Davies S, Cummins A et al (2011) Energy-1 (‘NRG-1’): don’t believe what the newspapers say about it being legal. BMJ Case Rep 2011:1–7. doi:10.1136/bcr.07.2010.3184

  • Wood DM, Measham F, Dargan PI (2012) ‘Our favourite drug’: prevalence of use and preference for mephedrone in the London night-time economy 1 year after control. J Subs Use 17(2):91–97. doi:10.3109/14659891.2012.661025

    Google Scholar 

  • Wright MJ Jr, Angrish D, Aarde SM et al (2012a) Effect of ambient temperature on the thermoregulatory and locomotor stimulant effects of 4-methylmethcathinone in Wistar and Sprague-Dawley rats. PLoS ONE 7(8):e44652. doi:10.1371/journal.pone.0044652

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wright MJ Jr, Vandewater SA, Angrish D, Dickerson TJ, Taffe MA (2012b) Mephedrone (4-methylmethcathinone) and d-methamphetamine improve visuospatial associative memory, but not spatial working memory, in rhesus macaques. Br J Pharmacol 167(6):1342–1352. doi:10.1111/j.1476-5381.2012.02091.x

    CAS  PubMed  Google Scholar 

  • Yamazaki M, Aoki Y, Kato H, Ito Y, Kontani H, Koshiura R (1987) Centrally acting muscle relaxant activities of 2-methyl-3-pyrrolidinopropiophenone derivatives. Yakugaku zasshi J Pharm Soc Jpn 107(9):705–710

    CAS  Google Scholar 

  • Yohannan JC, Bozenko JS Jr (2010) The characterization of 3, 4-methylenedioxypyrovalerone (MDPV). Microgram J 7(1):5–15

    Google Scholar 

  • Young R, Glennon RA (1993) Cocaine-stimulus generalization to two new designer drugs: methcathinone and 4-methylaminorex. Pharmacol Biochem Behav 45(1):229–231. doi:10.1016/0091-3057(93)90110-F

    CAS  PubMed  Google Scholar 

  • Zaitsu K, Katagi M, Kamata HT et al (2009) Determination of the metabolites of the new designer drugs bk-MBDB and bk-MDEA in human urine. Forensic Sci Int 188(1–3):131–139. doi:10.1016/j.forsciint.2009.04.001

    CAS  PubMed  Google Scholar 

  • Zaitsu K, Katagi M, Tatsuno M, Sato T, Tsuchihashi H, Suzuki K (2011) Recently abused β-keto derivatives of 3, 4-methylenedioxyphenylalkylamines: a review of their metabolisms and toxicological analysis. Forensic Toxicol 29(2):73–84. doi:10.1007/s11419-011-0111-8

    CAS  Google Scholar 

  • Zelger JL, Schorno HX, Carlini EA (1980) Behavioural effects of cathinone, an amine obtained from Catha edulis Forsk.: comparisons with amphetamine, norpseudoephedrine, apomorphine and nomifensine. Bull Narc 32(3):67–81

    CAS  PubMed  Google Scholar 

  • Zuba D, Byrska B (2013) Prevalence and co-existence of active components of ‘legal highs’. Drug Test Anal 5(6):420–429. doi:10.1002/dta.1365

  • Zuba D, Adamowicz P, Byrska B (2013) Detection of buphedrone in biological and non-biological material–two case reports. Forensic Sci Int 227(1–3):15–20. doi:10.1016/j.forsciint.2012.08.034

    CAS  PubMed  Google Scholar 

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  1. REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal

    Maria João Valente, Paula Guedes de Pinho, Maria de Lourdes Bastos, Félix Carvalho & Márcia Carvalho

  2. CEBIMED, Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Porto, Portugal

    Márcia Carvalho

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  1. Maria João Valente
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  2. Paula Guedes de Pinho
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Correspondence to Maria João Valente or Márcia Carvalho.

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Valente, M.J., Guedes de Pinho, P., de Lourdes Bastos, M. et al. Khat and synthetic cathinones: a review. Arch Toxicol 88, 15–45 (2014). https://doi.org/10.1007/s00204-013-1163-9

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