Khat—A Natural Source of Cathinone

  • Nilesh B. Patel
Part of the Current Topics in Neurotoxicity book series (Current Topics Neurotoxicity, volume 12)


Recently, a class of new psychoactive substances (NPS) has appeared as drugs of abuse. NPS comprise different drug classes; the most popular are synthetic cannabinomimetics and designer analogues of cathinone, an intermediate metabolite in a biosynthetic pathway, and a psychostimulant, found in the plants Catha edulis Forsk., Ephedra gerardiana sikkimensis, and Ephedra sinica. In C. edulis and E. gerardiana sikkimensis, cathinone is converted to norpseudoephedrine (cathine) and norephedrine, while in E. sinica the pathway continues to pseudoephedrine and ephedrine. While cathinone analogues are used for recreational purposes, cathinone, itself, is consumed only through chewing khat, i.e., the fresh leaves and twigs of the plant C. edulis Forsk., a practice similar to chewing of coca leaves. The use of khat is common among people living in Southwestern Arabia and Eastern Africa with an estimated 10–20 million daily users. This chapter describes the use of khat, its distribution and cultivation, the biosynthetic pathway that involves cathinone, the long delay in the discovery of cathinone, the neurochemistry of khat and cathinone, its effects on humans, and its dependency and addiction potential.


Khat Cathinone Novel psychoactive substances Catha edulis Forsk Ephedra gerardiana sikkimensis Ephedra sinica 


  1. Al-Motarreb A, Baker K, Broadley KJ (2002) Khat: pharmacological and medical aspects and its social use in Yemen. Phytother Res 16:403–413. Scholar
  2. Al-Mugahed L (2008) Khat chewing in Yemen: turning over a new leaf: khat chewing is on the rise in Yemen, raising concerns about the health and social consequences. Bull World Health Organ 86(10):741–742CrossRefGoogle Scholar
  3. Alles GA, Fairchild MD, Jensen M (1961) Chemical pharmacology of Catha edulis. J Med Pharm Chem 3:323–352CrossRefGoogle Scholar
  4. Anderson D, Beckerleg S, Hailu D, Klein A (eds) (2007) The Khat controversy: stimulating the debate on drugs. Berg, OxfordGoogle Scholar
  5. Appendino G, Minassi A, Taglialatela-Scafati O (2014) Recreational drug discovery: natural products as lead structures for synthesis of smart drugs. Nat Prod Rep 31(7):880–904CrossRefGoogle Scholar
  6. Atlabachew M, Combrinck S, Viljoen AM et al (2016) Isolation and in vitro permeation of phenylpropylamino alkaloids from Khat (Catha edulis) across oral and intestinal mucosal tissues. J Ethnopharmacol 194:307–315. Scholar
  7. Bailey WJ (1995) Methcathinone. Indiana Prevention Resource Center. Accessed 13 Nov 2017
  8. Beitter A (1901) Pharmakognostich-chemische Untersuchung der Catha edulis. Arch Pharm (Weinheim) 239:17–33CrossRefGoogle Scholar
  9. Calcagnetti DJ, Schechter MD (1993) Place preference for the psychostimulant cathinone is blocked by pretreatment with a dopamine release inhibitor. Prog Neuropsychopharmacol Biol Psychiatry 17:637–649CrossRefGoogle Scholar
  10. Colzato LS, Ruiz MJ, van den Wildenberg WP et al (2011a) Long-term effects of chronic khat use: impaired inhibitory control. Front Psychol 1:219. Scholar
  11. Colzato LS, Ruiz MJ, van den Wildenberg WP, Hommel B (2011b) Khat use is associated with impaired working memory and cognitive flexibility. PLoS ONE 6:e20602. Scholar
  12. Cox G, Rampes H (2003) Adverse effects of khat: a review. Adv Psych Treat 9:456–463CrossRefGoogle Scholar
  13. Emerson TS, Cisek JE (1993) Methcathinone: a Russian designer amphetamine infiltrates the rural Midwest. Ann Emerg Med 22(12):1897–1903CrossRefGoogle Scholar
  14. Accessed 13 October 2017Google Scholar
  15. Feyissa AM, Kelly JP (2008) A review of the neuropharmacological properties of khat. Progress Neuropsychopharmacol Biol Psych 32(5):1147–1166. Scholar
  16. Gebissa E (2004) Leaf of Allah: khat & agriculuture transformation in Harerge, Ethiopia 1875–1991. Ohio University Press, Athens, OhioGoogle Scholar
  17. Geisshusler S, Brenneisen R (1987) The content of psychoactive phenylpropyl and phenylpentenyl khatamins in Catha edulis Forsk of different origins. J Ethnopharmacol 19:269–277CrossRefGoogle Scholar
  18. Gerald O, Patel NB (2017) Lack of gross impairment of blood brain barrier integrity with binge-dose pattern of khat (Catha edulis Forsk) extract treatment. Society of Neuroscientists of Africa conference Abs No. MP-08 11–14 June 2017, Entebbe, UgandaGoogle Scholar
  19. Glennon RA, Young R, Martin BR, Dal Cason TA (1995) Methcathinone (“cat”): an enantiomeric potency comparison. Pharmacol Biochem Behav 50(4):601–606CrossRefGoogle Scholar
  20. Goerig M, Bacon D, van Zundert A (2012) Carl Koller, cocaine, and local anesthesia: some less known and forgotten facts. Reg Anesth Pain Med 37(3):318–324. Scholar
  21. Gosnell BA, Yracheta JM, Bell SM, Lane KE (1996) Intravenous self-administration of cathinone by rats. Behav Pharmacol 7(6):526–531PubMedPubMedCentralGoogle Scholar
  22. Gossop M, Darke S, Griffiths P et al (1995) The severity of dependence scale (SDS): psychometric properties of the SDS in English and Australian samples of heroin, cocaine and amphetamine users. Addiction 90:607–614CrossRefGoogle Scholar
  23. Groves RA, Hagel JM, Zhang Y et al (2015) Transcriptome profiling of Khat (Catha edulis) and Ephedra sinica reveals gene candidates potentially involved in amphetamine-type alkaloid biosynthesis. PLoS ONE 10(3):e0119701. Scholar
  24. Grue-Sorenson G, Spenser ID (1994) Biosynthetic route to the Ephedra alkaloids. J Am Chem Soc 166:6195–6200CrossRefGoogle Scholar
  25. Guantai A, Maitai C (1982) Relative distribution of cathinone and norpseudoephedrine in Catha edulis growing in Kenya. EAMJ 59:394–398Google Scholar
  26. Hagel JM, Krizevski R, Kilpatrick K et al (2011) Expressed sequence tag analysis of khat (Catha edulis) provides a putative molecular biochemical basis for the biosynthesis of phenylpropylamino alkaloids. Genet Mol Biol 34(4):640–646. Scholar
  27. Hersi A, Abdalla M (2013) Sharia law and legality of consumption of khat (Catha edulis): views of Australian Imams. Int J Humanit Soc Sci 3(21):248–257Google Scholar
  28. Hoffman R, Al’Absi M (2012) Working memory and speed of information processing in chronic khat users: preliminary findings. Eur Addict Res 19:1–6CrossRefGoogle Scholar
  29. Hunter FM (1877) An account of the British Settlement of Aden in Arabia. Frank Cass and Company Ltd Publishers, 1st edn. New impression 1968Google Scholar
  30. Hyde JF, Browning E, Adams R (1928) Synthetic homologs of d, l-ephedrine. J Am Chem Soc 50(8):2287–2292CrossRefGoogle Scholar
  31. Kalix P (1984) Effect of the alkaloid (-)-cathinone on the release of radioactivity from rat striatal tissue prelabelled with 3H-serotonin. Neuropsychobiology 12(2–3):127–129CrossRefGoogle Scholar
  32. Kalix P (1990) Pharmacological properties of the stimulant khat. Pharmac Ther 48:397–416CrossRefGoogle Scholar
  33. Kalix P (1991) The pharmacology of psychoactive alkaloids from ephedra and catha. J Ethnopharmacol 32:201–208CrossRefGoogle Scholar
  34. Kassim S, Islam S, Croucher R (2010) Validity and reliability of a Severity of Dependence Scale for khat (SDS-khat). J Ethnopharmacol 132(3):570–577. Scholar
  35. Kassim S, Hawash A, Johnston A, Croucher R (2012) Validation of self-reported khat chewing amongst khat chewers: an exploratory study. J Ethnopharmacol 140(1):193–196. Scholar
  36. Kassim S, Croucher R, Al’Absi M (2013) Khat dependence syndrome: a cross sectional preliminary evaluation amongst UK-resident Yemeni khat chewers. J Ethnopharmacol 146(3):835–841. Scholar
  37. Khattab NY, Amer G (1995) Undetected neuropsychological sequelae of khat chewing in standard aviation medical examination. Aviat Space Environ Med 66(8):739–744PubMedGoogle Scholar
  38. Kilkwang L, Patel NB (2017) Catha edulis Forsk (Khat) induces conditioned place preference in mice. Society of Neuroscientists of Africa Abs no MP-07. 11–14 June 2017, Entebbe, UgandaGoogle Scholar
  39. Klein A, Beckerleg S (2007) Building castles of spit—the role of khat chewing in worship, work and leisure. In: Goodman J, Lovejoy P, Sherrat A (eds) Consuming habits. Routledge, London, pp 238–254Google Scholar
  40. Krizevski R, Dudai N, Bar E, Lewinsohn E (2007) Developmental patterns of phenylpropylamino alkaloids accumulation in khat (Catha edulis, Forsk.). J Ethnopharmacol 114(3):432–438. Scholar
  41. Lee MR (2011) The history of ephedra (ma-huang). J R Coll Physicians Edinb 41:78–84CrossRefGoogle Scholar
  42. Lindemann L, Meyer CA, Jeanneau K et al (2008) Trace amine-associated receptor 1 modulates dopaminergic activity. J Pharmacol Exp Ther 324(3):948–956. Scholar
  43. Magdum SS (2011) An overview of khat. Addict Disord Treat 10(2):72–83. Scholar
  44. Nabuzoka D, Badhadhe FA (2000) Use and perception of khat among young Somalis in a UK city. Addict Res 8:5–26CrossRefGoogle Scholar
  45. Nakajima M, Dokam A, Alsameai A et al (2014) Severity of khat dependence among adult khat chewers: the moderating influence of gender and age. J Ethnopharmacol 155(3):1467–1472. Scholar
  46. Nakajima M, Hoffman R, Al’Absi M (2017) Level of khat dependence, use patterns, and psychological correlates in Yemen: a cross-sectional investigation. EMHJ 23(3):161–167PubMedGoogle Scholar
  47. Nielsen J (1985) Cathinone affects dopamine and 5-hydroxytryptamine neurons in vivo as measured by changes in metabolites and synthesis in four forebrain regions in the rat. Neuropharmacology 24:845–852CrossRefGoogle Scholar
  48. Nutt D, King LA, Saulsbury C, Blakemore C (2007) Development of a rational scale to assess the harm of drugs of potential misuse. Lancet 369(9566):1047–1053. Scholar
  49. Odenwald M (2014) Mental health problems associated with the use and abuse of khat (Catha edulis). In: Bentivoglio M, Cavalheiro EA, Kristensson K, Patel NB (eds) Neglected tropical diseases and conditions of the nervous system. Springer, New York, pp 293–305.
  50. Odenwald M, Lingenfelder B, Schauer M et al (2007) Screening for posttraumatic stress disorder among Somali ex-combatants: a validation study. Confl Health 1:10. Scholar
  51. Parke D (1957) Ethylaminopropiophenone compounds. US Patent 2802865, 13 August 1957Google Scholar
  52. Patel NB (2015) “Natural Amphetamine” khat: a cultural tradition or a drug of abuse? In: Taba P, Lees A, Sikk K (eds) International review of neurobiology, vol 120. Academic Press, Burlington, pp 235–255Google Scholar
  53. Patel SL, Wright S, Gammampila A (2005) Khat use among Somalis in four English cities. Home Office Online Report 47/05, United Kingdom. Accessed 13 Nov 2017Google Scholar
  54. Revel FG, Moreau JL, Gainetdinov RR et al (2011) TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity. Proc Natl Acad Sci USA 108(20):8485–8490. Scholar
  55. Saha S, Dollery C (2006) Severe ischaemic cardiomyopathy associated with khat chewing. J R Soc Med 99(6):316–318. Scholar
  56. Schechter MD (1991) Effect of learned behavior upon conditioned place preference to cathinone. Pharmacol Biochem Behav 38(1):7–11CrossRefGoogle Scholar
  57. Schorno X, Steinegger E (1978) The phenylalkylamines of Catha edulis Forsk.: the absolute configuration of cathinone. United Nations Document (MNAR/7/1978)Google Scholar
  58. Schorno X, Brennneisen R, Steinegger E (1982) Qualitative und quantative Untersuchungen uber das Vorkommen ZNS-aktiver phenylpropylamine in Handelsdrogen and uber deren Verteilung in verschiedenen organen von Catha edulis. Pharm Acta Helva 57:168–176Google Scholar
  59. Schuster CR, Johanson CE (1979) Behavioral studies of cathinone in monkeys and rats. In: Problems of drug dependence. NIDA Research Monograph 27, Proceedings of 41st annual scientific meeting of the committee on problems of drug dependence. US Government Printing Office, Washington, pp 324–325Google Scholar
  60. Shortall SE, Macerola AE, Rabbi TR et al (2013a) Behavioural and neurochemical comparison of chronic intermittent cathinone, mephedrone and MDMA administration to the rat. Eur Neuropsychopharmacol 23(9):1085–1095. Scholar
  61. Shortall SE, Green AR, Swift KM et al (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. Scholar
  62. Simmler LD, Buser TA, Donzelli M et al (2013) Pharmacological characterization of designer cathinones in vitro. Br J Pharmacol 168(2):458–470. Scholar
  63. Szendrei K (1980) The chemistry of khat. Bull Narc 32(3):5–35Google Scholar
  64. Toennes SW, Harder S, Schramm M et al (2003) Pharmacokinetics of cathinone, cathine and norephedrine after chewing khat leaves. Br J Clinical Pharmacol 56(1):125–130CrossRefGoogle Scholar
  65. United Nations Office on Drugs and Crime (2015) World Drug Report, p 1Google Scholar
  66. von Brücke T (1941) Über die zentral erregende Wirkung des Alkaloides Cathin. Naunyn Schmiedeberg’s Archiv für experimentelle Pathologie und Pharmakologie 198:100CrossRefGoogle Scholar
  67. Wagner G, Preston K, Ricaurte G et al (1982) Neurochemical similarities between d, l-cathinone and d-amphetamine. Drug Alcohol Depend 9:279–284CrossRefGoogle Scholar
  68. Ward C, Gatter P (2000) Qat in Yemen—towards a policy and action plan. Document of the World Bank, 108 pp. Accessed 13 Nov 2017
  69. Widler P, Mathys K, Brenneisen R et al (1994) Pharmacodynamics and pharmacokinetics of khat: a controlled study. Clin Pharmacol Ther 55(5):556–562CrossRefGoogle Scholar
  70. Widmann M, Warsame AH, Mikulica J et al (2014) Khat use, PTSD and psychotic symptoms among Somali refugees in Nairobi—a pilot study. Front Public Health 2:71. Scholar
  71. Wolfes O (1930) Uber das Vorkommen von D-nor-iso-Ephedrin in Catha edulis. Arch Pharm (Weinheim) 268:81–83CrossRefGoogle Scholar
  72. Wondemagegn AT, Cheme MC, Kibret KT (2017) Perceived psychological, economic, and social impact of khat chewing among adolescents and adults in Nekemte Town, East Welega Zone, West Ethiopia. Biomed Res Int. Scholar
  73. Woolverton WL, Johason CE (1984) Preference in rhesus monkeys given a choice between cocaine and d, l-cathinone. J Exp Anal Behav 41(1):35–43CrossRefGoogle Scholar
  74. World Health Organization Expert Committee on Dependence Producing Drugs (1965) 14th Report. Technical Report Series No. 312Google Scholar
  75. World Health Organization (2008) Khat chewing in Yemen: turning over a new leaf. Bull World Health Organ 86(10):741–742CrossRefGoogle Scholar
  76. Yanagita T (1979) Studies on cathinones: cardiovascular and behavioural effects in rats and self-administration experiments. In: Problems of drug dependence. NIDA Research Monograph 27, Proceedings of 41st Annual scientific meeting of the committee on problems of drug dependence. US Government Printing Office, Washington, pp 326–327Google Scholar
  77. Yanagita T (1986) Intravenous self-administration of cathinone and 2-amino-l-(2,5-dimethoxy-4-methyl)-phenylpropane in rhesus monkeys. Drug Alcohol Depend 17(2–3):135–141CrossRefGoogle Scholar
  78. Zahran MA, Khedr A, Dahmash A, El-Ameir YA (2014) Qat farms in Yemen: ecology, dangerous impacts and future promise. Egypt J Basic Appl Sci I:1–8. Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medical Physiology, School of MedicineCollege of Health Sciences, University of NairobiNairobiKenya

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