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Neurobiology of Khat (Catha edulis Forsk)

  • Nilesh B. Patel
Chapter

Abstract

Around 20 million individuals in eastern Africa and the Arabian Peninsula chew the fresh leaves and twigs of Catha edulis Forsk (khat) for its pyschostimulatory effect, a practice deeply rooted in their traditions and cultures. In 1975, the main active ingredient of khat, cathinone, was identified, and found to be structurally related to and with effects similar to amphetamines and other psychostimulants. Animal studies on the neurobiology of khat are sparse and sporadic, being a neglected area of research in the field of drugs of abuse, and most work has focused on the action of cathinone rather than on khat extracts. Like other psychostimulants, the target of khat and cathinone action on the central nervous system is the dopaminergic system involving the nucleus accumbens. Studies on peripheral tissue also show it effects on the serotoninergic system. In animal self-administration studies, cathinone exhibits an addictive and abuse potential and produces psychomotor sensitization. However, there is little information from either human or animal studies on the short- and long-term effect on brain function of daily or frequent khat use with different patterns of consumption; nor is there information on pre-natal and adolescent exposure to khat or its neurotoxic potential. More research on the effects of khat use is needed as it contains a cocktail of alkaloids which is consumed by the user.

Keywords

Drugs of abuse Cathinone Psychostimulants Miraa Qat Amphetamine 

References

  1. Al-Motarreb A, Baker K, Broadley KJ (2002) Khat: pharmacological and medical aspects and its social use in Yemen. Phytother Res 16:403–413PubMedCrossRefGoogle Scholar
  2. Banjaw MY, Schmidt WJ (2005) Behavioural sensitization following repeated intermittent oral administration of Catha edulis in rats. Behav Brain Res 156:181–189PubMedCrossRefGoogle Scholar
  3. Banjaw MY, Fendt M, Schmidt WJ (2005) Clozapine attenuates the locomotor sensitisation and the prepulse inhibition deficit induced by a repeated oral administration of Catha edulis extract and cathinone in rats. Behav Brain Res 160:365–373PubMedCrossRefGoogle Scholar
  4. 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):543–556PubMedCrossRefGoogle Scholar
  5. Braendan OJ (1979) Research on the chemical composition of khat. NIDA Res Monogr 27:320–321Google Scholar
  6. Calcagnetti DJ, Schechter MD (1992a) Increases in the locomotor activity of rats after intracerebral administration of cathinone. Brain Res Bull 29:843–846PubMedCrossRefGoogle Scholar
  7. Calcagnetti DJ, Schechter MD (1992b) Psychostimulant-induced activity is attenuated by two putative dopamine release inhibitors. Pharmacol Biochem Behav 43(4):1023–1031PubMedCrossRefGoogle Scholar
  8. Calcagnetti DJ, Schechter MD (1993) Place preference for the psychostimulant cathinone is blocked by pretreatment with a dopamine release inhibitor. Prog Neuropsychopharmacol Biol Psychiatry 17:637–649PubMedCrossRefGoogle Scholar
  9. Cleary L, Buber R, Docherty JR (2002) Effects of amphetamine derivatives and cathinone on noradrenaline-evoked contractions of rat right ventricle. Eur J Pharmacol 451(3):303–308PubMedCrossRefGoogle Scholar
  10. Connor JD, Rostom A, Makonnen E (2002) Comparison of effects khat extract and amphetamine on motor behaviors in mice. J Ethnopharmacol 8:65–71CrossRefGoogle Scholar
  11. Fleckenstein AE, Haughey HM, Metzger RR et al (1999) Differential effects of psychostimulants and related agents on dopaminergic and serotonergic transporter function. Eur J Pharmacol 382:45–49PubMedCrossRefGoogle Scholar
  12. Giannini AJ, Burge H, Shakeen M, Price WA (1986) Khat: another drug of abuse. J Psychoactive Drugs 18:155–158PubMedGoogle Scholar
  13. Glennon RA, Liebowitz SM (1982) Serotonin receptor affinity of cathinone and related analogues. J Med Chem 25:393–397PubMedCrossRefGoogle Scholar
  14. Gosnell BA, Yracheta JM, Bell SM, Lane KE (1996) Intravenous self-administration of cathinone by rats. Behav Pharmacol 7:526–531PubMedGoogle Scholar
  15. Goudie AJ, Atkinson J, West CR (1986) Discriminative properties of the psychostimulant dl-cathinone in a two lever operant task. Lack of evidence for dopaminergic mediation. Neuropharmacol 25:85–94CrossRefGoogle Scholar
  16. Halbach H (1979) Khat-the problem today. NIDA Res Monogr 27:318–319PubMedGoogle Scholar
  17. Houghton P, Ismail M, Salvage S (2011) Not cathinone alone – dopamine, khat constituents and brain tissue. http://darc-khat.middlesex.wikispaces.net/file/view/Not+cathinone+alone+_dopamine+khat+constituents+and+brain+tissue_+Houghton+et+al.pdf
  18. Huang D, Wilson MC (1986) Comparative discriminative stimulus properties of dl-cathinone, d-amphetamine, and cocaine in rats. Pharmacol Biochem Behav 24(2):205–210PubMedCrossRefGoogle Scholar
  19. Kalix P (1980a) Hypermotility of the amphetamine type induced by a constituent of khat leaves. Br J Pharmacol 68:11–13PubMedCentralPubMedCrossRefGoogle Scholar
  20. Kalix P (1980b) Hyperthermic response to (-)-cathinone, an alkaloid of Catha edulis (khat). J Pharm Pharmacol 32:662–663PubMedCrossRefGoogle Scholar
  21. Kalix P (1983) Effect of the alkaloid (-) cathinone on the release of radioactivityfrom rabbit atria prelabelled with 3H-norepinephrine. Life Sci 32:801–807PubMedCrossRefGoogle Scholar
  22. 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):127–129PubMedCrossRefGoogle Scholar
  23. Kalix P (1986) A comparison of the effects of some phenethylamines on the release of radioactivity from isolated rat caudate nucleus prelabelled with 3H-dopamine. Arzneimittelforschung 36:1019–10121PubMedGoogle Scholar
  24. Kalix P (1992) Cathinone, a natural amphetamine. Pharmacol Toxicol 70:77–86PubMedCrossRefGoogle Scholar
  25. Kalix P, Geisshüsler S, Brenneisen R (1987) The effect of phenylpentenyl-khatamines on the release of radioactivity from rat striatal tissue prelabelled with [3H]dopamine. J Pharm Pharmacol 39:135–137PubMedCrossRefGoogle Scholar
  26. Kite GC, Ismail M, Simmonds MS, Houghton PJ (2003) Use of doubly protonated molecules in the analysis of cathedulins in crude extracts of khat (Catha edulis) by liquid chromatography/serial mass spectrometry. Rapid Commun Mass Spectrom 17(14):1553–15564PubMedCrossRefGoogle Scholar
  27. Kuz’min AV, Evartan EE (1991) The intravenous self-administration of narcotics in mice. Zh Vyssh Nerv Deiat Im I P Pavlova 41:1253–1260PubMedGoogle Scholar
  28. Magdum SS (2011) An overview of khat. Addict Disord Their Treat 10:72–83CrossRefGoogle Scholar
  29. Mereu GP, Pacitti C, Argiolas A (1983) Effect of (-)-cathinone, a khat leaf constituent, on dopaminergic firing and dopamine metabolism in the rat brain. Life Sci 32:1383–1389PubMedCrossRefGoogle Scholar
  30. Nutt D, King LA, Saulsbury W, Blakemore C (2007) Development of a rational scale to assess the harm of drugs to potential users. Lancet 369:1047–1053PubMedCrossRefGoogle Scholar
  31. Odenwald M (2014) Mental health problems associated with the use and abuse of khat (Catha edulis). In: Bentivoglio M, Cavalheiro EA, Kristensson K, Patel N (eds) Neglected tropical diseases and conditions of the nervous system. Springer, New YorkGoogle Scholar
  32. Oyungu E, Kioy PG, Patel NB (2007) Effect of Catha edulis (khat) on behaviour and its potential to induce seizures in Sprague Dawley rats. East Afr Med J 84:219–225PubMedGoogle Scholar
  33. Oyungu E, Kioy PG, Patel NB (2009) Proconvulsant effect of khat (Catha edulis) in Sprague-Dawley rats. J Ethnopharmacol 121:476–478PubMedCrossRefGoogle Scholar
  34. Pehek EA, Schechter MD, Yamamoto BK (1990) Effects of cathinone and amphetamine on the neurochemistry of dopamine in vivo. Neuropharmacology 29:1171–1176PubMedCrossRefGoogle Scholar
  35. Rosecrans JA, Campbell OL, Dewey WL, Harris LS (1979) Discriminative stimulus and neurochemical mechanism of cathinone: a preliminary study. NIDA Res Monogr 27:328–329PubMedGoogle Scholar
  36. Saha S, Dollery C (2006) Severe ischaemic cardiomyopathy associated with khat chewing. J R Soc Med 99:316–318PubMedCentralPubMedCrossRefGoogle Scholar
  37. Schechter MD (1986a) Discriminative properties of l-cathinone compared to dl- and d-cathinone. Pharmacol Biochem Behav 24:1161–1165PubMedCrossRefGoogle Scholar
  38. Schechter MD (1986b) Induction of and recovery from tolerance to the discriminative stimulus properties of l-cathinone. Pharmacol Biochem Behav 25:13–16PubMedCrossRefGoogle Scholar
  39. Schechter MD (1986c) Dopaminergic mediation of a behavioral effect of l-cathinone. Pharmacol Biochem Behav 25:337–340PubMedCrossRefGoogle Scholar
  40. Schechter MD (1989) Temporal parameters of cathinone, amphetamine and cocaine. Pharmacol Biochem Behav 34:289–292PubMedCrossRefGoogle Scholar
  41. Schechter MD (1990a) Rats become acutely tolerant to cathine after amphetamine or cathinone administration. Psychopharmacology (Berl) 101:126–131CrossRefGoogle Scholar
  42. Schechter MD (1990b) Dopaminergic nature of acute cathine tolerance. Pharmacol Biochem Behav 36:817–820PubMedCrossRefGoogle Scholar
  43. Schechter MD (1991a) Effect of learned behavior upon conditioned place preference to cathinone. Pharmacol Biochem Behav 38:7–11PubMedCrossRefGoogle Scholar
  44. Schechter MD (1991b) Effect of serotonin depletion by p- chlorophenylalanine upon discriminative behaviours. Gen Pharmacol 22:889–8893PubMedCrossRefGoogle Scholar
  45. Schechter MD (1992) Effect of altering dopamine or serotonin neurotransmitters upon cathinone discrimination. Pharmacol Biochem Behav 41:37–41PubMedCrossRefGoogle Scholar
  46. Schechter MD, Bojaw W (1988) CGS 10746B is able to attenuate the effects of amphetamine: further evidence for dopaminergic mediation. Pharmacol Biochem Behav 30:1089–1092PubMedCrossRefGoogle Scholar
  47. Schechter MD, Glennon RA (1985) Cathinone, cocaine and methamphetamine: similarity of behavioral effects. Pharmacol Biochem Behav 22(6):913–916PubMedCrossRefGoogle Scholar
  48. Schechter MD, McBurney D (1991) Effect of repeated administrations upon cathinone discrimination and conditioned place preference. Gen Pharmacol 22:779–782PubMedCrossRefGoogle Scholar
  49. Schechter MD, Meehan SM (1993) Conditioned place preference produced by the psychostimulant cathinone. Eur J Pharmacol 232:135–138PubMedCrossRefGoogle Scholar
  50. Schechter MD, Rosecrans JA, Glennon RA (1984) Comparison of behavioral effects of cathinone, amphetamine and apomorphine. Pharmacol Biochem Behav 20:181–184PubMedCrossRefGoogle Scholar
  51. Schechter MD, Schechter JB, Calcagnetti DJ (1992) Direct microinjection of cathinone into the rat brain produces discriminative stimuli. Pharmacol Biochem Behav 42:619–623PubMedCrossRefGoogle Scholar
  52. Schmid CL, Bohn LM (2010) Serotonin, but not N-Methyltryptamines, activates the serotonin 2A receptor via a β-arrestin2/Src/Akt signaling complex in vivo. J Neurosci 30:13513–13524PubMedCentralPubMedCrossRefGoogle Scholar
  53. Schorno X, Steinegger E (1978) The phyenylalkylamines of Catha edulis forsk: the absolute configuration of cathinone. United Nations Document MNAR/7/1978Google Scholar
  54. Schuster CR, Johanson CE (1979) Behavioral studies of cathinone in monkeys and rats. NIDA Res Monogr 27:324–325PubMedGoogle Scholar
  55. UNODC United Nations Office on Drugs and Crime (1980) Bulletin Narcotics (3)Google Scholar
  56. Vollenweider FX (2001) Brain mechanism of hallucinogens and entactogens. Dialogues Clin Neurosci 3:265–279PubMedCentralPubMedGoogle Scholar
  57. Wagner GC, Preston K, Ricaurte GA, Schuster CR, Seiden LS (1982) Neurochemical similarities between d, l-cathinone and d-amphetamine. Drug Alcohol Depend 9:279–284PubMedCrossRefGoogle Scholar
  58. WHO Expert Committee on Addiction-Producing Drugs (1964) World Health Organization Technical Reprot Series No 273: pp 10 Google Scholar
  59. Wise RA, Bozarth MA (1987) A psychomotor stimulate theory of addiction. Psychol Rev 94:469–492PubMedCrossRefGoogle Scholar
  60. Woolverton WL, Johanson CE (1984) Preference in rhesus monkeys given a choice between cocaine and d, l-cathinone. J Exp Anal Behav 41:35–43PubMedCentralPubMedCrossRefGoogle Scholar
  61. Yanagita T (1979) Studies on cathinones: cardiovascular and behavioral effects in rats and self-administration experiment in rhesus monkeys. NIDA Res Monogr 27:326–327PubMedGoogle Scholar
  62. Yanagita T (1986) Intravenous self-administration of (-)-cathinone and 2-amino-1-(2,5-dimethoxy-4-methyl)phenylpropane in rhesus monkeys. Drug Alcohol Depend 17:135–141PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Physiology, School of Medicine, College of Health ScienceUniversity of NairobiNairobiKenya

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