The psychostimulant khat (Catha edulis) inhibits CYP2D6 enzyme activity in humans

Journal of Clinical Psychopharmacology

Volumn 35, Issue 6, 2015, Pages 694-699

  Bedada, Worku ^a   De Andrés, Fernando ^b   Engidawork, Ephrem ^a   Pohanka, Anton ^c   Beck, Olof ^c   Bertilsson, Leif ^c   Llerena, Adrián ^b   Aklillu, Eleni ^c  

^a ADDIS ABABA UNIVERSITY   (Ethiopia)

^b UNIVERSITY OF EXTREMADURA   (Spain)

^c KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

cathine; cathinone; CYP2D6; dextromethorphan; drug interaction; khat

Indexed keywords

CATHINONE; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; DEXTROMETHORPHAN; DEXTRORPHAN; NORPSEUDOEPHEDRINE; 3-METHOXYMORPHINAN; AMINO ACID RECEPTOR BLOCKING AGENT; CYP3A4 PROTEIN, HUMAN; CYTOCHROME P450 2D6 INHIBITOR; CYTOCHROME P450 3A;

ARTICLE; BLOOD SAMPLING; CATHA EDULIS; CROSSOVER PROCEDURE; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME INHIBITION; GENOTYPE; HERB DRUG INTERACTION; HUMAN; HUMAN EXPERIMENT; LIQUID CHROMATOGRAPHY; MALE; PRIORITY JOURNAL; TANDEM MASS SPECTROMETRY; ADULT; ANALOGS AND DERIVATIVES; BLOOD; CATHA; DRUG EFFECTS; ETHIOPIA; GENETICS; PLANT LEAF; YOUNG ADULT;

ADULT; CATHA; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 CYP2D6 INHIBITORS; CYTOCHROME P-450 CYP3A; DEXTROMETHORPHAN; DEXTRORPHAN; ETHIOPIA; EXCITATORY AMINO ACID ANTAGONISTS; HUMANS; MALE; PLANT LEAVES; YOUNG ADULT;

EID: 84947021687     PISSN: 02710749     EISSN: 1533712X     Source Type: Journal    
DOI: 10.1097/JCP.0000000000000413     Document Type: Article

References (39)

1. Al-Hebshi NN, Skaug N. Khat (Catha edulis)-an updated review. Addict Biol. 2005;10:299-307.
2. Hoffman R, Al'Absi M. Khat use and neurobehavioral functions: suggestions for future studies. J Ethnopharmacol. 2010;132:554-563.
3. Kassim S, Croucher R, al'Absi M. Khat dependence syndrome: a cross-sectional preliminary evaluation amongst UK-resident Yemeni khat chewers. J Ethnopharmacol. 2013;146:835-841.
4. Feyissa AM, Kelly JP. A review of the neuropharmacological properties of khat. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:1147-1166.
5. Berhanu D, Go VF, Ruff A, et al. Khat use among HIV voluntary counselling and testing centre clients in Ethiopia. Cult Health Sex. 2012;14: 1197-1212.
6. Gebrehanna E, Berhane Y, Worku A. Khat chewing among Ethiopian University students-a growing concern. BMC Public Health. 2014; 14:1198.
7. Kalix P. Cathinone, a natural amphetamine. Pharmacol Toxicol. 1992;70: 77-86.
8. Valente MJ, Guedes de Pinho P, de Lourdes Bastos M, et al. Khat and synthetic cathinones: a review. Arch Toxicol. 2014;88:15-45.
9. Brenneisen R, Geisshusler S, Schorno X. Metabolism of cathinone to (?)-norephedrine and (?)-norpseudoephedrine. J Pharm Pharmacol. 1986; 38:298-300.
10. Mathys K, Brenneisen R. 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. 1992;593:79-85.
11. Aklillu E, Herrlin K, Gustafsson LL, et al. Evidence for environmental influence on CYP2D6-catalysed debrisoquine hydroxylation as demonstrated by phenotyping and genotyping of Ethiopians living in Ethiopia or in Sweden. Pharmacogenetics. 2002;12:375-383.
12. Cascorbi I. Pharmacogenetics of cytochrome p4502D6: genetic background and clinical implication. Eur J Clin Invest. 2003;33(suppl 2): 17-22.
13. Pedersen AJ, Reitzel LA, Johansen SS, et al. In vitro metabolismstudies on mephedrone and analysis of forensic cases. Drug Test Anal. 2013;5: 430-438.
14. Pedersen AJ, Petersen TH, Linnet K. In vitro metabolism and pharmacokinetic studies on methylone. Drug Metab Dispos. 2013;41: 1247-1255.
15. Malaju MT, Asale GA. Association of khat and alcohol use with HIV infection and age at first sexual initiation among youths visiting HIV testing and counseling centers in Gamo-Gofa Zone, South West Ethiopia. BMC Int Health Hum Rights. 2013;13:10.
16. Izzo AA. Herb-drug interactions: an overview of the clinical evidence. Fundam Clin Pharmacol. 2005;19:1-16.
17. Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J. 2005;5:6-13.
18. Tadesse N, Awoke Ayele T, Birhanu Mengesha Z, et al. High prevalence of HIV/AIDS risky sexual behaviors among street youth in Gondar town: a community based cross sectional study. BMC Res Notes. 2013;6:234.
19. Fugh-Berman A, Ernst E. Herb-drug interactions: review and assessment of report reliability. Br J Clin Pharmacol. 2001;52:587-595.
20. Attef OA, Ali AA, Ali HM. Effect of khat chewing on the bioavailability of ampicillin and amoxycillin. J Antimicrob Chemother. 1997;39: 523-525.
21. de Andres F, Sosa-Macias M, Llerena A. A rapid and simple LC-MS/MS method for the simultaneous evaluation of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 hydroxylation capacity. Bioanalysis. 2014;6: 683-696.
22. Al-Saffar Y, Stephanson NN, Beck O. Multicomponent LC-MS/MS screening method for detection of new psychoactive drugs, legal highs, in urine-experience from the Swedish population. J Chromatogr B Analyt Technol Biomed Life Sci. 2013;930:112-120.
23. Dorado P, Heras N, Machin E, et al. CYP2D6 genotype and dextromethorphan hydroxylation phenotype in an Ecuadorian population. Eur J Clin Pharmacol. 2012;68:637-644.
24. Toennes SW, Harder S, Schramm M, et al. Pharmacokinetics of cathinone, cathine and norephedrine after the chewing of khat leaves. Br J Clin Pharmacol. 2003;56:125-130.
25. Toennes SW, Kauert GF. Excretion and detection of cathinone, cathine, and phenylpropanolamine in urine after kath chewing. Clin Chem. 2002;48: 1715-1719.
26. Aklillu E, Persson I, Bertilsson L, et al. Frequent distribution of ultrarapid metabolizers of debrisoquine in an Ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles. J Pharmacol Exp Ther. 1996;278:441-446.
27. Gebeyehu E, Engidawork E, Bijnsdorp A, et al. Sex and CYP3A5 genotype influence total CYP3A activity: high CYP3A activity and a unique distribution of CYP3A5 variant alleles in Ethiopians. Pharmacogenomics J. 2011;11:130-137.
28. Ingelman-Sundberg M. The human genome project and novel aspects of cytochrome P450 research. Toxicol Appl Pharmacol. 2005;207:52-56.
29. Ozdemir V, Naranjo CA, Shulman RW, et al. Determinants of interindividual variability and extent of CYP2D6 and CYP1A2 inhibition by paroxetine and fluvoxamine in vivo. J Clin Psychopharmacol. 1998; 18:198-207.
30. Bhui K, Craig T, Mohamud S, et al. Mental disorders among Somali refugees: developing culturally appropriate measures and assessing socio-cultural risk factors. Soc Psychiatry Psychiatr Epidemiol. 2006; 41:400-408.
31. Widmann M, Warsame AH, Mikulica J, et al. Khat use, PTSD and psychotic symptoms among Somali refugees in Nairobi-a pilot study. Front Public Health. 2014;2:71.
32. Kroll J, Yusuf AI, Fujiwara K. Psychoses, PTSD, and depression in Somali refugees in Minnesota. Soc Psychiatry Psychiatr Epidemiol. 2011;46: 481-493.
33. Bertilsson L, Dahl ML, Dalen P, et al. Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br J Clin Pharmacol. 2002;53:111-122.
34. Ravindranath V, Strobel HW. Cytochrome P450-mediated metabolism in brain: functional roles and their implications. Expert Opin Drug Metab Toxicol. 2013;9:551-558.
35. Bennett JW, Pybus BS, YadavaA, et al. Primaquine failure and cytochrome P-450 2D6 in Plasmodium vivax malaria. N Engl JMed. 2013;369: 1381-1382.
36. Kreth K, Kovar K, Schwab M, et al. Identification of the human cytochromes P450 involved in the oxidative metabolism of "Ecstasy"-related designer drugs. Biochem Pharmacol. 2000;59: 1563-1571.
37. Paillet-Loilier M, Cesbron A, Le Boisselier R, et al. Emerging drugs of abuse: current perspectives on substituted cathinones. Subst Abuse Rehabil. 2014;5:37-52.
38. Wu D, Otton SV, Inaba T, et al. Interactions of amphetamine analogs with human liver CYP2D6. Biochem Pharmacol. 1997;53: 1605-1612.
39. Dandara C, Huzair F, Borda-Rodriguez A, et al. H3Africa and the African life sciences ecosystem: building sustainable innovation. OMICS. 2014; 18:733-739.