Analytical and Bioanalytical Chemistry

, Volume 396, Issue 7, pp 2493–2502 | Cite as

Plasma and urine profiles of Δ9-tetrahydrocannabinol and its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol after cannabis smoking by male volunteers to estimate recent consumption by athletes

  • Rudolf Brenneisen
  • Pascale Meyer
  • Haithem Chtioui
  • Martial Saugy
  • Matthias Kamber
Original Paper

Abstract

Since 2004, cannabis has been prohibited by the World Anti-Doping Agency for all sports competitions. In the years since then, about half of all positive doping cases in Switzerland have been related to cannabis consumption. In doping urine analysis, the target analyte is 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), the cutoff being 15 ng/mL. However, the wide urinary detection window of the long-term metabolite of Δ9-tetrahydrocannabinol (THC) does not allow a conclusion to be drawn regarding the time of consumption or the impact on the physical performance. The purpose of the present study on light cannabis smokers was to evaluate target analytes with shorter urinary excretion times. Twelve male volunteers smoked a cannabis cigarette standardized to 70 mg THC per cigarette. Plasma and urine were collected up to 8 h and 11 days, respectively. Total THC, 11-hydroxy-Δ9-tetrahydrocannabinol (THC-OH), and THC-COOH were determined after hydrolysis followed by solid-phase extraction and gas chromatography/mass spectrometry. The limits of quantitation were 0.1–1.0 ng/mL. Eight puffs delivered a mean THC dose of 45 mg. Plasma levels of total THC, THC-OH, and THC-COOH were measured in the ranges 0.2–59.1, 0.1–3.9, and 0.4–16.4 ng/mL, respectively. Peak concentrations were observed at 5, 5–20, and 20–180 min. Urine levels were measured in the ranges 0.1–1.3, 0.1–14.4, and 0.5–38.2 ng/mL, peaking at 2, 2, and 6–24 h, respectively. The times of the last detectable levels were 2–8, 6–96, and 48–120 h. Besides high to very high THC-COOH levels (245 ± 1,111 ng/mL), THC (3 ± 8 ng/mL) and THC-OH (51 ± 246 ng/mL) were found in 65 and 98% of cannabis-positive athletes’ urine samples, respectively. In conclusion, in addition to THC-COOH, the pharmacologically active THC and THC-OH should be used as target analytes for doping urine analysis. In the case of light cannabis use, this may allow the estimation of more recent consumption, probably influencing performance during competitions. However, it is not possible to discriminate the intention of cannabis use, i.e., for recreational or doping purposes. Additionally, pharmacokinetic data of female volunteers are needed to interpret cannabis-positive doping cases of female athletes.

Figure

Urine concentration ranges of delta-9-tetrahydrocannabinol (THC) and its metabolites 11-hydroxy-delta-9-tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH) in athletes tested cannabispositive (15 ng/mL THC-COOH or more; N=81)

Keywords

Cannabis doping Clinical trial Plasma and urine levels Athletes’ samples 

Supplementary material

216_2009_3431_MOESM1_ESM.pdf (2 mb)
ESM 1Plasma and urine profiles of Δ9-tetrahydrocannabinol and its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol after cannabis smoking by male volunteers to estimate recent consumption by athletes (PDF 2053 kb)

References

  1. 1.
    Thevis M, Kuuranne T, Geyer H, Schänzer W (2009) Drug Test Anal 1:4–13CrossRefGoogle Scholar
  2. 2.
    Antidoping Agency Switzerland (2009) List of prohibited substances and methods (doping list). Antidoping Agency Switzerland, BerneGoogle Scholar
  3. 3.
    Saugy M, Avois L, Saudan C, Robinson N, Giroud C, Mangin P, Dvorak J (2006) Br J Sports Med 40(Suppl 1):i13–i15CrossRefGoogle Scholar
  4. 4.
    Lorente FO, Peretti-Watel P, Grelot L (2005) Addict Behav 30:1382–1391CrossRefGoogle Scholar
  5. 5.
    Wall ME, Perez-Reyes M (1981) J Clin Pharmacol 21:178S–189SGoogle Scholar
  6. 6.
    Fraser AD, Worth D (2004) Forensic Sci Int 143:147–152CrossRefGoogle Scholar
  7. 7.
    Mareck U, Fusshöller G, Geyer H, Haenelt N, Thevis M, Kamber M, Brenneisen R, Schänzer W (2006) In: Schänzer W, Geyer H, Gotzmann A, Mareck U (eds) Recent advances in doping analysis (14). Sport und Buch Strauss, Cologne, pp 101–109Google Scholar
  8. 8.
    Kamber M, Hintz O (2005) Annual report 2005. Antidoping Switzerland, BerneGoogle Scholar
  9. 9.
    Musshoff F, Madea B (2006) Ther Drug Monit 28:155–163CrossRefGoogle Scholar
  10. 10.
    Baselt RC, Cravey RH (1995) Disposition of toxic drugs and chemicals in man, 4th edn. Chemical Toxicology Institute, Foster CityGoogle Scholar
  11. 11.
    Perez-Reyes M, Lipton MA, Timmons MC, Wall ME, Brine DR, Davis KH (1973) Clin Pharmacol Ther 14:48–55Google Scholar
  12. 12.
    Lowe RH, Abraham TT, Darwin WD, Herning R, Cadet JL, Huestis MA (2009) Drug Alcohol Depend 105:24–32CrossRefGoogle Scholar
  13. 13.
    Perez-Reyes M, Timmons MC, Lipton MA, Davis KH, Wall ME (1972) Science 177:633–635CrossRefGoogle Scholar
  14. 14.
    Christensen HD, Freudenthal RI, Gidley JT, Rosenfeld R, Boegli G, Testino L, Brine DR, Pitt CG, Wall ME (1971) Science 172:165–167CrossRefGoogle Scholar
  15. 15.
    Iversen L (2000) The science of marijuana. Oxford University Press, OxfordGoogle Scholar
  16. 16.
    Cone EJ, Huestis MA (1993) Ther Drug Monit 15:527–532CrossRefGoogle Scholar
  17. 17.
    Abraham TT, Lowe RH, Pirnay SO, Darwin WD, Huestis MA (2007) J Anal Toxicol 31:477–485Google Scholar
  18. 18.
    Huestis M (1999) In: Nahas GG, Sutin K, Harvey D, Agurell S (eds) Marihuana and medicine. Humana, Totowa, pp 105–116Google Scholar
  19. 19.
    McGilveray IJ (2005) Pain Res Manag 10:15A–22AGoogle Scholar
  20. 20.
    Manno JE, Manno BR, Kemp PM, Alford DD, Abukhalaf IK, McWilliams ME, Hagaman FN, Fitzgerald MJ (2001) J Anal Toxicol 25:538–549Google Scholar
  21. 21.
    Skopp G, Potsch L (2008) J Anal Toxicol 32:160–164Google Scholar
  22. 22.
    Leighty EG, Fentiman AF Jr, Foltz RL (1976) Res Commun Chem Pathol Pharmacol 14:13–28Google Scholar
  23. 23.
    Johansson E, Halldin MM, Agurell S, Hollister LE, Gillespie HK (1989) Eur J Clin Pharmacol 37:273–277CrossRefGoogle Scholar
  24. 24.
    Haggerty GC, Deskin R, Kurtz PJ, Fentiman AF, Leighty EG (1986) Toxicol Appl Pharmacol 84:599–606CrossRefGoogle Scholar
  25. 25.
    Niedbala RS, Kardos KW, Fritch DF, Kardos S, Fries T, Waga J, Robb J, Cone EJ (2001) J Anal Toxicol 25:289–303Google Scholar
  26. 26.
    Toennes SW, Kauert GF, Steinmeyer S, Moeller MR (2005) Forensic Sci Int 152:149–155CrossRefGoogle Scholar
  27. 27.
    Fant RV, Heishman SJ, Bunker EB, Pickworth WB (1998) Pharmacol Biochem Behav 60:777–784CrossRefGoogle Scholar
  28. 28.
    Heishman SJ, Stitzer ML, Bigelow GE (1988) Pharmacol Biochem Behav 31:649–655CrossRefGoogle Scholar
  29. 29.
    Brenneisen R, ElSohly MA (1988) J Forensic Sci 33:1385–1404Google Scholar
  30. 30.
    Feng S, ElSohly MA, Salamone S, Salem MY (2000) J Anal Toxicol 24:395–402Google Scholar
  31. 31.
    International Conference on Harmonization (1996) Validation of analytical methods: methodology ICH Q2 BGoogle Scholar
  32. 32.
    Peters FT, Hartung M, Herbold M, Schmitt G, Daldrup T, Musshoff F (2004) Toxichem Krimtech 71:146–154Google Scholar
  33. 33.
    Peters FT, Drummer OH, Musshoff F (2007) Forensic Sci Int 165:216–224CrossRefGoogle Scholar
  34. 34.
    Davies KH, McDaniel IA, Caddel LW, Moody PL (1984) In: Agurell S, Dewey WL, Willette RE (eds) The cannabinoids: chemical, pharmacologic, and therapeutic aspects. Academic, New York, pp 97–109Google Scholar
  35. 35.
    Perez-Reyes M (1990) NIDA Res Monogr 99:42–62Google Scholar
  36. 36.
    Huestis MA, Henningfield JE, Cone EJ (1992) J Anal Toxicol 16:276–282Google Scholar
  37. 37.
    Kauert GF, Ramaekers JG, Schneider E, Moeller MR, Toennes SW (2007) J Anal Toxicol 31:288–293Google Scholar
  38. 38.
    Hunt CA, Jones RT (1980) J Pharmacol Exp Ther 215:35–44Google Scholar
  39. 39.
    Agurell S, Halldin M, Hollister L (1990) In: Watson R (ed) Biochemistry and physiology of substance abuse. CRC, Boca Raton, pp 138–172Google Scholar
  40. 40.
    McBurney LJ, Bobbie BA, Sepp LA (1986) J Anal Toxicol 10:56–64Google Scholar
  41. 41.
    Hollister L, Gillespie H, Ohlsson A, Lindgren J, Wahlen A, Agurell S (1981) J Clin Pharmacol 21:171S–177SGoogle Scholar
  42. 42.
    Huestis MA, Mitchell JM, Cone EJ (1996) J Anal Toxicol 20:441–452Google Scholar
  43. 43.
    Wall ME, Sadler BM, Brine D, Taylor H, Perez-Reyes M (1983) Clin Pharmacol Ther 34:352–363Google Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Rudolf Brenneisen
    • 1
  • Pascale Meyer
    • 1
  • Haithem Chtioui
    • 2
  • Martial Saugy
    • 3
  • Matthias Kamber
    • 4
  1. 1.Department of Clinical ResearchUniversity of BerneBerneSwitzerland
  2. 2.Clinical Investigation UnitUniversity Hospital of BerneBerneSwitzerland
  3. 3.Swiss Laboratory for Doping AnalysesEpalingesSwitzerland
  4. 4.Antidoping SwitzerlandBerne 22Switzerland

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