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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

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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.

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)

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Acknowledgements

Special thanks go to the staff of the CIU and Arno Hazekamp, University of Leiden, for assisting in the supply of the test material (Bedrobinol®). The study was supported by Antidoping Switzerland, Berne, Switzerland.

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Authors and Affiliations

  1. Department of Clinical Research, University of Berne, Murtenstr. 35, 3010, Berne, Switzerland

    Rudolf Brenneisen & Pascale Meyer

  2. Clinical Investigation Unit, University Hospital of Berne, 3010, Berne, Switzerland

    Haithem Chtioui

  3. Swiss Laboratory for Doping Analyses, 1066, Epalinges, Switzerland

    Martial Saugy

  4. Antidoping Switzerland, P.O. Box 606, 3000, Berne 22, Switzerland

    Matthias Kamber

Authors
  1. Rudolf Brenneisen
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  2. Pascale Meyer
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  3. Haithem Chtioui
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  4. Martial Saugy
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  5. Matthias Kamber
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Correspondence to Rudolf Brenneisen.

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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 (PDF 2053 kb)

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Brenneisen, R., Meyer, P., Chtioui, H. et al. 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. Anal Bioanal Chem 396, 2493–2502 (2010). https://doi.org/10.1007/s00216-009-3431-3

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  • DOI: https://doi.org/10.1007/s00216-009-3431-3

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