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Oral fluid cannabinoid concentrations following controlled smoked cannabis in chronic frequent and occasional smokers

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Abstract

Oral fluid (OF) is an alternative biological matrix for monitoring cannabis intake in drug testing, and drugged driving (DUID) programs, but OF cannabinoid test interpretation is challenging. Controlled cannabinoid administration studies provide a scientific database for interpreting cannabinoid OF tests. We compared differences in OF cannabinoid concentrations from 19 h before to 30 h after smoking a 6.8 % THC cigarette in chronic frequent and occasional cannabis smokers. OF was collected with the Statsure Saliva Sampler™ OF device. 2D-GC-MS was used to quantify cannabinoids in 357 OF specimens; 65 had inadequate OF volume within 3 h after smoking. All OF specimens were THC-positive for up to 13.5 h after smoking, without significant differences between frequent and occasional smokers over 30 h. Cannabidiol (CBD) and cannabinol (CBN) had short median last detection times (2.5–4 h for CBD and 6–8 h for CBN) in both groups. THCCOOH was detected in 25 and 212 occasional and frequent smokers’ OF samples, respectively. THCCOOH provided longer detection windows than THC in all frequent smokers. As THCCOOH is not present in cannabis smoke, its presence in OF minimizes the potential for false positive results from passive environmental smoke exposure, and can identify oral THC ingestion, while OF THC cannot. THC ≥ 1 μg/L, in addition to CBD ≥ 1 μg/L or CBN ≥ 1 μg/L suggested recent cannabis intake (≤13.5 h), important for DUID cases, whereas THC ≥ 1 μg/L or THC ≥ 2 μg/L cutoffs had longer detection windows (≥30 h), important for workplace testing. THCCOOH windows of detection for chronic, frequent cannabis smokers extended beyond 30 h, while they were shorter (0–24 h) for occasional cannabis smokers.

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Abbreviations

DRUID:

Driving Under the Influence of Drugs, Alcohol and Medicines

DUID:

Driving Under Influence of Drugs

LOQ:

Limit of Quantification

OF:

Oral fluid

SAMHSA:

Substance Abuse and Mental Health Services Administration

References

  1. United Nations Office on Drugs and Crime (UNODC) (2011) World Drug Report 2011. Vienna

  2. Substance Abuse and Mental Health Services Administration (SAMHSA) (2011) Results from the 2010 National Survey on Drug Use and Health: Summary of National Findings (trans: U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES SAaMHSA, Center for Behavioral Health Statistics and Quality). Substance Abuse and Mental Health Services Administration, Rockville, MD

  3. Substance Abuse and Mental Health Services Administration (2008) Results from the 2007 National Survey on Drug Use and Health: National Findings. NSDUH Series H-34. Department of Health and Human Services (DHHS), Rockville, MD

    Google Scholar 

  4. Lacey JH, Kelley-Baker T, Romano E, Brainard K, Ramirez A (2012) Results of the 2012 California Roadside Survey of Nighttime Weekend Drivers’ Alcohol and Drug Use

  5. Huestis MA, Verstraete A, Kwong TC, Morland J, Vincent MJ, De La Torre R (2011) Oral fluid testing: promises and pitfalls. Clin Chem 57(6):805–810

    Article  CAS  Google Scholar 

  6. Heltsley R, Depriest A, Black DL, Crouch DJ, Robert T, Marshall L, Meadors VM, Caplan YH, Cone EJ (2012) Oral fluid drug testing of chronic pain patients. II. Comparison of paired oral fluid and urine specimens. J Anal Toxicol 36(2):75–80. doi:10.1093/jat/bkr019

    Article  CAS  Google Scholar 

  7. Tsanaclis LM, Wicks JFC, Chasin AAM (2012) Workplace drug testing, different matrices different objectives. Drug Test Anal 4(2):83–88. doi:10.1002/dta.399

    Article  CAS  Google Scholar 

  8. Verstraete AG (2005) Oral fluid testing for driving under the influence of drugs: history, recent progress and remaining challenges. Forensic Sci Int 150(2–3):143–150

    Article  CAS  Google Scholar 

  9. Bosker WM, Huestis MA (2009) Oral fluid testing for drugs of abuse. Clin Chem 55(11):1910–1931

    Article  CAS  Google Scholar 

  10. Niedbala RS, Kardos KW, Fritch DF, Kunsman KP, Blum KA, Newland GA, Waga J, Kurtz L, Bronsgeest M, Cone EJ (2005) Passive cannabis smoke exposure and oral fluid testing. II. Two studies of extreme cannabis smoke exposure in a motor vehicle. J Anal Toxicol 29(7):607–615

    Article  CAS  Google Scholar 

  11. Moore C, Coulter C, Uges D, Tuyay J, van der Linde S, van Leeuwen A, Garnier M, Orbita J Jr (2011) Cannabinoids in oral fluid following passive exposure to marijuana smoke. Forensic Sci Int 212(1–3):227–230

    Article  CAS  Google Scholar 

  12. Lee D, Karschner EL, Milman G, Barnes AJ, Goodwin RS, Huestis MA (2012) Can oral fluid cannabinoid testing monitor medication compliance and/or cannabis smoking during oral THC and oromucosal Sativex administration? Drug Alcohol Depend. doi:10.1016/j.drugalcdep.2012.10.011

    Google Scholar 

  13. Milman G, Barnes A, Schwope D, Schwilke E, Goodwin R, Kelly D, Gorelick D, Huestis M (2011) Cannabinoids and metabolites in expectorated oral fluid after 8 days of controlled around-the-clock oral THC administration. Anal Bioanal Chem 401(2):599–607. doi:10.1007/s00216-011-5066-4

    Article  CAS  Google Scholar 

  14. Milman G, Barnes AJ, Schwope DM, Schwilke EW, Darwin WD, Goodwin RS, Kelly DL, Gorelick DA, Huestis MA (2010) Disposition of cannabinoids in oral fluid after controlled around-the-clock oral THC administration. Clin Chem 56(8):1261–1269. doi:10.1373/clinchem.2009.141853

    Article  CAS  Google Scholar 

  15. Milman G, Schwope DM, Schwilke EW, Darwin WD, Kelly DL, Goodwin RS, Gorelick DA, Huestis MA (2011) Oral fluid and plasma cannabinoid ratios after around-the-clock controlled oral {Delta}9-tetrahydrocannabinol administration. Clin Chem 57(11):1597–1606. doi:10.1373/clinchem.2011.169490

    Article  CAS  Google Scholar 

  16. Lee D, Schwope DM, Milman G, Barnes AJ, Gorelick DA, Huestis MA (2012) Cannabinoid disposition in oral fluid after controlled smoked cannabis. Clin Chem 58(4). doi:10.1373/clinchem.2011.177881

  17. Milman G, Schwope DM, Gorelick DA, Huestis MA (2012) Cannabinoids and metabolites in expectorated oral fluid following controlled smoked cannabis. Clin Chim Acta 413(7–8):765–770

    Article  CAS  Google Scholar 

  18. Lee D, Milman G, Barnes AJ, Goodwin RS, Hirvonen J, Huestis MA (2011) Oral fluid cannabinoids in chronic, daily cannabis smokers during sustained, monitored abstinence. Clin Chem:clinchem 2011:164822. doi:10.1373/clinchem.2011.164822

    Google Scholar 

  19. Perez-Reyes M (1990) Marijuana smoking: factors that influence the bioavailability of tetrahydrocannabinol. In: Chiang CN, Hawks RL (eds) Research findings on smoking of abused substances. NIDA Research Monograph #99, Rockville, pp 42–62

    Google Scholar 

  20. McClure E, Stitzer M, Vandrey R (2012) Characterizing smoking topography of cannabis in heavy users. Psychopharmacology 220(2):309–318. doi:10.1007/s00213-011-2480-4

    Article  CAS  Google Scholar 

  21. Azorlosa JL, Greenwald MK, Stitzer ML (1995) Marijuana smoking: effects of varying puff volume and breathhold duration. J Pharmacol Exp Ther 272:560–569

    CAS  Google Scholar 

  22. Toennes SW, Ramaekers JG, Theunissen EL, Moeller MR, Kauert GF (2008) Comparison of cannabinoid pharmacokinetic properties in occasional and heavy users smoking a marijuana or placebo joint. J Anal Toxicol 32:470–477

    Article  CAS  Google Scholar 

  23. Bergamaschi MM, Karschner EL, Goodwin RS, Scheidweiler KB, Hirvonen J, Queiroz RH, Huestis MA (2013) Impact of prolonged cannabinoid excretion in chronic daily cannabis smokers’ blood on per se drugged driving laws. Clin Chem 59(3):519–526. doi:10.1373/clinchem.2012.195503

    Article  CAS  Google Scholar 

  24. Huestis MA, Henningfield JE, Cone EJ (1992) Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. J Anal Toxicol 16:276–282

    Article  CAS  Google Scholar 

  25. Lee D, Vandrey R, Milman G, Bergamaschi M, Mendu DR, Murray JA, Barnes AJ, Huestis MA (2013) Oral fluid/plasma cannabinoid ratios following controlled oral THC and smoked cannabis administration. Anal Bioanal Chem. doi:10.1007/s00216-013-7159-8

    Google Scholar 

  26. Toennes SW, Ramaekers JG, Theunissen EL, Moeller MR, Kauert GF (2010) Pharmacokinetic properties of 9-tetrahydrocannabinol in oral fluid of occasional and chronic users. J Anal Toxicol 34(4):216–221

    Article  CAS  Google Scholar 

  27. Milman G, Barnes AJ, Lowe RH, Huestis MA (2010) Simultaneous quantification of cannabinoids and metabolites in oral fluid by two-dimensional gas chromatography mass spectrometry. J Chromatogr A 1217(9):1513–1521. doi:10.1016/j.chroma.2009.12.053

    Article  CAS  Google Scholar 

  28. Lowe RH, Karschner EL, Schwilke EW, Barnes AJ, Huestis MA (2007) Simultaneous quantification of delta9-tetrahydrocannabinol, 11-hydroxy-delta9-tetrahydrocannabinol, and 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid in human plasma using two-dimensional gas chromatography, cryofocusing, and electron impact-mass spectrometry. J Chromatogr A 1163:318–327

    Article  CAS  Google Scholar 

  29. Schwope DM, Karschner EL, Gorelick DA, Huestis MA (2011) Identification of recent cannabis use: whole-blood and plasma free and glucuronidated cannabinoid pharmacokinetics following controlled smoked cannabis administration. Clin Chem 57(10):1406–1414. doi:10.1373/clinchem.2011.171777

    Article  CAS  Google Scholar 

  30. Davis KH, McDaniel IA, Cadwell IW, Moody PL (1984) Some smoking characteristics of marijuana cigarettes. In: Agurell S, Dewey WL, Willette RE (eds) The cannabinoids: chemical, pharmacologic, and therapeutic aspects. Academic, Orlando, pp 97–109

    Chapter  Google Scholar 

  31. Kauert GF, Ramaekers JG, Schneider E, Moeller MR, Toennes SW (2007) Pharmacokinetic properties of delta9-tetrahydrocannabinol in serum and oral fluid. J Anal Toxicol 31(5):288–293

    Article  CAS  Google Scholar 

  32. Niedbala RS, Kardos KW, Fritch DF, Kardos S, Fries T, Waga J, Robb J, Cone EJ (2001) Detection of marijuana use by oral fluid and urine analysis following single-dose administration of smoked and oral marijuana. J Anal Toxicol 25(5):289–303

    Article  CAS  Google Scholar 

  33. Huestis MA, Cone EJ (2004) Relationship of Delta 9-tetrahydrocannabinol concentrations in oral fluid and plasma after controlled administration of smoked cannabis. J Anal Toxicol 28(6):394–399

    Article  CAS  Google Scholar 

  34. Maurer HH, Sauer C, Theobald DS (2006) Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine. Ther Drug Monit 28(3):447–453. doi:10.1097/01.ftd.0000211812.27558.6e

    Article  CAS  Google Scholar 

  35. Watanabe K, Matsunaga T, Yamamoto I, Funae Y, Yoshimura H (1995) Involvement of CYP2C in the metabolism of cannabinoids by human hepatic microsomes from an old woman. Biol Pharm Bull 18(8):1138–1141

    Article  CAS  Google Scholar 

  36. Vondracek M, Xi Z, Larsson P, Baker V, Mace K, Pfeifer A, Tjälve H, Donato MT, Gomez-Lechon MJ, Grafström RC (2001) Cytochrome P450 expression and related metabolism in human buccal mucosa. Carcinogenesis 22(3):481–488. doi:10.1093/carcin/22.3.481

    Article  CAS  Google Scholar 

  37. Yang S-P, Raner GM (2005) Cytochrome P450 expression and activities in human tongue cells and their modulation by green tea extract. Toxicol Appl Pharmacol 202(2):140–150

    Article  CAS  Google Scholar 

  38. Moore C, Rana S, Coulter C, Day D, Vincent M, Soares J (2007) Detection of conjugated 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid in oral fluid. J Anal Toxicol 31(4):187–194

    Article  CAS  Google Scholar 

  39. Fabritius M, Staub C, Mangin P, Giroud C (2013) Analysis of cannabinoids in oral fluid by liquid chromatography–tandem mass spectrometry. Forensic Toxicol 31(1):151–163. doi:10.1007/s11419-012-0168-z

    Article  CAS  Google Scholar 

  40. Lee D, Milman G, Schwope DM, Barnes AJ, Gorelick DA, Huestis MA (2012) Cannabinoid stability in authentic oral fluid after controlled cannabis smoking. Clin Chem 58(7):1101–1109. doi:10.1373/clinchem.2012.184929

    Article  CAS  Google Scholar 

  41. Niedbala R, Kardos K, Fritch D, Kardos S, Fries T, Waga J, Robb J, Cone E (2001) Detection of marijuana use by oral fluid and urine analysis following single-dose administration of smoked and oral marijuana. J Anal Toxicol 25:289–303

    Article  CAS  Google Scholar 

  42. Day D, Kuntz DJ, Feldman M, Presley L (2006) Detection of THCA in oral fluid by GC-MS-MS. J Anal Toxicol 30(9):645–650

    Article  CAS  Google Scholar 

  43. Moore C, Ross W, Coulter C, Adams L, Rana S, Vincent M, Soares J (2006) Detection of the marijuana metabolite 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid in oral fluid specimens and its contribution to positive results in screening assays. J Anal Toxicol 30(7):413–418

    Article  CAS  Google Scholar 

  44. Moore C, Coulter C, Rana S, Vincent M, Soares J (2006) Analytical procedure for the determination of the marijuana metabolite 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid in oral fluid specimens. J Anal Toxicol 30(7):409–412

    Article  CAS  Google Scholar 

  45. Scheidweiler K, Himes S, Chen X, Liu H-F, Huestis M (2013) 11-Nor-9-carboxy-∆9-tetrahydrocannabinol quantification in human oral fluid by liquid chromatography–tandem mass spectrometry. Anal Bioanal Chem. 1–9. doi:10.1007/s00216-013-7027-6

  46. Coulter C, Garnier M, Moore C (2012) Analysis of tetrahydrocannabinol and its metabolite, 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid, in oral fluid using liquid chromatography with tandem mass spectrometry. J Anal Toxicol 36(6):413–417. doi:10.1093/jat/bks039

    Article  CAS  Google Scholar 

  47. Lee PD, Chang YJ, Lin KL, Chang YZ (2012) Simultaneous determination of Delta9-tetrahydrocannabinol and 11-nor-9-carboxy-Delta9-tetrahydrocannabinol in oral fluid using isotope dilution liquid chromatography tandem mass spectrometry. Anal Bioanal Chem 402(2):851–859. doi:10.1007/s00216-011-5439-8

    Article  CAS  Google Scholar 

  48. Concheiro M, Lee D, Lendoiro E, Huestis MA (2013) Simultaneous quantification of Delta(9)-tetrahydrocannabinol, 11-nor-9-carboxy-tetrahydrocannabinol, cannabidiol and cannabinol in oral fluid by microflow-liquid chromatography-high resolution mass spectrometry. J Chromatogr A 1297:123–130. doi:10.1016/j.chroma.2013.04.071

    Article  CAS  Google Scholar 

  49. He X, Kozak M, Nimkar S (2012) Ultra-sensitive measurements of 11-Nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid in oral fluid by microflow liquid chromatography-tandem mass spectrometry using a benchtop quadrupole/orbitrap mass spectrometer. Anal Chem 84(18):7643–7647. doi:10.1021/ac3019476

    Article  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Dr D. M. Schwope for his contribution to the study design. This research was funded by the National Institutes of Health, Intramural Research Program, National Institute on Drug Abuse.

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Correspondence to Marilyn A. Huestis.

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Anizan, S., Milman, G., Desrosiers, N. et al. Oral fluid cannabinoid concentrations following controlled smoked cannabis in chronic frequent and occasional smokers. Anal Bioanal Chem 405, 8451–8461 (2013). https://doi.org/10.1007/s00216-013-7291-5

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  • DOI: https://doi.org/10.1007/s00216-013-7291-5

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