Analytical and Bioanalytical Chemistry

, Volume 405, Issue 23, pp 7269–7279 | Cite as

Oral fluid/plasma cannabinoid ratios following controlled oral THC and smoked cannabis administration

  • Dayong Lee
  • Ryan Vandrey
  • Garry Milman
  • Mateus Bergamaschi
  • Damodara R. Mendu
  • Jeannie A. Murray
  • Allan J. Barnes
  • Marilyn A. HuestisEmail author
Research Paper


Oral fluid (OF) is a valuable biological alternative for clinical and forensic drug testing. Evaluating OF to plasma (OF/P) cannabinoid ratios provides important pharmacokinetic data on the disposition of drug and factors influencing partition between matrices. Eleven chronic cannabis smokers resided on a closed research unit for 51 days. There were four 5-day sessions of 0, 30, 60, and 120 mg oral ∆9-tetrahydrocannabinol (THC)/day followed by a five-puff smoked cannabis challenge on Day 5. Each session was separated by 9 days ad libitum cannabis smoking. OF and plasma specimens were analyzed for THC and metabolites. During ad libitum smoking, OF/P THC ratios were high (median, 6.1; range, 0.2–348.5) within 1 h after last smoking, decreasing to 0.1–20.7 (median, 2.1) by 13.0–17.1 h. OF/P THC ratios also decreased during 5-days oral THC dosing, and after the smoked cannabis challenge, median OF/P THC ratios decreased from 1.4 to 5.5 (0.04–245.6) at 0.25 h to 0.12 to 0.17 (0.04–5.1) at 10.5 h post-smoking. In other studies, longer exposure to more potent cannabis smoke and oromucosal cannabis spray was associated with increased OF/P THC peak ratios. Median OF/P 11-nor-9-carboxy-THC (THCCOOH) ratios were 0.3–2.5 (range, 0.1–14.7) ng/μg, much more consistent in various dosing conditions over time. OF/P THC, but not THCCOOH, ratios were significantly influenced by oral cavity contamination after smoking or oromucosal spray of cannabinoid products, followed by time-dependent decreases. Establishing relationships between OF and plasma cannabinoid concentrations is essential for making inferences of impairment or other clinical outcomes from OF concentrations.


Cannabis Marijuana Delta9-tetrahydrocannabinol Oral fluid Plasma Ratio 









Driving under the influence of drugs


Limit of quantification


Oral fluid


Oral fluid to plasma






Ter in die (three times a day)



We acknowledge Sebastien Anizan and Marisol Castaneto for analytical assistance in data collection; Erin Karschner and David Schwope for plasma data in cross-study comparisons; and contributions from the clinical staff at the NIDA Intramural Research Program and Johns Hopkins Behavioral Pharmacology Research Unit.

Research Funding

This research was funded by grant R01 DA025044 from the National Institute on Drug Abuse and by the Intramural Research Program, National Institute on Drug Abuse, NIH. The funding sources had no role in study design, data collection and analysis, or presentation of results. This study was registered on (NCT00893074).

Supplementary material

216_2013_7159_MOESM1_ESM.pdf (578 kb)
ESM 1 (PDF 577 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg (outside the USA) 2013

Authors and Affiliations

  • Dayong Lee
    • 1
  • Ryan Vandrey
    • 2
  • Garry Milman
    • 1
  • Mateus Bergamaschi
    • 1
  • Damodara R. Mendu
    • 1
  • Jeannie A. Murray
    • 2
  • Allan J. Barnes
    • 1
  • Marilyn A. Huestis
    • 1
    Email author
  1. 1.Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Biomedical Research CenterBaltimoreUSA
  2. 2.Johns Hopkins University School of Medicine, Behavioral Biology Research CenterBaltimoreUSA

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