Phase I and II cannabinoid disposition in blood and plasma of occasional and frequent smokers following controlled smoked cannabis

Clin Chem. 2014 Apr;60(4):631-43. doi: 10.1373/clinchem.2013.216507. Epub 2014 Feb 21.


Background: Δ(9)-Tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) have been reported in blood from frequent cannabis smokers for an extended time during abstinence. We compared THC, 11-OH-THC, THCCOOH, cannabidiol, cannabinol, THC-glucuronide, and 11-nor-9-carboxy-THC-glucuronide (THCCOO-glucuronide) blood and plasma disposition in frequent and occasional cannabis smokers.

Methods: Frequent and occasional smokers resided on a closed research unit and smoked one 6.8% THC cannabis cigarette ad libitum. Blood and plasma cannabinoids were quantified on admission (approximately 19 h before), 1 h before, and up to 15 times (0.5-30 h) after smoking.

Results: Cannabinoid blood and plasma concentrations were significantly higher in frequent smokers compared with occasional smokers at most time points for THC and 11-OH-THC and at all time points for THCCOOH and THCCOO-glucuronide. Cannabidiol, cannabinol, and THC-glucuronide were not significantly different at any time point. Overall blood and plasma cannabinoid concentrations were significantly higher in frequent smokers for THC, 11-OH-THC, THCCOOH, and THCCOO-glucuronide, with and without accounting for baseline concentrations. For blood THC >5 μg/L, median (range) time of last detection was 3.5 h (1.1->30 h) in frequent smokers and 1.0 h (0-2.1 h) in 11 occasional smokers; 2 individuals had no samples with THC >5 μg/L.

Conclusions: Cannabis smoking history plays a major role in cannabinoid detection. These differences may impact clinical and impaired driving drug detection. The presence of cannabidiol, cannabinol, or THC-glucuronide indicates recent use, but their absence does not exclude it.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Chromatography, Liquid
  • Dronabinol / analogs & derivatives
  • Dronabinol / blood*
  • Female
  • Glucuronides / blood
  • Humans
  • Male
  • Marijuana Smoking / blood*
  • Metabolic Detoxication, Phase I*
  • Metabolic Detoxication, Phase II*
  • Tandem Mass Spectrometry
  • Tissue Distribution
  • Young Adult


  • Glucuronides
  • 11-hydroxy-delta(9)-tetrahydrocannabinol
  • 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid
  • Dronabinol