title: Phase I and II cannabinoid disposition in blood and plasma of occasional and frequent smokers following controlled smoked cannabis.
abstract: 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.
authors.affiliation: Chemistry and Drug Metabolism Section, Clinical Pharmacology and Therapeutic Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD;
authors.forename: Nathalie A
authors.initials: NA
authors.lastname: Desrosiers
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Himes
authors.forename: Karl B
authors.initials: KB
authors.lastname: Scheidweiler
authors.forename: Marta
authors.initials: M
authors.lastname: Concheiro-Guisan
authors.forename: David A
authors.initials: DA
authors.lastname: Gorelick
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid; D013759:Dronabinol / Q000031:analogs & derivatives / Q000097:blood*; D005260:Female; D020719:Glucuronides / Q000097:blood; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000097:blood*; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D020719:Glucuronides; C001427:11-hydroxy-delta(9)-tetrahydrocannabinol; C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; D013759:Dronabinol