title: Identification of recent cannabis use: whole-blood and plasma free and glucuronidated cannabinoid pharmacokinetics following controlled smoked cannabis administration.
abstract: BACKGROUND
  Δ⁹-Tetrahydrocannabinol (THC) is the most frequently observed illicit drug in investigations of accidents and driving under the influence of drugs. THC-glucuronide has been suggested as a marker of recent cannabis use, but there are no blood data following controlled THC administration to test this hypothesis. Furthermore, there are no studies directly examining whole-blood cannabinoid pharmacokinetics, although this matrix is often the only available specimen.
  
  
  METHODS
  Participants (9 men, 1 woman) resided on a closed research unit and smoked one 6.8% THC cannabis cigarette ad libitum. We quantified THC, 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), cannabinol (CBN), THC-glucuronide and THCCOOH-glucuronide directly in whole blood and plasma by liquid chromatography/tandem mass spectrometry within 24 h of collection to obviate stability issues.
  
  
  RESULTS
  Median whole blood (plasma) observed maximum concentrations (C(max)) were 50 (76), 6.4 (10), 41 (67), 1.3 (2.0), 2.4 (3.6), 89 (190), and 0.7 (1.4) μg/L 0.25 h after starting smoking for THC, 11-OH- THC, THCCOOH, CBD, CBN, and THCCOOH-glucuronide, respectively, and 0.5 h for THC-glucuronide. At observed C(max), whole-blood (plasma) detection rates were 60% (80%), 80% (90%), and 50% (80%) for CBD, CBN, and THC-glucuronide, respectively. CBD and CBN were not detectable after 1 h in either matrix (LOQ 1.0 μg/L).
  
  
  CONCLUSIONS
  Human whole-blood cannabinoid data following cannabis smoking will assist whole blood and plasma cannabinoid interpretation, while furthering identification of recent cannabis intake.
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Biomedical Research Center, Baltimore, MD 21224, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Schwope
authors.forename: Erin L
authors.initials: EL
authors.lastname: Karschner
authors.forename: David A
authors.initials: DA
authors.lastname: Gorelick
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000293:Adolescent; D000328:Adult; D002185:Cannabidiol / Q000097:blood; D002186:Cannabinoids / Q000097:blood / Q000493:pharmacokinetics*; D002187:Cannabinol / Q000097:blood; D002188:Cannabis; D013759:Dronabinol / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D020719:Glucuronides / Q000097:blood*; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000097:blood*; D008875:Middle Aged; D015813:Substance Abuse Detection; D055815:Young Adult
chemical_list: D002186:Cannabinoids; D020719:Glucuronides; D002185:Cannabidiol; C001427:11-hydroxy-delta(9)-tetrahydrocannabinol; C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; D013759:Dronabinol; D002187:Cannabinol