title: Predictive model accuracy in estimating last Δ9-tetrahydrocannabinol (THC) intake from plasma and whole blood cannabinoid concentrations in chronic, daily cannabis smokers administered subchronic oral THC.
abstract: BACKGROUND
  Determining time since last cannabis/Δ9-tetrahydrocannabinol (THC) exposure is important in clinical, workplace, and forensic settings. Mathematical models calculating time of last exposure from whole blood concentrations typically employ a theoretical 0.5 whole blood-to-plasma (WB/P) ratio. No studies previously evaluated predictive models utilizing empirically-derived WB/P ratios, or whole blood cannabinoid pharmacokinetics after subchronic THC dosing.
  
  
  METHODS
  Ten male chronic, daily cannabis smokers received escalating around-the-clock oral THC (40-120 mg daily) for 8 days. Cannabinoids were quantified in whole blood and plasma by two-dimensional gas chromatography-mass spectrometry.
  
  
  RESULTS
  Maximum whole blood THC occurred 3.0 h after the first oral THC dose and 103.5h (4.3 days) during multiple THC dosing. Median WB/P ratios were THC 0.63 (n=196), 11-hydroxy-THC 0.60 (n=189), and 11-nor-9-carboxy-THC (THCCOOH) 0.55 (n=200). Predictive models utilizing these WB/P ratios accurately estimated last cannabis exposure in 96% and 100% of specimens collected within 1-5h after a single oral THC dose and throughout multiple dosing, respectively. Models were only 60% and 12.5% accurate 12.5 and 22.5h after the last THC dose, respectively.
  
  
  CONCLUSIONS
  Predictive models estimating time since last cannabis intake from whole blood and plasma cannabinoid concentrations were inaccurate during abstinence, but highly accurate during active THC dosing. THC redistribution from large cannabinoid body stores and high circulating THCCOOH concentrations create different pharmacokinetic profiles than those in less than daily cannabis smokers that were used to derive the models. Thus, the models do not accurately predict time of last THC intake in individuals consuming THC daily.
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Karschner
authors.forename: David M
authors.initials: DM
authors.lastname: Schwope
authors.forename: Eugene W
authors.initials: EW
authors.lastname: Schwilke
authors.forename: Robert S
authors.initials: RS
authors.lastname: Goodwin
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Kelly
authors.forename: David A
authors.initials: DA
authors.lastname: Gorelick
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000465:Algorithms; D001822:Body Burden; D015992:Body Mass Index; D002186:Cannabinoids / Q000097:blood*; D013759:Dronabinol / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D005544:Forecasting; D008401:Gas Chromatography-Mass Spectrometry; D006213:Hallucinogens / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000097:blood / Q000378:metabolism*; D015233:Models, Statistical; D052616:Solid Phase Extraction; D055815:Young Adult
chemical_list: D002186:Cannabinoids; D006213:Hallucinogens; D013759:Dronabinol