title: Free and Glucuronide Whole Blood Cannabinoids' Pharmacokinetics after Controlled Smoked, Vaporized, and Oral Cannabis Administration in Frequent and Occasional Cannabis Users: Identification of Recent Cannabis Intake.
abstract: BACKGROUND
  There is increasing interest in markers of recent cannabis use because following frequent cannabis intake, Δ9-tetrahydrocannabinol (THC) may be detected in blood for up to 30 days. The minor cannabinoids cannabidiol, cannabinol (CBN), and THC-glucuronide were previously detected for ≤2.1 h in frequent and occasional smokers' blood after cannabis smoking. Cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-THCV might also be recent use markers, but their blood pharmacokinetics have not been investigated. Additionally, while smoking is the most common administration route, vaporization and edibles are frequently used.
  
  
  METHODS
  We characterized blood pharmacokinetics of THC, its phase I and phase II glucuronide metabolites, and minor cannabinoids in occasional and frequent cannabis smokers for 54 (occasional) and 72 (frequent) hours after controlled smoked, vaporized, and oral cannabis administration.
  
  
  RESULTS
  Few differences were observed between smoked and vaporized blood cannabinoid pharmacokinetics, while significantly greater 11-nor-9-carboxy-THC (THCCOOH) and THCCOOH-glucuronide concentrations occurred following oral cannabis. CBG and CBN were frequently identified after inhalation routes with short detection windows, but not detected following oral dosing. Implementation of a combined THC ≥5 μg/L plus THCCOOH/11-hydroxy-THC ratio <20 cutoff produced detection windows <8 h after all routes for frequent smokers; no occasional smoker was positive 1.5 h or 12 h following inhaled or oral cannabis, respectively.
  
  
  CONCLUSIONS
  Vaporization and smoking provide comparable cannabinoid delivery. CBG and CBN are recent-use cannabis markers after cannabis inhalation, but their absence does not exclude recent use. Multiple, complimentary criteria should be implemented in conjunction with impairment observations to improve interpretation of cannabinoid tests. Clinicaltrials.gov Identifier: NCT02177513.
authors.affiliation: Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD.|Program in Toxicology, University of Maryland, Baltimore, Baltimore, MD.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Newmeyer
authors.affiliation: Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD.
authors.forename: Madeleine J
authors.initials: MJ
authors.lastname: Swortwood
authors.affiliation: Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD.
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Barnes
authors.affiliation: Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD.
authors.forename: Osama A
authors.initials: OA
authors.lastname: Abulseoud
authors.affiliation: Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD; kscheidweiler@intra.nida.nih.gov.
authors.forename: Karl B
authors.initials: KB
authors.lastname: Scheidweiler
authors.affiliation: Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD.|University of Maryland School of Medicine, Baltimore, MD.
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002186:Cannabinoids / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000097:blood*; D008875:Middle Aged; D014835:Volatilization; D055815:Young Adult
chemical_list: D002186:Cannabinoids