title: Can oral fluid cannabinoid testing monitor medication compliance and/or cannabis smoking during oral THC and oromucosal Sativex administration?
abstract: OBJECTIVE
  We characterize cannabinoid disposition in oral fluid (OF) after dronabinol, synthetic oral Δ(9)-tetrahydrocannabinol (THC), and Sativex, a cannabis-extract oromucosal spray, and evaluate whether smoked cannabis relapse or Sativex compliance can be identified with OF cannabinoid monitoring.
  
  
  METHODS
  5 and 15 mg synthetic oral THC, low (5.4 mg THC, 5.0 mg cannabidiol (CBD)) and high (16.2 mg THC, 15.0 mg CBD) dose Sativex, and placebo were administered in random order (n=14). Oral fluid specimens were collected for 10.5 h after dosing and analyzed for THC, CBD, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH).
  
  
  RESULTS
  After oral THC, OF THC concentrations decreased over time from baseline, reflecting residual THC excretion from previously self-administered smoked cannabis. CBD and CBN also were rarely detected. After Sativex, THC, CBD and CBN increased greatly, peaking at 0.25-1 h. Median CBD/THC and CBN/THC ratios were 0.82-1.34 and 0.04-0.06, respectively, reflecting cannabinoids' composition in Sativex. THCCOOH/THC ratios within 4.5 h post Sativex were ≤ 1.6 pg/ng, always lower than after oral THC and placebo. THCCOOH/THC ratios increased throughout each dosing session.
  
  
  CONCLUSIONS
  Lack of measurable THC, CBD and CBN in OF following oral THC, and high OF CBD/THC ratios after Sativex distinguish oral and sublingual drug delivery routes from cannabis smoking. Low THCCOOH/THC ratios suggest recent Sativex and smoked cannabis exposure. These data indicate that OF cannabinoid monitoring can document compliance with Sativex pharmacotherapy, and identify relapse to smoked cannabis during oral THC medication but not Sativex treatment, unless samples were collected shortly after smoking.
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.
authors.forename: Dayong
authors.initials: D
authors.lastname: Lee
authors.forename: Erin L
authors.initials: EL
authors.lastname: Karschner
authors.forename: Garry
authors.initials: G
authors.lastname: Milman
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Barnes
authors.forename: Robert S
authors.initials: RS
authors.lastname: Goodwin
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000284:Administration, Oral; D000286:Administration, Sublingual; D000328:Adult; D002185:Cannabidiol; D002186:Cannabinoids / Q000008:administration & dosage* / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage* / Q000032:analysis; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000378:metabolism*; D055118:Medication Adherence; D009061:Mouth Mucosa / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage*; D012463:Saliva / Q000737:chemistry / Q000378:metabolism; D015813:Substance Abuse Detection / Q000379:methods* / Q000592:standards; D055815:Young Adult
chemical_list: D002186:Cannabinoids; D004338:Drug Combinations; D010936:Plant Extracts; D002185:Cannabidiol; D013759:Dronabinol; C587251:nabiximols