title: Oral fluid/plasma cannabinoid ratios following controlled oral THC and smoked cannabis administration.
abstract: Oral fluid (OF) is a valuable biological alternative for clinical and forensic drug testing. Evaluating OF to plasma (OF/P) cannabinoid ratios provides important pharmacokinetic data on the disposition of drug and factors influencing partition between matrices. Eleven chronic cannabis smokers resided on a closed research unit for 51 days. There were four 5-day sessions of 0, 30, 60, and 120 mg oral ∆(9)-tetrahydrocannabinol (THC)/day followed by a five-puff smoked cannabis challenge on Day 5. Each session was separated by 9 days ad libitum cannabis smoking. OF and plasma specimens were analyzed for THC and metabolites. During ad libitum smoking, OF/P THC ratios were high (median, 6.1; range, 0.2-348.5) within 1 h after last smoking, decreasing to 0.1-20.7 (median, 2.1) by 13.0-17.1 h. OF/P THC ratios also decreased during 5-days oral THC dosing, and after the smoked cannabis challenge, median OF/P THC ratios decreased from 1.4 to 5.5 (0.04-245.6) at 0.25 h to 0.12 to 0.17 (0.04-5.1) at 10.5 h post-smoking. In other studies, longer exposure to more potent cannabis smoke and oromucosal cannabis spray was associated with increased OF/P THC peak ratios. Median OF/P 11-nor-9-carboxy-THC (THCCOOH) ratios were 0.3-2.5 (range, 0.1-14.7) ng/μg, much more consistent in various dosing conditions over time. OF/P THC, but not THCCOOH, ratios were significantly influenced by oral cavity contamination after smoking or oromucosal spray of cannabinoid products, followed by time-dependent decreases. Establishing relationships between OF and plasma cannabinoid concentrations is essential for making inferences of impairment or other clinical outcomes from OF concentrations.
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Biomedical Research Center, Baltimore, MD 21224, USA.
authors.forename: Dayong
authors.initials: D
authors.lastname: Lee
authors.forename: Ryan
authors.initials: R
authors.lastname: Vandrey
authors.forename: Garry
authors.initials: G
authors.lastname: Milman
authors.forename: Mateus
authors.initials: M
authors.lastname: Bergamaschi
authors.forename: Damodara R
authors.initials: DR
authors.lastname: Mendu
authors.forename: Jeannie A
authors.initials: JA
authors.lastname: Murray
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Barnes
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000328:Adult; D002138:Calibration; D002186:Cannabinoids / Q000097:blood* / Q000493:pharmacokinetics; D013759:Dronabinol / Q000097:blood* / Q000493:pharmacokinetics; D008401:Gas Chromatography-Mass Spectrometry; D006213:Hallucinogens / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D057230:Limit of Detection; D008385:Marijuana Smoking; D012463:Saliva / Q000737:chemistry*
chemical_list: D002186:Cannabinoids; D006213:Hallucinogens; D013759:Dronabinol