Relationship of (9)-tetrahydrocannabinol concentrations
in oral fluid and plasma after controlled administration of smoked cannabis

Huestis MA, Cone EJ.
Intramural Research Program,
National Institute on Drug Abuse,
National Institutes of Health,
Baltimore, Maryland 21224.
J Anal Toxicol. 2004 Sep;28(6):394-9


Understanding the relationship of (9)-tetrahydrocannabinol (THC) concentrations in oral fluid and plasma is important in interpretation of oral fluid test results. Current evidence suggests that THC is deposited in the oral cavity during cannabis smoking. This "depot" represents the primary or sole source of THC found when oral fluid is collected and analyzed. In this research, oral fluid and plasma specimens were collected from six subjects following smoking of cannabis cigarettes containing 1.75% and 3.55% THC. There was at least one week between each cannabis administration. Plasma specimens were analyzed by gas chromatography-mass spectrometry (GC-MS) and paired oral fluid specimens were analyzed by radioimmunoassay (RIA). In addition, one individual's oral fluid specimens were also analyzed by GC-MS. These data are unique in that they represent simultaneous or near simultaneous collection of oral fluid and plasma specimens in subjects following controlled cannabis dosing. The first oral fluid specimen, collected from one subject at 0.2 h following initiation of smoking, contained a THC concentration of 5800 ng/mL (GC-MS). By 0.33 h, the THC concentration in oral fluid had fallen to 81 ng/mL. From approximately 0.3 h through 4.0 h, the mean (+/- SD) THC ratio of oral fluid to plasma THC concentrations was 1.18 (0.62) with a range of 0.5 to 2.2. Within 12 h, both oral fluid and plasma THC concentrations generally declined below 1 ng/mL. RIA analyses of oral fluid specimens for six subjects demonstrated the same pattern of initial high levels of contamination immediately after smoking, followed by rapid clearing, and a slower decline over 12 h. Mean THC oral fluid concentrations by RIA at 0.2 h were 864 ng/mL and 4167 ng/mL compared to plasma concentrations of 52 ng/mL and 230 ng/mL at 0.27 h following the low- and high-dose cannabis cigarettes, respectively. The similarity in oral fluid and plasma THC concentrations following the dissipation of the initial "contamination" indicates the likelihood of a physiological link between these specimens. Recent studies have shown that sublingual or transmucosal administration of pure THC results in direct absorption of intact THC into the bloodstream, thereby bypassing the gastrointestinal tract. The current study demonstrates that THC is deposited in the oral cavity and remains for up to 24 h following cannabis smoking. The decline in THC oral fluid concentration over this time suggests that there may be absorption of THC into blood as previously shown with pure THC. Passive cannabis exposure studies appear to indicate that positive oral fluid tests for THC can occur shortly after cannabis smoke exposure, but results were negative within 1 h. Consequently, when very recent passive exposure to cannabis smoke can be ruled out, it is concluded that a positive oral fluid test provides credible evidence of active cannabis use.

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