Pharmacokinetic Properties of  9-Tetrahydrocannabinol in Serum and Oral Fluid

Abstract

In a study on the effects of smoked cannabis (18.2 +/- 2.8 mg as low and 36.5 +/- 5.6 mg as high dose) paired blood and oral fluid samples were collected from 10 study participants up to 6 h after smoking and analyzed for the cannabinoids Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC (THC-OH) and 11-nor-9-carboxy-THC (THCA) using gas chromatography-mass spectrometry. Highest concentrations in serum were 47.8 +/- 35.0 and 79.1 +/- 42.5 microg/L at the end of smoking (low and high dose, respectively) and decreased to less than 1 microg/L during 6 h with elimination half-lives of 1.4 +/- 0.1 h calculated from 1 to 6 h, which is shorter than reported previously. The elimination half-lives of THC-OH (2.0 +/- 0.3 h) and THCA (3.4 +/- 0.9 h) were significantly higher. The THC concentrations in oral fluid were highest with 900 +/- 589 and 1041 +/- 652 microg/L (low and high dose, respectively) in the first sample collected at 0.25 h and decreased to 18 +/- 12 microg/L over 6 h with elimination half-lives of 1.5 +/- 0.6 h. The elimination half-life of THC in serum and oral fluid and between the two doses did not significantly differ. Oral fluid/serum ratios were 46 +/- 27 and 36 +/- 20 (low and high dose, respectively), which are higher than previously reported and might be based on sample collection and/or analytical issues. In conclusion, despite similar elimination rates of THC in serum and oral fluid, which appear incidental, the high differences in oral fluid/serum ratios are not a reliable basis for correlating THC concentrations in oral fluid and serum. The oral compartment and its kinetics for drugs, particularly THC, are not yet satisfactorily understood.

Comparison of cannabinoid concentrations in oral fluid and whole blood between occasional and regular cannabis smokers prior to and after smoking a cannabis joint

“…As expected and presented in previous studies [11,21,23], THC reached its highest concentration first, followed by 11-OH-THC and by THCCOOH. Median THC Tmax were 0.20 and 0.23 h for the heavy and occasional groups, respectively, while median 11-OH-THC Tmax were slightly delayed to 0.28 and 0.32 h and median THCCOOH Tmax even more to 0.38 and 0.40 h. The differences between both groups for the THC and THCCOOH were not significant.…”

“…Similar observations were drawn by Kauert et al in a study carried out with recreational cannabis users [23]. In our study, median THC T 1/2 were 0.8 and 1.0 h for the occasional and heavy smokers, respectively, while the corresponding value reported by Kauert et al was 1.4±0.1 h. Our calculated 11-OH-THC T 1/2 were 1.7 h for the heavy and 1.6 h for the occasional smokers versus 1.9 h, as reported by Kauert.…”

“…THC, THC-A, and CBN Cmax happened concurrently a short time after inhalation of the cannabis joint (T max=0.3-0.4 h). A similar observation has been already reported in several other studies [11,23,38,39]. For instance, the Cmax determined by Kauert et al [23] for THC was already measured in the first OF sample taken just 0.25 h after starting inhalation.…”

“…It was marginally significant for 11-OH-THC (p <0.05). THCCOOH T max values were slightly different from those reported by Kauert et al [23] (mean of 0.25 h) and by Toennes et al [21] (0.75 h for heavy and 0.25 h for occasional smokers).…”

“…Throughout the last decade, several studies have been carried out to determine PK parameters of cannabinoids in blood, plasma, or serum [16][17][18][19][20][21] in humans. Some other studies were performed with oral fluid only [22] or in tandem with serum [23] or plasma [11,24] with a limited number of ten participants in each study. Two, three, and more compartment PK and kinetic models have been applied with varying degrees of success to describe the cannabinoid time profiles [25].…”