Oral fluid cannabinoids in chronic frequent cannabis smokers during ad libitum cannabis smoking

Abstract

Oral fluid (OF) offers a simple, non-invasive, directly observable sample collection for clinical and forensic drug testing. Given that chronic cannabis smokers often engage in drug administration multiple times daily, evaluating OF cannabinoid pharmacokinetics during ad libitum smoking is important for practical development of analytical methods and informed interpretation of test results. Eleven cannabis smokers resided in a closed research unit for 51 days, and underwent four, 5-day oral delta-9-tetrahydrocannabinol (THC) treatments. Each medication period was separated by 9 days of ad libitum cannabis smoking from 12:00 to 23:00 h daily. Ten OF samples were collected from 9:00-22:00 h on each of the last ad libitum smoking days (Study Days 4, 18, 32, and 46). As the number of cannabis cigarettes smoked increased over the study days, OF THC, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH) also increased with a significant effect of time since last smoking (Δtime; range, 0.0-17.4 h) and ≥88% detection rates; concentrations on Day 4 were significantly lower than those on Days 32 and 46 but not Day 18. Within 30 min of smoking, median THC, CBN, and THCCOOH concentrations were 689 µg/L, 116 µg/L, and 147 ng/L, respectively, decreasing to 19.4 µg/L, 2.4 µg/L, and 87.6 ng/L after 10 h. Cannabidiol and 11-hydroxy-THC showed overall lower detection rates of 29 and 8.6%, respectively. Cannabinoid disposition in OF was highly influenced by Δtime and composition of smoked cannabis. Furthermore, cannabinoid OF concentrations increased over ad libitum smoking days, in parallel with increased cannabis self-administration, possibly reflecting development of increased cannabis tolerance.

Trial registration: ClinicalTrials.gov NCT00893074.

Keywords: cannabinoid; cannabis; delta-9-tetrahydrocannabinol; oral fluid.

Copyright © 2014 John Wiley & Sons, Ltd.

Figures

Figure 1

Median oral fluid cannabinoid concentrations in 11 chronic frequent cannabis smokers on the last days (Days 4, 18, 32, and 46) of ad libitum smoking sessions. (A, B, and C) Δ9-tetrahydrocannabinol (THC), 11-nor-9-carboxy-THC (THCCOOH), and cannabinol (CBN) median concentrations over time intervals in logarithmic scales. (D) THCCOOH median concentrations in arithmetic scale for more detailed illustration of the time course. Participants administered controlled (5 puffs) smoked cannabis dose at 11:30h and then allowed ad libitum cannabis smoking from 12:00 to 23:00h while oral fluid collection occurred from 9:00–22:00h. A single participant may contribute multiple data points to a single interval based on their smoking frequency. Concentrations were plotted with respect to time since last smoking. Data table indicates the number of samples included in each time interval.

Figure 2

Δ9-tetrahydrocannabinol (THC) concentrations in 440 oral fluid samples from 11 chronic frequent cannabis smokers on the last days (Days 4, 18, 32, and 46) of ad libitum smoking sessions. Participants administered controlled (5 puffs) smoked cannabis dose at 11:30h and then allowed ad libitum cannabis smoking from 12:00 to 23:00h while oral fluid collection occurred within 9:00–22:00h. Limit of quantification (LOQ) for THC was 0.5μg/L. Δtime indicates time since last cannabis smoking. Each marker represents an oral fluid sample.

Figure 3

11-nor-9-carboxy-tetrahydrocannabinol (THCCOOH) concentrations in 440 oral fluid samples from 11 chronic frequent cannabis smokers on the last days (Days 4, 18, 32, and 46) of ad libitum smoking sessions. Participants administered controlled (5 puffs) smoked cannabis dose at 11:30h and then allowed ad libitum cannabis smoking from 12:00 to 23:00h while oral fluid collection occurred within 9:00–22:00h. Limit of quantification (LOQ) for THCCOOH was 15ng/L. Δtime indicates time since last cannabis smoking. Each marker represents an oral fluid sample.

Figure 4

Cannabinol (CBN) concentrations in 440 oral fluid samples from 11 chronic frequent cannabis smokers on the last days (Days 4, 18, 32, and 46) of ad libitum smoking sessions. Participants administered controlled (5 puffs) smoked cannabis dose at 11:30h and then allowed ad libitum cannabis smoking from 12:00 to 23:00h while oral fluid collection occurred within 9:00–22:00h. Limit of quantification (LOQ) for CBN was 1μg/L. Δtime indicates time since last cannabis smoking. Each marker represents an oral fluid sample.

Figure 5

Δ9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-THC (THCCOOH) oral fluid concentration time plots in selected 3 participants (A, E, and N) on the last days (Days 4, 18, 32, and 46) of ad libitum smoking sessions. Participants administered controlled (5 puffs) smoked cannabis dose at 11:30h and then allowed ad libitum cannabis smoking from 12:00 to 23:00h, and oral fluid collection occurred between 9:00 and 22:00h. Concentrations were plotted with respect to time since last smoking. Limits of quantification (LOQ) were 0.5μg/L for THC and 15ng/L for THCCOOH.