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

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.