Free and Glucuronide Whole Blood Cannabinoids' Pharmacokinetics after Controlled Smoked, Vaporized, and Oral Cannabis Administration in Frequent and Occasional Cannabis Users: Identification of Recent Cannabis Intake

BACKGROUND There is increasing interest in markers of recent cannabis use because following frequent cannabis intake, Δ9-tetrahydrocannabinol (THC) may be detected in blood for up to 30 days. The minor cannabinoids cannabidiol, cannabinol (CBN), and THC-glucuronide were previously detected for ≤2.1 h in frequent and occasional smokers' blood after cannabis smoking. Cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-THCV might also be recent use markers, but their blood pharmacokinetics have not been investigated. Additionally, while smoking is the most common administration route, vaporization and edibles are frequently used. METHODS We characterized blood pharmacokinetics of THC, its phase I and phase II glucuronide metabolites, and minor cannabinoids in occasional and frequent cannabis smokers for 54 (occasional) and 72 (frequent) hours after controlled smoked, vaporized, and oral cannabis administration. RESULTS Few differences were observed between smoked and vaporized blood cannabinoid pharmacokinetics, while significantly greater 11-nor-9-carboxy-THC (THCCOOH) and THCCOOH-glucuronide concentrations occurred following oral cannabis. CBG and CBN were frequently identified after inhalation routes with short detection windows, but not detected following oral dosing. Implementation of a combined THC ≥5 μg/L plus THCCOOH/11-hydroxy-THC ratio <20 cutoff produced detection windows <8 h after all routes for frequent smokers; no occasional smoker was positive 1.5 h or 12 h following inhaled or oral cannabis, respectively. CONCLUSIONS Vaporization and smoking provide comparable cannabinoid delivery. CBG and CBN are recent-use cannabis markers after cannabis inhalation, but their absence does not exclude recent use. Multiple, complimentary criteria should be implemented in conjunction with impairment observations to improve interpretation of cannabinoid tests. Clinicaltrials.gov Identifier: NCT02177513

Sex and gender differences in tobacco smoking among adolescents in French secondary schools

Aim. We investigated the relationship between sex (genetic/biological) and gender (environmental/ cultural) factors in relation to adolescent tobacco smoking. Methods. A representative sample of 11,582 students from French secondary public schools participated in the study by completing a self-administered, standardised questionnaire. Results. Using the WHO classification for smoking in the youth, 15.6% of the adolescents were regular smokers, 7.7% occasional smokers, 17.9% experimental smokers and 4.8% ex-smokers, with no statistically significant gender difference. Taking non-smoking as a reference, puberty had a much greater effect on the likelihood of being a regular smoker [OR=18.0 (95% Confidence Interval: 9.6- 32)] than of being an experimental/occasional smoker [OR=3.7 (2.9-4.6)] among girls. For boys, the effect of puberty was not as great [OR=4.7 (3.5-6.5)] for regular vs. [OR=2.1 (1.8-2.5)] for experimental/occasional smokers). Similarly, illicit drug use had a larger effect on the likelihood of being regular smoker vs. non-smoker [OR=15.0 (12.0-20.0) in boys and 12 (8.8-16.0) in girls] than of being experimental/occasional smoker vs. a non-smoker [OR=4.8 (3.7-6.1) and 2.9 (2.1-3.9) respectively]. Other factors related to regular smoking were exposure to passive smoking and regular alcohol consumption. Living with both parents was a protective factor for life and regular smoking in both genders. Conclusions. Our results show that influential factors of sex-related (puberty), gender-specific (environmental tobacco smoking, alcohol consumption, drug abuse) or sex/gender (regular sexual intercourse) are related to the smoking behaviour in French adolescents.

Cannabinoids in Exhaled Breath following Controlled Administration of Smoked Cannabis

BACKGROUND Δ9-Tetrahydrocannabinol (THC), 11-nor-9-carboxy-THC (THCCOOH), and cannabinol (CBN) were measured in breath following controlled cannabis smoking to characterize the time course and windows of detection of breath cannabinoids. METHODS Exhaled breath was collected from chronic (≥4 times per week) and occasional (<twice per week) smokers before and after smoking a 6.8% THC cigarette. Sample analysis included methanol extraction from breath pads, solid-phase extraction, and liquid chromatography–tandem mass spectrometry quantification. RESULTS THC was the major cannabinoid in breath; no sample contained THCCOOH and only 1 contained CBN. Among chronic smokers (n = 13), all breath samples were positive for THC at 0.89 h, 76.9% at 1.38 h, and 53.8% at 2.38 h, and only 1 sample was positive at 4.2 h after smoking. Among occasional smokers (n = 11), 90.9% of breath samples were THC-positive at 0.95 h and 63.6% at 1.49 h. One occasional smoker had no detectable THC. Analyte recovery from breath pads by methanolic extraction was 84.2%–97.4%. Limits of quantification were 50 pg/pad for THC and CBN and 100 pg/pad for THCCOOH. Solid-phase extraction efficiency was 46.6%–52.1% (THC) and 76.3%–83.8% (THCCOOH, CBN). Matrix effects were −34.6% to 12.3%. Cannabinoids fortified onto breath pads were stable (≤18.2% concentration change) for 8 h at room temperature and −20°C storage for 6 months. CONCLUSIONS Breath may offer an alternative matrix for identifying recent driving under the influence of cannabis, but currently sensitivity is limited to a short detection window (0.5–2 h).