Urinary Excretion Profile of Cannabinoid Analytes Following Acute Administration of Oral and Vaporized Cannabis in Infrequent Cannabis Users.

Traditionally, smoking has been the predominant method for administering cannabis, but alternative routes of administration have become more prevalent. Additionally, research examining urinary cannabinoid excretion profiles has primarily focused on 11-nor-9-carboxy-∆9-tetrahydrocannabinol (∆9-THC-COOH), a metabolite of ∆9-tetrahydrocannabinol (∆9-THC), as the primary analyte. The aim of the current study was to characterize the urinary excretion profile of ∆9-THC-COOH, ∆9-THC, ∆8-tetrahydrocannabinol (∆8-THC), 11-hydroxy-∆9-tetrahydrocannabinol (11-OH-∆9-THC), ∆9-tetrahydrocannabivarin (THCV), 11-nor-∆9-tetrahydrocannabivarin-9-carboxlic acid (THCV-COOH), cannabidiol (CBD), cannabinol (CBN) and 8,11-dihydroxytetrahydrocannabinol (8,11-diOH-∆9-THC) following controlled administration of both oral and vaporized cannabis. Participants (n = 21, 11 men/10 women) who were infrequent cannabis users ingested cannabis-containing brownies (0, 10 and 25 mg ∆9-THC) and inhaled vaporized cannabis (0, 5 and 20 mg ∆9-THC) across six double-blind outpatient sessions. Urinary concentrations of ∆9-THC analytes were measured at baseline and for 8 h after cannabis administration. Sensitivity, specificity and agreement between the three immunoassays (IAs) for ∆9-THC-COOH (cutoffs of 20, 50 and 100 ng/mL) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) analyses (confirmatory cutoff concentrations of 15 ng/mL) were assessed. Urinary concentrations for ∆9-THC-COOH, ∆9-THC, 11-OH-∆9-THC, THCV, CBN and 8,11-diOH-∆9-THC all peaked at 5-6 h and 4 h following oral and vaporized cannabis administration, respectively. At each active dose, median maximum concentrations (Cmax) for detected analytes were quantitatively higher after oral cannabis administration compared to vaporized. Using current recommended federal workplace drug-testing criteria (screening via IA with a cutoff of ≥50 ng/mL and confirmation via LC-MS-MS at a cutoff of ≥15 ng/mL), urine specimens tested positive for ∆9-THC-COOH in 97.6% of oral sessions and 59.5% of vaporized sessions with active ∆9-THC doses. These data indicate that while ∆9-THC-COOH may serve as the most consistent confirmatory analyte under the current drug-testing guidelines, future work examining 11-OH-∆9-THC under similar parameters could yield an alternative analyte that may be helpful in distinguishing between licit and illicit cannabis products.

Rodent vertical sleeve gastrectomy alters maternal immune health and fetoplacental development.

Bariatric surgery is increasingly employed to improve fertility and reduce obesity-related co-morbidities in obese women. Surgical weight loss not only improves the chance of conception but reduces the risk of pregnancy complications including pre-eclampsia, gestational diabetes, and macrosomia. However, bariatric procedures increase the incidence of intrauterine growth restriction (IUGR), fetal demise, thromboembolism, and other gestational disorders. Using our rodent model of vertical sleeve gastrectomy (VSG), we tested the hypothesis that VSG in diet-induced, obese dams would cause immune and placental structural abnormalities that may be responsible for fetal demise during pregnancy. VSG dams studied on gestational day (G) 19 had reduced circulating T-cell (CD3+ and CD8+) populations compared with lean or obese controls. Further, local interleukin (IL) 1ß and IL 1 receptor antagonist (il1rn) cmRNA were increased in placenta of VSG dams. Placental barrier function was also affected, with increased transplacental permeability to small molecules, increased matrix metalloproteinase 9 expression, and increased apoptosis in VSG. Furthermore, we identified increased placental mTOR signaling that may contribute to preserving the body weight of the fetuses during gestation. These changes occurred in the absence of a macronutrient deficit or gestational hypertension in the VSG dams. In summary, previous VSG in dams may contribute to fetal demise by affecting maternal immune system activity and compromise placental integrity.