In recent years, the surge in use of tetrahydrocannabinol (THC) and cannabidiol (CBD) has increased the need for sensitive and specific analytical assays to measure the said compounds in patients, to establish dose–effect relationships and to gain knowledge of their pharmacokinetics and metabolism. We developed and validated an online extraction high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS-MS) method for simultaneous quantification of 17 cannabinoids and metabolites including THC and its metabolites, CBD and its metabolites and other minor cannabinoids in human plasma. CBD-glucuronide (CBD-gluc) standard was produced in-house by isolation of CBD-gluc from urine of patients using pure CBD oil. For calibration standards and quality control samples, human plasma was spiked with cannabinoids at varying concentrations within the working range of the respective compound and 200 µL of the plasma was extracted using a simple one-step protein precipitation procedure. The extracts were analyzed using online trapping LC/LC–atmospheric pressure chemical ionization–MS-MS running in the positive multiple reaction monitoring mode. The lower limit of quantification ranged from 0.78 to 7.8 ng/mL, and the upper limits of quantification were between 100 and 2,000 ng/mL. Inter-day analytical accuracy and imprecision ranged from 90.4% to 111% and from 3.1% to 17.4%, respectively. The analysis of plasma samples collected during clinical studies showed that (3R-trans)-cannabidiol-7-oic acid (7-CBD-COOH) was the major human metabolite with 5960% (59.6-fold) of CBD followed by 7-hydroxy-CBD (177%), CBD-gluc (157%) and 6α-hydroxy-CBD (39.8%); 6β-hydroxy-CBD was not detected in any of the samples. In the present study, we developed and validated a robust LC–MS-MS assay for the simultaneous quantification of cannabinoids and their metabolites, which has been used to measure >5,000 samples in clinical studies. Moreover, we were able to quantify CBD-gluc and showed that 7-CBD-COOH, 7-hydroxy-CBD and CBD-gluc are the major CBD metabolites in human plasma.

Background: Prenatal exposure to cannabis may influence childhood cognition and behavior, but the epidemiologic evidence is mixed. Even less is known about the potential impact of secondhand exposure to cannabis during early childhood. Objective: This study sought to assess whether prenatal and/or postnatal exposure to cannabis was associated with childhood cognition and behavior. Study design: This sub-study included a convenience sample of 81 mother–child pairs from a Colorado-based cohort. Seven common cannabinoids (including delta 9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD)) and their metabolites were measured in maternal urine collected mid-gestation and child urine collected at age 5 years. Prenatal and postnatal exposure to cannabis was dichotomized as exposed (detection of any cannabinoid) and not exposed. Generalized linear models examined the associations between prenatal or postnatal exposure to cannabis with the NIH Toolbox and Child Behavior Checklist T-scores at age 5 years. Results: In this study, 7% (n = 6) of the children had prenatal exposure to cannabis and 12% (n = 10) had postnatal exposure to cannabis, with two children experiencing this exposure at both time points. The most common cannabinoid detected in pregnancy was Δ9-THC, whereas the most common cannabinoid detected in childhood was CBD. Postnatal exposure to cannabis was associated with more aggressive behavior (β: 3.2; 95% CI: 0.5, 5.9), attention deficit/hyperactivity problems (β: 8.0; 95% CI: 2.2, 13.7), and oppositional/defiant behaviors (β: 3.2; 95% CI: 0.2, 6.3), as well as less cognitive flexibility (β: −15.6; 95% CI: −30.0, −1.2) and weaker receptive language (β: −9.7; 95% CI: −19.2, −0.3). By contrast, prenatal exposure to cannabis was associated with fewer internalizing behaviors (mean difference: −10.2; 95% CI: −20.3, −0.2) and fewer somatic complaints (mean difference: −5.2, 95% CI: −9.8, −0.6). Conclusions: Our study suggests that postnatal exposure to cannabis is associated with more behavioral and cognitive problems among 5-year-old children, independent of prenatal and postnatal exposure to tobacco. The potential risks of cannabis use (including smoking and vaping) during pregnancy and around young children should be more widely communicated to parents.

Cannabis is the most commonly used drug of abuse in pregnancy and after delivery. However, little is known regarding the disposition of cannabinoids in breast milk, although delta-9-tetrahydrocannabinol (THC), the main psychoactive component, is highly lipophilic. Quantification of cannabinoids in breastmilk is essential for clinical monitoring and research studies and breastmilk banks mainly rely on enzyme-linked immunosorbent assay (ELISA) in terms of screening for cannabinoids. To support clinical studies on disposition of cannabinoids in breastmilk, we validated a high-performance liquid chromatography–tandem mass spectrometry (LC–MS-MS) assay for the simultaneous quantification of 12 cannabinoids and their metabolites in human breast milk. Said assay was based upon a simple one-step protein precipitation, online column extraction and detection in the positive multiple reaction monitoring mode. After successful validation, the assay was used to analyze 30 samples from a clinical research study that had tested negative using an ELISA kit that is commonly used by breastmilk banks. In human breast milk, depending on the analyte, the lower limits of quantification of the LC–MS-MS assay ranged from 0.39 to 7.81 ng/mL. Acceptance criteria for intra- and inter-batch accuracy (85–115%) and imprecision (<15%) were met for all compounds. Mean extraction efficiencies were above 60% for all analytes. Mean matrix effect ranged from −12.5% to 44.5% except of THC-glucuronide for which significant matrix effects were noted. No carry-over was detected. Although cannabinoid-negative based on the ELISA, all 30 samples tested positive for THC using LC–MS-MS (0.8–130 ng/mL) and several also for 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD) and cannabigerol (CBG). We validated a sensitive and specific assay for the quantification of 12 cannabinoids in human breastmilk that outperformed an ELISA commonly used by breastmilk banks.

Background: Cannabis use is frequent in Parkinson's disease (PD), despite inadequate evidence of benefits and risks.Objective: The aim is to study short‐term efficacy and tolerability of relatively high cannabidiol (CBD)/low Δ‐9‐tetrahydrocannabinol (THC) to provide preliminary data for a longer trial.Methods: Persons with PD with ≥20 on motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) who had negative cannabis testing took cannabis extract (National Institute of Drug Abuse) oral sesame oil solution for 2 weeks, increasing to final dose of 2.5 mg/kg/day. Primary outcome was change in motor MDS‐UPDRS from baseline to final dose.Results: Participants were randomized to CBD/THC (n = 31) or placebo (n = 30). Mean final dose (CBD/THC group) was 191.8 ± 48.9 mg CBD and 6.4 ± 1.6 mg THC daily. Motor MDS‐UPDRS was reduced by 4.57 (95% CI, −8.11 to −1.03; P = 0.013) in CBD/THC group, and 2.77 (−4.92 to −0.61; P = 0.014) in placebo; the difference between groups was non‐significant: −1.80 (−5.88 to 2.27; P = 0.379). Several assessments had a strong placebo response. Sleep, cognition, and activities of daily living showed a treatment effect, favoring placebo. Overall adverse events were mild and reported more in CBD/THC than placebo group. On 2.5 mg/kg/day CBD plasma level was 54.0 ± 33.8 ng/mL; THC 1.06 ± 0.91 ng/mL.Conclusions: The brief duration and strong placebo response limits interpretation of effects, but there was no benefit, perhaps worsened cognition and sleep, and there was many mild adverse events. Longer duration high quality trials that monitor cannabinoid concentrations are essential and would require improved availability of research cannabinoid products in the United States. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.