Urinary Pharmacokinetic Profile of Cannabidiol (CBD), Δ9-Tetrahydrocannabinol (THC), and their Metabolites Following Oral and Vaporized CBD and Vaporized CBD-Dominant Cannabis Administration

The market for products containing cannabidiol (CBD) is booming globally. However, the pharmacokinetics of CBD in different oral formulations and the impact of CBD use on urine drug testing outcomes for cannabis (e.g., 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (∆9-THCCOOH)) are understudied. This study characterized the urinary pharmacokinetics of CBD (100 mg) following vaporization or oral administration (including 3 formulations: gelcap, pharmacy-grade syrup, or Epidiolex) as well as vaporized CBD-dominant cannabis (containing 100 mg CBD and 3.7 mg Δ9-THC) in healthy adults (n=18). A subset of participants (n=6) orally administered CBD syrup following overnight fasting (versus low-fat breakfast). Urine specimens were collected before and for 58 hours after dosing on a residential research unit. Immunoassay (IA) screening (cutoffs: 20, 50, 100 ng/mL) for ∆9-THCCOOH was performed, and quantitation of cannabinoids was completed via LC-MS-MS. Urinary CBD concentrations (ng/mL) were higher after oral (mean Cmax: 734; mean Tmax: 4.7 h, n=18) versus vaporized CBD (mean Cmax: 240; mean Tmax: 1.3 h, n=18), and oral dose formulation significantly impacted mean Cmax (Epidiolex=1274 ng/mL, capsule=776 ng/mL, syrup=151 ng/mL, n=6/group) with little difference in Tmax. Overnight fasting had limited impact on CBD excretion in urine, and there was no evidence of CBD conversion to ∆8- or ∆9-THC in any route or formulation in which pure CBD was administered. Following acute administration of vaporized CBD-dominant cannabis, 3 of 18 participants provided a total of 6 urine samples in which ∆9-THCCOOH concentrations ≥15 ng/mL. All 6 specimens screened positive at a 20 ng/mL IA cutoff, and 2 of 6 screened positive at a 50 ng/mL cutoff. These data show that absorption/elimination of CBD is impacted by drug formulation, route of administration, and gastric contents. Although pure CBD is unlikely to impact drug testing, it is possible that hemp products containing low amounts of ∆9-THC may produce a cannabis-positive urine drug test.

Assessment tools for problematic opioid use in palliative care: A scoping review

Background: Screening for problematic opioid use is increasingly recommended in patients receiving palliative care. Aim: To identify tools used to assess for the presence or risk of problematic opioid use in palliative care. Design: Scoping review. Data sources: Bibliographic databases (inception to January 31, 2020), reference lists, and grey literature were searched to find primary studies reporting on adults receiving palliative care and prescription opioids to manage symptoms from advanced cancer, neurodegenerative diseases, or end-stage organ diseases; and included tools to assess for problematic opioid use. There were no restrictions based on study design, location, or language. Results: We identified 42 observational studies (total 14,431 participants) published between 2009 and 2020 that used questionnaires ( n = 32) and urine drug tests ( n = 21) to assess for problematic opioid use in palliative care, primarily in US ( n = 38) and outpatient palliative care settings ( n = 36). The questionnaires were Cut down, Annoyed, Guilty, and Eye-opener (CAGE, n = 8), CAGE-Adapted to Include Drugs (CAGE-AID, n = 6), Opioid Risk Tool ( n = 9), Screener and Opioid Assessment for Patients with Pain (SOAPP; n = 3), SOAPP-Revised ( n = 2), and SOAPP-Short Form ( n = 5). Only two studies’ primary objectives were to evaluate a questionnaire’s psychometric properties in patients receiving palliative care. There was wide variation in how urine drug tests were incorporated into palliative care; frequency of abnormal urine drug test results ranged from 8.6% to 70%. Conclusion: Given the dearth of studies using tools developed or validated specifically for patients receiving palliative care, further research is needed to inform clinical practice and policy regarding problematic opioid use in palliative care.

Tapentadol is the least common opioid found in admission urine drug-test results at an intensive outpatient opioid-use disorder treatment program in Ohio: A brief report

Background: Previous data suggest that tapentadol, an atypical opioid with a putative dual mechanism of action, has relatively low rates of abuse. A better understanding of the rates of abuse among different prescription opioids may help clinicians when considering their potential risks and benefits. The results of urine drug tests (UDTs) may provide a unique opportunity to help answer this question.Method: To investigate different rates of prescription-opioid abuse in this retrospective study, we examined urine drug test results from patients seeking treatment at four facilities of an opioid-use-disorder (OUD) treatment program in Ohio. Urine specimens were collected on admission, one from each patient, in the regular course of care. The opioids reviewed in the present study were tapentadol, hydrocodone, oxycodone, hydromorphone, oxymorphone, and tramadol. Drug dispensing data, including morphine-milligram equivalents (MME) dispensed, were examined to adjust for the relative prevalence of each opioid being examined.Results: Data from 4,162 patients were examined. Tapentadol was the least common finding in UDT results in this cohort and remained so after adjusting for drug availability. The percentage of specimens positive for a given opioid ranged from 0.12 percent (tapentadol) to 7.04 percent (oxycodone). The availability and MME adjustments resulted in a change of rank order, with tapentadol remaining the lowest but tramadol replacing oxycodone as the prescription opioid with the highest rate of abuse.Conclusions: In this sample of UDT results from patients seeking treatment at an OUD program in Ohio, tapentadol was the least frequent finding among the opioids examined, and this remained true when adjusting for dispensing data. Factors potentially contributing to this difference may include pharmacological properties unique to tapentadol. Several important limitations notwithstanding, these findings are consistent with previous real-world evidence and warrant an ongoing line of inquiry.

A Prediction Model for Positive Infant Meconium and Urine Drug Tests

Objective This study aimed to determine the factors associated with positive infant drug screen and create a shortened screen and a prediction model. Study Design This is a retrospective cohort study of all infants who were tested for drugs of abuse from May 2012 through May 2014. The primary outcome was positive infant urine or meconium drug test. Multivariable logistic regression was used to identify independent risk factors. A combined screen was created, and test characteristics were analyzed. Results Among the 3,861 live births, a total of 804 infants underwent drug tests. Variables associated with having a positive infant test were (1) positive maternal urine test, (2) substance use during pregnancy, (3) ≤ one prenatal visit, and (4) remote substance abuse; each p-value was less than 0.0001. A model with an indicator for having at least one of these four predictors had a sensitivity of 94% and a specificity of 69%. Application of this screen to our population would have decreased drug testing by 57%. No infants had a positive urine drug test when their mother's urine drug test was negative. Conclusion This simplified screen can guide clinical decision making for determining which infants should undergo drug testing. Infant urine drug tests may not be needed when a maternal drug test result is negative. Key Points