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

Abstract 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.

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Urinary Pharmacokinetic Profile of Cannabinoids Following Administration of Vaporized and Oral Cannabidiol and Vaporized CBD-Dominant Cannabis

Journal of Analytical Toxicology ◽

10.1093/jat/bkz080 ◽

2019 ◽

Vol 44 (2) ◽

pp. 109-125 ◽

Cited By ~ 9

Author(s):

Tory R Spindle ◽

Edward J Cone ◽

David Kuntz ◽

John M Mitchell ◽

George E Bigelow ◽

...

Keyword(s):

Drug Testing ◽

Drug Effects ◽

Pharmacokinetic Profile ◽

Chemical Constituent ◽

Positive Urine ◽

Urine Drug ◽

Confirmatory Tests ◽

Federal Workplace ◽

The Impact ◽

Urine Specimens

Abstract Cannabis products in which cannabidiol (CBD) is the primary chemical constituent (CBD-dominant) are increasingly popular and widely available. The impact of CBD exposure on urine drug testing has not been well studied. This study characterized the urinary pharmacokinetic profile of 100-mg oral and vaporized CBD, vaporized CBD-dominant cannabis (100-mg CBD; 3.7-mg ∆9-THC) and placebo in healthy adults (n = 6) using a within-subjects crossover design. Urine specimens were collected before and for 5 days after drug administration. Immunoassay (IA) screening (cutoffs of 20, 50 and 100 ng/mL) and LC–MS-MS confirmatory tests (cutoff of 15 ng/mL) for 11-nor-9-carboxy-∆9-tetrahydrocannabinol (∆9-THCCOOH) were performed; urine was also analyzed for CBD and other cannabinoids. Urinary concentrations of CBD were higher after oral (mean Cmax: 776 ng/mL) versus vaporized CBD (mean Cmax: 261 ng/mL). CBD concentrations peaked 5 h after oral CBD ingestion and within 1 h after inhalation of vaporized CBD. After pure CBD administration, only 1 out of 218 urine specimens screened positive for ∆9-THCCOOH (20-ng/mL IA cutoff) and no specimens exceeded the 15-ng/mL confirmatory cutoff. After inhalation of CBD-dominant cannabis vapor, nine samples screened positive at the 20-ng/mL IA cutoff, and two of those samples screened positive at the 50-ng/mL IA cutoff. Four samples that screened positive (two at 20 ng/mL and two at 50 ng/mL) confirmed positive with concentrations of ∆9-THCCOOH exceeding 15 ng/mL. These data indicate that acute dosing of pure CBD will not result in a positive urine drug test using current federal workplace drug testing guidelines (50-ng/mL IA cutoff with 15-ng/mL confirmatory cutoff). However, CBD products that also contain ∆9-THC may produce positive urine results for ∆9-THCCOOH. Accurate labeling and regulation of ∆9-THC content in CBD/hemp products are needed to prevent unexpected positive drug tests and unintended drug effects.

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A Prediction Model for Positive Infant Meconium and Urine Drug Tests

American Journal of Perinatology ◽

10.1055/s-0040-1721688 ◽

2020 ◽

Author(s):

Elizabeth A. Simpson ◽

David A. Skoglund ◽

Sarah E. Stone ◽

Ashley K. Sherman

Keyword(s):

Prediction Model ◽

Drug Testing ◽

Clinical Decision Making ◽

Drugs Of Abuse ◽

Clinical Decision ◽

P Value ◽

Test Characteristics ◽

Drug Test ◽

Urine Drug ◽

Urine Drug Test

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

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Reduced urinary opioid levels from pain management patients associated with marijuana use

Pain Management ◽

10.2217/pmt-2019-0017 ◽

2019 ◽

Vol 9 (5) ◽

pp. 441-447

Author(s):

Melissa M Goggin ◽

Breane J Shahriar ◽

Andy Stead ◽

Gregory C Janis

Keyword(s):

Pain Management ◽

Drug Testing ◽

Marijuana Use ◽

Potential Interaction ◽

Test Results ◽

Opioid Use ◽

Target Drug ◽

Urine Drug ◽

Urine Drug Test ◽

Lower Urinary

Aim: Marijuana use has been postulated to modulate opioid use, dependence and withdrawal. Broad target drug testing results provide a unique perspective to identify any potential interaction between marijuana use and opioid use. Materials & methods: Using a dataset of approximately 800,000 urine drug test results collected from pain management patients of a time from of multiple years, creatinine corrected opioid levels were evaluated to determine if the presence of the primary marijuana marker 11-nor-carboxy-tetrahydrocannabinol (THC-COOH) was associated with statistical differences in excreted opioid concentrations. Results & conclusion: For each of the opioids investigated (codeine, morphine, hydrocodone, hydromorphone, oxycodone, oxymorphone, fentanyl and buprenorphine), marijuana use was associated with statistically significant lower urinary opiate levels than in samples without indicators of marijuana use.

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Legal issues related to drug testing in the clinical laboratory.

Clinical Chemistry ◽

10.1093/clinchem/34.3.633 ◽

1988 ◽

Vol 34 (3) ◽

pp. 633-636 ◽

Cited By ~ 5

Author(s):

R T Chamberlain

Keyword(s):

Drug Testing ◽

Clinical Laboratory ◽

Scientific Evidence ◽

Legal Issues ◽

Third Party ◽

Urine Drug Testing ◽

Urine Drug ◽

Chain Of Custody ◽

Urine Drug Test ◽

The Many

Abstract As has been reported many times by the lay press, urine drug testing may pose some unique challenges. The clinical laboratory interested in industrial drug testing (typically known as employee drug testing) should be aware of the many challenges that may be brought on by the fact that the result may be contested in an adversarial proceeding. This is what makes the urine drug test a forensic test. It may be one piece of evidence or the only piece of evidence used in an adversarial proceeding that may decide on punitive or rehabilitative action against an employee. As a result, unique standards for governmental contract laboratories have been proposed from the National Institute on Drug Abuse, and special proficiency testing and accreditation procedures have been promoted by professional societies. These standards illustrate the sensitive nature of the results. Because the results are subject to adversarial proceedings, all parties concerned in the testing process should be aware of the legal issues surrounding urine drug testing. There are constitutional and statutory issues as well as tort issues such as negligence, defamation, invasion of privacy, battery, infliction of emotional distress, and others. Laboratories should be especially aware of these issues, since they may be brought in as a third-party defendant to a suit or brought in as a participant in gathering the evidence. The laboratory should also be aware of other legal ramifications such as chain of custody, expert testimony, and the acceptability of scientific evidence.

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Observation of improved adherence with frequent urine drug testing in patients with pain

Journal of Opioid Management ◽

10.5055/jom.2014.0200 ◽

2014 ◽

Vol 10 (2) ◽

pp. 111 ◽

Cited By ~ 4

Author(s):

David A. Yee, BS ◽

Michelle M. Hughes, BA ◽

Alexander Y. Guo, MS ◽

Neveen H. Barakat, BS ◽

Stephanie A. Tse, BS ◽

...

Keyword(s):

Chronic Pain ◽

Drug Testing ◽

Patient Adherence ◽

Parent Drug ◽

The United States ◽

Limit Of Quantitation ◽

Urine Drug Testing ◽

Urine Drug ◽

Urine Drug Test ◽

The Relationship

Objective: To determine the relationship between urine drug testing (UDT) frequency and patient adherence for prescribed buprenorphine, carisoprodol, fentanyl, hydrocodone, methadone, morphine, and oxycodone. Setting: Patients with pain routinely seen by private practitioners. Design: A retrospective analysis was conducted on urinary excretion data analyzed by Millennium Laboratories between March 2008 and May 2011.Patient participants: Patients in the United States with chronic pain who underwent routine UDT to confirm adherence for prescribed medications. Interventions: Adherence for the urine drug test was defined as the presence of parent drug and/or metabolite(s) greater than or equal to the lower limit of quantitation. The percent of adherence for prescribed medications was compared to the average percent of the same in subjects with five or more visits.Main outcomes: Correlation analyses were used to determine the relationship between adherence for prescribed medications and number of visits.Results: There were 255,168 specimens submitted for testing from 166,755 individuals. When monitoring with more frequent visits (>=5 visits) adherence was higher by 1 percent for buprenorphine (89 percent vs 88 percent); 8 percent for carisoprodol (77 percent vs 69 percent); 5 percent for fentanyl (95 percent vs 90 percent); 7 percent for hydrocodone (83 percent vs 76 percent); 3 percent for methadone (96 percent vs 93 percent); 5 percent for morphine (92 percent vs 87 percent); and 8 percent for oxycodone (90 percent vs 82 percent).Conclusions: Adherence for prescribed medications is higher with frequent urine monitoring. UDT can be used as tool that may help improve this in patients with chronic pain.

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Family physicians’ proficiency in urine drug test interpretation

Journal of Opioid Management ◽

10.5055/jom.2007.0022 ◽

2007 ◽

Vol 3 (6) ◽

pp. 333 ◽

Cited By ~ 33

Author(s):

Gary M. Reisfield, MD ◽

Fern J. Webb, PhD ◽

Roger L. Bertholf, PhD ◽

Paul A. Sloan, MD ◽

George R. Wilson, MD

Keyword(s):

Family Medicine ◽

Drug Testing ◽

Opioid Therapy ◽

Physician Education ◽

Test Interpretation ◽

Multiple Choice Questions ◽

Drug Test ◽

Urine Drug Testing ◽

Urine Drug ◽

Urine Drug Test

Objective: To determine the proficiency in urine drug test interpretation among family medicine physicians who order these tests to monitor adherence in their patients on chronic opioid therapy.Methods: A seven-question instrument, consisting of six, five-option, single-best-answer multiple choice questions and one yes/no question was administered to 80 family medicine physicians attending a University of Kentucky Family Medicine Review Course. We calculated frequencies and performed χ2 analyses to examine bivariate associations between urine drug test utilization and interpretive knowledge.Results: The instrument was completed by 60/80 (75 percent) of eligible physicians (44 order urine drug testing; 16 do not). None of the physicians who order urine drug testing answered more than five of the seven questions correctly, and only 20 percent answered more than half correctly. Physicians who order urine drug testing performed better than physicians who do not order urine drug testing on only four of the seven questions, although there were no statistically significant differences between the groups on any question.Conclusions: Family medicine physicians who order urine drug testing to monitor their patients on chronic opioid therapy are not proficient in their interpretation. This study highlights the need for improved physician education in this area. It is imperative for physicians to work closely with certified laboratory professionals when ordering and interpreting urine drug tests.

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Does Performing Preplacement Workplace Hair Drug Testing Influence US Department of Transportation Random and Postaccident Urine Drug Test Positivity Rates?

Journal of Addiction Medicine ◽

10.1097/adm.0000000000000384 ◽

2018 ◽

Vol 12 (2) ◽

pp. 163-166

Author(s):

James W. Price

Keyword(s):

Drug Testing ◽

Department Of Transportation ◽

Drug Test ◽

Urine Drug ◽

Urine Drug Test

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Physician Renewal of Chronically Prescribed Controlled Substances Based on Urine Drug Test Results

Journal of Primary Care & Community Health ◽

10.1177/2150132719883632 ◽

2019 ◽

Vol 10 ◽

pp. 215013271988363

Author(s):

Fatima Hosain ◽

Josephine Lee ◽

Ashar Ata ◽

Ravneet K. Bhullar ◽

Andrew K. Chang

Keyword(s):

Drug Testing ◽

Illicit Drugs ◽

Retrospective Chart Review ◽

Primary Objective ◽

Test Results ◽

Controlled Substances ◽

Urine Drug Testing ◽

Urine Drug ◽

Urine Drug Test ◽

Physician Prescribing

Objective: The effect of specific urine drug testing (UDT) results on physician prescribing habits has not been well described. The primary objective was to report renewal rates of chronically prescribed controlled substances based on types of inconsistent UDT results. Methods: We conducted a retrospective chart review over a 5-month period comparing prescription renewals rates for patients with consistent versus inconsistent UDTs. Inconsistent UDTs were defined by prescribed drug not detected or the presence of heroin, cocaine, nonprescribed opioids, nonprescribed benzodiazepines, or marijuana. Results: Of the 474 UDTs reviewed, 214 (45.1%) were inconsistent. The most common findings among inconsistent UDTs, including overlapping results, were prescribed drug not detected (26.8%) and the presence of marijuana (20.7%), nonprescribed opioids (9.9%), and nonprescribed benzodiazepines (6.1%). In contrast, cocaine (5.5%) and heroin (0.4%) were less likely to be found on UDTs for this population. The relative risk (RR) of prescription renewal was 0.64 (95% CI 0.57-0.71) for inconsistent UDTs versus consistent UDTs. Within the inconsistent UDTs, the renewal rates when marijuana (79.6%) or nonprescribed opioids or benzodiazepines (63.6%) were present were much higher than when heroin or cocaine were present (0.0%; P < .001). Patients whose prescribed controlled substance was not detected had a 55.8% renewal rate. Conclusions: Prescription renewal rates were high when patient UDTs contained nonprescribed marijuana, opioids, and benzodiazepines, or when the prescribed drug was not detected. Prescription renewal rates were low when illicit drugs, such as heroin and cocaine, were detected.

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