Evaluation of the Canadian approved drug screening equipment cut-off levels for tetrahydrocannabinol (THC).

In 2018, Canada introduced roadside oral fluid (OF) screening devices, called Approved Drug Screening Equipment (ADSE), as an investigative tool in impaired driving investigations to detect tetrahydrocannabinol (THC), cocaine and/or methamphetamine in drivers. In this work, we compare the detection and concentration of THC in blood samples collected from suspected impaired drivers that tested positive at the roadside for THC on an ADSE. The two ADSEs that were utilized were the Dräger DrugTest® 5000 (DDT) and the Abbott SoToxa™ (SoToxa), both configured with a THC OF concentration cut-off concentration of 25 ng/mL. Blood samples were screened for cannabinoids using immunoassay and positive results were followed up by confirmation/quantitation of THC by ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS-MS). A total of 230 cases were available where a blood sample was collected from a suspected impaired driver subsequent to a positive THC screen result on an ADSE. The blood samples were taken an average of 1.4 hours (range = 9 minutes to 3.2 hours) after the ADSE test. THC was confirmed in 98% of blood samples with concentrations across all samples ranging from not detected (cut = off 0.5 ng/mL) to greater than 20 ng/mL. Further, 90% of the blood samples had a THC concentration of 2.0 ng/mL (the lower per se limit in Canada) or greater. A positive ADSE test of a suspected impaired driver may predict that the driver has a detectable level of THC in their blood, and there is a high likelihood that the THC blood concentration is 2.0 ng/mL or higher. Hence, ADSE may be a useful tool for law enforcement and aid in the development of grounds to believe that a driver is operating a conveyance with a THC concentration exceeding Canadian per se limits.

Impact of low-volume blood withdrawal on hematological biomarkers for the athlete biological passport.

This study investigated the impact of low-volume blood withdrawal on the hematological biomarkers currently considered for anti-doping purposes. After baseline measurement (D - 7), a 140 mL blood withdrawal was completed (D + 0) on 12 healthy volunteers, followed by weekly monitoring for 21 days (D + 7 - 21). Each visit consisted of a full blood count (Sysmex XN-1000) and duplicate blood volume measurements by CO-rebreathing. A significant decrease in total hemoglobin mass (Hbmass) (-2.3%, p = 0.007) and red blood cell volume (RBCV) (-2.8%, p = 0.028) was reported at D + 7. Despite no atypical passport finding (ATPF) when considering the athlete biological passport adaptive longitudinal model, hemoglobin concentration ([Hb]) increased significantly at D + 21 (+3.8%, p = 0.031). Besides, ferritin (FERR) was significantly downregulated at all points following blood withdrawal, with the largest decrease occurring at D + 7 (-26.6%, p < 0.001). Regardless of the presumable effect of blood reinfusion on ABP biomarkers, these results illustrate the challenge of monitoring hematological variables for the detection of low-volume blood withdrawal. Finally, this study outlines the sensitivity of FERR to altered erythropoiesis to support the implementation of iron markers as complementary variables for the longitudinal monitoring of blood doping, despite the potential influence of confounding factors (e.g., iron supplementations).

Determination of urinary deanol-N-oxide excretion profiles after ingestion of nutritional supplements containing deanol.

2-(Dimethylamino)ethan-1-ol (Deanol) is a widely produced chemical used by both industry and consumers in a variety of applications. Meclofenoxate, a stimulant classified on the World Anti-Doping Agency Prohibited List, metabolizes into deanol and, presumably, its main metabolite deanol-N-oxide. Hence, using liquid chromatography-tandem mass spectrometry, a quantitative detection method for deanol-N-oxide in urine was developed. Subsequently, the urinary excretion of deanol-N-oxide after oral application of 130 mg of deanol was determined in six volunteers, and urine samples of a cohort of 180 male and female athletes from different sports were analyzed. In addition, urinary deanol-N-oxide was determined in an exploratory study with one volunteer ingesting 250 mg of meclofenoxate. The developed test method allowed for limits of detection and quantification for deanol-N-oxide at 0.05 and 0.15 µg/mL, respectively. Urinary deanol-N-oxide cmax levels were found between 100 and 250 µg/mL 2-5 h post-administration of 130 mg of deanol. Similarly, urine samples collected after the administration of 250 mg of meclofenoxate exhibited cmax levels of 115 µg/mL. In contrast, deanol-N-oxide urine concentrations of pre-administration specimens and 180 routine doping control urine sample were between 0.3 and 1.3 µg/mL and below limit of quantification and 1.8 µg/mL, respectively. The study suggests that the use of deanol and meclofenoxate results in significantly elevated urinary deanol-N-oxide levels. Whether or not monitoring deanol-N-oxide in doping controls can support decision-making processes concerning the detection of meclofenoxate use necessitates further investigations taking into consideration the elimination kinetics of 4-chlorophenoxyacetic acid, the main metabolite of meclofenoxate, and deanol-N-oxide.

Simple Method for the Determination of THC and THC-COOH in Human Postmortem Blood Samples by Gas Chromatography-Mass Spectrometry.

A simple and sensitive analytical method was developed for qualitative and quantitative analysis of Δ9-tetrahydrocannabinol (Δ9-THC) and its metabolite 11-nor-Δ9-tetrahydrocannabinol-carboxylic acid (Δ9-THC-COOH) in human postmortem blood using gas chromatography/mass spectrometry (GC-MS) in selected ion monitoring (SIM) mode. The method involved a liquid-liquid extraction in two steps, one for Δ9-THC and a second one for Δ9-THC-COOH. The first extract was analyzed using Δ9-THC-D3 as internal standard. The second extract was derivatized and analyzed using Δ9-THC-COOH-D3 as internal standard. The method was shown to be very simple, rapid, and sensitive. The method was validated for the two compounds, including linearity (range 0.05-1.5 µg/mL for Δ9-THC and 0.08-1.5 µg/mL for Δ9-THC-COOH), and the main precision parameters. It was linear for both analytes, with quadratic regression of calibration curves always higher than 0.99. The coefficients of variation were less than 15%. Extraction recoveries were superior to 80% for both compounds. The developed method was used to analyze 41 real plasma samples obtained from the Forensic Toxicology Service of the Institute of Forensic Sciences of Santiago de Compostela (Spain) from cases in which the use of cannabis was involved, demonstrating the usefulness of the proposed method.

Detection time comparison of non-hydrolysed sulphated metabolites of metenolone, mesterolone and 17α-methyltestosterone analysed by four different mass spectrometric techniques.

The frequent detection of anabolic androgenic steroids (AAS) indicates their popularity among rule-breaking athletes. The so called long-term metabolites play a crucial role in their detection, and non-hydrolysed sulphated metabolites have gained renewed interest, as research has demonstrated their extended detection time compared to the more conventional markers (e.g., for metenolone and mesterolone). Their potential has been investigated using liquid and gas chromatography-mass spectrometry (LC- and GC-MS). However, due to their complementary nature, chances are that the most promising metabolite on one technique does not necessarily exhibit the same behaviour on the other and vice versa. Therefore, a comparison was carried out where as a trial model, metenolone, mesterolone and 17α-methyltestosterone were selected and the most likely long-term sulphated metabolites identified on four mass spectrometric instruments. Additionally, using a modified sample preparation procedure, comparison between conventional and non-hydrolysed sulphated metabolites between different GC-MS instruments was also included. When focusing on each individual marker, no cases were observed where a single metabolite provided a superior detection time on all instruments. Furthermore, for each AAS, there were incidences where a metabolite provided the best detection time on one instrument but could only be detected for a shorter period or not at all on other instruments. This demonstrates that metabolite detection windows and hence their added-value as target substance are unique and dependent on the analytical technique and not only on their pharmacokinetic behaviour. Consequently, in each case, a metabolite versus instrument evaluation is needed to maximise the probabilities of detecting doping offences.

Urine Drug Test Results Among Adolescents and Young Adults in an Outpatient Office-Based Opioid Treatment Program.

PURPOSE: Urine drug testing (UDT) is an important feature of outpatient treatment for opioid use disorder, but associations with patient characteristics among adolescent and young adult patients are unknown. This study assessed UDT results in office-based opioid treatment and characteristics associated with treatment compliance. METHODS: This was a retrospective study of adolescent and young adult patients enrolled in office-based opioid treatment between January 1, 2009, and December 31, 2020. UDT results were described as positive results or expected and unexpected results. Expected results were negative UDTs for opioids, marijuana (THC [tetrahydrocannabinol]), or cocaine/methamphetamine, or a positive UDT for buprenorphine. Unexpected results were positive UDTs for opioids, THC, or cocaine/methamphetamine, or a negative UDT for buprenorphine. Treatment compliance was defined as ≥75% of UDTs provided being expected results. Counts and percentages described UDT results. Regressions evaluated associations between patient characteristics (retention time, age, sex, race/ethnicity, insurance, and comorbid mental health diagnoses) with treatment compliance, and assessed change of positivity rates for UDTs over time. RESULTS: A total of 407 patients were included. Overall, 305 patients (74.9%) demonstrated treatment compliance. Rates of expected UDT results increased with longer retention time (p <.001), except for methamphetamine. Buprenorphine expected results ranged from 77.0% to 96.5%. Diagnosis of stimulant use disorder was associated with decreased compliance (p = .04), while diagnoses of depression, anxiety, nicotine use disorder, and post-traumatic stress disorder were associated with increased compliance (p ≤.04). DISCUSSION: Proportion of expected UDT results increased with retention time. Diagnosis of specific mental health conditions affected treatment compliance. Further research regarding long-term health outcomes is needed.

THC and THC-COOH hair concentrations: Influence of age, gender, consumption habits, cosmetics treatment, and hair features.

Evaluation of Cannabis consumption is required for many purposes (i.e., workplace drug testing and driving license renewal). Hair analysis represents the most adopted and reliable approach for the investigation of repeated or chronic exposure to Cannabis. The main markers are the Δ9-tetrahydrocannabinol (THC) and its main metabolite, 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), as stated by the Society of Hair Testing (SoHT) and the European Workplace Drug Testing Society (EWDTS). In this paper we presented an observational study on the hair concentrations of THC and THC-COOH and influences due to age, gender, consumption habits, and hair features. Data were collected from analysis of scalp hair samples (3-cm proximal segment) provided by subjects tested for THC consumption for personal purposes (i.e., workplace drug testing, personal use proving). The subjects provided an informed consent and a short questionnaire. A new analytical method was previously developed and then adopted. It consisted in a hydrolysis (1 mL of 1 M NaOH at 65 °C, 20 min) and a liquid-liquid extraction (with hexane/ethyl acetate,90/10, v/v in presence of 1.5 mL of H2SO4 1 M) of 25 mg of hair. A liquid chromatograph - tandem mass spectrometer (LC-MS/MS) equipped with a C18 column was used. The acquisition was in multiple reaction monitoring for the following transitions: 315→259, 193 m/z, for THC; 318→196, 123 m/z, for THC-d3; 345→299, 193 m/z for THC-COOH; 348→196, 302 m/z for THC-COOH-d3. Correlation between THC and THC-COOH hair concentrations was analyzed by Spearman's rank correlation coefficient. In order to study the influences of several variables, a new value, Sqrt(THC*THCCOOH), was adopted. Its effectiveness and reliability were proved by the Principal Component Analysis. Relationships between the Sqrt(THC*THCCOOH) and the variables were studied through the Stepwise regression (p = 0.05). The normality of data distribution was tested by the Shapiro-Wilk test. The Lower limits of quantification were 10.0 (THC) and 0.2 (THC-COOH) pg/mg. Accuracy and precision always met the acceptable criteria. Recoveries were > 78% and ion suppression was observed for both the compounds. Data from 126 hair samples were included in this study: 54 subjects(42.9%) were positive both for THC and THC-COOH; none of the samples was positive for a single substance. Concentrations ranged from 0.18 to 1.75 ng/mg (median: 0.78 ng/mg) for THC and from 0.04 to 0.85 ng/mg (median: 0.31 ng/mg) for THC-COOH. Cannabinoids levels seemed to decrease with the age, with lower amounts in the subjects aged > 40 years (p < 0.05). Also years of consumption seemed to have a significant impact on hair concentrations, as higher levels were observed in consumers from > 10 years (p = 0.013). Moreover, this study further provided evidences of a significant reduction of THC and THC-COOH in bleached hair (p = 0.042).

Usefulness of serum androgen isotope ratio mass spectrometry (IRMS) to detect testosterone supplementation in women.

The detection of testosterone intake is facilitated by monitoring the urinary steroid profile in the athlete biological passport. This technique can be used with confidence to identify target samples for isotope ratio mass spectrometry. Regrettably, most research has been performed on male subjects resulting in a method that does not account for females' steroid concentration and/or variation. This study evaluates the usefulness of the carbon isotope ratio (CIR) in serum of female subjects. Two steroid sulphates are targeted in serum, androsterone and epiandrosterone. Both exhibit statistically significant depletion of their CIR after 10 weeks of daily (10 mg) transdermal testosterone administration. Of the 21 female subjects, samples from six individuals were identified as adverse analytical findings; additionally, four were found atypical considering the serum CIR. The urinary athlete biological passport was not sufficiently sensitive to identify target serum samples for isotope ratio mass spectroscopy. Of the six with a suspicious passport, only two could be confirmed using the serum CIR of androsterone and epiandrosterone. This study shows that CIR analysis in serum cannot be considered the sole confirmatory solution to detect testosterone doping in women due to low sensitivity. However, this analysis has the potential to be used as a complementary method in certain situations to confirm exogenous testosterone in women.

Addressing recent challenges in isotope ratio mass spectrometry: Development of a method applicable to 1-androstene-steroids, 6α-hydroxy-androstenedione, and androstatrienedione.

In 2020, the confirmation of the non-endogenous origin of several pseudo-endogenous steroids by means of isotope ratio mass spectrometry (IRMS) was recommended by the World Anti-Doping Agency (WADA), in addition to previously established target analytes for IRMS in sports drug testing. To date, however, IRMS-based methods validated in accordance with current WADA regulations have not been available. Therefore, the aim of this research project was the development and validation of a method to determine the carbon isotope ratios (CIR) of all newly considered pseudo-endogenous steroids, encompassing the anabolic androgenic steroids comprising a 1-ene-core structure (5α-androst-1-ene-3ß,17ß-diol, 5α-androst-1-ene-3,17-dione [1AD], 17ß-hydroxy-5α-androst-1-en-3-one, 3α-hydroxy-5α-androst-1-ene-17-one [1AND], and 3ß-hydroxy-5α-androst-1-ene-17-one [1EpiAND]), as well as steroids referred to as hormone and metabolic modulators (androsta-1,4,6-triene-3,17-dione [TRD] and its main metabolite 17ß-hydroxy-androsta-1,4,6-triene-3-one) and 6α- and 6ß-hydroxy-androst-4-ene-3,17-dione. With peak purity of target analytes being critical for IRMS analyses, a twofold high-performance liquid chromatography (HPLC)-based sample purification was employed, with all analytes being acetylated between the first and second HPLC fractionation. Using established gas chromatography/combustion/IRMS instrumentation, limits of quantification were estimated at 10 ng/ml for a 20 ml urine aliquot for all analytes, except for 1AND (20 ng/ml), and combined measurement uncertainties were estimated between 0.4‰ and 0.9‰. For proof-of-concept, samples collected after the single oral administration of a nutritional supplement containing 1AD and 1EpiAND were analyzed as well as existing excretion study urine samples obtained after the administration of 4-androstenedione and TRD. Based on the obtained results, the developed method was considered to be fit-for-purpose.

Application of single hair analysis in a doping case involving amphetamine.

A previously published method for single hair analysis has been applied to a doping case for further clarification. Amphetamine could be detected in multiple micro segments resulting in two distinct concentration peaks in several hairs. The consumption of a contaminated food supplement as possible source for the amphetamine is discussed.

Development and Implementation of One-Step, Broad-Spectrum, High-Sensitivity Drug Screening by Tandem Mass Spectrometry in a Pediatric Population.

BACKGROUND: Drug screening by immunoassay is common in pediatric populations. However, false-positive and -negative results due to antibody cross-reactivity and dilute urine are frequent and underappreciated. Accurate ascertainment of drug exposure in children has significant clinical and medico-legal consequences. DESIGN AND METHODS: We developed and characterized an LC-MS/MS drug screening assay to supplant immunoassay and detect 38 compounds at the lowest concentrations distinguishable from analytic noise. Once implemented, we conducted a retrospective analysis of 3985 pediatric urine drug screens performed a year before (n = 1663) and after (n = 2322) implementation to examine the frequency and breadth of drug detection in our pediatric population. RESULTS: Using immunoassay, 23% (293/1269) of samples from the general pediatric and 37% (147/394) of nursery populations had presumptively positive results. Of the presumptive positive compounds, 85% (288/338) from the general pediatric population and 40% (65/162) from the nursery cohort were confirmed by mass spectrometry. After LC-MS/MS implementation, 31% (628/2052) of general pediatric, and 18% (48/270) of the nursery samples were positive for 1 or more compounds. In the nursery population, immunoassays over-detected the presence of THC but under-detected exposure to cocaine. CONCLUSION: A broadly targeted, analytically sensitive LC-MS/MS drug screening assay detects a larger number and variety of compounds in a single step compared to a screen-then-confirm approach initiated by immunoassay in our pediatric population. Rapid delivery of accurate results enables timely, appropriate disposition of patients in a variety of settings including the emergency department and labor/delivery.

A proposed approach to confirm heroin administration - Regional differences in heroin purity is a major factor.

In forensic toxicology, a marker of street heroin use is urgent especially in the absence of urinary 6-monoacetylmorphine. ATM4G, the Glucuronide of Acetylated product of Thebaine compound 4 Metabolite (ATM4), arising from byproducts of street heroin synthesis has been considered as a useful marker in some European studies. However, whether ATM4G is a universal marker particularly in Southeast Asia due to 'street' heroin with high purity, it's still unclear. To investigate putative markers for different regions, ATM4G and other metabolites including the Acetylated product of Thebaine compound 3 Metabolite (ATM3) and thebaol, also originated from thebaine were detected in 552 urine samples from heroin users in Taiwan. Results were compared with that from samples collected in the UK and Germany. Only a sulfo-conjugate of ATM4, ATM4S, was detected in 28 Taiwanese users using a sensitive MS3 method whilst out of 351 samples from the UK and Germany, ATM4G was present in 91. Thebaol-glucuronide was first time detected in 118. No markers were detected in urine following herbal medicine use or poppy seed ingestion. The presence of ATM4S/ATM4G might be affected by ethnicities and heroin supplied in regions. Thebaol-glucuronide is another putative marker with ATM4G and ATM4S for street heroin use.

Urine Drug Screening in the Era of Designer Benzodiazepines: Comparison of Three Immunoassay Platforms, LC-QTOF-MS and LC-MS-MS.

This study investigated the presence of designer benzodiazepines in 35 urine specimens obtained from emergency department patients undergoing urine drug screening. All specimens showed apparent false-positive benzodiazepine screening results (i.e., confirmatory testing using a 19-component liquid chromatography-tandem mass spectrometry (LC-MS-MS) panel showed no prescribed benzodiazepines at detectable levels). The primary aims were to identify the possible presence of designer benzodiazepines, characterize the reactivity of commercially available screening immunoassays with designer benzodiazepines and evaluate the risk of inappropriately ruling out designer benzodiazepine use when utilizing common urine drug screening and confirmatory tests. Specimens were obtained from emergency departments of a single US Health system. Following clinically ordered drug screening using Abbott ARCHITECT c assays and laboratory-developed LC-MS-MS confirmatory testing, additional characterization was performed for investigative purposes. Specifically, urine specimens were screened using two additional assays (Roche cobas c502 and Siemens Dimension Vista) and LC-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) to identify presumptively positive species, including benzodiazepines and non-benzodiazepines. Finally, targeted, qualitative LC-MS-MS was performed to confirm the presence of 12 designer benzodiazepines. Following benzodiazepine detection using the Abbott ARCHITECT, benzodiazepines were subsequently detected in 28/35 and 35/35 urine specimens using Siemens and Roche assays, respectively. LC-QTOF-MS showed the presumptive presence of at least one non-Food and Drug Administration (FDA)-approved benzodiazepine in 30/35 specimens: flubromazolam (12/35), flualprazolam (11/35), flubromazepam (2/35), clonazolam (4/35), etizolam (9/35), metizolam (5/35), nitrazepam (1/35) and pyrazolam (1/35). Two or three designer benzodiazepines were detected concurrently in 13/35 specimens. Qualitative LC-MS-MS confirmed the presence of at least one designer benzodiazepine or metabolite in 23/35 specimens, with three specimens unavailable for confirmatory testing. Urine benzodiazepine screening assays from three manufacturers were cross-reactive with multiple non-US FDA-approved benzodiazepines. Clinical and forensic toxicology laboratories using traditionally designed LC-MS-MS panels may fail to confirm the presence of non-US FDA-approved benzodiazepines detected by screening assays, risking inappropriate interpretation of screening results as false positives.

Longitudinal evaluation of multiple biomarkers for the detection of testosterone gel administration in women with normal menstrual cycle.

In women, hormonal fluctuations related to the menstrual cycle may impose a great source of variability for some biomarkers of testosterone (T) administration, which can ultimately disrupt the sensitivity of their longitudinal monitoring. In this study, the sensitivity of the current urinary and haematological markers of the Athlete Biological Passport (ABP), as well as serum steroid biomarkers, was investigated for the monitoring of a 28-day T gel treatment combined with endogenous fluctuation of the menstrual cycle in 14 healthy female subjects. Additionally, the analysis of urinary target compounds was performed on a subset of samples for endogenous/exogenous origin via isotope ratio mass spectrometry (IRMS). In serum, concentrations of T and dihydrotestosterone (DHT) increased significantly during the treatment, whereas in urine matrix the most affected biomarkers were found to be the ratios of testosterone/epitestosterone (T/E) and 5α-androstane-3α,17ß-diol/epitestosterone (5αAdiol/E). The detection capability of both urinary biomarkers was heavily influenced by [E], which fluctuated depending on the menstrual cycle, and resulted in low sensitivity of the urinary steroidal ABP module. On the contrary, an alternative approach by the longitudinal monitoring of serum T and DHT concentrations with the newly proposed T/androstenedione ratio showed higher sensitivity. The confirmatory IRMS results demonstrated that less than one third of the tested urine samples fulfilled the criteria for positivity. Results from this study demonstrated that the 'blood steroid profile' represents a powerful complementary approach to the 'urinary module' and underlines the importance of gathering bundle of evidence to support the scenario of an endogenous prohibited substance administration.

Biotin as a masking agent in chorionic gonadotropin assays utilizing biotinylated antibodies.

Biotin interference in streptavidin/biotin-based immunoassays has been recently recognized as a confounding factor in clinical settings. Depending on the nature of the assay, the presence of excess biotin in patient samples can cause falsely high or low results. One of the platforms known to be affected, Roche Cobas, is widely used in anti-doping laboratories to test for intact chorionic gonadotropin (hCG) in urine. While biotin levels in blood have been well studied, less is known about urinary biotin due to its limited clinical significance. Having analyzed over 4,000 urine samples, we have established a reference range for urinary biotin with a median concentration of approximately 12 ng/ml. However, a significant number of samples contain much higher amounts, with a maximum approaching 10 µg/ml, suggesting biotin supplementation. Consequently, the tolerance of hCG STAT assay towards biotin was investigated over a wide concentration range. The apparent hCG concentration was found to decrease almost linearly as biotin increased from 100 to 1,000 ng/ml, with only 10% of the expected value reported by the assay as biotin reached 1,000 ng/ml. Further increase of biotin resulted in a progressive, albeit more moderate, decline in measured hCG concentration. To avoid a false negative result in the context of anti-doping analysis, it is highly recommended to monitor biotin in urine and perform diafiltration before hCG measurement in samples with elevated biotin to remove the interference.

Analytical strategy for the detection of ecdysterone and its metabolites in vivo in uPA(+/+)-SCID mice with humanized liver, human urine samples, and estimation of prevalence of its use in anti-doping samples.

Ecdysteroids are of interest as potential sport performance enhancers, due to their anabolic effects. The current study aimed to analyze levels of the most abundant ecdysteroid, ecdysterone (20-hydroxyecdysone, 20-OHE) in easily available dietary supplements, and, outline an analytical strategy for its detection, and that, of its metabolites, (1) following administration of pure 20-OHE to uPA(+/+)-SCID mice with humanized liver, (2) in a human volunteer after ingestion of two supplements, one with a relatively low, and the other a high, concentration of 20-OHE, and, (3) to estimate the prevalence of use of 20-OHE in elite athletes (n = 1000). Of the 16 supplements tested, only five showed detectable levels of 20-OHE, with concentrations ranging from undetectable up to 2.3 mg per capsule. Urine of uPA(+/+)-SCID urine showed the presence of 20-OHE and its metabolite, 14 deoxy ecdysterone, within 24 hours (hr) of ingestion. In humans, both the parent and the metabolite were detectable within 2 to 5 hr of ingestion, with the metabolite being detectable for longer than the parent. After ingestion of a low dose supplement, the parent and metabolite were detectable for 70 and 48 hr, while following the higher dose it was 96 and 48 hr, respectively. Analysis of urines from athletes (n = 1000) confirmed four positives for 20-OHE, suggesting a prevalence of use of 0.4%. Prevalence of its use by elite athletes was relatively low, however, this needs to be confirmed in other populations, and with other related ecdysteroids.

Sleep time differs among people who co-use cocaine and cannabis compared to people who only use cocaine.

OBJECTIVE: People who use cocaine experience numerous sleep problems and often use cannabis to mitigate these problems. However, co-using cocaine and cannabis may result in worse sleep outcomes when compared to using cocaine only. The current study examined group differences in subjective sleep outcomes among people who use cocaine and people who co-use cocaine and cannabis. METHODS: Participants were 82 individuals with cocaine use disorder who were enrolled in a randomized clinical trial for cocaine treatment. Sleep outcomes, assessed at baseline prior to treatment, were measured with the Saint Mary's Hospital Sleep Questionnaire and included total sleep time, perceived sleep quality, difficulty falling asleep, and daytime alertness. Analysis of covariance and Kruskal-Wallis tests were used to compare sleep outcomes between participants with urine samples that tested positive for both cocaine and cannabis at baseline, those who tested positive for cocaine only, and those who tested negative for all drugs. RESULTS: Total reported sleep time was highest among those with a drug negative urine, followed by those with a cocaine positive urine and those who tested positive for cocaine and cannabis. There were no differences in perceived sleep quality, difficulty falling asleep, or daytime alertness between groups. CONCLUSIONS: People who co-use cocaine and cannabis may report reduced sleep time relative to those who only use cocaine. Co-use of cannabis may exacerbate sleep difficulties in people who use cocaine by decreasing total sleep time, although it is important to note that the groups each reported similar sleep quality. Implications for treatment and directions for future research are discussed.

Random urine drug testing among patients receiving opioid therapy for cancer pain.

BACKGROUND: There is limited information regarding the true frequency of nonmedical opioid use (NMOU) among patients receiving opioid therapy for cancer pain. Data to guide patient selection for urine drug testing (UDT) as well as the timing and frequency of ordering UDT are insufficient. This study examined the frequency of abnormal UDT among patients with cancer who underwent random UDT and their characteristics. METHODS: Demographic and clinical information for patients with cancer who underwent random UDT were retrospectively reviewed and compared with a historical cohort that underwent targeted UDT. Random UDT was ordered regardless of a patient's risk potential for NMOU. Targeted UDT was ordered on the basis of a physician's estimation of a patient's risk for NMOU. RESULTS: In all, 552 of 573 eligible patients (96%) underwent random UDT. Among these patients, 130 (24%) had 1 or more abnormal results; 38 of the 88 patients (43%) who underwent targeted UDT had 1 or more abnormal results. When marijuana was excluded, 15% of the random group and 37% of the targeted group had abnormal UDT findings (P < .001). It took a shorter time from the initial consultation to detect 1 or more abnormalities with the random test than the targeted test (median, 130 vs 274 days; P = .02). Abnormal random UDT was independently associated with younger age (P < .0001), male sex (P = .03), Cut Down, Annoyed, Guilty, and Eye Opener-Adapted to Include Drugs positivity (P = .001), and higher Edmonton Symptom Assessment System anxiety (P = .01). CONCLUSIONS: Approximately 1 in 4 patients receiving opioids for cancer pain at a supportive care clinic who underwent random UDT had 1 or more abnormalities. Random UDT detected abnormalities earlier than the targeted test. These findings suggest that random UDT is justified among patients with cancer pain.