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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 (Δ9-THCCOOH)) are understudied. This study characterized the urinary pharmacokinetics of CBD (100 mg) following vaporization or oral administration (including three formulations: gelcap, pharmacy-grade syrup and 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 h after dosing on a residential research unit. Immunoassay (IA) screening (cutoffs: 20, 50 and 100 ng/mL) for Δ9-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 = 1,274 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 Δ8- or Δ9-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 six urine samples in which Δ9-THCCOOH concentrations ≥15 ng/mL. All six specimens screened positive at a 20 ng/mL IA cutoff, and two of six 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 Δ9-THC may produce a cannabis-positive urine drug test.

The growing use of cannabidiol (CBD) products by the general public is expected to result in an increase in the prevalence of CBD and the CBD metabolites in drug testing laboratories. CBD converts into tetrahydrocannabinol (THC) under acid conditions which could produce false-positive results, but little is known about how the presence of the urinary metabolite of CBD, 7-carboxy-cannabidiol (7-COOH-CBD), would affect urine drug testing for 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH). As the operators of the National Laboratory Certification Program (NLCP), we prepared a set of performance testing samples containing 7-COOH-CBD for cannabinoid testing at the laboratories accredited by the NLCP to investigate if 7-COOH-CBD can produce false-positive results for THC-COOH during immunological screening analysis and if 7-COOH-CBD can be converted to THC-COOH. At concentrations up to 2,500 ng/mL, 7-COOH-CBD was not reactive by immunoassay in any of the four different immunoassay kits used. Additionally, we did not observe any significant conversion of 7-COOH-CBD to THC-COOH in assays used by NLCP-certified laboratories. However, we did see conversion when we requested that selected laboratories retest their samples using derivatization with perfluorinated anhydrides in combination with perfluorinated alcohols or when samples containing 7-COOH-CBD were exposed to acid for an extended time.

Oral cannabis products (a.k.a. “edibles”) have increased in popularity in recent years. Most prior controlled pharmacokinetic evaluations of cannabis have focused on smoked cannabis and included males who were frequent cannabis users. In this study, 17 healthy adults (8 females), with no cannabis use in at least the past 2 months, completed 4 double-blind outpatient sessions where they consumed cannabis brownies containing Δ9-tetrahydrocannabinol (THC) doses of 0, 10, 25 or 50 mg. Whole blood and oral fluid specimens were collected at baseline and for 8 h post-brownie ingestion. Enzyme-linked immunosorbent assay (ELISA) and liquid chromatography–tandem mass spectrometry (LC–MS-MS) were used to measure THC and relevant metabolites. In whole blood, concentrations of THC and 11-hydroxy-THC (11-OH-THC) peaked 1.5–2 h after brownie consumption, decreased steadily thereafter, and typically returned to baseline within 8 h. Blood concentrations for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) and THCCOOH-glucuronide were higher than THC and 11-OH-THC and these metabolites were often still detected 8 h post-brownie consumption. Women displayed higher peak concentrations for THC and all metabolites in whole blood compared to men, at least partially owing to their lower body weight/body mass index. Detection of THC in oral fluid was immediate and appeared to reflect the degree of cannabis deposition in the oral cavity, not levels of THC circulating in the blood. THC concentrations were substantially higher in oral fluid than in blood; the opposite trend was observed for THCCOOH. Agreement between ELISA and LC–MS-MS results was high (i.e., over 90%) for blood THCCOOH and oral fluid THC but comparatively low for oral fluid THCCOOH (i.e., 67%). Following oral consumption of cannabis, THC was detected in blood much later, and at far lower peak concentrations, compared to what has been observed with inhaled cannabis. These results are important given the widespread use of toxicological testing to detect recent use of cannabis and/or to identify cannabis intoxication.

Most research on cannabis pharmacokinetics has evaluated inhaled cannabis, but oral (“edible”) preparations comprise an increasing segment of the cannabis market. To assess oral cannabis pharmacokinetics and pharmacodynamics, healthy adults (N = 6 per dose) were administered cannabis brownies containing 10, 25 or 50 mg 9-tetrahydrocannabinol (THC). Whole blood and oral fluid specimens were obtained at baseline and then for 9 days post-exposure; 6 days in a residential research setting and 3 days as outpatients. Measures of subjective, cardiovascular and performance effects were obtained at baseline and for 8 h post-ingestion. The mean Cmax for THC in whole blood was 1, 3.5 and 3.3 ng/mL for the 10, 25 and 50 mg THC doses, respectively. The mean maximum concentration (Cmax) and mean time to maximum concentration (Tmax) of 11-OH-THC in whole blood were similar to THC. Cmax blood concentrations of THCCOOH were generally higher than THC and had longer Tmax values. The mean Tmax for THC in oral fluid occurred immediately following oral dose administration, and appear to reflect local topical residue rather than systemic bioavailbility. Mean Cmax oral fluid concentrations of THCCOOH were lower than THC, erratic over time and mean Tmax occurred at longer times than THC. The window of THC detection ranged from 0 to 22 h for whole blood (limit of quantitation (LOQ) = 0.5 ng/mL) and 1.9 to 22 h for oral fluid (LOQ = 1.0 ng/mL). Subjective drug and cognitive performance effects were generally dose dependent, peaked at 1.5–3 h post-administration, and lasted 6–8 h. Whole blood cannabinoid concentrations were significantly correlated with subjective drug effects. Correlations between blood cannabinoids and cognitive performance measures, and between oral fluid and all pharmacodynamic outcomes were either non-significant or not orderly by dose. Quantitative levels of cannabinoids in whole blood and oral fluid were low compared with levels observed following inhalation of cannabis. The route of administration is important for interpretation of cannabinoid toxicology.

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.

Hydromorphone (HM), a prescription opioid and metabolite of morphine and hydrocodone, has been included in proposed revisions to the Mandatory Guidelines for Federal Workplace Drug Testing Programs. This study characterized the time course of HM in hydrolyzed and non-hydrolyzed urine specimens. Twelve healthy subjects were administered a single 8 mg controlled-release HM dose, followed by periodic collection of pooled urine specimens for 54 h following administration. Analysis of total and free HM was conducted by liquid chromatography tandem mass spectrometry at a 50 ng/mL limit of quantitation. Detection periods were determined over a range of thresholds from 50 to 2,000 ng/mL. HM was detected in 85.3% and 47.6% of hydrolyzed and non-hydrolyzed post-dose specimens, respectively. Initial detection of total HM was frequently observed in the first 4-6 h following dosing. The period of detection at the 50 ng/mL threshold averaged 52.3 h for total HM and 38.0 h for free HM. These data support that HM detection is optimized by using low thresholds (50-100 ng/mL) and including conjugated HM in the analysis.

Introduction The use and availability of oral and inhalable products containing cannabidiol (CBD) as the principal constituent has increased with expanded cannabis/hemp legalization. However, few controlled clinical laboratory studies have evaluated the pharmacodynamic effects of oral or vaporized CBD or CBD-dominant cannabis. Methods Eighteen healthy adults (9 men; 9 women) completed four, double-blind, double-dummy, drug administration sessions. Sessions were separated by ≥1 week and included self-administration of 100 mg oral CBD, 100 mg vaporized CBD, vaporized CBD-dominant cannabis (100 mg CBD; 3.7 mg THC), and placebo. Study outcomes included: subjective drug effects, vital signs, cognitive/psychomotor performance, and whole blood THC and CBD concentrations. Results Vaporized CBD and CBD-dominant cannabis increased ratings on several subjective items (e.g., Like Drug Effect) relative to placebo. Subjective effects did not differ between oral CBD and placebo and were generally higher for CBD-dominant cannabis compared to vaporized CBD. CBD did not increase ratings for several items typically associated with acute cannabis/THC exposure (e.g., Paranoid). Women reported qualitatively higher ratings for Pleasant Drug Effect than men after vaporized CBD and CBD-dominant cannabis use. CBD-dominant cannabis increased heart rate compared to placebo. Cognitive/psychomotor impairment was not observed in any drug condition. Conclusions Vaporized CBD and CBD-dominant cannabis produced discriminable subjective drug effects, which were sometimes stronger in women, but did not produce cognitive/psychomotor impairment. Subjective effects of oral CBD did not differ from placebo. Future research should further elucidate the subjective effects of various types of CBD products (e.g., inhaled, oral, topical), which appear to be distinct from THC-dominant products.

As cannabis has become more accessible, use of alternative methods for cannabis administration such as vaporizers has become more prevalent. Most prior controlled pharmacokinetic evaluations have examined smoked cannabis in frequent (often daily) cannabis users. This study characterized the urinary excretion profile of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH), the primary analytical outcome for detection of cannabis use, among infrequent cannabis users following controlled administration of both smoked and vaporized cannabis. Healthy adults (N = 17), with a mean of 398 (range 30–1,825) days since last cannabis use, smoked and vaporized cannabis containing 0, 10, and 25 mg of Δ9-tetrahydrocannabinol (THC) across six outpatient sessions. Urinary concentrations of THCCOOH were measured at baseline and for 8 h after cannabis administration. Sensitivity, specificity, and agreement between three immunoassays (IA) for THCCOOH (with cutoffs of 20, 50, and 100 ng/mL) and gas chromatography-mass spectrometry (GC/MS) results (confirmatory concentration of 15 ng/mL) were assessed. THCCOOH concentrations peaked 4–6 h after cannabis administration. Median maximum concentrations (Cmax) for THCCOOH were qualitatively higher after administration of vaporized cannabis compared to equal doses of smoked cannabis. Urine THCCOOH concentrations were substantially lower in this study relative to prior examinations of experienced cannabis users. The highest agreement between IA and GC/MS was observed at the 50 ng/mL IA cutoff while sensitivity and specificity were highest at the 20 and 100 ng/mL IA cutoffs, respectively. Using federal workplace drug-testing criteria (IA cutoff of 50 ng/mL and GC/MS concentration ≥15 ng/mL) urine specimens tested positive in 47% of vaporized sessions and 21% of smoked sessions with active THC doses (N = 68). Urinary concentrations of THCCOOH are dissimilar after administration of smoked and vaporized cannabis, with qualitatively higher concentrations observed after vaporization. Infrequent users of cannabis may excrete relatively low concentrations of THCCOOH following acute inhalation of smoked or vaporized cannabis.

Currently, an unprecedented number of individuals can legally access cannabis. Vaporization is increasingly popular as a method to self-administer cannabis, partly due to perception of reduced harm compared with smoking. Few controlled laboratory studies of cannabis have used vaporization as a delivery method or evaluated the acute effects of cannabis among infrequent cannabis users. This study compared the concentrations of cannabinoids in whole blood and oral fluid after administration of smoked and vaporized cannabis in healthy adults who were infrequent users of cannabis. Seventeen healthy adults, with no past-month cannabis use, self-administered smoked or vaporized cannabis containing Δ9-tetrahydrocannabinol (THC) doses of 0, 10 and 25 mg in six double-blind outpatient sessions. Whole blood and oral fluid specimens were obtained at baseline and for 8 h after cannabis administration. Cannabinoid concentrations were assessed with enzyme-linked immunosorbent assay (ELISA) and liquid chromatography–tandem mass spectrometry (LC–MS-MS) methods. Sensitivity, specificity and agreement between ELISA and LC–MS-MS results were assessed. Subjective, cognitive performance and cardiovascular effects were assessed. The highest concentrations of cannabinoids in both whole blood and oral fluid were typically observed at the first time point (+10 min) after drug administration. In blood, THC, 11-OH-THC, THCCOOH and THCCOOH-glucuronide concentrations were dose-dependent for both methods of administration, but higher following vaporization compared with smoking. THC was detected longer in oral fluid compared to blood and THCCOOH detection in oral fluid was rare and highly erratic. For whole blood, greater detection sensitivity for ELISA testing was observed in vaporized conditions. Conversely, for oral fluid, greater sensitivity was observed in smoked sessions. Blood and/or oral fluid cannabinoid concentrations were weakly to moderately correlated with pharmacodynamic outcomes. Cannabis pharmacokinetics vary by method of inhalation and biological matrix being tested. Vaporization appears to be a more efficient method of delivery compared with smoking.

The increasing use of highly potent strains of cannabis prompted this new evaluation of human toxicology and subjective effects following passive exposure to cannabis smoke. The study was designed to produce extreme cannabis smoke exposure conditions tolerable to drug-free nonsmokers. Six experienced cannabis users smoked cannabis cigarettes [5.3% Δ(9)-tetrahydrocannabinol (THC) in Session 1 and 11.3% THC in Sessions 2 and 3] in a closed chamber. Six nonsmokers were seated alternately with smokers during exposure sessions of 1 h duration. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Oral fluid, whole blood and subjective effect measures were obtained before and at multiple time points after each session. Oral fluid was analyzed by ELISA (4 ng/mL cutoff concentration) and by LC-MS-MS (limit of quantitation) for THC (1 ng/mL) and total THCCOOH (0.02 ng/mL). Blood was analyzed by LC-MS-MS (0.5 ng/mL) for THC, 11-OH-THC and free THCCOOH. Positive tests for THC in oral fluid and blood were obtained for nonsmokers up to 3 h following exposure. Ratings of subjective effects correlated with the degree of exposure. Subjective effect measures and amounts of THC absorbed by nonsmokers (relative to smokers) indicated that extreme secondhand cannabis smoke exposure mimicked, though to a lesser extent, active cannabis smoking.

Oxycodone (OC) is recommended to be included as an analyte tested in the proposed Substance Abuse and Mental Health Services Administration (SAMHSA's) Mandatory Guidelines for Federal Workplace Drug Testing Programs using Oral Fluid (OF) Specimens. This study demonstrates the time course of OC and metabolites, noroxycodone (NOC), oxymorphone (OM) and noroxymorphone (NOM), in near-simultaneous paired OF and whole blood (BL) specimens by liquid chromatography-tandem mass spectrometry (LC-MS-MS) (limit of detection = 1 ng/mL OF, 5 ng/mL BL). A single dose of OC 20 mg controlled-release was administered to 12 healthy subjects followed by specimen collections for 52 h. Analyte prevalence was as follows: OF, OC > NOC > OM; and BL, OC > NOC > NOM. OC and NOC were frequently detected within 15-30 min in OF and 30 min to 2 h in BL. NOM and OM appeared between 1.5-5 h post-dose. The mean OF-to-BL (OF:BL) ratios and correlations were 5.4 for OC (r = 0.719) and 1.0 for NOC (r = 0.651). The period of detection for OF exceeded BL by ∼2-fold at similar cutoff concentrations. At a 1 ng/mL cutoff for OF, the mean detection time was 34 h for OC and NOC. These data provide new information that should facilitate interpretation of OC test results.

Current hair testing methods that rely solely on quantification of parent drug compounds are unable to definitively distinguish between drug use and external contamination. One possible solution to this problem is to confirm the presence of unique drug metabolites that cannot be present through contamination, such as phase II glucuronide conjugates. This work demonstrates for the first time that codeine-6-glucuronide, hydromorphone-3-glucuronide, oxymorphone-3-glucuronide, morphine-3-glucuronide and morphine-6-glucuronide are present at sufficient concentrations to be quantifiable in hair of opioid users and that their concentrations generally increase as the concentrations of the corresponding parent compounds increase. Here, we present a validated liquid chromatography tandem mass spectrometry method to quantify codeine-6-glucuronide, dihydrocodeine-6-glucuronide, hydromorphone-3-glucuronide, morphine-3-glucuronide, morphine-6-glucuronide, oxymorphone-3-glucuronide, codeine, dihydrocodeine, dihydromorphine, hydrocodone, hydromorphone, morphine, oxycodone, oxymorphone and 6-acetylmorphine in human hair. The method was used to analyze 46 human hair samples from known drug users that were confirmed positive for opioids by an independent laboratory. Glucuronide concentrations in samples positive for parent analytes ranged from ~1 to 25 pg/mg, and most samples had glucuronide concentrations in the range of ~1 to 5 pg/mg. Relative to the parent concentrations, the average concentrations of the four detected glucuronides were as follows: codeine-6-glucuronide, 2.33%; hydromorphone-3-glucuronide, 0.94%; oxymorphone-3-glucuronide, 0.77%; morphine 3-glucuronide, 0.59%; and morphine-6-glucuronide, 0.93%.

Increased cannabis potency has renewed concerns that secondhand exposure to cannabis smoke can produce positive drug tests. A systematic study was conducted of smoke exposure on drug-free participants. Six experienced cannabis users smoked cannabis cigarettes (5.3% THC in Session 1 and 11.3% THC in Sessions 2 and 3) in a sealed chamber. Six non-smokers were seated with smokers in an alternating manner. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Non-smoking participant specimens (collected 0‐34 h) were analyzed with four immunoassays at different cutoff concentrations (20, 50, 75 and 100 ng/mL) and by GC-MS (LOQ 5 0.75 ng/mL). No presumptive positives occurred for non-smokers at 100 and 75 ng/mL; a single positive occurred at 50 ng/mL; and multiple positives occurred at 20 ng/ mL. Maximum THCCOOH concentrations by GC-MS for non-smokers ranged from 1.3 to 57.5 ng/mL. THCCOOH concentrations generally increased with THC potency, but room ventilation substantially reduced exposure levels. These results demonstrate that extreme cannabis smoke exposure can produce positive urine tests at commonly utilized cutoff concentrations. However, positive tests are likely to be rare, limited to the hours immediately post-exposure, and occur only under environmental circumstances where exposure is obvious.

Hydrocodone (HC) is a highly misused prescription drugs in the USA. Interpretation of urine tests for HC is complicated by its metabolism to two metabolites, hydromorphone (HM) and dihydrocodeine (DHC), which are also available commercially and are misused. Currently, there is interest in including HC and HM in the federal workplace drug-testing programs. This study characterized the disposition of HC in human urine. Twelve healthy, drug-free, adults were administered a single, oral 20 mg immediate-release dose of HC in a controlled clinical setting. Urine specimens were collected at timed intervals for up to 52 h and analyzed by LC-MS-MS (limit of quantitation = 50 ng/mL) with and without enzymatic hydrolysis. All specimens were also analyzed for creatinine and specific gravity (SG). HC and norhydrocodone (NHC) appeared within 2 h followed by HM and DHC. Peak concentrations of HC and metabolites occurred at 3-9 h. Peak hydrolyzed concentrations were in the order: NHCHCHMDHC. Only HM was excreted extensively as a conjugated metabolite. At a cutoff concentration of 50 ng/mL, detection times were ∼28 h for HC, 40 h for NHC, 26 h for HM and 16 h for DHC. Some specimens did not contain HC, but most contained NHC, thereby facilitating interpretation that HC was the administered drug. Creatinine and SG measures were highly correlated. Creatinine corrections of HC urinary data had variable effects of lowering or raising concentrations. These data suggest that drug-testing requirements for HC should include a hydrolysis step and a test for HM.

Importance Vaporization is an increasingly popular method for cannabis administration, and policy changes have increased adult access to cannabis drastically. Controlled examinations of cannabis vaporization among adults with infrequent current cannabis use patterns (>30 days since last use) are needed. Objective To evaluate the acute dose effects of smoked and vaporized cannabis using controlled administration methods. Design, Setting, and Participants This within-participant, double-blind, crossover study was conducted from June 2016 to January 2017 at the Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, and included 17 healthy adults. Six smoked and vaporized outpatient experimental sessions (1-week washout between sessions) were completed in clusters (order counterbalanced across participants); dose order was randomized within each cluster. Interventions Cannabis containing Δ9-tetrahydrocannabinol (THC) doses of 0 mg, 10 mg, and 25 mg was vaporized and smoked by each participant. Main Outcomes and Measures Change from baseline scores for subjective drug effects, cognitive and psychomotor performance, vital signs, and blood THC concentration. Results The sample included 17 healthy adults (mean [SD] age, 27.3 [5.7] years; 9 men and 8 women) with no cannabis use in the prior month (mean [SD] days since last cannabis use, 398 [437] days). Inhalation of cannabis containing 10 mg of THC produced discriminative drug effects (mean [SD] ratings on a 100-point visual analog scale, smoked: 46 [26]; vaporized: 69 [26]) and modest impairment of cognitive functioning. The 25-mg dose produced significant drug effects (mean [SD] ratings, smoked: 66 [29]; vaporized: 78 [24]), increased incidence of adverse effects, and pronounced impairment of cognitive and psychomotor ability (eg, significant decreased task performance compared with placebo in vaporized conditions). Vaporized cannabis resulted in qualitatively stronger drug effects for most pharmacodynamic outcomes and higher peak concentrations of THC in blood, compared with equal doses of smoked cannabis (25-mg dose: smoked, 10.2 ng/mL; vaporized, 14.4 ng/mL). Blood THC concentrations and heart rate peaked within 30 minutes after cannabis administration and returned to baseline within 3 to 4 hours. Several subjective drug effects and observed cognitive and psychomotor impairments persisted for up to 6 hours on average. Conclusions and Relevance Vaporized and smoked cannabis produced dose-orderly drug effects, which were stronger when vaporized. These data can inform regulatory and clinical decisions surrounding the use of cannabis among adults with little or no prior cannabis exposure. Trial Registration ClinicalTrials.gov Identifier: NCT03676166.

Morphological changes in hair subjected to decontamination protocols were evaluated by scanning electron microscopy (SEM) as part of the National Laboratory Certification Program's (NLCP) efforts to develop proficiency testing materials in support of Federal Workplace Drug Testing programs. Hair from five different donors was evaluated. Hair samples were subjected to three decontamination protocols: (1) aqueous phosphate buffer, (2) methanol or (3) methylene chloride as models for aqueous, alcohol and polar organic solvent protocols, respectively. Under these protocols, samples of hair were treated for 225 min (aqueous), 15 min (alcohol), or 15 min (polar organic). After decontamination, hair strands were sputter coated with gold/palladium (AuPd) and observed by SEM. Modest lifting of cuticle scales was observed in hair treated with methanol and methylene chloride consistent with some changes to the cell membrane complex (CMC) between cuticle scales. Damage resulting from aqueous buffer treatment ranged from substantial degradation to apparent complete loss of cuticle scales. Fracture structures consistent with cuticle damage were also observed. Each decontamination protocol had a different impact on the cuticle of the hair shaft.

Cannabis is the most widely used illicit drug. Many individuals are incidentally exposed to secondhand cannabis smoke, but little is known about the effects of this exposure. This report examines the physiological, subjective, and behavioral/cognitive effects of secondhand cannabis exposure, and the influence of room ventilation on these effects.Non-cannabis-using individuals were exposed to secondhand cannabis smoke from six individuals smoking cannabis (11.3% THC) ad libitum in a specially constructed chamber for 1h. Chamber ventilation was experimentally manipulated so that participants were exposed under unventilated conditions or with ventilation at a rate of 11 air exchanges/h. Physiological, subjective and behavioral/cognitive measures of cannabis exposure assessed after exposure sessions were compared to baseline measures.Exposure to secondhand cannabis smoke under unventilated conditions produced detectable cannabinoid levels in blood and urine, minor increases in heart rate, mild to moderate self-reported sedative drug effects, and impaired performance on the digit symbol substitution task (DSST). One urine specimen tested positive at using a 50 ng/ml cut-off and several specimens were positive at 20 ng/ml. Exposure under ventilated conditions resulted in much lower blood cannabinoid levels, and did not produce sedative drug effects, impairments in performance, or positive urine screen results.Room ventilation has a pronounced effect on exposure to secondhand cannabis smoke. Under extreme, unventilated conditions, secondhand cannabis smoke exposure can produce detectable levels of THC in blood and urine, minor physiological and subjective drug effects, and minor impairment on a task requiring psychomotor ability and working memory.

LacTekTM tests are competitive enzyme-linked immunosorbent assays intended for rapid detection of antimicrobial residues in bovine milk. In this study, the LacTek test protocol was modified for use with extracts of bovine tissue to detect β-lac-tam, tetracycline, and sulfamethazine residues. Testperformance characteristics—precision, accuracy, ruggedness, practicability, and analytical specificity and sensitivity—were investigated. Results suggest that LacTek tests can be easily adapted to detect antimicrobial residues in extracts of lean ground beef. However, positive samples may not contain residues at violative concentrations (i.e., Canadian maximum residue limits), and therefore, additional analysis would be required for final confirmation and quantitation (e.g., chromatography).

Interpretation of marijuana-positive urine tests requires an understanding of the excretion pattern of marijuana metabolites in humans. However, limited urinary excretion data from controlled clinical studies of marijuana use are available. In this study, six subjects smoked a single marijuana cigarette (placebo, 1.75% delta 9-tetrahydrocannabinol [THC], or 3.55% THC) each week while residing on the clinical ward of the Addiction Research Center. Individual urine specimens were collected for 7 days after drug administration and analyzed for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH) by gas chromatography-mass spectrometry (GC-MS) with a limit of detection of 0.5 ng/mL. Substantial intersubject variability in patterns of THCCOOH excretion was noted between subjects and between doses. Mean THCCOOH concentrations in the first urine collections were 47 +/- 22.3 ng/mL and 75.3 +/- 48.9 ng/mL after the 1.75 and 3.55% THC cigarettes, respectively. Mean peak urine THCCOOH concentrations averaged 89.8 +/- 31.9 ng/mL and 153.4 +/- 49.2 ng/mL after smoking of approximately 15.8 mg and 33.8 mg THC, respectively. The mean times of peak urine concentration were 7.7 +/- 0.8 h after the 1.75% THC and 13.9 +/- 3.5 h after the 3.55% THC dose. Mean GC-MS THCCOOH detection times for the last positive urine sample after the smoking of a single 1.75 or 3.55% THC cigarette were 33.7 +/- 9.2 h and 88.6 +/- 9.5 h, respectively, when a 15-ng/mL cutoff concentration was used. An average of 93.9 +/- 24.5 micrograms THCCOOH (range, 34.6-171.6 micrograms) was excreted by each subject during the 7-day period after smoking of a single 1.75% THC cigarette. The average amount of THCCOOH excreted in the same time period after the high dose was 197.4 +/- 33.6 micrograms (range, 107.5-305.0 micrograms). This represented an average of only 0.54 +/- 0.14% and 0.53 +/- 0.09% of the original amount of THC in the low-and high-dose cigarettes, respectively. These data provide a detailed complication of THCCOOH concentrations in urine after administration of marijuana that may aid in the interpretation of urine cannabinoid results.

Self-contained drug-testing kits are currently being marketed for a variety of drugs of abuse. These tests are designed to provide rapid access to test results without the need for laboratory facilities. This report describes a validity study of the accuPINCH THC test, a self-contained test for cannabinoids in urine. Three healthy male volunteers with a history of marijuana use participated in the clinical study. Each subject smoked one, two, or four marijuana cigarettes (2.6% THC) on each test day. Urine samples were collected and incorporated into a specimen set consisting of 178 clinical samples, 72 urine samples containing known amounts of drug, and 50 drug-free urine samples. The specimen set was randomized and analyzed under blind conditions by the accuPINCH test and by gas chromatography-mass spectrometry (GC-MS) for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH). AccuPINCH results were interpreted independently by three readers as positive at either two calibration points (positive A100 ng/mL THCCOOH; positive Bor = 100 ng/mL THCCOOH) or negative. Concordance analysis was performed by comparison of the accuPINCH results with GC-MS. In addition, the effects of changes in sample turbidity, temperature, and assay reading time on test outcome were assessed. For the clinical samples, positive B results were associated exclusively with THCCOOH concentrations greater than or equal to 15 ng/mL, whereas positive A and negative results were obtained at all concentrations. All drug-free urine samples were interpreted as either negative or positive A. The test demonstrated relatively low cross-reactivity with THC and other cannabinoids.(ABSTRACT TRUNCATED AT 250 WORDS)

In urine drug testing, enantiomer analysis is used to determine whether a positive methamphetamine result could be due to use of an over-the-counter (OTC) nasal inhaler containing L-methamphetamine. D-methamphetamine at more than 20% of the total is considered indicative of a source other than an OTC product. This interpretation is based on a 1991 Department of Health and Human Services (HHS) Technical Advisory. We performed studies to verify the methamphetamine enantiomer content of current OTC nasal inhalers and to evaluate current laboratory testing capabilities. This study demonstrated that OTC inhalers contain less than 1% D-methamphetamine. A proficiency testing (PT) set for HHS-certified laboratories performing methamphetamine enantiomer testing found D-methamphetamine percentages that were consistently 1 to 3% higher than theoretical due to optical impurity of the derivatizing reagent N-trifluoroacetyl-L-prolyl chloride (L-TPC). The PT results also demonstrate that laboratories can accurately determine 20% D-methamphetamine in samples with total methamphetamine concentrations down to 250 ng/mL. Based on these studies, the guideline of >20% D-methamphetamine is appropriate for interpreting results obtained using current laboratory methods.

Proposed changes to the Health and Human Services Guidelines for forensic urine drug testing will lower the required cannabinoid immunoassay cutoff concentration from 100 to 50 micrograms/L. We investigated the effect of this change on the sensitivity, specificity, and efficiency of eight cannabinoid immunoassays: Syva Emit d.a.u. 100; Syva Emit II 100; Syva Emit d.a.u. 50; Syva Emit II 50; Roche Abuscreen Online; Roche Abuscreen radioimmunoassay; Diagnostic Reagents; and Abbott ADx. All specimens also were assayed by gas chromatography/mass spectrometry. Lowering the cutoff concentration from 100 to 50 micrograms/L increased efficiencies and sensitivities for all immunoassays, with minor decreases in specificity (1.0-2.6%). There was a 23.2-53.6% increase in the number of true-positive specimens identified. Thus, lowering the cannabinoid immunoassay cutoff concentration from 100 to 50 micrograms/L resulted in detection of a substantial number of additional true-positive specimens, with an accompanying small increase in unconfirmed positive results.

Recently, a number of "quick tests" became available for use in on-site drug testing. These tests offer advantages in simplicity, ease of performance, and rapid access to test results. However, there is a paucity of data on the validity of these tests for the detection of drugs of abuse. This report describes a validity study of the EZ-SCREEN cannabinoid test for the detection of cannabinoids in urine. Three healthy, male volunteers with a history of marijuana use participated in the study. Each subject smoked 1, 2, or 4 marijuana cigarettes (2.6% THC) on each test day. Urine samples were collected and incorporated into a specimen set consisting of 178 clinical urine samples, 72 urine samples containing known amounts of drug, and 50 drug-free urine samples. The specimen set was randomized and analyzed under blind conditions by the EZ-SCREEN test and by GC/MS for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH). Results were interpreted independently by three readers. Concordance analysis was performed by comparison of results of the EZ-SCREEN test with GC/MS. The EZ-SCREEN test was highly sensitive and produced positive results at a standard THCCOOH concentration of 5 ng/mL. While showing high sensitivity to THCCOOH, the assay demonstrated low cross-reactivity with delta 9-tetrahydrocannabinol (THC) and other cannabinoids. No false-positive results were recorded with 50 drug-free urine samples, but one reader recorded eight undecided results. Overall agreement between the three readers for the EZ-Screen results was approximately 80%. Delayed readings and photocopy readings tended to be less accurate than readings obtained at 3 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Urine specimens collected after heroin, morphine, and codeine administration were tested by four commercial opiate immunoassays (TDx, CAC, ABUS, and EMIT) and GC/MS. Quantitative immunoassay results (morphine equivalents) were compared with results by GC/MS for total morphine, free morphine, or total codeine. Mean detection times for the broadly cross-reacting immunoassays (TDx, ABUS, and EMIT, 300 ng/mL cutoff) ranged from 15-44 hours following heroin and morphine administration and 33-54 hours following codeine administration. Detection times obtained with CAC (25 ng/mL cutoff) tended to be somewhat shorter as a result of the high selectivity of the antibody for free morphine. High correlations over a wide concentration range were obtained for TDx, CAC, and ABUS versus GC/MS, with specimens collected after heroin and morphine administration. EMIT showed a high correlation over a narrow concentration range (0-1000 ng/mL) with heroin and morphine specimens, but responses plateaued at higher concentrations. There was substantial variability in immunoassay responses with specimens collected after codeine administration. Generally, this study demonstrated that immunoassay responses for opiate urine testing can be used as a semi-quantitative guide for GC/MS confirmation; however, the presence of codeine increased variability and diminished the accuracy of the immunoassay response.

Four commercial immunoassays, TDx Opiates (TDx), Coat-A-Count Morphine in Urine (CAC), Abuscreen Radioimmunoassay for Morphine (ABUS) and Emit d.a.u. Opiate Assay (EMIT), were tested for sensitivity, specificity, and accuracy with urine specimens containing known amounts of opiates and opiate metabolites. The immunoassays were evaluated in a semiquantitative mode by comparison of morphine equivalents to GC/MS assay of free and total morphine and codeine or to target concentrations. In all cases, the apparent sensitivities of the assays were higher than those required for detection of morphine at cutoffs mandated by the Health and Human Services guidelines for testing of Federal workers. The apparent specificities of the immunoassays varied considerably. The CAC assay was found to be highly selective for free morphine, whereas TDx, ABUS, and EMIT demonstrated broad cross-reactivity with other opiates. Comparison of semiquantitative results from the immunoassays with GC/MS data indicated a high degree of accuracy for determination of morphine levels. Generally, the patterns of sensitivity and cross-reactivity were unique for each assay, indicating that a detailed knowledge of assay performance characteristics is necessary for accurate interpretation of forensic urine testing data.

The urinary excretion profile of free and conjugated codeine and morphine was determined by GC/MS for four healthy male subjects after intramuscular administration of 60- and 120-mg doses of codeine. Codeine and metabolites were rapidly excreted with the majority of drug appearing in the first 24 h. No dose-related differences in metabolism were observed. The initial ratio of total codeine to total morphine was substantially greater than 1.0 but declined over time. For two of the four subjects, the codeine-morphine ratio declined below 1.0 late in the elimination phase. With a 300-ng/mL cutoff, one subject tested positive on more than one occasion for total morphine and negative for codeine during the terminal elimination phase. The data indicate that urine codeine-morphine ratios are not reliable indices of the type of opiate exposure.

The urinary excretion patterns of 6-acetylmorphine (6-AM), free morphine, and total morphine were determined by GC/MS assay for six human subjects who received single doses of 3.0 and 6.0 mg of heroin hydrochloride. Clinical specimens were collected and combined with standardized drug urines into a 400 specimen/standard set. The urines were coded, randomized, and analyzed under blind conditions. The GC/MS assay had a limit of sensitivity of 0.81 ng/mL for 6-AM and displayed a linear response across a concentration range of 1-100 ng/mL. Following heroin administration, 6-AM was excreted rapidly with an average half-life of 0.6 h. This resulted in a very short detection time for 6-AM with a range of 2-8 h at the most sensitive cutoff limit. This short detection time limits the usefulness of 6-AM as a marker for identification of heroin abusers to a period immediately after drug use. In contrast, free morphine and total morphine were detectable up to approximately 24 h after heroin administration. The average half-life for free morphine was 3.6 h and for total morphine was 7.9 h. After morphine and codeine administration, no 6-AM was detected by GC/MS above the 0.81-ng/mL detection limit of the assay. It is concluded that the presence of 6-AM in urine can be interpreted with confidence to mean that heroin, or 6-AM, was administered within 24 h of specimen collection and that the presence of 6-AM in urine is not caused by morphine or codeine administration.

A sensitive method for the detection and quantitation of lysergic acid diethylamide (LSD) in urine was developed. After initial solvent extraction, the compound was further purified by liquid-liquid extraction or by solid-phase extraction. The trimethylsilyl derivative of LSD was detected by gas chromatography-mass spectrometry (GC-MS) operated in the electron-impact mode with selected-ion monitoring. The presence of LSD was confirmed by comparing retention times and relative abundances of ions of unknowns with that of a standard. The recovery of this procedure was greater than 89%. The intra-run and inter-run coefficients of variation were less than 5% and less than 7%, respectively. This procedure allows detection of LSD concentrations as low as 29 pg/ml. Quantitation of LSD was linear over the concentration range 50-2000 pg/ml.

The National Laboratory Certification Program undertook an evaluation of the dynamics of external contamination of hair with cocaine (COC) while developing performance testing materials for Federal Drug-Free Workplace Programs. This characterization was necessary to develop performance materials that could evaluate the efficacy of hair testing industry's decontamination procedures. Hair locks (blonde to dark brown/black) from five different individuals were contaminated with cocaine HCl. Hair locks were then treated with a synthetic sweat solution and hygienic treatments to model real-life conditions. Hair locks were shampooed daily (Monday through Friday) for 10 weeks, and samples of the hair locks were analyzed for COC, benzoylecgonine (BE), cocaethylene (CE), and norcocaine (NCOC). Three commercial analytical laboratories analyzed samples under three protocols: no decontamination procedure, individual laboratory decontamination, or decontamination by an extended buffer procedure at RTI International. Results indicated substantial and persistent association of all four compounds with all hair types. Hair that was not decontaminated had significantly greater quantities of COC and BE than did hair that was decontaminated. The only hair samples below detection limits for all four compounds were those decontaminated 1 h after contamination. Additionally, BE/COC ratios increased significantly over the 10-week study (regardless of decontamination treatment). From 21 days postcontamination until the end of the study, the mean BE/COC ratio for all hair types exceeded 0.05, the proposed Federal Mandatory Guidelines requirement. The largest variability in results was observed for samples decontaminated by participant laboratories. This suggests that current laboratory decontamination strategies will increase variability of performance testing sample results. None of the decontamination strategies used in the study were effective at removing all contamination, and some of the contaminated hair in this study would have been reported as positive for cocaine use based on the proposed Federal Mandatory Guidelines.

Reports of prolonged drug excretion have provided the basis for the common assumption that cannabinoid metabolites may he detected in urine for a week or longer. The accuracy, sensitivity, and specificity of immunoassays for the detection of cannabinoids and metabolites are unique for a specific assay and may change overtime. it is important that individuals who select assays and those who interpret test results be aware of qualitative and quantitative changes that occur. In the present study, detection times of cannabinoids in urine were determined using cannabinoid immunoassays with 20-, 50-, and 100-ng/mL cutoffs and using gas chromatography-mass spectrometry (GC-MS). Six subjects each smoked a single marijuana cigarette (placebo, 1.75, or 3.55% delta9-tetrahydrocannabinol [THC]) each week while residing on the clinical ward of the Addiction Research Center. Each urine specimen was analyzed under blind conditions by immunoassay according to the manufacturer's instructions. The following cannabinoid reagents were evaluated: EMIT d.a.u. 100, EMIT d.a.u. 50, EMIT d.a.u. 20, EMIT II 100, EMIT II 50, Abuscreen OnLine, and Abuscreen RIA, DRI, and ADx. All urine specimens were also analyzed for 11-nor-9-carboxy-delta9-THC by GC-MS using a 15-ng/mL cutoff. Urinary cannabinoid detection times varied substantially across assays, subjects, doses, and cutoff concentrations. Detection times were shorter than previously assumed. Mean detection times increased from a maximum of 0.5 days after the low dose to 1.5 days after the high dose using the 100-ng/mL cutoff. Mean detection times were less than 1 day following the low dose and less than 2 days following high-dose exposure using the 50-ng/mL cutoff. Mean detection times ranged from 1 to 5 days after the low dose and from 3 to 6 days after the high dose using the 20-ng/mL cutoff immunoassay. GC-MS detection times were approximately twice as long as mean detection times using an immunoassay with a cutoff of 50 ng/mL. Differences in sensitivity and specificity between the available immunoassay products affected the efficiency of detection of marijuana use. These results indicate that recent reductions in cannabinoid cutoffs by military and federally mandated programs will increase detection times and improve sensitivity, as expected. However, monitoring acute marijuana usage with a commercial cannabinoid immunoassay that has a 50-ng/mL cutoff concentration provides only a narrow window of detection of 1-2 days.

Urine levels of free and total morphine were determined by GC/MS for four male subjects who received single doses of 20 mg of morphine sulfate intramuscularly. Peak concentrations were observed within 10 h for both conjugated and free morphine; thereafter, levels declined rapidly. Initially, free morphine represented from 25 to 34% of the total amount of morphine present, but this ratio declined after 12 h to an average of only 5.9% of total morphine. Free morphine accounted for an overall mean of 6.8% of the dose excreted in urine and conjugated morphine for 58.6%. The mean excretion half-life for free morphine was 6.6 h and for conjugated morphine was 8.2 h. The lower concentration and shorter half-life of free morphine resulted in a shorter detection time for free morphine versus total morphine at a 300-ng/mL cutoff. An equivalent detection time for free morphine was obtained when its cutoff was lowered to 25 ng/mL. The possibility that morphine is metabolized to codeine was unequivocally ruled out by the finding of an absence of codeine at or above the LOD of the GC/MS assay in all clinical specimens collected after morphine administration.

We present a technique of femoral cardiopulmonary bypass that allows excellent venous drainage. This is accomplished by augmenting the venous return with a centrifugal pump.

We present a technique of myocardial protection using retrograde cold blood cardioplegia. This safe and simple method allows excellent continuous and homogeneous cooling of the heart during the ischemic period in all types of open heart operations.

An analytical procedure for simultaneous determination of codeine and morphine In urine Is described. The detection of codeine and morphine Is based on liquid-liquid extraction and derlvatlzatlon to the scetylated compounds. The acetylated codeine and morphine are separated by capillary gas chromatography and Identified mass apectrometrlcally by selected Ion monitoring (SIM). Quantitative determination was carried out by SIM using nalorphlna as Internal standard. Excellent Ilnserlty was obtained over a concentration range of 25 to 800 ng/mL. The overall recovery for codeine and morphine In the extraction was found to be 58% and 40%, respectively. The on-column sensitivity for both compounds was 2 ng at a peak-to-noise ratio of 5:1. The derivatives, acetylcodelne, dlscetylmorphlne, and dlacetylnalorphlne were stable at room temperature for 72 hr. ing procedures including silylation 09,26,29,30), pentafluorobenzylation (27), trifluoroacetylation (27,28,36), pentafluoropropionylation (20,25,31), heptafluorobutyrylation (21,22), and acetylation (12,23) are being used. The perfluoroesters are unstable in the presence of moisture (22,28,32,35) due to the strong negative inductive effects of fluorine atoms in the molecule. Therefore, the preparation and handling of these derivatives require anhydrous conditions. The trimethylsilyl derivatives are also known to be moisture sensitive. In addition, abnormal silylation at the double bond in the allylic alcohol moiety of codeine has been reported (29). Such unusual silylation is also expected in other opiate compounds having that functionality. An acetylation procedure with detection of products utilizing a packed GLC column and flame ionization detection is known (12,23). Possible overlapping of undesirable compounds having the same retention time as that of acetylcodeine and diacetylmorphine must be considered. Therefore, a method is described here to separate and identify codeine and morphine in urine by capillary column gas chromatography and electron impact (EI) selected ion monitoring (SIM) mass spectroscopy.

Five drug-free male subjects ingested marijuana-laced brownies in a double-blind crossover study designed to test for behavioral effects, physiologic effects, and urinary cannabinoid metabolites produced as a result of consumption of marijuana plant material cooked in foodstuff. On three separate occasions, each subject consumed two brownies which contained 1.6 g of marijuana plant material. Placebo marijuana plant material (0% THC) was mixed with marijuana plant material (2.8% THC) so that each subject ingested equivalent marijuana plant material of 0, 1, and 2 marijuana cigarettes (2.8% THC). Subjects scored significantly higher on behavioral measures after consumption of brownies containing THC than with placebo; however, the effects were slow to appear and variable. Peak effects occurred 2.5 to 3.5 h after dosing. Modest changes in pulse and blood pressure also were noted. Urinalyses by EMIT d.a.u. assay and Abuscreen RIA for cannabinoids and GC/MS assay for THCCOOH indicated that substantial amounts of marijuana-related metabolites were excreted over a period of 3 to 14 days. No positives were produced as a result of ingestion of placebo brownies.

Embryotoxicity and fetal toxicity of nickel chloride (NiCl/sub 2/) and nickel subsulfide (Ni/sub 3/S/sub 2/) were studied in Fischer rats. Injection of NiCl/sub 2/ (16 mg of Ni/kg, im) on Day 8 of gestation reduced the man number of live pups per dam and resulted in diminisehd body weights of fetuses on Day 20 of gestation and of weanlings at 4 to 8 weeks after birth. Injection of Ni/sub 2/S/sub 2/ (80 mg of Ni/kg, im) on Day 6 of gestation reduced the mean number of live pups per dam. No congenital anomalies were found in fetuses from any Ni-treated dams, including dams that recieved 10 im injections of NiCl/sub 2/ (2 mg of Ni/kg, twice daily, on Days 6 to 10 of gestation). /sup 63/NiCl/sub 2/ (12 mg of Ni/kg, im) was administered to a group of nonpregnant female rats and to groups of pregnant rats on Day 8 or 18 of gestation. After 24 hr, the relative concentrations of /sup 63/Ni in tissues were: kidney > serum > adrenal approx. = lung approx. = ovary > spleen approx. = heart approx. = liver > skeletal muscle. Pituitary /sup 63/Ni concentrations were much higher in pregnant rats than inmore » non-pregnant females. /sup 63/Ni concentrations in products of conception (embryos and embryonic membranes) on Day 9 and in placentas on Day 19 were equivalent to /sup 63/Ni concentrations in adrenal, lung, and ovary tissues of the dams. Autoradiography of fetuses and placentas on Day 19 of gestation showed /sup 63/Ni localization in fetal urinary bladders and in the basal laminae and yolk sacs of the placentas. These studies show (a) that im injection of NiCl/sub 2/ and Ni/sub 3/S/sub 2/ during early gestation causes embryonic mortality at dosages that do not cause maternal mortality, and (b) that /sup 63/Ni(II) can cross the feto-maternal barriers and enter the fetuses during late gestation.« less

The carcinogenicity of nickel compounds in industrial workers and in experimental animals has been comprehensively reviewed in several publications.(1–5) Increased incidences of cancers of the lung and nasal cavities have been documented by epidemiological investigations of nickel refinery workers in Wales,(6,7) Canada,(8,0) Norway,(10) and Russia.(11) One of the present authors (Sunderman) maintains a tabulation of respiratory cancers that have occurred in workers who were exposed to nickel compounds in industrial operations. As of January 1977, this tabulation included 447 cases of lung cancer and 142 cases of cancers of the nose and paranasal sinuses. In addition to increased risk of respiratory tract cancers, increased risk of laryngeal cancers has been found in Norwegian nickel refinery workers,(10) and increased risk of gastric carcinomas and soft tissue sarcomas have been reported in Russian nickel refinery workers.(11) Three cases of renal cancer occurred among 225 Canadian workers who were involved in electrolytic refining of nickel.(8) Since renal cancer is rare, it seems possible that the renal cancers in these workers might have been related to occupational exposures to nickel compounds. To date, the identity of the nickel compounds that induce cancers in nickel workers remains uncertain, although principal attention is currently focused upon (a) insoluble dusts of nickel subsulfide (Ni3S2) and nickel oxides (NiO; Ni2O3); (b) the vapor of nickel carbonyl (Ni (CO) 4); and (c) soluble aerosols of nickel sulfate or chloride (NiSO4, NiCl2). (2,4,12)

In two separate studies, 5 drug-free male volunteers with a history of marijuana use were passively exposed to the sidestream smoke of 4 and 16 marijuana cigarettes (2.8% delta-9-tetrahydrocannabinol [THC]) for 1 h each day for 6 consecutive days. A third study was similarly performed with 2 marijuana-naive subjects passively exposed to the smoke of 16 marijuana cigarettes. Passive smoke exposure was conducted in a small, unventilated room. Room air levels of THC and CO were monitored frequently. All urine specimens were collected and analyzed by EMIT d.a.u. assay, Abuscreen radioimmunoassay and GC/MS. The studies show that significant amounts of THC were absorbed by all subjects at the higher level of passive smoke exposure (eg., smoke from 16 marijuana cigarettes), resulting in urinary excretion of significant amounts of cannabinoid metabolites. However, it seems improbable that subjects would unknowingly tolerate the noxious smoke conditions produced by this exposure. At the lower level of passive marijuana-smoke exposure, specimens tested positive only infrequently or were negative. Room air levels of THC during passive smoke exposure appeared to be the most critical factor in determining whether a subject produced cannabinoid-positive urine specimens.

Available methods for determining PCP use are based on the presence of the parent drug in urine. PCP, however, is very potent and is extensively metabolized; it is therefore present in urine in only small quantities. This work was undertaken to determine whether an amino acid metabolite of PCP, 5-(N-(1'-phenylcyclohexyl)amino)pentanoic acid, can be used to determine PCP use. A solid phase adsorption technique was developed to extract the amino acid metabolite from urine. Recovery averaged 93%, and subsequent GC/MS analysis was free from interference. Analysis of 67 urine samples demonstrated that the amino acid metabolite exists in human urine in significant quantities.

Exposure of pregnant rats to inhalation of nickel carbonyl on days 7 or 8 of gestation frequently causes the progeny to develop ocular anomalies, including anophthalmia and microphthalmia. The incidence of extraocular anomalies is very low. The specificity of nickel carbonyl for induction of ocular anomalies in rats appears to be unique among known teratogenic agents.