This paper presents a historical review of antimicrobial use in food animals, the causes of residues in meat and milk, the types of residues found, their regulation in Canada, tests used for their detection, and test performance parameters, with an emphasis on immunoassay techniques. The development of residue detection methods began shortly after the introduction of antimicrobials to food animal production in the late 1940s. From initial technical concerns expressed by the dairy industry to the present public health and international trade implications, there has been an ongoing need for reliable, sensitive, and economical methods for the detection of antimicrobial residues in food animal products such as milk and meat. Initially there were microbial growth inhibition tests, followed by more sensitive and specific methods based on receptor binding, immunochemical, and chromatographic principle. An understanding of basic test performance parameters and their implications is essential when choosing an analytical strategy for residue testing. While each test format has its own attributes, none test will meet all the required analytical needs. Therefore the use of a tiered or integrated system employing assays designated for screening and confirmation is necessary to ensure that foods containing violative residues are not introduced into the food chain.
Key Points Question How does smoked and vaporized cannabis acutely influence subjective drug effects, cognitive and psychomotor performance, and cardiovascular measures in healthy adults who infrequently use cannabis (>30 days since last use)? Findings In a crossover trial of 17 healthy adults, inhalation of smoked and vaporized cannabis containing 10 mg of Δ9-tetrahydrocannabinol (THC) produced discriminative drug effects and modest impairment of cognitive functioning, while inhalation of a 25-mg dose of THC was associated with pronounced drug effects, increased incidence of adverse effects, and significant impairment of cognitive and psychomotor ability. Vaporized cannabis produced greater pharmacodynamic effects and higher concentrations of THC in blood compared with equal doses of smoked cannabis. Meaning Significant, sometimes adverse, drug effects can occur at relatively low THC doses in infrequent cannabis users, and accordingly these data should be considered with regard to regulation of retail cannabis products and education for individuals initiating cannabis use.
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.
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.
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