PubMed · 12915426
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
Joep Killestein, Bernard M J Uitdehaag, Chris H Polman. 2003-08-13. Cannabinoids and immune function.. https://doi.org/10.1001/jama.290.6.754-b
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Subjects with a history of chronic marijuana use were screened for cannabinoids in urine specimens with the EMIT((R)) II Plus cannabinoids assay with a cut-off value of 50 ng/ml. All presumptively positive specimens were submitted for confirmatory analysis for the major urinary cannabinoid metabolite (Delta(9)-THC-COOH) by GC-MS with a cut-off value of 15 ng/ml. Creatinine was analyzed in each specimen as an index of dilution. Huestis and Cone [J. Anal. Toxicol. 22 (1998) 445] reported that serial monitoring of Delta(9)-THC-COOH to creatinine ratios in paired urine specimens collected at least 24h apart could differentiate new drug use from residual Delta(9)-THC-COOH excretion. The best accuracy (85.4%) for predicting new marijuana use was a Delta(9)-THC-COOH/creatinine ratio > or =0.5 (dividing the Delta(9)-THC-COOH to creatinine ratio of specimen 2 by the specimen 1 ratio). In a previous study in this laboratory [J. Anal. Toxicol. 23 (1999) 531], urine specimens were collected from chronic marijuana users at least 24h apart and dilute urine specimens (creatinine values <2.2 micromol/l) were excluded from the data analysis. The objective of the present study was to determine whether creatinine corrected urine specimens positive for cannabinoids could differentiate new marijuana use from the excretion of residual Delta(9)-THC-COOH in chronic users of marijuana based on the Huestis 0.5 ratio. Urine specimens (N=946) were collected from 37 individuals with at least 48h between collections. All urine specimens were included in the data review irrespective of creatinine concentration. The mean urinary Delta(9)-THC-COOH concentration was 302.4 ng/ml, mean Delta(9)-THC-COOH/creatinine ratio (ng/ml Delta(9)-THC-COOH/(mmol/l) creatinine) was 29.3 and the Huestis ratio calculation indicated new drug use in 83% of all sequentially paired urine specimens. The data were sub-divided into three groups (A-C) based on the mean Delta(9)-THC-COOH/creatinine values. Interindividual Delta(9)-THC-COOH/creatinine mean values ranged from 2.2 to 13.8 in group A (264 specimens, N=15 subjects) where 80.7% of paired specimens indicated new drug use. In group B, mean Delta(9)-THC-COOH/creatinine values ranged from 15.3 to 37.8 in 444 specimens (N=14 subjects) and 83.3% of paired specimens indicated new drug use. In group C, individual mean Delta(9)-THC-COOH/creatinine values were >40.1 (41.3-132.5) in 238 urine specimens (N=8 subjects) and 85.3% of paired urine specimens indicated new marijuana use. Correcting Delta(9)-THC-COOH excretion for urinary dilution and comparing Delta(9)-THC-COOH/creatinine concentration ratios of sequentially paired specimens (collected at least 48h apart) provided an objective indicator of new marijuana use in this population.
This article describes a fully automated procedure for detecting cannabinoids in human hair samples. The procedure uses alkaline hydrolysis and headspace solid-phase dynamic extraction (HS-SPDE), followed by on-coating derivatization and gas chromatography-mass spectrometry (GC-MS). SPDE is a further development of solid-phase microextraction (SPME), based on an inside needle capillary absorption trap. It uses a hollow needle with an internal coating of polydimethylsiloxane as extraction and pre-concentration medium. Ten mg of hair were washed with deionised water, petroleum ether and dichloromethane. After adding deuterated internal standards, the sample was hydrolyzed with sodium hydroxide and directly submitted to HS-SPDE. After absorption of analytes for an on-coating derivatization procedure, the SPDE-needle was directly placed into the headspace of a second vial containing N-methyl-N-trimethylsilyl-trifluoroacetamide before GC-MS analysis. The limit of detection was 0.14 ng/mg for Delta(9)-tetrahydrocannabinol, 0.09 ng/mg for cannabidiol, and 0.12ng/mg for cannabinol. Absolute recoveries were in the range of 0.6 to 8.4%. Linearity was verified over a range from 0.2 to 20 ng/mg, with coefficients of correlation between 0.998 and 0.999. Intra- and inter-day precision were determined at two different concentrations and resulted in ranges between 2.3 and 6.0% (intra-day) and 3.3 and 7.6% (inter-day). Compared with conventional methods of hair analysis, this automated HS-SPDE-GC-MS procedure is substantially faster. It is easy to perform without using solvents and with minimal sample quantities, and it yields the same sensitivity and reproducibility. Compared to SPME, we found a higher extraction rate, coupled with a faster automated operation and greater stability of the device.
A series of 1-pentyl-1H-indol-3-yl-(1-naphthyl)methanes (9-11) and 2-methyl-1-pentyl-1H-indol-3-yl-(1-naphthyl)methanes (12-14) have been synthesized to investigate the hypothesis that cannabimimetic 3-(1-naphthoyl)indoles interact with the CB(1) receptor by hydrogen bonding to the carbonyl group. Indoles 9-11 have significant (K(i)=17-23nM) receptor affinity, somewhat less than that of the corresponding naphthoylindoles (5, 15, 16). 2-Methyl-1-indoles 12-14 have little affinity for the CB(1) receptor, in contrast to 2-methyl-3-(1-naphthoyl)indoles 17-19, which have affinities comparable to those of 5, 15, 16. A cannabimimetic indene hydrocarbon (26) was synthesized and found to have K(i)=26+/-4nM. Molecular modeling and receptor docking studies of naphthoylindole 16, its 2-methyl congener (19) and indolyl-1-naphthylmethanes 11 and 14, combined with the receptor affinities of these cannabimimetic indoles, strongly suggest that these cannabinoid receptor ligands bind primarily by aromatic stacking interactions in the transmembrane helix 3-4-5-6 region of the CB(1) receptor.