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Biomedical subjects

E J Cone

Publications and source records attributed to E J Cone.

At least 163 records · Page 9Linked to original sources
PubMedDate not supplied

Confirmation of cocaine in human saliva after intravenous use.

The presence of cocaine was confirmed in the saliva of two male human subjects who had received intravenous doses of cocaine. For one subject, the saliva:plasma concentration ratios varied from 2.96 to 0.5 over time following drug administration. Correlations of saliva to plasma cocaine levels were highly significant (p less than 0.001) across doses of 15, 20, and 40 mg of intravenously administered cocaine. These findings are important in that they allow monitoring blood levels of cocaine after intravenous infusion in a non-invasive manner, and could form the basis for development of a non-invasive screen for active cocaine levels in saliva.

Cocaine↗
PubMedDate not supplied

Passive inhalation of marijuana smoke: urinalysis and room air levels of delta-9-tetrahydrocannabinol.

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.

Adult↗
PubMedDate not supplied

Lack of validity of the KDI Quik Test Drug Screen for detection of benzoylecgonine in urine.

The validity of the Quik Test Drug Screen for detection of benzoylecgonine was assessed by testing, in random order under blind conditions, 50 aliquots of drug-free urine and 50 aliquots of urine containing 6000 ng/mL of benzoylecgonine. Three independent readers of the test results had an average overall accuracy of only 50%. Each specimen also was tested by TDx assay for cocaine metabolite. In contrast to the Quik Test, the TDx assay was completely accurate. The false positive and false negative rates of the Quik Test Drug Screen for benzoylecgonine in urine were found to be unacceptably high, and its use in urine testing for cocaine abuse is not recommended.

Cocaine↗
PubMedDate not supplied

Marijuana-laced brownies: behavioral effects, physiologic effects, and urinalysis in humans following ingestion.

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.

Adult↗
PubMedDate not supplied

Correlation of saliva cocaine levels with plasma levels and with pharmacologic effects after intravenous cocaine administration in human subjects.

The behavioral and physiologic effects of single, intravenous bolus doses of cocaine in 5 male human subjects were correlated with cocaine levels in saliva and blood. All measures were performed under double-blind conditions. Two test doses of cocaine (15 mg and 40 mg) and one placebo test dose were administered to each subject in a random, cross-over design. Each test day was separated by a minimum of 48 h. Cocaine levels in saliva and blood significantly (p less than or equal to 0.05) correlated with responses on self-rating scales for drug sensation (Feel Drug scale), psychotomimetic effects (LSD scale), and feelings of rush (Rush scale). Significant (p less than or equal to 0.01) correlations also were obtained with cocaine biofluid levels and pulse rate. The close relationship observed between cocaine saliva levels and cocaine-induced behavior and physiologic effects presents the opportunity for development of a new noninvasive method for detection of current cocaine use.

Adult↗
PubMedDate not supplied

Prolonged occurrence of cocaine in human saliva and urine after chronic use.

Cocaine was detected by immunoassay in saliva and urine of chronic cocaine addicts for 5-10 days during abstinence. Confirmation by a less sensitive but highly specific GC/MS assay of unmetabolized cocaine was successful in saliva through the first 24 h of collection and for the initial 4-5 days in urine. Cocaine saliva concentrations and subject scores for cocaine craving and depression declined during this time and correlated significantly. The presence of unmetabolized cocaine in these biofluids long after the last drug administration suggests that multiple dosing and high exposure to cocaine in man leads to accumulation in deep body compartments and subsequent slow release back into circulation and eventual excretion. The prolonged presence of cocaine in saliva and urine may have implications in testing for cocaine use and in treatment of cocaine withdrawal.

Adult↗
PubMedDate not supplied

Testing human hair for drugs of abuse. I. Individual dose and time profiles of morphine and codeine in plasma, saliva, urine, and beard compared to drug-induced effects on pupils and behavior.

The time course of appearance of morphine and codeine in beard after single dose administration in two human subjects was monitored by radioimmunoassay and confirmed by gas chromatography/mass spectrometry. Both morphine and codeine appeared in beard approximately 7-8 days after drug administration at a time when drug levels in urine, plasma, and saliva were not detectable and drug-induced effects had disappeared. Drug levels in beard appeared to be dose-related suggesting that hair analysis can provide evidence of time and degree of drug exposure.

Behavior↗
PubMedDate not supplied

Forensic drug testing for opiates: I. Detection of 6-acetylmorphine in urine as an indicator of recent heroin exposure; drug and assay considerations and detection times.

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.

Gas Chromatography-Mass Spectrometry↗
PubMedDate not supplied

Forensic drug testing for opiates. II. Metabolism and excretion rate of morphine in humans after morphine administration.

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.

Adult↗
PubMedDate not supplied

Forensic drug testing for opiates, III. Urinary excretion rates of morphine and codeine following codeine administration.

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.

Codeine↗
PubMedDate not supplied

Testing human hair for drugs of abuse. III. Identification of heroin and 6-acetylmorphine as indicators of heroin use.

Hair samples from 20 documented heroin users contained 6-acetylmorphine, a unique metabolite of heroin, in all samples. Heroin was identified in smaller amounts in seven of these samples. The identity of 6-acetylmorphine and heroin was established by comparison of full scan spectra of extracts to standard reference materials. The presence of 6-acetylmorphine generally predominated over heroin, morphine, and codeine. The mean concentrations of analytes were as follows: 6-acetylmorphine, 0.90 ng/mg, N = 20; heroin, 0.17 ng/mg, N = 7; morphine, 0.26 ng/mg, N = 20; codeine, 0.18 ng/mg, N = 15. Analysis of hair samples obtained from 10 drug-free control subjects were negative for 6-acetylmorphine, morphine, and codeine. However, a small interfering peak was observed at the retention time for heroin. Control samples soaked in aqueous solutions of heroin and 6-acetylmorphine were found to be contaminated, even though an initial wash step was included in the analysis. These data suggest that hair analysis for 6-acetylmorphine can be used to differentiate heroin users from other types of opiate exposure (e.g., poppy seed, licit morphine, and codeine); however, environmental contamination can potentially produce false positives during opiate testing.

Adult↗
PubMedDate not supplied

Testing human hair for drugs of abuse. II. Identification of unique cocaine metabolites in hair of drug abusers and evaluation of decontamination procedures.

Two unique metabolites of cocaine, cocaethylene and norcocaine, were identified by GC/MS in the hair of cocaine users. Their presence cannot be explained by environmental contamination; thus, their presence together with cocaine provides convincing evidence that cocaine is excreted in hair after active cocaine administration. The amount of cocaine in hair predominated over all metabolites generally by a factor of 5-10. Two washing procedures were evaluated for their efficiency in removal of cocaine from environmentally contaminated hair. Neither procedure completely removed cocaine, suggesting that false positives can result from environmental contamination. Analysis of the methanolic wash of the hair of cocaine users also revealed the presence of cocaine metabolites, indicating that washing removes cocaine from the interior as well as from the exterior surface of hair during decontamination procedures.

Adult↗
PubMedDate not supplied

Forensic drug testing for opiates. IV. Analytical sensitivity, specificity, and accuracy of commercial urine opiate immunoassays.

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.

Forensic Medicine↗
PubMedDate not supplied

Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana.

delta 9-Tetrahydrocannabinol (THC), the primary psychoactive constituent of marijuana, is rapidly transferred from lungs to blood during smoking. Oxidative metabolism of THC yields the active metabolite, 11-hydroxy-delta 9-tetrahydrocannabinol (11-OH-THC), and the inactive metabolite, 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH). Characterization of THC's absorption phase is important because of the rapidity with which THC penetrates the central nervous system to produce psychoactive effects. This study incorporated a highly automated procedure to sample blood and to capture rapid drug level changes during and following smoking. Human subjects smoked one marijuana cigarette (placebo, 1.75%, or 3.55% THC) once a week according to a randomized, crossover, double-blind Latin square design. Samples were analyzed by GC/MS for THC, 11-OH THC, and THCCOOH. THC levels increased rapidly, peaked prior to the end of smoking, and quickly dissipated. Mean peak 11-OH-THC levels were substantially lower than THC levels and occurred immediately after the end of smoking. THCCOOH levels increased slowly and plateaued for an extended period. The mean peak time for THCCOOH was 113 min and a correspondingly longer time course of detection was observed. This study provides the first complete pharmacokinetic profile of the absorption of THC and appearance of metabolites during marijuana smoking. These findings have implications for understanding the mechanisms underlying the performance-impairing effects of marijuana, as well as for aiding forensic interpretation of cannabinoid blood levels.

Absorption↗
PubMedDate not supplied

Blood cannabinoids. II. Models for the prediction of time of marijuana exposure from plasma concentrations of delta 9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH)

Two mathematical models are described for the prediction of time of marijuana use from the analysis of a single plasma sample for cannabinoids. The models were derived from cannabinoid data obtained from a controlled clinical study of acute marijuana smoking. Model I was based on plasma delta 9-tetrahydrocannabinol (THC) concentrations and Model II was based on the ratio of 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH) to THC in plasma. The two models were validated with cannabinoid data from nine published and unpublished clinical studies. The data included plasma samples obtained from infrequent and frequent marijuana smokers and after oral marijuana administration. Cannabinoid plasma concentrations had been determined by a variety of analytical methods. The accuracy of model prediction was evaluated by comparison of the predicted time of prior drug use to the actual time of exposure. Predictions of time of exposure were generally accurate but tended to overestimate time immediately after smoking and tended to underestimate later times. A second assessment of the validity of the models was made by determining if actual time of use was within the 95% confidence interval. Model I correctly predicted the time of exposure within the 95% confidence interval for 235 of 261 samples (90.0%), and Model II was correct in 232 of 260 samples (89.2%). These prediction models may be beneficial to forensic scientists in the interpretation of cannabinoid plasma levels.

Administration, Oral↗
PubMedDate not supplied

Forensic drug testing for opiates. V. Urine testing for heroin, morphine, and codeine with commercial opiate immunoassays.

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.

Codeine↗
PubMedDate not supplied

Disposition of heroin and its metabolites in heroin-related deaths.

Although many deaths occur annually from heroin intoxication, the presence of heroin has not been reported in postmortem tissues. Recognizing heroin's susceptibility to rapid chemical and metabolic hydrolysis, extraction procedures were developed for the efficient recovery of heroin, 6-acetylmorphine, and morphine from postmortem tissue utilizing solid-phase extraction coupled with gas chromatography/mass spectrometry. From heroin-related deaths, 21 sets of blood and urine specimens were collected. The mode of death in these cases was categorized as rapid, delayed, or undetermined. Compared with delayed deaths, rapid deaths were characterized by the following trends: higher mean concentrations of 6-acetylmorphine, free morphine, and total opiates in blood; a higher ratio of free morphine concentrations to total opiate concentrations in blood; lower mean concentrations of 6-acetylmorphine and morphine in urine; greater likelihood of 6-acetylmorphine detection in blood; and lesser likelihood of heroin detection in urine. The study also included analysis of multiple tissue specimens from two subjects who died of heroin intoxication. Heroin was identified in urine and injection-site tissue. Concentrations of 6-acetylmorphine in cerebrospinal fluid, spleen, and brain were substantially higher than in blood, liver, lung, and kidney. All specimens were positive for morphine. Heroin metabolites were detected in hair specimens. The identification of heroin and 6-acetylmorphine in biological tissues effectively established the presence of heroin in cases of acute narcotic intoxication. These studies demonstrated that measurement of heroin and its metabolites provides useful information for the differential diagnosis of heroin-related deaths.

Drug Overdose↗