benzoylecgonine and Opioid-Related-Disorders

Qualitative urinalysis methods of monitoring cocaine use may over-detect frequency of use, possibly decreasing the ability of clinical trials to detect effective treatments. Quantitative urinalysis and newly developed criteria for identifying new cocaine use were evaluated as alternative measures of cocaine use. Urine specimens collected in a cocaine dosing study in non-treatment-seeking subjects (n = 5) and a cocaine treatment trial (n = 37) were analyzed for the cocaine metabolite, benzoylecgonine, with qualitative and quantitative methods. Pharmacokinetic criteria ('New Use' rules) were applied to quantitative data to identify occasions of new cocaine use. Results were compared to known cocaine administrations in the laboratory study and to self-reported drug use and qualitative urinalysis for subjects in the clinical trial. New Use criteria correctly identified cocaine administrations in the cocaine dosing study in all but a small number of specimens. In the clinical trial, quantitative urinalysis and estimated New Uses provided more information about patterns and frequency of use than qualitative urinalysis in the different treatment conditions in the clinical trial. Interpretation of quantitative urinalysis with New Use rules appears to be a useful method for monitoring treatment outcome and may be more accurate than traditional qualitative urinalysis in estimating frequency of cocaine use.

Topics: Adolescent; Adult; Aged; Cocaine; Cross-Over Studies; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Single-Blind Method; Substance Abuse Detection

This controlled study tested the efficacy of the selective serotonergic reuptake inhibitor fluoxetine in the out-patient treatment of primary crack cocaine dependence. Thirty-two subjects were randomly assigned, 16 in each group, to placebo or fluoxetine, 40 mg/day, in a double-blind controlled trial over a 12-week period. Outcome measures included quantitative urine benzoylecgonine concentration, self-reports of cocaine use and craving, and treatment retention. Subjects assigned to fluoxetine were retained in treatment significantly longer than those on placebo: a median of 11 weeks compared to 3 weeks (logrank test, P < 0.001). Because of the poor retention in the placebo group, between-groups comparisons of outcome were limited to the first 6 weeks of treatment. No differences in cocaine use or craving were found between the two groups over weeks 1 to 6. The significant improvement in retention associated with fluoxetine may support further study of this medication in the treatment of cocaine dependence.

Topics: Adult; Ambulatory Care; Cocaine; Crack Cocaine; Double-Blind Method; Female; Fluoxetine; Humans; Male; Opioid-Related Disorders; Selective Serotonin Reuptake Inhibitors; Substance Abuse Detection; Treatment Outcome

A dramatic shift has occurred over the last decade in the route of cocaine administration by drug abusers in the United States. The favored route has changed from intranasal and intravenous use to administration of cocaine ("crack") by the smoking route. The reasons for this shift are not well understood but may include social and environmental factors such as the ease and convenience of the smoking route, avoidance of needle-transmitted disease, and possible pharmacological differences produced by the different routes of administration. This study examined the influences exerted by changes in the route of administration on pharmacokinetic parameters and drug-induced behavioral and physiological effects of cocaine. Six male subjects who provided informed consent and had a recent history of cocaine use by the intravenous and smoked routes participated in a blind, double-dummy, crossover study conducted on a clinical research ward. On different occasions, subjects received single doses of cocaine by the intravenous (25 mg, cocaine HCl), intranasal (32 mg, cocaine HCl), and smoked (42 mg, cocaine base) routes. Physiological and behavioral measures were collected prior to and periodically after drug administration. Concurrent blood samples were collected and analyzed for cocaine and metabolites by gas chromatography-mass spectrometry, Plasma concentrations of cocaine and benzoylecgonine were fitted to pharmacokinetic models by nonlinear regression analysis. Behavioral measures of "good" drug effects and "liking" were higher by the smoked route than the intravenous route, but physiological changes were approximately equal at equivalent plasma concentrations of cocaine. Intranasal cocaine administration was characterized by lower cocaine plasma concentrations and a slower onset of pharmacological effects that were generally of lesser magnitude than those observed by other routes of administration. Overall, this study demonstrated that cocaine administration by the smoked route produced substantially higher behavioral responses than an equivalent dose of cocaine administered by the intravenous route. This finding suggests that smoked cocaine (crack) has a higher abuse liability and greater dependence-producing properties than equivalent doses of cocaine administered by the intravenous or intranasal route.

Topics: Administration, Inhalation; Administration, Intranasal; Adult; Biological Availability; Cocaine; Cross-Over Studies; Double-Blind Method; Gas Chromatography-Mass Spectrometry; Heart Rate; Humans; Illicit Drugs; Injections, Intravenous; Male; Opioid-Related Disorders; Regression Analysis

Fentanyl and analogues such as butyrylfentanyl, carfentanil, 4-fluorobutyrylfentanyl, and furanylfentanyl may be either added to, or sold as, heroin. Fentanyl and carfentanil have approximately 100 and 10,000 times the potency of morphine, respectively, and there is thus a high risk of death with the use of these drugs.. We looked for fentanyl/fentanyl analogues using liquid chromatography-high resolution mass spectrometry (LC-HRMS) in selected biological samples obtained post-mortem February 2017-end January 2018. Suspicion of fentanyl poisoning arose from the circumstances of death, a history of heroin use, and the geographical area in which the deceased was discovered, supplemented by drugs intelligence data.. Of the 84 deaths investigated, fentanyl and/or a fentanyl analogue were detected in 40 (48%). The fentanyls encountered were carfentanil (N = 17), fentanyl (9), carfentanil and fentanyl together (12), and fentanyl, carfentanil, 4-fluorobutyrylfentanyl, and butyrylfentanyl together (2). The median (range) post-mortem blood fentanyl concentration was 2.66 (0.21-107) μg/L and the median (range) carfentanil concentration was 0.24 (0.03-1.66) μg/L. The most prevalent compounds present together with fentanyls were ethanol [N = 28, median (range) post-mortem blood concentration: 44 (<10-249) mg/dL)], benzoylecgonine [N = 22, 0.64 (<0.05-3.17) mg/L] and free morphine [N = 20, 0.05 (<0.05-0.34) mg/L]. Deaths in hospital excluded, median blood free morphine, and ethanol concentrations were significantly lower in deaths where fentanyl/fentanyl analogues were present, but there was much overlap with the blood concentrations of these analytes in the non-fentanyl related deaths. A routine drugs of abuse assay using LC-HRMS identified fentanyl with 100% sensitivity and carfentanil with 89% sensitivity.. Given their potency, misuse of fentanyl and its analogues is likely to cause severe toxicity. A simple LC-HRMS method detected all cases in which fentanyl was identified post-mortem and most of the cases in which carfentanil was detected.

Topics: Adult; Analgesics, Opioid; Central Nervous System Depressants; Chromatography, Liquid; Cocaine; Ethanol; Fentanyl; Humans; Mass Spectrometry; Middle Aged; Morphine; Opioid-Related Disorders; Substance Abuse Detection; Young Adult

In this case report, we present an evaluation of the distribution of postmortem concentrations of butyr-fentanyl in a fatality attributed principally to the drug. A man who had a history of intravenous drug abuse was found unresponsive on the bathroom floor of his home. Drug paraphernalia was located on the bathroom counter. Toxicology testing, which initially screened positive for fentanyl by enzyme-linked immunosorbent assay, subsequently confirmed butyr-fentanyl, which was then quantitated by gas chromatography-mass spectrometry-specific ion monitoring (GC-MS SIM) analysis following liquid-liquid extraction. The butyr-fentanyl peripheral blood concentration was quantitated at 58 ng/mL compared with the central blood concentration of 97 ng/mL. The liver concentration was 320 ng/g, the vitreous was 40 ng/mL, the urine was 670 ng/mL and the gastric contained 170 mg. Acetyl-fentanyl was also detected in all biological specimens tested. Peripheral blood concentration was quantitated at 38 ng/mL compared with the central blood concentration of 32 ng/mL. The liver concentration was 110 ng/g, the vitreous was 38 ng/mL, the urine was 540 ng/mL and the gastric contained <70 mg. The only other drug detected was a relatively low concentration of benzoylecgonine. The cause of death was certified as acute butyr-fentanyl, acetyl-fentanyl and cocaine intoxication, and the manner of death was certified as accident.

Topics: Adult; Analgesics, Opioid; Cocaine; Drug Overdose; Enzyme-Linked Immunosorbent Assay; Fatal Outcome; Fentanyl; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Liquid-Liquid Extraction; Male; Opioid-Related Disorders; Substance Abuse, Intravenous

In a series of licit and illicit drug-related deaths, qualitative and quantitative analyses on extracts of adipose tissue and skin were performed by GC/MS. In all cases, the adipose tissue was found to contain drugs at concentrations lower than, approximately equal to, or even greater than the concentrations of the same analytes found in the blood, which may reflect a consequence of long-term chronic exposure, or acute intoxication, or some combination of both. Approximately one cubic inch of skin with adipose tissue was removed from the mid to lower abdominal region adjacent to the midline incision during autopsy. The drugs were recovered from the specimens following incubation and alkaline, acidic, and alkaline chloroform back extraction of one to three grams of tissue. Deuterated analogs of the analytes were added to the matrix at the beginning of the incubation period. Cocaine and free morphine (from heroin) were readily identified in several cases. The presence of these illicit drugs in adipose tissue raises significant forensic questions, especially the use of 'sweat patches' to monitor recent cocaine or heroin use in chronic drug users.

Topics: Adipose Tissue; Cocaine; Cocaine-Related Disorders; Deuterium; Gas Chromatography-Mass Spectrometry; Heroin; Heroin Dependence; Humans; Illicit Drugs; Male; Morphine; Narcotics; Opioid-Related Disorders; Radiopharmaceuticals; Skin; Substance Abuse Detection; Sweat

Substance abuse worsens the course of schizophrenia and significantly impairs the relationship between the patient and the health care team. Recent advances in laboratory studies of substance abuse and the pharmacology of schizophrenia open up new possibilities for pharmacotherapy of substance abuse in schizophrenia patients. D1 dopaminergic receptor agonists may directly block the drive for stimulant use. D2 dopaminergic receptor antagonists may indirectly block the drive for stimulant and nicotine use, while opioid antagonists appear to reduce the drive to use alcohol. New generations of neuroleptics with serotonin (5-HT2) receptor antagonism and/or 5-HT1A agonist activity may reduce substance abuse in schizophrenia patients who self-medicate negative symptoms or neuroleptic side effects. Pharmacotherapy efficacy may be enhanced by adding contingency management, social skills training, and other manualized programs. Tables are provided of potentially useful medications. Preliminary results are presented of cocaine-abusing schizophrenia patient treated with desipramine and traditional neuroleptics.

Topics: Alcoholism; Antipsychotic Agents; Cocaine; Flupenthixol; Humans; Imipramine; Marijuana Abuse; Opioid-Related Disorders; Schizophrenia; Self Medication; Substance-Related Disorders; Tobacco Use Disorder

In clinical trials of potential pharmacotherapies for cocaine addiction, objective determination of subject relapse relies on qualitative urine analysis for benzoylecgonine, the major metabolite of cocaine. Unlike qualitative analysis, quantitative measurement allows differentiation between continued cocaine use and a single use, as well as identification of changes in the quantity of cocaine used at different times. The only quantitative technique that has been used is expensive and not generally feasible. This study was performed to modify an existing qualitative technique for use as a new simple and readily available quantitative method for identifying cocaine use among research subjects. Benzoylecgonine levels in 24-hour urine specimens collected from 11 cocaine-addicted subjects hospitalized in a research setting were measured semi-quantitatively by fluorescence polarization immunoassay. Accurate results required thorough mixing of urine specimens prior to analysis. At admission, eight subjects had urinary benzoylecgonine levels > or = 0.30 microgram/ml, the standard positive/negative cut-off used in qualitative analysis. The mean half-life of benzoylecgonine during initial elimination was 0.46 +/- 0.08 (SEM, n = 8) days. Benzoylecgonine (BE)/creatinine (C) levels remained > or = 0.30 microgramBE/mgC for 4.8 +/- 0.5 (n = 8) days and > or = 0.03 microgramBE/mgC for 10.5 +/- 1.5 (n = 8) days. Relapses in three subjects could be identified by quantitative analysis. This study indicates that quantitation of benzoylecgonine in daily urine specimens provides a sensitive, objective index to cocaine use.

Topics: Adolescent; Adult; Cocaine; Creatinine; Female; Fluorescence Polarization Immunoassay; Half-Life; Humans; Male; Metabolic Clearance Rate; Opioid-Related Disorders; Patient Compliance; Substance Abuse Detection

We evaluated the EZ-SCREEN Test Kit (Editek, Inc., Burlington, NC), a point-of-care screening test for the presence of cocaine metabolite (benzoylecgonine; BE), cannabinoids (tetrahydrocannabinol; THC) and opiates in urine. Patient specimens (n = 34) were tested in the laboratory using both Abbott Laboratories ADx (ADx) and EZ-SCREEN (EZS-LAB), and by the nursing staff of an inpatient substance abuse treatment program using the EZ-SCREEN (EZS-RN). We found comparable analytical efficiency between methods used in the laboratory (> 95% for all three analytes with EZS-LAB and ADx) but lower efficiency for THC and BE with point-of-care testing (approximately 82% for EZS-RN). Efficiency for EZS-RN opiates was 100%. We conclude that the EZ-SCREEN Test Kit may not be suitable for use in a busy clinical setting, unless specific measures are taken to insure the accuracy of point-of-care testing (e.g., minimal interruption or distraction, careful training). We recommend that prior to routine use of point-of-care testing products they be evaluated under normal working conditions with personnel who will eventually be required to perform routine testing.

Topics: Cocaine; Dronabinol; Humans; Marijuana Abuse; Narcotics; Nursing Assessment; Opioid-Related Disorders; Patient Care Team; Point-of-Care Systems; Reagent Kits, Diagnostic; Sensitivity and Specificity; Substance Abuse Detection; Substance-Related Disorders