Comparison of Cocaine/Crack Biomarkers Concentrations in Oral Fluid, Urine and Plasma Simultaneously Collected From Drug Users.

The use of oral fluid (OF) as an alternative specimen for drug analysis has become very popular in forensic toxicology. Many clinical studies have evaluated the correlations between concentrations of cocaine and its metabolites in OF and other matrices, but results have shown high variability. In addition, there are no data available regarding the correlations between biomarkers of crack-cocaine use in different matrices. This study evaluated the relationship between concentrations of cocaine/crack-cocaine biomarkers in OF, urine and plasma samples collected from cocaine users. All samples were analyzed for the presence of cocaine (COC), benzoylecgonine (BZE) and anhydroecgonine (AEC) by a validated liquid chromatography-mass spectrometry method. Median COC, BZE and AEC concentrations ranged from 4.20 to 33.26 ng/mL, from 13.03 to 3,615.86 ng/mL and from 7.40 to 1,892.5 ng/mL across matrices, respectively. The relationship between drug concentrations in OF versus plasma (OF/P) and OF versus urine (OF/U) was evaluated by their coefficients of determination (R2). Least-squares regression analyses demonstrated significant correlations between OF/P and OF/U for cocaine and BE (P < 0.05), with R2 = 0.17, 0.07 for cocaine and R2 = 0.73, 0.45 for BE, respectively. The correlation coefficients (r) found for BZE, COC and AEC in OF/P and OF/U were 0.85 and 0.67 (P < 0.05); 0.41 and 0.26 (P < 0.05); and 0.30 and -0.37 (P > 0.05), respectively. Many factors contribute to the variability of drug correlation ratios in studies involving random samples, including uncertainty about the time of last administration and dosage. Overall, we found significant R2 values for COC and BZE in OF/P and OF/U, but not for AEC. Despite the good correlations found in some cases, especially for BZE, the large variation in drug concentrations seen in this work suggests that OF concentrations should not be used to estimate concentrations of COC, BZE or AEC in plasma and/or urine.

Analysis of Urinary Biomarkers for Smoking Crack Cocaine: Results of a Danish Laboratory Study.

Crack cocaine (free-base cocaine) smokers belong to a subgroup of marginalized drug users exposed to severe health risks and great social harm. Detection of the urinary, pyrolytic biomarker methylecgonidine (MED) and its metabolite ecgonidine (ED) secures an unambiguous confirmation of crack cocaine smoking. Although prevalence studies of cocaine based upon self-reporting may not be accurate, laboratory analysis is seldom used for neither diagnostic purpose nor early identification of crack cocaine smoking, which is far more severe than snorting cocaine. A new analytical method was validated for MED, ED and other relevant cocaine metabolites using automated liquid handling and column switching coupled to liquid chromatography and tandem mass spectrometry. Limit of quantification was 30 ng/mL for ED and MED. This method was applied in a laboratory study of urine samples (n = 110) from cocaine users in Denmark subjected to routine drugs-of-abuse testing. Crack cocaine smoking was confirmed by the presence of MED and/or ED. Eighty-four samples (76.4%) were found positive for crack cocaine smoking in this group of problematic cocaine users. MED was only detected in 5.9% of the positive samples. The study shows a prevalence 3-fold higher to that recently suggested by European Monitoring Centre for Drugs and Drug Addiction. We therefore advocate that the urinary biomarkers MED and ED are included in routine testing methods for clinical toxicology. This may lead to an earlier identification of crack cocaine smoking and possibly prevent a more severe drug use.

Contingency management to reduce methamphetamine use and sexual risk among men who have sex with men: a randomized controlled trial.

BACKGROUND: Methamphetamine use is associated with HIV acquisition and transmission among men who have sex with men (MSM). Contingency management (CM), providing positive reinforcement for drug abstinence and withholding reinforcement when abstinence is not demonstrated, may facilitate reduced methamphetamine use and sexual risk. We compared CM as a stand-alone intervention to a minimal intervention control to assess the feasibility of conducting a larger, more definitive trial of CM; to define the frequency of behavioral outcomes to power such a trial; and, to compute preliminary estimates of CM's effectiveness. METHODS: We randomly assigned 127 MSM from Seattle, WA who use methamphetamine to receive a 12-week CM intervention (n = 70) or referral to community resources (n = 57). RESULTS: Retention at 24 weeks was 84%. Comparing consecutive study visits, non-concordant UAI declined significantly in both study arms. During the intervention, CM and control participants were comparably likely to provide urine samples containing methamphetamine (adjusted relative risk [aRR] = 1.09; 95%CI: 0.71, 1.56) and to report non-concordant UAI (aRR = 0.80; 95%CI: 0.47, 1.35). However, during post-intervention follow-up, CM participants were somewhat more likely to provide urine samples containing methamphetamine than control participants (aRR = 1.21; 95%CI: 0.95, 1.54, P = 0.11). Compared to control participants, CM participants were significantly more likely to report weekly or more frequent methamphetamine use and use of more than eight quarters of methamphetamine during the intervention and post-intervention periods. CONCLUSIONS: While it is possible to enroll and retain MSM who use methamphetamine in a trial of CM conducted outside drug treatment, our data suggest that CM is not likely to have a large, sustained effect on methamphetamine use.

Cocaine and metabolites urinary excretion after controlled smoked administration.

Understanding cocaine and metabolites urinary excretion following smoking is important for interpretation of urine test results in judicial, workplace and treatment settings. In National Institute on Drug Abuse approved studies on a secure research unit, six subjects smoked placebo, 10, 20, and 40 mg cocaine with a precise dose delivery device and six different subjects smoked 42 mg cocaine in a glass pipe. Urine specimens (n = 700) were collected for up to seven days and analyzed for cocaine (COC), benzoylecgonine (BE), ecgonine methylester (EME), m-hydroxybenzoylecgonine (mOHBE), p-hydroxybenzoylecgonine (pOHBE), norbenzoylecgonine (NBE), and ecgonine (EC) by gas chromatography-mass spectrometry. Results (mean +/- SE) for the 40-mg precise delivery doses are as follows: (Table can not be represented) Mean C(max) for all analytes linearly increased with increasing dose. T(max) was not dose-dependent. All metabolites were detected in some subjects within 2 h. EC concentrations were significantly higher after smoked cocaine in a precise delivery coil compared to a glass "crack" pipe.

Comparison of desipramine or carbamazepine to placebo for crack cocaine-dependent patients.

The authors compared the effects of desipramine or carbamazepine to placebo in an intensive outpatient program for cocaine abuse. Subjects recruited from an urban drug treatment program were randomly assigned to a double-blind, placebo-controlled, eight-week trial of desipramine, carbamazepine, or placebo. Patient ratings, urine drug screens, and blood samples were obtained weekly. Using survival analysis, the three groups did not differ in time to drop out of treatment. While subjects improved over time on all self-ratings related to cocaine use, mood, and craving, only two items related to mood were significantly different over time as a function of treatment group. Subjects in the two treated groups reported significantly more improvement on self-ratings of depression and irritability. No treatment differences were noted for sustained abstinence or for proportion of positive urine drug screens. Desipramine subjects who attained a minimum blood level were retained in treatment significantly longer than placebo or other non-compliant treatment groups. This finding supports previous reports of a possible role for desipramine in cocaine abuse treatment.

Urinary elimination of cocaine metabolites in chronic cocaine users during cessation.

We previously showed that chronic cocaine use by active illicit users produced a longer plasma half-life than expected based on acute low-dose cocaine studies. Here we report urinary excretion patterns of cocaine metabolites as benzoylecgonine (BE) equivalents from 18 of the same individuals, housed for up to 14 days on a closed research unit. In addition, we evaluated whether creatinine normalization of BE equivalents increased mean detection time and reduced mean within-subject variability. All urine voids (N = 953) were individually assayed; BE equivalents were determined semi-quantitatively by FPIA. Compared to concentration in first void after admission, BE equivalents decreased to approximately 33%, 8%, and 4% at 24, 48, and 72 h, respectively. Mean +/- SD (range) time to first negative specimen (BE equivalents < 300 ng/mL) was 43.6 +/- 17.1 (16-66) h. BE equivalents fluctuated considerably across successive specimens; 69% of participants tested positive at least once after testing negative, and the mean time to last positive specimen was 57.5 +/- 31.6 (11-147) h after the first specimen. Thus, mean cocaine metabolite detection times were consistent with prolonged elimination, with 63% of participants testing positive longer than the expected 48-h window of detection after admission to the unit. Mean time to last positive after last use of cocaine, known by self-report only, was approximately 81 +/- 34 (34-162) h. Creatinine normalization, with the cut-off of 300 ng BE equivalents/mg creatinine, increased detection time: mean time to first negative specimen was 54.8 +/- 20.7 (20-100) h, and mean time to last positive specimen was 88.4 +/- 51.0 (35.6-235) h. Compared with the concentration in the first void after admission, BE equivalents/creatinine decreased to approximately 56%, 6%, and 5% at 24, 48, and 72 h. However, creatinine normalization did not reduce the fluctuation of BE equivalents across successive specimens. Thus, creatinine normalized values may be useful when the goal is to maximize the probability or duration of cocaine metabolite detection, but may be less useful in determining whether an individual has used cocaine since a previous specimen collection.

Cocaine exposure and developmental outcome from birth to 6 months.

The theoretical framework for many of the early studies of prenatal cocaine exposure has been rooted in the basic concepts of teratology/developmental toxicology. Few have published longitudinal analyses of the complex interplay between the relative effects of prenatal cocaine exposure and perinatal and environmental factors on development. The purpose of this paper was to use structural equation modeling to describe the direct and indirect effects of prenatal drug exposure on developmental outcome from birth to age 6 months. Key variables considered for study include prenatal drug exposure, perinatal medical characteristics, maternal/caregiver/family characteristics, the home environment, and neurobehavioral outcomes. We prospectively enrolled 154 predominantly crack-using women. A priori exclusion criteria included: <18 years old, major illnesses diagnosed prior to pregnancy, chronic use of legal drugs, and any use of illicit drugs other than cocaine and marijuana. From the pool of noncocaine users, 154 subjects were matched to users on pregnancy risk, parity, race, and socioeconomic status. At the end of each trimester, experienced staff conducted private interviews prompting memory of amount and timing of past drug use. Urine specimens were collected at two unanticipated times; positive screens were confirmed by gas chromatography/mass spectroscopy. Measures analyzed include medical (birth) and developmental (birth, 1 month, 6 months) assessments, all performed by blinded evaluators, as well as caregiver characteristics and environmental factors (birth, 1 month). A series of four theoretical models was tested, one for each time point (birth, 1 month, 6 months) and a longitudinal model spanning birth to 6 months. Key findings include direct effects of prenatal cocaine exposure on development at birth in the birth model and on development at birth and 6 months in the longitudinal model. In addition, indirect effects of prenatal cocaine exposure were identified on development at birth, 1 month, and 6 months, mediated through the prenatal use of alcohol and tobacco and the birth head circumference. Implications of these and other findings, including the advantages and limitations of structural equation modeling, are discussed.

The validity of adult arrestee self-reports of crack cocaine use.

Despite the many problems associated with crack use, little validated empirical evidence about the prevalence of crack cocaine exists. Researchers that track crack cocaine use have relied on self-reports to differentiate crack and powder cocaine. Prior research suggests that the accuracy of self-reports for the use of a variety of illicit substances is relatively low. To examine the validity of self-reports of crack use, this article employs a newly developed technology to detect specifically the presence of markers of crack cocaine in urine specimens. With a sample of 2327 arrestees from six cities that participate in the Arrestee Drug Abuse Monitoring (ADAM) Program, both face-to-face interview and urinalysis data were examined. Using a positive urinalysis result as the validity standard, we assessed the extent to which arrestees underreport crack cocaine use as compared to the use of marijuana, opiates,and methamphetamine. Logistic regression models were also de veloped to predict the factors that relate to underreporting. The results showed a considerable amount of underreporting for all the drug measures. In most cases, only about half the people who had a positive urinalysis test for drugs admitted using drugs. Overall, the least amount of underreporting occurred for the use of marijuana (63.6% told the "truth"), followed by methamphetamine (56.1% told the truth), crack (48.2% told the truth), and opiate (45.9% told the truth). Female crack users, as compared to male crack users, were more likely to admit using crack. Black arrestees were more likely to admit using crack than white or Hispanic arrestees. Arrestees with a history of prior drug treatment or a prior arrest, as compared to those without such histories, were more likely to admit using crack. The older the arrestee was, the more likely the arrestee would admit using crack. The more money an arrestee spent on drugs, the more likely the arrestee would admit using crack. Differences in underreporting were also observed across the six cities in this study. The implications of these findings for the monitoring of crack use are discussed.

Mediators of drug treatment outcomes.

Treatment for drug use, like the process by which a person comes to use illicit drugs, may be seen to be at least in part a psychosocial process involving emotional, cognitive, and relationship domains. Treatment programs attempt to improve the psychosocial functioning of clients with the ultimate goal of effecting change in drug-use behaviors. In a longitudinal study of clients in an intensive outpatient treatment program using a cognitive behavioral model to treat crack cocaine use, it was found that length of treatment was directly associated with improvement in emotional well-being, cognitive functioning, and relationships. Of the three psychosocial domains, improvement in relationships had the strongest effect on self-reported decreases in cocaine usage, verified by urinalysis. Improvement in cognitive functioning had a small impact on cocaine use, whereas improvement in emotional well-being had almost no independent effect in this cognitive behavioral treatment program.

Validity of self-reported crack cocaine use among homeless persons in treatment.

The validity of self-reported crack cocaine use among 131 homeless persons participating in an outpatient substance abuse treatment research demonstration project was assessed by comparing the concordance of self-report and urinalysis results. The subjects were participants in either a Usual Care outpatient program or an Enhanced Care day treatment program that included drug free contingent work therapy and housing. For all subjects across four evaluation points, the false negative classification by self-report (i.e., denied verified use) rate for crack cocaine use was 32.0%. Denied verified use was greater in Usual Care (34.9%) than in Enhanced Care clients (23.7%) and greater at follow-up as compared to treatment entry for all clients. The findings are explained in terms of social desirability and the influence of treatment contingencies and greater accountability specific to the Enhanced Care program. The need for validation of self-reported cocaine use data among homeless persons in settings where contingencies are present and in other drug treatment or research settings is recommended.