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Over the last decade, hair analysis has become a routine procedure in most forensic laboratories and, complementary to blood and urine, hair is a unique biological matrix which gives the opportunity to establish a temporal consumption profile. Despite hair is widely used to identify drug use, environmental contamination continues to represent a challenging factor of this procedure, especially for cocaine (COC). In the last few years several strategies have been proposed in order to distinguish between actual use and external contamination, however the commonly detected COC metabolites probably are insufficient for demonstrating cocaine use through hair testing. Thus, the aim of this study is to develop an ultra high performance liquid cromatography - tandem mass spectrometry (UHPLC-MS/MS) method able to detect and quantify hydroxy-COC metabolites, as specific markers of COC abuse, in hair samples from COC consumers, thus enabling unambiguous evidence of COC consumption. At the beginning, since no commercial reference materials were available, COC-positive hair samples were tested using parent ion scan-based analysis to extract hydroxy COC metabolites target ions. Once identified, the reference materials were synthesized by our analytical laboratory allowing the development of the first UHPLC-MS/MS validated method to quantify p- and m-isomers of hydroxy COC, as well as hydroxy benzoylecgonine (BE) and hydroxy norcocaine (NCOC). The method was successfully applied to a large number of COC-positive hair samples and introduced into a routine procedure for testing drug ingestion in order to evaluate for the first-time hydroxy metabolites of COC ranges in hair and their correlation with COC and BE., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Abusive use of drugs is a public health problem worldwide. The use of these substances by pregnant or lactating women can have many serious side effects in newborns. Among the commonest causes of addiction in drug users is cocaine in powdered form, inhaled, intravenously injected or smoked form (crack). Fast screening and a confirmation test using high specificity and sensitivity instruments such as LC-MS or GC/MS, can provide data to qualify and quantify chemical substances present in biological samples such as breast milk or meconium. Cocaine and/or crack can be detected through biomarkers or the unchanged molecule, enabling the form of cocaine use to be distinguished through the analytes. These methods must be carefully developed and validated according to internationally recognized guidelines. Thus, the study of biological matrices in which it can be detected through the development of simple and quick analytical methods can help prevent intoxication and diagnose the symptoms of dependency such as seizures, especially in babies, providing appropriate medical care., (Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: A number of demographic factors, psychiatric disorders, and childhood risk factors have been associated with cocaine dependence (CD) and opioid dependence (OD), but little is known about their relevance to the rate at which dependence develops. Identification of the subpopulations at elevated risk for rapid development of dependence and the risk factors that accelerate the course of dependence is an important public health goal., Methods: Data were derived from cocaine dependent (n=6333) and opioid dependent (n=3513) participants in a multi-site study of substance dependence. Mean age was approximately 40 and 40% of participants were women; 51.9% of cocaine dependent participants and 29.5% of opioid dependent participants self-identified as Black/African-American. The time from first use to dependence was calculated for each substance and a range of demographic, psychiatric, and childhood risk factors were entered into ordinal logistic regression models to predict the (categorical) transition time to CD and OD., Results: In both the cocaine and opioid models, conduct disorder and childhood physical abuse predicted rapid development of dependence and alcohol and nicotine dependence diagnoses were associated with slower progression to CD or OD. Blacks/African Americans were at greater risk than European Americans to progress rapidly to OD., Conclusions: Only a subset of factors known to be associated with CD and OD predicted the rate at which dependence developed. Nearly all were common to cocaine and opioids, suggesting that sources of influence on the timing of transitions to dependence are shared across the two substances., (© 2013.)

Objectives: The present study examined the compatibility of the current DSM-IV and proposed DSM-5 diagnostic criteria for cocaine use disorders (CUD) among state prison inmates, and evaluated the diagnostic utility of the proposed criteria in accounting for DSM-IV "diagnostic orphans" (i.e., individuals who meet one or two of the diagnostic criteria for substance dependence yet fail to report indications of substance abuse)., Method: Data were derived from routine clinical assessments of adult male inmates (N=6871) recently admitted to the Minnesota Department of Corrections state prison system from 2000 to 2003. An automated (i.e., computer-prompted) version of the Substance Use Disorder Diagnostic Schedule-IV (SUDDS-IV; Hoffmann & Harrison, 1995) was administered to all inmates as part of routine assessments. DSM-IV and DSM-5 criteria were coded using proposed guidelines., Results: The past 12-month prevalence of DSM-IV CUDs was 12.7% (Abuse, 3.8%, Dependence, 8.9%), while 11.0% met past 12-month DSM-5 criteria for a CUD (Moderate [MCUD], 1.7%; Severe [SCUD], 9.3%). When DSM-5 criteria were applied, 11.8% of the DSM-IV diagnostic orphans received a MCUD diagnosis. The vast majority of those with no diagnosis (99.6%) continued to have no diagnosis, and a similar proportion who met dependence criteria (98.4%) met SCUD criteria of the proposed DSM-5. Most of the variation in diagnostic classifications was accounted for by those with a current abuse diagnosis., Conclusions: The proposed DSM-5 criteria perform similarly to DSM-IV criteria in terms of the observed past 12-month CUD prevalence and diagnostic classifications. The proposed criteria appear to account for diagnostic orphans that may warrant a diagnosis. DSM-IV abuse cases were most affected when DSM-5 criteria were applied. Additional criteria, beyond those included in the proposed DSM-5 changes, concerning use to relieve emotional stress and preoccupation with use were frequently endorsed by those with a proposed DSM-5 diagnosis., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A gas chromatography-mass spectrometry method for the determination of ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate in hair samples was developed, validated and applied to real samples. Ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate are fatty acid ethyl esters (FAEE) which are known to be direct biotransformation products of ethanol. Their presence in the body fluids and tissue is therefore indicative of alcohol intake and, in particular, FAEE concentration in hair higher than 0.5 ng/mg is indicative of excessive chronic alcohol consumption. The method was applied to 80 hair samples formerly found positive for cocaine and FAEE analytical results were compared with the presence of cocaethylene, a cocaine metabolite formed only when alcohol and cocaine are used together. According to our data the two biomarkers (FAEE and cocaethylene in hair) are tools of great value in the assessment of the diagnosis of use of cocaine and ethanol. In fact, discrepancies were noted and might be related to various factors including differences in consumption habits and thus permitting to distinguish the use of both substances non-concurrently or concurrently. Also, the determination of both markers may, in some cases, discriminate the use of moderate or heavy alcohol amounts when associated with cocaine. Finally, in a population of non-cocaine-users our results support FAEE as valuable means in the assessment of excessive alcohol chronic use., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Homeless individuals (n=187) entering contingency management (CM) for cocaine dependence were assessed for PTSD diagnosis, and a subset of 102 participants reporting traumatic exposure also periodically completed a self-report measure of PTSD symptoms. Patients with PTSD in full remission at 6 months (end of active treatment) and 12 months (end of aftercare) used substances much less frequently during aftercare than those with no PTSD diagnosis. Those whose PTSD diagnosis improved to full remission status during active treatment, and remained in full remission at 12 months, also had superior substance use outcomes. Severity of PTSD symptoms at 6 months, but not baseline or 2 months, was associated with substance use across treatment phases. Substance use during aftercare, however, was better predicted by changes in PTSD symptom severity. Patients whose PTSD symptoms improved more during active treatment fared better during aftercare than those with less improvement. Findings suggest homeless individuals with comorbid PTSD entering CM for cocaine dependence are not necessarily at increased risk for substance use compared to those without the comorbidity. However, course of PTSD does predict substance use, with the potential for CM to be unusually effective for those who respond with substantial, lasting improvements in PTSD., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Purpose: To investigate whether cocaine use is associated with early retinal vascular abnormalities., Design: Population-based cross-sectional study., Settings: Inner-city neighborhoods in Baltimore, Maryland., Study Population: Sixty-eight participants were recruited from an ongoing observational study, investigating cardiovascular complications of human immunodeficiency virus (HIV) infection and cocaine use in African Americans aged between 25 and 54 years. Those with hypertension and known cardiovascular/cerebrovascular diseases were excluded., Observation Procedures: Ophthalmoscopic examinations and fundus photography of the retinas of these subjects were performed after pupillary dilation. The largest angle of arterial bifurcation (LAAB), central retinal artery equivalent (CRAE), and central retinal vein equivalent (CRVE) were measured by single-masked fundus image examiners., Main Outcome Measures: LAAB, CRAE, and CRVE., Results: Among the 68 study subjects, 52 (76.5%) were chronic cocaine users and 16 (23.5%) were non-cocaine users. Univariate and multivariate analyses indicated that the LAAB was associated with age and duration of cocaine use of more than 10 years. The LAAB was also inversely associated with very low-density lipoproteins levels. Multivariate analysis indicated a positive association between CRVE and cocaine use. CRAE was also associated with intravenous injection. We confirmed that CRAE was inversely associated with age. HIV infection was not found to be associated with any retinal vascular parameters., Conclusions: Cocaine use is associated with increased retinal arterial branching angle and venular caliber. The retinal vascular changes provided the first evidence that cocaine use has an effect on the retinal vascular system.

Cocaine is currently one of the most widespread abuse drugs in the world. Since hair cocaine concentrations are a reliable marker of exposition to the drug, an original liquid chromatographic method has been developed for the determination of cocaine in human hair. The chromatographic analysis was carried out on a Hydro-RP C18 column, using a mobile phase containing a phosphate buffer (pH 3.0)-acetonitrile-methanol (75:15:10, v/v/v). Native cocaine fluorescence was monitored at 315nm while exciting at 230nm. Mirtazapine was used as the internal standard. Sample pre-treatment was carried out by incubative extraction with 0.1M HCl followed by solid-phase extraction with C2 cartridges. Good linearity was obtained over a working range of 0.3-100.0ng/mg. Both extraction yield (>89%) and precision values (R.S.D.<6.2%) were highly satisfactory. The method was successfully applied to hair samples collected from cocaine users. Thus, the method is suitable for the long-term monitoring of cocaine use by means of hair testing.

Our goal in the current report was to design a new functional magnetic resonance imaging (fMRI) task to probe the role of the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) in processing of salient symptom-related cues during the simultaneous performance of an unrelated task in drug-addicted persons. We used a novel fMRI color-word drug Stroop task in 14 individuals with cocaine use disorders; subjects had to press for color of drug vs. matched neutral words. Although there were no accuracy or speed differences between the drug and neutral conditions in the current sample of subjects, drug words were more negatively valenced than the matched neutral words. Further, consistent with prior reports in individuals with other psychopathologies using different Stroop fMRI paradigms, our more classical color-word Stroop design revealed bilateral activations in the caudal-dorsal anterior cingulate cortex (cdACC) and hypoactivations in the rostro-ventral anterior cingulate cortex/medial orbitofrontal cortex (rACC/mOFC). A trend for larger rACC/mOFC hypoactivations to the drug than neutral words did not survive whole-brain corrections. Nevertheless, correlation analyses indicated that (1) the more the cdACC drug-related activation, the more negative the valence attributed to the drug words (r=-0.86, P<0.0001) but not neutral words; and (2) the more the rACC/mOFC hypoactivation to drug minus neutral words, the more the errors committed specifically to the drug minus neutral words (r=0.85, P<0.0001). Taken together, results suggest that this newly developed drug Stroop fMRI task may be a sensitive biobehavioral assay of the functions recruited for the regulation of responses to salient symptom-related stimuli in drug-addicted individuals.

Lack of disclosure of substance use is common in research and treatment settings and is frequently higher at follow-up than at baseline interviews. The aim of this study was to determine predictors of cocaine use disclosure at follow-up among 525 individuals who reported and tested positive for baseline use. Measurements included self-reported quantity and frequency of use, and hair analysis by radioimmune assay. Forty-two percent of individuals with biochemical evidence of continued cocaine use denied this use. In adjusted analyses, self-reported substance abuse treatment contact after enrollment was associated with lower disclosure (OR 0.63, 95% CI 0.43, 0.93). Other predictors were race, hair cocaine level, and opiates in hair. Failure to stop use after seeking treatment may result in reduced disclosure of continued use, possibly because of unwillingness to admit failure.

This article reports findings from a study that investigated treatment outcomes among crack/cocaine users over a 18-month period. From a cohort of 229 subjects, three groups emerged: (1) those who had reported ongoing, stable abstinence from crack/cocaine; (2) those who had consistently used during the period; and (3) those who reported cycling between abstinence and use during the follow-up period. Analyses of variance (ANOVA) were conducted to compare the three groups in terms of intake characteristics, including demographic profile, previous treatment, motivational factors, and functioning in seven Addiction Severity Index (ASI) domains. Length of time involved in aftercare and Twelve Step participation after treatment were also contrasted among the three groups. Results showed that subjects who achieved sustained abstinence from crack/cocaine also did better in other domains such as employment, family, legal, and psychiatric than others. Stable abstinence was also significantly associated with a longer period of aftercare and frequent attendance at Twelve Step programs. Logistic regression analyses further estimated the significant impact of the posttreatment factors on the achievement of sustained abstinence. The implications of these findings for treatment services research are discussed.

A double-blind, placebo-controlled clinical trial examining the joint action of naltrexone (NTX) in combination with relapse prevention (RP) therapy for the treatment of cocaine dependence was conducted. Eighty-five participants who achieved initial abstinence during the intake evaluation and detoxification phase of the study were randomized into 1 of 4 combined NTX (0 vs. 50 mg) by therapy (RP vs. Drug Counseling) experimental conditions for the 12-week outpatient treatment phase of the study. A random effects regression model to test for group differences on percentage of cocaine-positive urines indicated a significant time by medication by therapy interaction, suggesting less cocaine use over time among subjects receiving RP-50 mg than those in the other conditions. No differences were found for retention or time until first cocaine-positive urine. Naltrexone was well tolerated by participants, with acceptable rates of medication compliance observed. Treatment integrity measures confirmed successful manipulation of the psychotherapy. These results are consistent with the notion that substance use in dependent patients can be reduced with a combination of coping skills training and pharmacologic treatments.

Although toxins exert their impact on a molecular level, they may yield molar effects by affecting areas large enough to be visualized by neuroimaging techniques. Therefore, neuroimaging of the brain may be used to render the macroscopic sequelae of neurotoxins visible. Toxic agents may induce brain edema or atrophy, demyelination, infarctions, calcifications, hemorrhages, or changes of perfusion, metabolism or receptor density. Although they do not readily disclose their nature, clues as to the offending agent may in some instances be gleaned from the pattern, distribution, and appearance of the cerebral changes. Intoxication, however, has always to be proved or substantiated independently by appropriate means. This paper deals with the extent and certainty to which conclusions as to some of the most common offending substances may be drawn from pictures of the brain.

The Medical Outcomes Study Short Form 36 (SF-36) was administered to 443 not-in-treatment, crack-cocaine smokers to explore the relationship between frequency of crack, alcohol, and tobacco use, addiction to these drugs, and health status. The reliability of the SF-36 with crack smokers was also assessed. Statistically significant, negative associations emerged between frequency of crack use and all SF-36 subscales except physical functioning. There were not significant associations between frequency of alcohol or tobacco use and any SF-36 subscale. Self-assessed addiction to crack was strongly and negatively associated with all SF-36 subscales: alcohol and tobacco addiction were also negatively associated with health status, but not to the degree of crack. The SF-36 produces reliable data on the health status of crack users and, as such, may have a useful role in assessments involving crack-using populations.

Clinical observations have indicated that alcohol may be employed by cocaine/crack users to attenuate negative effects of cocaine, especially when "coming down" from a cocaine binge. This issue was examined by interviewing 66 dual cocaine/alcohol users, with opiate dependence histories, enrolled in methadone treatment. A path analysis model was specified to test several hypotheses concerning the possible modulating effects of alcohol use on cocaine use. About 60% of the subjects reported often employing alcohol to ameliorate discomfort associated with tapering or ceasing cocaine/crack use. The main findings were: (a) more intense cocaine/crack craving and feeling that cocaine/crack use was out of control both led to increased use of alcohol to come down; (b) the more frequently alcohol was used to come down, the less use of cocaine/crack; and (c) more cocaine/crack use and more use of alcohol to come down both led to increased heavy alcohol use. Thus, treating alcohol abuse in this population must take into account the important function it serves in modulating cocaine/crack use.

This study sought to establish the validity of the Cocaine Effect Expectancy Questionnaire (CEEQ), and the Marijuana Effect Expectancy Questionnaire (MEEQ) in discriminating between patterns of drug use in a clinical population. Prior research with these questionnaires has involved primarily nonclinical samples. Expectancy literature has yielded ambiguous results in demonstrating the role of both positive and negative expectancies in regards to drug use patterns. The sample consisted of 149 males on an inpatient V.A. substance abuse unit. On the CEEQ, cocaine users, particularly frequent users, endorsed fewer global positive cocaine expectancies than infrequent or nonusers. Present-infrequent users endorsed greater arousal effects than either present-frequent or nonusers. Nonusers of cocaine endorsed greater relaxation than present users. On the MEEQ, nonusers expected more negative effects from marijuana than users. Present users expected greater relaxation and craving effects than past users or nonusers. These results indicate different roles for positive and negative expectancies in cocaine and marijuana use.

This article assesses the reliability and validity of the Cocaine Selective Severity Assessment (CSSA), a measure of cocaine abstinence signs and symptoms. Interrater reliability and scale internal consistency were high. Initial CSSA scores were significantly higher in cocaine-dependent subjects than in alcohol-dependent subjects. Initial CSSA scores were highly correlated with recent cocaine use and with severity measures from the Addiction Severity Index (ASI) including the interviewer severity rating and composite score in the drug section. Among cocaine-dependent subjects, initial CSSA scores were higher for those who failed to achieve abstinence or who subsequently dropped out of treatment. Further, CSSA scores showed consistent and marked declines over time for subjects who continued in treatment and remained abstinent. The CSSA appears to be a reliable and valid measure of cocaine abstinence symptoms and a useful predictor of negative outcomes in cocaine dependence treatment.