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Differentiation between granulomatosis with polyangiitis (GPA) limited to the upper airways and cocaine-induced midline destructive lesion (CIMDL) may be particularly difficult because of their common histopathologic features and antineutrophil cytoplasmic antibody (ANCA) profiles. We herein present a case involving a young woman with an initial diagnosis of GPA based on upper and lower airway manifestations and constitutional symptoms, histopathologic evidence of granulomas, a positive cytoplasmic ANCA indirect immunofluorescent test result, and proteinase 3 positivity by enzyme-linked immunosorbent assay (ELISA). CIMDL was confirmed based on the appearance of a hard palate perforation, positivity for methylecgonine on urine toxicology, a positive perinuclear ANCA indirect immunofluorescent test result, and subsequent human neutrophil elastase (HNE) ANCA positivity by ELISA. Finally, based on the coexistence of CIMDL, constitutional symptoms, and lower airway manifestations, the diagnosis was modified to cocaine-induced GPA mimic. Urine toxicology for cocaine and HNE ELISA are indicated in young patients with GPA who develop limited airway disease to check for the presence of CIMDL and cocaine-/levamisole-induced ANCA-associated vasculitis. Continued abstinence from cocaine is the first-choice therapy for both CIMDL and cocaine-induced GPA mimic., Competing Interests: Declaration of conflicting interestThe authors declare the there are no conflicts of interest.

Aim: This retrospective study examined the prevalence of combined ethanol and cocaine use, which produces an enhanced psychoactive effect through formation of the active metabolite cocaethylene, compared to combined use of ethanol and two other common recreational drugs, cannabis and amphetamine, based on urine drug test results., Methods: The study was based on >30,000 consecutive samples from routine urine drug testing in 2020, and 2627 samples from acute poisonings in the STRIDA project (2010-2016), in Sweden. Drug testing for ethanol (i.e. ethyl glucuronide and ethyl sulfate), cocaine (benzoylecgonine), cannabis (Δ9-THC-COOH) and amphetamine was done by routine immunoassay screening and LC-MS/MS confirmatory methods. Seven samples testing positive for cocaine and ethyl glucuronide were also analyzed for cocaethylene by LC-HRMS/MS., Results: Among routine samples for which testing of ethanol and cocaine had been requested, 43% tested positive for both substances, compared with 24% for ethanol and cannabis and 19% for ethanol and amphetamine (P < 0.0001). Among the drug-related intoxications, 60% of cocaine-positive samples were also positive for ethanol, compared to 40% for cannabis and ethanol and 37% for amphetamine and ethanol. Cocaethylene was detected (range 1.3-150 μg/L) in all randomly selected samples testing positive for ethanol and cocaine use., Conclusions: These results, which were based on objective laboratory measures, indicated that combined ethanol and cocaine exposure was more prevalent than expected from drug use statistics. This may relate both to the common use of these substances in party and nightlife settings, and the amplified and prolonged pharmacological effect by the active metabolite cocaethylene., (© The Author(s) 2023. Medical Council on Alcohol and Oxford University Press.)

The purpose of this study was to compare results from five commercial hair testing laboratories conducting workplace drug testing with regard to bias, precision, selectivity and decontamination efficiency. Nine blind hair specimens, including cocaine-positive drug user specimens (some contaminated with methamphetamine) and negative specimens contaminated with cocaine, were submitted in up to five replicates to five different laboratories. All laboratories correctly identified cocaine in all specimens from drug users. For an undamaged hair specimen from a cocaine user, within-laboratory Coefficients of Variation (CVs) of 5-22% (median 8%) were reported, showing that it is possible to produce a homogenous proficiency testing sample from drug user hair. Larger CVs were reported for specimens composed of blended hair (up to 29%) and curly/damaged hair (19-67%). Quantitative results appeared to be method-dependent, and the reported cocaine concentrations varied up to 5-fold between the laboratories, making interlaboratory comparisons difficult. All laboratories reported at least one positive result in specimens contaminated with cocaine powder, followed by sweat and shampoo treatments. Benzoylecgonine, norcocaine, cocaethylene and hydroxylated cocaine metabolites were all detected in cocaine powder-contaminated specimens. This indicates that current industry standards for analyzing and reporting positive cocaine results are not completely effective at identifying external contamination. Metabolite ratios between meta- or para-hydroxy-cocaine and cocaine were 6- and 10-fold lower in contaminated specimens compared to those observed in cocaine user specimens, supporting their potential use in distinguishing samples positive due to contamination and drug use., (Published by Oxford University Press 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Cocaine and some of its main adulterants, such as levamisole, can cause multiple cutaneous and mucosal manifestations, including ischemic complications, neutrophilic dermatoses, midline destructive lesions, and vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). Striking systemic symptoms are generally not seen. In all these conditions, positive test results may be observed for antinuclear antibodies, antiphospholipid antibodies, and various ANCAs, sometimes with characteristic staining patterns. Histology typically shows vascular changes, such as leukocytoclastic vasculitis, necrotizing vasculitis, and thrombi. We review the clinical, serologic, and histologic features of cutaneous and mucosal conditions associated with the use of cocaine and also look at pathophysiologic mechanisms, differential diagnoses, and treatments., (Copyright © 2022 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

A highly discussed step in hair sample preparation for forensic analytics is the applied decontamination. The here presented investigations aim to gain insight and give recommendations on how to conduct this decontamination for the analysis of cocaine consumption in hair. Key insights were gained from the investigation of cocaine consumer hair, which was artificially contaminated in a humid atmosphere with 13C6 labelled cocaine and from cocaine powder contaminated hair. Several decontamination protocols were investigated, whereby the usage of a decontamination protocol consisting of multiple short repetitive washes allowed to visualize the wash out of (13C6-) cocaine. Multiple methanol washes proved to be an efficient and simple decontamination approach. Our findings showed that decontamination protocols can successfully wash out recent cocaine contaminations. They were observed to be rather quickly washed out, whereas cocaine from consumption or "older" cocaine contaminations were shown to eliminate both at a constant rate (from inner hair compartments). Thus, the usage of decontamination protocols to differentiate between consumption and contamination was shown to be limited. As contamination can happen any time at any level, only the application of elaborated decision trees, based on cocaine metabolite ratios and thresholds, can provide the distinction between consumption and contamination. Thus, the authors highly recommend the usage of such tools on all hair samples analyzed for cocaine consumption., (© The Author(s) 2020. Published by Oxford University Press.)

Background: Cocaine use is a growing global health problem and patients with cocaine use disorders (CUD) present several complications, including high rates of major depression. These subjects present two types of major depressive disorder (MDD): primary major depressive disorder (P-MDD) and cocaine-induced major depressive disorder (CI-MDD). To improve treatment, it is necessary to distinguish between both types. The aim of this study was to assess the differences in depressive symptomatology criteria (P-MDD vs CI-MDD) in CUD patients., Methods: Secondary data analysis was carried out with a cross-sectional sample of 160 patients presenting CUD and MDD. Clinical assessment was performed using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM). A differential diagnosis was obtained between P-MDD and CI-MDD., Results: Men represented 80% of the sample, the mean age was 38.61 years, and 64.5% had elementary studies. CI-MDD diagnosis (61.3%) was more frequent than P-MDD (38.7%). There was a younger age of CUD onset in CI-MDD patients. In addition, 79.4% of the patients had another substance use disorder diagnosis. The criterion "Changes in weight or appetite" was more prevalent (57.1%) in P-MDD group., Conclusions: We found differences in the criterion "Changes in weight or appetite". Further research is needed in this field to establish a differential diagnosis and thus provide better treatment for CUD patients.

We are using real-life data in order to determine the prevalence of driving with the presence of cocaine and/or benzoylecgonine (BZE), their concentrations, and their use in combination with other drugs. This study assessed data on Spanish drivers with confirmed drug-positive results recorded by the Spanish National Traffic Agency from 2011-2016. Frequencies of positivity for cocaine and/or BZE and concentration of such substances were obtained. Comparisons and univariate and multivariate regression analyses were performed. Drivers who tested positive for cocaine and/or BZE accounted for 48.59% of the total positive results for drugs. In positive cases for both cocaine and BZE, other substances were detected in 81.74%: delta-9-tetrahydrocannabinol (THC) (68.19%), opioids (20.78%) and amphetamine-like substances (16.76%). In the multivariate logistic regression analysis, the frequency of cocaine and/or BZE positive cases decreased with age (OR:0.97) and were less likely among women (OR:0.63). Concentrations (ng/mL) of cocaine (249.30) and BZE (137.90) were higher when both substances were detected together than when detected alone. Positivity to cocaine represented an important proportion among Spanish drivers who tested positive for drugs, and polysubstance use was especially observed in more than 8 out of 10 positive cases for cocaine and/or BZE.

Background: Cocaine has a short biological half-life, but inactive urine metabolites may be detectable for a week following use. It is unclear if patients who test positive for cocaine but have a normal electrocardiogram and vital signs have a greater percentage of hemodynamic events intraoperatively., Methods: A total of 328 patients with a history of cocaine use who were scheduled for elective noncardiac surgery under general anesthesia were enrolled. Patients were categorized into cocaine-positive versus cocaine-negative groups based on the results of their urine cocaine toxicology test. The primary aim of this study was to evaluate whether asymptomatic cocaine-positive patients had similar percentages of intraoperative hemodynamic events, defined as (1) a mean arterial blood pressure (MAP) of <65 or >105 mm Hg and (2) a heart rate (HR) of <50 or >100 beats per minute (bpm) compared to cocaine-negative patients. The study was powered to assess if the 2 groups had an equivalent mean percent of intraoperative hemodynamic events within specific limits using an equivalence test of means consisting of 2 one-sided tests., Results: The cocaine-positive group had a blood pressure (BP) that was outside the set limits 19.4% (standard deviation [SD] 17.7%) of the time versus 23.1% (SD 17.7%) in the cocaine-negative group (95% confidence interval [CI], 0.5-7.0). The cocaine-positive group had a HR outside the set limits 9.6% (SD 16.2%) of the time versus 8.2% (SD 14.9%) in the cocaine-negative group (95% CI, 4.3-1.5). Adjusted for age, sex, body mass index (BMI), smoking status, and the presence of comorbid hypertension, renal disease, and psychiatric illness, the cocaine-positive and cocaine-negative patients were similar within a 7.5% margin of equivalence for MAP data (β coefficient = 2%, P = .003, CI, 2-6) and within a 5% margin of equivalence for HR data (β coefficient = 0.2%, P < .001, CI, 4-3)., Conclusions: Asymptomatic cocaine-positive patients undergoing elective noncardiac surgery under general anesthesia have similar percentages of intraoperative hemodynamic events compared to cocaine-negative patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 International Anesthesia Research Society.)

Hydroxycocaines in hair were investigated with many hundreds of head and body hair samples. All samples were washed by a published extensive aqueous method prior to confirmation by LC-MS/MS. Concentrations, percent of cocaine, and ratios of para- and meta-hydroxycocaines to ortho-hydroxycocaine are presented. Hydroxycocaines as percent of cocaine did not appear to be affected by cocaine concentrations, but were shown to increase with cocaethylene concentrations. Stability of hydroxycocaines over a year of ambient storage was demonstrated. Ortho-hydroxycocaine was shown to be formed by exposure of cocaine-positive hair to peroxide, while para- and meta-hydroxycocaines were not. Presence of para- or meta-hydroxycocaine at > 0.05% of cocaine is proposed as indicating ingestion of cocaine. This indicator prevents black hair from being more likely interpreted as positive for ingestion than lighter colored hair., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

'Tree-in-bud' (TIB) appearance in computed tomography (CT) chest is most commonly a manifestation of infection. We here describe an unusual cause of TIB during the COVID-19 pandemic. A young male patient who had a history of fever, cough, and respiratory distress presented in the emergency department. As these symptoms matched with coronavirus infection, the COVID-19 test was done, which was found negative. He was then moved to the intensive care unit where he developed severe acute respiratory distress syndrome and was put on mechanical ventilation. Further workup did not reveal any source of infection, as all his cultures were negative, but his CT chest showed a tree-in-bud appearance. After obtaining a detailed history from his friends, the patient was found a chronic abuser of inhaled cocaine and treated with intravenous steroids. Subsequently, he was weaned from the ventilator and discharged from the intensive care unit after becoming asymptomatic.

Diffuse alveolar haemorrhage (DAH) is characterised by diffuse pulmonary opacities, respiratory failure, a falling haemoglobin level along with presence of hemosiderin-laden macrophages on bronchoalveolar lavage (BAL). Finding the underlying aetiology of DAH can be challenging but of importance as the treatment and prognosis are largely determined by it. We report a case of DAH with underlying cocaine abuse, a rare cause for the same.

The finding that drugs and metabolites can be detected from fingerprints is of potential relevance to forensic science and as well as toxicology and clinical testing. However, discriminating between dermal contact and ingestion of drugs has never been verified experimentally. The inability to interpret the result of finding a drug or metabolite in a fingerprint has prevented widespread adoption of fingerprints in drug testing and limits the probative value of detecting drugs in fingermarks. A commonly held belief is that the detection of metabolites of drugs of abuse in fingerprints can be used to confirm a drug has been ingested. However, we show here that cocaine and its primary metabolite, benzoylecgonine, can be detected in fingerprints of non-drug users after contact with cocaine. Additionally, cocaine was found to persist above environmental levels for up to 48 hours after contact. Therefore the detection of cocaine and benzoylecgonine (BZE) in fingermarks can be forensically significant, but do not demonstrate that a person has ingested the substance. In contrast, the data here shows that a drug test from a fingerprint (where hands can be washed prior to donating a sample) CAN distinguish between contact and ingestion of cocaine. If hands were washed prior to giving a fingerprint, BZE was detected only after the administration of cocaine. Therefore BZE can be used to distinguish cocaine contact from cocaine ingestion, provided donors wash their hands prior to sampling. A test based on the detection of BZE in at least one of two donated fingerprint samples has accuracy 95%, sensitivity 90% and specificity of 100% (n = 86).

Background: Cocaine is a psychostimulant drug with high addictive proprieties. Evidence suggests that cocaine use leads to critical changes in the immune system, with significant effects on T, B, and natural killer (NK) cells and influencing peripheral levels of cytokines. The presence of abstinence-related symptoms during detoxification treatment is known to influence the prognosis. Here, our aim was to investigate immune profiles in women with cocaine use disorder (CUD) according to withdrawal symptoms severity. Methods: Blood samples and clinical data were collected at onset of detoxification treatment of 50 women with CUD. The patients were stratified according to Cocaine Selective Severity Assessment (CSSA) scores in low withdrawal (L-W) and high withdrawal (H-W) categories. In addition, we also included a control group with 19 healthy women as reference to immune parameters. Peripheral blood was collected and lymphocyte subsets were phenotyped by multi-color flow cytometry (B cells, CD4 + T, CD8 + T, NK cells, and different stages of T-cell differentiation). PBMCs from patients and healthy controls were stimulated in vitro with phytohemagglutinin (1%) for 72 h to assess the production of Th1/Th2/Th17 cytokines. Results: Following stimulation, lymphocytes from women with CUD produced increased levels of Th1/Th2/Th17 cytokines. However, higher levels of IL-2 and IL-17 were observed only in the L-W group, while higher levels of IL-6 were detected in the H-W group compared to controls. H-W group showed lower percentage of early-differentiated Th cells (CD4 + CD27 + CD28 + ), elevated percentage of Th cells (CD3 + CD4 + ), intermediate-differentiated Th cells (CD4 + CD27 - CD28 + ), and B cells (CD3 - CD19 + ). Both CUD groups showed decreased percentages of naïve T cells (CD3 + CD4 + CD45RA + and CD3 + CD8 + CD45RA + ). Conclusion: Our data demonstrated that CUD can lead to increased production of Th1/Th2/Th17 cytokines and lymphocyte changes., (Copyright © 2019 Zaparte, Schuch, Viola, Baptista, Beidacki, do Prado, Sanvicente-Vieira, Bauer and Grassi-Oliveira.)

Introduction: Currently, hair straightening has become a regular hair treatment for women but likewise for men. Several studies have shown that thermal straightening has an influence on the concentration of ethyl glucuronide and of drugs of abuse content in hair. Heat treatment of hair may decrease concentrations of cocaine (COC) and of cocaethylene (CE) in hair and increase concentrations of benzoylecgonine (BZE). The goal of this study was to evaluate the influence of thermal straightening on anhydroecgonine methyl ester (AEME), a known cocaine smoking marker, in hair., Method: 42 positive COC hair samples were treated in vitro with iron plates heated to 200°C. During this treatment one lock of hair was put sequentially 30 times in contact with a hair straightener during 2s, the other lock was not treated. The hair samples were analyzed by a validated GC/MS method for AEME, COC and its metabolites BZE, norcocaine (NC), ecgonine methyl ester (EME) and CE., Results: After treatment, a median increase of concentrations was observed for AEME (110.3%) and BZE (27.6%) whereas a median decrease was found for COC (56.9%), NC (46.7%), EME (33.3%) and CE (41.7%). The median BZE/COC ratio of 0.6 in not treated hair increased to 1.5 in treated hair., Conclusion: Regarding our in vitro results, AEME may be produced by thermal hair straightening. Therefore, the presence of AEME in hair should not be used as an irrefutable prove of cocaine smoking. Our study shows that for the interpretation of AEME results in hair, potential heat treatment of hair should be considered. A ratio BZE/COC higher 1 appears to be a good marker to identify thermal treatment of hair before collection. Finally, thermal straightening should be documented during hair collection and should also be considered for the interpretation of COC results in hair., (Copyright © 2019. Published by Elsevier B.V.)

Given that external contamination must be considered in hair analysis, there is still a demand for reliable tools to differentiate between incorporation of drugs into the hair as a result of drug consumption and of the hair shaft by external contamination. With the aim of establishing alternative discrimination parameters, some of the hydroxy metabolites of cocaine i.e., para- and meta-hydroxycocaine and para- and meta-hydroxybenzoylecgonine were measured together with cocaine, benzoylecgonine, cocaethylene, and norcocaine in five seized street cocaine samples and in hair samples from different cohorts: cohort 1 (in vivo external contamination study, n = 28), cohort 2 (individuals with self-reported cocaine use, n = 92), and cohort 3 (individuals with suspected cocaine use or contamination, n = 198). Statistical evaluation of the data of cohort 1 and 2 using ROC curves yielded metabolic ratios indicating cocaine use. Based on these results, a decision workflow was established for the discrimination between cocaine use and external contamination. The power of this approach was finally statistically validated across the different cohorts., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To describe and compare the clinical and anatomical characteristics and outcomes of patients with and without known cocaine use who underwent thoracic endovascular repair for type B aortic dissections., Methods: Between January 2012 and January 2017, 186 patients underwent thoracic endovascular repair for type B aortic dissection at our institution. Clinical data and anatomical characteristics were collected under an institutional review board-approved protocol. Survival, reintervention, complications, and characteristics of dissection were compared between patients with cocaine use (C+; n = 14) and those with no known cocaine use (C-; n = 172)., Results: Cocaine users were more likely to be young African American males who smoked. They tended to present with more extensive dissections as evidenced by larger false lumen diameters. They also had higher rates of endoleaks and more reinterventions., Conclusions: These results suggest that special care should be taken to provide close follow-up for these patients., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Pneumothorax is one of the respiratory toxic effects of cocaine inhalation. The literature counts several cases, some associated to other respiratory conditions such as pneumomediastinum, haemoptysis and others not requiring surgical treatment., Aim: We present a series of nonHIV cocaine-inhaler subjects who underwent video-assisted thoracoscopic surgery (VATS) for isolated spontaneous pneumothorax., Design: Nine subjects, with a mean age of 24 ± 4 years, admitting cocaine inhalation, developed spontaneous pneumothorax and underwent 10 surgical treatments by means of VATS, at our Institution., Results: Previous pneumothorax occurred in six cases episodes ranged from 0 to 5 (mean 1.6 ± 1.6). Chest computed tomography (CT) scan showed abnormalities in seven cases. All subjects underwent lung apicectomy, apical pleurectomy and mechanical pleurodesis. Seven subjects had also bullectomy. In all cases the visceral pleura was partially covered by fibrinous exudate. Histology of the lung showed small foreign body granulomatous inflammation in fibrotic and/or emphysematous pulmonary parenchyma. Relapse of pneumothorax occurred in one subject at 60 days and it was surgically treated. Mean follow-up was 150 ± 38 months (range 120-239). All subjects are now well, with no evidence of pneumothorax., Conclusions: Spontaneous pneumothorax in cocaine-inhaler subjects is a reality of which physicians need to be aware. Chest CT scan might not reveal abnormalities. Macroscopically the lung might presents bullae and/or peculiar visceral pleura. Foreign body granulomas observed in the specimens suggest that the particulate component of inhaled substances can injure the lung. Surgical treatment of the bullous disease and mechanical pleurodesis can provide a long-term follow-up without relapse of pneumothorax., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cocaine can cause a myriad of changes in the lung, which can range from bronchoconstriction to destruction of the alveolar-capillary membrane and acute lung injury. Cocaine-induced bronchospasm is a diagnosis of exclusion that should be considered when the clinical presentation of acute hypoxic and hypercapneic respiratory failure cannot be explained by chronic obstructive pulmonary disease or asthma exacerbation, anaphylaxis to food or medications, exercise, or infection. Here, we present two patients with acute hypoxic and hypercapneic respiratory failure that was ultimately attributed to cocaine use shortly prior to symptom onset., (© 2019 Marshfield Clinic.)

There are many underlying mechanisms for cocaine-associated myocardial infarction, and the culprit must be elucidated for appropriate therapeutic management. Optical coherence tomography provides unique insights when angiography alone has limited diagnostic value; it also aids in the decision between conservative management and revascularization strategy and guides coronary interventions.

Background: Hair analysis is a suitable way to discriminate between coca chewers and consumers of manufactured cocaine using the coca alkaloids hygrine (HYG) and cuscohygrine (CUS) as markers. In the present preliminary study it was examined whether CUS and HYG can be detected in hair of occasional and moderate coca chewers or coca tea drinkers, whether CUS and HYG appear in hair of PACO consumers (smoking coca paste waste), and whether anhydroecgonine methyl ester (AEME) is a useful cocaine smoking marker in this context., Method: Three groups were included: 10 volunteers from Buenos Aires with occasional or moderate chewing of coca leaves or drinking coca tea, 20 Argentinean PACO smokers and 8 German cocaine users. The hair samples (1-4 segments) were analyzed by a validated LC-MS/MS method for cocaine (COC), norcocaine (NC), benzoylecgonine (BE), ecgonine methyl ester (EME), cocaethylene (CE), cinnamoylcocaine (CIN), tropacocaine (TRO), AEME, CUS and HYG. For comparison, eight samples of coca leaves or coca tea were analyzed., Results: Only low concentrations of COC were found in hair of seven occasional users of coca leaves or coca tea (0.010-0.051 ng/mg). For three moderate chewers of coca leaves all compounds were detected including AEME but except TRO. The hair samples of PACO smokers contained much higher concentrations of COC (0.027-341 ng/mg, mean 37.4 ng/mg) and its metabolites. CUS was not found in these samples but traces of HYG were seen in 8 of 37 hair segments. AEME as a marker for coca smoking was detected in hair of 15 smokers. In comparison to COC, the concentrations of EME and CIN were higher for PACO smokers than for German cocaine consumers. AEME (56 ± 20 μg/g) was detected in all coca leave and coca tea samples which explains the detection of this substance in hair of coca chewers. Therefore, its use for differentiation between coca chewers and PACO smokers is limited., Conclusion: CUS remains to be the most suitable marker in hair for chewing coca leaves or drinking coca tea more frequently than two times per month since it does not appear in hair of Argentinean PACO smokers and German cocaine users. Contrary to a previous proposal, the ratios CIN/COC and EME/COC appeared not to be applicable as criteria for this purpose because of the higher concentration of these alkaloids in hair of PACO smokers. More research is needed to assess the value of AEME in hair of South American coca leave or cocaine users., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A reliable method based on high-performance liquid chromatography-tandem mass spectrometry has been developed for the assessment of coca alkaloids/metabolites [cocaine (COC), benzoylecgonine (BE), cocaethylene (CE), ecgonine methyl ester (EME), anhydroecgonine methyl ester (AEME), tropococaine (TRO), transcinnamoylcocaine (trCIN), cuscohygrine (CUS) and hygrine (HYG)] in oral fluid samples from cocaine abusers and from coca leaves consumers (coca leaves chewers and coca tea drinkers). Oral fluid samples were collected by the passive drool technique (spitting), and after centrifugation the supernatant was treated for protein removal by adding acidified acetonitrile. The developed method was fully validated according to the international criteria and good results have been obtained (intraday and inter-day precisions were lower than ±20%, intraday and inter day accuracy was within the 75-116% range, and LODs/LOQs was lower and close to cut-off values for COC and BE). The proposed method has been successfully applied to oral fluid samples from cocaine abusers, and also from coca leave chewers and coca tea drinkers. CUS and HYG were only found in oral fluid from people who chewed coca leaves and drank coca tea and were not detected in cocaine abusers. Both CUS and HYG could be good markers in oral fluid for distinguishing people who consume coca leaves legally (coca leave chewers and coca tea drinkers) from those who consume illegal cocaine., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The consequences of cocaine use are multisystemic, such as, for instance, renal failure, hepatotoxicity and pulmonary toxicity, with renal alterations being the focus of the present study. The use of substances that modify the base composition of cocaine (or adulterants) aiming to potentiate its effects also has an impact on these manifestations. The present study aims to report three cases with different diagnosis of acute kidney injury related to cocaine use., Case Presentation: Case 01 - A 30-year-old female patient, who regularly used cocaine, started to have lower-limb edema, which showed a progressive and ascending evolution, affecting the face a few days later, associated with an isolated febrile episode and oligoanuria. The presence of cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA) was verified: reactive 1:80, with renal biopsy compatible with rapidly progressive glomerulonephritis (RPGN). Case 02 - A 34-year-old female patient, with difficult-to-control hypertension and a frequent user of cocaine, showed generalized sudden edema together with diffuse and progressive pruritus associated with oliguria, fever, nausea, and vomiting. Schistocyte screening was positive, with negative direct Coombs test, and negative serologies for hepatitis B, C and HIV, as well as negative anti-double-stranded DNA, Anti-SSA and Anti-SSB. The renal biopsy was compatible with thrombotic microangiopathy, associated with moderate interstitial fibrosis and acute tubular necrosis Case 03 - A 25-year-old male patient who had been a cocaine user for 5 years had a sudden onset of generalized disabling myalgia (especially in the lower limbs) associated with recent frontotemporal headache, palpitation, dizziness, and a non-measured febrile episode; the patient had used cocaine at the night before symptom onset. CPK was 1731 U/L.The final probable diagnosis was AKI secondary to cocaine-induced rhabdomyolysis., Conclusions: In conclusion basically, 05 etiologies of acute kidney injury should always be remembered: rhabdomyolysis, thrombotic microangiopathy, vasculitis, acute interstitial nephritis and renal infarction. Emphasis should be given to rhabdomyolysis due to its higher prevalence. Considering the increasing rates of cocaine use, especially with the use of adulterating substances, these pathologies will likely be increasingly prevalent.

Major depressive disorder (MDD) is the most prevalent comorbid mental disorder among people with substance use disorders. The MDD can be both primary and substance-induced and its accurate diagnosis represents a challenge for clinical practice and treatment response. Recent studies reported alterations in the circulating expression of inflammatory mediators in patients with psychiatric disorders, including those related to substance use. The aim of the study was to explore TNF-α, IL-1β, CXCL12, CCL2, CCL11 (eotaxin-1) and CX3CL1 (fractalkine) as potential biomarkers to identify comorbid MDD and to distinguish primary MDD from substance-induced MDD in patients with substance disorders. Patients diagnosed with cocaine (CUD, n = 64) or alcohol (AUD, n = 65) use disorders with/without MDD were recruited from outpatient treatment programs [CUD/non-MDD (n = 31); CUD/primary MDD (n = 18); CUD/cocaine-induced MDD (N = 15); AUD/non-MDD (n = 27); AUD/primary MDD (n = 16) and AUD/alcohol-induced MDD (n = 22)]. Sixty-two healthy subjects were also recruited as control group. Substance and mental disorders were assessed according to "Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision" (DSM-IV-TR) and a blood sample was collected for determinations in the plasma. The cocaine group showed lower TNF-α (p<0.05) and CCL11 (p<0.05), and higher IL-1β (p<0.01) concentrations than the control group. In contrast, the alcohol group showed higher IL-1β (p<0.01) and lower CXCL12 (p<0.01) concentrations than the control group. Regarding MDD, we only observed alterations in the cocaine group. Thus, CUD/MDD patients showed lower IL-1β (p<0.05), CXCL12 (p<0.05) and CCL11 (p<0.05), and higher CXC3CL1 (p<0.05) concentrations than CUD/non-MDD patients. Moreover, while CUD/primary MDD patients showed higher CCL11 (p<0.01) concentrations than both CUD/non-MDD and CUD/cocaine-induced MDD patients, CUD/cocaine-induced MDD patients showed lower CXCL12 (p<0.05) concentrations than CUD/non-MDD patients. Finally, a logistic regression model in the cocaine group identified CXCL12, CCL11 and sex to distinguish primary MDD from cocaine-induced MDD providing a high discriminatory power. The present data suggest an association between changes in inflammatory mediators and the diagnosis of primary and substance-induced MDD, namely in CUD patients., Competing Interests: The authors have declared that no competing interests exist.

A recombinant humanized anticocaine monoclonal antibody, h2E2, has shown potential in the preclinical phases for the treatment of cocaine abuse. The standard tests for cocaine usage are the detection of benzoylecgonine (BE) and cocaine in the urine. This includes workplace drug screens as well as in clinical trials for potential treatments of cocaine abuse. By sequestering cocaine into the plasma compartment, h2E2 prevents cocaine from entering the brain. Due to the altered disposition of cocaine in the presence of h2E2, we investigated the effects of h2E2 on cocaine and metabolite levels in the urine of rats to clarify the use of BE as an endpoint measurement for effectiveness in future clinical trials. The urine concentrations of cocaine and metabolites were considerably altered in the presence of h2E2. After a single injection of h2E2 (120 mg/kg) and cocaine hydrochloride (0.56 mg/kg), the concentration of cocaine and BE excreted into the urine of rats decreased by 92% and 91%, respectively, from vehicle controls. Due to the significant decrease in urinary excretion, BE is not an appropriate indicator of cocaine usage in the presence of h2E2. Another endpoint measurement must be selected for the measurement of cocaine usage in the upcoming clinical trials of h2E2. In contrast to the effects on cocaine and BE urinary excretion, there was a 3-fold increase in ecgonine methyl ester (EME) in the presence of h2E2. Therefore, we conclude that EME is a more appropriate measurement of cocaine intake in the presence of h2E2., (Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.)

Although cocaine induced myopathy and myotoxicity are described in the literature, we report a rare case of cocaine induced paraspinal myositis presenting with acute sciatic symptoms. A 35-year-old man presented with acute left-sided sciatica and was discharged from the emergency department (ED). He subsequently attended ED the following day in severe pain and bilateral sciatic symptoms, but denied symptoms of neurogenic bowel/bladder disturbance. Clinical examination was limited by severe pain: focal midline lumbar tenderness was elicited on palpation, per rectal and limb examinations were within normal limits with no significant neurological deficit. He was admitted for observation and pain management. His blood tests revealed a leucocyte count of 21.5×10 9 /L, C reactive protein of 89 mg/L and deranged renal function with creatinine of 293 μmol/L. An urgent lumbar spine MRI was arranged to rule out a discitis or epidural abscess. Lumbar MRI did not demonstrate any features of discitis but non-specific appearances of paraspinal inflammation raised the suspicion of a paraspinal myositis. Creatinekinase (CK) was found to be 66329 IU/L and a detailed history revealed he was a cocaine user. Paraspinal muscle biopsy confirmed histological features compatible with myositis. Other serological tests were negative, including anti-GBM, ANCA, ANA, Rheumatoid factor, Hep B, Hep C, myositis specific ENA, Treponema pallidum , Borrelia burgdorferi , Rickettsia , Leptospira , EBV and CMV. There was good clinical response to treatment with prednisolone 20 mg OD with an improvement in renal function, CK levels and CRP. He had resumed normal activities and return to work at 6-week follow-up. A detailed social history including substance misuse is important in patients presenting to the ED-especially in cases of severe musculoskeletal pain with no obvious localising features. Drug induced myotoxicity, although rare, can result in symptomatic patients with severe renal failure., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Numerous studies suggest that exercise may be an effective adjunct treatment for substance use disorders. It has been suggested that exercise-induced improvements in inhibitory control may reduce craving for the substance of abuse. However, this potential mechanism has seldom been researched., Objectives: The aim of the ExAlCo Study is to examine how acute bouts of exercise, at varying intensities, impact on craving for cocaine or alcohol. Cerebral haemodynamic responses during cognitive tests of inhibitory control, and exposure to substance-related cue imagery, will also be assessed using functional near-infrared spectroscopy., Design: The study is a crossover randomised controlled trial. Participants will be recruited from inpatient and outpatient psychiatric treatment centres, on the approval of their treating physician. A healthy control group will be recruited using online advertising. All participants will undergo each of three conditions in randomised order: 20 min of cycle ergometry at 50-60% of maximum heart rate; 20 min of exercise at 70-80% of maximum heart rate; and 20 min of quiet reading. Immediately before and after each condition, participants will be asked to complete a computerised Stroop test, watch a film containing substance-related images and self-report craving levels. During the Stroop test and film viewing, participants' neural activity will be measured via functional near-infrared spectroscopy., Outcomes: The primary outcome measures are self-reported craving, inhibitory control and cerebral haemodynamic response to the Stroop test and a substance-related film. It is hoped that the findings from this study will shed more light on the role of exercise in the treatment of substance use disorders, particularly its scope in preventing relapse through reduced craving severity., Trial Registration: ClinicalTrials.gov, NCT03502486 . Registered retrospectively on 5 April 2018.

Background: Clinical guidelines recommend psychosocial interventions for cocaine and/or amphetamine addiction as first-line treatment, but it is still unclear which intervention, if any, should be offered first. We aimed to estimate the comparative effectiveness of all available psychosocial interventions (alone or in combination) for the short- and long-term treatment of people with cocaine and/or amphetamine addiction., Methods and Findings: We searched published and unpublished randomised controlled trials (RCTs) comparing any structured psychosocial intervention against an active control or treatment as usual (TAU) for the treatment of cocaine and/or amphetamine addiction in adults. Primary outcome measures were efficacy (proportion of patients in abstinence, assessed by urinalysis) and acceptability (proportion of patients who dropped out due to any cause) at the end of treatment, but we also measured the acute (12 weeks) and long-term (longest duration of study follow-up) effects of the interventions and the longest duration of abstinence. Odds ratios (ORs) and standardised mean differences were estimated using pairwise and network meta-analysis with random effects. The risk of bias of the included studies was assessed with the Cochrane tool, and the strength of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We followed the PRISMA for Network Meta-Analyses (PRISMA-NMA) guidelines, and the protocol was registered in PROSPERO (CRD 42017042900). We included 50 RCTs evaluating 12 psychosocial interventions or TAU in 6,942 participants. The strength of evidence ranged from high to very low. Compared to TAU, contingency management (CM) plus community reinforcement approach was the only intervention that increased the number of abstinent patients at the end of treatment (OR 2.84, 95% CI 1.24-6.51, P = 0.013), and also at 12 weeks (OR 7.60, 95% CI 2.03-28.37, P = 0.002) and at longest follow-up (OR 3.08, 95% CI 1.33-7.17, P = 0.008). At the end of treatment, CM plus community reinforcement approach had the highest number of statistically significant results in head-to-head comparisons, being more efficacious than cognitive behavioural therapy (CBT) (OR 2.44, 95% CI 1.02-5.88, P = 0.045), non-contingent rewards (OR 3.31, 95% CI 1.32-8.28, P = 0.010), and 12-step programme plus non-contingent rewards (OR 4.07, 95% CI 1.13-14.69, P = 0.031). CM plus community reinforcement approach was also associated with fewer dropouts than TAU, both at 12 weeks and the end of treatment (OR 3.92, P < 0.001, and 3.63, P < 0.001, respectively). At the longest follow-up, community reinforcement approach was more effective than non-contingent rewards, supportive-expressive psychodynamic therapy, TAU, and 12-step programme (OR ranging between 2.71, P = 0.026, and 4.58, P = 0.001), but the combination of community reinforcement approach with CM was superior also to CBT alone, CM alone, CM plus CBT, and 12-step programme plus non-contingent rewards (ORs between 2.50, P = 0.039, and 5.22, P < 0.001). The main limitations of our study were the quality of included studies and the lack of blinding, which may have increased the risk of performance bias. However, our analyses were based on objective outcomes, which are less likely to be biased., Conclusions: To our knowledge, this network meta-analysis is the most comprehensive synthesis of data for psychosocial interventions in individuals with cocaine and/or amphetamine addiction. Our findings provide the best evidence base currently available to guide decision-making about psychosocial interventions for individuals with cocaine and/or amphetamine addiction and should inform patients, clinicians, and policy-makers., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: MJO is a consultant to Acadia Pharmaceuticals, Genomind, Johnson & Johnson/Janssen, Otsuka/Lundbeck, Sage Therapeutics, Sunovion, and Supernus Pharmaceuticals, and has received research funding from Palo Alto Health Sciences. All other authors have declared that no competing interests exist.

Aims: Little is known about outcomes of drug abuse related to attainment of stable housing. This study examined outcomes of cocaine use and service provision in an urban homeless sample., Methods: Two-year longitudinal study of systematically selected homeless individuals (N = 255) in St. Louis, Missouri from 1999 to 2001. The sample was interviewed three times annually using a structured diagnostic interview. Urine drug testing was conducted at every interview, and service utilisation data were obtained from the structured interviews and the agency-provided service use data., Results: Cocaine use disorder and cocaine use proved to be distinct concepts because they predicted different outcomes across time. Cocaine use predicted subsequent poor housing outcomes, but stable housing had no apparent effect on subsequent use of cocaine. Service use predicted neither subsequent reduced cocaine use nor attainment of stable housing. Services used were appropriate to type of mental health need, but cocaine use may have reduced successful utilisation of appropriate psychiatric services., Conclusion: These findings reinforce the concept that homelessness represents a complex phenomenon and consequently, service systems need to address multiple problems. Service approaches are needed that simultaneously address the complex needs of homeless individuals.

Aim: To estimate the prevalence of drug and polydrug use among drunk-drivers during the driving license regranting program, in order to assess the inclusion of toxicological tests on hair and urine samples in the systematic methodology in this category of subjects., Short Summary: A total of 2160 drunk-drivers were tested for alcohol and drugs during driving license regranting. Thirty-one subjects showed alcohol use, 212 illicit drug use and, among these, 131 were polydrug users. Nineteen different patterns of drug and polydrug use were found. Cocaine was detected in 165 subjects., Methods: The study was performed on 2160 drunk-drivers examined at Legal Medicine and Toxicology Unit of the University of Padova, in a 3-year-period (2014-2017). The positivity for one or more illicit drugs in hair or urine samples was confirmed by LC/MS and GC/MS methods. Chi-square test, Fischer's exact test and Cochran-Armitage Trend test were used to study the correlation between general characteristics of the examined sample and the presence of drug/polydrug use., Results: Thirty-one subjects showed alcohol use, 212 illicit drug use and, among these, 131 were polydrug users. Nineteen different patterns of drug and polydrug use were found. Cocaine was detected in 165 subjects in whom 122 showed a concurrent use of alcohol and cocaine, identified through the detection of cocaethylene in hair samples. No significant association and/or trends between drug/polydrug use and the general characteristics of the sample were detected., Conclusions: The results show that drug and polydrug use among drunk-drivers should be subjected to toxicological as well as alcohological monitoring, especially in the regranting procedure. The implementation of this procedure could improve the knowledge of dimensions of the issue, providing a powerful means for the reduction of phenomenon of driving under the influence of alcohol and drugs.

Objective: To evaluate the nutritional status of crack users and to analyze its correlation with drug use profiles., Methods: Cross-sectional study with 108 crack users. Anthropometric data were assessed through body mass index (BMI) and bioimpedance (BIA) measurements. A blood test to analyze hematocrit, hemoglobin, glucose, and lipid profiles was also performed. Crack use was determined through a standardized interview., Results: Based on BMI and BIA, most individuals were eutrophic (about 70%). Regarding hematological parameters, we found that hemoglobin and hematocrit levels were below normal for 32.4 and 30.6% of patients, respectively. Considering normal parameters, a large part of the sample (60.2%) had low levels of HDL cholesterol and high levels of triglycerides (38%). There were no significant correlations between drug profile and nutritional variables., Conclusion: This is a pioneering study that examines the nutritional status of crack users. Our results showed that most crack users present normal anthropometric findings and the prevalence of underweight is low. However, blood analysis showed changes and a specific type of malnutrition.

Approximately 10% of the U.S. population 12 years and older reported using illicit substances in 2015. This article reviews the clinical effects and treatment of persons who use cocaine, methamphetamines, 3,4-methylenedioxymethamphetamine (MDMA), synthetic cannabinoids, and synthetic cathinones ("bath salts"). Cocaine blocks the reuptake of the monoamine transporters dopamine, norepinephrine, and serotonin. Immediate clinical effects include increased energy and euphoria, as well as hypertension and arrhythmias. Acute myocardial infarction, seizures, hallucinations, hyperthermia, and movement disorders are among the possible adverse effects. Like cocaine, methamphetamine blocks reuptake of monoamine transporters, but also stimulates dopamine release and has a longer duration of action. Methamphetamine misuse is associated with severe dental problems. MDMA is a stimulant and psychedelic with a chemical structure similar to serotonin. Adverse effects include serotonin syndrome, hyponatremia, long-term memory impairment, and mood disorders. Synthetic cannabinoids can have a more intense and long-lasting effect than natural cannabis. Acute intoxication may cause severe cardiac and respiratory complications and seizures. Synthetic cathinones are marketed as cheap substitutes for other stimulants. Their effects are similar to those of other stimulants, and they are addictive. Psychosocial intervention is the main form of treatment for addiction to these substances. Promising therapies include disulfiram and substitution therapy for cocaine misuse disorders, and mirtazapine for methamphetamine use disorder.

Drugs which are commonly smoked or sniffed (e.g. cocaine), can contaminate hair through smoke or dust; therefore testing for metabolites, especially hydroxy metabolites, is highly recommended. The presence of hydroxy metabolites in street-cocaine (COC) has been discussed. To check if detection of hydroxy metabolites definitely proves ingestion, the presence of these metabolites in street COC samples has to be checked. It is expected that the more hydrophilic hydroxy metabolites of COC are incorporated into the hair-matrix to a lesser extent. For this study 576 COC positive hair samples (≥0.1ng COC/mg hair) were analysed by LC-MS/MS for benzoylecgonine (BE), norcocaine (NC), cocaethylene (CE), ortho-, meta- and para-hydroxy COC (o-, m-, p-OH-COC), meta- and para-hydroxy BE (m-, p-OH-BE), and meta- and para-hydroxy NC (m-, p-OH-NC). The results were compared with the respective metabolite/COC concentration ratios in 146 street COC samples, confiscated by the Bavarian police. Peak areas were used to estimate BE/COC, NC/COC, CE/COC and hydroxy metabolites/COC. Similar metabolic ratios were found for o-OH-COC in 88% of the samples, but for p-OH-COC and m-OH-COC only in 5.1% and 6.8%, respectively. Notably, p- and m-OH-BE as well as p- and m-OH-NC could not be identified from seized samples. We propose that area ratios exceeding the ratios of street COC more than twice or identification of OH-BE and OH-NC enable to differentiate COC consumption from contamination. Using these criteria, consumption of the drug could be proven in 92% of COC positive samples. As detection of meta- and para-hydroxy metabolites using the above mentioned criteria is a reliable tool to distinguish between ingestion and external contamination, it is recommended to implement their measurement into daily routine work., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Substance abuse is increasingly prevalent among young adults, but data on cardiovascular outcomes remain limited., Objectives: The objectives of this study were to assess the prevalence of cocaine and marijuana use in adults with their first myocardial infarction (MI) at ≤50 years and to determine its association with long-term outcomes., Methods: The study retrospectively analyzed records of patients presenting with a type 1 MI at ≤50 years at 2 academic hospitals from 2000 to 2016. Substance abuse was determined by review of records for either patient-reported substance abuse during the week before MI or substance detection on toxicology screen. Vital status was identified by the Social Security Administration's Death Master File. Cause of death was adjudicated using electronic health records and death certificates. Cox modeling was performed for survival free from all-cause and cardiovascular death., Results: A total of 2,097 patients had type 1 MI (mean age 44.0 ± 5.1 years, 19.3% female, 73% white), with median follow-up of 11.2 years (interquartile range: 7.3 to 14.2 years). Use of cocaine and/or marijuana was present in 224 (10.7%) patients; cocaine in 99 (4.7%) patients, and marijuana in 125 (6.0%). Individuals with substance use had significantly lower rates of diabetes (14.7% vs. 20.4%; p = 0.05) and hyperlipidemia (45.7% vs. 60.8%; p < 0.001), but they were significantly more likely to use tobacco (70.3% vs. 49.1%; p < 0.001). The use of cocaine and/or marijuana was associated with significantly higher cardiovascular mortality (hazard ratio: 2.22; 95% confidence interval: 1.27 to 3.70; p = 0.005) and all-cause mortality (hazard ratio: 1.99; 95% confidence interval: 1.35 to 2.97; p = 0.001) after adjusting for baseline covariates., Conclusions: Cocaine and/or marijuana use is present in 10% of patients with an MI at age ≤50 years and is associated with worse all-cause and cardiovascular mortality. These findings reinforce current recommendations for substance use screening among young adults with an MI, and they highlight the need for counseling to prevent future adverse events., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Cocaine use has been associated with adverse cardiovascular outcomes in patients with coronary artery disease (CAD). It is unclear whether this is due to direct effects of cocaine or other factors., Hypothesis: Cocaine use is associated with worse outcomes in patients undergoing cardiac catheterization METHODS: We used the Veterans Affairs database to identify veterans undergoing coronary catheterization between 2007 and 2014. We analyzed association between cocaine use and 1-year all-cause mortality, myocardial infarction (MI), and cerebrovascular accident (CVA) among veterans with obstructive CAD (N = 122 035). To explore factors contributing to these associations, we sequentially adjusted for cardiac risk factors, risky behaviors, and clinical conditions directly affected by cocaine., Results: 3082 (2.5%) veterans were cocaine users. Cocaine users were younger (median 58.2 vs 65.3 years; P < 0.001), more likely to be African American (58.9% vs 10.6%; P < 0.001), and had fewer traditional cardiac risk factors. After adjustment for cardiac risk factors, cocaine was associated with increased risk of mortality (HR: 1.23, 95% CI: 1.08-1.39), MI (HR: 1.40, 95% CI: 1.07-1.83), and CVA (HR: 1.88, 95% CI: 1.38-2.57). With continued adjustment, increased CVA risk remained significantly associated with cocaine use, whereas MI risk was mediated by risky behaviors and mortality was fully explained by conditions directly affected by cocaine., Conclusions: Cocaine use is associated with adverse cardiac events in veterans with CAD. Contributors to this association are multifaceted and specific to individual cardiovascular outcomes, including associated risky behaviors and direct effects of cocaine. Effective intervention programs to reduce cardiac events in this population will require multiple components addressing these factors., (© 2018 Wiley Periodicals, Inc.)

In this study, a quantitative polarity switching liquid chromatography coupled with a tandem mass spectrometer (LC-MS/MS) method was developed to detect and quantify cocaine and metabolites (cocaethylene, benzoylecgonine and meta-hydroxybenzoylecgonine), phencyclidine (PCP) and barbiturates (phenobarbital and butalbital) in meconium. Accuracy and precision samples at 0.0125% and 75% of the upper limit of quantitation (ULOQ) were analyzed in triplicate over 5 days with accuracy above 84% and average %CV values below 11%. Within-run (n = 15) and between-run (n = 15) %CV values were ≤5%. Analytical measurement ranges were reproducible and linear (R ≥ 0.995) for cocaine and metabolites (20-2,000 ng/g), PCP (10-1,000 ng/g) and barbiturates (50-5,000 ng/g). Accuracy of 100 ± 20% was observed at (the limits of detection) 10 ng/g for cocaine and metabolites, 2.5 ng/g for PCP and 25 ng/g for barbiturates. No carryover was observed at 2X ULOQ and no interfering substances were identified. Sample preparation recoveries were 53-83%. Fifty-one authentic patient samples previously characterized correlated with the newly developed test having R2 values ≥0.996. This combined method allows accurate quantitation of the targeted drugs in a complex matrix while decreasing sample preparation and analysis time with reduced sample volume. Clinical data and positivity rates were similar to previously published positivity rates. Validation data and positivity rate agreement signifies a reliable and robust assay.

Background: Cocaine use has a high prevalence in the United States and can be associated with significant cardiovascular disease, even in asymptomatic users. β-Adrenergic receptor hyperactivation is the underlying pathophysiologic pathway of cocaine cardiotoxicity. β-Blocker therapy is controversial in patients with active cocaine use., Hypothesis: β-Blocker therapy is associated with clinical improvement in patients with heart failure despite active cocaine use., Methods: In a single-center, retrospective chart analysis, patients with newly diagnosed heart failure and active cocaine use who had been started on β-blocker therapy were reviewed. The New York Heart Association (NYHA) functional class and the left ventricular ejection fraction (LVEF) were recorded at baseline and after 12 monthsnthsnths of β-blocker use. Patients were excluded if they had been on prior β-blocker therapy, had other reasons for volume overload, had chronic kidney disease stages G4 or G5, or had a life expectancy <12 months., Results: Thirty-eight patients were identified; most were African American males. A statistically significant improvement was found in both NYHA functional class (P < 0.0001) and LVEF (P < 0.0001) after 12 months of β-blocker therapy. No major adverse cardiovascular events occurred in this population., Conclusions: β-Blocker use in cocaine users with heart failure with a reduced ejection fraction is associated with a lower NYHA functional class and a higher LVEF at 12-month follow-up. No major adverse cardiovascular events were observed., (© 2018 Wiley Periodicals, Inc.)

Despite having been extensively discussed over the last decade, the differentiation between systemic exposure and external contamination still continues to be one of the limitations of hair testing for drugs. For this reason, we consider it worthwhile to re-state some basic principles in this short review. Various studies investigating a diversity of wash protocols, most using artificially contaminated hair with cocaine, have been valuable in evaluating wash efficacy and in understanding the incorporation of drugs in hair. However, assessments of wash efficacy made with real hair samples, as opposed to artificially contaminated samples, provide a different perspective, and demonstrate how rarely external contamination affects the interpretation of results. Data from a large number of hair samples from crack cocaine users, confirmed the usefulness of our protocol to remove most of the externally deposited cocaine. The data showed that hair levels of cocaine and benzoylecgonine in crack cocaine users were overall high with ratio of benzoylecgonine to cocaine in all samples above 0.1. The wash residue concentrations of cocaine ranged from not detected to 21ng/mg with a median of 0.5ng/mg. Cocaine was detected in the wash residue in 105 out of 138 samples. The wash to hair cocaine ratio ranged from not detected to 0.36 with a median of 0.02. The wash to hair cocaine ratios were below 0.07 in 133 cases. The five cases that produced wash to hair ratios above 0.1, one sample was at 0.11, three at 0.13 and one at 0.36, possibly because these cases were at the lower end of cocaine levels, however, we could not rule out that the hair was contaminated. Whilst it is not possible to differentiate between the drug extracted from the hair and the drug attached to the outside of the hair, we can compare levels of drug in the wash residue with levels detected in the hair sample. In addition, further diagnostic criteria must be applied to minimise potential misdiagnosis of external contamination. When drugs are detected in hair, individuals have clearly been in an environment where drugs are present, but it is only on rare occasions that it is unclear whether this is the result of drug use or of external contamination, and, in those cases, the results of testing need to be interpreted in the light of corroborating evidence from clinical data or social context., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Cocaine use disorder (CUD) is a debilitating condition with no NICE-recommended medication or specific psychosocial interventions. In the United Kingdom (UK), general counselling (treatment-as-usual; TAU) is widely delivered, but has limited effectiveness. We tested the feasibility, safety and preliminary efficacy of a novel, adjunctive psychosocial intervention for CUD, called 'memory-focused cognitive therapy' (MFCT)., Methods: We did a two-arm, external pilot randomised controlled trial at a specialist community National Health Service addictions clinic in London, UK. 30 adults (≥18years), voluntarily seeking treatment for CUD (enrolled ≥14days; all with moderate-to-severe DSM5 CUD), were individually randomised (1:1) to a control group (ongoing TAU; 3×90min CUD cognitive conceptualisation assessments; 2×30min cocaine-related cue-induction procedures; and 3×30min research follow-ups); or to an intervention group (ongoing TAU; 3×90min cognitive conceptualisation assessments; 2×30min cocaine-related cue-induction procedures; 5×120min, one-to-one, MFCT sessions [in 1week]; and 3×60min research follow-ups and MFCT-relapse prevention). The primary outcome was the total percentage score on the frequency version of the Craving Experiences Questionnaire (CEQ-F) at 1-month follow-up after the intensive intervention week (clinical endpoint; recall period past 2weeks; higher score indicating greater craving). Secondary outcomes at the 1-month follow-up were percentage days abstinent (PDA) from cocaine, and longest period (days) of continuous abstinence (LPA) in the prior 28days. Outcomes were analysed as an unadjusted group mean difference (with Hedge's g effect size [ES]) and a 95% Confidence Interval [CI] for the primary outcome and a 90% CI for the secondary outcomes. Exploratory, multivariable linear (primary outcome) and Poisson regression models (secondary outcomes), with sex, age, months of regular cocaine use, baseline outcome score, and group estimated the effectiveness of the intervention. The trial is registered with the ISCRTN (ISRCTN16462783)., Findings: Between July 15, 2015, and November 27, 2016, 58 patients were assessed for eligibility and 30 participants were randomised (14 to the control group and 16 to the intervention). With outcome data collected for all participants at the endpoint, the intervention group mean CEQ-F score (14·77; SD 21·47) was lower than the control group mean (51·75; SD 22·72); ES -1·62; 95% CI -2·45 to -0·80. MFCT was associated with more cocaine abstinence in the intervention group (PDA 85·94; SD 18·96) than the control group (PDA 54·59; SD 30·29); ES 1·19; 90% CI 0·54 to 1·84. There was also greater maximum abstinence in the intervention group (LPA 15·69; SD 10·10) than the control group (6·00; SD 7·36); ES 1·06; 90% CI 0·41 to 1·70. Exploratory, confounder-adjusted regression models for this preliminary effect supported the treatment association for reduced craving experiences (CEQ-F Coef. -28·25; 95% CI -45·15 to -11·35); more abstinence (PDA Incidence Rate Ratio [IRR] 1·56; 95% CI 1·31 to 1·88); and greater maximum abstinence (LPA IRR 2·56; 95% CI 1·96 to 3·35), although relative weak unmeasured confounding could overturn these model-adjusted exposure-outcome associations. There were four serious adverse events (among three participants). None were judged related to study procedures or interventions., Interpretation: In this first external pilot randomised controlled trial of MFCT for CUD, we have shown that the intervention and control procedures and acceptable feasible and safe, and report preliminary evidence that MFCT is associated with reduced craving and increased abstinence. These findings support progression to a substantive trial., Funding Source: UK National Institute for Health Research, Biomedical Research Centre., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

The κ-opioid receptor (KOP-r) system and its endogenous ligands, the dynorphins, are involved in the neurobiological regulation of addictive states, and of mood. There are limited data on the impact of selective KOP-r antagonism in humans on basic biobehavioral functions, or on addictive diseases and mood disorders. Previously studied selective KOP-r antagonists have unusual pharmacodynamic and pharmacokinetic properties (slow development of KOP-r selectivity, extremely long duration of action) that limit translation to human studies. A recently developed selective KOP-r-antagonist, Opra Kappa (LY2456302; CERC-501), has medication-like duration of action, oral bioavailability, and target engagement. The current study is the first investigation of the effects of a KOP-r-antagonist in cocaine-dependent persons in comparison with normal volunteers. In a stress-minimized inpatient setting, we determined the neuroendocrine and neurobehavioral effects of repeated administration of an active dose of Opra Kappa (10 mg p.o. daily, four consecutive days in comparison with an initial baseline day). Healthy volunteers (n=40), persons diagnosed with cocaine dependence in early abstinence (<2 months, EACD) (n=23), and drug-free former cocaine-dependent persons (7-month to 25-year abstinence, DFFCD) (n=7) were studied, with measurements including circulating neuroendocrine hormones, affect, and, in cocaine-dependent persons, cocaine craving. Modest adverse events related to Opra Kappa included pruritus, observed in a subset of individuals. No significant change was observed in serum prolactin levels following Opra Kappa administration, but modest increases in circulating adrenocorticotropic hormone and cortisol were observed. No significant changes were noted in measures of depression or cocaine craving in this stress-minimized setting. Overall, these studies demonstrate that effects of 10 mg Opra Kappa are largely consistent with those predicted for a selective KOP-r antagonist. This medication regimen was tolerable, and is therefore feasible for further studies in cocaine-dependent persons.

A 50-year-old man presented with acute onset dyspnea following cocaine use. He had severe aortic stenosis (AS), mild mitral regurgitation (MR) due to mitral valve prolapse, and no coronary artery disease on recent coronary angiography. He was in acute heart failure with signs of impending cardiogenic shock. Urgent bedside echocardiography revealed hyperdynamic left ventricular systolic function with acute severe MR from a ruptured chordae tendineae. The acute cocaine-induced spike of his already elevated left ventricular systolic pressure from severe AS likely precipitated chordal rupture of his vulnerable mitral valve. This patient underwent emergent mitral and aortic valve replacements. Although cocaine use has been associated with a myriad of cardiovascular complications, acute MR due to chordal rupture has not, to our knowledge, been previously reported in this setting. Prompt diagnosis with echocardiography and surgical intervention are of paramount importance in the management of acute MR., Competing Interests: Conflict of Interest Disclosure: The authors have completed and submitted the Methodist DeBakey Cardiovascular Journal Conflict of Interest Statement and none were reported.

Background: The aim of this study was to compare sociodemographic characteristics, patterns of drug use, and risky sexual behaviour among female and male users of crack cocaine., Methods: Between 2012 and 2013, we conducted a cross-sectional study of 919 crack cocaine users (783 men and 136 women) in Central Brazil using face-to-face interviews. Blood samples were collected to test for syphilis. The Chi-Square Automatic Interaction Detector (CHAID) was used to explore the differences between genders. We implemented two models: the first model included previous incarceration and variables related to patterns of drug use, and the second model included variables related to sexual risky behaviours and syphilis exposure., Results: Women consumed more crack cocaine than men on a regular basis; however, poly-drug use was more common among men. More women than men reported exchanging sex for money and/or drugs and inconsistent condom use during sexual intercourse; women also reported more sexual partners. In addition, the frequency of sexual violence was higher for women than men. A higher proportion of women than men were positive for syphilis (27.2% vs. 9.2%; p < 0.001). The CHAID decision tree analysis identified seven variables that differentiated the genders: previous incarceration, marijuana use, daily crack cocaine consumption, age at first illicit drug use, sexual violence, exchange of sex for money and/or drugs, and syphilis exposure., Conclusion: Our findings demonstrate a difference in patterns of crack cocaine consumption and sexual risky behaviours between genders, thus indicating a need for gender-specific interventions in this population.

Cocaine is a widely used illicit substance and has previously been described as a risk factor for aortic dissection. We present a case of a young recreational cocaine user with uncontrolled hypertension who presented to hospital with acute chest pain and was diagnosed with an acute aortic dissection. The patient's last use of powdered cocaine was 3 days prior. A workup for secondary hypertension was negative and no other risk factors for aortic dissection were determined. In hospital, the patient was medically managed with multiple antihypertensive agents, was provided with education regarding the risk of ongoing stimulant use and resources to support his goal of abstinence. This case highlights the importance of considering a diagnosis of aortic dissection in a young patient presenting with acute chest pain, underscores the need for a thorough substance use history and provides a novel example of the potential danger of even recreational cocaine use., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: A single LC-MS equipment was used to validate three methods for simultaneously analyzing cocaine (COC), benzoylecgonine (BZE), cocaethylene (CE), anhydroecgonine methyl ester (AEME) and anhydroecgonine (AEC) in oral fluid (OF), urine and plasma., Methods: The methods were carried out using a Kinetex HILIC column for polar compounds at 30°C. Mobile phase with isocratic condition of acetonitrile: 13mM ammonium acetate pH 6.0: methanol (55:35:10 v/v/v) at 0.8mL/min flow rate was used., Results: After buffer dilution (OF) and protein precipitation (urine and plasma), calibration curve ranges were 4.25-544ng/mL for oral fluid and 5-320ng/mL for urine and plasma with correlation coefficients (r) between 0.9947 and 0.9992. The lowest concentration of the calibration curves were the lower limit of quantification. No major matrix effect could be noted, demonstrating the efficiency of the cleaning procedure., Discussion: The methods were fully validated and proved to be suitable for analysis of 124 cocaine and/or crack cocaine users. Among the subjects, 56.5% reported daily use of cocaine in the previous three months. Results show a high prevalence of the analytes, with BZE as the most prevalent (94 cases), followed by COC (93 cases), AEC (70 cases), CE (33 cases) and AEME (13 cases). In addition, the concentration of BZE in urine was higher compared to OF and plasma found in the real samples, showing the facility of accumulation in chronic users in matrices with a large detection window., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Hair testing is a recognized approach when it comes to accessing historical drug use. According to the World Drug Report of United Nations Office on Drugs and Crime (UNODC) 2015, Brazil is the largest cocaine (COC) market in South America. New analytical methodologies to detect crack/cocaine analytes in hair samples are highly desirable. Here, a method consisting of a liquid-phase microextraction (LPME) as a clean-up step, followed by gas chromatography-mass spectrometry (GC-MS) analysis has been proposed. The new validated method consisted of a washing step; an overnight incubation with methanol and a quick derivatization with butylchloroformate. Once derivatized, the samples were then submitted to the LPME procedure. Limits of detection (LoD) and quantitation (LoQ) obtained were of 0.1 and 0.5ng/mg for COC 0.4 and 0.5ng/mg for anhydroecgonine methyl ester (AEME); 0.03 and 0.05 for cocaethylene (CE), respectively and 0.05ng/mg for both LoD and LoQ for benzoylecgonine (BZE). All calibration curves were linear over the scope applied, from LoQ up to 20ng/mg, with a r 2 >0.99. Precision and accuracy assays showed acceptable %RSD values, according to international guidelines. Twelve postmortem head hair samples stemming from the Institute of Legal Medicine of Sao Paulo (IML-SP) have been analyzed, from which seven have shown to be positive for COC (0.75->20ng/mg) and BZE (0.1->20ng/mg). Apart from COC's main metabolite, four samples were also positive for CE (0.1-3.9ng/mg) and three samples for AEME (0.5-4.9ng/mg). To conclude, the LPME technique together with GC-MS analysis have shown promising results and were able to meet the demand of the laboratory of analyzing postmortem hair samples to look for all four analytes., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Levamisole is an antihelminthic drug with immunomod- ulatory properties. Recent estimates suggest the majority of the cocaine in the United States is adulterated with levamisole. Le- vamisole-induced necrosis syndrome (LINES) is characterized by vasculitis, neutropenia, and purpura that progresses to skin necro- sis. Diagnosis relies on physical examination ndings and history of previous cocaine use. The purpose of this case series is to describe the pathophysiology, diagnosis, and management of LINES. The au- thors' institutional database was reviewed from 2008 to 2015, and they found 3 patients with LINES. Subsequent management and outcomes data are discussed. Patients had a variety of outcomes ranging from local wound care to necrosis and amputation of pha- langes. Patients with LINES can have a wide variety of outcomes; thus, this syndrome must be aggressively managed. Psychotherapy should also be utilized to help patients with further cocaine use. Levamisole-induced necrosis syndrome incidence is expected to in- crease, and all providers should be aware of this patient population.