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Background: Methadone maintenance is an effective treatment for opioid use disorder (OUD), yet many methadone-maintained patients (MMPs) struggle with cocaine use during OUD recovery. The current study aimed to identify whether prefrontal cortex (PFC) activity during a risky decision-making task was associated with cocaine use during a 90-day follow-up in MMPs., Methods: MMPs (N = 28) attended a single neuroimaging session wherein PFC activity was measured using functional near-infrared spectroscopy (fNIRS) during the Balloon Analogue Risk Task (BART). Trait impulsivity was assessed via the Barratt Impulsiveness Scale version 11 (BIS-11). Following the neuroimaging session, MMPs were tracked via electronic health records for 90 days to determine treatment outcomes including cocaine use verified by urine drug screens., Results: During the BART, MMPs who used cocaine displayed increased neural activity in the right PFC during active decision-making (F 1, 22  = 14.75, p = 0.001) and the right dorsolateral PFC during active minus passive decision-making (F 1, 22  = 5.56, p = 0.028) compared to participants who did not use cocaine. Receiver operating characteristic curves confirmed that neural activity in the right PFC during active decision-making (AUC = 0.841, 95% CI, 0.697-0.985, p = 002), and in the right dorsolateral PFC during active minus passive decision-making (AUC = 0.805, 95% CI, 0.643-0.968, p = 0.006) was associated with continued cocaine use. MMPs who used cocaine versus those who did not reported increased trait impulsivity on the BIS-11 Total Score (t=-2.28, p = 0.031)., Conclusions: The fNIRS device is portable, relatively easy to use, and potentially feasible for use in methadone outpatient programs to assess propensity for negative treatment outcomes such as continued cocaine use., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Cocaine use disorder (CUD) is a common problem in the United States and worldwide. The mechanisms by which cocaine induces acute cardiovascular toxicity are various. When systemically absorbed through inhaled or intravenous routes, cocaine induces an acute rise in the heart rate (HR) and blood pressure (BP) leading to a significant increase in the cardiac output (CO) and myocardial oxygen demand. Subjects with chronic CUD represent a special population that has experienced long-term cocaine exposure, often without showing signs of cardiovascular disease. We herein present prospectively collected data on the acute hemodynamic effects of intravenous cocaine in a cohort of nontreatment-seeking individuals with CUD without cardiovascular disease., Methods and Results: Baseline physiologic data were collected while participants underwent infusion of escalating doses of cocaine (10, 20, and 40 mg administered over 2 minutes) at baseline and after receiving single-blind placebo treatment. Continuous noninvasive hemodynamic monitoring was performed throughout the infusion sessions using the ccNexfin finger cuffs (Edwards Lifesciences Corp, Irvine, CA). The recorded arterial BP tracings allowed for the measurement of beat-to-beat changes in HR, BP, stroke volume, CO, and systemic vascular resistance (SVR). None of the subjects experienced a treatment-related serious adverse event. Cocaine produced significant dose-dependent increases in median HR, BP, CO, and +dP/dt (a measure of cardiac contractility) and a significant dose-dependent reduction in median SVR., Conclusions: Intravenous cocaine in a cohort of otherwise healthy subjects with CUD produced dose-dependent increases in CO, largely explained by an increase in HR, accompanied by a dose-dependent decrease in SVR.

Introduction: Personality disorders (PD) and substance use disorders (SUD) have a high prevalence and an important health and socioeconomic impact so, it is interesting to study the relationship between them. The objectives of the study are: to compare the prevalence of SUD between patients with and without diagnosis of PD, to analyze if any PD is related to the SUD, and if a specific PD is associated with a specific SUD., Material and Methods: Cross-sectional study in 837 patients from centers of attention to drug addiction and mental health in Madrid, Spain. The Mini International Neuropsychiatric Interview (MINI) and the Personality Diagnostic Questionnaire-4+ (PDQ4+) are used to detect mental disorder and PD, respectively., Results: SUD is significantly higher in antisocial PD (p<0.01); sedative (p<0.01) and alcohol (p<0.05) use disorder in borderline PD; cocaine (p<0.05) and alcohol (p<0.01) use disorder in paranoid PD; and alcohol use disorder in histrionic PD (p<0.01). The SUD for cocaine is lower in obsessive- compulsive PD (p<0.05) and depressive PD (p<0.01). There is a positive correlation between the number of PD of a subject and the number of SUD that it presents. The risk of an alcohol [OR of 1,08 CI (1,01-1,16)] or sedatives [OR of 1,08 CI (1,001-1,17)] use disorders increases if an individual presents more than one type of PD., Conclusions: There is not differences of SUD prevalence between PD and not PD groups. We found an association between SUD and PD of cluster B (antisocial, borderline and histrionic) and also with paranoid PD. The SUD are more common among man with the exception of sedatives.

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.)

This review aims to consolidate the available information on use of electroretinography as a diagnostic tool in psychiatry. The electroretinogram (ERG) has been found to have diagnostic utility in cocaine withdrawal (reduced light-adapted b-wave response), major depressive disorder (reduced contrast gain in pattern ERG), and schizophrenia (reduced a- and b-wave amplitudes). This review examines these findings as well as the applicability of ERG to substance use disorder, Alzheimer's disease, autism spectrum disorder, panic disorder, eating disorders, attention deficit hyperactivity disorder, and medication use. While there have been promising results, current research suffers from a lack of specificity. Further research that quantifies anomalies in ERG present in psychiatric illness is needed., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

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.)

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.)

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: There is growing emphasis in the field of psychiatry on the need to identify candidate biomarkers to aid in diagnosis and clinical management of addictive disorders. MicroRNAs (miRNAs) are small nucleotide sequences with the ability to regulate gene expression at the transcriptomic level. However, the role of miRNAs as potential biomarkers for addiction is still underexplored. Based on translational and clinical findings, we compared the expression levels of microRNA-124 (miR-124), microRNA-181 (miR-181), and microRNA-212 (miR-212) between a group of females with cocaine use disorder (CUD; n = 30) and a group of healthy female controls (HC; n = 20)., Methods: Blood expression levels of miR-124, miR-181, and miR-212 in the HC and CUD group were determined by qPCR, using two miRNAs as endogenous controls (miR-24 and miR-126). Substance use behavior was assessed by self-report using the Addiction Severity Index (ASI-6) and depressive symptoms severity was measured using the Beck Depressive Inventory (BDI-II). Urine screen test was performed to detect cocaine metabolites., Results: Mir-124 and miR-181 were upregulated in the CUD group (p > 0.01). Furthermore, increased cognitive/affective depression symptoms were identified among a CUD subgroup with the higher miR-181 expression levels (p > 0.05). No significant difference in expression levels was found for miR-212., Conclusions: MiR-124 and miR-181 show promise as biomarkers for CUD when assessed in the peripheral blood. Further investigation is needed to elucidate the molecular mechanisms underlying these associations and to validate target genes regulated by these miRNAs., (Copyright © 2019 Elsevier Ltd. 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: Cocaine is associated with deleterious effects in the heart, including HFrEF. Although β-blockers are recommended for this condition in other populations, their use is discouraged in cocaine users due to the possibility of exacerbating cocaine-related cardiovascular complications. This study was designed to determine if patients with heart failure and a reduced ejection fraction (HFrEF) who continue to use cocaine have better outcomes when they receive β-blocker therapy than when they do not., Methods: We performed a retrospective analysis of 72 β-blocker-naïve patients with HFrEF and active cocaine use. Patients who were prescribed β-blockers as part of their therapy were compared to those who were not, and clinical and structural outcomes were compared after 12 months of treatment., Results: When patients with HFrEF and active cocaine use received β-blocker therapy, they were more likely to have an improvement in their New York Heart Association functional class (p = 0.0106) and left ventricular ejection fraction (p = 0.0031) than when they did not receive β-antagonists. In addition, the risk of cocaine-related cardiovascular events (p = 0.0086) and of heart failure hospitalizations (p = 0.0383) was significantly lower in patients who received β-blockade than those who did not., Conclusions: β-Blocker therapy is associated with improvement in the exercise tolerance and the left ventricular ejection fraction in patients with HFrEF and active cocaine use. They are also associated with a lower incidence of cocaine-related cardiovascular events and HFrEF-related readmissions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Prenatal cocaine exposure (PCE) has been linked to child/adolescent behavior problems and substance use in several longitudinal cohort studies. It is unclear whether these effects extend into adulthood and influence young adult behavior problems and substance use and, if so, whether they are mediated by childhood and adolescent experiences., Methods: These data are from an ongoing longitudinal study of individuals born to women who were recruited early in pregnancy. Trimester-specific data on prenatal drug exposure were obtained. Caregivers and offspring were assessed at delivery and at 1, 3, 7, 10, 15, and 21 years postpartum. This report is from age 21, when 225 offspring (52% females; 54% African American, 46% Caucasian) reported on behavior problems, emotion regulation, and substance use., Results: There were significant direct associations between PCE and early initiation of marijuana, 21-year emotion regulation problems, arrest history, and Conduct Disorder. The relation between PCE and young adult internalizing behavior was mediated by adolescent mood symptoms. The association between PCE and 21-year marijuana use was mediated by early initiation of marijuana use., Conclusions: PCE has both direct and indirect long-term associations with young adult development. Using statistical models that considered the complex interrelationships among PCE and adult outcomes, we demonstrated that the direct effects of PCE on young adult emotion regulation problems, arrest history, and Conduct Disorder are not completely explained by earlier adolescent behavior. Moreover, the analyses suggesting mediated pathways from PCE to young adult problems identify crucial variables to target interventions for exposed children and adolescents., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.

Background: Since 2000, heroin use patterns have shifted within the United States. How this change may relate to polydrug use among local heroin users is unknown. Although polydrug use has been studied, user perceptions of drug use in terms of health risks, arrest risk, availability, cost, liking, and dependence have not been considered., Methods: Data are presented from a brief, face-to-face survey conducted in 2016 of 200 non-in-treatment heroin users from Cleveland, OH. We assessed the use of and attitudes on alcohol, marijuana, methamphetamine, heroin, crack cocaine, powder cocaine, and prescription drugs. We estimated polydrug (concurrent past month) use with cluster analysis and latent profiles. Regression analysis estimated the strength of relationships between attitudes and frequency of use., Results: We identified five clusters: Cluster 1 used heroin concomitantly with alcohol and occasionally crack; Cluster 2 used heroin and crack cocaine daily; Cluster 3 used heroin daily and almost exclusively; Cluster 4 used heroin and marijuana daily; and Cluster 5 were part-time drug users. Drug use frequency was associated with liking and being anxious when drugs could not be obtained. High perceived availability of heroin and cocaine and low cost facilitated polydrug use., Conclusions: Understanding polydrug use clusters among heroin users is important for addressing the larger opioid epidemic. Users' perceptions of a drug's availability and cost appeared to facilitate polydrug use and justify more detailed future research on drug access., (Copyright © 2018. Published by Elsevier B.V.)

Background: Polysubstance use (PSU) is prevalent among individuals with substance use disorders, but the vast majority of preclinical substance use research has focused on individual substances in isolation. Cocaine has been prevalent in the repertoire of persons who use more than one illicit substance., Methods: We conducted a meta-analysis combining results from literature searches and secondary data analyses to estimate the prevalence of simultaneous and concurrent cocaine + alcohol and cocaine + cannabis use among cocaine users. We next summarized the small body of literature on behavioral, cognitive and neurobiological consequences of cocaine PSU across species, with a focus on alcohol and cannabis. Finally, we used systematic literature searches to assess the extent to which human and animal studies on the neurobiological consequences of cocaine include PSU subjects., Results: The estimated prevalence of simultaneous and concurrent alcohol use among human cocaine users was 74% and 77%, respectively. The estimated prevalence of simultaneous and concurrent cannabis use among cocaine users was 38% and 64%, respectively. Consumption of alcohol or cannabis with cocaine enhances subjective responses to cocaine, concomitant with changes in cocaine metabolism that increase blood cocaine levels, and, in the case of alcohol, produce the psychoactive metabolite cocaethylene. There is also consistent evidence for neurobiological effects of cocaine + alcohol combinations. However, animal PSU research with cocaine lags behind human research., Conclusion: Based on the prevalence and known consequences of PSU, consideration of PSU in both human and animal research is vital for understanding patterns of substance use., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.

Rationale: Theoretical accounts highlight the importance of drug-related cues for the development and persistence of drug-taking behavior. Few studies have evaluated the ability of spatially contiguous drug cues to bias decisions between two concurrently presented non-drug reinforcers., Objective: Evaluate the contribution of spatially contiguous cocaine cues to choice between two concurrently presented monetary reinforcers METHODS: Participants with cocaine use disorder completed a cued concurrent choice task. Two cues (one cocaine and one control image) were presented side-by-side followed by concurrent monetary offers below each image. Concurrent choice was measured for cocaine-side advantageous, equal, and disadvantageous concurrent monetary offers. The primary dependent measure was bias for selecting cocaine-cued monetary reinforcers. Three experiments tested selectivity of cocaine-cued bias in individuals with a cocaine use history (Experiment 1), replication when including additional control trials (Experiment 2), and a potential attentional mechanism evaluated using eye-tracking technology (Experiment 3)., Results: Significant and robust cocaine-cued bias at equal monetary value was observed in three experiments (mean percent choice = 65-77%) and higher Drug Abuse Screening Test (DAST) scores were associated with greater cocaine-choice bias. These experiments demonstrated that cocaine-cued bias was (1) selective to individuals with a cocaine use history, (2) specific to trials involving a cocaine cue, and (3) partially associated with attentional bias., Conclusions: These experiments provide evidence that drug-related cues can influence choice and potentially promote maladaptive decision making during concurrent choice events. Future research evaluating prospective associations of drug-cued bias with drug-associated behaviors will help reveal the clinical relevance for substance use disorder.

Cocaine is an illegal drug; its abuse and toxicity are a public health problem due to its high morbidity and mortality. Cocaine can affect the cardiovascular, central nervous and respiratory systems. The case of a 42-year-old male without history of chronic or degenerative diseases, but previous cocaine consumption is presented in this report. The patient is admitted to the Emergency Department given that the clinical presentation included hemoptysis and dyspnea with mild to minimal activity, which evolved to orthopnea. Advanced airway management was required and supportive care at the Intensive Care Unit was provided. Imaging studies showed evidence compatible with alveolar hemorrhage diagnosis. In search of an autoimmune etiology, an antibody-screening panel was requested, reporting negative results for autoimmune disorders. The patient management was based on corticosteroid therapy and plasmapheresis to counter the persistent hemoptysis and hemoglobin serum level decline. The management strategy was based on the clinical suspicion of vasculitis and a torpid clinical evolution. Pulmonary sepsis ensued, resulting in patient's death. The necropsy report describes the primary cause of death as diffuse alveolar hemorrhage secondary to diffuse alveolar injury. This case report presents the detailed clinical, imagining and histopathological findings of a patient with alveolar hemorrhage secondary to cocaine consumption, as well as a review of the literature., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Cocaine use in Australia is increasing, with approximately 2.5% of the surveyed population having used cocaine. In the USA, levamisole, a widely used anti-helminthic veterinary drug has been increasingly detected as a cutting agent in cocaine seizures. Levamisole is known to cause agranulocytosis in humans. We ascertained the prevalence of levamisole-adulterated cocaine, detectable in the urine from patients that had undergone a pathology request for a urine drug screen. We assayed routinely requested urines that were positive for cocaine on immunoassay with liquid chromatography high resolution quadrupole time of flight mass spectrometry (LC-QToF). We investigated available urine samples from a period of 2 years that had a positive result for cocaine. In addition, we examined samples that were below the cut-off for cocaine on immunoassay. Specimens were analysed for the presence of levamisole and other 'unknown' drugs. In the period under investigation the laboratory examined 3665 urine samples for cocaine: 1.4% (n = 51) of the samples were positive for cocaine by immunoassay and half of these (n = 26, 51%) were further examined by LC-QToF. In addition, we examined 10 samples that were negative by immunoassay (as defined by AS/NZS 4308:2008). Levamisole was detected in the urine of cocaine users in approximately 75% of cases. Other illicit drugs were also frequently found in this cohort. The most common illicit drugs detected were methamphetamine, ecstasy and cannabis. Australian cocaine is widely adulterated with levamisole. Cocaine users are at risk of levamisole related health problems in addition to the problems related to cocaine., (Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Cocaine use causes significant cardiovascular morbidity from its hemodynamic effects. It is less clear whether cocaine promotes atherosclerosis. Vascular inflammation is one of the earliest steps in the pathophysiology of atherosclerosis. We hypothesized that cocaine results in an increase in inflammatory markers. Study objective was to measure the acute effects of intravenous cocaine on biomarkers of vascular inflammation. Eleven chronic cocaine users were enrolled. After a drug-free period, they received intravenous cocaine at 0.36 mg/kg dose in an in-hospital controlled environment. Serum levels of soluble CD40 ligand, monocyte chemoattractant protein-1, interleukin 6, and soluble intercellular adhesion molecule-1 were measured at baseline, 6 h, 24 h, and 6 days after cocaine challenge and at baseline for controls. After cocaine challenge, sCD40 ligand levels decreased in subjects and were significantly lower at 24 h. MCP-1 levels decreased and were significantly lower at the 6-day time point. No significant changes in IL-6 or sICAM-1 level were found. In conclusion, intravenous cocaine did not result in an increase in levels of inflammatory markers. Levels of MCP-1 and sCD40L decreased significantly. This unexpected finding suggests that chronic effects of cocaine on inflammation may be different from acute effects or that higher dosing may have differential effects as compared to lower dose used here.

Background: Cocaine abuse has been reported as leading to impaired cognitive function. However, cocaine abusers commonly also abuse alcohol, which can itself produce cognitive impairment. This study, therefore, aimed to examine the potential confounding effect of alcohol abuse on neuropsychological test performance in cocaine and alcohol abusing individuals, comparing them with individuals who abused alcohol alone and non-abusing controls., Methods: Nineteen cocaine abusers who also met DSM-IV criteria for alcohol abuse/dependence (14 m, 5f; mean age 38.65 ± 3.83) and 20 matched individuals who met criteria for alcohol abuse/dependence alone (12 m, 8f; mean age 38.19 ± 4.82) were administered a battery of neuropsychological tests covering executive function, memory, language and visual/visuospatial function after two to four weeks of abstinence. Nineteen matched healthy controls (8 m, 11f; mean age 37.01 ± 5.98) were also tested., Results: Both the cocaine + alcohol group and the alcohol group performed significantly more poorly than the healthy controls on the executive (ESs 2.13 and 2.57) and memory tests (ESs 0.58 and 1.06). The findings were similar for language (ESs 0.92 and 1.69), where the cocaine + alcohol abusers additionally performed significantly better than the alcohol abusers. Both patient groups were impaired on two of the five tests of visual/visuospatial function, with better performance by the cocaine + alcohol group on one of them., Conclusions: Chronic cocaine abuse does not appear from this study to be associated with cognitive impairment over and above that which can be attributed to co-existent alcohol abuse., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.)

Background: The use of β-blocker therapy in the setting of acute coronary syndrome (ACS) associated with cocaine consumption (ACS-ACC) is discouraged due to the risk of coronary vasoconstriction. We examined the prognostic value of β-blocker therapy in a contemporary ACS cohort., Methods and Results: Prospective, single-center study conducted between January 2001 and December 2014 that examined cocaine use among young (≤50-year-old) consecutive patients admitted with an ACS. During the study period, 1002 patients were admitted; of these, 57 (5.7%) had a positive cocaine urine test We collected data on clinical characteristics and major adverse cardiovascular events (MACE) during follow-up. Among ACS-ACC patients, 33 (57.9%) received β-blocker therapy during hospital admission and after discharge. During a median follow-up of 4.0 (IQR: 2.4-6.5) years after the index event, 2 (6.1%) patients treated with β-blocker therapy died and 6 (18.2%) experienced hospital re-admission for myocardial infarction (MI); in contrast, there were 5 (20.8%) deaths and 5 (20.8%) readmissions due to MI in patients without β-blocker therapy. Lower rates of MACE were observed in patients treated with β-blocker therapy (30.3%) than those without β-blocker therapy (41.7%). The 90-day survival was higher in patients treated with β-blocker therapy (87.5% vs. 100%; Log rank test p = 0.035)., Conclusions: In patients with ACS-ACC, β-blocker treatment was associated with a significantly better clinical outcome, with lower rates of death and MI. Our findings support the evidence for long-term β-blocker administration in high-risk patients and highlight the need for large prospective multicenter studies of β-blocker treatment in ACS-ACC., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A molecularly imprinted polymer - Mn-doped ZnS quantum dot-based fluorescence probe for cocaine abuse screening has been prepared and applied to complex samples such as serum and oral fluid. The fluorescent sensing material was prepared by anchoring a selective MIP for COC on the surface of polyethylene glycol (PEG) modified Mn-doped ZnS quantum dots (QDs). Simple and low cost methods have thus been optimized for assessing cocaine abuse in serum and oral fluid by monitoring fluorescence quenching when cocaine (COC) is present (optimized operating conditions with 1.5mL of 200mgL -1 MIP-coated QDs solution, pH 5.5, and 15min before fluorescence scanning). The matrix effect was found to be important when analyzing oral fluid and serum, and several strategies based on centrifugation for oral fluid and solid phase extraction (SPE) for serum were explored. Two analytical methods were developed for oral fluid. The first one (direct method) requires a centrifugation step (6°C, 4000rpm, 20min) to avoid the matrix effect, and allows for cocaine determination by using an aqueous calibration (1:20 dilution). The second method was developed for oral fluid sampled by Salivette devices, and also requires a further centrifugation (6°C, 4000rpm, 20min) of the recovered oral fluid. This method, however, requires the standard addition technique (1:20 dilution) because of the existence of the matrix effect. Regarding serum samples, a direct method (serum dilution) was not possible, and an SPE procedure was needed to avoid the matrix effect (use of aqueous calibration). The limits of detection and quantification when using the Salivette method were 0.035mgL -1 and 0.117mgL -1, respectively; whereas, 0.015mgL -1 (LOD) and 0.050mgL -1 (LOQ) were obtained for serum., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Urine adulteration is a concern among patients treated for opioid use disorder. Quantitative urine testing for buprenorphine (B) and norbuprenorphine (NB), and the appropriate interpretation of B and NB levels, can facilitate constructive conversations with patients that may lead to modifications in the treatment plan, and strengthening of the patient-provider relationship., Case Summary: Three cases are presented in which discordant urine B and NB levels were recognized. Each patient was submerging buprenorphine/naloxone strips in their urine to mask ongoing illicit drug use. The authors used an approach to addressing intentional adulteration of urine samples that adheres to the principles of harm-reduction, the centrality of the patient-provider relationship, and the acknowledgment that ongoing illicit drug use and subsequent dishonesty about disclosure may be common among persons with substance use disorders. Each of the three patients ultimately endorsed diluting their urine, which allowed for strengthening of the patient-provider relationship and modifications to their treatment plans. Two of the three patients stabilized and achieved abstinence, while the third was eventually referred to a methadone treatment program., Conclusion: Providers should routinely monitor B and NB levels, rather than qualitative screening alone, and discordant levels should elicit a timely conversation with the patient. The authors use of a nonjudgmental approach to address urine adulteration, including giving patients an opportunity to reflect on potential solutions, has been effective at helping patients and providers to reestablish a therapeutic alliance and maintain retention in treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Crack-cocaine is an important public health problem in Brazil and worldwide. It is a potent form of cocaine which results in rapid and damaging stimulating effects on the central nervous system through inhibition of the dopamine transporter. Some studies have suggested that both food and drugs - including crack, can act on the same brain reward mechanisms, altering the dopamine pathways that modulate behavioral responses. Our hypothesis was that leptin, a well-known peptide that modulates energy metabolism and appetite, can be used as a biomarker for drug use., Methods: Anthropometric data, drug use profiles, and leptin serum levels were evaluated in a cross-sectional study of 40 crack-cocaine users., Results: Leptin showed an inverse correlation with the severity of crack use, and this correlation remained when corrected by body mass index (BMI) and body composition by bioimpedance (BIA). The majority of subjects were eutrophic or overweight/obese considering BMI and BIA, and these variables were not significantly associated with the severity of crack use, but positively correlated with leptin levels., Conclusions: Our preliminary findings suggest that leptin could be involved in drug use severity, perhaps through pathways similar to those whereby it modulates food intake. Considering the anthropometric parameters, these findings provide additional evidence that low weight is not predominant in crack users., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.)