Epidemiology, clinical features and management of patients presenting to European emergency departments with acute cocaine toxicity: comparison between powder cocaine and crack cocaine cases.

Objective: To analyse the epidemiology, clinical picture and emergency department (ED) management of a large series of patients who presented to European EDs after cocaine consumption, comparing data from powder (C1 group) and crack (C2 group) consumers. Methods: Between October 2013 and December 2016, the Euro-DEN Plus Registry recorded 17,371 consecutive acute recreational drug toxicity presentations to 22 EDs in 14 European countries. Epidemiological and demographic data, co-ingestion of alcohol and other drugs, clinical features, ED management and outcome (death) were analysed for cocaine cases, and comparison of clinical picture in C1 and C2 patients were performed adjusting for alcohol and other drug co-ingestion. Results: We included 3002 cases (C1: 2600; C2: 376; mixed consumption: 26): mean age 32(9) years, 23% female. The proportion of presentations involving cocaine varied significantly between countries (>30% in Malta, Spain, France, Denmark) and only centres in France, United Kingdom, Poland, Ireland and Malta recorded crack-related cases. Cocaine was frequently used with ethanol (74.3%, C1>C2) and other drugs (56.8%, C2>C1), the most frequent amphetamine (19.4%, C1>C2) and opioids (18.9%, C2>C1). C2 patients were more likely to have clinically significant episodes of hypotension (adjusted OR = 2.35; 95%CI = 1.42-3.89), and bradypnea (1.81; 1.03-3.16) and systolic blood pressure >180 mmHg on ED arrival (2.59; 1.28-5.25); while less likely anxiety (0.51; 0.38-0.70), chest pain (0.47; 0.31-0.70), palpitations (0.57; 0.38-0.84), vomiting (0.54; 0.32-0.90), and tachycardia on ED arrival (0.52; 0.39-0.67). Sedative drugs were given in 29.3%. The median length of hospital stay was 4:02 h, 22.1% patients were hospitalized, and 0.4% (n = 12) died. Conclusion: Cocaine is commonly involved in European ED presentations with acute recreational drug toxicity, but there is variation across Europe not just in the involvement of cocaine but in the proportion related to powder versus crack. Some differences in clinical picture and ED management exist between powder cocaine and crack consumers.

Detoxification, oxidative stress, and cytogenotoxicity of crack cocaine in the brown mussel Perna perna.

The presence of cocaine and its metabolites and by-products has been identified in different aquatic matrices, making crack cocaine the target of recent studies. The aim of this study was to evaluate the sublethal effects of crack on the brown mussel Perna perna. Mussels were exposed to three concentrations of crack cocaine (0.5, 5.0, and 50.0 µg L-1) for 168 h. Gills, digestive glands, and hemolymph were extracted and analyzed after three different exposure times using a suite of biomarkers (EROD, DBF, GST, GPX, LPO, DNA damage, ChE, and lysosomal membrane stability [LMS]). After 48 and 96 h of exposure, EROD, DBF, GST, GPX activities and DNA strand breaks in the gills increased significantly after 48 and 96 h of exposure. Alterations in LMS were also observed in the mussels exposed to all crack concentrations after 96 and 168 h. Our results demonstrated that crack cocaine is metabolized by CYP-like and GST activities in the gills. GPX was not able to prevent primary genetic damage, and cytotoxic effects in the hemocytes were also observed in a dose- and time-dependent response. Our study shows that the introduction of illicit drugs into coastal ecosystems must be considered a threat to marine organisms.

Occurrence of bacterial and toxic metals contamination in illegal opioid-like drugs in Iran: a significant health challenge in drug abusers.

BACKGROUND: The toxic metals and/or bacterial contaminants in illicit drugs are the main health problems in drug users worldwide. Hence, the potential risks of these contaminants were evaluated in some of the illicit drugs during 2015 and 2016. METHODS: The metals analysis were performed using graphite furnace atomic absorption spectrophotometry. In addition, all microbiological analysis stages, including handling procedures, dilution, and culture media, were conducted in accordance with the US Pharmacopeia (USP) which are harmonized with the European Pharmacopoeia (EP). RESULTS: In the present study, the highest lead (Pb; 138.10 ± 75.01 µg/g) and chromium (Cr; 447.38 ± 20.27 µg/g) levels were detected in opium samples. In addition, the highest prevalence of microbial contamination was observed in opium samples, and the lowest was recorded in heroin samples. Clostridium tetani, with about 50% of contaminant, was the most common bacteria in the analyzed samples. CONCLUSIONS: Our results indicate that Pb exposure as well as bacterial contamination could be the major threats for drug users. Graphical Abstract ᅟ.

DARK Classics in Chemical Neuroscience: Cocaine.

In this Review, we consider the story of cocaine from its humble origins in South America to its status as one of the most abused substances in 21st century society. The synthesis and biosynthesis of cocaine are discussed, as well as its pharmacokinetics, metabolism, pharmacology, and importance in modern neuroscience and molecular imaging.

The DARK Side of Total Synthesis: Strategies and Tactics in Psychoactive Drug Production.

Humankind has used and abused psychoactive drugs for millennia. Formally, a psychoactive drug is any agent that alters cognition and mood. The term "psychotropic drug" is neutral and describes the entire class of substrates, licit and illicit, of interest to governmental drug policy. While these drugs are prescribed for issues ranging from pain management to anxiety, they are also used recreationally. In fact, the current opioid epidemic is the deadliest drug crisis in American history. While the topic is highly politicized with racial, gender, and socioeconomic elements, there is no denying the toll drug mis- and overuse is taking on this country. Overdose, fueled by opioids, is the leading cause of death for Americans under 50 years of age, killing ca. 64,000 people in 2016. From a chemistry standpoint, the question is in what ways, if any, did organic chemists contribute to this problem? In this targeted review, we provide brief historical accounts of the main classes of psychoactive drugs and discuss several foundational total syntheses that ultimately provide the groundwork for producing these molecules in academic, industrial, and clandestine settings.

Analysis of cocaine/crack biomarkers in meconium by LC-MS.

Fetal exposure to illicit drugs is a worldwide problem, since many addicted women do not stop using it during pregnancy. Cocaine consumed in powdered (snorted or injected) or smoked (crack cocaine) form are harmful for the baby and its side effects are not completely known. Meconium, the first stool of a newborn, is a precious matrix usually discarded, that may contain amounts of substances consumed in the last two trimesters of pregnancy. Analyzing this biological matrix it is possible to detect the unaltered molecule of cocaine (COC) or its metabolite benzoylecgonine (BZE) and pyrolytic products anhydroecgonine methyl ester (AEME) and anhydroecgonine (AEC). A liquid chromatography mass spectrometry (LC-MS) method was validated for meconium samples after solvent extraction, followed by direct injection of 10µL. Linearity covered a concentration range of 15 to 500ng/mg with a lower limit of quantification (LLOQ) of 15ng/mg for all analytes. Matrix effect was evaluated and showed adequate results. Detection of illicit substances usage can be crucial for the baby, since knowing that can help provide medical care as fast as possible. The method proved to be simple and fast, and was applied to 17 real meconium samples.

Correlation between cocaine prices and purity with trends in emergency department visits in a major metropolitan area.

Illicit drug use not only causes acute and chronic adverse health outcomes but also results in a significant burden to health care providers. The objective of this study is to examine the relationship between cocaine prices and purity with emergency department (ED) visits for the Chicago-Naperville-Joliet metropolitan area. Our primary outcome was number of cocaine-related ED visits per quarter provided by the Drug Abuse Warning Network. The predictor variables of cocaine purity and price were provided by the System to Retrieve Information from Drug Evidence database. Autoregressive integrated moving average (ARIMA) regressions were used to estimate the effects of cocaine price and purity on cocaine-related ED visits. Although cocaine prices did not change substantially over time, cocaine purity decreased by over 30 % between 2006 and 2010. ARIMA regression results suggest that cocaine-related ED visits were not significantly associated with powder or crack cocaine prices; however, a decrease in powder cocaine purity was associated with 2,081 fewer ED visits overall from 2007 to 2010. The cocaine trade continues to be a major public health and law enforcement threat to large metropolitan cities like Chicago. Regular monitoring of cocaine purity levels may provide early warning of impending changes in cocaine-related ED visits for law enforcement and health care providers.

Purity and adulterant analysis of crack seizures in Brazil.

Cocaine represents a serious problem to society. Smoked cocaine is very addictive and it is frequently associated with violence and health issues. Knowledge of the purity and adulterants present in seized cocaine, as well as variations in drug characteristics are useful to identify drug source and estimate health impact. No data are available regarding smoked cocaine composition in most countries, and the smoked form is increasing in the Brazilian market. The purpose of the present study is to contribute to the current knowledge on the status of crack cocaine seized samples on the illicit market by the police of São Paulo. Thus, 404 samples obtained from street seizures conducted by the police were examined. The specimens were macroscopically characterized by color, form, odor, purity, and adulterant type, as well as smoke composition. Samples were screened for cocaine using modified Scott test and thin-layer chromatographic (TLC) technique. Analyses of purity and adulterants were performed with gas chromatography equipped with flame ionization detector (GC-FID). Additionally, smoke composition was analyzed by GC-mass spectrometry (MS), after samples burning. Samples showed different colors and forms, the majority of which is yellow (74.0%) or white (20.0%). Samples free of adulterants represented 76.3% of the total. Mean purity of the analyzed drug was 71.3%. Crack cocaine presented no correlations between macroscopic characteristics and purity. Smoke analysis showed compounds found also in the degradation of diesel and gasoline. Therefore, the drug marketed as crack cocaine in São Paulo has similar characteristics to coca paste. High purity can represent a greater risk of dependency and smoke compounds are possibly worsening drug health impact.

Powder and crack cocaine use among opioid users: is all cocaine the same?

OBJECTIVES: Problematic cocaine use is highly prevalent and is a significant public health concern. However, few investigations have distinguished between the 2 formulations of cocaine (ie, powder and crack cocaine) when examining the characteristics of cocaine use. Moreover, research has yet to assess the patterns of powder and crack cocaine use among opioid users, a clinical population in which problematic cocaine use is increasingly common. Using a within-subjects design, this study examined whether opioid users reported different patterns and features of powder and crack cocaine use, along with distinct trajectories and consequences of use. METHODS: Seventy-three clients enrolled in a low-threshold methadone maintenance treatment were interviewed regarding their lifetime use of powder and crack cocaine. RESULTS: Compared with crack cocaine, initiation and peak use of powder cocaine occurred at a significantly younger age. In relation to recent cocaine use, participants were significantly more likely to report using crack cocaine than using powder cocaine. Differences in routes of administration, polysubstance use, and criminal activity associated with cocaine use were also found between the 2 forms of cocaine. CONCLUSIONS: Results suggest that it may not be appropriate to consider powder and crack cocaine as diagnostically and clinically equivalent. As such, researchers may wish to distinguish explicitly between powder and crack cocaine when assessing the characteristics and patterns of cocaine use among substance users and treat these 2 forms of cocaine separately in analyses.

Development and practical application of accelerated solvent extraction for the isolation of cocaine/crack biomarkers in meconium samples.

A method using accelerated solvent extraction (ASE) for the isolation of cocaine/crack biomarkers in meconium samples, followed by solid phase extraction (SPE) and the simultaneous quantification by gas chromatography-mass spectrometry (GC-MS) was developed and validated. Initially, meconium samples were submitted to an ASE procedure, which was followed by SPE with Bond Elut Certify I cartridges. The analytes were derivatizated with PFP/PFPA and analyzed by GC-MS. The limits of detection (LOD) were between 11 and 17ng/g for all analytes. The limits of quantification (LOQ) were 30ng/g for anhydroecgonine methyl ester, and 20ng/g for cocaine, benzoylecgonine, ecgonine methyl ester and cocaethylene. Linearity ranged from the LOQ to 1500ng/g for all analytes, with a coefficients of determination greater than 0.991, except for m-hydroxybenzoylecgonine, which was only qualitatively detected. Precision and accuracy were evaluated at three concentration levels. For all analytes, inter-assay precision ranged from 3.2 to 18.1%, and intra-assay precision did not exceed 12.7%. The accuracy results were between 84.5 and 114.2% and the average recovery ranged from 17 to 84%. The method was applied to 342 meconium samples randomly collected in the University Hospital-University of São Paulo (HU-USP), Brazil. Cocaine biomarkers were detected in 19 samples, which represent 5.6% of exposure prevalence. Significantly lower birth weight, length and head circumference were found for the exposed newborns compared with the non-exposed group. This is the first report in which ASE was used as a sample preparation technique to extract cocaine biomarkers from a complex biological matrix such as meconium samples. The advantages of the developed method are the smaller demand for organic solvents and the minor sample handling, which allows a faster and accurate procedure, appropriate to confirm fetal exposure to cocaine/crack.

Plasmapheresis and steroid treatment of levamisole-induced vasculopathy and associated skin necrosis in crack/cocaine users.

BACKGROUND: Levamisole was removed from the market due to complications of agranulocytosis and skin necrosis. Levamisole has been reported in a high proportion of seized cocaine in North America and has been associated with multiple cases of skin necrosis. OBJECTIVE: We report three cases of levamisole/cocaine-induced skin necrosis who responded to treatment with plasmapheresis and immunosuppression. RESULTS: Three patients presented with painful necrotic skin lesions on the ears, cheeks, breasts, and buttocks. The extremities were involved in two patients and the upper respiratory tract mucosa in one patient. All had markers of immune activation, with elevated C-reactive protein, antinuclear antibody, and perinuclear antineutrophil cytoplasmic antibody. Skin biopsy in all cases revealed a mixed pattern of thrombosis and vasculitis within dermal vessels, with overlying ischemic ulceration of skin and soft tissues. One patient required extensive débridement of the skin and soft tissue of the calves and also had respiratory involvement. All patients were treated with plasmapheresis and immunosuppression with rapid stabilization and/or improvement of the lesions. CONCLUSION: Levamisole is frequently added to crack/cocaine; we report three patients who developed vascular lesions and skin necrosis after using cocaine/levamisole. These improved with plasmapheresis and immunosuppression as well as abstention from the drugs; one patient with severe disease required débridement and skin grafting.

Composición química de muestras de bazuco incautado en Colombia primer semestre de 2010 / Quantifying the chemical composition of crack-cocaine (bazuco) samples seized in Colombia during the first half of 2010

Objetivos Cuantificar cocaína e identificar otros componentes bajo las condiciones de estudio en muestras de bazuco incautadas en Colombia que proceden del Laboratorio de Estupefacientes del Instituto Nacional de Medicina Legal y Ciencias Forenses Regional Bogotá durante el primer semestre de 2010. Métodos Estudio analítico exploratorio de corte transversal con el fin de caracterizar químicamente muestras de bazuco por la metodología analítica de cromatografía de gases con espectrometría de masas de trampa iónica desarrollada y validada en el Laboratorio de Toxicología Facultad de Medicina Universidad Nacional de Colombia Sede Bogotá. Resultados De las 109 muestras analizadas se encontró la concentración de cocaína como base entre 4 y 70 % p/p, con una media de 37 % p/p. El 73 % de las muestras tiene una concentración entre el 20 y 50 % p/p. Otros alcaloides de coca como tropacocaína, transcinamoilcocaína, norcocaína y ecgoninametilester fueron identificados. Se identifico cafeína en el 57 % de las muestras y fenacetina en el 2,8 % como adulterantes presentes. Discusión Se realiza un análisis sobre la importancia toxicológica de los resultados para los consumidores de bazuco dada la característica de consumidores crónicos.

Objectives Quantifying crack-cocaine (known locally as bazuco or smokable cocaine base paste-PBC) use and identifying other components in study conditions regarding samples of crack-cocaine seized in Colombia and held by the Colombian Institute of Legal Medicine and Forensic Science Narcotics Laboratory in Bogota during the first half of 2010. Methods A cross-sectional, exploratory analytical study was carried out for chemically characterizing crack-cocaine samples by the gas chromatography analytical methodology using ion trap mass spectrometry developed and validated in the Universidad National de Colombia's Medicine Faculty's Toxicology Laboratory in Bogota. Results A 4 % to 70 % w/w cocaine base concentration was found in the 109 samples tested (37 % w/w mean); 73 % of the samples had 20 % to 50 % w/w concentration. Other coca alkaloids were identified, such astropacocaine, trans-cinnamoylcocaine, norcocaine and ecgonine methyl ester. Caffeine was identified as an adulterantin 57 % of the samples and phenacetin in 2.8 % of them. Discussion The toxicological significance of the results concerning crack-cocaine consumers was quantified, given the profile for chronic users.

[Quantifying the chemical composition of crack-cocaine (bazuco) samples seized in Colombia during the first half of 2010]. / Composición química de muestras de bazuco incautado en Colombia primer semestre de 2010.

OBJECTIVES: Quantifying crack-cocaine (known locally as bazuco or smokable cocaine base paste-PBC) use and identifying other components in study conditions regarding samples of crack-cocaine seized in Colombia and held by the Colombian Institute of Legal Medicine and Forensic Science Narcotics Laboratory in Bogota during the first half of 2010. METHODS: A cross-sectional, exploratory analytical study was carried out for chemically characterizing crack-cocaine samples by the gas chromatography analytical methodology using ion trap mass spectrometry developed and validated in the Universidad National de Colombia's Medicine Faculty's Toxicology Laboratory in Bogota. RESULTS: A 4 % to 70 % w/w cocaine base concentration was found in the 109 samples tested (37 % w/w mean); 73 % of the samples had 20 % to 50 % w/w concentration. Other coca alkaloids were identified, such astropacocaine, trans-cinnamoylcocaine, norcocaine and ecgonine methyl ester. Caffeine was identified as an adulterantin 57 % of the samples and phenacetin in 2.8 % of them. DISCUSSION: The toxicological significance of the results concerning crack-cocaine consumers was quantified, given the profile for chronic users.

An analysis of cocaine powder in the Netherlands: content and health hazards due to adulterants.

AIMS: To report on trends in the content and adulterants present in street cocaine (powder) in the Netherlands and to describe the associated health hazards. DESIGN AND PARTICIPANTS: Drug consumers handed in samples of cocaine powder from 1999 to 2007 for analysis. Reports were compiled of users' experiences with the samples received. MEASUREMENTS AND ANALYSIS: Linear regression analysis was used to assess the trend in adulterated cocaine powder across the study period, and comparison of reported adverse effects of adulterated with those of unadulterated cocaine by Fisher's exact test. FINDINGS: There has been a statistically significant upward trend in the occurrence of adulterated cocaine powder over the years. Adulterated cocaine was associated more frequently with reported adverse effects than unadulterated cocaine. Phenacetin, hydroxyzine and diltiazem appeared to be three adulterants contributing to these adverse effects. CONCLUSIONS: An increase in adulterants was detected in the analysed cocaine powder between 1999 and 2007. This increase is associated with relatively more adverse effects with cocaine use. The cardiac and hallucinatory effects that were reported more frequently are not understood clearly. Adverse effects are likely to be due to several factors, including interactions of adulterants with cocaine and the route of administration.

Is there epidemiological evidence to support the idea that a cocaine dependence syndrome emerges soon after onset of cocaine use?

The present study uses latent class methods and multiple regression to shed light on hypothesized cocaine dependence syndromes experienced by community residents, who initiated cocaine use within 24 months of survey assessment, and explores possible variation in risk. Identified within public use data files from the United States National Household Surveys on Drug Abuse (NHSDA), and with assessments completed between 1995 and 1998, the study sample consists of 927 recent-onset cocaine users, defined as having initiated cocaine use no more than 24 months prior to assessment (approximate median elapsed time since onset of use approximately 12-13 months). The NHSDA included items to assess seven clinical features often associated with cocaine dependence, which were used in latent class modeling. Empirically derived latent classes, in conjunction with prior theory, tend to support a three-class solution, according to which 4% of recent-onset users are members of a class that resembles the DSM-IV cocaine dependence syndrome (mean: 5.4 clinical features (CF)); 16% might be in a cocaine dependence prodrome (mean: 2.4 CF); 80% of recent-onset cocaine users had few or no clinical features (mean<1 CF). Results from latent class regressions indicate that susceptibility to rapid transition from first cocaine use to onset of the LCA-assigned cocaine dependence syndrome might depend upon whether the user starts smoking crack-cocaine and, independently, age at first cocaine use.