Juliana Nichterwitz Scherer

Simultaneous determination of cocaine/crack and its metabolites in oral fluid, urine and plasma by liquid chromatography-mass spectrometry and its application in drug users

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

High levels of brain-derived neurotrophic factor are associated with treatment adherence among crack-cocaine users

Due to the complexity of crack -cocaine addiction treatment, the identification of biological markers that could help determining the impact or outcome of drug use has become a major subject of study. Therefore, we aim to evaluate the association of Brain-Derived Neurotrophic Factor (BDNF) and Thiobarbituric Acid Reactive Substances (TBARS) levels in crack -cocaine users with treatment adherence and with drug addiction severity. A sample of 47 male inpatient crack- cocaine users were recruited in a treatment unit, and blood samples were collected at admission and discharge in order to measure BDNF and TBARS serum levels. Subjects were split into 2 groups: treatment non-completers (n=23) and treatment completers (n=24). The completer group had a tendency of higher levels of BDNF than non-completers at admission (16.85±3.24 vs. 14.65±5.45, p=0.10), and significant higher levels at discharge (18.10±4.88 vs. 13.91±4.77, p=0.001). A negative correlation between BDNF levels at admission and years of crack use was observed. We did not find significant changes in TBARS levels during inpatient treatment, although the completer group tended to decrease these levels while non-completers tend to increase it. These findings suggest an association between higher levels of BDNF and better clinical outcomes in crack- cocaine users after detoxification. We believe that the variation in BDNF and TBARS found here add evidence to literature data that propose that such biomarkers could be used to better understand the physiopathology of crack- cocaine addiction.

Oral Fluid Testing for Cocaine: Analytical Evaluation of Two Point-of-Collection Drug Screening Devices.

The use of point-of-collection testing (POCT) devices for drugs of abuse in oral fluid (OF) is an advantageous tool that has been used for different purposes-particularly traffic enforcement. However, even with the widespread report of cocaine consumption, the reliability of POCT devices has been reported in different magnitudes. This study evaluated the reliability of two POCT devices for the detection of cocaine in OF samples of 110 cocaine users: (i) the DDS2™ (cutoff = 30 ng/mL) and (ii) the Multi-Drugs Multi-Line-Twist Screen Test Device™ (MDML) (cutoff = 20 ng/mL). Results of the screening tests were compared with a Liquid Chromatography-Mass Spectrometry (LC-MS) assay. Sensitivity, specificity and accuracy of DDS2™ were 100, 77.77 and 80% when compared with LC-MS with a cutoff of 30 ng/mL, and 88.89, 89.15 and 89.09% with a cutoff of 10 ng/mL. The MDML™ device achieved sensitivity, specificity and accuracy of 100, 65.6 and 70.9% when compared with LC-MS with a cutoff of 20 ng/mL, and 92.6, 71.1 and 76.6% with a cutoff of 10 ng/mL. When compared with a 10 ng/mL cutoff, the DDS2™ achieved reliability parameters higher than 80%. On the other hand, the MDML™ device did not achieve the minimal recommendation of 80% for all parameters at the same time. Taking into consideration the reliability results showed here, the authors believe that the use of these POCT devices seems to be suitable for cocaine detection in forensic tests only if all positive specimens are further confirmed by a validated method.

Reliability of point-of-collection testing devices for drugs of abuse in oral fluid: A systematic review and meta-analysis

&NA; Point‐of‐collection testing (POCT) devices for drugs of abuse are used to screen for the presence of psychoactive substances (PAS) in different types of settings and environments. However, these quick and advantageous tools also present disadvantages, including low‐reliability measures in comparison to chromatographic assays. Therefore, this article presents a systematic review and meta‐analysis of studies evaluating the reliability of measurements of PAS detection in oral fluid using POCT devices. The reliability measures for detection of the five most important drug classes – cocaine, amphetamines, benzodiazepines, cannabinoids and opioids, are reported. The article also presents a subgroup analysis considering the reliability estimates for the different POCT devices that were evaluated by the studies contemplated in the review. A discussion considering the strengths and limitations of POCT techniques was performed in order to guide policymakers, traffic agents and other professionals who also conduct such tests. The use of POCT devices often involves legal and moral aspects of the subjects tested, which demands critical evaluation of these devices before they are implemented in different settings.

Active Brazilian crack cocaine users: nutritional, anthropometric, and drug use profiles

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.

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

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

Anxiety and depression symptoms in Brazilian sexual minority ecstasy and LSD users

BACKGROUND This study examined drug use patterns and psychiatric symptoms of anxiety and depression among young Brazilian sexual minority ecstasy and LSD users and compared findings with those reported for their heterosexual peers. METHOD This cross-sectional study employed targeted sampling and ethnographic mapping approaches via face-to-face interviews conducted at bars and electronic music festivals using an adapted, semi-structured version of the Global Appraisal of Individual Needs questionnaire. The sample comprised 240 male and female young adults who had used ecstasy and/or LSD in the 90 days prior to the interview and who were not on treatment for alcohol and drug abuse. RESULTS Of the 240 subjects enrolled (mean age: 22.9±4.5 years), 28.7% were gay or bisexuals. Multivariate regression analysis showed that the prevalence of depression symptoms in the past 12 months in the sexual minority group was 37% higher than among heterosexuals (prevalence ratio [PR]=1.79; 95% confidence interval [95%CI] 1.03-3.11; p=0.037). CONCLUSION Strategies should be developed to assess and address individual needs and treatment approaches should be tailored to address depressive symptoms in young, sexual minority club drug users.

Leptin levels and its correlation with crack-cocaine use severity: A preliminary study

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.

Brain-derived neurotrophic factor in substance use disorders: A systematic review and meta-analysis

BACKGROUND Brain-derived neurotrophic factor (BDNF) is associated with several neurodegenerative and psychiatric disorders. It is not clear, however, whether BDNF levels are modified in substance use disorders (SUDs). METHODS We conducted a systematic search of electronic databases to identify studies comparing peripheral plasma or serum BDNF levels in adults with SUDs vs. non-user controls. Forty studies were included in the meta-analysis involving a total of 2238 participants with SUDs and 2574 controls. RESULTS After trim and fill adjustment, current drug users presented lower serum BDNF levels (SMD = -0.99, 95%CI -1.40 to -0.58, I2 = 95.9) than non-user controls. However, this difference disappears during withdrawal. Studies using serum or plasma BDNF samples have shown different results. Subgroup analysis revealed lower levels of serum BDNF in alcohol users (SMD = -0.70, 95%CI -1.15 to -0.25, I2 = 89.81) and crack/cocaine users (SMD = -1.78, 95%CI -2.92 to -0.65, I2 = 97.59) than controls. Meta-regression analysis revealed that gender, age, and age of first use moderate the effects of drug use in peripheral BDNF levels. CONCLUSIONS Peripheral BDNF levels are decreased in the serum, but not the plasma, of active drug users. Altogether, these findings suggest that BDNF levels may be related to acute use and addiction severity and also point to BDNFs potential utility as a biomarker in this population.

Hepatitis C: clinical and biological features related to different forms of cocaine use

INTRODUCTION Hepatitis C virus (HCV) infection is related with several liver diseases such as cirrhosis and hepatocellular carcinomas, leading to more than 0.5 million deaths every year and to a great global burden. It is known that injection drug users show a high prevalence of HCV infection, being considered a risk group for this disease. Cocaine users seem to be in greater risk than other drug users, and several hypotheses for this association are being studied. AIM To review data on HCV infection in cocaine users, taking into consideration the relevance of the different routes of drug administration and other risk behaviors. METHODS This was a narrative review performed in the main scientific databases. RESULTS AND CONCLUSION Data suggest that cocaine use could be associated with HCV infection due to the specificities of cocaine consumption pattern, even in those subjects who do not inject drugs, in addition to other risky behaviors, such as tattooing and unprotected sex. Injectable cocaine users seem to be more susceptible to contamination than users who do not inject drugs. However, evidence is pointing to the possibility of infection by sharing drug paraphernalia other than syringes. Moreover, specific immune system impairments caused by cocaine use are also being linked with HCV infection susceptibility, persistence and increased pathological effects.