The remarkable involvement of the immune system in CUD is also evidenced by the interaction of cocaine with dopamine receptors expressed in immune cells, such as T and B lymphocytes and NK cells These receptors are able to regulate different cellular processes, including apoptosis, proliferation, and differentiation Moreover, an imbalance in the inflammatory profile was described in CUD.
Also, results of a previous study conducted by Irwin et al. Lewandowski et al. Lower plasma levels of Th1 and Th17 cytokines in the first week of detoxification were observed in women with CUD when compared to the control group. This profile, however, changes at the end of treatment. IL-6 was also elevated in women with history of CM and diminished in women without CM in comparison with the control group.
7. Opportunities for in Vitro Assessment of Immunotoxicity
Now looking at the Th2 profile, IL-4 and IL showed higher expression in smoked cocaine users than in controls Araos et al. They suggested that cocaine users can be stratified according to cocaine symptom severity and presence of psychiatric comorbidities. This strategy allows proinflammatory markers to be used as predictors of cocaine dependence. Another study showed that, during detoxification treatment, patients may present behaviors attributed to the abstinence period, including anxiety, irritability, depression, attention, and memory deficits, as well as respiratory and circulatory impairments 21 — It is already known that some of these behaviors are associated with neuroinflammation in different neurodegenerative diseases 24 and psychiatric disorders 25 , In the case of substance abuse, the appropriate assessment of such behaviors seems to be extremely critical for predicted success or failure with regard to treatment.
Previous studies showed that individuals with higher CSSA scores exhibit severe addictive behavior and are more likely to discontinue treatment In order to explore the immune alterations caused by smoked cocaine use, peripheral blood mononuclear cells PBMCs were stimulated in vitro to evaluate the production of Th1, Th2, and Th17 cytokines. The present study focuses on female CUD patients based on clinical studies showing that women: 1 start using cocaine earlier than men 28 ; 2 report higher amounts of cocaine consumption when compared to men seeking treatment 29 ; 3 report higher craving and withdrawal symptoms to cocaine than men, and are more vulnerable to develop CUD, showing greater drug use escalation 1.
The CUD samples were recruited at an inpatient unit from Southern Brazil and comprises 50 female adults facing detoxification treatment. Patients included in this study were 18 years or older, had positive urine test for cocaine and fulfilled the diagnosis of CUD. Exclusion criteria includes pregnancy and diagnoses of any neurologic, infectious, inflammatory, or metabolic diseases. Non-addicted individuals were recruited through advertisement in social media and all were screened for drug abuse or dependence.
The exclusion criteria used in the CUD sample was also applied in the control sample. In addition, we chose to include only controls with low or medium socioeconomic status SES to match the SES background of the clinical group. Controls were free of anti-inflammatory medications for at least 30 days at time of blood collection. This project was carried out in accordance with the Declaration of Helsinki and all subjects signed an informed consent form previously approved by the Research Ethics Committees of the participating institutions.
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The ASI-6 is a semi-structured interview and it was used to assess the patterns of substance use behavior crack-cocaine, tobacco, alcohol, and cannabis , including data regarding the age of experimentation of licit and illicit drugs, as well as data on recent substance consumption last 30 days before treatment enrollment. The ASI-6 was also performed in non-addicted controls. The CSSA was used to assess the severity of crack-cocaine withdrawal symptoms.
Each of the 18 individual items of the CSSA is scored on a 0—7 scale, in which 0 represents no symptoms and 7 represents maximum severity. The signs and symptoms included on the CSSA assessment were crack-cocaine craving, appetite changes, sleep disturbances, lethargy, depressed mood, and bradycardia, which are manifestations that commonly occur after abrupt cessation of crack-cocaine use.
The CSSA total score was computed by the sum of each individual item score.
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Peripheral blood 10 mL was collected from each participant 4 days after the beginning of the detoxification treatment by venipuncture in EDTA tubes. PHA is a polyclonal mitogen widely used in immunological studies, triggering the T-cell activation, cytokine production and proliferation in vitro The detection limits for these assays ranged from 2.
A comprehensive panel of lymphocyte subsets was identified by multicolor flow cytometry. After staining, cells were washed, resuspended, and analyzed by flow cytometry All data were analyzed by the Flowjo 7. All variables were tested for normality of distribution by Shapiro—Wilk test. Considering the median value For categorical variables, differences between groups were compared using chi-square X 2 test.
General linear models or Kruskal—Wallis were used to analyze differences between cocaine addicted groups and healthy non-addicted individuals. Post-hoc analysis were performed to compare differences between groups. Pearson and Spearman tests were used to correlation analysis. Demographic and clinical data are depicted in Table 1.
No participants reported injected cocaine use. While no significant group differences were detected regarding age, income, and ethnicity, both CUD groups had significantly lower mean BMI compared with the healthy non-addicted control group. Figure 1. Th-1 cytokines after in vitro stimulation in women with CUD and healthy controls. Figure 2. Kruskal—Wallis test was carried out to compare statistical differences. Data are shown as median with interquartile range. Figure 3. Th related cytokine after in vitro stimulation in women with CUD and healthy controls.
Cell supernatants collected from L-W group had higher levels of IL than controls. Statistical significant group differences are indicated.