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Despite the high prevalence of cannabis consumption, there is limited information about cannabis based on scientific evidence available and targeted toward young adults, especially considering accessible language and ease of access. The present study aimed to develop the proof of concept of a chatbot for the dissemination of evidence and scientific information about cannabis, focused on a young adult audience. The proof of concept involved stages of literature review, conversation flow development, content evaluation through a panel of experts ( n  = 10) and usability analysis using a sample of potential users (young adults, n  = 10). The chatbot developed presents information on epidemiology, toxicology, acute and chronic effects of cannabis use, information on cannabis use disorder, and the use of cannabinoids for medicinal purposes. The content evaluation through the Health Education Content Validation Instrument concluded that the tool was considered to have a good structure and content (Content Validity Index > 0,78; overall score = 9.0/10.0). The tool also proved to be functional and highly usable according to the analysis with the System Usability Scale (overall usability score = 9.2/10.0) . Digital strategies such as chatbots can help in health education and scientific communication within stigmatized areas, such as the consumption of psychoactive substances.

Background: Shortening telomere length (TL) is an important ageing marker associated with substance use disorder (SUD). However, the influence of psychiatric and clinical comorbidities and alcohol-related outcomes has not been much explored in the context of TL in individuals with alcohol use disorder (AUD) and may be a source of heterogeneity in AUD studies. Therefore, our aim was to investigate the influence of AUD, alcohol-related outcomes, and common psychiatric comorbidities on TL in men with AUD and healthy controls (HC)., Methods: Men with AUD (n = 108, mean age = 52.4, SD = 8.6) were recruited in a detoxification unit, and HC (n = 80, mean age = 50.04, SD = 9.1) from the blood bank, both located in Brazil. HC had no current or lifetime diagnosis of any substance use disorder. Psychiatric comorbidities were assessed using SCID-I. TL ratio was measured in triplicates using quantitative multiplex PCR., Results: Telomere length did not differ between individuals with AUD and HC (p = 0.073) or was associated with AUD-related outcomes, trauma, or clinical comorbidities. Individuals with externalizing disorders had longer TL when comparing with those with internalizing disorders (p = 0.018) or without comorbidity (p = 0.018)., Conclusion: Our findings indicate that TL was influenced by the presence of psychiatric comorbidity rather than case or control status. These results were adjusted for potential confounders, such as age., Competing Interests: Conflict of interest Dr. Grevet was on the speaker's bureau for Novartis and Shire for 3 years. All other authors report no potential conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Our aim was to analyze the association between criminal behavior and impulsivity in individuals with drug addiction and investigate whether impulsiveness mediates the relationship between drug use severity and legal problems., Methods: This cross-sectional study included 773 men diagnosed with addiction (295 alcohol users and 478 users of crack/polysubstance) while undergoing addiction treatment. The BIS-11 and ASI-6 were applied to assess impulsivity, criminal behavior, and drug use., Results: The prevalence of criminal behavior was 41.7% ( n  = 123) in alcohol users and 64.9% ( n  = 310) in users of crack/polysubstance. Earlier use of different substances and higher impulsivity scores were observed in individuals with criminal history. Mediation analyses revealed that impulsiveness acts as a mediator factor between substance use and criminal behavior, enhancing the severity of legal problems., Conclusion: Our findings can help in deciding on tailored treatment strategies, focusing not only on substance use, but also on the prevention of social problems, criminality, and impulsivity.

Several theories have been proposed to explain the complex diagnostic aspects related to addiction disorders and their development. Recent frameworks tend to focus on dimensional perspectives of symptoms rather than categorical systems, since substance use disorders are frequently comorbid with other psychiatric and especially personality disorders. However, useful transdiagnostic models that could integrate clinical evaluation derived from neuroscientific theories are lacking. In the present manuscript, the authors propose a model based on a new paradigm, in an attempt to better explain this complex, multifaceted phenomenon. The new paradigm presupposes that emotions and behavior are a response to risk prediction. Individuals make choices and engage in actions to manage potential risks/rewards in order to seek or maintain homeostasis in their internal and external environments - a mechanism that the authors call predostatic (predictive mechanism with homeostatic purpose). The model considers three main modes of the predostatic mind: (1) Alarm Mode, activated by high and/or imminent risk prediction; (2) Seek Mode, activated by long-term risk or reward prediction; and (3) Balance Mode, a self-regulating state of mind related to low risk prediction, a soothing system and a calm state. Addiction is seen as a chronic dysregulation of organism systems leading to internalizing or externalizing phenomena mainly related to the Seek and Alarm Modes, which are persistently activated by reward and risk prediction, respectively, thus hindering Balance. Addiction neuroscience research has shown that chronic drug use or engagement in addictive behaviors can lead to neuroadaptations in the brain reward circuitry, disrupting normal balance and the regulation of reward processes. This dysregulation can contribute to persistent drug-seeking/addictive behaviors despite negative consequences. This newly proposed dynamic and integrative model, named dysregulation based on externalizing and internalizing phenomena of the three main modes of the predostatic mind (DREXI3), proposes six dysregulation dimensions with basic emotional and behavioral symptoms, such as neurophysiological alterations, impulsivity, compulsion, cognitive impairment/psychosis, mood, and anxiety/anger. In this paper, the authors explain the rationale behind DREXI3 and present some hypothetical clinical examples to better illustrate the use of the model in clinical practice. The development of this innovative model could possibly guide tailored treatment interventions in the addiction field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Loreto, Sordi, de Castro, Ornell, Guarnieri, Roza, Schuch, da Silveira Cima, Pechansky, Grevet, Grassi-Oliveira, von Diemen and Kessler.)

Objective: This study investigated the relationship between impulsivity and early trauma through a network analysis in individuals diagnosed with different substance use disorders., Methods: In a cross-sectional design, the sample included 556 men with substance use disorders (195 with alcohol use, 157 with cocaine/crack use, and 214 with polysubstance use). Early trauma and impulsive behavior were assessed using the Childhood Trauma Questionnaire and the Barratt Impulsiveness Scale, respectively. The connection between trauma and impulsivity was assessed using network analysis through a fused graphical lasso algorithm., Results: No connection was observed between impulsivity and trauma networks in individuals with alcohol use disorder. In those with cocaine use disorder, networks were linked through the motor domain and sexual abuse nodes. Inverse connections were observed between the emotional neglect node and perseverance, but not the non-planning node. In polysubstance use, the connection between impulsivity and trauma networks was weak, with the cognitive complexity node connecting to the trauma network through physical abuse. There connections were inversely proportional between the motor domain and emotional neglect nodes, as well as between cognitive instability and physical neglect., Conclusion: Our results suggest that the relationship between the type of early (childhood) trauma and the expression of impulsivity could lead to different substance use profiles., Competing Interests: The authors report no conflicts of interest.

Brain-derived neurotrophic factor (BDNF) is involved in several drug-induced brain neuroadaptations. The impact of withdrawal from substances that have different neurological mechanisms on BDNF levels is unclear. Our goal was to compare serum BDNF levels in inpatients with alcohol or crack cocaine use disorders during the early withdrawal period, and to evaluate the association with substance-related outcomes. We performed a follow-up study with 101 men under detoxification treatment (drug preference: alcohol [n = 37] and crack cocaine [n = 64]). Blood samples were collected on the 1st and 15th days of hospitalization to measure serum BDNF levels. Serum BDNF levels increased during the early stage of withdrawal (28.2 ± 10.0 vs. 32.6 ± 13.3, p < 0.001), similarly in individuals with alcohol and crack cocaine use. In the alcohol group, BDNF levels on the 15th day of hospitalization were negatively correlated with age (r = -0.394, p = 0.023). Delta BDNF levels were also negatively correlated with BDNF on the 1st day of hospitalization (p = 0.011). No significant correlation was found regarding substance-related outcomes. This is the first study to compare BDNF levels in alcohol and crack cocaine users undergoing similar treatment conditions. These findings could be related to clinical improvement after abstinence or even to drug withdrawal itself, decreasing neuronal injury. Furthermore, age may be a crucial factor, hindering the recovery of neuroplasticity in alcohol users., Competing Interests: Conflicts of interest Dr. Kapczinski reports personal fees from Janssen - Johnson & Johnson, INCT-CNPq 2014/50 891-1 grants, Canada Foundation for Innovation grants, outside the submitted work. Other authors report no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Abstract: In much of the West, including Brazil, drug use has increased since social distancing began in response to the pandemic. Use of smoked and modified drugs, and their impacts on health, may contribute to aggravate the effects of the pandemic. However, studies on the relationship between use of smoked drugs and the new coronavirus are still scarce and have not received enough attention in global health recommendations. This paper aims to briefly review the relationship between use of smoked drugs and acute respiratory syndrome coronavirus 2 [SARS-CoV-2]. Recent studies also suggest that drug consumption increases the risk of contamination by SARS-CoV-2 and leads to worse prognosis, particularly consumption of drugs that affect lung function. Use of smoked drugs, especially tobacco, is strongly associated with lung diseases that are risk factors for contamination by SARS-CoV-2. It is essential to develop strategies based on specific characteristics of drug users and for mental health professionals to be included in strategic teams. It is also necessary to invest in information campaigns regarding risks and prevention of harm caused by smoked drugs as well as to design strategies that facilitate access to psychosocial treatment during the pandemic., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Introduction: High rates of early hospital discharge are often observed in crack cocaine users and are related to adverse outcomes and increased public spending. This study evaluated clinical and sociodemographic factors associated with early treatment discharge among crack users., Methods: The sample comprised 308 men diagnosed with crack cocaine use disorder (crack only), aged 18 to 65 years, admitted between 2013 and 2017 to a male-only hospital unit to treat substance use disorders. Sociodemographic and clinical data were obtained using the Addiction Severity Index, 6th version, and a Sociodemographic Questionnaire., Results: Early discharge (within 7 days) was significantly associated with lack of own income, insufficient family support, being single, and recent homelessness. Regarding drug use, lower treatment retention was related to younger age of crack use onset, recent alcohol use, and nicotine use. Factors such as age, skin color, and educational level showed no relation to the outcome., Conclusion: Our findings suggest that presence of characteristics verifiable at the time of admission may be related to crack users' treatment retention. Identification of these factors can contribute to target interventions in order to improve treatment adherence in crack cocaine users., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Introduction: Burnout syndrome (BS) in healthcare professionals (HCP) has been a major concern, and even more so during the coronavirus disease 2019 (COVID-19) pandemic. The need for adequate tools to assess BS is urgent. The objective of this study was to validate the Brazilian Portuguese version of the Copenhagen Burnout Inventory (CBI) in HCP., Methods: The sample comprised 1,054 Brazilian HCP. Data were collected for 1 month (May-2020 to June-2020) using an online self-administered questionnaire., Results: All three CBI dimensions demonstrated optimal reliability. All consistency measures attained values > 0.90. Split-half correlation values with Spearman-Brown reliability were higher than 0.8. The parallel analysis suggested two factors: personal burnout (PB) and work-related burnout (WB) items were associated with factor 1, and client-related burnout (CB) items were associated with factor 2., Conclusion: Our study corroborates the validity of the Brazilian Portuguese version of the CBI, pointing to a close relation between PB and WB in HCP. A public domain tool with evidence quality to ensure sufficient content validity can aid in burnout evaluation and encourage both expansion of the research field and accurate detection and treatment of this syndrome in Brazilian HCP., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Introduction: Consumption of substances has been associated with cognitive impairment. The Mini Mental State Examination (MMSE) is an easy-to-apply screening tool used to assess cognitive functions., Objectives: To evaluate the cognitive performance of individuals with alcohol (AUD) and/or crack cocaine use disorder (CUD) and polysubstance use using the MMSE and to investigate the impact of substance use profile and the moderation effect of educational level on MMSE performance., Methods: Cross-sectional study with 508 adult male inpatients diagnosed with substance use disorders (245 with AUD, 85 with CUD, and 178 with polysubstance use). Cognitive performance was assessed using the MMSE scale (total and composite scores)., Results: Individuals with AUD had worse total MMSE scores and scored worse for all three MMSE components compared to individuals with polysubstance use (p < 0.001, oral/written language comprehension, p < 0.001, attention/memory, and p = 0.007, motor functions). MMSE scores were positively correlated with educational level (p < 0.017), but were not associated with age, recent drug use, or years of drug use. Educational level moderated the impact of substance use on MMSE performance, especially total score and composite language comprehension score. Individuals with a low educational level (≤ 8 years) had worse performance than those with a high educational level (≥ 9 years), mainly in individuals with AUD (p < 0.001)., Discussion: Individuals with a low educational level and alcohol use are more prone to present cognitive impairment than crack cocaine users, especially involving language aspects. Better-preserved cognitive function could impact treatment adherence and might guide the decision of therapeutic strategies., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Introduction: Changes in brain-derived neurotrophic factor (BDNF) have been linked to the neuroadaptative consequences of chronic alcohol use and associated with disease severity and prognosis. Few studies have evaluated the influence of drug withdrawal and clinical and sociodemographic data on BDNF levels in severe alcohol users., Objectives: Our goals were (1) to evaluate variation in BDNF levels during alcohol withdrawal and, (2) to assess the influence of putative confounding factors on BDNF levels., Methods: Our sample consists of 62 men with alcohol use disorder undergoing a detoxification process. Serum BDNF levels were measured using a commercial sandwich-ELISA kit, at two points: before and after the detoxification period., Results: We found an increase in BDNF levels during alcohol withdrawal (25.4±9.6 at admission vs. 29.8±10.2 ng/ml at discharge; p < 0.001), even after controlling for potential confounders (positive family history, number of days between blood sample collections, and age) (Generalized Estimating Equation: coefficient = -4.37, 95% confidence interval [95%CI] -6.3; -2.4; p < 0.001). Moreover, individuals who had first-degree relative with alcohol dependence had smaller increases in BDNF levels than individuals with no family history (14.8 [95%CI -5.3; 35.6] vs. 35.3 [95%CI 15.4; 74.8]; p = 0.005)., Conclusions: In summary, variation in BDNF levels seems to be influenced by withdrawal in severe alcohol users. A positive family history of alcohol dependence could also be a factor that influences variation in this biomarker., Competing Interests: Flavio Kapczinski has received personal fees from Janssen/Johnson & Johnson. No other conflicts of interest declared concerning the publication of this article.

Objectives: To compare suicide rates observed in Brazil after the onset of the COVID-19 pandemic with the estimated rate based on suicide deaths between 2010 and 2020, and identify sociodemographic variables associated with this outcome., Methods: Ecological time-series study. Data were obtained from Brazilian Unified Health System Department of Information Technology (DATASUS), with the structural break of the data set in March 2020. The number of actual suicides observed and the number of expected suicides if there were no COVID-19 pandemic were analyzed through bayesian structural time series modeling., Results: The overall incidence of suicides in Brazil remained stable after the start of the COVID-19 pandemic compared to what would be expected. However, there was a significant increase in suicide deaths among women (6.9%) and older adult (9.1%). Analysis by macro-regions of the country showed significant increases in suicide deaths in the Center-West (7.4%), Northeast (5.7%), and Southeast (10%). Stratified analyses revealed differences according to age, sex, education, and skin color., Conclusions: Despite stability in the overall number of suicides, this phenomenon occurs heterogeneously among different population groups and regions of Brazil. Rates have increased in populations with a history of poor access to health, which may have been more severely impacted by the pandemic., Competing Interests: The authors report no conflicts of interest.

Objective: To assess differences in blood inflammatory cytokines between people with alcohol use disorder (AUD) and healthy controls (HC)., Methods: Searches were performed from inception through April 14, 2021. Meta-analyses with random-effects models were used to calculate the standardized mean difference ([SMD], 95%CI), and potential sources of heterogeneity were explored trough meta-regressions and subgroup analysis., Results: The meta-analysis included 23 studies on the following 14 cytokines: tumor necrosis factor (TNF)-a, IL-1, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, IL15, interferon (IFN)-g and sCD14. There were significantly higher concentrations of IL-6 (n=462 AUD and 408 HC; SMD = 0.523; 95%CI 0.136-0.909; p = 0.008) in AUD than HC. No significant differences were found in the other 13 cytokines., Conclusion: We found that IL-6 levels were significantly higher in individuals with AUD than HC and that other cytokines were not altered. This can be explained by the small number of studies, their methodological heterogeneity, and confounding factors (active use, abstinence, quantity, and physical or psychiatric illnesses, for example). Despite a great deal of evidence about alcohol and inflammatory diseases, studies assessing the role of neuroimmune signaling in the development and severity of AUD are still lacking., Competing Interests: The authors report no conflicts of interest.

Introduction: Several barriers for mental health help-seeking were identified among medical students, including minimizing mental illness. Studies examining aspects particular to those who perceive psychological impairment but do not access treatment are necessary for planning interventions., Aims: To identify help-seeking barriers based on the students' perception about their need for treatment and psychiatric symptoms. Methods: Cross-sectional study assessing 436 Brazilian medical students (833 attending the medical school = 52.3% response rate). Data collection covered sociodemographic data, mental health, academic environment, and Beck Inventories of Depression (BDI) and Anxiety (BAI). Non-parametric tests and hierarchical logistic regression were used to compare students undergoing treatment, those willing to access treatment, and the ones reporting no need for treatment., Results: Among the 382 students who completed the survey (87.6% completion rate), 38.5% ( n  = 147) were in treatment, and 33% ( n  = 126) were in need. Moderate to severe risk of alcohol abuse was observed in 45.9% ( n  = 50) of students reporting no need for treatment. Regression models suggested that perceiving need for treatment - whether already undergoing it or not - was associated with the severity of depressive symptoms (OR 1.14 [95% CI 1.07-1.21]), female assigned sex (OR 2.18 [95% CI 1.23-3.88]), LGBTQ+ (OR 2.47 [95% CI 1.09-5.60]) and reporting good relationship with the family (OR 0.26 [95% CI 0.08-0.83]). Models comparing students in treatment and those in need, pointed that the factors associated with lacking mental health care were age (OR 0.90 [95% CI 0.82-0.99]), perception of a heavy workload (OR 2.43 [95% CI 1.35-4.38]) and good relationship with colleagues (OR 3.51 [95% CI 1.81-6.81])., Discussion: Social variables and the severity of depressive symptoms are positively associated with perceived need for treatment. Age and academic environment factors were related to help-seeking behavior among students with appropriate self-awareness. We discuss these findings' implications for planning interventions.

Objective: This study aimed to evaluate whether progression from first drug use to crack-cocaine use differs according to gender, and whether the report of sexual or physical violence impacts the time of progression., Methods: We interviewed 896 crack-cocaine users (548 men; 348 women) from addiction treatment units. Cox regression models evaluated the time of progression from first drug use to crack use. We analyzed gender differences according to the absence or presence of sexual or physical violence, also considering whether violence, when present, had occurred before or after the onset of crack use., Results: Women presented a faster progression to crack use regardless of exposure to sexual or physical violence (p < 0.05). Compared to unexposed men, there was a similar progression for men exposed to sexual or physical violence before the first use of crack (p = 0.167 and p = 0.393, respectively). In both genders, we observed a faster progression among individuals exposed to these types of violence after the onset of crack use (p < 0.01)., Conclusions: We found a faster progression to crack use among women and among individuals exposed to sexual and physical violence after the onset of crack use. These results encourage differentiated treatment strategies, focused on gender and individual characteristics., Competing Interests: The authors report no conflicts of interest.

Objective: To compare the prevalence and subtypes of childhood maltreatment (CM) between individuals with and without substance use disorder (SUD) and investigate the influence of different traumas on the preferential use of substances and the severity of dependence., Methods: The sample consisted of 1,040 men with SUD (alcohol users [n=315], crack-cocaine users [n=406], multiple-substance users [n=319]) and 201 controls. The Childhood Trauma Questionnaire (CTQ) and the Addiction Severity Index-6 (ASI-6) were used to assess CM and drug-use patterns., Results: Individuals with SUD had a higher prevalence of CM than controls (63.4 vs. 28.1%, respectively). Exposure to physical trauma was associated with alcohol use disorder and severity of alcohol use. In contrast, emotional trauma was associated with use of multiple substances and severity of drug use in crack-cocaine users., Conclusions: This study corroborates the association of CM with SUD susceptibility. Our results suggest that the type of CM may influence preferential substance use and addiction severity. In this sense, physical traumas are more associated with alcohol use, while emotional and sexual traumas favor use of multiple drugs, especially crack cocaine. These findings may help the development of tailored prevention and intervention strategies., Competing Interests: The authors report no conflicts of interest.

Objective: To identify factors associated with mental health of older adults during the pandemic and to provide strategies to mitigate their psychosocial impact in the elderly., Method: An integrative text mining analysis in Medline was performed to identify studies on the mental health of older adults during the pandemic. Subsequently, statistical topic modeling was performed to identify the most prevalent terms and topics discussed in included studies., Results: A total of 29 studies were retrieved until July 1st 2020, including a majority of letters (12 studies) and commentaries (8 studies). The most frequent terms overall were: loneliness ( n = 137), support ( n = 132), home ( n = 102), suicide ( n = 96) and help ( n = 94). The most prevalent terms were then divided in five topics: home (33%), suicide (32%), apps (15%), loneliness (12%) and physical activity (9%). Additionally, a section focused on low- and middle-income countries was included. A summary of strategies to mitigate the effects of pandemic in mental health of older adults was also provided., Conclusion: These factors demonstrate the importance of developing strategies for psychosocial support that take into consideration the particularities of the elderly. Different levels of care are immediately necessary to diminish the devastating impact of the pandemic in the mental health of older adults.

Objective: Conduct a systematic review and meta-analysis to evaluate levels of anger among substance users compared to non-user controls and to analyze the possible association between anger and psychoactive substance use (PSU)., Methods: The procedures of this review followed the Meta-Analyzes of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four electronic databases (MEDLINE, EMBASE, BIREME, PsycINFO) were searched., Results: Twelve studies were included in the meta-analysis; 10 used the State-Trait Anger Expression Inventory (STAXI) anger trait subscale and two used the Buss-Perry-Aggression Questionnaire (BPAQ) anger subscale. The sample included 2,294 users of psychoactive substances and 2,143 non-users, all male. The mean difference in anger scale scores between users and non-users was 2.151 (95%CI 1.166-3.134, p ≤ 0.00, inconsistency index [I2] = 98.83) standard deviations. Age and abstinence duration did not moderate the difference in anger between substance users and non-users., Conclusion: Users of psychoactive substances had elevated anger scores compared to non-users, which represents a high risk of relapse. It is suggested that PSU treatment programs include intensive anger management modules, focusing on factors such as dealing with daily stressors, family conflicts, frustrations, and problems.

Background: Studies have reported the worsening of psychiatric symptoms during the COVID-19 pandemic. However, few studies have evaluated the impact on the access to mental health services during COVID-19. Our aim was to analyze temporal trends and prediction of appointments held in Brazil's public health system, to compare the observed and expected number of mental healthcare appointments during the COVID-19 pandemics., Methods: An ecological time-series study was performed, analyzing mental health appointments before and during the pandemic (from 2016 and 2020) from the Brazilian governmental database. The structural break in the data series was assessed using the Chow test, with the break considered in March 2020. Bayesian structural time-series models were used to estimate current average appointments and the predicted expectation if there was no pandemic., Findings: Compared to the expected, between March and August 2020 about 28% less outpatient appointments in mental health were observed, totaling 471,448 individuals with suspended assistance. Group appointments and psychiatric hospitalizations were also severely impacted by the pandemic (decreased of 68% and 33%, respectively). On the other hand, mental health emergency consultations and home care increased during this period (36% and 52%, respectively)., Interpretation: Our findings demonstrate a dramatic change in mental health assistance during the COVID-19 pandemic, which corroborates a recent WHO survey. This phenomenon can aggravate the mental health crisis and generate a parallel pandemic that may last for a longer time than the COVID-19 pandemic., Funding: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001., Competing Interests: The authors have no conflicts of interest., (© 2021 The Authors.)

The COVID-19 pandemic is a public health emergency. Individuals with substance use disorder have a higher risk of infection and may suffer from more severe forms of the disease. Our goal is to investigate the prevalence of risk factors for COVID-19 severity in individuals with different substance use and explore whether specific types of substance are potentially associated with more clinical risk factors which could increase morbimortality in this population. The sample included 821 men hospitalized at an inpatient Addiction unit (305 alcohol users, 233 cocaine/crack users, and 283 multiusers). Data were collected using the Addiction Severity Index version 6. The most prevalent risk factors for COVID-19 severity observed in our sample were: smoking (82.5%), arterial hypertension (26.6%), respiratory problems (23.4%), and history of homelessness (25.1%). Arterial hypertension and cirrhosis occurred more frequently among alcohol users. Multiusers lived in the streets longer and had a higher prevalence of HIV than alcohol users. Overall, 28% of the sample had three or more risk factors. The frequency of risk factors was high and this scenario suggests that these individuals could be more susceptible to worse COVID-19 prognosis. Therefore, prevention strategies directed at specific characteristics of substance users merit attention during the pandemic., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The coronavirus disease (COVID-19) pandemic is one of the greatest contemporary challenges. Feelings of fear and uncertainty triggered by this pandemic have had noxious effects on people's mental health. This seems to have increased during quarantine and there is evidence of an intensification of rewarddirected behavior. Nevertheless, there are few studies dealing with pornography consumption during this period. The aim of this manuscript is to contextualize this phenomenon during the pandemic and suggest some clinical recommendations on the matter., Competing Interests: No conflicts of interest declared concerning the publication of this article.

The pandemic resulting from COVID-19 has led to the collapse of the health system in dozens of countries. Parallel to clinical risk, the appearance or intensification of psychiatric symptoms has also been documented. The identification of groups at risk is essential for the establishment of preventive and therapeutic strategies. Cancer patients appear to be especially vulnerable both from a clinical and psychiatric perspective. Problems related to contamination and the cancer treatments themselves are intertwined, causing a sum of patients' fears to arise, which can cause mental effects. This study aims to review and investigate the impact of COVID-19 on the mental health of cancer patients and indicate possible support strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bandinelli, Ornell, von Diemen and Kessler.)

The COVID-19 pandemic is unquestionably impacting on the mental health of the population worldwide. Fear of contamination can both increase levels of stress in healthy individuals and intensify psychiatric symptoms in patients with pre-existing conditions, especially obsessive-compulsive disorder (OCD). During the COVID-19 pandemic, the imminent risk of contamination creates a logical need for self-surveillance and hygiene habits. However, this kind of information can have drastic implications for subjects with OCD, since cognitive distortions and compensatory strategies (cleansing rituals) are no longer irrational or oversized - rather, these ideas become legitimate and socially accepted, generating plausible validation for the intensification of compulsive cleaning rituals. Patients who presented remission of OCD symptoms would be more likely to have a relapse, and subclinical patients may scale up and ultimately be diagnosed with OCD due to the reinforcement of their habits, emotions and thoughts., Competing Interests: No conflicts of interest declared concerning the publication of this article.

The COVID-19 pandemic has brought major challenges to healthcare systems and public health policies globally, as it requires novel treatment and prevention strategies to adapt for the impact of the pandemic. Individuals with substance user disorders (SUD) are at risk population for contamination due to multiple factors-attributable to their clinical, psychological and psychosocial conditions. Moreover, social and economic changes caused by the pandemic, along with the traditional difficulties regarding treatment access and adherence-will certainly worsen during this period, therefore aggravate their condition. In addition, this population are potential vectors of transmission. In that sense, specific strategies for prevention and treatment must be discussed. health care professionals dealing with SUD must be aware of the risks and challenges they will meet during and after the COVID-19 outbreak. Addiction care must be reinforced, instead of postponed, in order to avoid complications of both SUD and COVID-19 and to prevent the transmission of coronavirus., Competing Interests: The authors declare no conflicts of interest., (© 2020 Elsevier B.V. All rights reserved.)

Introduction Drug-related crimes, especially drug trafficking, account for a large part of incarcerations not only in Brazil, but also worldwide. It is not clear whether the change in the drug law has contributed to the increase in the number of drug trafficking prisoners. Few studies have investigated gender differences and the growth of drug trafficking offenses in the Brazilian southern state of Rio Grande do Sul. Objective To investigate the growth of the prison population in the state of Rio Grande do Sul, emphasizing incarcerations for drug trafficking and gender differences. Method This was an ecological study using secondary data collected from official databases of the Brazilian National Penitentiary Department (Departamento Penitenciário [DEPEN]), affiliated with the Brazilian Ministry of Justice. Results Between 2006 and 2015, incarcerations increased by 27% (25% men, 83% women). Incarcerations for drug trafficking accounted for 11% of total arrests in 2006 (11% men, 20% women) and 45% in 2015 (47% men, 91% women), corresponding to an increase of 427% (415% among men, 723% among women). Conclusions Imprisonment for drug trafficking has increased considerably, especially among women. This may be due to factors such as: increase of drug trafficking, increase in the numbers of gangs in the state, and changes in the Brazilian drug law. These results highlight an emerging challenge in public health from the perspective of human rights and gender.

Background: Suicide is a severe health problem, with high rates in individuals with addiction. Considering the lack of studies exploring suicide predictors in this population, we aimed to investigate factors associated with attempted suicide in inpatients diagnosed with cocaine use disorder using two analytical approaches., Methods: This is a cross-sectional study using a secondary database with 247 men and 442 women hospitalized for cocaine use disorder. Clinical assessment included the Addiction Severity Index, the Childhood Trauma Questionnaire, and the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, totalling 58 variables. Descriptive Poisson regression and predictive Random Forest algorithm were used complementarily to estimate prevalence ratios and to build prediction models, respectively. All analyses were stratified by gender., Results: The prevalence of attempted suicide was 34% for men and 50% for women. In both genders, depression (PRM = 1.56, PRW = 1.27) and hallucinations (PRM = 1.80, PRW = 1.39) were factors associated with attempted suicide. Other specific factors were found for men and women, such as childhood trauma, aggression, and drug use severity. The men's predictive model had prediction statistics of AUC = 0.68, Acc. = 0.66, Sens. = 0.82, Spec. = 0.50, PPV = 0.47 and NPV = 0.84. This model identified several variables as important predictors, mainly related to drug use severity. The women's model had higher predictive power (AUC = 0.73 and all other statistics were equal to 0.71) and was parsimonious., Conclusions: Our findings indicate that attempted suicide is associated with depression, hallucinations and childhood trauma in both genders. Also, it suggests that severity of drug use may be a moderator between predictors and suicide among men, while psychiatric issues shown to be more important for women., Competing Interests: The authors have declared that no competing interests exist.

Background: Dysregulation of the hypothalamic-pituitaryadrenal (HPA) axis has been associated with craving and early relapse among individuals with substance use disorders. However, no association has been postulated regarding treatment retention and prognosis in crack cocaine users., Objective: Our aim was to investigate the association between morning salivary cortisol levels and treatment retention in crack cocaine users., Methods: 44 male crack cocaine users were recruited from a detoxification unit. Saliva collection was performed in the morning of the second treatment day. Substance use profile was assessed using the Addiction Severity Index., Results: The median length of stay in inpatient treatment was 7 days (IQR 3-16). Treatment retention was associated with cortisol levels (r = -0.324; p = 0.032), especially in the group with positive family history. Moreover, treatment retention was correlated with age (r = 0.333, p = 0.027), and number of days of tobacco use (r = 0.332, p = 0.028) and crack use (r = 0.327, p = 0.031). A Cox regression model was performed and showed that inpatients with above normal cortisol levels (≥0.69 µg/dL) presented a worse prognostic related to treatment retention (HR = 2.39, CI95% 1.1-5.1, p = 0.024)., Conclusion: Several factors could contribute to increased cortisol levels in these patients, e.g. craving, dysregulation of the HPA axis, chronic drug use, stress due to confinement, and substance abstinence. Nevertheless, our findings could guide further studies about new biomarkers in crack cocaine use disorder, since HPA axis dysregulation at the time of treatment admittance may be a prognostic marker for treatment retention., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: To evaluate the association between childhood trauma (CT) and serum levels of brain-derived neurotrophic factor (BDNF) and thiobarbituric acid-reactive substances (TBARS) during crack-cocaine withdrawal., Method: Thirty-three male crack-cocaine users were recruited at admission to a public addiction treatment unit. Serum BDNF and TBARS levels were evaluated at intake and discharge. Information about drug use was assessed by the Addiction Severity Index-6th Version (ASI-6); CT was reported throughout the Childhood Trauma Questionnaire (CTQ). CTQ scores were calculated based on a latent analysis model that divided the sample into low-, medium-, and high-level trauma groups., Results: There was a significant increase in BDNF levels from admission to discharge, which did not differ across CT subgroups. For TBARS levels, we found a significant time vs. trauma interaction (F2,28 = 6.357, p = 0.005,ηp 2 = 0.312). In participants with low trauma level, TBARS decreased, while in those with a high trauma level, TBARS increased during early withdrawal., Conclusion: TBARS levels showed opposite patterns of change in crack-cocaine withdrawal according to baseline CT. These results suggest that CT could be associated with more severe neurological impairment during withdrawal.

Objective: To evaluate aggressiveness in individuals receiving treatment for alcohol and crack cocaine use, both alone and in combination with one another, in order to compare them to control subjects with no history of drug problems, using the State-Trait Anger Expression Inventory. Method: The sample consisted of 67 men aged 18-65   years, divided into four groups: alcohol ( n  =   13); crack cocaine ( n  =   25); crack cocaine + alcohol ( n  =   16) and controls ( n  =   13). Participants completed the following instruments: socioeconomic questionnaire, the Wechsler Abbreviated Scale of Intelligence and the State-Trait Anger Expression Inventory. Results: Individuals with alcohol dependence alone, or comorbid with crack cocaine dependence, showed elevated levels of aggression and anger, though these varied according to the drug of abuse. Concurrent users of alcohol and crack cocaine had the highest levels of aggression, followed by isolated alcohol users, suggesting an association between alcohol consumption and aggression. Conclusion: The present findings suggest that alcohol and aggression levels may be associated with violent behavior. Concurrent use of alcohol and crack cocaine was related to higher levels of aggression, which may be associated with more severe alterations in behavior and impulse control.

Crack cocaine use disorder (CUD) has been related to sex differences. This work aimed to compare the severity of drug use and the severity of other negative related outcomes in males and females with CUD. A total of 1344 inpatients (798 males and 546 females) with crack cocaine use disorder (CUD) were evaluated by a detailed multidimensional clinical assessment, including addiction severity and trauma exposure. Linear regression predicted higher drug use severity (β = 0.273, p < 0.001) and more problems in domains related to childcare issues (β = 0.321), criminal involvement (β = 0.108), work-related problems (β = 0.281) and social support impairments (β = 0.142) for females, all with p < 0.001. Alcohol problems were predicted to be higher in males (β = -0.206, P < 0.001). Females had higher rates of other mental disorders, particularly trauma and stress-related disorders (OR: 3.206, CI: 2.22, 4.61). Important sex differences also emerged in trauma history and HIV infection prevalence. CUD has a more severe clinical presentation among females facing early abstinence. Sex differences in the CUD course indicate the need for consideration of sex-specific interventions and research., Competing Interests: The authors have declared that no competing interests exist.

The incidence of driving under the influence of psychoactive substances (DUI) and its recidivism can be curtailed by the proper identification of specific and predictive characteristics among drug users. In this sense, interpersonal violence (IV), psychiatric comorbidity and impulsivity seem to play an important role in DUI engagement according to previous studies. There are, however, limited data originated from low and middle income countries. In the present study, drug-using Brazilian drivers reporting DUI (n = 75) presented a higher prevalence of bipolar disorders (BD; DUI: 8% vs. non-DUI: 0%, p < 0.001), lower prevalence of obsessive-compulsive disorder (OCD; DUI: 0% vs. non-DUI: 12.6%, p < 0.001), and higher prevalence of childhood trauma (DUI: 65.3% vs. non-DUI: 46.8%, p = 0.022) than those not reporting DUI (n = 79). The evaluation of impulsivity though the Barratt Impulsivity Scale, which give impulsivity scores ranging from 30 to 120, showed higher impulsivity scores in the DUI group (80.4 ± 8) than in the non-DUI group (77.2 ± 10, p = 0.045). In general, subjects were young adults (mean age of 36 ± 9 years), Caucasians (58.4%), not married (61.0%), and with elementary schooling (40.3%) with no significant differences in demographic characteristics between drivers with and without DUI behavior. A multiple Poisson regression model showed that individuals reporting IV as perpetrators and history of childhood trauma were more likely to report DUI (PR: 1.66, 95%CI 1.22-2.7; PR: 1.57, 95%CI 1.02-2.42, respectively). The overlapping of violent situations (childhood trauma, IV and DUI) in some individuals presented here corroborates literature data suggesting that DUI can be an externalizing expression of a range of risky behavior, such as impulsiveness and aggressiveness. Moreover, while BD and higher impulsivity scores seem to act as risk factors for DUI, OCD was shown as a protective factor. These results corroborate the hypothesis that individuals with high risk for DUI could probably be identified by multidimensional assessment of cognitive, risky taking, and personality traits, which perhaps could facilitate the development of focused interventions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Club drug users are high risk and vulnerable population for adverse drug-related consequences and sexual risk behaviors. Few investigations have addressed the possible interrelationship between early trauma and PTSD among young club drug using populations. Objective: Exposure to traumatic experiences - especially in childhood, has been linked to risk behaviors exposure and substance use disorder. This study aimed to assess and compare drug use patterns and the presence of childhood sexual abuse (CSA) experiences among ecstasy and LSD users with and without Posttraumatic Stress Disorder (PTSD). Method: This cross-sectional study employed targeted sampling and ethnographic mapping approaches via face-to-face interviews conducted at bars and electronic music festivals. The Global Appraisal of Individual Needs questionnaire was used as the primary assessment instrument. Participants were from 18 to 39 years of age, had used ecstasy and/or LSD in the 90 days prior to the interview, and were not in treatment for alcohol and other drug problems. Results: Out of the 240 participants, 123 (51.2%) presented PTSD symptoms. Those presenting PTSD were younger, less educated, with lower income, and presented higher drug use severity than those without PTSD symptoms. Moreover, a higher prevalence of sexual risk behavior was verified among those with PTSD. There was an association between PTSD symptoms and CSA history, where 64.2% of individuals with PTSD also presented CSA, compared to 47% among those without PTSD (p = .028). Individuals with co-occurring history of CSA and PTSD symptoms reported earlier use of ecstasy, LSD, and cocaine compared to individuals with a history of CSA but without PTSD. Conclusions: In the present study, participants with a history of PTSD demonstrate a history of CSA, as well as pronounced severity in several areas - precocity of use, severity of addiction, and greater exposure to situations of sexual risk. Thus, a cycle of traumatization may be established through early potential trauma, which can remain unprocessed and contribute to earlier and more severe substance use and sexual risk behaviors. Identification of PTSD symptoms and risk for HIV and other STIs among young club drug users is critical to address focused treatment approaches for this vulnerable population.

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, I 2  = 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, I 2  = 89.81) and crack/cocaine users (SMD = -1.78, 95%CI -2.92 to -0.65, I 2  = 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 BDNF's potential utility as a biomarker in this population., (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.)

The study had the goal to evaluate psychoactive substance use severity, violence, physical and emotional health of crack users who seeks specialized treatment in Psychosocial Care Centers for Alcohol and Drugs (CAPSad) concerning housing status. This is a multicenter cross-sectional study in six Brazilian capitals with 564 crack users categorized into two groups (1) users who have been homeless sometime in life (n = 266) and (2) individuals who have never lived on streets (n = 298). To assess the substance use severity and the characteristics of the individuals, the Addiction Severity Index, 6th version (ASI-6) was used. Group 1 users showed worse indicators regarding alcohol, medical and psychiatric problems, employment and family support subscales, as well as greater involvement with legal problems, violence, sexual abuse, suicide risk and health related problems such as HIV/AIDS, hepatitis and tuberculosis. In addition they have lower income to pay for basic needs. After analysis and control for possible confounders, not having enough income to pay for basic needs, showing depression symptoms, and having been arrested for theft remained statistically significant. This study evaluated more deeply drug use severity and housing status of crack users. Interventions developed in outpatient treatment should be designed and tailored to specific profiles and demands of drug users, especially homeless individuals.

Background: Substance use disorders are associated with the increased risk of driving under the influence (DUI), but little is known about crack-cocaine and its relationship with road traffic crashes (RTC)., Method: A multicenter sample of 765 crack-cocaine users was recruited in six Brazilian capitals in order to estimate the prevalence of DUI and RTC involvement. Legal, psychiatric, and drug-use aspects related with traffic safety were evaluated using the Addiction Severity Index - 6th version (ASI-6) and the Mini International Neuropsychiatric Interview., Results: Seventy-six (28.3%) current drivers reported accident involvement following crack-cocaine use. Among drivers (n=269), 45.7% and 30.5% reported DUIs in the past 6 months and 30 days, respectively. Drivers reporting DUI's in the past month (n=82) had higher scores in the "psychiatric", "legal", and "family problems" subscales from the ASI-6, and lower scores in the "family social support" subscale in comparison to those without a history of DUIs (n=187). An overall high prevalence of psychiatric comorbidity and substance consumption was observed. Participants with 5+ years of crack-cocaine use were more likely to have been in a RTC (RR=1.52, 95%IC: 1.02-2.75), independently of marijuana use, binge drinking and psychiatric comorbidities., Conclusion: The high prevalence of RTC and DUI involvement among crack-using drivers supports the idea that they are at a high risk group regarding traffic safety. Years of crack consumption seem to be associated with RTC involvement. Also, the presence of psychiatric comorbidities, poly-drug use, and cognitive impairment usually associated with crack addiction could yield additional risk of accidents., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Epigenetic mechanisms are involved in normal behavior and are implicated in several brain neurodegenerative conditions, psychiatric and inflammatory diseases as well. Moreover, it has been demonstrated that sepsis lead to an imbalance in acetylation of histones and that histone deacetylase inhibitors (HDACi) can reverse this condition. In the present study, we evaluated the effects of a microinjection of sodium butyrate (SB, HDACi) into cerebral ventricle on aversive memory in rats submitted to the sepsis. Rats were given a single intraventricular injection of artificial cerebrospinal fluid (ACSF) or SB and immediately after the stereotaxic surgery and the drug infusion, the animals were subjected to cecal ligation and perforation (CLP). The animals were killed twenty four hours or ten days after sepsis induction and the prefrontal cortex, hippocampus, striatum and cortex were obtained to the determination of histone deacetylase activity. In a separate cohort of animals 10 days after sepsis induction, it was performed the inhibitory avoidance task. SB administration was able to reverse the impairment in aversive memory and inhibited the HDAC activity in prefrontal cortex and hippocampus 10 days after CLP. These support a role for an epigenetic mechanism in the long-term cognitive impairments observed in sepsis survivors animals., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Rationale: An important goal of addiction research is to discover neurobiological markers that could predict the severity of addiction and help to determine appropriate treatment. Brain-derived neurotrophic factor (BDNF) and thiobarbituric acid reactive substances (TBARS) are being related to cerebral plasticity and impairment caused by substance abuse., Objectives: This study aims to evaluate alteration of TBARS and BDNF levels among crack cocaine users during early drug withdrawal and its relationship to severity of drug use., Methods: Forty-nine adults crack cocaine users were recruited at a public psychiatric hospital with a specialized addiction treatment unit. Blood sample was collected at intake and discharge for the analysis of TBARS and BDNF measures. Information about drug use was assessed by the Addiction Severity Index 6th Version (ASI-6). Detailed information about crack cocaine use was obtained through the "Profile of the crack cocaine user." Severity of crack use was estimated using information from age of first crack use, years of crack use, and crack rocks used in the previous 30 days., Results: There is a positive correlation between TBARS levels and severity of crack cocaine use (R = 0.304, p = 0.04) and a negative correlation between BDNF and severity of crack cocaine use (R = -0.359, p = 0.01) at discharge. Also, we found an inverse correlation between TBARS and BDNF levels (R = -0.294, p = 0.004) at discharge., Conclusions: Our findings suggest that BDNF and TBARS could be possible markers for the severity of drug use. Further studies may show how those markers could be related to staging, prognosis, and treatment in crack cocaine dependence.

The effects of modafinil (MD) on behavioral and oxidative damage to protein and lipid in the brain of rats were evaluated. Wistar rats were given a single administration by gavage of water or MD (75, 150, or 300 mg/kg). Behavioral parameters were evaluated in open-field apparatus 1, 2, and 3 h after drug administration. Thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation were measured in the brain. MD increased locomotor activity at the highest dose 1 and 3 h after administration. MD administration at the dose of 300 mg/kg increased visits to the center of open-field 1 h after administration; however, 3 h after administration, all administered doses of MD increased visits to the open-field center. MD 300 mg/kg increased lipid damage in the amygdala, hippocampus, and striatum. Besides, MD increased protein damage in the prefrontal cortex, amygdala, and hippocampus; however, this effect varies depending on the dose administered. In contrast, the administration of MD 75 and 300 mg/kg decreased the protein damage in the striatum. This study demonstrated that the MD administration induces behavioral changes, which was depending on the dose used. In addition, the effects of MD on oxidative damage parameters seemed to be in specific brain region and doses.

Several evidences have demonstrated that oxidative stress has a central role in bipolar disorder (BD). Recently, studies have been suggested histone deacetylases (HDAC) as a possible target for new medications in treatment of mood disorders. In this study, we investigated the effects of sodium butyrate (SB, a histone deacetilase inhibitor) on oxidative stress in rats submitted to an animal model of mania induced by d-amphetamine (d-AMPH). Wistar rats were first given d-AMPH or saline (Sal) for 14 days, and then, between days 8 and 14, rats were treated with SB or Sal. Locomotor activity and risk-taking behavior were assessed by open-field test and oxidative stress was measured in prefrontal cortex, amygdala, hippocampus and striatum. The results showed that SB reversed and prevented d-AMPH-induced behavioral effects. The d-AMPH administration induced oxidative damage in all brain structures analyzed. Depending on the cerebral area and technique, SB was able to reverse this impairment. The present study reinforces the need for more studies of HDAC inhibitors as possible target for new medications in treatment for BD., (Copyright © 2013. Published by Elsevier Ltd.)