Objective: To compare plasma concentrations of cannabidiol (CBD) following oral administration of two formulations of the drug (powder and dissolved in oil), and to evaluate the effects of these distinct formulations on responses to emotional stimuli in healthy human volunteers. Methods: In a randomized, double-blind, placebo-controlled, parallel-group design, 45 healthy male volunteers were randomly assigned to three groups of 15 subjects that received either 150 mg of CBD powder; 150 mg of CBD dissolved in corn oil; or placebo. Blood samples were collected at different times after administration, and a facial emotion recognition task was completed after 150 min. Results: There were no significant differences across groups in the subjective and physiological measures, nor in the facial emotion recognition task. However, groups that received the drug showed statistically significant differences in baseline measures of plasma CBD, with a significantly greater difference in favor of the oil formulation. Conclusion: When administered as a single 150-mg dose, neither formulation of oral CBD altered responses to emotional stimuli in healthy subjects. The oil-based CBD formulation resulted in more rapid achievement of peak plasma level, with an approximate fourfold increase in oral bioavailability.

Objective: The aim of the present study was to analyze the body sway response in specific phobia (SP) patients and healthy controls while viewing neutral, phobic, and disgusting images. Methods: The participants’ heart rate (HR) and skin conductance were also recorded during the procedure. Nineteen patients with arachnophobia and 19 healthy volunteers matched by age, gender, and years of education underwent a postural control test on a stabilometric platform. Results: The platform recorded increased body sway in the SP group when exposed to spider images (SPI). The SP group presented increases in most parameters (SD, velocity, frequency, area, p ≤ 0.05) when viewing pictures of the SPI category. Psychometric measures of subjective anxiety (State-Trait Anxiety Inventory, STAI) and physiological states (HR; skin conductance responses; spontaneous fluctuations in skin conductance) showed increased anxiety (p ≤ 0.05) in the SP group compared to healthy volunteers. High anxiety levels were observed throughout the assessment, including the task of exposure to SPI (p ≤ 0.05). No significant effect or correlation was found between skin conductance and body sway measures (p > 0.05). Conclusions: The results of the postural control test suggest the occurrence of a defensive escape response in SP, in agreement with previous evidence.

Objective: To assess the efficacy of cannabidiol (CBD) in the management of crack-cocaine craving and the treatment of frequent withdrawal symptoms. Methods: Thirty-one men with a diagnosis of crack-cocaine dependence were enrolled in a randomized, double-blind, placebo-controlled trial. We applied neuropsychological tests and assessed craving intensity, anxiety and depression symptoms, and substance use patterns at baseline and at the end of the trial. The participants were treated with CBD 300 mg/day or placebo for 10 days. During this period, we used a technique to induce craving and assessed the intensity of symptoms before and after the induction procedure. Results: Craving levels reduced significantly over the 10 days of the trial, although no differences were found between the CBD and placebo groups. Craving induction was successful in both groups, with no significant differences between them. Indicators of anxiety, depression, and sleep alterations before and after treatment also did not differ across groups. Conclusion: Under the conditions of this trial, CBD was unable to interfere with symptoms of crack-cocaine withdrawal. Further studies with larger outpatient samples involving different doses and treatment periods would be desirable and timely to elucidate the potential of CBD to induce reductions in crack-cocaine self-administration.

Current pharmacotherapy of Parkinson’s disease (PD) is palliative and unable to modify the progression of neurodegeneration. Treatments that can improve patients’ quality of life with fewer side effects are needed, but not yet available. Cannabidiol (CBD), the major non-psychotomimetic constituent of cannabis, has received considerable research attention in the last decade. In this context, we aimed to critically review the literature on potential therapeutic effects of CBD in PD and discuss clinical and preclinical evidence supporting the putative neuroprotective mechanisms of CBD. We searched MEDLINE (via PubMed) for indexed articles published in English from inception to 2019. The following keywords were used: cannabis; cannabidiol and neuroprotection; endocannabinoids and basal ganglia; Parkinson’s animal models; Parkinson’s history; Parkinson’s and cannabidiol. Few studies addressed the biological bases for the purported effects of CBD on PD. Six preclinical studies showed neuroprotective effects, while three targeted the antidyskinetic effects of CBD. Three human studies have tested CBD in patients with PD: an open-label study, a case series, and a randomized controlled trial. These studies reported therapeutic effects of CBD on non-motor symptoms. Additional research is needed to elucidate the potential effectiveness of CBD in PD and the underlying mechanisms involved.

Objective: Cannabidiol (CBD), one of the non-psychotomimetic compounds of Cannabis sativa, causes anxiolytic-like effects in animals, with typical bell-shaped dose-response curves. No study, however, has investigated whether increasing doses of this drug would also cause similar curves in humans. The objective of this study was to compare the acute effects of different doses of CBD and placebo in healthy volunteers performing a simulated public speaking test (SPST), a well-tested anxiety-inducing method. Method: A total of 57 healthy male subjects were allocated to receive oral CBD at doses of 150 mg (n=15), 300 mg (n=15), 600 mg (n=12) or placebo (n=15) in a double-blind procedure. During the SPST, subjective ratings on the Visual Analogue Mood Scale (VAMS) and physiological measures (systolic and diastolic blood pressure, heart rate) were obtained at six different time points. Results: Compared to placebo, pretreatment with 300 mg of CBD significantly reduced anxiety during the speech. No significant differences in VAMS scores were observed between groups receiving CBD 150 mg, 600 mg and placebo. Conclusion: Our findings confirm the anxiolytic-like properties of CBD and are consonant with results of animal studies describing bell-shaped dose-response curves. Optimal therapeutic doses of CBD should be rigorously determined so that research findings can be adequately translated into clinical practice.

ABSTRACT Introduction and Objective The R.E.N.A.L. nephrometry system (RNS) has been validated in multiple open, laparoscopic and robotic partial nephrectomy series. The aim of this study was to test the accuracy of R.E.N.A.L. nephrometry system in predicting perioperative outcomes in surgical treatment of kidney tumors <7.0cm in a prospective model. Materials and Methods Seventy-one patients were selected and included in this prospective study. We evaluate the accuracy of RNS in predicting perioperative outcomes (WIT, OT, EBL, LOS, conversion, complications and surgical margins) in partial nephrectomy using ROC curves, univariate and multivariate analyses. R.E.N.A.L. was divided in 3 groups: low complexity (LC), medium complexity (MC) and high complexity (HC). Results No patients in LC group had WIT >20 min, versus 41.4% and 64.3% MC and HC groups respectively (p=0.03); AUC=0.643 (p=0.07). RNS was associated with convertion rate (LC:28.6% ; MC:47.6%; HC:77.3%, p=0.02). Patients with RNS <8 were most often subjected to partial nephrectomy (93% x 72%, p=0.03) and laparoscopic partial nephrectomy (56.8% x 28%, p=0.02), AUC=0.715 (p=0.002). The RNS was also associated with operative time. Patients with a score >8 had 6.06 times greater chance of having a surgery duration >180 min. (p=0.017), AUC=0.63 (p=0.059). R.E.N.A.L. score did not correlate with EBL, complications (Clavien >3), LOS or positive surgical margin. Conclusion R.E.N.A.L. score was a good method in predicting surgical access route and type of nephrectomy. Also was associated with OT and WIT, but with weak accuracy. Although, RNS was not associated with Clavien >3, EBL, LOS or positive surgical margin.

Abstract Background: Neuroimaging studies are an invaluable source of information about the physiopathology of schizophrenia. Arterial spin labeling (ASL) is a new magnetic resonance technique (MRI) that is able to effectively evaluate brain function without the use of radiation. Objective: To make a systematic review of studies using ASL to compare resting-state regional cerebral blood flow (rCBF) patterns in patients with schizophrenia and healthy controls. Methods: Original articles were searched for on PubMed, Scopus, Web of Science and PsycINFO electronic databases. The search terms used were ‘arterial’, ‘spin’, ‘labeling’, and ‘schizophrenia’. Only studies comparing resting-state rCBF were included, a qualitative synthesis was then performed. Results: Ten articles were included in the review among a total of 22. Decreased rCBF in schizophrenia patients was described in the anterior cingulate, cuneus, fusiform gyrus, frontal lobe, left middle frontal gyrus, inferior frontal gyrus, lingual gyrus, middle occipital gyrus, and parietal lobe. The putamen was the only region with increased rCBF in schizophrenia. Discussion: The evidence of the studies reviewed lends support to the concept of hipofrontality in schizophrenia. rCBF alterations were found in regions classically associated with schizophrenia. ASL seems to be valid, and reliable tool to assess schizophrenia.

Abstract Background: Studies found inconsistent frequencies of social anxiety disorder (SAD) in Parkinson's disease (PD) (9.7%-50%). Previous reports did not test the impact of applying DSM-IV restrictive criteria that recommends the exclusion of secondary cases when diagnosing SAD in PD. Objective: Our aim is to estimate the frequency of social anxiety according to DSM-IV criteria and according to an inclusive broader approach. Methods: One hundred and ten PD patients were assessed for the presence of SAD using SCID-I, diagnosis of social anxiety were determined according to two different criteria: following and not following DSM-IV recommendation for exclusion of cases though to be secondary to a general medical condition. Results: SAD was present in 34 (31%) of patients, but 17 (15.5%) were secondary to a general medical condition. Patients with SAD were significantly younger, had earlier disease onset, had more severe PD symptoms, and were more frequently depressed. There was no difference in demographic and clinical features between primary and secondary SAD. Discussion: We conclude that the use of different diagnostic criteria may have a massive impact in the estimation of frequency of SAD in PD.

Objective: To examine association of sociodemographic characteristics, personality traits, social skills, and work variables with anxiety, depression, and alcohol dependence in medical residents. Methods: A total of 270 medical residents completed the following self-report instruments: sociodemographic and work questionnaire, Patient Health Questionnaire-4 (PHQ-4), Alcohol Use Disorders Identification Test-3 (AUDIT-3), Revised NEO-Five Factor Inventory (NEO-FFI-R), and Social Skills Inventory (SSI-Del-Prette). Data were analyzed using descriptive statistics and univariate and multivariate logistic regression analyses. Results: Multivariate analysis showed an association of neuroticism (odds ratio [OR] 2.60, p < 0.001), social skills (OR 0.41, p < 0.01), and number of shifts (OR 1.91, p = 0.03) with anxiety or depression, and of male sex (OR 3.14, p = 0.01), surgical residency (OR 4.40, p = 0.001), extraversion (OR 1.80, p < 0.01), and number of shifts (OR 2.32, p = 0.04) with alcohol dependence. Conclusion: The findings support a multidetermined nature of mental health problems in medical residents, in addition to providing data that may assist in the design of preventive measures to protect the mental health of this group.

Objectives: Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. Methods: Open-label trial conducted in an inpatient psychiatric unit. Results: Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. Conclusions: These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.

Objective: Schizophrenia is one of the most severe psychiatric disorders, and its current treatment relies on antipsychotic medications with only partial effectiveness. Clozapine is an atypical antipsychotic with a specific profile of action indicated for treatment-resistant schizophrenia. Neuroimaging studies assessing the effects of clozapine could help shed light on the neural underpinnings of the effects of this drug in the brain. The objective of this study was to review the available literature on the structural and functional neuroimaging findings associated with use of clozapine. Method: We conducted a systematic review of the indexed literature using the PubMed, BIREME, and ISI Web of Knowledge search engines and the following keywords: clozapine, neuroimaging, computed tomography, MRI, functional magnetic resonance, PET, SPECT, and DTI. Results: A total of 23 articles were included in the review. In structural studies, the use of clozapine was associated with volume reductions in the basal ganglia, especially the caudate nucleus, where functional neuroimaging studies also found decreased perfusion. In the frontal lobe, clozapine treatment was associated with increased gray matter volume and reduced perfusion. Conclusion: The results of the studies reviewed suggest that the use of clozapine is associated with distinctive structural and functional neuroimaging findings that are not shared with other antipsychotics.

Objective: To assess the discriminative capacity of the Kenny Music Performance Anxiety Inventory (K-MPAI), in its version adapted for Brazil, in a sample of 230 Brazilian adult musicians. Method: The Social Phobia Inventory (SPIN) was used to assess the presence of social anxiety indicators, adopting it as the gold standard. The Mann-Whitney U test and the receiver operating characteristic (ROC) curve were used for statistical analysis, with p ≤ 0.05 set as the significance level. Results: Subjects with social anxiety indicators exhibited higher mean total K-MPAI scores, as well as higher individual scores on 62% of its items. The area under the ROC curve was 0.734 (p = 0.001), and considered appropriate. Within the possible cutoff scores presented, the score -15 had the best balance of sensitivity and specificity values. However, the score -7 had greater specificity and accuracy. Conclusion: The K-MPAI showed appropriate discriminant validity, with a marked association between music performance anxiety and social anxiety. The cutoff scores presented in the study have both clinical and research value, allowing screening for music performance anxiety and identification of possible cases.

O objetivo desse estudo foi analisar uma série de casos de pacientes brasileiros com doença de Niemann-Pick tipo C (NP-C). Método Correlação entre manifestações clínicas, alterações laboratoriais, estudo molecular e resposta ao tratamento foram realizadas. Resultado A amostra consiste de 5 pacientes com idade entre 8 e 26 anos. Paralisia do olhar vertical supranuclear, ataxia cerebelar, demência, distonia e disartria estavam presentes em todos os casos. Coloração de filipina na cultura de fibroblastos mostrou padrão “clássico” em dois pacientes e padrão “variante” em três casos. O estudo molecular encontrou mutações no gene NPC1 em todos os alelos. O tratamento com miglustate foi realizado em 4 pacientes. Conclusão Embora coloração de filipina seja utilizada para confirmar o diagnóstico, o histiócito azul-marinho no aspirado de medula óssea frequentemente auxilia a confirmar o diagnóstico de NP-C. A mutação p.P1007A está correlacionada com o padrão “ variante” na coloração de filipina. A resposta ao tratamento com miglustate parece estar correlacionada com a idade e escore de desabilidade no momento do diagnóstico.

The aim of the study was to analyze a series of Brazilian patients with Niemann-Pick disease type C (NP-C). Method Correlations between clinical findings, laboratory data, molecular findings and treatment response are presented. Result The sample consisted of 5 patients aged 8 to 26 years. Vertical supranuclear gaze palsy, cerebellar ataxia, dementia, dystonia and dysarthria were present in all cases. Filipin staining showed the “classical” pattern in two patients and a “variant” pattern in three patients. Molecular analysis found mutations in the NPC1 gene in all alleles. Miglustat treatment was administered to 4 patients. Conclusion Although filipin staining should be used to confirm the diagnosis, bone marrow sea-blue histiocytes often help to diagnosis of NP-C. The p.P1007A mutation seems to be correlated with the “variant” pattern in filipin staining. Miglustat treatment response seems to be correlated with the age at disease onset and disability scale score at diagnosis.

Objective: To investigate the effects of cannabidiol (CBD) on mitochondrial complex and creatine kinase (CK) activity in the rat brain using spectrophotometry. Method: Male adult Wistar rats were given intraperitoneal injections of vehicle or CBD (15, 30, or 60 mg/kg) in an acute (single dose) or chronic (once daily for 14 consecutive days) regimen. The activities of mitochondrial complexes and CK were measured in the hippocampus, striatum, and prefrontal cortex. Results: Both acute and chronic injection of CBD increased the activity of the mitochondrial complexes (I, II, II-III, and IV) and CK in the rat brain. Conclusions: Considering that metabolism impairment is certainly involved in the pathophysiology of mood disorders, the modulation of energy metabolism (e.g., by increased mitochondrial complex and CK activity) by CBD could be an important mechanism implicated in the action of CBD.