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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.

BackgroundLevodopa-induced dyskinesias (LID) in Parkinson’s disease (PD) are frequent complications, and the endocannabinoid system has a role on its pathophysiology.ObjectiveTo test the hypothesis that the functioning of the endocannabinoid system would be altered in PD and in LID by measuring plasma and CSF levels of α-N-arachidonoylethanolamine (AEA) and 2-arachidonoyl-glycerol (2-AG) in patients with PD with and without LID and in healthy controls.MethodsBlood and CSF samples were collected from 20 healthy controls, 23 patients with PD without LID, and 24 patients with PD with LID. The levels of AEA and 2-AG were measured using a highly sensitive column switching ultrahigh-performance liquid chromatography-tandem mass spectrometry method.ResultsWhen pooled together, patients with PD had lower plasma and CSF levels of 2-AG and higher CSF levels of AEA compared to healthy controls (Mann-Whitney statistics = 303.0, p = 0.02). Patients with PD without LID had lower CSF levels of 2-AG (Kruskal-Wallis statistics = 7.76, p = 0.02) and higher CSF levels of AEA levels than healthy controls (Kruskal-Wallis statistics = 8.81, p = 0.01).ConclusionsThe findings suggest that the endocannabinoid system participates in the pathophysiology of PD symptoms, but its role in the pathophysiology of LID is still unclear.

Introduction Some individuals are more susceptible to recalling false information about events that never happened in their life. Nevertheless, there are several factors, such as personality characteristics, that appear to be related to memory performance. Social anxiety also provokes memory deficits for events that happen to other people, because these individuals tend to focus on their own inner selves rather than on external signs. Objective To investigate the influence of the personality characteristics of individuals with social anxiety disorder (SAD) on memory performance. Methods In this study, 183 university students had their memory tested using a complex emotional story about a mother and her son. Only subjects without clinical symptoms of depression and general anxiety (N = 148; 61 with SAD) were included in the study. Participants were compared for differences in personality characteristics using the Factorial Inventory of Personality and for SAD using the Social Phobia Inventory. Results The main results showed that memory performance of individuals with low percentile ranks in the personality characteristic dominance, i.e., those with low self-esteem, remembered more true information about the story than those with high scores when they did not have SAD. Conclusion The results are helpful to foster better understanding of the personality characteristics related to SAD, such as low dominance, which implies low self-esteem and difficulties with trust and with imposing themselves on others. The results could help development and improvement of techniques for therapeutic intervention.

Recent trials using cannabidiol (CBD) have shown that most acute and prolonged adverse effects of CBD are mild to moderate, with rare serious adverse effects (SAEs). This review focused on analyzing SAEs of CBD and their possible relation to drug-drug interactions.We systematically analyzed the SAEs reported in randomized controlled trials (RCTs) involving the administration of oral CBD for at least 1 week in both healthy volunteers and clinical samples.SAEs related to CBD in RCT are rare and include mainly elevated transaminases, convulsion, sedation, lethargy, and upper respiratory tract infections. Elevated transaminases are related to concomitant valproate use, while sedation, lethargy, and upper respiratory tract infections are related to concomitant clobazam use. Epileptic patients should be monitored when using CBD concomitantly with these and other antiepileptic drugs for other possible drug-drug interactions.

Cannabidiol (CBD) is a non-psychotomimetic compound of the Cannabis sativa that has been used for the treatment of severe epilepsy as well as other diseases of nervous system. However, toxicity studies of CBD have great relevance to guarantee the patients safety. In this context, morphological analyses of zebrafish can contribute to evaluate the teratogenic potential, as well as evaluation of acetylcholinesterase activity and motor activity of zebrafish are valuable tools to verify the neurotoxicity potential. In the present work, we use this methodology to test the toxicity of CBD to zebrafish embryos. No malformation was observed in morphological analysis of embryos exposed to all tested concentrations of CBD. Although, twenty per cent of embryos exposed to maximal dose of CBD (300 μg/L) hatched after 96hpf, while embryos in control solution had already hatched in this period. Embryos exposed to CBD did not show differences in acetylcholinesterase activity, but embryos exposed to CBD 20–300 μg/L were 1.4 up to 1.7-fold more active when compared to the control. Despite that, at 48 hpf, motor activity returned to control values. Our results suggest that the effects observed after CBD exposure are intimately related to CB1 receptor that is present in zebrafish since early stages of development. The present work showed early light effects induced by CBD exposure in concentrations that did not alter biochemical activity.

AIMS: The treatment of schizophrenia with antipsychotics is still unsatisfactory. Therefore, the search for new treatments and prevention is crucial, and animal models are fundamental tools for this objective. Preclinical and clinical data evidence the antipsychotic profile of sodium nitroprusside (SNP), a nitric oxide (NO) donor. We aimed to investigate SNP in treating and/or preventing the schizophrenia‐related behaviors presented by the spontaneously hypertensive rats (SHR) strain. METHODS: Wistar rats (WR) and SHRs were submitted to two schemes of treatment: (i) a single injection of SNP or vehicle in adulthood; (ii) a long‐term early treatment from 30 to 60 postnatal day with SNP or vehicle. The following behaviors were evaluated 24 hours after the acute treatment or 30 days after the long‐term treatment: locomotion, social interaction, and contextual fear conditioning. RESULTS: Spontaneously hypertensive rats presented hyperlocomotion, decreased social interaction, and impaired contextual fear conditioning. Single injection of SNP decreased social interaction in both strains and induced a deficit in contextual fear conditioning in WR. Oppositely, early treatment with SNP prevented the behavioral abnormalities in adult SHRs without promoting any effects in WR. CONCLUSION: Our preclinical data point to SNP as a preventive and safe strategy with a broad range of effectiveness to the positive, negative, and cognitive symptoms of schizophrenia.

Ayahuasca is a natural psychedelic brew, which contains dimethyltryptamine (DMT). Its potential as a psychiatric medicine has recently been demonstrated and its non-medical use around the world appears to be growing. We aimed to investigate well-being and problematic alcohol use in ayahuasca users, and ayahuasca’s subjective effects. An online, self-selecting, global survey examining patterns of drug use was conducted in 2015 and 2016 (n = 96,901). Questions were asked about: use of ayahuasca, lysergic acid diethylamide (LSD) and magic mushrooms; demographics, current well-being and past-year problematic alcohol use of past-year ayahuasca users and comparison drug users; and subjective effects of ayahuasca and comparison drugs. Ayahuasca users (n = 527) reported greater well-being than both classic psychedelic users (n = 18,138) and non-psychedelic drug-using respondents (n = 78,236). Ayahuasca users reported less problematic drinking than classic psychedelic users, although both groups reported greater problematic drinking than the other respondents. Ayahuasca’s acute subjective effects usually lasted for six hours and were most strongly felt one hour after consumption. Within our online, self-selecting survey, ayahuasca users reported better well-being than comparison groups and less problematic drinking than classic psychedelic users. Future longitudinal studies of international samples and randomised controlled trials are needed to dissect the effects of ayahuasca on these outcomes.

Depression is the most common psychiatric disorder in Parkinson's disease (PD). The aim of this study was to compare PD patients with current Major Depressive Disorder (MDD), lifetime MDD, and no MDD using three neuroimaging techniques. A total of 43 PD patients were selected and divided into three groups: (i) current MDD (n = 15), (ii) previous MDD without current MDD (n = 10); and (iii) control group (no current or lifetime MDD; n = 18). All participants underwent magnetic resonance imaging to evaluate cortical thickness, cortical and subcortical volume, and spectroscopy in the bilateral putamen and cingulate cortex. Volumetric analysis showed volume decreases in frontal and temporal areas, bilateral amygdala, and left cerebellar white matter in the lifetime MDD group compared to the control group. Furthermore, the volumes of the anterior cingulate cortex, right amygdala, and left cerebellar white matter were smaller in the group with current MDD compared to the control group. Regarding cortical thickness, the left rostral anterior cingulate gyrus of the group with previous MDD was thinner compared to the control group. There was a weak negative correlation between the NAA/Cre ratio in the right putamen and depressive symptoms. The results suggested current and lifetime MDD have a negative impact on the neurodegenerative process of PD, with decreased volume and/or reduction of cortical thickness in temporal and frontal areas, anterior cingulate cortex, amygdala, and cerebellar white matter.

Background and aimsAyahuasca is a dimethyltryptamine- and β-carboline-rich hallucinogenic beverage traditionally used by indigenous groups of Northwest Amazonian for ritual and therapeutic purposes. Animal and human studies suggest that ayahuasca has antidepressant and anxiolytic potentials and has a good safety profile. However, anxiety-like reactions may also occur after ayahuasca intake, although they are rare.MethodsCase report.ResultsHere, we describe a case of a non-medicated, symptom-free young female with generalized anxiety disorder, who experienced intense anxiety, panic, and hopelessness during and for 3 days after participating in an ayahuasca ritual. The symptoms appeared in the first hours after ayahuasca intake and were gradually reducing in the following hours/days, but were intense enough to cause significant suffering to her, who needed to seek psychiatric help and restarted pharmacological treatment.ConclusionsAlthough “bad/horror trips” with anxiety features may occur during the acute ...

This study reports a fast, sensitive, and selective column switching ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine the endocannabinoids (eCBs), anandamide (AEA), and 2-arachidonoylglycerol (2-AG) in plasma samples. This bidimensional system used a restricted access media column (RP-8 ADS, 25 mm × 4 mm × 25 μM) in the first dimension and a core-shell Kinetex C18 (100 mm × 2, 1.7 mm × 1 μM) column in the second dimension, followed by detection in a mass spectrometer triple quadrupole (multiple reactions monitoring mode) operating in the positive mode. RP-8 ADS was used for trace enrichment of eCBs (reverse phase partitioning) and macromolecular matrix size exclusion; the core-shell column was used for the chromatographic separation. The column switching UHPLC-MS/MS method presented a linear range spanning from 0.1 ng mL−1 (LOQ) to 6 ng mL−1 for AEA and from 0.04 ng mL−1 (LOQ) to 10 ng mL−1 for 2-AG. Excluding the LLOQ values, the precision assays provided coefficients of variation lower than 8% and accuracy with relative standard error values lower than 14%. Neither carryover nor matrix effects were detected. This high-throughput column switching method compared to conventional methods is time saving as it involves fewer steps, consumes less solvent, and presents lower LLOQ. The column switching UHPLC-MS/MS method was successfully applied to determine AEA and 2-AG in plasma samples obtained from Alzheimer’s disease patients.

Tetrahydrocannabinol (THC) and cannabidiol (CBD) are phytocannabinoids being linked with modulation of anxiety and depression. The recognition of emotions in facial expressions (REFE) is impaired in these disorders. Both drugs could modulate anxiety and mood by interfering with REFE. Thus, a systematic review of controlled trials assessing the effects of THC and CBD on REFE was performed. Ten studies describing seven distinct experiments were found (n = 170). THC (7.5-15 mg) did not alter REFE in three experiments, but reduced task performance in other three experiments. CBD did not alter REFE in two experiments, but improved task performance and counteracted the effects of THC in one experiment. THC (≥ 10 mg) and CBD (600 mg) showed opposite effects on brain activation, skin conductance, and anxiety measures with negative/threatening faces. The limited number of studies precludes firm conclusions on the effects of these substances on REFE. Further controlled trials are needed to elucidate the effects of THC and CBD on REFE. The PROSPERO ID for this study is CRD42019135085.

Background:Cannabidiol (CBD) is one of the main components of Cannabis sativa and has anxiolytic properties, but no study has been conducted to evaluate the effects of CBD on anxiety signs and symptoms in patients with Parkinson’s disease (PD). This study aimed to evaluate the impacts of acute CBD administration at a dose of 300 mg on anxiety measures and tremors induced by a Simulated Public Speaking Test (SPST) in individuals with PD.Methods:A randomised, double-blinded, placebo-controlled, crossover clinical trial was conducted. A total of 24 individuals with PD were included and underwent two experimental sessions within a 15-day interval. After taking CBD or a placebo, participants underwent the SPST. During the test, the following data were collected: heart rate, systemic blood pressure and tremor frequency and amplitude. In addition, the Visual Analog Mood Scales (VAMS) and Self-Statements during Public Speaking Scale were applied. Statistical analysis was performed by repeated-measures analysis of variance (ANOVA) while considering the drug, SPST phase and interactions between these variables.Results:There were statistically significant differences in the VAMS anxiety factor for the drug; CBD attenuated the anxiety experimentally induced by the SPST. Repeated-measures ANOVA showed significant differences in the drug for the variable related to tremor amplitude as recorded by the accelerometer.Conclusion:Acute CBD administration at a dose of 300 mg decreased anxiety in patients with PD, and there was also decreased tremor amplitude in an anxiogenic situation.

A selective and sensitive method that uses automated in-tube solid-phase microextraction coupled to ultra-performance liquid chromatography–tandem mass spectrometry (in-tube SPME/UHPLC–MS/MS) was developed to determine cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) in plasma samples. A new dummy molecularly imprinted monolithic capillary (MIP monolith) for in-tube SPME was prepared by in situ polymerization in a fused silica capillary; hydrogenated cannabidiol was employed as dummy template. Fourier Transform Infrared Spectroscopy (FTIR) confirmed that the synthesis reagents were incorporated into the polymer chain. On the basis of the microscopy images (scanning electron microscopy – SEM and transmission electron microscopy – TEM), the MIP monolithic phase presented larger pores than the non-imprinted monolithic phase (NIP monolith), as well as a skeleton comprising clusters consisting of microspheres. By optimizing the polymerization conditions, the MIP monolith specifically recognized CBD and Δ9-THC. The MIP monolith had CBD and Δ9-THC sorption capacity of 148.05 and 44.49 ng cm−3, respectively. The capillary was reused over fifty times without significant changes in its extraction efficiency. For both CBD and Δ9-THC, in-tube SPME/UHPLC–MS/MS presented linear range from 10 to 300 ng mL−1, precision with coefficient of variation (CV) values ranging from 0.2% to 19.1% (LLOQ), and accuracy with relative standard deviation (RSD) values spanning from −9.3% to 19.6% (LLOQ). The developed method was successfully applied to determine cannabinoid levels in plasma samples from volunteer patients in treatment with CBD.

This systematic review and meta-analysis examines whether physician depressive symptoms are associated with the risk for perceived or observed medical errors., Key Points Question What are the magnitude and direction of associations between physician depressive symptoms and medical errors? Findings In this systematic review and meta-analysis of 11 studies involving 21 517 physicians, physicians with a positive screening for depression were highly likely to report medical errors. Examination of longitudinal studies demonstrated that the association between physician depressive symptoms and medical errors is bidirectional. Meaning This study found that physician depressive symptoms were associated with medical errors, highlighting the relevance of physician well-being to health care quality and underscoring the need for systematic efforts to prevent or reduce depressive symptoms among physicians., Importance Depression is highly prevalent among physicians and has been associated with increased risk of medical errors. However, questions regarding the magnitude and temporal direction of these associations remain open in recent literature. Objective To provide summary relative risk (RR) estimates for the associations between physician depressive symptoms and medical errors. Data Sources A systematic search of Embase, ERIC, PubMed, PsycINFO, Scopus, and Web of Science was performed from database inception to December 31, 2018. Study Selection Peer-reviewed empirical studies that reported on a valid measure of physician depressive symptoms associated with perceived or observed medical errors were included. No language restrictions were applied. Data Extraction and Synthesis Study characteristics and RR estimates were extracted from each article. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using subgroup meta-analysis and metaregression. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was followed. Main Outcomes and Measures Relative risk estimates for the associations between physician depressive symptoms and medical errors. Results In total, 11 studies involving 21 517 physicians were included. Data were extracted from 7 longitudinal studies (64%; with 5595 individuals) and 4 cross-sectional studies (36%; with 15 922 individuals). The overall RR for medical errors among physicians with a positive screening for depression was 1.95 (95% CI, 1.63-2.33), with high heterogeneity across the studies (χ2 = 49.91; P

Introduction Previous studies have shown attenuated cortisol awakening response in patients with posttraumatic stress disorder (PTSD). Case presentation A 15-year-old girl, a survivor of acute sexual violence, received a 7-day oral treatment with cannabidiol. She was followed-up from the first 24 hours after the event for 6 months, for assessment of the effects of this treatment on the reconsolidation of memories related to the traumatic event. Discussion Cannabidiol treatment did not prevent the onset of PTSD. Cortisol awakening responses after the onset of the disorder were attenuated compared with those observed in the same individual before the onset of PTSD, in line with previous evidence from studies comparing groups with and without PTSD.

Social anxiety disorder (SAD), or social phobia, is one of the most common types of anxiety disorder, with a lifetime prevalence that can reach 15%. Pharmacological treatments for SAD have moderate efficacy and are associated with significant adverse reactions. Therefore, recent studies have focused on searching for new treatments for this disorder. Preclinical studies and preliminary evidence in humans suggest that the phytocannabinoid cannabidiol and the neuropeptide oxytocin have anxiolytic effects. In the present text, we review this evidence and its implications for pharmacological treatment. We conclude that although current available studies show promising results regarding both the safety and efficacy of cannabidiol and oxytocin for the treatment of SAD, most studies were performed using single or few doses of these compounds, with small sample sizes. Therefore, future studies should explore the anxiolytic potential of these compounds using long-term, placebo-controlled designs with larger samples to elucidate the possible use of these compounds in the treatment of SAD.

Objective: 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. Methods: 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. Results: 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. Conclusions: Additional research is needed to elucidate the potential effectiveness of CBD in PD and the underlying mechanisms involved.

The behavioural effects elicited by chemical constituents of Cannabis sativa, such as cannabidiol (CBD), on the ventromedial hypothalamus (VMH) are not well understood. There is evidence that VMH neurons play a relevant role in the modulation of unconditioned fear-related defensive behavioural reactions displayed by laboratory animals.This study was designed to explore the specific pattern of distribution of the CBA panic attack-like state was triggered in Wistar rats by intra-VMH microinjections of N-methyl-D-aspartate (NMDA). One of three different doses of CBD was microinjected into the VMH prior to local administration of NMDA. In addition, the most effective dose of CBD was used after pre-treatment with the CBThe morphological procedures demonstrated distribution of labelled CBThese findings suggest that CBD causes panicolytic-like effects and reduces unconditioned fear-induced antinociception when administered in the VMH, and these effects are mediated by the CB

Cannabidiol (CBD), a major cannabinoid of hemp, does not bind to CB1 receptors and is therefore devoid of psychotomimetic properties. Under acidic conditions, CBD can be transformed to delta9-tetrahydrocannabinol (THC) and other cannabinoids. It has been argued that this may occur also after oral administration in humans. However, the experimental conversion of CBD to THC and delta8-THC in simulated gastric fluid (SGF) is a highly artificial approach that deviates significantly from physiological conditions in the stomach; therefore, SGF does not allow an extrapolation to in vivo conditions. Unsurprisingly, the conversion of oral CBD to THC and its metabolites has not been observed to occur in vivo, even after high doses of oral CBD. In addition, the typical spectrum of side effects of THC, or of the very similar synthetic cannabinoid nabilone, as listed in the official Summary of Product Characteristics (e.g., dizziness, euphoria/high, thinking abnormal/concentration difficulties, nausea, tachycardia) has not been observed after treatment with CBD in double-blind, randomized, controlled clinical trials. In conclusion, the conversion of CBD to THC in SGF seems to be an in vitro artifact.

Serotonergic hallucinogens produce alterations of perceptions, mood, and cognition, and have anxiolytic, antidepressant, and antiaddictive properties. These drugs act as agonists of frontocortical 5-HT2A receptors, but the neural basis of their effects are not well understood. Thus, we conducted a systematic review of neuroimaging studies analyzing the effects of serotonergic hallucinogens in man. Studies published in the PubMed, Lilacs, and SciELO databases until 12 April 2016 were included using the following keywords: "ayahuasca", "DMT", "psilocybin", "LSD", "mescaline" crossed one by one with the terms "mri", "fmri", "pet", "spect", "imaging" and "neuroimaging". Of 279 studies identified, 25 were included. Acute effects included excitation of frontolateral/frontomedial cortex, medial temporal lobe, and occipital cortex, and inhibition of the default mode network. Long-term use was associated with thinning of the posterior cingulate cortex, thickening of the anterior cingulate cortex, and decreased neocortical 5-HT2A receptor binding. Despite the high methodological heterogeneity and the small sample sizes, the results suggest that hallucinogens increase introspection and positive mood by modulating brain activity in the fronto-temporo-parieto-occipital cortex.

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.

Objective: To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline). Methods: Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection. Results: Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression. Conclusion: Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.

The prevalence rates of depression and anxiety are at least two times higher in diabetic patients, increasing morbidity and mortality. Cannabidiol (CBD) has been identified as a therapeutic agent viable to treat diverse psychiatric disorders. Thus, this study aimed to investigate the effect of CBD treatment (once a day for 14 days starting two weeks after diabetes induction; at doses of 0, 3, 10 or 30 mg/kg, i.p.) on depression- and anxiety-like behaviors associated with experimental diabetes induced by streptozotocin (60 mg/kg; i.p.) in rats. Levels of plasma insulin, blood glucose, and weight gain were evaluated in all experimental groups, including a positive control group treated with imipramine. The rats were tested in the modified forced swimming test (mFST) and elevated plus maze (EPM) test. Besides, the levels of serotonin (5-HT), noradrenaline (NA) and dopamine (DA) in two emotion-related brain regions, the prefrontal cortex (PFC) and hippocampus (HIP) were evaluated using high-pressure liquid chromatography. Our results showed that CBD treatment (only at the higher dose of 30 mg/kg) reduced the exaggerated depressive- and anxiogenic-like behaviors of diabetic (DBT) rats, which may be associated with altered 5-HT, NA and/or DA levels observed in the PFC and HIP. Treatment with CBD (higher dose) also induced a significant increase in weight gain and the insulin levels (and consequently reduced glycemia) in DBT rats. The long-term CBD effects gave rise to novel therapeutic strategies to limit the physiological and neurobehavioral deficits in DBT rats. This approach provided evidence that CBD can be useful for treating psychiatry comorbidities in diabetic patients.

Bipolar disorder (BD) is commonly associated with comorbidities, especially substance use disorders. In light of this, the present review aimed to investigate the prevalence and clinical correlates of cannabis use in BD. Studies evaluating the prevalence of cannabis use among patients with BD and studies reporting a dichotomous sample of patients with cannabis use compared to those without the use were included. Meta-analyses using random-effects models were performed, and sources of heterogeneity were explored using meta-regression. The search resulted in 2918 publications, of which 53 were included. The prevalence of cannabis use was 24% (95%CI:18–29; k = 35; n = 51,756). Cannabis use was significantly associated with being younger, male, and single; having fewer years of education and an earlier onset of affective symptoms; and lifetime psychotic symptoms, suicide attempts, and use of tobacco, alcohol, and other substances. In conclusion, cannabis use present in almost one-quarter of patients with BD and is associated with factors that are highly relevant for both clinical practice and public health.

Background: Recognition of emotions in facial expressions (REFE) is a key aspect of social cognition. Anxiety and mood disorders are associated with deficits in REFE, and anxiolytics and antidepressants reverse these deficits. Recent studies have shown that serotonergic hallucinogens (i.e. ayahuasca, dimethyltryptamine, psilocybin, lysergic acid diethylamide [LSD], and mescaline) have anxiolytic and antidepressant properties, but their effects on REFE are not well understood. The purpose of the study was to conduct a systematic review analyzing the effects of serotonergic hallucinogens on REFE in humans. Methods: Studies published in the PubMed, PsycINFO, and Web of Science databases until 19 October 2018 which analyzed the effects of serotonergic hallucinogens on REFE in humans were included. Results: Of the 62 studies identified, 8 studies were included. Included studies involved the administration of a single or a few doses of LSD or psilocybin, and most trials were randomized and controlled with placebo. LSD and psilocybin reduced the recognition of negative emotions in most studies and modulated amygdala activity to these stimuli, which was correlated with antidepressive effects in patients. Both drugs were well tolerated. Conclusions: Serotonergic hallucinogens reduced the recognition of negative emotions by modulating amygdala activity. Despite the small sample sizes, results suggest that serotonergic hallucinogens show promising beneficial effects on deficits in REFE.

Background. As the survival of preterm infants has increased significantly, germinal matrix hemorrhage (GMH) has become an important public health issue. Nevertheless, treatment strategies for the ...

Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Asthma remains a major public health problem and, at present, there are no effective interventions capable of reversing airway remodelling. Cannabidiol (CBD) is known to exert immunomodulatory effects through the activation of cannabinoid-1 and − 2 (CB1 and CB2) receptors located in the central nervous system and immune cells, respectively. However, as the role of CBD on airway remodelling and the mechanisms of CB1 and CB2 aren’t fully elucidated, this study was designed to evaluate the effects of cannabidiol in this scenario. Allergic asthma was induced in Balb/c mice exposed to ovalbumin, and respiratory mechanics, collagen fibre content in airway and alveolar septa, cytokine levels, and CB1 and CB2 expression were determined. Moreover, expressions of CB1 and CB2 in induced sputum of asthmatic individuals and their correlation with airway inflammation and lung function were also evaluated. CBD treatment, regardless of dosage, decreased airway hyperresponsiveness, whereas static lung elastance only reduced with high dose. These outcomes were accompanied by decreases in collagen fibre content in both airway and alveolar septa and the expression of markers associated with inflammation in the bronchoalveolar lavage fluid and lung homogenate. There was a significant and inverse correlation between CB1 levels and lung function in asthmatic patients. CBD treatment decreased the inflammatory and remodelling processes in the model of allergic asthma. The mechanisms of action appear to be mediated by CB1/CB2 signalling, but these receptors may act differently on lung inflammation and remodelling.

Aim The Structured Clinical Interview for the DSM is one of the most used diagnostic instruments in clinical research worldwide. The current Clinician Version of the instrument (SCID-5-CV) has not yet been assessed in respect to its psychometric qualities. We aimed to assess the clinical validity and different reliability indicators (interrater test-retest, joint interview, face-to-face vs telephone application) of the SCID-5-CV in a large sample of 180 non-prototypical and psychiatric patients based on interviews conducted by raters with different levels of clinical experience. Methods The SCID-5-CV was administered face-to-face and by telephone by 12 psychiatrists/psychologists who took turns as raters and observers. Clinical diagnoses were established according to DSM-5 criteria and the longitudinal, expert, all data (LEAD) procedure. We calculated the percentage of agreement, diagnostic sensitivity and specificity, and the level of agreement (kappa) for diagnostic categories and specific diagnoses. Results The percentage of positive agreement between the interview and clinical diagnoses ranged between 73% and 97% and the diagnostic sensitivity/specificity were >0.70. In the joint interview, the levels of positive agreement were high (>75%) and kappa levels were >0.70 for most diagnoses. The values were less expressive, but still adequate, for interrater test-retest interviews. Conclusion The SCID-5-CV presented excellent reliability and high specificity as assessed with different methods. The clinical validity of the instrument was also confirmed, which supports its use in daily clinical practice. We highlight the adequacy of the instrument to be used via telephone and the need for careful use by professionals with little experience in psychiatric clinical practice.

Most diabetic patients describe moderate to severe pain symptoms whose pharmacological treatment is palliative and poorly effective. Cannabidiol (CBD) has shown promising results in painful conditions. Then, we aimed to investigate the potential antinociceptive effect of CBD over the mechanical allodynia in streptozotocin-induced diabetic (DBT) rats, as well as its involved mechanisms. Wistar adult male diabetic rats were treated acutely or sub-chronically (for 14 days) with CBD (0.1, 0.3 or 3 mg/kg, intraperitoneal; i.p.) and had their mechanical threshold assessed using the electronic Von Frey. Acute treatment with CBD (at doses of 0.3 and 3 mg/kg) exerted a significant anti-allodynic effect, which is not associated with locomotor impairment. The antinociceptive effect of CBD (3 mg/kg) was not altered by the pre-treatment with CB1 or CB2 receptor antagonists (AM251 and AM630; respectively; both at a dose of 1 mg/kg, i.p.) nor by glycine receptor antagonist (strychnine hydrochloride, 10 μg/rat, intrathecal, i.t.). However, this effect was completely prevented by the pre-treatment with the selective 5-HT1A receptor antagonist WAY 100135 (3 μg/rat, i.t.). Sub-chronic treatment with CBD (0.3 or 3 mg/kg) induced a sustained attenuation of the mechanical allodynia in DBT rats. DBT rats presented significantly lower spinal cord levels of serotonin, which was prevented by the daily treatment with CBD (0.3 mg/kg). Taken together, our data suggest that CBD may be effective in the treatment of painful diabetic neuropathy and this effect seems to be potentially mediated by the serotonergic system activation through 5-HT1A receptors.

Studies suggest that the endocannabinoid and endovanilloid systems are implicated in the pathophysiology of schizophrenia. The Spontaneously Hypertensive Rats (SHR) strain displays impaired contextual fear conditioning (CFC) attenuated by antipsychotic drugs and worsened by pro-psychotic manipulations. Therefore, SHR strain is used to study emotional processing/associative learning impairments associated with schizophrenia and effects of potential antipsychotic drugs. Here, we evaluated the expression of CB1 and TRPV1 receptors in some brain regions related to the pathophysiology of schizophrenia. We also assessed the effects of drugs that act on the endocannabinoid/endovanilloid systems on the CFC task in SHRs and control animals (Wistar rats - WRs). The following drugs were used: AM404 (anandamide uptake/metabolism inhibitor), WIN55-212,2 (non-selective CB1 agonist), capsaicin (TRPV1 agonist), and capsazepine (TRPV1 antagonist). SHRs displayed increased CB1 expression in prelimbic cortex and cingulate cortex area 1 and in CA3 region of the dorsal hippocampus. Conversely, SHRs exhibited decreases in TRPV1 expression in prelimbic and CA1 region of dorsal hippocampus and increases in the basolateral amygdala. AM404, WIN 55,212-2 and capsaicin attenuated SHRs CFC deficit, although WIN 55,212-2 worsened SHRs CFC deficit in higher doses. WRs and SHRs CFC were modulated by distinct doses, suggesting that these strains display different responsiveness to cannabinoid and vanilloid drugs. Treatment with capsazepine did not modify CFC in either strains. The effects of AM404 on SHRs CFC deficit was not blocked by pretreatment with rimonabant (CB1 antagonist) or capsazepine. These results reinforce the involvement of the endocannabinoid/endovanilloid systems in the SHRs CFC deficit and point to these systems as targets to treat the emotional processing/cognitive symptoms of schizophrenia.

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.

Iron accumulation in the brain has been recognized as a common feature of both normal aging and neurodegenerative diseases. Cognitive dysfunction has been associated to iron excess in brain regions in humans. We have previously described that iron overload leads to severe memory deficits, including spatial, recognition, and emotional memory impairments in adult rats. In the present study we investigated the effects of neonatal iron overload on proteins involved in apoptotic pathways, such as Caspase 8, Caspase 9, Caspase 3, Cytochrome c, APAF1, and PARP in the hippocampus of adult rats, in an attempt to establish a causative role of iron excess on cell death in the nervous system, leading to memory dysfunction. Cannabidiol (CBD), the main non-psychotropic component of Cannabis sativa, was examined as a potential drug to reverse iron-induced effects on the parameters analyzed. Male rats received vehicle or iron carbonyl (30 mg/kg) from the 12th to the 14th postnatal days and were treated with vehicle or CBD (10 mg/kg) for 14 days in adulthood. Iron increased Caspase 9, Cytochrome c, APAF1, Caspase 3 and cleaved PARP, without affecting cleaved Caspase 8 levels. CBD reversed iron-induced effects, recovering apoptotic proteins Caspase 9, APAF1, Caspase 3 and cleaved PARP to the levels found in controls. These results suggest that iron can trigger cell death pathways by inducing intrinsic apoptotic proteins. The reversal of iron-induced effects by CBD indicates that it has neuroprotective potential through its anti-apoptotic action.

Background Genetic and epigenetic variations of the serotonin transporter gene (SLC6A4) have been related to the etiology of depression. The 5-HTTLPR polymorphism at the SLC6A4 promoter region has two variants, a short allele (S) and a long allele (L), in which the S allele results in lower gene transcription and has been associated with depression. The short S-allele of 5-HTTLPR polymorphism of this gene has been associated with depression. In addition to molecular mechanisms, exposure to early life risk factors such as maternal depression seems to affect the development of depression in postnatal life. The present study investigated the association of 5-HTTLPR polymorphism and CpG DNA methylation (5mC) levels of an AluJb repeat element at the SLC6A4 promoter region in mother–child pairs exposed to maternal depression. Methods We analyzed DNA samples from 60 subjects (30 mother–child pairs) split into three groups, with and without major depression disorder (DSM-IV) among children and mothers. The genotyping of 5-HTTLPR polymorphism and quantification of 5mC levels was performed by qualitative PCR and methylation-sensitive restriction enzyme digestion, and real-time quantitative PCR (MSRED-qPCR), respectively. Results The sample analyzed presented a higher frequency of S allele of 5-HTTLPR (67.5%). Despite the high frequency of this allele, we did not find statistically significant differences between individuals carrying at least one S allele between the depression and healthy control subjects, or among the mother–child pair groups with different patterns of occurrence of depression. In the group where the mother and child were both diagnosed with depression, we found a statistically significant decrease of the 5mC level at the SLC6A4 promoter region. Limitations The limitations are the relatively small sample size and lack of gene expression data available for comparison with methylation data. Conclusion In this study, we demonstrated a repeat element specific 5mC level reduction in mother–child pairs, concordant for the diagnosis of depression.

Background The identification of facial emotions is a key skill as it promotes rapid and accurate recognition of emotions and enables better communication and greater social adaptation. More recent studies have suggested that impaired social interactions may be related to deficits in social cognition and therefore in the recognition of facial expressions, contributing to social disturbance among individuals with borderline personality disorder (BPD). Objective To present the results of an empirical study assessing the recognition of facial emotion expressions in women with BPD, having as reference a group of healthy women from the general population. Methods The subjects (40 female with BPD and 40 controls) were assessed with a dynamic task on a computer screen for recognition of facial expressions of emotion. Results The BPD group had a lower accuracy in perceiving emotions of fear and surprise and slowness in recognising happiness. Logistic regression analyses also identified an association between BPD and higher sensitivity in the recognition of anger. Discussion Women with BPD made more mistakes in the recognition of negative emotions, which can bias the behaviour and regulation of affective states, favouring in turn the emergence of some typical symptoms associated with BPD.

The absence of the adhesio interthalamica (AI; also called interthalamic adhesion or massa intermedia) and the presence of a large cavum septum pellucidum (CSP) later in life have been related to neurodevelopmental alterations and have not been systematically investigated in epilepsy to date. This study carried out a MRI evaluation of the AI and CSP in a large sample with mesial temporal lobe epilepsy (MTLE). A total of 179 patients, classified according to the side of the epileptogenic focus, and 156 age- and sex-balanced healthy controls were assessed. Between-group comparisons of the prevalence and length of both AI and CSP were conducted. Neuropsychological assessments were also performed in 160 MTLE patients. The patients exhibited reduction in the AI prevalence (P

Many studies suggest that the substantia nigra, pars reticulata (SNpr), a tegmental mesencephalic structure rich in γ-aminobutyric acid (GABA)- and cannabinoid receptor-containing neurons, is involved in the complex control of defensive responses through the neostriatum-nigral disinhibitory and nigro-tectal inhibitory GABAergic pathways during imminently dangerous situations. The aim of the present work was to investigate the role played by CB1-cannabinoid receptor of GABAergic pathways terminal boutons in the SNpr or of SNpr-endocannabinoid receptor-containing interneurons on the effect of intra-nigral microinjections of cannabidiol in the activity of nigro-tectal inhibitory pathways. GABAA receptor blockade in the deep layers of the superior colliculus (dlSC) elicited vigorous defensive behaviour. This explosive escape behaviour was followed by significant antinociception. Cannabidiol microinjection into the SNpr had a clear anti-aversive effect, decreasing the duration of defensive alertness, the frequency and duration of defensive immobility, and the frequency and duration of explosive escape behaviour, expressed by running and jumps, elicited by transitory GABAergic dysfunction in dlSC. However, the innate fear induced-antinociception was not significantly changed. The blockade of CB1 endocannabinoid receptor in the SNpr decreased the anti-aversive effect of canabidiol based on the frequency and duration of defensive immobility, the frequency of escape expressed by running, and both the frequency and duration of escape expressed by jumps. These findings suggest a CB1 mediated endocannabinoid signalling in cannabidiol modulation of panic-like defensive behaviour, but not of innate fear-induced antinociception evoked by GABAA receptor blockade with bicuculline microinjection into the superior colliculus, with a putative activity in nigro-collicular GABAergic pathways.

Objective: It is our aim to elaborate on the new developments in regard to the respiratory subtype (RS) of panic disorder (PD) since it was first described. We will present psychopathological features, diagnostic criteria, genetic and physiopathological hypotheses, as well as therapeutic and prognostic characteristics. Method: Two searches were performed in the Thomson Reuters Web of Knowledge (http://wokinfo.com/): 1 - search terms: “panic disorder” AND (“respiratory symptom” OR “respiratory symptoms” OR “respiratory subtype” OR “respiratory panic” OR “cardiorespiratory”); 2 - all articles citing Briggs and colleagues’ 1993 article “Subtyping of Panic Disorder by Symptom Profile” (Br J Psychiatry 1993;163: 201-9). Only those articles involving human subjects and written English were included. Results: In comparison with patients of the non-respiratory subtype (NRS), RS patients showed greater familial history of PD, and higher comorbidity rates for anxiety disorders and depressive disorders. These patients were also more sensitive to CO 2 , hyperventilation and caffeine. Conclusion: Certain characteristics, such as heightened sensitivity to CO 2 and the higher incidence of a family history of PD, clearly distinguished the Respiratory Subtype patients from the Non-Respiratory. Nonetheless, some studies failed to demonstrate differential responses to pharmacological treatment and CBT across the subtypes. RS patients seem to respond faster than NRS to pharmacological treatment with antidepressants and benzodiazepines, but more studies are needed to confirm this finding.

Psychedelic agents have a long history of use by humans for their capacity to induce profound modifications in perception, emotion and cognitive processes. Despite increasing knowledge of the neural mechanisms involved in the acute effects of these drugs, the impact of sustained psychedelic use on the human brain remains largely unknown. Molecular pharmacology studies have shown that psychedelic 5-hydroxytryptamine (5HT)2A agonists stimulate neurotrophic and transcription factors associated with synaptic plasticity. These data suggest that psychedelics could potentially induce structural changes in brain tissue. Here we looked for differences in cortical thickness (CT) in regular users of psychedelics. We obtained magnetic resonance imaging (MRI) images of the brains of 22 regular users of ayahuasca (a preparation whose active principle is the psychedelic 5HT2A agonist N,N-dimethyltryptamine (DMT)) and 22 controls matched for age, sex, years of education, verbal IQ and fluid IQ. Ayahuasca users showed significant CT differences in midline structures of the brain, with thinning in the posterior cingulate cortex (PCC), a key node of the default mode network. CT values in the PCC were inversely correlated with the intensity and duration of prior use of ayahuasca and with scores on self-transcendence, a personality trait measuring religiousness, transpersonal feelings and spirituality. Although direct causation cannot be established, these data suggest that regular use of psychedelic drugs could potentially lead to structural changes in brain areas supporting attentional processes, self-referential thought, and internal mentation. These changes could underlie the previously reported personality changes in long-term users and highlight the involvement of the PCC in the effects of psychedelics.

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-A u sberg 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.

Background Chronic pelvic pain (CPP) is a complex condition wich is associated with emotional factors, specially depression and anxiety. Objectives To make a systematic review to provide a detailed summary of relevant literature on the association between CPP and different psychiatric disorders/symptoms. Methods A systematic review of articles in the international literature published between 2003 and 2014 was performed in the electronic databases PubMed, PsycINFO, LILACS, and SciELO using the terms (chronic pelvic pain) AND (psychiatry OR psychiatric OR depression OR anxiety OR posttraumatic stress OR somatoform). The searches returned a total of 529 matches that were filtered according to predefined inclusion and exclusion criteria. A total of 18 articles were selected. Results The investigations focused mainly on the assessment of depression and anxiety disorders/symptoms, with rather high rates (17-38.6%). Depression and anxiety symptoms were more prevalent among women with CPP compared to healthy groups. Comparisons between groups with CPP and with specific pathologies that also have pain as a symptom showed that depression indicators are more frequent in CPP. Depressive symptoms tend to be more common in CPP and have no particular association with pain itself, the core feature of CPP. Discussion Other aspects of CPP seem to play a specific role in this association. Anxiety and other psychiatric disorders require further investigation so that their impact on CPP can be better understood.

Background: Among the many cannabinoids in the cannabis plant, cannabidiol (CBD) is a compound that does not produce the typical subjective effects of marijuana. Objectives: The aim of the present review is to describe the main advances in the development of the experimental and clinical use of cannabidiol CBD in neuropsychiatry. Methods: A non-systematic search was performed for studies dealing with therapeutic applications of CBD, especially performed by Brazilian researchers. Results: CBD was shown to have anxiolytic, antipsychotic and neuroprotective properties. In addition, basic and clinical investigations on the effects of CBD have been carried out in the context of many other health conditions, including its potential use in epilepsy, substance abuse and dependence, schizophrenia, social phobia, post-traumatic stress, depression, bipolar disorder, sleep disorders, and Parkinson. Discussion: CBD is an useful and promising molecule that may help patients with a number of clinical conditions. Controlled clinical trials with different neuropsychiatric populations that are currently under investigation should bring important answers in the near future and support the translation of research findings to clinical settings.

Endocannabinoids (ECs) are endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors [cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2)]. Many ECs have been characterized; anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) are still considered the primary ECs signaling mediators. Dysregulation of ECs has been implicated in a wide range of pathologies, including neurodegenerative diseases. Understanding how ECs participate in neurological diseases is important to describe the pathology and to establish new treatments. Considering the physicochemical properties of ECs, liquid chromatography coupled to tandem mass spectrometry has become the reference method to determine these endogenous substances, in trace levels, in different biological samples. This review describes the recent advances in LC-MS/MS methods designed to determine ECs in complex biological matrixes. The advantages, limitations, selectivity, matrix effect, and sensitivity associated with each approach are emphasized. This article comprises three sections: (I) sample preparation techniques (conventional, microextraction, and online systems), (II) chromatographic methods (especially LC-MS/MS), and (III) relationship between ECs levels and neurodegenerative diseases.

Background Despite the general agreement regarding the central role of the clinical learning environment in graduate medical education, its assessment remains challenging owing to the lack of available standardized measures. We report on the cross-cultural adaptation and psychometric assessment of the Brazilian-Portuguese version of Seelig’s Resident Questionnaire. Methods The present study was performed in two steps. First, a cross-cultural translation and adaptation of the Resident Questionnaire was conducted through multiple translations, synthesis of versions, back-translation, content validation, and face validation. Subsequently, a sample of 288 (72%) resident physicians enrolled in 40 residency programs at a Brazilian university hospital completed the following measures: 1) the Brazilian-Portuguese version of the Resident Questionnaire (for factor analysis and to determine internal consistency, reliability, and validity); 2) three existing, validated psychometric measures (to determine convergent and divergent validity); and 3) a self-report questionnaire. Results Confirmatory factor analysis results provided support for the three-dimensional model of the Resident Questionnaire in use on a sample of Brazilian resident physicians, having been previously verified for use in American samples. All three factors (emotional distress, learning environment satisfaction, and workload satisfaction) verified in the confirmatory factor analysis showed good internal consistency (α > .80), reliability (Raykov’s rho > .80), and correlations in the expected directions and magnitude with measures of depressive symptoms, duty hours, organizational conditions, and emotional exhaustion. Conclusions This study is the first to adapt a measure of the clinical learning environment of residency programs into Brazilian Portuguese. Our findings suggest that the adapted version of the Resident Questionnaire is valid and reliable for assessing Brazilian residency programs. This free, easy-access, and fast-application instrument may be a useful standardized measure for research and educational purposes concerning the clinical learning environments of resident physicians.

Cannabis is the most commonly used illicit substance worldwide and the prevalence of users continues to increase. Over the last 2 decades, the world has seen significant changes regarding cannabis for recreational use as well as application in its use as a therapeutic medicine. This is likely to have influenced the decreasing perception of risks associated with the use of cannabis. Cannabis, however, is not benign and, depending on the pattern of its use, can incur a range of harmful effects, which have implications when prescribing medicinal cannabinoids for individuals. Based on research evidence from recreational use of cannabis as well as the emerging data from trials of medicinal cannabis, we propose some clinical domains that will need specific considerations when prescribing medicinal cannabis.

Altres ajuts: SB has been funded by the National Insitute for Health Research (NIHR), UK through a Clinician Scientist award (NIHR-CS-11-001) and also received support from the Medical Research Council (MRC), UK (MR/J012149/1; MC_PC_14105 v.2). JAC is recipient of Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq, Brazil) productivity. Altres ajuts: MSCBS/PNSD PI101-2006 Altres ajuts: MSCBS/PNSD PI041731-2011 Introduction: Hippocampal neuroanatomy is affected by genetic variations in dopaminergic candidate genes and environmental insults, such as early onset of chronic cannabis exposure. Here, we examine how hippocampal total and subregional volumes are affected by cannabis use and functional polymorphisms of dopamine-relevant genes, including the catechol-O-methyltransferase (COMT), dopamine transporter (DAT1), and the brain-derived neurotrophic factor (BDNF) genes. Material and Methods: We manually traced total hippocampal volumes and automatically segmented hippocampal subregions using high-resolution MRI images, and performed COMT, DAT1, and BDNF genotyping in 59 male Caucasian young adults aged 18-30 years. These included 30 chronic cannabis users with early-onset (regular use at