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Abstract Autophagy is a lysosomal catabolic process essential to cell homeostasis and is related to the neuroprotection of the central nervous system. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid present in Cannabis sativa. Many therapeutic actions have been linked to this compound, including autophagy activation. However, the precise underlying molecular mechanisms remain unclear, and the downstream functional significance of these actions has yet to be determined. Here, we investigated CBD-evoked effects on autophagy in human neuroblastoma SH-SY5Y and murine astrocyte cell lines. We found that CBD-induced autophagy was substantially reduced in the presence of CB1, CB2 and TRPV1 receptor antagonists, AM 251, AM 630 and capsazepine, respectively. This result strongly indicates that the activation of these receptors mediates the autophagic flux. Additionally, we demonstrated that CBD activates autophagy through ERK1/2 activation and AKT suppression. Interestingly, CBD-mediated autophagy activation is dependent on the autophagy initiator ULK1, but mTORC1 independent. Thus, it is plausible that a non-canonical pathway is involved. Our findings collectively provide evidence that CBD stimulates autophagy signal transduction via crosstalk between the ERK1/2 and AKT kinases, which represent putative regulators of cell proliferation and survival. Furthermore, our study sheds light on potential therapeutic cannabinoid targets that could be developed for treating neurodegenerative disorders.

Health care workers from low- and middle-income countries have been playing a critical role in overcoming the challenges related to the COVID-19 pandemic; yet little is known about the relationship between workplace protections and wellbeing of Brazilian health care workers during the pandemic. This study aimed to evaluate whether Brazilian health care workers were satisfied with their workplace measures to protect their physical and mental health during the pandemic, and to assess the associations of such levels of satisfaction with indicators of burnout. Licensed Brazilian health care professionals were recruited via popular media between 5/19/2020 and 8/23/2020 to complete an online survey including questions about their demographic/professional characteristics, satisfaction with their workplace protective measures during the pandemic, and validated questionnaires assessing neuroticism, resilient coping, and symptoms of burnout. Most participants reported being dissatisfied with their workplace measures to protect their physical (516, 56.3%) and mental health (756, 82.5%). In multivariable analysis adjusted for personal and environmental factors, dissatisfaction with workplace physical health protections was significantly associated with higher levels of emotional exhaustion (B = 1.08, 95% CI = 0.47–1.69) and depersonalization (B = 0.61, 95% CI = 0.10–1.12), and dissatisfaction with workplace mental health protections significantly associated with higher levels emotional exhaustion (B = 1.17, 95% CI = 0.40–1.95). Efforts to improve both physical and mental health protective measures are critical to guarantee that health care workers continue to provide care at their maximum capacity.

(1) Background: With the massive demand for the use and commercialization of medicinal cannabidiol (CBD) products, new randomized clinical trials (RCTs) are being published worldwide, with a constant need for safety and efficacy evaluation. (2) Methods: We performed an update on a systematic review published in 2020 that focused on analyzing the serious adverse effects (SAEs) of CBD in RCTs and its possible association with drug interactions. We also updated the report of the most prevalent CBD adverse effects (AEs). We systematically searched EMBASE, MEDLINE/PubMed, and Web of Science without language restriction for RCTs that reported adverse effects after repeated oral CBD administration for at least one week in healthy volunteers or clinical samples published from January 2019 to May 2022. The included studies were assessed for methodological quality by the Quality Assessment of Controlled Intervention Studies tool. The present review is registered on PROSPERO, number CRD42022334399. (3) Results: Twelve studies involving 745 randomized subjects analyzed were included (range 1.1–56.8 y). A total of 454 participants used CBD in the trials. The most common AEs of CBD were mild or moderate and included gastrointestinal symptoms (59.5%), somnolence (16.7%), loss of appetite (16.5%), and hypertransaminasemia (ALT/AST) (12.8%). Serious adverse effects include mainly hypertransaminasemia with serum levels elevations greater than three times the upper limit of the normal (6.4%), seizures (1.3%), and rash (1.1%). All SAEs reported in the studies were observed on CBD as an add-on therapy to anticonvulsant medications, including clobazam and valproate. (4) Conclusion: Recent RCTs involving oral CBD administration for at least a week suggest that CBD has a good safety and tolerability profile, confirming previous data. However, it can potentially interact with other drugs and its use should be monitored, especially at the beginning of treatment.

Schizophrenia and autism spectrum disorders (ASD) are psychiatric neurodevelopmental disorders that cause high levels of functional disabilities. Also, the currently available therapies for these disorders are limited. Therefore, the search for treatments that could be beneficial for the altered course of the neurodevelopment associated with these disorders is paramount. Preclinical and clinical evidence points to cannabidiol (CBD) as a promising strategy. In this review, we discuss clinical and preclinical studies on schizophrenia and ASD investigating the behavioral, molecular, and functional effects of chronic treatment with CBD (and with cannabidivarin for ASD) during neurodevelopment. In summary, the results point to CBD's beneficial potential for the progression of these disorders supporting further investigations to strengthen its use.

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.

Schizophrenia is a severe psychiatric disorder that involves positive, negative and cognitive symptoms. Prepulse inhibition of startle reflex (PPI) is a paradigm that assesses the sensorimotor gating functioning and is impaired in schizophrenia patients as well as in animal models of this disorder. Recent data point to the participation of the endocannabinoid system in the pathophysiology and pharmacotherapy of schizophrenia. Here, we focus on the effects of cannabinoid drugs on the PPI deficit of animal models of schizophrenia, with greater focus on the SHR (Spontaneously Hypertensive Rats) strain, and on the future prospects resulting from these findings.

Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory and neuroprotective effects. In Parkinson’s disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson’s disease. The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats. Male Wistar rats received four injections of CBD (0.5 or 5 mg/kg) or vehicle (days 2-5). On days 3 and 5, animals received also one injection of 1 mg/kg reserpine or vehicle. Locomotor activity, vacuous chewing movements and catalepsy were assessed from day 1 to day 7. On days 8 and 9, we evaluated animals’ performance on the plus-maze discriminative avoidance task, for learning/memory assessment. CBD (0.5 and 5 mg/kg) attenuated the increase in catalepsy behavior and in oral movements – but not the decrease in locomotion – induced by reserpine. CBD (0.5 mg/kg) also ameliorated the reserpine-induced memory deficit in the discriminative avoidance task. Our data show that CBD is able to attenuate motor and cognitive impairments induced by reserpine, suggesting the use of this compound in the pharmacotherapy of Parkinson’s disease and tardive dyskinesia.

Animal studies and preliminary clinical trials have shown that cannabidiol-enriched extracts may have beneficial effects for children with treatment-resistant epilepsy. However, these compounds are not yet registered as medicines by regulatory agencies. We describe the cases of two children with treatment-resistant epilepsy (Case A with left frontal dysplasia and Case B with Dravet Syndrome) with initial symptom improvement after the introduction of CBD extracts followed by seizure worsening after a short time. The children presented typical signs of intoxication by ∆9-THC (inappropriate laughter, ataxia, reduced attention, and eye redness) after using a cannabidiol-enriched extract. The extract was replaced by the same dose of purified cannabidiol with no ∆9-THC in both cases, which led to improvement in intoxication signs and seizure remission. These cases support pre-clinical and preliminary clinical evidence suggesting that cannabidiol may be effective for some patients with epilepsy. Moreover, the cases highlight the need for randomized clinical trials using high-quality and reliable substances to ascertain the safety and efficacy of cannabinoids as medicines.

This study examined the knowledge of nursing students in regard to using antidepressant medication and proposes actions such that nurses contribute to a safe and effective antidepressant therapy. This cross-sectional and descriptive study was conducted in a public nursing school in the state of São Paulo, Brazil, between March and November 2008. Fifty-two (19%) out of the 273 participants were using or had used antidepressants. Instruction concerning the use of antidepressants was provided by physicians. Even after receiving instruction concerning the antidepressant treatment before its administration, the majority of users (cII1=0.07, p> 0.05) still had doubts about its use. Fluoxetine was the most prevalent antidepressant. Actions to improve knowledge concerning the use of antidepressant medications, their side and therapeutic effects, seem to be necessary and relevant.Este estudio tuvo como objetivo examinar los conocimientos de los estudiantes que utilizan los antidepresivos y proponer acciones que contribuyan para que los enfermeros realicen una terapia segura y eficaz. Este es un estudio descriptivo transversal realizado en una Escuela de Enfermería pública en el estado de Sao Paulo entre marzo y noviembre de 2008. De los 273 participantes del estudio, 52 (19%) participantes utilizan o han utilizado antidepresivos. La orientación se realizó principalmente por el médico. Incluso, con la orientación previa a la administración de antidepresivos, la mayoría de los estudiantes (cII1 = 0,07, p> 0,05) tiene dudas sobre el uso de antidepresivos. La fluoxetina es el fármaco más utilizado. Acciones para generar mayor conocimiento sobre el uso y efectos terapéuticos de los antidepresivos por parte de las enfermeras, parecen necesarias y apropiadas.Este estudo teve como objetivos analisar o nível de conhecimento de estudantes universitários de enfermagem que usam antidepressivos e propor ações para que os enfermeiros contribuam para a farmacoterapia antidepressiva segura e efetiva. Trata-se de estudo transversal e descritivo, realizado em uma Escola de Enfermagem pública do Estado de São Paulo, entre março e novembro de 2008. Dos 273 estudantes entrevistados, 52 (19%) participantes utilizam ou já utilizaram antidepressivos. A orientação do uso dessa classe medicamentosa foi realizada majoritariamente pelo médico. Mesmo com a orientação pré-administração do antidepressivo, a maioria dos usuários (cII1=0,07; p>0,05) tem dúvida a respeito do uso de antidepressivos. A fluoxetina foi o medicamento antidepressivo mais utilizado. Ações para produzir maior conhecimento quanto ao uso, efeitos colaterais e terapêuticos dos antidepressivos, por parte dos enfermeiros, parecem ser necessárias e oportunas.

A maconha é a droga ilícita mais utilizada. Apesar disto, apenas um pequeno número de estudos investigaram as conseqüências neurotóxicas de longo prazo do uso de cannabis. As técnicas de neuroimagem se constituem em poderosos instrumentos para investigar alterações neuroanatômicas e neurofuncionais e suas correlações clínicas e neuropsicológicas. Uma revisão computadorizada da literatura foi conduzida nos indexadores MEDLINE e PsycLIT entre 1966 e novembro de 2004 com os termos 'cannabis', 'marijuana', 'neuroimaging', 'magnetic resonance', 'computed tomography', 'positron emission tomography', 'single photon emission computed tomography", 'SPET', 'MRI' e 'CT'. Estudos de neuroimagem estrutural apresentam resultados conflitantes, com a maioria dos estudos não relatando atrofia cerebral ou alterações volumétricas regionais. Contudo, há uma pequena evidência de que usuários de longo prazo que iniciaram um uso regular no início da adolescência apresentam atrofia cerebral assim como redução na substância cinzenta. Estudos de neuroimagem funcional relatam aumento na atividade neural em regiões que podem estar relacionadas com intoxicação por cannabis e alteração do humor (lobos frontais mesial e orbital) e redução na atividade de regiões relacionadas com funções cognitivas prejudicadas durante a intoxicação aguda. A questão crucial se efeitos neurotóxicos residuais ocorrem após o uso prolongado e regular de maconha permanece obscura, não existindo até então estudo endereçando esta questão diretamente. Estudos de neuroimagem com melhores desenhos, combinados com avaliação cognitiva, podem ser elucidativos neste aspecto.Cannabis is the most widely used illicit drug. Despite this, only a small number of studies have investigated the long-term neurotoxic consequences of cannabis use. Structural and functional neuroimaging techniques are powerful research tools to investigate possible cannabis-induced pathophysiological changes. A computer literature review was conducted in the MEDLINE and PsycLIT databases between 1966 and November of 2004 with the search terms 'cannabis', 'marijuana', 'neuroimaging', 'magnetic resonance', 'computed tomography', 'positron emission tomography', 'single photon emission computed tomography", 'SPET', 'MRI' and 'CT'. Structural neuroimaging studies have yielded conflicting results. Most studies report no evidence of cerebral atrophy or regional changes in tissue volumes, and one study suggested that long-term users who started regular use on early adolescence have cerebral atrophy as well as reduction in gray matter. However, several methodological shortcomings limit the interpretation of these results.Functional neuroimaging studies have reported increases in neural activity in regions that may be related with cannabis intoxication or mood-change effects (orbital and mesial frontal lobes, insula, and anterior cingulate) and decreases in activity of regions related with cognitive functions impaired during acute intoxication.The important question whether residual neurotoxic effects occur after prolonged and regular use of cannabis remains unclear, with no study addressing this question directly. Better designed neuroimaging studies, combined with cognitive evaluation, may be elucidative on this issue.

After a hundred-years of its publication, the Karl Jaspers' book, General Psychopathology, is still an indispensable book to psychiatrists and for all those who study psychopathology. It's a clear delineation of the phenomenological method for describing the symptoms of mental disorders that remains unmatched until nowadays. The book focuses on the relevance of phenomenological and hermeneutical methods in psychopathology. Although this work is grounded in the clinical thought and practices of the late nineteenth and early twentieth centuries, Jaspers' delineation of psychiatric methods in this work is still evaluated as unmatched to this day, a work that is indispensable to contemporary psychiatry. Jaspers also contributed with important articles and book reviews to psychiatric periodicals during the first two decades of the twentieth century.

The growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using neuroimaging techniques to determine the effect of cannabis on brain structure and function. We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents.Papers published until August 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only neuroimaging studies involving chronic cannabis users with a matched control group were considered.One hundred and forty-two studies were identified, of which 43 met the established criteria. Eight studies were in adolescent population. Neuroimaging studies provide evidence of morphological brain alterations in both population groups, particularly in the medial temporal and frontal cortices, as well as the cerebellum. These effects may be related to the amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of resting global and brain activity during the performance of several cognitive tasks both in adolescents and adults, which may indicate compensatory effects in response to chronic cannabis exposure.However, the results pointed out methodological limitations of the work conducted to date and considerable heterogeneity in the findings.Chronic cannabis use may alter brain structure and function in adult and adolescent population. Further studies should consider the use of convergent methodology, prospective large samples involving adolescent to adulthood subjects, and data-sharing initiatives.