Effect of two oral formulations of cannabidiol on responses to emotional stimuli in healthy human volunteers: pharmaceutical vehicle matters

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.

Increased body sway in phobic patients exposed to images of spiders

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.

Cannabidiol for the treatment of crack-cocaine craving: an exploratory double-blind study

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.

Associations between primary health care strategies and outcomes of mental disorders

Objective: To investigate associations between the percentage and severity of mental disorders (MD) and three different primary health care (PHC) strategies in Brazil: traditional care (TC), the Family Health Strategy (FHS), and FHS with shared mental health care (FHS+SC). Methods: Random samples were selected from three different areas of a Brazilian city. Each area was served by a different PHC strategy (TC, FHS, or FHS+SC). Five mental health professionals, blinded to the type of PHC strategy delivered in each area, conducted interviews using the Mini International Neuropsychiatric Interview (MINI) and other specific instruments to assess the prevalence and severity of MD. Results: 530 subjects were interviewed. The TC strategy was significantly associated with a higher percentage of MD when compared to FHS and FHS+SC. These results were not affected by adjustment for sociodemographic variables. The difference in prevalence of MD between the two FHS areas (with and without SC) was not statistically significant. No significant differences in MD severity were observed across the three PHC strategies. Conclusion: Areas covered by FHS showed a lower percentage of MD than those covered by TC. Presence of SC did not influence the prevalence of MD, suggesting that mental-health training of FHS teams may have minimized the influence of SC.

Biological bases for a possible effect of cannabidiol in Parkinson's disease

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.

Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test

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.

Effects of sodium nitroprusside in the prevention of schizophrenia-like symptoms induced by ketamine - A translational double-blind study

Abstract Background: Recent evidence has shown improvements in schizophrenia symptoms after the infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor. In the rat model of schizophrenia using ketamine injection, pretreatment with SNP seems to prevent behavioral changes associated with positive symptoms for up to one week. Objective: We investigated whether SNP would have preventative effects on psychogenic symptoms induced by ketamine in healthy subjects. Methods: Healthy subjects (N = 38) were assigned to distinct groups that received SNP in different doses (0.15, 0.25, and 0.5 mcg/kg/min). First, participants received an infusion of SNP or placebo over 75 minutes. After 10 minutes, they were injected for 1 minute with a bolus of 0.26 mg/kg of ketamine and a maintenance dose was started 5 minutes later, with 0.25 mg/kg/h of ketamine for 50 minutes. Results: Ketamine-induced psychopathological alterations induced were reduced by SNP, as assessed with the Brief Psychological Rating Scale. Scores in the objective subscale of the Clinician-Administered Dissociative States Scale were also lower in SNP sessions compared to placebo. SNP had protective effects against deterioration in facial emotion and identity recognition tasks induced by ketamine. Discussion: Our findings support the view that SNP has preventative properties against psychotic manifestations.

Características básicas do transtorno do pânico / Basic features of panic disorder

O objetivo é caracterizar o Transtorno do Pânico (TP) com ênfase em seu diagnóstico e tratamento. O TP é um dos transtornos de ansiedade, caracterizado por ataques de pânico recorrentes acompanhados por uma persistente preocupação com ataques adicionais e alterações mal adaptativas do comportamento (Associação Americana de Psiquiatria - DSM-V). Sua etiologia ainda não é conhecida, mas deve envolver uma interação de fatores genéticos, de desenvolvimento e ambientais que resultam em altera- ções no funcionamento de algumas áreas cerebrais. O tratamento farmacológico de primeira escolha é com o uso de antidepressivos inibidores seletivos da recaptação de serotonina, os quais apresentam uma latência de 20 a 30 dias para o início do efeito. (AU)

The aim of this paper is to characterize the Panic Disorder (PD) with an emphasis on diagnosis and treatment. PD is one of the anxiety disorders, characterized by recurrent panic attacks accompanied by a persistent preoccupation with additional attacks and maladaptive behavioral changes (American Psychiatric Association ­ DSM-V). Its etiology is not known, but should involve an interaction of genetic, developmental and environmental factors that result in changes in the functioning of some brain areas. The pharmacological treatment of choice is with the use of selective serotonin reuptake inhibitors, which has a latency of 20 for 30 days for the beginning of the therapeutic effect. (AU)

Características básicas do transtorno de ansiedade generalizada / Basic features of generalized anxiety disorder

Este texto é dirigido à alunos de graduação com o objetivo de caracterizar o Transtorno de Ansiedade Generalizada (TAG) com ênfase em seu diagnóstico e tratamento. O TAG é um dos transtornos psiquiá- tricos mais subdiagnosticados. Caracteriza-se por preocupação persistente e excessiva acompanhada de sintomas físicos relacionados a hiperatividade autonômica e a tensão muscular. Apresenta comorbidade frequente com depressão e outros transtornos de ansiedade. A abordagem psicoterápica, num sentido amplo, deve ser prioritária no tratamento desse distúrbio e o tratamento farmacológico, quando indicado, não deve ser a única opção terapêutica. (AU)

This text is addressed to medical undergraduate students with aim to characterize Generalized Anxiety Disorder (GAD) with emphasis on diagnosis and treatment. GAD is one of the most psychiatric disorders under-diagnosed. The main characteristic of GAD is persistent and excessive worry accompanied by physical symptoms related to autonomic hyperactivity and muscle tension. The comorbidity with depression and other anxiety disorders is frequently. The psychotherapeutic approach, in a wide sense, must be a priority in the treatment of this disease and, when indicated, the pharmacological treatment should not be the only therapeutic option. (AU)

Acute and chronic administration of cannabidiol increases mitochondrial complex and creatine kinase activity in the rat brain

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. .

A Faculdade de Medicina de Ribeirão Preto e a Reforma Universitária: o sonho de 1968 / The School of Medicine of Ribeirão Preto and the university reform: the dream of 1968

O objetivo dessa revisão é descrever a participação de docentes e discentes da Faculdade de Medicina de Ribeirão Preto (FMRP) nas discussões sobre a reforma da Universidade de São Paulo (USP), que ocorreram no ano de 1968. Essas discussões ocorreram em comissões compostas por igual número de docentes e discentes (comissões paritárias) e resultaram numa proposta de reforma aprovada por uma assembléia da FMRP, especialmente criada com essa finalidade. O artigo discute, também, o contexto e a influência dessas discussões na reforma aprovada pelo Conselho Universitário da USP, no início de 1969 e que ficou conhecido como Estatuto Hélio Lourenço.

The objective of this review is to describe the participation of the lecturers and students of the School of Medicine of Ribeirão Preto (FMRP) in discussions on reform of the University of São Paulo (USP), which occurred in the year 1968. These discussions occurred in committees composed of equal numbers of lecturers and students (parity committees) and resulted in a proposal for reform adopted by an assemblyof the FMRP, specially created for this purpose. The paper discuss also the context and influence of these discussions in the reform approved by the University Council at the beginning of 1969 and that became known as Hélio Lourenço's statute.

Confiabilidade da entrevista clínica estruturada para o DSM-IV - versäo clínica" traduzida para o português / Reliability of the structured clinical interview for DSM-IV - clinical version translated into portuguese

Objetivos: Verificar a confiabilidade da "Entrevista Clínica Estruturada para o DSM-IV - Versäo Clínica (SCID-CV)" traduzida para o português. Métodos: Foram submetidos, a duas entrevistas independentes (teste-reteste), 45 pacientes psiquiátricos em seguimento no Hospital das Clínicas da Faculdade de Medicina de Ribeiräo Preto da Universidade de Säo Paulo (HC-FMRP/USP). Os dados foram analisados pelo Coeficiente Kappa (K). Resultados: O Kappa ponderado foi excelente (Kw=0,83). A confiabilidade foi estatisticamente significante em transtorno do humor (K=0,87); transtornos psicóticos (K=0,90); transtornos relacionados ao uso de substância (K=0,76); transtornos de ansiedade (K=0,61); e nas categorias diagnósticas específicas analisadas, exceto em agorafobia sem história de transtorno do pânico (K=0,04). Conclusões: A SCID-CV traduzida e adaptada para o português apresenta, em geral, boa confiabilidade, mas a ausência de questões e critérios diagnósticos específicos no próprio instrumento em diagnósticos, como agorafobia sem história de transtorno de pânico, diminuiu sua confiabilidade

Complexidade do diagnostico diferencial em psiquiatria: relato de sindrome catatonita / The complexity of the differential diagnosis in psychiatry exemplified by a catatonic syndrome

Os autores relatam um caso de sindrome catatonica que evoluiu com afasia apos um provavel episodio infeccioso do sistema nervoso central (encefalite viral?), que nao foi confirmado por exames complementares...

Serviço de emergências psiquiátricas em hospital geral universitário: estudo prospectivo / Psychiatric emergency service in a school general hospital: a prospective study

Objetivo: Realizar estudo transversal de serviço regionalizado de emergências psiquiátricas inserido em hospital universitário de emergências pela caracterizaçäo da clientela e do atendimento. Método: Os dados foram colhidos por um protocolo, sendo considerados todos os atendimentos realizados durante dois meses. Resultados: Foram preenchidos 600 protocolos que corresponderam a 96,5 por cento dos atendimentos efetuados no período estudado, referentes a 487 pacientes. A maioria desses era do sexo masculino, sem vínculos conjugais, com baixa escolaridade, profissionalmente inativa e morava com familiares. Os diagnósticos mais freqüentes foram transtorno do uso de substância psicoativa (26,3 por cento), esquizofrenias (15,5 por cento), episódio maníaco (11,8 por cento), depressäo maior (10,9 por cento) e transtornos näo-psicóticos (10,9 por cento), havendo diferenças entre os sexos quanto à proporçäo de algumas categorias diagnósticas. Após o atendimento inicial, 2/3 recebeu medicaçäo e 1/2 permaneceu em observaçäo, sendo que 1/4 permaneceu mais de 10h no serviço. Cerca de 20 por cento dos atendimentos resultaram em internaçäo integral e 60 por cento, em encaminhamentos para seguimento ambulatorial. Alta por evasäo representou apenas 2,0 por cento dos atendimentos. Os usuários repetitivos näo diferiram daqueles que tiveram atendimento único quanto a estado civil, vínculo empregatício e condiçöes de moradia, mas apresentaram maior freqüência de internaçöes anteriores e de transtornos psicóticos. Conclusöes: O serviço atendeu pacientes com quadros psiquiátricos graves, em real situaçäo de urgência, sendo observada uma ampliaçäo das funçöes do serviço de emergências psiquiátricas e sua efetiva inserçäo na rede pública de serviços de saúde mental

Políticas de saúde mental e mudanças na demanda de serviços de emergência / Mental health policies and changes in the emergency services profile

Objetivo: Verificar as mudanças ocorridas em um serviço de emergências psiquiátricas de um hospital universitário de Ribeiräo Preto, SP (EP-RP), em funçäo de mudanças nas políticas de saúde mental da regiäo. Métodos: Os dados sobre os atendimentos foram colhidos em arquivos do EP-RP, no período de 1988 a 1997. Foram estudadas as variáveis sexo, faixa etária, procedência e diagnóstico principal. Os dados sobre as mudanças nas políticas de saúde mental, na regiäo, foram obtidos de documentos das secretarias de saúde do estado e do município. Resultados: O aumento a cada ano do número de atendimentos realizados acompanhou o progressivo envolvimento do EP-RP na rede de serviços de saúde mental. Em 1995, a procura pelo serviço foi 2,3 vezes maior do que em 1988. Nesse período, o atendimento EP-RP deu apoio às mudanças nas políticas de saúde mental na regiäo, que resultaram na reduçäo de 654 leitos psiquiátricos. Em 1996 e 1997, houve uma diminuiçäo do total de atendimentos em cerca de 20 por cento com relaçäo a 1995, acompanhando o aumento do número e da capacidade de atendimento dos serviços extra-hospitalares. A partir de 1990, o serviço passou a atender uma maior proporçäo de pacientes mais velhos, do sexo masculino, com diagnóstico de dependência de substâncias e transtornos psicóticos e uma proporçäo menor de quadros näo psicóticos. Conclusöes: As mudanças observadas no EP-RP correlacionam-se com as das políticas de saúde mental na regiäo de Ribeiräo Preto, como a instalaçäo da Central de Vagas Psiquiátricas, em 1990, a reduçäo de leitos psiquiátricos a partir de 1993 e a criaçäo e/ou ampliaçäo de serviços extra-hospitalares a partir de 1995

Efeito da d-fenfluramina na ansiedade induzida por uma simulaçäo de falar em público / Effect of d-fenfluramine on anxiety induced by a simulated public speaking test

Com o intuito de continuar a investigaçäo sobre a funçäo da serotonina (5-HT) na ansiedade, 43 volunt rios sadios receberam, em condiçöes duplo-cegas, d-fenfluramina (15 a 30mg VO) ou placebo e foram submetidos a um teste de simulaçäo de falar em público, que consiste em falar em frente a uma videocâmara. O procedimento provocou aumento significativo da ansiedade subjetiva e da pressäo arterial sistólica. A droga atenuou esse aumento sem causar sedaçäo física ou mental. Além disso, a d-fenfluramina näo alterou de maneira significativa os parâmetros fisiológicos. A d-fenfluramina libera 5-Ht dos terminais nervosos e bloqueia sua recaptaçäo, estimulando indiretamente receptores 5-HT pós-sin pticos. Dessa forma, os resultados sugerem que a 5-HT inibe o substrato neural da ansiedade induzida pelo teste de simulaçäo de falar em público