Abstract Introduction The Internet Gaming Disorder Scale – Short Form (IGDS9-SF) assesses the severity, harmful effects and/or consequences of excessive online and offline gaming. Its conciseness and theoretical foundations on current diagnostic criteria of gaming disorders make it a useful resource for clinical and screening settings. Objective To describe the process of cross-cultural adaptation of the IGDS9-SF to the Brazilian context. Methods The cross-cultural adaptation involved the steps of independent translation of the instrument, synthesis version, back-translation, pre-test and elaboration of the final version. Content validity assessment was conducted by a multidisciplinary committee of experts and consisted of both a quantitative analysis (calculation of content validity coefficients – CVC) and a qualitative analysis (assessment of the experts’ comments and suggestions). The pre-test sample consisted of 30 gamers with variable sociodemographic characteristics. Results The cross-cultural adaptation of the scale followed the proposed protocol, and the CVC was satisfactory (≥ 0.83) for all the structures and equivalences assessed. Most of the suggestions made by the experts were accepted (mainly adjustments and language standardization). The gamers who participated in the pre-test judged the scale easy to understand and did not suggest changes. Discussion The Brazilian version of the IGDS9-SF showed adequate content validity and is available for researchers and clinicians, as well as for the investigation of additional psychometric characteristics.

Abstract Background Therapeutic properties of ibogaine in the treatment of addiction are attracting both clinicians and patients to its use. Since ibogaine is not an authorized medicine, the quality of these products is not always known, increasing the probability of adverse reactions. Objective This study collects different types of iboga-derived samples from treatment providers, vendors and online buyers to analyse their content. Methods Analysis of iboga products (n = 16) was performed using gas chromatography and mass spectrometry methods (GC/MS). Products included Iboga root bark, Total Alkaloids (TA), Purified Total Alkaloids (PTA HCl), ibogaine hydrochloride (ibogaine HCl) and one Voacanga africana root bark. Results The content of ibogaine was highly variable, ranging from 0.6% to 11.2% for products sold as iboga root bark, from 8.2% to 32.9% for products sold as TA, 73.7% for one sample sold as PTA and from 61.5% to 73.4% for products sold as ibogaine HCl. One sample did not show any iboga alkaloids. Other alkaloids and unknown substances were found in almost all samples. Discussion The purity of iboga products is highly variable. These results should be taken into consideration by suppliers and users, especially regarding correct dosing to avoid overdose, as well as potential interactions with other substances.

Abstract Background Ayahuasca is a botanical hallucinogenic preparation traditionally used by indigenous populations of Northwestern Amazonian countries for ritual and therapeutic purposes. It is rich in β-carboline alkaloids and N,N-dimethyltryptamine (DMT). Preclinical, observational, and experimental studies suggest that ayahuasca and its alkaloids have anxiolytic and antidepressive effects. We recently reported in an open-label trial that ayahuasca administration was associated with significant decreases in depression symptoms for 2-3 weeks after the experimental session in 17 patients with treatment-resistant major depressive disorder. Objectives To investigate if the experiment had any long-lasting effects on patients Methods Eight patients were interviewed 4 to 7 years after ayahuasca intake. Results Our results suggest that ayahuasca was well tolerated and that symptom reductions were limited to a few weeks. Importantly, most patients believed that the experience was among the most important of their lives, even 4-7 years later. Discussion To the best of our knowledge, this is the first long-term follow-up of a clinical sample that participated in an ayahuasca trial. Further studies with different and repeated dosing should be designed to further explore the antidepressive and anxiolytic effects of ayahuasca.

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.

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

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.

Durante os últimos 40 anos, a esquizofrenia foi considerada, principalmente, como o resultado de disfunções dopaminérgicas no cérebro. Esta revisão descreve e discute algumas descobertas sobre a neurotransmissão mediada pelo óxido nítrico na esquizofrenia. A busca foi feita nas bases PubMed, SciELO e LILACS usando-se os termos schizophrenia e nitric oxide plasma levels ou nitric oxide serum levels, sem limites de tempo. As listas de referências dos artigos selecionados foram examinadas em busca de outras publicações pertinentes. Dentre 15 artigos passíveis de serem incluídos, 10 preenchiam os critérios estabelecidos para a revisão e metanálise. Esses estudos incluíram 505 pacientes com esquizofrenia e 339 voluntários saudáveis. Não foram encontradas diferenças significativas entre pacientes e voluntários saudáveis quanto aos níveis plasmáticos de nitrito total (effect size g = 0,285, IC 95% = -0,205 a 0,774, p = 0,254). No entanto, o exame separado dos estudos envolvendo pacientes em tratamento antipsicótico apresentou diferenças significativas entre pacientes e voluntários saudáveis (effect size g = 0,663, IC 95% = 0,365 to 0,961, p < 0,001), demonstrando que pacientes em tratamento possuem níveis plasmáticos mais altos de óxido nítrico. Esses resultados sugerem que os antipsicóticos podem aumentar os níveis plasmáticos de óxido nítrico e que a via nitrérgica (e sua estimulação) constituiria um alvo propício para o desenvolvimento de novos tratamentos para pacientes com esquizofrenia.

For the last 40 years, schizophrenia has been considered to be the result primarily of a dysfunction in brain dopaminergic pathways. In this review, it is described and discussed findings concerning nitric oxide-mediated neurotransmission in schizophrenia. Studies were searched in PubMed, SciELO, and LILACS using the terms schizophrenia and nitric oxide plasma levels or nitric oxide serum levels, with no time limit. The reference lists of selected articles were also hand-searched for additional articles. From 15 potential reports, 10 were eligible to be included in the review and meta-analysis. These studies included a total of 505 patients with schizophrenia and 339 healthy volunteers. No significant difference was found between patients and healthy controls regarding total nitrite plasma/serum levels (effect size g = 0.285, 95%CI = -0.205 to 0.774, p = 0.254). However, when studies with patients under antipsychotic treatment were examined separately, there was a significant difference between patients and healthy volunteers (effect size g = 0.663, 95%CI = 0.365 to 0.961, p < 0.001), showing that patients under treatment have higher levels of plasma/serum nitric oxide than controls. These results suggest that antipsychotics increase nitric oxide plasma/serum levels and that the nitrergic pathway would be a fertile target for the development of new treatments for patients with schizophrenia.

A Fobia Específica (SP do inglês) é caracterizada por medos irracionais associados à evitação de estímulos específicos. Nos últimos anos, técnicas de neuroimagem vêm sendo empregadas na tentativa de melhor compreender a neurobiologia dos transtornos de ansiedade. O objetivo do presente estudo é realizar uma revisão sistemática dos artigos que utilizaram neuroimagem para estudar a SP. A busca na literatura foi realizada por intermédio de indexadores eletrônicos, utilizando-se as palavras-chave: imaging, neuroimaging, PET, spectroscopy, functional magnetic ressonance, structural magnetic ressonance, SPECT, MRI, DTI e tractography, cruzadas individualmente com os termos simple phobia e specific phobia. Foram encontrados 115 artigos, sendo 38 deles selecionados para a presente revisão. Desses, 24 usaram fMRI, 11 usaram PET, 1 usou SPECT, 2 usaram MRI estrutural e nenhum artigo de espectroscopia. Verifica-se que os estudos na área foram publicados recentemente e que, até o momento, o substrato neuroanatômico deste transtorno não está consolidado. Apesar das diferenças metodológicas entre os estudos, os resultados convergem para maior ativação na ínsula, cíngulo anterior, amídala e córtex préfrontal e orbitofrontal dos pacientes expostos a situações phobia related quando comparados aos controles. Esses achados reforçam hipóteses a respeito da hiperativação de uma determinada rede de estruturas neuroanatômicas envolvidas no transtorno de SP.

OBJECTIVE: Specific phobia (SP) is characterized by irrational fear associated with avoidance of specific stimuli. In recent years, neuroimaging techniques have been used in an attempt to better understand the neurobiology of anxiety disorders. The objective of this study was to perform a systematic review of articles that used neuroimaging techniques to study SP. METHOD:A literature search was conducted through electronic databases, using the keywords: imaging, neuroimaging, PET, spectroscopy, functional magnetic resonance, structural magnetic resonance, SPECT, MRI, DTI, and tractography, combined with simple phobia and specific phobia. One-hundred fifteen articles were found, of which 38 were selected for the present review. From these, 24 used fMRI, 11 used PET, 1 used SPECT, 2 used structural MRI, and none used spectroscopy. RESULT: The search showed that studies in this area were published recently and that the neuroanatomic substrate of SP has not yet been consolidated. CONCLUSION: In spite of methodological differences among studies, results converge to a greater activation in the insula, anterior cingulate cortex, amygdala, and prefrontal and orbitofrontal cortex of patients exposed to phobia-related situations compared to controls. These findings support the hypotheses of the hyperactivation of a neuroanatomic structural network involved in SP.

OBJETIVO: Revisar os principais avanços no potencial uso terapêutico de alguns compostos canabinoides em psiquiatria. MÉTODO: Foi realizada busca nos bancos de dado PubMed, SciELO e Lilacs e identificados estudos e revisões da literatura sobre o uso terapêutico dos canabinoides em psiquiatria, em particular canabidiol, rimonabanto, Δ9-tetraidrocanabinol e seus análogos. RESULTADOS: O canabidiol demonstrou apresentar potencial terapêutico como antipsicótico, ansiolítico, antidepressivo e em diversas outras condições. O Δ9-tetraidrocanabinol e seus análogos demonstraram efeitos ansiolíticos, na dependência de cannabis, bem como adjuvantes no tratamento de esquizofrenia, apesar de ainda carecerem de mais estudos. O rimonabanto demonstrou eficácia no tratamento de sintomas subjetivos e fisiológicos da intoxicação pela cannabis e como adjuvante no tratamento do tabagismo. Os potenciais efeitos colaterais, de induzir depressão e ansiedade limitaram o uso clínico deste antagonista CB1. CONCLUSÃO: Os canabinoides têm demonstrado que podem ter amplo interesse terapêutico em psiquiatria, porém mais estudos controlados são necessários para confirmar estes achados e determinar a segurança destes compostos.

OBJECTIVE: To review the main advances related to the potential therapeutic use of cannabinoid compounds in psychiatry. METHOD: A search was performed in the online databases PubMed, ScieELO, and Lilacs for studies and literature reviews concerning therapeutic applications of cannabinoids in psychiatry, especially cannabidiol, rimonabant, Δ9-tetrahydrocannabinol, and their analogues. RESULTS: Cannabidiol was found to have therapeutic potential with antipsychotic, anxiolytic, and antidepressant properties, in addition to being effective in other conditions. Δ9-tetrahydrocannabinol and its analogues were shown to have anxiolytic effects in the treatment of cannabis dependence and to function as an adjuvant in the treatment of schizophrenia, although additional studies are necessary to support this finding. Rimonabant was effective in the treatment of the subjective and physiological symptoms of cannabis intoxication and functioned as an adjuvant in the treatment of tobacco addiction. The potential to induce adverse reactions such as depression and anxiety restrained the clinical use of this CB1 antagonist. CONCLUSION: Cannabinoids may be of great therapeutic interest to psychiatry; however, further controlled trials are necessary to confirm the existing findings and to establish the safety of such compounds.

OBJETIVO: Medicina translacional pode ser descrita como a aplicação integrada de ferramentas farmacológicas inovadoras, biomarcadores, métodos e tecnologias clínicas e delineamentos de pesquisa para aumentar o conhecimento a respeito das doenças. A pesquisa translacional oferece uma oportunidade para aplicar os achados de pesquisa básica na clínica cotidiana. O Instituto Nacional de Ciência e Tecnologia - Medicina Translacional foi criado com seis centros (Universidade Federal do Rio Grande do Sul, Universidade de São Paulo-Ribeirão Preto, Universidade Federal do Rio de Janeiro, Pontifícia Universidade Católica do Rio Grande do Sul, Universidade Estadual de Santa Catarina e uma core facility que serve a todos os centros). Os objetivos deste projeto são divididos em quatro dimensões: institucional, pesquisa, formação de recursos humanos e transferência de tecnologia para a comunidade e setor produtivo. MÉTODO: Neste artigo, são apresentadas algumas das estratégias utilizadas para atingir os objetivos do Instituto Nacional de Ciência e Tecnologia - Medicina Translacional: 1) Desenvolvimento de modelos animais para o transtorno bipolar; 2) Estratégias de investigação neurocomportamental e disfunções cognitivas dos transtornos cerebrais; 3) Modelos experimentais de funcionamento cerebral e comportamento, proliferação celular e câncer; 4)Teste de Simulação de Falar em Público e 5) Realidade Virtual para indução de Pânico e Agorafobia. CONCLUSÃO: O Instituto Nacional de Ciência e Tecnologia - Medicina Translacional possui como foco principal o desenvolvimento de metodologias mais úteis para aumentar a aplicabilidade dos conhecimentos da pesquisa básica em medicina.

OBJECTIVE: Translational medicine has been described as the integrated application of innovative pharmacology tools, biomarkers, clinical methods, clinical technologies and study designs to improve the understanding of medical disorders. In medicine, translational research offers an opportunity for applying the findings obtained from basic research to every-day clinical applications. The National Science and Technology Institute for Translational Medicine is comprised of six member institutions (Universidade Federal do Rio Grande do Sul, Universidade de São Paulo-Ribeirão Preto, Universidade Federal do Rio de Janeiro, Pontifícia Universidade Católica do Rio Grande do Sul, Universidade Estadual de Santa Catarina and a core facility that serves all centers). The objectives of the project are divided into four areas: Institutional, Research, Human Resources and Technology for the Community and Productive Sector. METHOD: In this manuscript, we describe some of the approaches used to attain the main objectives of the National Science and Technology Institute for Translational Medicine, which include the development of 1) animal models for bipolar disorder; 2) strategies to investigate neurobehavioral function and cognitive dysfunction associated with brain disorders; 3) experimental models of brain function and behavior, neuropsychiatric disorders, cell proliferation, and cancer; 4) Simulated Public Speaking and 5) Virtual reality simulation for inducing panic disorder and agoraphobia. CONCLUSION: The main focus of the National Science and Technology Institute for Translational Medicine is the development of more useful methods that allow for a better application of basic research-based knowledge to the medical field.

OBJETIVO: Descobertas relativas a possíveis disfunções do sistema canabinóide endógeno na esquizofrenia e sua relação com o prejuízo cognitivo característico da doença têm aumentado durante a última década. Estudos com modelos animais, voluntários saudáveis e pacientes psicóticos sugerem claramente que o canabidiol possui efeitos antipsicóticos. Este estudo investigou os efeitos do canabidiol sobre a atenção seletiva por meio do Stroop Color Word Test e a responsividade eletrodérmica a estímulos auditivos em 28 pacientes com esquizofrenia. MÉTODO: Duas sessões experimentais foram realizadas, a primeira sem a administração de drogas. Na segunda sessão, os sujeitos foram divididos em três grupos que receberam dose única de canabidiol 300mg, canabidiol 600mg ou placebo. RESULTADOS: Os três grupos não diferiram significativamente no que se refere às medidas eletrodérmicas nas duas sessões experimentais. Os três grupos apresentaram melhora da primeira para a segunda avaliação, com os grupos placebo e canabidiol 300mg superiores ao grupo canabidiol 600mg. CONCLUSÃO: A administração aguda de canabidiol em dose única parece não ter efeitos benéficos sobre o desempenho de pacientes com esquizofrenia no Stroop Color Word Test, embora estes dados não sejam suficientes para refutar a hipótese de que a administração continuada de canabidiol possa resultar em melhora no funcionamento cognitivo em esquizofrenia.

OBJECTIVE: The last decade has seen increasing evidence of dysfunctions in the endogenous cannabinoid system in schizophrenia and of its relationship with the typical cognitive impairment of the disorder. Studies in animal models, healthy volunteers, and psychotic patients clearly suggest an antipsychotic-like effect of cannabidiol. This study investigated the effects of cannabidiol on selective attention in 28 schizophrenic patients using the Stroop Color Word Test and on these patients' electrodermal responsiveness to auditive stimuli. METHOD: The subjects attended two experimental sessions, the first one without the administration of drugs. In the second session the subjects were divided into three groups that received either a single dose of cannabidiol 300mg or cannabidiol 600mg or placebo. RESULTS: The three groups did not differ significantly with respect to electrodermal measures in the two experimental sessions. When the first and second sessions were compared improved performance was found in all three groups, with patients who received placebo and cannabidiol 300mg performing better than those who received cannabidiol 600mg. CONCLUSION: The single, acute administration of cannabidiol seems to have no beneficial effects on the performance of schizophrenic patients in the Stroop Color Word Test, although the hypothesis that chronic administration may lead to improvement cannot be disregarded.