Therapeutical use of the cannabinoids in psychiatry

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

Long-term effects of ayahuasca in patients with recurrent depression: a 5-year qualitative follow-up

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

O uso do canabidiol (CBD) no tratamento da doença de Parkinson e suas comorbidades

Background: Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by motor (bradykinesia, tremors, stiffness) and non-motor (psychotic, mood and sleep disorders) symptoms. The available pharmacological treatments are not effective for a significant portion of the patients. Recent research suggests that the phytocannabinoid cannabidiol (CBD) could be effective in treating some PD symptoms. Objectives: To review the preclinical and clinical studies of the effects of CBD on the symptoms of PD. Methods: Narrative review of the main basic and clinical studies on the effects of CBD on the symptoms of PD. Due to the small number of clinical studies, research with other cannabinoids was also included. Results: A total of 15 articles were included in the review: 5 preclinical studies involving the administration of CBD and 10 studies with patients involving the administration of different cannabinoids (cannabis, nabilone, CBD). Most of the basic studies reported a positive effect of CBD on PD-related behavior or biochemical changes. Observational and clinical studies using smoked cannabis, oral cannabis extract, nabilone (synthetic cannabinoid) and CBD suggest that these cannabinoids can reduce motor (bradykinesia, tremors, stiffness) and non-motor (psychotic, mood and sleep disorders, quality of life) symptoms of PD. Moreover, they are well tolerated substances with few significant adverse effects. Conclusion: Although CBD has shown favorable results in both preclinical and clinical studies, this evidence is not yet sufficient to indicate the use of this cannabinoid in patients with PD. New controlled studies should be performed with different dosages of CBD to replicate this data.Fundamento: A doença de Parkinson (DP) é um transtorno neurodegenerativo crônico caracterizado por sintomas motores (bradicinesia, tremores, rigidez) e não motores (transtornos psicóticos, do humor e do sono). Os tratamentos farmacológicos disponíveis não são eficazes para uma parcela significativa dos pacientes. Pesquisas recentes sugerem que o fitocanabinóide canabidiol (CBD) poderia ser eficaz no tratamento de alguns sintomas da DP. Objetivos: Revisar os estudos pré-clínicos e clínicos dos efeitos do CBD nos sintomas da DP. Métodos: Revisão narrativa dos principais estudos básicos e clínicos sobre os efeitos do CBD nos sintomas da DP. Devido ao número pequeno de estudos clínicos, pesquisas com outros canabinóides também foram incluídas. Resultados: No total, 15 artigos foram incluídos na revisão: 5 estudos pré-clínicos envolvendo a administração de CBD e 10 estudos com pacientes envolvendo a administração de diferentes canabinóides (maconha, nabilona, CBD). A maioria dos estudos básicos mostraram um efeito positivo do CBD em comportamentos ou alterações bioquímicas relacionadas à DP. Estudos observacionais e clínicos com uso de maconha fumada, extrato oral de maconha, nabilona (canabinóide sintético) e CBD sugerem que estes canabinóides podem reduzir sintomas motores (bradicinesia, tremores, rigidez) e não motores (transtornos psicóticos, do humor e do sono, qualidade de vida) da DP. Além disso, são substâncias bem toleradas e com poucos efeitos adversos significativos. Conclusão: Embora o CBD tenha demonstrado resultados favoráveis tanto em estudos pré-clínicos como em estudos clínicos, estas evidências ainda não são suficientes para indicar o uso deste canabinóide em pacientes com distúrbios do DP. Novos estudos controlados devem ser realizados com diferentes dosagens de CBD para replicar estes dados

The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network

The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.The Brazilian Federal Agencies: CNPq, CAPES; FINEP; The Sao Paulo State financial agency (FAPESP)

Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain

Clinical and neurobiological findings suggest that the cannabinoids and the endocannabinoid system may be implicated in the pathophysiology and treatment of schizophrenia. We described that the spontaneously hypertensive rats (SHR) strain presents a schizophrenia behavioral phenotype that is specifically attenuated by antipsychotic drugs, and potentiated by proschizophrenia manipulations. Based on these findings, we have suggested this strain as an animal model of schizophrenia. the aim of this study was to evaluate the effects of cannabinoid drugs on the deficit of prepulse inhibition (PPI) of startle, the main paradigm used to study sensorimotor gating impairment related to schizophrenia, presented by the SHR strain. the following drugs were used: (1) WIN55212,2 (cannabinoid agonist), (2) rimonabant (CB1 antagonist), (3) AM404 (anandamide uptake inhibitor), and (4) cannabidiol (CBD; indirect CB1/CB2 receptor antagonist, among other effects). VVistar rats (VVRs) and SHRs were treated with vehicle (VEH) or different doses of WIN55212 (0.3, 1, or 3 mg/kg), rimonabant (0.75, 1.5, or 3 mg/kg), AM404 (1, 5, or 10 mg/kg), or CBD (15, 30, or 60 mg/kg). VEH-treated SHRs showed a decreased PPI when compared to VVRs. This PPI deficit was reversed by 1 mg/kg WIN and 30 mg/kg CBD. Conversely, 0.75 mg/kg rimonabant decreased PPI in SHR strain, whereas AM404 did not modify it. Our results reinforce the role of the endocannabinoid system in the sensorimotor gating impairment related to schizophrenia, and point to cannabinoid drugs as potential therapeutic strategies.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Pharmacol, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Lab Interdisciplinar Neurociencias Clin, BR-04039032 São Paulo, BrazilUniv São Paulo, Dept Neurosci & Behav, BR-14049 Ribeirao Preto, BrazilNatl Council Sci & Technol Dev, Natl Inst Sci & Technol Translat Med, Ribeirao Preto, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Lab Interdisciplinar Neurociencias Clin, BR-04039032 São Paulo, BrazilFAPESP: FAPESP - 2010/07994-3Web of Scienc

Neuroimagem do transtorno de fobia específica: uma revisão sistemática da literatura

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

Desempenho de pacientes esquizofrênicos no Stroop Color Word Test e responsividade eletrodérmica após administração aguda de canabidiol (CBD)

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.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

An analytical study of iboga alkaloids contained in Tabernanthe iboga-derived products offered by ibogaine treatment providers

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