Performance of schizophrenic patients in the Stroop Color Word Test and electrodermal responsiveness after acute administration of cannabidiol (CBD)

original article Performance of schizophrenic patients in the Stroop Color Word Test and electrodermal responsiveness after acute administration of cannabidiol (CBD) Desempenho de pacientes esquizofrênicos no Stroop Color Word Test e responsividade eletrodérmica após administração aguda de canabidiol (CBD) Jaime E. C. Hallak,1,2 João Paulo Machado-de-Sousa,1,2 José Alexandre S. Crippa,1,2 Rafael Faria Sanches,1,2 Clarissa Trzesniak,1,2 Cristiano Chaves,1,2 Sandra Aparecida Bernardo,1 Simone Cecílio Regalo,2,3 Antonio Waldo Zuardi1,2 University Hospital of the Ribeirão Preto Medical School, Department of Neuroscience and Behavior, Universidade de São Paulo (USP), Ribeirão Preto (SP), Brazil 2 Instituto Nacional de Ciência e Tecnologia – Translacional em Medicina (CNPq) 3 Dentistry School of Ribeirão Preto, Department of Morphology, Stomatology and Physiology, Universidade de São Paulo (USP), Ribeirão Preto (SP), Brazil 1 Abstract 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. Resumo 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. Descritores: Esquizofrenia; Cognição; Canabidiol; Transtornos psicóticos Descriptors: Schizophrenia; Cognition; Cannabidiol; Psychotic disorders Introduction In the middle of the 19th century, Moreau first employed Submitted: March 30, 2009 Accepted: October 1, 2009 56 • Revista Brasileira de Psiquiatria • vol 32 • nº 1 • mar2010 marijuana as an experimental psychotomimetic substance.1 The discovery of cannabinoid receptors2 and endogenous ligands3 Correspondence Jaime E. C. Hallak Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto – USP Av. dos Bandeirantes, 3900, 3º andar 14048-900 Ribeirão Preto, SP, Brazil Tel.: (+55 16) 3602-2853 Fax: (+55 16) 3602-2703 E-mail: CBD and cognition in schizophrenia (anandamide – palmityl ethanolamide, 2-arachidonyl glycerol) supported the notion of a central neuromodulatory cannabinoid system, and there seems to exist a complete system with multiple cannabinoid receptors and anandamide-related compounds.4 There is evidence suggesting an association between Cannabis and psychosis or schizophrenia: the use of marijuana is more prevalent among patients with schizophrenia as compared to the healthy population;5 the extended use of marijuana can trigger psychotic episodes in schizophrenic patients;6 and increased anandamide levels have been found in the liquor of schizophrenic patients as compared with healthy controls.7 Additionally, cannabinoid agonists impair many cognitive functions (especially memory and attention) and similarities have been reported between the cognitive impairment seen in schizophrenia and that provoked by intoxication with Cannabis.8,9 Consistent with a potential contribution of the cannabinoid system to the physiopathology of schizophrenia, the highest densities of cannabinoid receptors are found in brain regions reported to be implicated in schizophrenia, including the PFC, basal ganglia, hippocampus, and anterior cingulate cortex.9 The association between cannabis and psychosis could be understood both as a hyperfunctioning of the endocannabinoid system and as an attempt to overcome a possible functional deficit of this system in patients with psychosis. Scientific evidence gives support to attempts at testing cannabinoid antagonists as a possible therapeutic strategy for the treatment of psychiatric disorders.10 Since the 1970s, pioneering studies on CBD effects have been conducted in Brazil.11,12 Many of these studies have suggested that Cannabidiol (CBD), a cannabinoid devoid of the typical psychological effects of cannabis in humans,12 acts as an antagonist of the effects of D9-THC when administered simultaneously.12,13 The study involving healthy volunteers suggested that CBD reduces both the anxiety and the psychotomimetic effects of D9-THC, leading to the proposition that this effect is due to an action of CBD itself.12 The antipsychotic-like properties of CBD have been investigated in animal models using behavioral and neurochemical techniques which suggested that CBD has a pharmacological profile similar to that of atypical antipsychotic drugs.14 The results of two studies on healthy volunteers using perception of binocular depth inversion and ketamine-i (...truncated)