Cannabidiol prevents lipopolysaccharide-induced sickness behavior and alters cytokine and neurotrophic factor levels in the brain.

BACKGROUND: Major depressive disorder (MDD) affects millions of people worldwide. While the exact pathogenesis is yet to be elucidated, the role of neuro-immune signaling has recently emerged. Despite major advances in pharmacotherapy, antidepressant use is marred by limited efficacy and potential side effects. Cannabidiol (CBD), a phytocannabinoid, exerts antidepressant-like effects in experimental animals. This study investigated the impact of CBD on sickness behavior (SB), a measure of depressive-like response, and neuro-immune changes induced by lipopolysaccharides (LPS) in mice. METHODS: Socially isolated rodents were administered with LPS to trigger SB. and treated with CBD or its vehicle. Animals were submitted to forced swimming test, to evaluate depressive-like behavior, and to open field test, to evaluate locomotory activity. Immediately after behavioral analyses, animals were euthanized and had their hypothalamus, prefrontal cortex and hippocampus dissected, to proceed neurotrophins and cytokines analyses. ELISA was used to detect IL-1ß, BDNF and NGF; and cytometric beads array to measure IL-2, IL-4, IL-6, IFN-γ, TNF-α and IL-10 levels. RESULTS: CBD effectively prevented SB-induced changes in the forced swim test without altering spontaneous locomotion. This phytocannabinoid also partially reversed LPS-evoked IL-6 increase in both the hypothalamus and hippocampus. In addition, CBD prevented endotoxin-induced increase in BDNF and NGF levels in the hippocampus of SB animals. CONCLUSIONS: Apparently, CBD prevents both behavioral and neuro-immunological changes associated with LPS-induced SB, which reinforces its potential use as an antidepressant which modulates neuroinflammation. This opens up potentially new therapeutic avenues in MDD.

Wistar Audiogenic Rats (WAR) exhibit altered levels of cytokines and brain-derived neurotrophic factor following audiogenic seizures.

Increasing body of evidence suggests that inflammatory and neurotrophic factors might be important for epileptogenesis. Most animal studies demonstrated altered levels of these mediators in drug-induced models of seizures and epilepsy. In the present study, we investigated the production of cytokines and a neurotrophin in the brain of Wistar Audiogenic Rats (WAR), a genetic model of epilepsy, stimulated with high-intensity sound. Four hours after stimulation, animals were decapitated and the hippocampus, inferior colliculus, striatum and cortex were removed for evaluation of the levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α and brain derived neurotrophic factor (BDNF). All the cytokines and BDNF levels were increased in the cortex. Increased levels of TNF-α and IL-6 were also observed in the striatum. Finally, TNF-α also increased in the inferior colliculus after the seizures induced by high-intensity sound. Although different studies have demonstrated that the levels of cytokines and BDNF increase in animal models of epilepsy induced by chemical stimuli, we provided here evidence that these mediators are also increased in WAR, a genetic model of epilepsy. Thus, the observed increase in these mediators might be involved in the pathophysiology of epilepsy.

Good rate of clinical response to cholinesterase inhibitors in mild and moderate Alzheimers disease after three months of treatment: an open-label study / Boa taxa de resposta clínica aos inibidores da colinesterase na doença de Alzheimer leve e moderada, após três meses de tratamento: um estudo Aberto

Life expectancy in Brazil has increased markedly over the last 30 years. Hence, age-related disorders, such as Alzheimer's disease (AD), warrant special attention due to their high prevalence in the elderly. Pharmacologic treatment of AD is based on cholinesterase inhibitors (ChEI) and memantine, leading to modest clinical benefits both in the short and long-term. However, clinical response is heterogeneous and needs further investigation. OBJECTIVE: To investigate the rate of response to ChEI in AD after three months of treatment. METHODS: Patients with mild or moderate dementia due to probable AD or to AD associated with cerebrovascular disease were included in the study. The subjects were assessed at baseline and again after three months of ChEI treatment. Subjects were submitted to the Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale, Katz Basic Activities of Daily Living, Pfeffer Functional Activities Questionnaire, Neuropsychiatric Inventory and Cornell Scale for Depression in Dementia. Good response was defined by a gain of >ou = 2 points on the MMSE after three months of treatment in relation to baseline. RESULTS: Seventy-one patients, 66 (93%) with probable AD and five (7%) with AD associated with cerebrovascular disease, were evaluated. The good response rate at three months was 31.0%, being 37.2% and 21.4% in mild and moderate dementia, respectively. There were no significant differences on most tests, except for improvement in hallucinations, agitation and dysphoria in moderate dementia patients.CONCLUSION: The rate of good clinical response to ChEI was higher than usually reported. Specific behavioral features significantly improved in the subgroup of moderate dementia.

A expectativa de vida no Brasil aumentou significativamente nos últimos 30 anos. Desse modo, transtornos relacionados à idade, como a doença de Alzheimer (DA), merecem especial atenção, devido à elevada prevalência. O tratamento farmacológico da DA se baseia nos inibidores da colinesterase (IChE) e na memantina, com melhora modesta em curto e longo prazo. Entretanto, a resposta clínica é heterogênea e necessita maior investigação. OBJETIVO: Investigar a taxa de resposta aos IChE em pacientes com DA após três meses de tratamento. MÉTODOS: Pacientes com demência leve ou moderada devida à DA ou DA com doença cerebrovascular foram avaliados antes e após três meses de uso de IChE. Todos foram submetidos ao Mini-Exame do Estado Mental (MEEM), Escala de Demência Mattis, avaliação das atividades básicas de vida diária de Katz, Questionário de Pfeffer, Inventário Neuropsiquiátrico e Escala de Depressão de Cornell. Boa resposta foi definida pelo ganho de > ou = 2 pontos no MEEM em relação à primeira consulta, após três meses.RESULTADOS: Setenta e um pacientes, 66 (93%) com DA provável e cinco (7%) com DA associada à doença cerebrovascular, foram avaliados. A taxa de boa resposta clínica em três meses foi de 31.0%, sendo 37,2% e 21,4% na demência leve e moderada, respectivamente. Não houve diferença significativa na maioria dos testes, exceto para melhora de alucinação, agitação e depressão em pacientes com demência moderada. CONCLUSÃO: A taxa de boa resposta clínica aos IChE foi superior à encontrada na literatura. Observou-se melhora de alguns sintomas comportamentais em pacientes com DA moderada.

Good rate of clinical response to cholinesterase inhibitors in mild and moderate Alzheimer's disease after three months of treatment: An open-label study.

Life expectancy in Brazil has increased markedly over the last 30 years. Hence, age-related disorders, such as Alzheimer's disease (AD), warrant special attention due to their high prevalence in the elderly. Pharmacologic treatment of AD is based on cholinesterase inhibitors (ChEI) and memantine, leading to modest clinical benefits both in the short and long-term. However, clinical response is heterogeneous and needs further investigation. OBJECTIVE: To investigate the rate of response to ChEI in AD after three months of treatment. METHODS: Patients with mild or moderate dementia due to probable AD or to AD associated with cerebrovascular disease were included in the study. The subjects were assessed at baseline and again after three months of ChEI treatment. Subjects were submitted to the Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale, Katz Basic Activities of Daily Living, Pfeffer Functional Activities Questionnaire, Neuropsychiatric Inventory and Cornell Scale for Depression in Dementia. Good response was defined by a gain of ≥2 points on the MMSE after three months of treatment in relation to baseline. RESULTS: Seventy-one patients, 66 (93%) with probable AD and five (7%) with AD associated with cerebrovascular disease, were evaluated. The good response rate at three months was 31.0%, being 37.2% and 21.4% in mild and moderate dementia, respectively. There were no significant differences on most tests, except for improvement in hallucinations, agitation and dysphoria in moderate dementia patients. CONCLUSION: The rate of good clinical response to ChEI was higher than usually reported. Specific behavioral features significantly improved in the subgroup of moderate dementia.

A expectativa de vida no Brasil aumentou significativamente nos últimos 30 anos. Desse modo, transtornos relacionados à idade, como a doença de Alzheimer (DA), merecem especial atenção, devido à elevada prevalência. O tratamento farmacológico da DA se baseia nos inibidores da colinesterase (IChE) e na memantina, com melhora modesta em curto e longo prazo. Entretanto, a resposta clínica é heterogênea e necessita maior investigação. OBJETIVO: Investigar a taxa de resposta aos IChE em pacientes com DA após três meses de tratamento. MÉTODOS: Pacientes com demência leve ou moderada devida à DA ou DA com doença cerebrovascular foram avaliados antes e após três meses de uso de IChE. Todos foram submetidos ao Mini-Exame do Estado Mental (MEEM), Escala de Demência Mattis, avaliação das atividades básicas de vida diária de Katz, Questionário de Pfeffer, Inventário Neuropsiquiátrico e Escala de Depressão de Cornell. Boa resposta foi definida pelo ganho de ≥2 pontos no MEEM em relação à primeira consulta, após três meses. RESULTADOS: Setenta e um pacientes, 66 (93%) com DA provável e cinco (7%) com DA associada à doença cerebrovascular, foram avaliados. A taxa de boa resposta clínica em três meses foi de 31.0%, sendo 37,2% e 21,4% na demência leve e moderada, respectivamente. Não houve diferença significativa na maioria dos testes, exceto para melhora de alucinação, agitação e depressão em pacientes com demência moderada. CONCLUSÃO: A taxa de boa resposta clínica aos IChE foi superior à encontrada na literatura. Observou-se melhora de alguns sintomas comportamentais em pacientes com DA moderada.