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  • Alzheimer's Dementia, Brain Function, Immune Function
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Cannabidiol (CBD) enhanced the hippocampal immune response and autophagy of APP/PS1 Alzheimer’s mice uncovered by RNA-seq

Please use this link to access this publication. Abstract Alzheimer's disease (AD) is a central nervous system disease characterized by dementia, which has now become a major threat to global health. Cannabidiol (CBD) is a natural component extracted from the hemp plant and exhibits multiple mechanisms to improve the pathological process of AD in vitro and in vivo. However, its underlying molecular mechanism is still unclear. This study attempts to reveal its common mechanism through transcriptome sequence. We performed transcriptome sequence in the hippocampus of 6 month old APP/PS1 mice chronically treated with CBD for one month or 30 days. In addition, Aβ plaques...
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CBD Suppression of EAE Is Correlated with Early Inhibition of Splenic IFN-γ + CD8+ T Cells and Modest Inhibition of Neuroinflammation

Please use this link to access this publication. Abstract In this study cannabidiol (CBD) was administered orally to determine its effects and mechanisms in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). We hypothesized that 75 mg/kg of oral CBD given for 5 days after initiation of disease would reduce EAE severity through suppression of either the early peripheral immune or late neuroimmune response. EAE was induced in C57BL/6 mice at two different magnitudes, and peripheral inflammatory and neuroinflammatory responses were measured at days 3, 10, and 18. Th1, Th17, Tc1, Tc17, Tregs, and myeloid derived suppressor cells (MDSC) were identified from...
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The Impact of Cannabidiol on Human Brain Function: A Systematic Review

Abstract Background: Accumulating evidence suggests that the non-intoxicating cannabinoid compound cannabidiol (CBD) may have antipsychotic and anxiolytic properties, and thus may be a promising new agent in the treatment of psychotic and anxiety disorders. However, the neurobiological substrates underlying the potential therapeutic effects of CBD are still unclear. The aim of this systematic review is to provide a detailed and up-to-date systematic literature overview of neuroimaging studies that investigated the acute impact of CBD on human brain function. Methods: Papers published until May 2020 were included from PubMed following a comprehensive search strategy and pre-determined set of criteria for article selection. We included studies...
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Cannabinoids and Neurogenesis: The Promised Solution for Neurodegeneration?

Abstract The concept of neurons as irreplaceable cells does not hold true today. Experiments and evidence of neurogenesis, also, in the adult brain give hope that some compounds or drugs can enhance this process, helping to reverse the outcomes of diseases or traumas that once were thought to be everlasting. Cannabinoids, both from natural and artificial origins, already proved to have several beneficial effects (e.g., anti-inflammatory, anti-oxidants and analgesic action), but also capacity to increase neuronal population, by replacing the cells that were lost and/or regenerate a damaged nerve cell. Neurogenesis is a process which is not highly represented in literature as neuroprotection, though...
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Systematic review of the impact of cannabinoids on neurobehavioral outcomes in preclinical models of traumatic and nontraumatic spinal cord injury

Abstract Study design Systematic review. Objectives To evaluate the impact of cannabinoids on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic spinal cord injury (SCI), with the aim of determining suitability for clinical trials involving SCI patients. Methods A systematic search was performed in MEDLINE and Embase databases, following registration with PROPSERO (CRD42019149671). Studies evaluating the impact of cannabinoids (agonists or antagonists) on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic SCI were included. Data extracted from relevant studies, included sample characteristics, injury model, neurobehavioural outcomes assessed and study results. PRISMA guidelines were followed and the SYRCLE checklist was used to assess...
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Mini-review: The therapeutic role of cannabinoids in neuroHIV

Abstract In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is considered a chronic disease with an inflammatory component that specifically targets the brain and causes a high prevalence of HIV-1-associated neurocognitive disorders (HAND). The endocannabinoid (eCB) system has attracted interest as a target for treatment of neurodegenerative disorders, due to the potential anti-inflammatory and neuroprotective properties of cannabinoids, including its potential therapeutic use in HIV-1 neuropathogenesis. In this review, we summarize what is currently known about the structural and functional changes of the eCB system under conditions of HAND. This will be followed by summarizing the current clinical...
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A phase 1b randomised, placebo-controlled trial of nabiximols cannabinoid oromucosal spray with temozolomide in patients with recurrent glioblastoma

Abstract Background Preclinical data suggest some cannabinoids may exert antitumour effects against glioblastoma (GBM). Safety and preliminary efficacy of nabiximols oromucosal cannabinoid spray plus dose-intense temozolomide (DIT) was evaluated in patients with first recurrence of GBM. Methods Part 1 was open-label and Part 2 was randomised, double-blind, and placebo-controlled. Both required individualised dose escalation. Patients received nabiximols (Part 1, n = 6; Part 2, n = 12) or placebo (Part 2 only, n = 9); maximum of 12 sprays/day with DIT for up to 12 months. Safety, efficacy, and temozolomide (TMZ) pharmacokinetics (PK) were monitored. Results The most common treatment-emergent adverse events (TEAEs; both parts) were vomiting, dizziness, fatigue, nausea...
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Acute Δ9-tetrahydrocannabinol prompts rapid changes in cannabinoid CB1 receptor immunolabeling and subcellular structure in CA1 hippocampus of young adult male mice

Please use this link to access this publication. Abstract The use and abuse of cannabis can be associated with significant pathophysiology, however, it remains unclear whether (1) acute administration of Δ-9-tetrahydrocannabinol (THC) during early adulthood alters the cannabinoid type 1 (CB1) receptor localization and expression in cells of the brain, and (2) THC produces structural brain changes. Here we use electron microscopy and a highly sensitive pre-embedding immunogold method to examine CB1 receptors in the hippocampus cornu ammonis subfield 1 (CA1) 30 min after male mice were exposed to a single THC injection (5 mg/kg). The findings show that acute exposure to THC can significantly decrease...
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Cannabinoid receptor activation acutely increases synaptic vesicle numbers by activating synapsins in human synapses

Please use this link to access this publication. Abstract Cannabis and cannabinoid drugs are central agents that are used widely recreationally and are employed broadly for treating psychiatric conditions. Cannabinoids primarily act by stimulating presynaptic CB1 receptors (CB1Rs), the most abundant G-protein-coupled receptors in brain. CB1R activation decreases neurotransmitter release by inhibiting presynaptic Ca2+ channels and induces long-term plasticity by decreasing cellular cAMP levels. Here we identified an unanticipated additional mechanism of acute cannabinoid signaling in presynaptic terminals that regulates the size of synaptic vesicle pools available for neurotransmitter release. Specifically, we show that activation of CB1Rs in human and mouse neurons rapidly recruits...
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Cannabis, Cannabinoids, and Brain Morphology: A Review of the Evidence

Please use this link to access this publication. Abstract Cannabis and cannabinoid-based products are increasingly being accepted and commodified globally. Yet there is currently limited understanding of the effect of the varied cannabinoid compounds on the brain. Exogenous cannabinoids interact with the endogenous cannabinoid system that underpins vital functions in the brain and body, and they are thought to perturb key brain and cognitive function. However, much neuroimaging research has been confined to observational studies of cannabis users, without examining the specific role of the various cannabinoids (Δ9-tetrahydrocannabinol, cannabidiol, etc.). This review summarizes the brain structural imaging evidence to date associated with cannabis use,...
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