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Alzheimer's disease cannabinoids

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https://www.readbyqxmd.com/read/28412919/neurological-disorders-in-medical-use-of-cannabis-an-update
#1
Renata Solimini, Maria Concetta Rotolo, Simona Pichini, Roberta Pacifici
Medical cannabis is increasingly used as a treatment or adjunct treatment with different levels of efficacy in several neurological disorders or related symptoms (such as multiple sclerosis, autism, Parkinson and Alzheimer disease, Tourette's syndrome, Huntington's disease, neuropathic pain, epilepsy, headache), as well as in other medical conditions (e.g. nausea and vomiting, glaucoma, appetite stimulation, cancer, inflammatory conditions, asthma). Nevertheless, a number of neurological adverse effects from use of medical cannabis on the short- and on the long- term have been reported, in addition to other adverse health events...
April 13, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28409931/1-4-18-f-fluorobenzyl-4-tetrahydrofuran-2-yl-methyl-piperazine-a-novel-suitable-radioligand-with-low-lipophilicity-for-imaging-sigma-1-receptors-in-the-brain
#2
Yingfang He, Fang Xie, Jiajun Ye, Winnie Deuther-Conrad, Bixiao Cui, Liang Wang, Jie Lu, Jörg Steinbach, Peter Brust, Yiyun Huang, Jie Lu, Hongmei Jia
We have designed and synthesized novel piperazine compounds with low lipophilicity as σ1 receptor ligands. 1-(4-Fluorobenzyl)-4-((tetrahydrofuran-2-yl)methyl)piperazine (10) possessed low nanomolar σ1 receptor affinity and high selectivity toward the vesicular acetylcholine transporter (>2000-fold), σ2 receptors (52-fold), adenosine A2A, adrenergic α2, cannabinoid CB1, dopamine D1, D2L, γ-aminobutyric acid A (GABAA), NMDA, melatonin MT1, MT2 and serotonin 5-HT1 receptors. The corresponding radiotracer [(18)F]10 demonstrated high brain uptake and extremely high brain-to-blood ratios in biodistribution studies in mice...
April 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28408985/new-drugs-in-psychiatry-focus-on-new-pharmacological-targets
#3
REVIEW
Filippo Caraci, Gian Marco Leggio, Salvatore Salomone, Filippo Drago
The approval of psychotropic drugs with novel mechanisms of action has been rare in recent years. To address this issue, further analysis of the pathophysiology of neuropsychiatric disorders is essential for identifying new pharmacological targets for psychotropic medications. In this report, we detail drug candidates being examined as treatments for psychiatric disorders. Particular emphasis is placed on agents with novel mechanisms of action that are being tested as therapies for depression, schizophrenia, or Alzheimer's disease...
2017: F1000Research
https://www.readbyqxmd.com/read/28315677/rimonabant-a-selective-cannabinoid1-receptor-antagonist-protects-against-light-induced-retinal-degeneration-in-vitro-and-in-vivo
#4
Tomoyo Imamura, Kazuhiro Tsuruma, Yuki Inoue, Tomohiro Otsuka, Yuta Ohno, Shiho Ogami, Shinsaku Yamane, Masamitsu Shimazawa, Hideaki Hara
The endocannabinoid system is involved in some neurodegenerative diseases such as Alzheimer's disease. An endogenous constellation of proteins related to cannabinoid1 receptor signaling, including free fatty acids, diacylglycerol lipase, and N-acylethanolamine-hydrolyzing acid amidase, are localized in the murine retina. Moreover, the expression levels of endogenous agonists of cannabinoid receptors are changed in the vitreous fluid. However, the role of the endocannabinoid system in the retina, particularly in the light-induced photoreceptor degeneration, remains unknown...
May 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28300462/an-update-on-the-advancements-in-the-treatment-of-agitation-in-alzheimer-s-disease
#5
REVIEW
Anton P Porsteinsson, Inga M Antonsdottir
Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are associated with significant negative outcomes for patients and their caregivers. Agitation, one of the most distressing NPS, lacks safe and effective long term interventions. Nonpharmacological interventions are suggested as first-line treatment, but aren't effective for every patient, resulting in pharmacological interventions for some patients, consisting of off-label use of antipsychotics, sedative/hypnotics, anxiolytics, acetylcholinesterase inhibitors, memantine, and antidepressants; where efficacy doesn't necessarily outweigh associated risks...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28276775/cannabinoids-therapeutic-use-what-is-our-current-understanding-following-the-introduction-of-thc-thc-cbd-oromucosal-spray-and-others
#6
REVIEW
Mauro Maccarrone, Rafael Maldonado, Miguel Casas, Thomas Henze, Diego Centonze
The complexity of the endocannabinoid (eCB) system is becoming better understood and new drivers of eCB signaling are emerging. Modulation of the activities of the eCB system can be therapeutic in a number of diseases. Research into the eCB system has been paralleled by the development of agents that interact with cannabinoid receptors. In this regard it should be remembered that herbal cannabis contains a myriad of active ingredients, and the individual cannabinoids have quite distinct biological activities requiring independent studies...
April 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28218780/microrna-139-modulates-alzheimer-s-associated-pathogenesis-in-samp8-mice-by-targeting-cannabinoid-receptor-type-2
#7
Y Tang, J S Bao, J H Su, W Huang
Alzheimer's disease (AD) is a neurodegenerative disorder, and is the most common type of dementia in the elderly population. Growing evidence indicates that microRNAs (miRNAs) play a crucial role in neuroinflammation associated with AD progression. In this study, we analyzed the expression of microRNA-139 (miR-139) as well as the learning and memory function in AD. We observed that the miR-139 expression was significantly higher in the hippocampus of aged senescence accelerated mouse prone 8 (SAMP8) mice (2...
February 16, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28215162/gut-brain-axis-role-of-lipids-in-the-regulation-of-inflammation-pain-and-cns-diseases
#8
Roberto Russo, Claudia Cristiano, Carmen Avagliano, Carmen De Caro, Giovanna La Rana, Giuseppina Mattace Raso, Roberto Berni Canani, Rosaria Meli, Antonio Calignano
The human gut is a composite anaerobic environment with a large, diverse and dynamic enteric microbiota, represented by more than 100 trillion microorganisms, including at least 1000 distinct species. The discovery that a different microbial composition can influence behavior and cognition, and in turn the nervous system can indirectly influence enteric microbiota composition, has significantly contributed to establish the well-accepted concept of gut-brain axis. This hypothesis is supported by several evidence showing mutual mechanisms, which involve the vague nerve, the immune system, the hypothalamic-pituitary-adrenal (HPA) axis modulation and the bacteria-derived metabolites...
February 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28210207/cannabinoid-receptor-2-signaling-in-neurodegenerative-disorders-from-pathogenesis-to-a-promising-therapeutic-target
#9
REVIEW
Tommaso Cassano, Silvio Calcagnini, Lorenzo Pace, Federico De Marco, Adele Romano, Silvana Gaetani
As a consequence of an increasingly aging population, the number of people affected by neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, is rapidly increasing. Although the etiology of these diseases has not been completely defined, common molecular mechanisms including neuroinflammation, excitotoxicity and mitochondrial dysfunction have been confirmed and can be targeted therapeutically. Moreover, recent studies have shown that endogenous cannabinoid signaling plays a number of modulatory roles throughout the central nervous system (CNS), including the neuroinflammation and neurogenesis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28025562/cannabidiol-modulates-the-expression-of-alzheimer-s-disease-related-genes-in-mesenchymal-stem-cells
#10
Rosaliana Libro, Francesca Diomede, Domenico Scionti, Adriano Piattelli, Gianpaolo Grassi, Federica Pollastro, Placido Bramanti, Emanuela Mazzon, Oriana Trubiani
Mesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of several neurodegenerative disorders, including Alzheimer's disease (AD). The main neuropathological hallmarks of AD are senile plaques, composed of amyloid beta (Aβ), and neurofibrillary tangles, formed by hyperphosphorylated tau. However, current therapies for AD have shown limited efficacy. In this study, we evaluated whether pre-treatment with cannabidiol (CBD), at 5 μM concentration, modulated the transcriptional profile of MSCs derived from gingiva (GMSCs) in order to improve their therapeutic potential, by performing a transcriptomic analysis by the next-generation sequencing (NGS) platform...
December 23, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27789118/adverse-structural-and-functional-effects-of-marijuana-on-the-brain-evidence-reviewed
#11
REVIEW
David E Mandelbaum, Suzanne M de la Monte
The growing use and legalization of cannabis are leading to increased exposures across all age groups, including in adolescence. The touting of its medicinal values stems from anecdotal reports related to treatment of a broad range of illnesses including epilepsy, multiple sclerosis, muscle spasms, arthritis, obesity, cancer, Alzheimer disease, Parkinson disease, post-traumatic stress, inflammatory bowel disease, and anxiety. However, anecdotal data and the high level of interest in this treatment must not obscure objective assessments of any potential and realized short- and long-term adverse effects of cannabis, particularly with respect to age of onset and chronicity of exposure...
January 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/27757991/cannabinoids-prevent-the-amyloid-%C3%AE-induced-activation-of-astroglial-hemichannels-a-neuroprotective-mechanism
#12
Rosario Gajardo-Gómez, Valeria C Labra, Carola J Maturana, Kenji F Shoji, Cristian A Santibañez, Juan C Sáez, Christian Giaume, Juan A Orellana
The mechanisms involved in Alzheimer's disease are not completely understood and how astrocytes and their gliotransmission contribute to this neurodegenerative disease remains to be fully elucidated. Previous studies have shown that amyloid-β peptide (Aβ) induces neuronal death by a mechanism that involves the excitotoxic release of ATP and glutamate associated to astroglial hemichannel opening. We have demonstrated that synthetic and endogenous cannabinoids (CBs) reduce the opening of astrocyte Cx43 hemichannels evoked by activated microglia or inflammatory mediators...
January 2017: Glia
https://www.readbyqxmd.com/read/27714895/gingival-stromal-cells-as-an-in-vitro-model-cannabidiol-modulates-genes-linked-with-amyotrophic-lateral-sclerosis
#13
Thangavelu Soundara Rajan, Domenico Scionti, Francesca Diomede, Gianpaolo Grassi, Federica Pollastro, Adriano Piattelli, Lucio Cocco, Placido Bramanti, Emanuela Mazzon, Oriana Trubiani
Research in recent years has extensively investigated the therapeutic efficacy of mesenchymal stromal cells in regenerative medicine for many neurodegenerative diseases at preclinical and clinical stages. However, the success rate of stem cell therapy remains less at translational phase. Lack of relevant animal models that potentially simulate the molecular etiology of human pathological symptoms might be a reason behind such poor clinical outcomes associated with stem cell therapy. Apparently, self-renewal and differentiation ability of mesenchymal stem cells may help to study the early developmental signaling pathways connected with the diseases, such as Alzheimer's disease, Amyotrophic lateral sclerosis (ALS), etc...
October 7, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27695396/vascular-dysfunction-in-a-transgenic-model-of-alzheimer-s-disease-effects-of-cb1r-and-cb2r-cannabinoid-agonists
#14
Jorge Navarro-Dorado, Nuria Villalba, Dolores Prieto, Begoña Brera, Ana M Martín-Moreno, Teresa Tejerina, María L de Ceballos
There is evidence of altered vascular function, including cerebrovascular, in Alzheimer's disease (AD) and transgenic models of the disease. Indeed vasoconstrictor responses are increased, while vasodilation is reduced in both conditions. β-Amyloid (Aβ) appears to be responsible, at least in part, of alterations in vascular function. Cannabinoids, neuroprotective and anti-inflammatory agents, induce vasodilation both in vivo and in vitro. We have demonstrated a beneficial effect of cannabinoids in models of AD by preventing glial activation...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27586843/selective-modulator-of-cannabinoid-receptor-type-2-reduces-memory-impairment-and-infarct-size-during-cerebral-hypoperfusion-and-vascular-dementia
#15
Shalini Jayant, Bhupesh Sharma
Vascular dementia is the highly devastating neurodegenerative disorder after Alzheimer's disease (AD) and mainly found in aged people but the effectual therapeutic target is still not there. Chronic cerebral hypoperfusion (CCH) has been broadly found in vascular dementia (VaD) patients. CCH is thought to link with neurodegenerative disorders and their subsequent cognitive deteriorate on. This study has been framed to examine the role of a selective agonist of cannabinoid receptor type 2(CB2); 1-phenylisatin in CCH induced VaD...
September 2, 2016: Current Neurovascular Research
https://www.readbyqxmd.com/read/27567873/delineating-the-efficacy-of-a-cannabis-based-medicine-at-advanced-stages-of-dementia-in-a-murine-model
#16
Ester Aso, Pol Andrés-Benito, Isidro Ferrer
Previous reports have demonstrated that the combination of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) botanical extracts, which are the components of an already approved cannabis-based medicine, reduce the Alzheimer-like phenotype of AβPP/PS1 transgenic mice when chronically administered during the early symptomatic stage. Here, we provide evidence that such natural cannabinoids are still effective in reducing memory impairment in AβPP/PS1 mice at advanced stages of the disease but are not effective in modifying the Aβ processing or in reducing the glial reactivity associated with aberrant Aβ deposition as occurs when administered at early stages of the disease...
October 4, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27561138/a-systematic-review-of-the-evidence-for-medical-marijuana-in-psychiatric-indications
#17
Samuel T Wilkinson, Rajiv Radhakrishnan, Deepak Cyril D'Souza
OBJECTIVE: Marijuana has been approved for a number of psychiatric conditions in many states in the US including posttraumatic stress disorder (PTSD), agitation in Alzheimer's disease, and Tourette's disorder. In this systematic review, we examine the strength of evidence for the efficacy of marijuana and other cannabinoids for these psychiatric indications. DATA SOURCES: The literature (MEDLINE) was searched for studies published between January 1980 and March 2015 using search terms related to marijuana and other cannabinoids and the specific diagnosis...
August 2016: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/27488857/decreased-in-vivo-availability-of-the-cannabinoid-type-2-receptor-in-alzheimer-s-disease
#18
Rawaha Ahmad, Andrey Postnov, Guy Bormans, Jan Versijpt, Mathieu Vandenbulcke, Koen Van Laere
PURPOSE: The cannabinoid type 2 receptor (CB2R) is expressed by immune cells such as monocytes and macrophages. In the brain, CB2R is primarily found on microglia. CB2R upregulation has been reported in animal models of Alzheimer's disease, with a preferential localization near amyloid beta (Aβ) plaques, and in patients post mortem. We performed in vivo brain imaging and kinetic modelling of the CB2R tracer [(11)C]NE40 in healthy controls (HC) and in patients with Alzheimer's disease (AD) to investigate whether higher CB2R availability regionally colocalized to Aβ deposits is present in vivo...
November 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27450295/type-2-cannabinoid-receptors-in-neurodegeneration
#19
Tiziana Bisogno, Sergio Oddi, Alessandra Piccoli, Domenico Fazio, Mauro Maccarrone
Based on its wide expression in immune cells, type-2 cannabinoid (CB2) receptors were traditionally thought to act as "peripheral receptors" with an almost exclusively immunomodulatory function. However, their recent identification in mammalian brain areas, as well as in distinct neuronal cells, has opened the way to a re-consideration of CB2 signaling in the context of brain pathophysiology, synaptic plasticity and neuroprotection. To date, accumulated evidence from several independent preclinical studies has offered new perspectives on the possible involvement of CB2 signaling in brain and spinal cord traumatic injury, as well as in the most relevant neurodegenerative disorders like Alzheimer's disease, Parkinson's disease and Huntington's chorea...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27364363/endocannabinoid-system-in-neurological-disorders
#20
Roberta Ranieri, Chiara Laezza, Maurizio Bifulco, Daniela Marasco, Anna M Malfitano
BACKGROUND: Several studies support the evidence that the endocannabinoid system and cannabimimetic drugs might have therapeutic potential in numerous pathologies. These pathologies range from neurological disorders, atherosclerosis, stroke, cancer to obesity/metabolic syndrome and others. METHODS: In this paper we review the endocannabinoid system signaling and its alteration in neurodegenerative disorders like multiple sclerosis, Alzheimer's disease, Parkinson's disease and Huntington's disease and discuss the main findings about the use of cannabinoids in the therapy of these pathologies...
2016: Recent Patents on CNS Drug Discovery
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