Tag Archives: neuroprotective

Cannabidiol protects an in vitro model of the blood-brain barrier from oxygen-glucose deprivation via PPARγ and 5-HT1A receptors.

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“In vivo and in vitro studies have demonstrated a protective effect of cannabidiol (CBD) in reducing infarct size in stroke models and against epithelial barrier damage in numerous disease models.

We aimed to investigate whether CBD also affects blood-brain barrier (BBB) permeability following ischaemia.

CONCLUSIONS AND IMPLICATIONS:

These data suggest that preventing permeability changes at the BBB could represent an as yet unrecognized mechanism of CBD-induced neuroprotection in ischaemic stroke, a mechanism mediated by activation of PPARγ and 5-HT1A receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/26497782

Neuroprotective effect of endogenous cannabinoids on ischemic brain injury induced by the excess microglia-mediated inflammation.

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“Increasing evidence has demonstrated the role of endogenous cannabinoids system (ECS) on protecting brain injury caused by ischemia (IMI). Papers reported that microglia-mediated inflammation has become one of the most pivotal mechanisms for IMI. This study was aimed to investigate the potential roles of ECS on neuron protection under microglia-mediated inflammation. Inflammatory cytokines level both in vitro (BV-2 cells) and in vivo (brain tissue from constructed IMI model and brain-isolated microglia) was detected. ECS levels were detected, and its effects on inflammations was also analyzed. Influence of microglia-mediated inflammation on neuron injury was analyzed. Moreover, the effects of ECS on protecting neuron injury were also analyzed. Our results showed that the levels of inflammatory cytokines including TNFα and IL-1β were higher while IKBα was lower in IMI model brain tissue, brain-isolated microglia and BV-2 cells compared to the control. Inflammation was activated in microglia, as well as the activation of ECS characterized by the increasing level of AEA and 2-AG. Furthermore, the activated microglia-mediated self-inflammation performed harmful influence on neurons via suppressing cell viability and inducing apoptosis. Moreover, ECS functioned as a protector on neuron injury though promoting cell proliferation and suppressing cell apoptosis which were caused by the activated BV-2 cells (LPS induced for 3 h). Our data suggested that ECS may play certain neuroprotective effects on microglia-mediated inflammations-induced IMI through anti-inflammatory function.”

http://www.ncbi.nlm.nih.gov/pubmed/27398146

Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis.

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“Proliferator-activated receptor γ (PPARγ) activation can result in transcription of proteins involved in oxidative stress defence and mitochondrial biogenesis which could rescue mitochondrial dysfunction in Parkinson’s disease (PD). The PPARγ agonist pioglitazone is protective in models of PD; however side effects have limited its clinical use.

The cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) may have PPARγ dependent anti-oxidant properties. Here we investigate the effects of Δ9-THC and pioglitazone on mitochondrial biogenesis and oxidative stress.

We found that only Δ9-THC was able to restore mitochondrial content in MPP+ treated SH-SY5Y cells in a PPARγ dependent manner by increasing expression of the PPARγ co-activator 1α (PGC-1α), the mitochondrial transcription factor (TFAM) as well as mitochondrial DNA content.

… unlike pioglitazone, Δ9-THC resulted in a PPARγ dependent reduction of MPP+ induced oxidative stress.

We therefore suggest that, in contrast to pioglitazone, Δ9-THC mediates neuroprotection via PPARγ-dependent restoration of mitochondrial content which may be beneficial for PD treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/27366949

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=10314&path[]=32486

Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids

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“The beta amyloid (Aβ) and other aggregating proteins in the brain increase with age and are frequently found within neurons. The mechanistic relationship between intracellular amyloid, aging and neurodegeneration is not, however, well understood.

We use a proteotoxicity model based upon the inducible expression of Aβ in a human central nervous system nerve cell line to characterize a distinct form of nerve cell death caused by intracellular Aβ.

It is shown that intracellular Aβ initiates a toxic inflammatory response leading to the cell’s demise. Aβ induces the expression of multiple proinflammatory genes and an increase in both arachidonic acid and eicosanoids, including prostaglandins that are neuroprotective and leukotrienes that potentiate death.

Cannabinoids such as tetrahydrocannabinol stimulate the removal of intraneuronal Aβ, block the inflammatory response, and are protective.

Altogether these data show that there is a complex and likely autocatalytic inflammatory response within nerve cells caused by the accumulation of intracellular Aβ, and that this early form of proteotoxicity can be blocked by the activation of cannabinoid receptors.”

http://www.nature.com/articles/npjamd201612

“Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells. Preliminary lab studies at the Salk Institute find THC reduces beta amyloid proteins in human neurons.” http://www.salk.edu/news-release/cannabinoids-remove-plaque-forming-alzheimers-proteins-from-brain-cells/

β-Caryophyllene, a phytocannabinoid attenuates oxidative stress, neuroinflammation, glial activation, and salvages dopaminergic neurons in a rat model of Parkinson disease.

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“Parkinson disease (PD) is a neurodegenerative disease characterized by progressive dopaminergic neurodegeneration in the substantia nigra pars compacta (SNc) area.

The present study was undertaken to evaluate the neuroprotective effect of β-caryophyllene (BCP) against rotenone-induced oxidative stress and neuroinflammation in a rat model of PD.

The findings demonstrate that BCP provides neuroprotection against rotenone-induced PD and the neuroprotective effects can be ascribed to its potent antioxidant and anti-inflammatory activities.”

http://www.ncbi.nlm.nih.gov/pubmed/27316720

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/23138934

http://www.thctotalhealthcare.com/category/parkinsons-disease/

Cannabinoid receptor agonism suppresses tremor, cognition disturbances and anxiety-like behaviors in a rat model of essential tremor.

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“Cognitive and motor disturbances are serious consequences of tremor induced by motor disorders. Despite a lack of effective clinical treatment, some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of tremor.

In the current study, the effects of WIN55, 212-2 (WIN), a cannabinoid receptor (CBR) agonist, on harmaline-induced motor and cognitive impairments was studied.

The neuroprotective and anxiolytic effects of WIN demonstrated in the current study can be offered cannabinoid receptor (CBR) agonism as a potential neuroprotective agent in the treatment of patients with tremor that manifest mental dysfunctions.”

http://www.ncbi.nlm.nih.gov/pubmed/27317835

Current Status and Prospects for Cannabidiol Preparations as New Therapeutic Agents.

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“There is growing pressure for states and the federal government to legalize the use of cannabis products for medical purposes in the United States.

Sixteen states have legalized (or decriminalized possession of) products high in cannabidiol (CBD) and with restricted Δ9 -tetrahydrocannabinol (Δ9 -THC) content. In most of these states, the intent is for use in refractory epileptic seizures in children, but in a few states, the indications are broader.

The objectives of this review are to provide an overview of the pharmacology and toxicology of CBD; to summarize some of the regulatory, safety, and cultural issues relevant to the further exploitation of its antiepileptic or other pharmacologic activities; and to assess the current status and prospects for clinical development of CBD and CBD-rich preparations for medical use in the United States.

Unlike Δ9 -THC, CBD elicits its pharmacologic effects without exerting any significant intrinsic activity on the cannabinoid receptors (CB1 and CB2 ), whose activation results in the psychotropic effects characteristic of Δ9 -THC, and CBD possesses several pharmacologic activities that give it a high potential for therapeutic use.

CBD exhibits antiepileptic, anxiolytic, antipsychotic, and antiinflammatory properties.

In combination with Δ9 -THC, CBD has received regulatory approvals in several European countries and is currently under study in U.S. Food and Drug Administration-registered trials in the United States.

A number of states have passed legislation to allow for the use of CBD-rich, limited Δ9 -THC-content preparations of cannabis for certain pathologic conditions. CBD is currently being studied in several clinical trials and is at different stages of clinical development for various medical indications.

Judging from clinical findings reported so far, CBD and CBD-enriched preparations have great potential utility, but uncertainties regarding sourcing, long-term safety, abuse potential, and regulatory dilemmas remain.”

http://www.ncbi.nlm.nih.gov/pubmed/27285147

Neuroprotection by Cannabinoids in Huntington’s Disease

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“A Double Blind, Randomized, Cross Over, Placebo Controlled Phase 2 Clinical Trial to Asses Neuroprotection by Cannabinoids in Huntington’s Disease.”

ClinicalTrials.gov

“Huntington’s disease (HD) is a progressive neurodegenerative disorder, related to an abnormal expansion of CAG triplets in the huntingtin gene, characterized by motor, cognitive and behavioral abnormalities, without known effective symptomatic treatment and without known disease slowing strategy. The most severe neuropathological lesions observed in HD take place in the striatum, one brain area important in motor control and rich in cannabinoid receptors (CBR). CBR are subdivided in two classes: CB1R are located in neurons and play a role in neuronal function; CB2R in brain are located mostly in microglia and modulate neuroinflammation.

CBR disappear early in the course of HD, before there is a massive drop out of cells in the striatum. Cannabinoid transmission is also an early event in brains of animal models of HD. In R6/2 mice, which carry large CAG expansions and develop an early and severe HD phenotype the suppression of the CB1R gene further accelerate the development of a severe clinical syndrome and the characteristic brain inclusions and abnormalities of synaptic density. R6/2 treated mice treated with cannabinoids improve their clinical phenotype, their brain lesions, the synaptic density and the levels of BNDF, a neurotrophic factor which enhances survival and resistance of striatal neurons.

Preliminary studies of cannabinoids in patients with HD have shown that these compounds are safe in these patients.”

https://clinicaltrials.gov/show/NCT01502046

Reversal effect of simvastatin on the decrease in cannabinoid receptor 1 density in 6-hydroxydopamine lesioned rat brains.

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“Cannabinoid 1(CB1) receptors are closely correlated to the dopaminergic system and involved in cognitive function. Since statins have been used to regulate the progression of Parkinson’s disease (PD) via its anti-inflammation and neuroprotective effects, we asked if statins affect the CB1 receptors in the 6-hydroxydopamine (6-OHDA) lesioned rat.

Our data suggest a critical role of CB1 receptors in treating PD with simvastatin, and implicate CB1 receptors as a potential therapeutic target in the treatment of PD.”

http://www.ncbi.nlm.nih.gov/pubmed/27155397

Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview.

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“The word dementia describes a class of heterogeneous diseases which etiopathogenetic mechanisms are not well understood. There are different types of dementia, among which, Alzheimer’s disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) are the more common.

Currently approved pharmacological treatments for most forms of dementia seem to act only on symptoms without having profound disease-modifying effects. Thus, alternative strategies capable of preventing the progressive loss of specific neuronal populations are urgently required.

In particular, the attention of researchers has been focused on phytochemical compounds that have shown antioxidative, anti-amyloidogenic, anti-inflammatory and anti-apoptotic properties and that could represent important resources in the discovery of drug candidates against dementia.

In this review, we summarize the neuroprotective effects of the main phytochemicals belonging to the polyphenol, isothiocyanate, alkaloid and cannabinoid families in the prevention and treatment of the most common kinds of dementia.

We believe that natural phytochemicals may represent a promising sources of alternative medicine, at least in association with therapies approved to date for dementia.”

http://www.ncbi.nlm.nih.gov/pubmed/27110749