Tag Archives: Cannabinoids

Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimer’s disease.

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“Microglial activation is an invariant feature of Alzheimer’s disease (AD). It is noteworthy that cannabinoids are neuroprotective by preventing β-amyloid (Aβ)-induced microglial activation both in vitro and in vivo… the phytocannabinoid cannabidiol (CBD) has shown anti-inflammatory properties in different paradigms…

Cannabinoids, whether plant-derived, synthetic, or endocannabinoids, exert their functions through activation of cannabinoid receptors, two of which have been well characterized to date: CB1 and CB2. Cannabinoids are neuroprotective against excitotoxicity and acute brain damage, both in vitro and in vivo. Several mechanisms account for the neuroprotection afforded by this type of drug such as blockade of excitotoxicity, reduction of calcium influx, antioxidant properties of the compounds, or enhanced trophic factor support. A decrease in proinflammatory mediators brought about by cannabinoids may be also involved in their neuroprotection… Cannabidiol (CBD), the major plant-derived nonpsychotropic constituent of marijuana, is of potential therapeutic interest in different disease conditions (e.g., inflammation)…

…this kind of drug with neuroprotective and anti-inflammatory effects may be of interest in the prevention of AD inflammation, in particular CB2-selective agonists, which are devoid of psychoactive effects…

Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo…

CBD is able to modulate microglial cell function in vitro and induce beneficial effects in an in vivo model of AD.

Given that CBD lacks psychoactivity, it may represent a novel therapeutic approach for this neurological disease.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102548/

Differential transcriptional profiles mediated by exposure to the cannabinoids cannabidiol and Δ9-tetrahydrocannabinol in BV-2 microglial cells.

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“Apart from their effects on mood and reward, cannabinoids exert beneficial actions such as neuroprotection and attenuation of inflammation. The immunosuppressive activity of cannabinoids has been well established. We previously showed that the psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD) differ in their anti-inflammatory signalling pathways.

CONCLUSIONS AND IMPLICATIONS:

These observations indicated that CBD, but much less than THC, induced a cellular stress response in microglial cells and suggested that this effect could underlie its anti-inflammatory activity.”

http://www.ncbi.nlm.nih.gov/pubmed/21542829

Cannabinoids Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Inhibit the Lipopolysaccharide-activated NF-κB and Interferon-β/STAT Proinflammatory Pathways in BV-2 Microglial Cells

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“Cannabinoids have been shown to exert anti-inflammatory activities in various in vivo and in vitro experimental models as well as ameliorate various inflammatory degenerative diseases. Δ9-Tetrahydrocannabinol (THC)is a major constituent of Cannabis and serves as an agonist of the cannabinoid receptors CB1 and CB2.

The second major constituent of Cannabis extract is cannabidiol (CBD). CBD lacks the psychoactive effects that accompany the use of THC. Moreover, CBD was demonstrated to antagonize some undesirable effects of THC, including intoxication, sedation, and tachycardia, while sharing neuroprotective, anti-oxidative, anti-emetic, and anti-carcinogenic properties. Both THC and CBD have been shown to exert anti-inflammatory properties and to modulate the function of immune cells…

In summary, our results show that although both THC and CBD exert anti-inflammatory effects, the two compounds engage different, although to some extent overlapping, intracellular pathways. Both THC and CBD decrease the activation of proinflammatory signaling…

 The cannabinoids by moderating or disrupting these signaling networks may show promise as anti-inflammatory agents.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804319/

Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia.

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Psychopharmacology

“Nighttime agitation occurs frequently in patients with dementia and represents the number one burden on caregivers today. Current treatment options are few and limited due to substantial side effects.

OBJECTIVES:

The aim of the study was to measure the effect of the cannabinoid dronabinol (THC) on nocturnal motor activity.

RESULTS:

Compared to baseline, dronabinol led to a reduction in nocturnal motor activity. These findings were corroborated by improvements in Neuropsychiatric Inventory total score as well as in subscores for agitation, aberrant motor, and nighttime behaviors . No side effects were observed.

CONCLUSIONS:

The study suggests that dronabinol (THC) was able to reduce nocturnal motor activity and agitation in severely demented patients. Thus, it appears that dronabinol (THC) may be a safe new treatment option for behavioral and circadian disturbances in dementia.”

http://www.ncbi.nlm.nih.gov/pubmed/16521031

https://link.springer.com/article/10.1007%2Fs00213-006-0343-1

Regulation of cannabinoid CB1 receptors in the central nervous system by chronic cannabinoids.

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“The potential therapeutic benefits of certain cannabinoid-mediated effects, as well as the use of marijuana for its psychoactive properties, has raised interest in understanding the cellular adaptations produced by chronic administration of this class of drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/14977366

Cannabinoids and neurodegenerative diseases.

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“Although significant advances have taken place in recent years on our understanding of the molecular mechanisms of different neurodegenerative diseases, its translation into effective therapeutic treatments has not been as successful as could be expected. There is still a dramatic lack of curative treatments for the most frequent disorders and only symptomatic relief for many others. Under this perspective, the search for novel therapeutic approaches is demanding and significant attention and efforts have been directed to studying additional neurotransmission systems including the endocannabinoid system (ECS).

The neuroprotective properties of exogenous as well as endogenous cannabinoids have been known for years and the underlying molecular mechanisms have been recently unveiled. As discussed later, antioxidative, antiglutamatergic and antiinflammatory effects are now recognized as derived from cannabinoid action and are known to be of common interest for many neurodegenerative processes.

 Thus, these characteristics make cannabinoids attractive candidates for the development of novel therapeutic strategies.

 The present review will focus on the existing data regarding the possible usefulness of cannabinoid agents for the treatment of relevant neurological pathologies for our society such as Alzheimer’s disease, multiple sclerosis, Huntington’s disease and amyotrophic lateral sclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/19839933

Cannabinoid CB1 receptor stimulation affords neuroprotection in MPTP-induced neurotoxicity by attenuating S100B up-regulation in vitro.

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 “…the involvement of the endocannabinoid system was investigated by using selective inhibitors of endocannabinoid inactivation (cellular re-uptake or enzymatic hydrolysis) and selective cannabinoid CB1 and CB2 receptor antagonists and by silencing the CB1 receptor…

 Our data suggest that selective activation of CB1 receptors by either exogenous or endogenous cannabinoids might afford neuroprotection…”

http://www.ncbi.nlm.nih.gov/pubmed/17639288

Contrasting protective effects of cannabinoids against oxidative stress and amyloid-β evoked neurotoxicity in vitro.

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“Cannabinoids have been widely reported to have neuroprotective properties in vitro and in vivo. In this study we compared the effects of CB1 and CB2 receptor-selective ligands, the endocannabinoid anandamide and the phytocannabinoid cannabidiol, against oxidative stress and the toxic hallmark Alzheimer’s protein, β-amyloid (Aβ)…

 …the endocannabinoid anandamide protects neuronal cells from Aβ exposure via a pathway unrelated to CB1 or CB2 receptor activation…protective effect of cannabidiol against oxidative stress…

…divergent pathways for neuroprotection of these two cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/22233683

Distribution patterns of cannabinoid CB1 receptors in the hippocampus of APPswe/PS1ΔE9 double transgenic mice.

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Abstract

“Cannabinoids have neuroprotective effects that are exerted primarily through cannabinoid CB1 receptors in the brain. This study characterized CB1 receptor distribution in the double transgenic (dtg) APP(swe)/PS1(ΔE9) mouse model for Alzheimer’s disease. Immunohistochemical labeling of CB1 protein in non-transgenic mice revealed that CB1 was highly expressed in the hippocampus, with the greatest density of CB1 protein observed in the combined hippocampal subregions CA2 and CA3 (CA2/3). CB1 immunoreactivity in the CA1 and CA2/3 hippocampal regions was significantly decreased in the dtg APP(swe)/PS1(ΔE9) mice compared to non-transgenic littermates. Reduced CB1 expression in dtg APP(swe)/PS1(ΔE9) mice was associated with astroglial proliferation and elevated expression of the cytokines inducible nitric oxide synthase and tumor necrosis factor alpha. This finding suggests an anti-inflammatory effect of cannabinoids that is mediated by CB1 receptor, particularly in the CA2/3 region of the hippocampus. Furthermore, the study suggests a decreased CB1 receptor expression may result in diminished anti-inflammatory processes, exacerbating the neuropathology associated with Alzheimer’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/21192920

Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-kappaB involvement.

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“In view of the pro-inflammatory scenario observed in Alzheimer’s disease, in the recent years anti-inflammatory drugs have been proposed as potential therapeutic agents. We have previously shown that cannabidiol, the main non-psychotropic component from Cannabis sativa, possess a variegate combination of anti-oxidant and anti-apoptotic effects that protect PC12 cells from Abeta toxicity. In parallel, cannabidiol has been described to have anti-inflammatory properties in acute models of inflammation …

The here reported data increases our knowledge about the possible neuroprotective mechanism of cannabidiol, highlighting the importance of this compound to inhibit beta-amyloid induced neurodegeneration, in view of its low toxicity in humans.”

http://www.ncbi.nlm.nih.gov/pubmed/16490313