New insights into antimetastatic and antiangiogenic effects of cannabinoids.

“Cannabinoids exert antitumorigenic effects via multiple mechanisms.

Of these, antimetastatic and antiangiogenic actions have attracted considerable interest in the past years…

This chapter reviews the cell- and substance-specific antitumorigenic mechanisms of cannabinoids with particular consideration of their antimetastatic/anti-invasive and antiangiogenic actions.

In addition, beneficial interactions of cannabinoids with currently used chemotherapeutics as well as the influence of cannabinoids on tumor-immune surveillance are addressed.

Collectively, the currently available data suggest cannabinoids as a potential tool in modern cancer pharmacotherapy.”

http://www.ncbi.nlm.nih.gov/pubmed/25619715

http://www.thctotalhealthcare.com/category/cancer/

Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice.

“Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects…

These results indicate that repeated treatment with CBD, similar to clozapine, reverses the psychotomimetic-like effects and attenuates molecular changes observed after chronic administration of an NMDAR antagonist.

These data support the view that CBD may have antipsychotic properties.”  http://www.ncbi.nlm.nih.gov/pubmed/25618402

“Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug… a controlled clinical trial comparing CBD with an atypical antipsychotic drug have confirmed that this cannabinoid can be a safe and well-tolerated alternative treatment for schizophrenia.” http://www.ncbi.nlm.nih.gov/pubmed/16612464

“A critical review of the antipsychotic effects of cannabidiol: 30 years of a translational investigation… These results support the idea that CBD may be a future therapeutic option in psychosis, in general and in schizophrenia, in particular.” http://www.ncbi.nlm.nih.gov/pubmed/22716160

http://www.thctotalhealthcare.com/category/schizophrenia/

The effects of Δ9-tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis

“Cannabis is taken as self-medication by patients with inflammatory bowel disease for symptomatic relief.

Cannabinoid receptor agonists decrease inflammation in animal models of colitis, but their effects on the disturbed motility is not known. (-)-Cannabidiol (CBD) has been shown to interact with Δ9-tetrahydrocannabinol (THC) in behavioural studies, but it remains to be established if these cannabinoids interact in vivo in inflammatory disorders.

Therefore the effects of CBD and THC alone and in combination were investigated in a model of colitis…

In this model of colitis, THC and CBD not only reduced inflammation but also lowered the occurrence of functional disturbances. Moreover the combination of CBD and THC could be beneficial therapeutically, via additive or potentiating effects.

As the two phytocannabinoids modulate the immune system and differ in their pharmacological profile, their combination could be more beneficial than either drug alone. Additionally CBD could not only potentiate the therapeutic effects of THC, but also attenuate some of its undesirable effects…”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931570/

http://www.thctotalhealthcare.com/category/colitis/

Protective effects of cannabidiol on lesion-induced intervertebral disc degeneration.

“Disc degeneration is a multifactorial process that involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content…

Cannabidiol (CBD) is the major nonpsychotropic phytocannabinoid of Cannabis sativa (up to 40% of Cannabis extracts). Contrary to most cannabinoids, CBD does not produce psychotomimetic or cognitive effects. Interesting, in the last years it has been suggest that CBD produces a plethora of others pharmacological effects, including antioxidant, neuroprotective, anti-proliferative, anti-anxiety, hypnotic and antiepileptic, anti-nausea, anti-ischemic, anti-hyperalgesic, and anti-inflammatory…

The present study investigated the effects of cannabidiol intradiscal injection in the coccygeal intervertebral disc degeneration induced by the needle puncture model using magnetic resonance imaging (MRI) and histological analyses…

 Cannabidiol significantly attenuated the effects of disc injury induced by the needle puncture. Considering that cannabidiol presents an extremely safe profile and is currently being used clinically, these results suggest that this compound could be useful in the treatment of intervertebral disc degeneration.

 In summary our study revealed anti-degenerative effects of intradiscal microinjection of CBD 120 nmol. CBD represents one of the most promising candidates present in the Cannabis sativa plant for clinical use due to its remarkable lack of cognitive or psychotomimetic actions.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269422/

http://www.thctotalhealthcare.com/category/spinal-cord-injury/

Cannabidiol protects against doxorubicin-induced cardiomyopathy by modulating mitochondrial function and biogenesis.

“Doxorubicin (DOX) is a widely used, potent chemotherapeutic agent; however, its clinical application is limited because of its dose-dependent cardiotoxicity. DOX’s cardiotoxicity involves increased oxidative/nitrative stress, impaired mitochondrial function in cardiomyocytes/endothelial cells, and cell death.

Cannabidiol is a non-psychotropic constituent of marijuana, which is well-tolerated in humans, with antioxidant, anti-inflammatory, and recently discovered antitumor properties.

We aimed to explore the effects of cannabidiol in a well-established mouse model of DOX-induced cardiomyopathy…

Treatment with cannabidiol markedly improved DOX-induced cardiac dysfunction, oxidative/nitrative stress and cell death. Cannabidiol also enhanced the DOX-induced impaired cardiac mitochondrial function and biogenesis.

These data suggest that cannabidiol may represent a novel cardioprotective strategy against DOX-induced cardiotoxicity, and the above described effects on mitochondrial function and biogenesis may contribute to its beneficial properties described in numerous other models of tissue injury.”

http://www.ncbi.nlm.nih.gov/pubmed/25569804

Proapoptotic effect of endocannabinoids in prostate cancer cells.

“Recent evidence shows that derivatives of Cannabis sativa and its analogs may exert a protective effect against different types of oncologic pathologies.

The purpose of the present study was to detect the presence of cannabinoid receptors (CB1 and CB2) on cancer cells with a prostatic origin and to evaluate the effect of the in vitro use of synthetic analogs…

Based on these results, we suggest that endocannabinoids may be a beneficial option for the treatment of prostate cancer that has become nonresponsive to common therapies.”

http://www.ncbi.nlm.nih.gov/pubmed/25606819

http://www.thctotalhealthcare.com/category/prostate-cancer/

Cannabinoid Signaling and Neuroinflammatory Diseases: A Melting pot for the Regulation of Brain Immune Responses.

“The concept of the central nervous system (CNS) as an immune-privileged site, essentially due to the presence of the blood brain barrier, appears to be overly simplistic. Indeed, within healthy CNS immune activities are permitted and are required for neuronal function and host defense, not only due to the presence of the resident innate immune cells of the brain, but also by virtue of a complex cross-talk of the CNS with peripheral immune cells.

Nonetheless, long-standing and persisting neuroinflammatory responses are most often detrimental and characterize several neuroinflammatory diseases, including multiple sclerosis, Alzheimer’s disease and amyotrophic lateral sclerosis.

A growing body of evidence suggests that Cannabis sativa-derived phytocannabinoids, as well as synthetic cannabinoids, are endowed with significant immunoregulatory and anti-inflammatory properties, both in peripheral tissues and in the CNS, through the activation of cannabinoid receptors.

In this review, the immunomodulatory effects of cannabinoid signaling on the most relevant brain immune cells will be discussed. In addition, the impact of cannabinoid regulation on the overall integration of the manifold brain immune responses will also be highlighted, along with the implication of these compounds as potential agents for the management of neuroinflammatory disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/25601726

Cannabidiol increases survival and promotes rescue of cognitive function in a murine model of Cerebral Malaria.

Neuroscience

“Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparuminfection that might cause permanent neurological deficits.

Cannabidiol (CBD) is a nonpsychotomimetic compound of Cannabis sativa with neuroprotective properties.

In the present work, we evaluated the effects of CBD in a murine model of CM.

CBD treatment resulted in an increase in BDNF expression in the hippocampus and decreased levels of proinflammatory cytokines in the hippocampus (TNF-α) and prefrontal cortex (IL-6).

Our results indicate that CBD exhibits neuroprotective effects in CM model and might be useful as an adjunctive therapy to prevent neurological symptoms following this disease.”

http://www.ncbi.nlm.nih.gov/pubmed/25595981

“Cannabidiol adjuvant treatment increases survival in the murine model of CM. Cannabidiol adjuvant treatment promotes rescue of behavioral and cognitive function.”

https://www.sciencedirect.com/science/article/pii/S0306452215000196

http://www.thctotalhealthcare.com/category/malaria/

Two non-psychoactive cannabinoids reduce intra-cellular lipid levels and inhibit hepatosteatosis.

“Obesity and associated metabolic syndrome have quickly become a pandemic and a major detriment to human health globally.

The presence of non-alcoholic fatty liver disease (NAFLD; hepatosteatosis) in obesity has been linked to the worsening of the metabolic syndrome, including the development of insulin resistance and cardiovascular disease. Currently, there are few options to treat NAFLD, including life style changes and insulin sensitizers.

Recent evidence suggests that the cannabinoids Δ9-tetrahydrocannabivarin (THCV) and cannabidiol (CBD) improve insulin sensitivity; we aimed at studying their effects on lipid levels…

THCV and CBD directly reduce accumulated lipid levels in vitro in a hepatosteatosis model and adipocytes.

…these cannabinoids are able to increase yolk lipid mobilization and inhibit the development of hepatosteatosis respectively.

CONCLUSIONS:

Our results suggest that THCV and CBD might be used as new therapeutic agents for the pharmacological treatment of obesity- and metabolic syndrome-related NAFLD/hepatosteatosis.”

http://www.ncbi.nlm.nih.gov/pubmed/25595882

http://www.thctotalhealthcare.com/category/obesity-2/

Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma.

“Glioblastoma (GBM) resistance to therapy is the most common cause of tumor recurrence, which is ultimately fatal in 90% of the patients 5 years after initial diagnosis. A sub-population of tumor cells with stem-like properties, glioma stem cells (GSCs), is specifically endowed to resist or adapt to the standard therapies, leading to therapeutic resistance.

Several anticancer agents, collectively termed redox therapeutics, act by increasing intracellular levels of reactive oxygen species (ROS).

In this study, we investigated mechanisms underlying GSC response and resistance to cannabidiol (CBD), a non-toxic, non-psychoactive cannabinoid and redox modulator.

…we demonstrated that combining CBD treatment with the inhibition of system Xc resulted in synergistic ROS increase leading to robust antitumor effects, that is, decreased GSC survival, self-renewal, and invasion.

Our investigation provides novel mechanistic insights into the antitumor activity of redox therapeutics and suggests that combinatorial approaches using small molecule modulators of ROS offer therapeutic benefits in GBM.”

http://www.ncbi.nlm.nih.gov/pubmed/25590811

http://www.thctotalhealthcare.com/category/gllomas/