Tag Archives: treatment

Cannabinoids prevent the amyloid β-induced activation of astroglial hemichannels: A neuroprotective mechanism.

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“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.

Nevertheless, whether CBs could prevent the astroglial hemichannel-dependent death of neurons evoked by Aβ is unknown.

We report that CBs fully prevented the hemichannel activity and inflammatory profile evoked by Aβ in astrocytes.

Moreover, CBs fully abolished the Aβ-induced release of excitotoxic glutamate and ATP associated to astrocyte Cx43 hemichannel activity, as well as neuronal damage in hippocampal slices exposed to Aβ.

Consequently, this work opens novel avenues for alternative treatments that target astrocytes to maintain neuronal function and survival during AD.”

https://www.ncbi.nlm.nih.gov/pubmed/27757991

An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse.

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“Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients.

Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for “CBD botanical drug substance,” on mucosal inflammation and hypermotility in mouse models of intestinal inflammation.

In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation.

These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.”

 https://www.ncbi.nlm.nih.gov/pubmed/27757083

Effects of Marijuana on ictal and interictal EEG activity in idiopathic generalized epilepsy.

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“Marijuana-based treatment for refractory epilepsy shows promise in surveys, case series and clinical trials.

However, literature on their electroencephalography (EEG) effects is sparse.

Our objective is to analyze the effect of marijuana on EEG in a 24-year-old patient with idiopathic generalized epilepsy (IGE) treated with cannabis.

Using a novel approach to electroencephalographic data, we demonstrate a decrease in interictal and ictal electrographic events during marijuana use.

Larger samples of patients and EEG, with standardized cannabinoid formulation and dosing are needed to validate our findings.”

 https://www.ncbi.nlm.nih.gov/pubmed/27763968

Δ9-THC Intoxication by Cannabidiol-Enriched Cannabis Extract in Two Children with Refractory Epilepsy: Full Remission after Switching to Purified Cannabidiol.

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“Animal studies and preliminary clinical trials have shown that cannabidiol (CBD)-enriched extracts may have beneficial effects for children with treatment-resistant epilepsy.

We describe the cases of two children with treatment-resistant epilepsy (Case A with left frontal dysplasia and Case B with Dravet Syndrome) with initial symptom improvement after the introduction of CBD extracts followed by seizure worsening after a short time.

The children presented typical signs of intoxication by Δ9-THC (inappropriate laughter, ataxia, reduced attention, and eye redness) after using a CBD-enriched extract.

The extract was replaced by the same dose of purified CBD with no Δ9-THC in both cases, which led to improvement in intoxication signs and seizure remission.

These cases support pre-clinical and preliminary clinical evidence suggesting that CBD may be effective for some patients with epilepsy.

Moreover, the cases highlight the need for randomized clinical trials using high-quality and reliable substances to ascertain the safety and efficacy of cannabinoids as medicines.”

https://www.ncbi.nlm.nih.gov/pubmed/27746737

Chronic stress leads to epigenetic dysregulation of neuropeptide-Y and cannabinoid CB1 receptor in the mouse cingulate cortex.

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“Persistent stress triggers a variety of mechanisms, which may ultimately lead to the occurrence of anxiety- and depression-related disorders.

Epigenetic modifications represent a mechanism by which chronic stress mediates long-term effects. Here, we analyzed brain tissue from mice exposed to chronic unpredictable stress (CUS), which induced impaired emotional and nociceptive behaviors.

As endocannabinoid (eCB) and neuropeptide-Y (Npy) systems modulate emotional processes, we hypothesized that CUS may affect these systems through epigenetic mechanisms.

We found reduced Npy expression and Npy type 1 receptor (Npy1r) signaling, and decreased expression of the cannabinoid type 1 receptor (CB1) in the cingulate cortex of CUS mice specifically in low CB1-expressing neurons.

Our findings suggest that epigenetic alterations in the Npy and CB1 genes represent one of the potential mechanisms contributing to the emotional imbalance induced by CUS in mice, and that the Npy and eCB systems may represent therapeutic targets for the treatment of psychopathologies associated with or triggered by chronic stress states.”

https://www.ncbi.nlm.nih.gov/pubmed/27737789

Central Aspects of Nausea and Vomiting in GI Disorders.

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“Nausea and vomiting result from continuous interactions among gastrointestinal, central nervous system, and autonomic nervous system. Despite being closely associated, central pathways of nausea and vomiting appear to be at least partly different and nausea is no longer considered only a penultimate step of vomiting. Although our understanding of central pathways of nausea has improved over the last one decade, it is still very basic.

Afferent pathways from gastrointestinal tract via vagus, vestibular system, and chemoreceptor trigger zone project to nucleus tractus solitarius which, in turn, relays the signal to central pattern generator initiating multiple downstream pathways. This central nausea pathway appears to be under constant modulation by autonomic nervous system and cerebral cortex.

There is also some evidence that central pathway of chronic nausea is different from that of acute nausea and closely resembles that of neuropathic pain. This improved understanding has modified the way we can approach the treatment of acute and chronic nausea.

While conventional therapies such as antiemetics (antiserotoninergic, antihistaminic, antidopaminergic) and prokinetics are commonly used to manage acute nausea, they are not as effective in improving chronic nausea.

Recently, neuromodulators such as tricyclic antidepressants, gabapentin, olanzapine, benzodiazepines, and cannabinoids have been shown to have antinausea effect.

There is a need to study the utility of these drugs in managing chronic functional nausea. Improving our understanding of central and peripheral circuitry of nausea will allow us to better utilize the currently available drugs and develop new therapeutic options.”

https://www.ncbi.nlm.nih.gov/pubmed/27734216

A New Study Suggests Cannabis Could Treat Cervical Cancer

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“A new study suggests that cannabis might be useful in treating cervical cancer.

Through in vitro, or test tube/petri dish, analysis, researchers from the biochemistry department at North-West University in Potchefstroom, South Africa found that the non-psychotropic cannabinoid, or chemical compound, CBD (cannabidiol), taken from a Cannabis sativa extract, could hold anticarcinogenic properties. They pointed out that cannabis acted on the cancerous cells through apoptosis, or a process of cell death, causing only the cancerous cells to kill themselves, and inhibiting their growth.

Cervical cancer is no longer a leading cause of death as much as it used to be in the United States, thanks in large part to the widespread use of pap smears, but it’s still a widespread threat. And in Sub-Saharan Africa, it kills 250,000 women every year. “This makes it the most lethal cancer amongst black women and calls for urgent therapeutic strategies,” the study’s authors wrote in the BMC Complementary and Alternative Medicine journal. “In this study we compare the anti-proliferative effects of crude extract of Cannabis sativa and its main compound cannabidiol on different cervical cancer cell lines.”

It will take much more research before cannabis can be integrated into official cervical cancer treatments in sub-Saharan Africa. But earlier studies also shows that cannabis has been useful in treating not only the symptoms of cancer and chemotherapy, but also the cancer itself.

One study from the journal of Current Clinical Pharmacology found that cannabis served as a preventative agent, reducing inflammation, which researchers also said was useful in reducing the likelihood of cancer. Another study from Oncology Hematology also noted cannabis’ anti-cancer effects, explaining how the plant’s cannabinoids inhibited tumor growth in vitro, such as in a petri dish or test tube, and in vivo, or a living organism.

A handful of other studies have also looked into cannabis as a treatment specifically for cervical cancer. Another from the University Hospital in Geneva, Switzerland, found that the cannabinoids, including the body’s own endocannabinoids, offered “attractive opportunities for the development of novel potent anticancer drugs.”

With that said, often medical marijuana is ingested via capsules, tinctures, vaporizable oils, and other non-smokeable, more pharmaceutical-style forms. Should cannabis eventually become approved for cervical cancer treatment in Africa, it may be up for debate whether whole plant therapy (in which all the cannabinoids work synergistically through the “entourage effect”) or specific cannabinoid therapy is best.”

http://motherboard.vice.com/read/a-new-study-suggests-cannabis-could-treat-cervical-cancer

Dendritic Cell Regulation by Cannabinoid-Based Drugs.

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“Cannabinoid pharmacology has made important advances in recent years after the cannabinoid system was discovered.

Studies in experimental models and in humans have produced promising results using cannabinoid-based drugs for the treatment of obesity and cancer, as well as neuroinflammatory and chronic inflammatory diseases.

Moreover, as we discuss here, additional studies also indicates that these drugs have immunosuppressive and anti-inflammatory properties including modulation of immune cell function.

Thus, manipulation of the endocannabinoid system in vivo may provide novel therapeutic strategies against inflammatory disorders.

At least two types of cannabinoid receptors, cannabinoid 1 and cannabinoid 2 receptors are expressed on immune cells such as dendritic cells (DC). Dendritic cells are recognized for their critical role in initiating and maintaining immune responses.

Therefore, DC are potential targets for cannabinoid-mediated modulation.

Here, we review the effects of cannabinoids on DC and provide some perspective concerning the therapeutic potential of cannabinoids for the treatment of human diseases involving aberrant inflammatory processes.”

https://www.ncbi.nlm.nih.gov/pubmed/27713374

Cannabinoids and Dementia: A Review of Clinical and Preclinical Data.

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“The endocannabinoid system has been shown to be associated with neurodegenerative diseases and dementia.

We review the preclinical and clinical data on cannabinoids and four neurodegenerative diseases: Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD) and vascular dementia (VD).

Numerous studies have demonstrated an involvement of the cannabinoid system in neurotransmission, neuropathology and neurobiology of dementias. In addition, several candidate compounds have demonstrated efficacy in vitro.

However, some of the substances produced inconclusive results in vivo. Therefore, only few trials have aimed to replicate the effects seen in animal studies in patients. Indeed, the literature on cannabinoid administration in patients is scarce.

While preclinical findings suggest causal treatment strategies involving cannabinoids, clinical trials have only assessed the suitability of cannabinoid receptor agonists, antagonists and cannabidiol for the symptomatic treatment of dementia.

Further research is needed, including in vivo models of dementia and human studies.”

https://www.ncbi.nlm.nih.gov/pubmed/27713372

Dysregulation of the endocannabinoid signaling system in the cerebellum and brainstem in a transgenic mouse model of spinocerebellar ataxia type-3

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“Spinocerebellar ataxia type-3 (SCA-3) is a rare disease but it is the most frequent type within the autosomal dominant inherited ataxias. The disease lacks an effective treatment to alleviate major symptoms and to modify disease progression.

Our recent findings that endocannabinoid receptors and enzymes are significantly altered in the post-mortemcerebellum of patients affected by autosomal-dominant hereditary ataxias suggest that targeting the endocannabinoid signaling system may be a promising therapeutic option.

Our goal was to investigate the status of the endocannabinoid signaling system in a transgenic mouse model of SCA-3, in the two CNS structures most affected in this disease –cerebellum and brainstem-.

These animals exhibited progressive motor incoordination, imbalance, abnormal gait, muscle weakness, and dystonia, in parallel to reduced in vivobrain glucose metabolism, deterioration of specific neuron subsets located in the dentate nucleus and pontine nuclei, small changes in microglial morphology, and reduction in glial glutamate transporters.

Concerning the endocannabinoid signaling, our data indicated no changes in CB2 receptors. By contrast, CB1 receptors increased in the Purkinje cell layer, in particular in terminals of basket cells, but they were reduced in the dentate nucleus.

We also measured the levels of endocannabinoid lipids and found reductions in anandamide and oleanolamideoyleth in the brainstem. These changes correlated with an increase in the FAAH enzyme in the brainstem, which also occurred in some cerebellar areas, whereas other endocannabinoid-related enzymes were not altered.

Collectively, our results in SCA-3 mutant mice confirm a possible dysregulation in the endocannabinoid system in the most important brain structures affected in this type of ataxia, suggesting that a pharmacological manipulation addressed to correct these changes could be a promising option in SCA-3.”

http://www.sciencedirect.com/science/article/pii/S0306452216305012