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

Posted on by

Image result for glia journal

“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

Overexpression of cannabinoid receptor 1 promotes renal cell carcinoma progression.

Posted on by

Image result for Tumour Biol.

“Renal cell carcinoma (RCC) is a common urologic tumor with a poor prognosis.

Cannabinoid receptor 1 (CB1), which is a G protein-coupled receptor, has recently been reported to participate in the genesis and development of various cancers.

However, the exact role of CB1 in RCC is unknown. The aim of this study was to determine the role of CB1 in RCC cell lines and RCC prognosis, thus underlying its potential as a therapeutic target.

CB1 expression is functionally associated to cellular proliferation, apoptosis, and invasion ability of RCC.

Our data suggest that CB1 might be a potential target for RCC clinical therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/27757850

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

Posted on by

Image result for Front Pharmacol.

“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

ENDOCANNABINOIDS AND SLEEP.

Posted on by

Image result for Neuroscience & Biobehavioral Reviews

“Sleep is regulated by several brain structures, neurotransmitters and neuromodulators.

Endocannabinoids (eCBs) are a group of lipids with modulatory activity in the brain and bind mainly to cannabinoid receptors CB1R and CB2R, thereby modulating several brain functions, (memory, mood, food intake, pain perception).

Oleoylethanolamide and palmitoylethanolamide belong to the N-acylethanolamides (NAEs) family, another type of active endogenous lipids. They bind to the peroxisome proliferator-activated receptor α but not to CB1R, thereby modulating food satiety, inflammation and pain.

Both eCBs and NAEs seem to be regulating the sleep-wake cycle.

Our objective is to analyze the experimental evidence published in the literature and to discuss if eCBs and NAEs are actually sleep modulators.

Studies suggested 1. eCBs and NAEs are under circadian control. 2. NAEs promote wake. 3. eCBs promote non-rapid-eye movement. 4. eCBs also promote rapid-eye-movement sleep by interacting with melanin-concentrating hormone neurons in the lateral hypothalamus. 5. The pharmacological blockade of the CB1R reduces sleep while increasing wake. 6. eCBs restore sleep in a model of insomnia in rats.”

https://www.ncbi.nlm.nih.gov/pubmed/27756691

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

Posted on by

Image result for J Clin Neurophysiol.

“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

Mild Traumatic Brain Injury Produces Neuron Loss That Can Be Rescued by Modulating Microglial Activation Using a CB2 Receptor Inverse Agonist.

Posted on by

Image result for Front Neurosci.

“We have previously reported that mild TBI created by focal left-side cranial blast in mice produces widespread axonal injury, microglial activation, and a variety of functional deficits.

We have also shown that these functional deficits are reduced by targeting microglia through their cannabinoid type-2 (CB2) receptors using 2-week daily administration of the CB2 inverse agonist SMM-189.

Overall, our findings indicate that SMM-189 rescues damaged neurons and thereby alleviates functional deficits resulting from TBI, apparently by selectively modulating microglia to the beneficial M2 state.

CB2 inverse agonists thus represent a promising therapeutic approach for mitigating neuroinflammation and neurodegeneration.”

 https://www.ncbi.nlm.nih.gov/pubmed/27766068

Structure of primary cannabinoid receptor is revealed

Posted on by

“Findings give insight into designing safe and effective cannabinoid medications.”

Illustration of the CB1 receptor.

“New research is providing a more detailed view into the structure of the human cannabinoid (CB1) receptor. These findings provide key insights into how natural and synthetic cannabinoids including tetrahydrocannabinol (THC)—a primary chemical in marijuana—bind at the CB1 receptor to produce their effects. The research was funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.”

https://www.nih.gov/news-events/news-releases/structure-primary-cannabinoid-receptor-revealed

“‘Marijuana receptor’ uncovered in new study”  http://www.medicalnewstoday.com/articles/313564.php

Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose.

Posted on by

Image result for Transl Psychiatry.

“Although all current antipsychotics act by interfering with the action of dopamine at dopamine D2 receptors, two recent reports showed that 800 to 1000 mg of cannabidiol per day alleviated the signs and symptoms of schizophrenia, although cannabidiol is not known to act on dopamine receptors. Because these recent clinical findings may indicate an important exception to the general rule that all antipsychotics interfere with dopamine at dopamine D2 receptors, the present study examined whether cannabidiol acted directly on D2 receptors, using tritiated domperidone to label rat brain striatal D2 receptors. It was found that cannabidiol inhibited the binding of radio-domperidone with dissociation constants of 11 nm at dopamine D2High receptors and 2800 nm at dopamine D2Low receptors, in the same biphasic manner as a dopamine partial agonist antipsychotic drug such as aripiprazole. The clinical doses of cannabidiol are sufficient to occupy the functional D2High sites. it is concluded that the dopamine partial agonist action of cannabidiol may account for its clinical antipsychotic effects.”

https://www.ncbi.nlm.nih.gov/pubmed/27754480

Cannabis as Secondary Drug Is Not Associated With a Greater Risk of Death in Patients With Opiate, Cocaine, or Alcohol Dependence.

Posted on by

Image result for Journal of Addiction Medicine

“To assess the impact of cannabis use as secondary drug on mortality of patients with other major substance use disorders.

Positive urinary cannabis did not confer an increased risk of death in patients with severe opiate, cocaine or alcohol dependence.”

https://www.ncbi.nlm.nih.gov/pubmed/27753720

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

Posted on by

Image result for Front Pharmacol

“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