Category Archives: Uncategorized

Long-term benefit from immune modulation and anti-inflammatory treatment in metastatic mesothelioma.

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Respiratory Medicine Case Reports“A 64 year old male heating engineer was investigated for a persistent cough and found to have epithelioid mesothelioma with pleural effusion, lung nodules and increased thoracic lymph nodes. He declined standard of care treatment following his own research and he was enrolled in a named patient programme of IMM-101. He was advised to correct his low vitamin D3 level and to start using anti-inflammatories such as aspirin, bromelain and low dose Naltrexone. At review one year later a CT scan showed no change and he continued on the regimen. Four years after the diagnosis a CT scan showed that there was a modest but definite progression of the left malignant pleural thickening, and a new right-sided effusion, enlargement of several intrathoracic nodes which had been noted on the early scans. The chest wall lump eventually broke down and required local radiotherapy. He then developed abdominal pain and found to have peritoneal disease. Last year he obtained the cannabinoids CBD and THC which slowed down the disease and a CT scan after he had been on this for six months, showed that his disease was fairly stable with marginal progression.”

https://www.ncbi.nlm.nih.gov/pubmed/31788420

“The patient gave his full written consent for this report and is keen that others can benefit from this treatment.”

https://www.sciencedirect.com/science/article/pii/S2213007119303168?via%3Dihub

Has Cannabis Use Among Youth Increased After Changes in Its Legal Status? A Commentary on Use of Monitoring the Future for Analyses of Changes in State Cannabis Laws.

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“As US states move toward various forms of adult access to cannabis, there has been a great interest in measuring the impact of such changes on adolescent cannabis use.

Using the Washington Health Youth Survey, we estimate that after recreational cannabis legalization past 30-day cannabis use prevalence in grade 8 decreased by 22.0%, in grade 10 prevalence decreased by 12.7%, and no effect in grade 12.

These trends are consistent with those in states without recreational cannabis laws, suggesting that legalization did not impact adolescent use prevalence.”

https://www.ncbi.nlm.nih.gov/pubmed/31792712

https://link.springer.com/article/10.1007%2Fs11121-019-01068-4

Short-term effects of cannabis consumption on cognitive performance in medical cannabis patients.

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Publication Cover “This observational study examined the acute cognitive effects of cannabis.

We hypothesized that cognitive performance would be negatively affected by acute cannabis intoxication.

Contrary to expectations, performance on neuropsychological tests remained stable or even improved during the acute intoxication stage (THC; d: .49-.65, medium effect), and continued to increase during Recovery (d: .45-.77, medium-large effect).

Contrary to our hypothesis, there was no psychometric evidence for a decline in cognitive ability following THC intoxication.”

https://www.ncbi.nlm.nih.gov/pubmed/31790276

https://www.tandfonline.com/doi/abs/10.1080/23279095.2019.1681424?journalCode=hapn21

The Bee Community of Cannabis sativa and Corresponding Effects of Landscape Composition.

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Image result for environmental entomology“Industrial hemp, Cannabis sativa (Cannabaceae), is a newly introduced and rapidly expanding crop in the American agricultural landscape. As an exclusively wind-pollinated crop, hemp lacks nectar but produces an abundance of pollen during a period of floral dearth in agricultural landscapes. These pollen resources are attractive to a range of bee species but the diversity of floral visitors and their use of hemp across a range of agricultural contexts remains unclear. We made repeated sweep net collections of bees visiting hemp flowers on farms in New York, which varied in both landscape context and phenotypic traits of hemp varieties. We identified all bee visitors to the species level and found that hemp supported 16 different bee species. Landscape simplification negatively impacted the abundance of bees visiting hemp flowers but did not affect the species richness of the community. Plant height, on the other hand, was strongly correlated with bee species richness and abundance for hemp plots with taller varieties attracting a broader diversity of bee species. Because of its temporally unique flowering phenology, hemp has the potential to provide a critical nutritional resource to a diverse community of bees during a period of floral scarcity and thereby may help to sustain agroecosystem-wide pollination services for other crops in the landscape. As cultivation of hemp increases, growers, land managers, and policy makers should consider its value in supporting bee communities and take its attractiveness to bees into account when developing pest management strategies.”

https://www.ncbi.nlm.nih.gov/pubmed/31789341

https://academic.oup.com/ee/advance-article/doi/10.1093/ee/nvz141/5634339

Alcohol Binge-Induced Cardiovascular Dysfunction Involves Endocannabinoid-CB1-R Signaling.

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 JACC: Basic to Translational Science“Excessive binge alcohol drinking may adversely affect cardiovascular function. In this study we characterize the detailed hemodynamic effects of an acute alcohol binge in mice using multiple approaches and investigate the role of the endocannabinoid-cannabinoid 1 receptor (CB1-R) signaling in these effects. Acute alcohol binge was associated with elevated levels of cardiac endocannabinoid anandamide and profound cardiovascular dysfunction lasting for several hours and redistribution of circulation. These changes were attenuated by CB1-R antagonist or in CB1-R knockout mice. Our results suggest that a single alcohol binge has profound effects on the cardiovascular system, which involve endocannabinoid-CB1-R signaling.”

https://www.ncbi.nlm.nih.gov/pubmed/31768478

“Alcohol is one of the most frequently used intoxicants in the United States. Binge alcohol drinking is a major contributor of emergency department visits. Binge alcohol drinking may adversely affect cardiovascular function. Here we show that acute alcohol intoxication is associated with elevated levels of cardiac endocannabinoid anandamide and profound cardiovascular dysfunction and blood redistribution lasting for several hours. The adverse cardiovascular effects of acute alcohol intoxication are attenuated by CB1-R antagonist or in CB1-R knockout mice. A single alcohol binge has profound effect on the cardiovascular system, which involves endocannabinoid-CB1-R signaling.”

https://www.sciencedirect.com/science/article/pii/S2452302X19301755?via%3Dihub

The synthetic cannabinoid dehydroxylcannabidiol restores the function of a major GABAA receptor isoform in a cell model of hyperekplexia.

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Image result for journal of biological chemistry“The functions of the glycine receptor (GlyR) and γ-aminobutyric acid type A receptor (GABAAR) are both impaired in hyperekplexia, a neurological disorder that is usually caused by GlyR mutations.

Although emerging evidence indicates that cannabinoids can directly restore normal GlyR function, whether they affect the GABAAR in hyperekplexia remains unknown.

Here, we show that dehydroxylcannabidiol (DH-CBD), a synthetic nonpsychoactive cannabinoid, restores both the GABA- and glycine-activated currents (IGABA and IGly ) in HEK-293 cells co-expressing a major GABAAR isoform (α1β2γ2) and GlyRα1 carrying a human hyperekplexia-associated mutation (GlyRα1 R271Q). Using co-immunoprecipitation and FRET assays, we found that DH-CBD disrupts the protein interaction between GABAAR and GlyRα1 R271Q

Furthermore, a point mutation of GlyRα1, changing Ser-296 to Ala-296, which is critical for cannabinoid binding on GlyR, significantly blocked the DH-CBD-induced restoration of IGABA and IGly currents. This S296A substitution also considerably attenuated the DH-CBD-induced disruption of the interaction between GlyRα1 R271Q and GABAAR.

These findings suggest that because it restores the functions of both GlyRα1 and GABAAR, DH-CBD may represent a potentially valuable candidate drug to manage hyperekplexia.”

https://www.ncbi.nlm.nih.gov/pubmed/31757808

http://www.jbc.org/content/early/2019/11/22/jbc.RA119.011221

Investigating the causal effect of cannabis use on cognitive function with a quasi-experimental co-twin design.

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Drug and Alcohol Dependence“It is unclear whether cannabis use causes cognitive decline; several studies show an association between cannabis use and cognitive decline, but quasi-experimental twin studies have found little support for a causal effect.

Here, we evaluate the association of cannabis use with general cognitive ability and executive functions (EFs) while controlling for genetic and shared environmental confounds in a longitudinal twin study.

CONCLUSIONS:

We found little support for a potential causal effect of cannabis use on cognition, consistent with previous twin studies. Results suggest that cannabis use may not cause decline in cognitive ability among a normative sample of cannabis users.”

https://www.ncbi.nlm.nih.gov/pubmed/31753729

“Overall, there was little evidence for causal effect of cannabis on cognition.”

https://www.sciencedirect.com/science/article/abs/pii/S0376871619304892?via%3Dihub

Cannabinoid receptor 2 activation decreases severity of cyclophosphamide-induced cystitis via regulating autophagy.

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Publication cover image“Cannabinoids have been shown to exert analgesic and anti-inflammatory effects, and the effects of cannabinoids are mediated primarily by cannabinoid receptors 1 and 2 (CB1 and CB2).

The objective of this study was to determine efficacy and mechanism of CB2 activation on cyclophosphamide (CYP)-induced cystitis in vivo.

CONCLUSIONS:

Activation of CB2 decreased severity of CYP-induced cystitis and ameliorated bladder inflammation. CB2 activation is protective in cystitis through the activation of autophagy and AMPK-mTOR pathway may be involved in the initiation of autophagy.”

https://www.ncbi.nlm.nih.gov/pubmed/31729056

https://onlinelibrary.wiley.com/doi/abs/10.1002/nau.24205

The Cannabinoid WIN 55,212-2 Reduces Delayed Neurologic Sequelae After Carbon Monoxide Poisoning by Promoting Microglial M2 Polarization Through ST2 Signaling.

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 “Delayed neurologic sequelae (DNS) are among the most serious complications of carbon monoxide (CO) poisoning caused partly by elevated neuroinflammation.

WIN 55,212-2, a non-selective agonist of cannabinoid receptors, has been demonstrated to have anti-inflammatory properties in various brain disorders.

The anti-inflammatory action of WIN 55,212-2 is potentially associated with driving microglial M2 polarization. ST2 signaling is important in regulating inflammatory responses and microglial polarization. Therefore, we aimed to investigate the neuroprotective effect of WIN 55,212-2 on DNS after CO poisoning and elucidate its relationship with ST2-mediated microglial M2 polarization.

The behavioral tests showed that treatment with WIN 55,212-2 significantly ameliorates the cognitive impairment induced by CO poisoning.

This behavioral improvement was accompanied by reduced neuron loss, decreased production of pro-inflammatory cytokines, and a limited number of microglia in the hippocampus. Moreover, WIN 55,212-2 elevated the protein expression of IL-33 (the ligand of ST2) and ST2, increased the ratio of CD206-positive (M2 phenotype) and ST2-positive microglia, and augmented production of M2 microglia-associated cytokines in the hippocampus of CO-exposed rats.

Furthermore, we observed that the WIN 55,212-2-mediated increases in ST2 protein expression, CD206-positive and ST2-positive microglia, and microglia-associated cytokines were blocked by the cannabinoid receptor 2 (CB2R) antagonist AM630 but not by the cannabinoid receptor 1 (CB1R) antagonist AM251. In contrast, the WIN 55,212-2-induced upregulation of the IL-33 protein expression was inhibited by AM251 but not by AM630.

Altogether, these findings reveal cannabinoid receptors as promising therapeutic agents for CO poisoning and identify ST2 signaling-related microglial M2 polarization as a new mechanism of cannabinoid-induced neuroprotection.”

https://www.ncbi.nlm.nih.gov/pubmed/31732924

https://link.springer.com/article/10.1007%2Fs12031-019-01429-2

Cannabidiol Protects Dopaminergic Neuronal Cells from Cadmium.

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ijerph-logo“The protective effect of cannabidiol (CBD), the non-psychoactive component of Cannabis sativa, against neuronal toxicity induced by cadmium chloride (CdCl2 10 μM) was investigated in a retinoic acid (RA)-differentiated SH-SY5Y neuroblastoma cell line.

CBD (1 μM) was applied 24 h before and removed during cadmium (Cd) treatment. In differentiated neuronal cells, CBD significantly reduced the Cd-dependent decrease of cell viability, and the rapid reactive oxygen species (ROS) increase.

CBD significantly prevented the endoplasmic reticulum (ER) stress (GRP78 increase) and the subcellular distribution of the cytochrome C, as well as the overexpression of the pro-apoptotic protein BAX. Immunocytochemical analysis as well as quantitative protein evaluation by western blotting revealed that CBD partially counteracted the depletion of the growth associated protein 43 (GAP43) and of the neuronal specific class III β-tubulin (β3 tubulin) induced by Cd treatment.

These data showed that Cd-induced neuronal injury was ameliorated by CBD treatment and it was concluded that CBD may represent a potential option to protect neuronal cells from the detrimental effects of Cd toxicity.”

https://www.ncbi.nlm.nih.gov/pubmed/31718076

https://www.mdpi.com/1660-4601/16/22/4420