Monthly Archives: September 2019

The non-euphoric phytocannabinoid cannabidivarin counteracts intestinal inflammation in mice and cytokine expression in biopsies from UC pediatric patients.

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Pharmacological Research“Patients with ulcerative colitis (UC) using marijuana have been reported to experience symptomatic benefit.

Cannabidivarin (CBDV) is a safe non-psychoactive phytocannabinoid able to activate TRPA1, a member of TRP channels superfamily, which plays a pivotal role in intestinal inflammation.

Here, we have investigated the potential intestinal anti-inflammatory effect of CBDV in mice and in biopsies from pediatric patients with active UC.

Our preclinical study shows that CBDV exerts intestinal anti-inflammatory effects in mice via TRPA1, and in children with active UC.

Since CBDV has a favorable safety profile in humans, it may be considered for possible clinical trials in patients with UC.”

https://www.ncbi.nlm.nih.gov/pubmed/31553934

https://linkinghub.elsevier.com/retrieve/pii/S1043661819311077

Cannabidiol Is a Novel Modulator of Bacterial Membrane Vesicles.

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 Image result for frontiers in cellular and infection microbiology“Membrane vesicles (MVs) released from bacteria participate in cell communication and host-pathogen interactions.

Roles for MVs in antibiotic resistance are gaining increased attention and in this study we investigated if known anti-bacterial effects of cannabidiol (CBD), a phytocannabinoid from Cannabis sativa, could be in part attributed to effects on bacterial MV profile and MV release.

We found that CBD is a strong inhibitor of MV release from Gram-negative bacteria (E. coli VCS257), while inhibitory effect on MV release from Gram-positive bacteria (S. aureus subsp. aureus Rosenbach) was negligible. When used in combination with selected antibiotics, CBD significantly increased the bactericidal action of several antibiotics in the Gram-negative bacteria.

In addition, CBD increased antibiotic effects of kanamycin in the Gram-positive bacteria, without affecting MV release. CBD furthermore changed protein profiles of MVs released from E. coli after 1 h CBD treatment.

Our findings indicate that CBD may pose as a putative adjuvant agent for tailored co-application with selected antibiotics, depending on bacterial species, to increase antibiotic activity, including via MV inhibition, and help reduce antibiotic resistance.”

https://www.ncbi.nlm.nih.gov/pubmed/31552202

https://www.frontiersin.org/articles/10.3389/fcimb.2019.00324/full 

Δ9-Tetrahydrocannabinol During Adolescence Attenuates Disruption of Dopamine Function Induced in Rats by Maternal Immune Activation.

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Image result for frontiers in behavioral neuroscience“Here, we hypothesized that adolescent Δ9-tetrahydrocannabinol (THC) worsens the impact of prenatal maternal immune activation (MIA) on ventral tegmental area (VTA) dopamine cells in rat offspring.

Adolescent THC attenuated several MIA-induced effects.

Contrary to our expectations, adolescent THC did not worsen MIA-induced deficits.”

https://www.ncbi.nlm.nih.gov/pubmed/31551729

https://www.frontiersin.org/articles/10.3389/fnbeh.2019.00202/full

Cannabis use in cancer: a survey of the current state at BC Cancer before recreational legalization in Canada.

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Image result for Curr Oncol.“Cancer patients experience multiple symptoms throughout their illness, and some report benefit from the use of cannabis. There are concerns that many patients are accessing products inappropriate for their situation and potentially putting themselves at risk.

In the present study, we aimed to capture the prevalence of cannabis use among cancer patients at BC Cancer before recreational legalization in Canada and to identify the reasons that patients take cannabis, the various routes of administration they use, and the reasons that prior users stopped.

RESULTS:

Of surveys sent to 2998 patients, 821 (27.4%) were returned and included in analysis. Of those respondents, 23% were currently using cannabis-based products, almost exclusively for medical purposes, and an additional 28% had been users in the past (most often recreationally). Of the patients currently using cannabis, 31% had medical authorization. The most common symptoms that the current users were targeting were pain, insomnia, nausea, and anxiety; many were also hoping for anticancer effects.

CONCLUSIONS:

More than half the respondents had tried cannabis at some time, and almost one quarter of respondents were currently taking cannabis to help manage their symptoms or treat their cancer, or both. Many more patients would consider use with appropriate guidance from a health care professional. More research is needed to inform physicians and patients about safe uses and doses and about the potential adverse effects of cannabis use.”

https://www.ncbi.nlm.nih.gov/pubmed/31548810

A Novel Highly Selective Cannabinoid CB2 Agonist Reduces in Vitro Growth and TGF-beta Release of Human Glial Cell Tumors.

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“Cannabinoid receptors have been detected in human gliomas and cannabinoids have been proposed as novel drug candidates in the treatment of brain tumors.

Aim of this study was to test the in vitro antitumor activity of COR167, a novel cannabinoid CB2-selective agonist displaying high binding affinity for human CB2 receptors, on tumor cells isolated from human glioblastoma multiforme and anaplastic astrocytoma.

RESULTS:

COR167 was found to significantly reduce the proliferation of both glioblastoma and anaplastic astrocytoma in a dose-dependent manner at lower doses than other known, less specific CB2 agonists. This activity is independent of apoptosis and is associated with significant reduction of TGF-beta 1 and 2 levels in supernatants of glioma cell cultures.

CONCLUSIONS:

These findings add to the role of cannabinoid CB2 receptor as a possible pharmacological target to counteract glial tumor growth and encourage further work to explore any other pharmacological effect of this novel CB2 agonist useful in the treatment of human gliomas.”

https://www.ncbi.nlm.nih.gov/pubmed/31549596

http://www.eurekaselect.com/175066/article

Potential of Cannabinoid Receptor Ligands as Treatment for Substance Use Disorders.

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 “Substance use disorder (SUD) is a major public health crisis worldwide, and effective treatment options are limited.

During the past 2 decades, researchers have investigated the impact of a variety of pharmacological approaches to treat SUD, one of which is the use of medical cannabis or cannabinoids.

Significant progress was made with the discovery of rimonabant, a selective CB1 receptor (CB1R) antagonist (also an inverse agonist), as a promising therapeutic for SUDs and obesity. However, serious adverse effects such as depression and suicidality led to the withdrawal of rimonabant (and almost all other CB1R antagonists/inverse agonists) from clinical trials worldwide in 2008.

Since then, much research interest has shifted to other cannabinoid-based strategies, such as peripheral CB1R antagonists/inverse agonists, neutral CB1R antagonists, allosteric CB1R modulators, CB2R agonists, fatty acid amide hydrolase (FAAH) inhibitors, monoacylglycerol lipase (MAGL) inhibitors, fatty acid binding protein (FABP) inhibitors, or nonaddictive phytocannabinoids with CB1R or CB2R-binding profiles, as new therapeutics for SUDs.

In this article, we first review recent progress in research regarding the endocannabinoid systems, cannabis reward versus aversion, and the underlying receptor mechanisms. We then review recent progress in cannabinoid-based medication development for the treatment of SUDs.

As evidence continues to accumulate, neutral CB1R antagonists (such as AM4113), CB2R agonists (JWH133, Xie2-64), and nonselective phytocannabinoids (cannabidiol, β-caryophyllene, ∆9-tetrahydrocannabivarin) have shown great therapeutic potential for SUDs, as shown in experimental animals.

Several cannabinoid-based medications (e.g., dronabinol, nabilone, PF-04457845) that entered clinical trials have shown promising results in reducing withdrawal symptoms in cannabis and opioid users.”

https://www.ncbi.nlm.nih.gov/pubmed/31549358

https://link.springer.com/article/10.1007%2Fs40263-019-00664-w

Agitation, Oxidative Stress, and Cytokines in Alzheimer Disease: Biomarker Analyses From a Clinical Trial With Nabilone for Agitation.

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 Image result for journal of geriatric psychiatry and neurology

“The endocannabinoid system has been a target of interest for agitation in Alzheimer disease (AD) because of potential behavioral effects and its potential impact on mechanisms implicated in AD such as oxidative stress (OS) and neuroinflammation.

We explored whether serum markers of OS and neuroinflammation were associated with response to the cannabinoid nabilone in agitated patients with AD (N = 38).

These findings suggest that OS and neuroinflammation may be associated with agitation severity, while nabilone may have anti-inflammatory effects.”

https://www.ncbi.nlm.nih.gov/pubmed/31547752

https://journals.sagepub.com/doi/abs/10.1177/0891988719874118?journalCode=jgpb

Comparative studies of endocannabinoid modulation of pain.

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Philosophical Transactions of the Royal Society B: Biological Sciences cover image

“Cannabinoid-based therapies have long been used to treat pain, but there remain questions about their actual mechanisms and efficacy. From an evolutionary perspective, the cannabinoid system would appear to be highly conserved given that the most prevalent endogenous cannabinoid (endocannabinoid) transmitters, 2-arachidonyl glycerol and anandamide, have been found throughout the animal kingdom, at least in the species that have been analysed to date. This review will first examine recent findings regarding the potential conservation across invertebrates and chordates of the enzymes responsible for endocannabinoid synthesis and degradation and the receptors that these transmitters act on. Next, comparisons of how endocannabinoids modulate nociception will be examined for commonalities between vertebrates and invertebrates, with a focus on the medicinal leech Hirudo verbana. Evidence is presented that there are distinct, evolutionarily conserved anti-nociceptive and pro-nociceptive effects. The combined studies across various animal phyla demonstrate the utility of using comparative approaches to understand conserved mechanisms for modulating nociception. This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.”

https://www.ncbi.nlm.nih.gov/pubmed/31544609

https://royalsocietypublishing.org/doi/10.1098/rstb.2019.0279

Antiproliferative and antioxidant effect of polar hemp extracts (Cannabis sativa L., Fedora cv.) in human colorectal cell lines.

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Publication Cover “Total phenolic content and antioxidant activity of polar extracts of edible resources from Fedora hemp cultivar (Cannabis sativa L.), namely seed, flour and oil, were evaluated. The main components in the polar extracts were identified using HPLC-DAD and HPLC-ESI-MS/MS. As expected, the molecular profile of components from seeds and flour was strictly similar, dominated by N-trans-caffeoyltyramine. The profile of oil polar extracts contained hydroxycinnamic acid derivatives and cannabinoids at lower extent. While the extracts from hemp seed and flour did not interfere with growth of Caco-2 and HT-29 cell, the one from oil (150 µg/mL) significantly reduced cell viability after 24 h of treatment. This effect was associated with the activation of apoptotic cell death and was independent from the antioxidant capacity of the oil polar extract. Notably, HT-29 cells differentiated with sodium butyrate were not sensitive to the cytotoxic effect of the oil extract.”

https://www.ncbi.nlm.nih.gov/pubmed/31544542

https://www.tandfonline.com/doi/abs/10.1080/09637486.2019.1666804?journalCode=iijf20

A National Survey of Marijuana Use Among US Adults With Medical Conditions, 2016-2017.

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Image result for JAMA network“This study found that marijuana use was more common among adults with medical conditions than those without such conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/31539078/

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2751558