Emerging therapeutic targets in cancer induced bone disease: A focus on the peripheral type 2 cannabinoid receptor.

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“Skeletal complications are a common cause of morbidity in patients with primary bone cancer and bone metastases. The type 2 cannabinoid (Cnr2) receptor is implicated in cancer, bone metabolism and pain perception. Emerging data have uncovered the role of Cnr2 in the regulation of tumour-bone cell interactions and suggest that agents that target Cnr2 in the skeleton have potential efficacy in the reduction of skeletal complications associated with cancer.

This review aims to provide an overview of findings relating to the role of Cnr2 receptor in the regulation of skeletal tumour growth, osteolysis and bone pain, and highlights the many unanswered questions and unmet needs.

This review argues that development and testing of peripherally-acting, tumour-, Cnr2-selective ligands in preclinical models of metastatic cancer will pave the way for future research that will advance our knowledge about the basic mechanism(s) by which the endocannabinoid system regulate cancer metastasis, stimulate the development of a safer cannabis-based therapy for the treatment of cancer and provide policy makers with powerful tools to assess the science and therapeutic potential of cannabinoid-based therapy.

Thus, offering the prospect of identifying selective Cnr2 ligands, as novel, alternative to cannabis herbal extracts for the treatment of advanced cancer patients.”

https://www.ncbi.nlm.nih.gov/pubmed/28274851

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Can we make cannabis safer?

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“Cannabis use and related problems are on the rise globally alongside an increase in the potency of cannabis sold on both black and legal markets. Additionally, there has been a shift towards abandoning prohibition for a less punitive and more permissive legal stance on cannabis, such as decriminalisation and legalisation. It is therefore crucial that we explore new and innovative ways to reduce harm.

Research has found cannabis with high concentrations of its main active ingredient, δ-9-tetrahydrocannabinol (THC), to be more harmful (in terms of causing the main risks associated with cannabis use, such as addiction, psychosis, and cognitive impairment) than cannabis with lower concentrations of THC. By contrast, cannabidiol, which is a non-intoxicating and potentially therapeutic component of cannabis, has been found to reduce the negative effects of cannabis use.

Here, we briefly review findings from studies investigating various types of cannabis and discuss how future research can help to better understand and reduce the risks of cannabis use.”  https://www.ncbi.nlm.nih.gov/pubmed/28259650

“Studies examining the protective effects of CBD have shown that CBD can counteract the negative effects of THC.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797438/

“CBD may also potentiate some of Δ9-THC’s beneficial effects as it reduces Δ9-THC’s psychoactivity to enhance its tolerability and widen its therapeutic window.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707667/

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InMed Announces Progress on COPD Treatment Using Cannabinoids

InMed Announces Progress on COPD Treatment Using Cannabinoids

“Recent research has indicated that cannabinoid-based therapies might be effective in ameliorating the most important symptoms of COPD.”

“Researchers have observed that cannabinoids can be bronchodilatory, immunosuppressive, and anti-inflammatory, suggesting that cannabinoid-based therapies might offer safer and more effective treatment options for COPD.”

“Additionally, studies have suggested that cannabinoids might help promote better sleep, support the immune system, work as an expectorant, relieve pain, and have anti-microbial properties.”

https://copdnewstoday.com/2016/12/08/inmed-announces-progress-copd-treatment-using-cannabinoids/

http://www.thctotalhealthcare.com/category/copd-chronic-obstructive-pulmonary-disease/

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Pharmacological management of agitation and aggression in Alzheimer’s Disease: a review of current and novel treatments.

“Agitation and aggression are common neuropsychiatric symptoms of Alzheimer’s disease and are highly prevalent in people with dementia. When pharmacological intervention becomes necessary, current clinical practice guidelines recommend antipsychotics, cholinesterase inhibitors (ChEIs), and some antidepressants.

However, those interventions have modest to low efficacy, and those with the highest demonstrated efficacy have significant safety concerns. As a result, current research is focusing on novel compounds that have different mechanisms of action and that may have a better balance of efficacy over safety.

The purpose of this review is to evaluate novel pharmacological therapies for the management of agitation and aggression in AD patients. We performed a comprehensive literature search to identify recent novel drugs that are not included in most clinical practice guidelines or are currently undergoing clinical trials for the treatment of agitation and/or aggression in AD.

This review suggests that novel treatments, such as cannabinoids, lithium, non-steroidal anti-inflammatory drugs, analgesics, narcotics, and newer antiepileptic drugs, may provide a safer alternative treatment options for the management of agitation and aggression in AD and requires further study in order to clarify their risks and benefits.”

http://www.ncbi.nlm.nih.gov/pubmed/27137221

http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/

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Discovery of KLS-13019, a Cannabidiol-Derived Neuroprotective Agent, with Improved Potency, Safety, and Permeability.

“Cannabidiol is the nonpsychoactive natural component of C. sativa that has been shown to be neuroprotective in multiple animal models.

Our interest is to advance a therapeutic candidate for the orphan indication hepatic encephalopathy (HE). HE is a serious neurological disorder that occurs in patients with cirrhosis or liver failure.

Although cannabidiol is effective in models of HE, it has limitations in terms of safety and oral bioavailability.

Herein, we describe a series of side chain modified resorcinols that were designed for greater hydrophilicity and “drug likeness”, while varying hydrogen bond donors, acceptors, architecture, basicity, neutrality, acidity, and polar surface area within the pendent group.

Our primary screen evaluated the ability of the test agents to prevent damage to hippocampal neurons induced by ammonium acetate and ethanol at clinically relevant concentrations.

Notably, KLS-13019 was 50-fold more potent and >400-fold safer than cannabidiol and exhibited an in vitro profile consistent with improved oral bioavailability.”

http://www.ncbi.nlm.nih.gov/pubmed/27096053

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MAPPING CANNABINOID RECEPTOR 1 ALLOSTERIC SITE(S): CRITICAL MOLECULAR DETERMINANT AND SIGNALING PROFILE OF GAT100 – A NOVEL, POTENT AND IRREVERSIBLY BINDING PROBE.

“One of the most abundant G-protein coupled receptors (GPCRs) in brain, the cannabinoid 1 receptor (CB1R) is a tractable therapeutic target for treating diverse psychobehavioral and somatic disorders.

Adverse on-target effects associated with small-molecule CB1R orthosteric agonists and inverse agonists/antagonists have plagued their translational potential. Allosteric CB1R modulators offer a potentially safer modality through which CB1R signaling may be directed for therapeutic benefit.

Rational design of candidate, drug-like CB1R allosteric modulators requires greater understanding of the architecture of the CB1R allosteric endodomain(s) and the capacity of CB1R allosteric ligands to tune the receptor’s information output.

These data help inform the engineering of newer-generation, druggable CB1R allosteric modulators and demonstrate the utility of GAT100 as a covalent probe for mapping structure-function correlates characteristic of the druggable CB1R allosteric space.”

http://www.ncbi.nlm.nih.gov/pubmed/27046127

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Dietary Supplement Therapies for Inflammatory Bowel Disease: Crohn’s Disease and Ulcerative Colitis.

“Inflammatory bowel disease (IBD) including ulcerative colitis and Crohn’s disease are chronic relapsing and remitting chronic diseases for which there is no cure.

The treatment of IBD frequently requires immunosuppressive and biologic therapies which carry an increased risk of infections and possible malignancy.

There is a continued search for safer and more natural therapies in the treatment of IBD.

This review aims to summarize the most current literature on the use of dietary supplements for the treatment of IBD. Specifically, the efficacy and adverse effects of vitamin D, fish oil, probiotics, prebiotics, curcumin, Boswellia serrata, aloe vera and cannabis sativa are reviewed.”

http://www.ncbi.nlm.nih.gov/pubmed/26561079

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A synergistic interaction of 17-β-estradiol with specific cannabinoid receptor type 2 antagonist/inverse agonist on proliferation activity in primary human osteoblasts.

“The bone remodeling process is influenced by various factors, including estrogens and transmitters of the endocannabinoid system. In osteoblasts, cannabinoid receptors 2 (CB-2) are expressed at a much higher level compared to CB-1 receptors. Previous studies have shown that estrogens could influence CB-2 receptor expression.

In the present study, the possible interactions of a specific CB-2 agonist and a specific CB-2 antagonist/inverse agonist with 17-β-estradiol were investigated in primary human osteoblasts (HOB)…

In conclusion, for the first time a synergistic interaction between 17-β-estradiol and specific CB-2 antagonist/inverse agonist was observed in HOB.

Understanding the molecular pathways of this interaction would be of great importance in developing more efficient and safer drugs for treating or preventing bone diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/26171165

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European rating of drug harms.

“The present paper describes the results of a rating study performed by a group of European Union (EU) drug experts using the multi-criteria decision analysis model for evaluating drug harms.

Alcohol, heroin and crack emerged as the most harmful drugs (overall weighted harm score 72, 55 and 50, respectively). The remaining drugs had an overall weighted harm score of 38 or less, making them much less harmful than alcohol.

The outcome of this study shows that the previous national rankings based on the relative harms of different drugs are endorsed throughout the EU.

The results indicates that EU and national drug policy measures should focus on drugs with the highest overall harm, including alcohol and tobacco, whereas drugs such as cannabis and ecstasy should be given lower priority including a lower legal classification.”

http://www.ncbi.nlm.nih.gov/pubmed/25922421

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

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A safer alternative: Cannabis substitution as harm reduction.

“Harm reduction is a set of strategies that aim to minimise problems associated with drug use while recognising that for some users, abstinence may be neither a realistic nor a desirable goal.

In this paper, we aim for deeper understandings of older adult cannabis users’ beliefs and substitution practices as part of the harm reduction framework..

Study participants described using cannabis as a safer alternative for alcohol, illicit drugs and pharmaceuticals based on their perceptions of less adverse side effects, low-risk for addiction and greater effectiveness at relieving symptoms, such as chronic pain.

Cannabis substitution can be an effective harm reduction method for those who are unable or unwilling to stop using drugs completely.”

http://www.ncbi.nlm.nih.gov/pubmed/25919477

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

 

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