Targeting Cannabinoid Receptors in Brain Tumors

Posted on May 4, 2016 by David

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“Cannabinoids, the active components of Cannabis sativa L., act in the body by mimicking endogenous substances — the endocannabinoids — that activate specific cell surface receptors.

Cannabinoids exert various palliative effects in cancer patients. In addition, cannabinoids inhibit the growth of different types of tumor cells, including glioma cells, in laboratory animals. They do so by modulating key cell signaling pathways, mostly the endoplasmic reticulum stress response, thereby inducing antitumoral actions such as the apoptotic death of tumor cells and the inhibition of tumor angiogenesis.

Of interest, cannabinoids seem to be selective antitumoral compounds as they kill glioma cells but not their nontransformed astroglial counterparts.

On the basis of these preclinical findings, a pilot clinical study of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) in patients with recurrent glioblastoma multiforme has been recently run. The fair safety profile of Δ⁹-THC, together with its possible growth-inhibiting action on tumor cells, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.”

http://link.springer.com/chapter/10.1007%2F978-0-387-74349-3_17

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

Posted on May 4, 2016 by David

“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/

Study: Cannabinoids Limit Neuroblastoma Cell Proliferation

Posted on May 3, 2016 by David

Study: Cannabinoids Limit Neuroblastoma Cell Proliferation

“The administration of the cannabinoids THC and CBD limit cancer activity in neuroblastoma cells in culture and in animals, according to preclinical data published in the journal Current Oncology.

Neuroblastoma is an aggressive form of childhood cancer that often goes inadequately addressed by conventional treatment.

Investigators reported that both types of cannabinoids reduced neuroblastoma cell viability, but that CBD demonstrated superior anti-cancer ability. The study is the first to document the anti-cancer properties of CBD in this particular cancerous cell line.

They concluded, “Our findings about the activity of CBD in nbl (neuroblastoma) support and extend previous findings about the anti-tumor activities of CBD in other tumors and suggest that cannabis extracts enriched in CBD and not in THC could be suitable for the development of novel non-psychotropic therapeutic strategies in nbl.” http://enewspf.com/2016/04/21/study-cannabinoids-limit-neuroblastoma-cell-proliferation/

“In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791143/?report=reader

Synthetic Cannabinoids versus Natural Marijuana: A Comparison of Expectations

Posted on May 3, 2016 by David

“A new study evaluated the expected outcomes of both synthetic and natural marijuana.

An article entitled “Comparison of Outcome Expectancies for Synthetic Cannabinoids and Botanical Marijuana,” from The American Journal of Drug and Alcohol Abuse, studied the expected outcomes of both synthetic and natural marijuana.

186 adults who had previously used both synthetic and natural marijuana, as well as 181 who had previously used only botanical marijuana, were surveyed about their expected outcomes of using either type of cannabinoid.

The results showed that the expected negative effects were significantly higher for synthetic marijuana than for natural marijuana across both categories of use history.

Despite the more commonly expected negative effects of synthetic cannabinoids, the most cited reasons for using these compounds were wider availability, avoiding a positive drug test, curiosity, perceived legality, and cost.

Authors concluded, “Given growing public acceptance of recreational and medical marijuana, coupled with negative perceptions and increasing regulation of synthetic cannabinoid compounds, botanical marijuana is likely to remain more available and more popular than synthetic cannabinoids.”

https://www.sciencedaily.com/releases/2016/04/160427081800.htm

“Comparison of outcome expectancies for synthetic cannabinoids and botanical marijuana.” http://www.ncbi.nlm.nih.gov/pubmed/26910181

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Comparison of outcome expectancies for synthetic cannabinoids and botanical marijuana.

Posted on May 3, 2016 by David

“Although initially developed for medical purposes, synthetic cannabinoids have also been consumed for recreational purposes.

To evaluate whether agreement with positive and negative outcome expectancies differed for synthetic cannabinoids versus botanical marijuana, and assess reported reasons for using synthetic cannabinoids.

A significant interaction revealed that participants who had used both synthetic cannabinoids and botanical marijuana indicated lower agreement with positive expectancies for synthetic cannabinoids, and higher agreement with positive expectancies for botanical marijuana, than did those participants who used only botanical marijuana.

There was no interaction between type of drug and use history on agreement with negative expectancies, and participants agreed more strongly with negative outcome expectancies for synthetic cannabinoids than for botanical marijuana whether they had used one or both types of these drugs.

The most frequently provided reasons for using synthetic cannabinoids included availability, perceived legality, cost, curiosity, and social interaction.

Given growing public acceptance of recreational and medical marijuana, coupled with negative perceptions and increasing regulation of synthetic cannabinoid compounds, botanical marijuana is likely to remain more available and more popular than synthetic cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/26910181

The endogenous cannabinoid system protects against colonic inflammation

Posted on May 3, 2016 by David

“Excessive inflammatory responses can emerge as a potential danger for organisms’ health.

Our results indicate that the endogenous cannabinoid system represents a promising therapeutic target for the treatment of intestinal disease conditions characterized by excessive inflammatory responses.

The major active constituent of the plant Cannabis sativa (marijuana), Δ⁹-tetrahydrocannabinol, and a variety of natural and synthetic cannabinoids have been shown to possess antinociceptive and anti-inflammatory activities.

For millennia, Cannabis preparations have been used in folk medicine for the treatment of a wide variety of disorders, including those affecting the gastrointestinal tract. A century ago, extracts of Cannabis were used in the US to treat gastrointestinal pain of different origins, gastroenteritis, and diarrhea. There are also anecdotal reports suggesting that marijuana may be effective in alleviating symptoms of Crohn disease.

In conclusion, this study shows that the endogenous cannabinoid system is physiologically involved in the protection against excessive inflammation in the colon, both by dampening smooth muscular irritation caused by inflammation and by controlling cellular pathways leading to inflammatory responses.

These results strongly suggest that modulation of the physiological activity of the endogenous cannabinoid system during colonic inflammation might be a promising therapeutic tool for the treatment of several diseases characterized by inflammation of the gastrointestinal tract.”

https://www.jci.org/articles/view/19465

“A mouse study demonstrated that endogenous cannabinoid system signaling is likely to provide intrinsic protection against colonic inflammation. As a result, a hypothesis that phytocannabinoids and endocannabinoids may be useful in the risk reduction and treatment of colorectal cancer has been developed.” http://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#section/_7

Driving the need to feed: Insight into the collaborative interaction between ghrelin and endocannabinoid systems in modulating brain reward systems.

Posted on May 3, 2016 by David

“Independent stimulation of either the ghrelin or endocannabinoid system promotes food intake and increases adiposity. Given the similar distribution of their receptors in feeding associated brain regions and organs involved in metabolism, it is not surprising that evidence of their interaction and its importance in modulating energy balance has emerged. This review documents the relationship between ghrelin and endocannabinoid systems within the periphery and hypothalamus (HYP) before presenting evidence suggesting that these two systems likewise work collaboratively within the ventral tegmental area (VTA) to modulate non-homeostatic feeding. Mechanisms, consistent with current evidence and local infrastructure within the VTA, will be proposed.”

http://www.ncbi.nlm.nih.gov/pubmed/27136126

Getting into the weed: the role of the endocannabinoid system in the brain-gut axis.

Posted on May 3, 2016 by David

“The actions of cannabis are mediated by receptors that are part of an endogenous cannabinoid system.

The endocannabinoid system (ECS) consists of the naturally occurring ligands N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG), their biosynthetic and degradative enzymes, and the cannabinoid receptors CB1 and CB2.

The ECS is a widely distributed transmitter system that controls gut functions peripherally and centrally. It is an important physiologic regulator of gastrointestinal motility.

Polymorphisms in the gene encoding CB1 (CNR1) have been associated with some forms of irritable bowel syndrome. The ECS is involved in the control of nausea and vomiting and visceral sensation. The homeostatic role of the ECS also extends to the control of intestinal inflammation.

We review the mechanisms by which the ECS links stress and visceral pain. CB1 in sensory ganglia controls visceral sensation, and transcription of CNR1 is modified through epigenetic processes under conditions of chronic stress. These processes might link stress with abdominal pain.

The ECS is also involved centrally in the manifestation of stress, and endocannabinoid signaling reduces the activity of hypothalamic-pituitary-adrenal pathways via actions in specific brain regions-notably the prefrontal cortex, amygdala, and hypothalamus.

Agents that modulate the ECS are in early stages of development for treatment of gastrointestinal diseases. Increasing our understanding of the ECS will greatly advance our knowledge of interactions between the brain and gut and could lead to new treatments for gastrointestinal disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/27133395

New review sheds light on cannabinoids anticancer mechanisms

Posted on May 2, 2016 by David

cannabinoids, cancer

“The palliative effects of cannabinoids on cancer-related symptoms are well established.

In fact, many drugs comprised of delta-9-tetrahydrocannabinol (THC) or its synthetic analogues are currently approved in Canada for use in the management of chemotherapy-induced nausea and vomiting, pain relief, and appetite stimulation.

While this may provide adequate treatment to the symptoms endured by cancer patients, what if cannabis can all together treat and cure cancer?

Latest discoveries on cannabinoids and their anticancer properties focus on their molecular mechanisms of action and have been discussed in a recently published review article in Current Oncology, a peer-reviewed journal (Velasco, Sanchez, & Guzman, 2016).

It is important to begin by understanding that our body possesses an endogenous cannabinoid system.”

https://news.liftcannabis.ca/2016/04/21/new-review-sheds-light-cannabinoids-anticancer-mechanisms/

“Anticancer mechanisms of cannabinoids” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791144/

Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent

Posted on May 2, 2016 by David

“Cannabinoid compounds, both nonspecific as well as agonists selective for either cannabinoid receptor 1 (CB₁) or cannabinoid receptor 2 (CB₂), have been shown to modulate the tumor microenvironment by inducing apoptosis in tumor cells in several model systems.

The mechanism of this modulation remains only partially delineated, and activity induced via the CB₁ and CB₂ receptors may be distinct despite significant sequence homology and structural similarity of ligands.

The results of this work characterize the actions of a CB₂-selective agonist on breast cancer cells in a syngeneic murine model representing how a clinical presentation of cancer progression and metastasis may be significantly modulated by a G-protein-coupled receptor.”

https://www.dovepress.com/modulation-of-breast-cancer-cell-viability-by-a-cannabinoid-receptor-2-peer-reviewed-article-BCTT