Tag Archives: anti-inflammatory

Reversal effect of simvastatin on the decrease in cannabinoid receptor 1 density in 6-hydroxydopamine lesioned rat brains.

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“Cannabinoid 1(CB1) receptors are closely correlated to the dopaminergic system and involved in cognitive function. Since statins have been used to regulate the progression of Parkinson’s disease (PD) via its anti-inflammation and neuroprotective effects, we asked if statins affect the CB1 receptors in the 6-hydroxydopamine (6-OHDA) lesioned rat.

Our data suggest a critical role of CB1 receptors in treating PD with simvastatin, and implicate CB1 receptors as a potential therapeutic target in the treatment of PD.”

http://www.ncbi.nlm.nih.gov/pubmed/27155397

Stimulated CB1 Cannabinoid Receptor Inducing Ischemic Tolerance and Protecting Neuron from Cerebral Ischemia.

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“Anandamide system is mainly made up of cannabinoid receptors, their endogenous ligands and some related enzymes. Activation of the system mediates various molecular events, thereafter leading to vasodilation, bradycardia and anti-inflammation.

The stimulated cannabinoid receptors may take part in protection of endothelial cells from injury and therefore can be potential targets in therapy for some diseases, especially cardio or cerebral vascular disturbances.

Cerebral ischemia is a deadly disease that modern people have to face and will probably face for a long period of time. Ischemic tolerance has the protective effect of brain as an endogenous event in cerebral ischemia, in which variety of inducers such as transient cerebral ischemia, hypoxia, hypothermia and drug agents are involved.

Most of cannabinoid 1 receptors (CB1Rs), a member in G protein-coupled receptor family, exist in central nervous systems.

Mechanism of neuroprotection mediated by the receptor is considered through facilitating neurotransmitter release and regulating other molecular events. In this review, advance of the neuroprotection against cerebral ischemia and the mechanism of the action are overviewed.”

http://www.ncbi.nlm.nih.gov/pubmed/27142423

“Cerebral ischemia or brain ischemia, is a condition that occurs when there isn’t enough blood flow to the brain to meet metabolic demand. This leads to limited oxygen supply or cerebral hypoxia and leads to the death of brain tissue, cerebral infarction, or ischemic stroke. It is a sub-type of stroke along with subarachnoid hemorrhage and intracerebral hemorrhage. There are two kinds of ischemia: focal ischemia: confined to a specific region of the brain; global ischemia: encompasses wide areas of brain tissue.”  http://www.columbianeurosurgery.org/conditions/cerebral-ischemia/

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

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“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/

The endogenous cannabinoid system protects against colonic inflammation

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“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

New review sheds light on cannabinoids anticancer mechanisms

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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/

Mustard vesicants alter expression of the endocannabinoid system in mouse skin.

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“Vesicants including sulfur mustard (SM) and nitrogen mustard (NM) are bifunctional alkylating agents that cause skin inflammation, edema and blistering. This is associated with alterations in keratinocyte growth and differentiation.

Endogenous cannabinoids, including N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoyl glycerol (2-AG), are important in regulating inflammation, keratinocyte proliferation and wound healing.

Their activity is mediated by binding to cannabinoid receptors 1 and 2 (CB1 and CB2), as well as peroxisome proliferator-activated receptor alpha (PPARα). Levels of endocannabinoids are regulated by fatty acid amide hydrolase (FAAH).

We found that CB1, CB2, PPARα and FAAH were all constitutively expressed in mouse epidermis and dermal appendages. Topical administration of NM or SM, at concentrations that induce tissue injury, resulted in upregulation of FAAH, CB1, CB2 and PPARα, a response that persisted throughout the wound healing process.

Inhibitors of FAAH including a novel class of vanillyl alcohol carbamates were found to be highly effective in suppressing vesicant-induced inflammation in mouse skin.

Taken together, these data indicate that the endocannabinoid system is important in regulating skin homeostasis and that inhibitors of FAAH may be useful as medical counter measures against vesicants.”

http://www.ncbi.nlm.nih.gov/pubmed/27125198

The Endocannabinoid System: An Osteopathic Perspective

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“A person is the product of dynamic interaction between body, mind, and spirit—This holistic principle is exemplified by cannabinoid receptors, which span the field of psychoneuroimmunology. Taken together, CB1, CB2, and their endocannabinoid ligands represent a microcosm of mind-body medicine. The primary purpose of the current article is to review the expanding endocannabinoid literature beginning with exogenous compounds—Cannabis and plant cannabinoids—and then shift to the endogenous system, highlighting embryology and development, neuroprotection, autonomics and immunity, inflammation, apoptosis, hunger and feeding, and nociception and pain.” http://jaoa.org/article.aspx?articleid=2093607

Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview.

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“The word dementia describes a class of heterogeneous diseases which etiopathogenetic mechanisms are not well understood. There are different types of dementia, among which, Alzheimer’s disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) are the more common.

Currently approved pharmacological treatments for most forms of dementia seem to act only on symptoms without having profound disease-modifying effects. Thus, alternative strategies capable of preventing the progressive loss of specific neuronal populations are urgently required.

In particular, the attention of researchers has been focused on phytochemical compounds that have shown antioxidative, anti-amyloidogenic, anti-inflammatory and anti-apoptotic properties and that could represent important resources in the discovery of drug candidates against dementia.

In this review, we summarize the neuroprotective effects of the main phytochemicals belonging to the polyphenol, isothiocyanate, alkaloid and cannabinoid families in the prevention and treatment of the most common kinds of dementia.

We believe that natural phytochemicals may represent a promising sources of alternative medicine, at least in association with therapies approved to date for dementia.”

http://www.ncbi.nlm.nih.gov/pubmed/27110749

Advances towards the Discovery of GPR55 Ligands.

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“The G-protein-coupled receptor 55 (GPR55) was identified in 1999.

It was proposed as a novel member of the endocannabinoid system due to the fact that some endogenous, plant-derived and synthetic cannabinoid ligands act on GPR55. However, the complexity of the cellular downstream signaling pathways related to GPR55 activation delayed the discovery of selective GPR55 ligands.

It was only a few years ago that the high throughput screening of libraries of pharmaceutical companies and governmental organizations allowed to identify selective GPR55 agonists and antagonists. Since then, several GPR55 modulator scaffolds have been reported.

The relevance of GPR55 has been explored in diverse physiological and pathological processes revealing its role in inflammation, neuropathic pain, bone physiology, diabetes and cancer.

Considering GPR55 as a new promising therapeutic target, there is a clear need for new selective and potent GPR55 modulators. This review will address a current structural update of GPR55 ligands.”

http://www.ncbi.nlm.nih.gov/pubmed/27109575

Anandamide and its metabolites: what are their roles in the kidney?

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 “Anandamide (AEA) is the N-acyl ethanolamide of arachidonic acid, an agonist of cannabinoid and non-cannabinoid receptors in the body. The kidneys are enriched in AEA and in enzymes that metabolize AEA, but the roles of AEA and its metabolites in the kidney remain poorly understood.

This system likely is involved in the regulation of renal blood flow and hemodynamics and of tubular sodium and fluid reabsorption. It may act as a neuromodulator of the renal sympathetic nervous system. AEA and its cyclooxygenase-2 metabolites, the prostamides, in the renal medulla may represent a unique antihypertensive system involved in the long-term control of blood pressure. AEA and its metabolites are also implicated as modulators of inflammation and mediators of signaling in inflammation.

AEA and its metabolites may be influential in chronic kidney disease states associated with inflammation and cardiovascular diseases associated with hyperhomocysteinemia. The current knowledge of the roles of AEA and its derivatives highlights the need for further research to define and potentially exploit the role of this endocannabinoid system in the kidney.”

http://www.ncbi.nlm.nih.gov/pubmed/27100705