Application of carbon nanotubes as the carriers of the cannabinoid, 2-arachidonoylglycerol: Towards a novel treatment strategy in colitis.

Posted on November 27, 2016 by David

“Treatment of colitis has remained a major clinical challenge.

The cannabinoid, 2-arachidonoyglycerol (2-AG), has shown beneficial effects in colitis, however, poor solubility or rapid hydrolysis may limit its efficiency. According to the high biocompatibility of carbon nanotubes (CNTs) and their ability for controlled drug delivery, we aimed to prepare multi-walled CNTs-2-AG (MWCNTs-2-AG) complex in order to improve the pharmacological profile of 2-AG and evaluate the therapeutic potential of this nanocomplex in a rat model of colitis.

Aminated MWCNTs and MWCNTs-2-AG complex exhibited significantly lower cytotoxicity than acidified MWCNTs. Once daily intrarectal application of MWCNTs-2-AG complex (containing 2mg/kg of 2-AG) 2days before and 8days after the induction of colitis effectively reduced the macroscopic and microscopic injuries, malondialdehyde, tumour necrosis factor-α, and interlukin-1β concentrations, and myeloperoxidase activity. While, free 2-AG (2mg/kg), and acidified or aminated MWCNTs showed no beneficial effects.

SIGNIFICANCE:

Amino-functionalized MWCNTs appear as the suitable carriers for 2-AG which provide a sustained concentration for this cannabinoid leading to the promising therapeutic effects in the experimental colitis.”

https://www.ncbi.nlm.nih.gov/pubmed/27888115

Activation of Cannabinoid Receptor 2 Ameliorates DSS-Induced Colitis through Inhibiting NLRP3 Inflammasome in Macrophages.

Posted on September 10, 2016 by David

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“Activation of cannabinoid receptor 2 (CB2R) ameliorates inflammation, but the underlying mechanism remains unclear.

In the present study, we examined whether activation of CB2R could suppress the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome.

We conclude that activation of CB2R ameliorates DSS-induced colitis through enhancing autophagy that may inhibit NLRP3 inflammasome activation in macrophages.”

http://www.ncbi.nlm.nih.gov/pubmed/27611972

Abnormal cannabidiol attenuates experimental colitis in mice, promotes wound healing and inhibits neutrophil recruitment.

Posted on July 16, 2016 by David

“Non-psychotropic atypical cannabinoids have therapeutic potential in a variety of inflammatory conditions including those of the gastrointestinal tract.

Here we examined the effects of the atypical cannabinoid abnormal cannabidiol (Abn-CBD) on wound healing, inflammatory cell recruitment and colitis in mice.

TNBS-induced colitis was attenuated by treatment with Abn-CBD.

Abn-CBD is protective against TNBS-induced colitis, promotes wound healing of endothelial and epithelial cells and inhibits neutrophil accumulation on HUVEC monolayers.

Thus, the atypical cannabinoid Abn-CBD represents a novel potential therapeutic in the treatment of intestinal inflammatory diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/27418880

ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

Posted on April 19, 2016 by David

Image result for Curr Clin Pharmacol.

“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from many centuries.

Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries.

The research of drugs acting on endocannabinoid system has seen many ups and down in recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions.

Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system.

Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.

Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite of some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists.

One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that acts selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted.

Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.

In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent changes in the expression of cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601

P414 Cannabidiol for symptomatic treatment of ulcerative colitis: Results from a randomised, double-blind, placebo-controlled, parallel group, multi-centred pilot study

Posted on February 27, 2015 by David

“There is accumulating evidence that cannabidiol (CBD) has anti-inflammatory properties that could be exploited for the symptomatic relief of IBD.

This proof-of-concept double blind, randomised, placebo controlled trial assessed the efficacy, safety and tolerability of CBD botanical drug substance (BDS) in patients with mild to moderate UC…

…several signals suggest that GWP42003 may be beneficial for the symptomatic treatment of UC…”

https://www.ecco-ibd.eu/index.php/publications/congress-abstract-s/abstracts-2015/item/p414-cannabidiol-for-symptomatic-treatment-of-ulcerative-colitis-results-from-a-randomised-double-blind-placebo-controlled-parallel-group-multi-centred-pilot-study.html

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

Conformational Restriction Leading to a Selective CB2 Cannabinoid Receptor Agonist Orally Active Against Colitis.

Posted on February 24, 2015 by David

“The CB2 cannabinoid receptor has been implicated in the regulation of intestinal inflammation.

Following on from the promising activity of a series of 4-oxo-1,4-dihydroquinoline-3-carboxamide, we developed constrained analogues based on a 2H-pyrazolo[4,3-c]quinolin-3(5H)-one scaffold, with improved affinity for the hCB2 receptor and had very high selectivity over the hCB1 receptor.

Importantly, the lead of this series (26, hCB2: K i = 0.39 nM, hCB1: K i > 3000 nM) was found to protect mice against experimental colitis after oral administration.”

http://www.ncbi.nlm.nih.gov/pubmed/25699149

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

The effects of Δ9-tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis

Posted on January 27, 2015 by David

“Cannabis is taken as self-medication by patients with inflammatory bowel disease for symptomatic relief.

Cannabinoid receptor agonists decrease inflammation in animal models of colitis, but their effects on the disturbed motility is not known. (-)-Cannabidiol (CBD) has been shown to interact with Δ9-tetrahydrocannabinol (THC) in behavioural studies, but it remains to be established if these cannabinoids interact in vivo in inflammatory disorders.

Therefore the effects of CBD and THC alone and in combination were investigated in a model of colitis…

In this model of colitis, THC and CBD not only reduced inflammation but also lowered the occurrence of functional disturbances. Moreover the combination of CBD and THC could be beneficial therapeutically, via additive or potentiating effects.

As the two phytocannabinoids modulate the immune system and differ in their pharmacological profile, their combination could be more beneficial than either drug alone. Additionally CBD could not only potentiate the therapeutic effects of THC, but also attenuate some of its undesirable effects…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931570/

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

Cannabinoids Alleviate Experimentally Induced Intestinal Inflammation by Acting at Central and Peripheral Receptors.

Posted on October 3, 2014 by David

“… an attempt to further investigate the role of cannabinoid (CB) system in the pathogenesis of inflammatory bowel diseases…

CONCLUSIONS:

This is the first evidence that central and peripheral CB receptors are responsible for the protective and therapeutic action of cannabinoids in mouse models of colitis.

Our observations provide new insight to CB pharmacology and validate the use of novel ligands AM841 and CB13 as potent tools in CB-related research.”

http://www.ncbi.nlm.nih.gov/pubmed/25275313

Cannabinoids drug for inflammatory bowel

Posted on June 24, 2014 by David

“Researchers from the University of Bath, UK has found that Cannabinoids derived from Cannabis has found to be effective in the treatment of inflammatory bowel diseases like Crohn’s disease and ulcerative colitis.

“The system that responds to cannabis in the brain is present and functioning in the lining of the gut,” lead researcher Dr. Karen Wright, of the University of Bath, explained to Reuters Health. “There is an increased presence of one component of this system during inflammatory bowel diseases,” she explained.

The report of the study was published in the Journal of Gastroenterology in which she has explained the location of CB1 and CB2 receptors in human colon tissue which binds to the Cannabinoid. She has used Human colon cell lines to establish the binding of the cannabinoid compounds and in her wound healing experiments.

Increased CB2 receptors are found in colonic tissue characteristic of inflammatory bowel disease. They found that the Cannabinoids helps in wound healing of the surface by CB1 related receptor mechanism.

“Cannabinoids, which we make ourselves, as well as synthetic Cannabinoids, can promote wound healing in the gut, which is extremely interesting given that inflammatory bowel disease involves damaged gut linings,” Wright said.”

http://www.medindia.net/news/view_news_main.asp?x=4578

Marijuana can treat autoimmune diseases, scientific study states

Posted on June 9, 2014 by David

“Weed enthusiasts are getting their case for nationwide decriminalization of marijuana bolstered considerably by a new scientific study that promises the controversial plant can treat multiple medical maladies.

Scientists at the University of South Carolina have discovered marijuana’s potential to treat autoimmune diseases — such as arthritis, lupus, colitis and multiple sclerosis — in which chronic inflammation plays a pivotal role.

The Journal of Biological Chemistry published the researchers’ findings that state marijuana’s potential key role in fighting these diseases lies in its capacity to suppress certain immune functions, most particularly inflammation.

The study examined whether marijuana’s main active constituent, tetrahydrocannabinol (THC), could affect DNA through “epigenetic” pathways.

The group of molecules with the capacity to alter DNA and the functioning of genes it controls is collectively referred to as the epigenome. It includes a group of molecules called histones, which are responsible for inflammation, both beneficial and harmful.

The research team, led by Mitzi Nagarkatti, Prakash Nagarkatti and Xiaoming Yang, found that THC can, indeed, affect DNA expression through epigenetic pathways by altering histones.

As recreational and medical use of marijuana become more acceptable in developed countries, more research is being conducted and more potential health applications are being uncovered.

Marijuana already has a variety of medical uses including treatment of chronic pain, nausea, vomiting and the wasting syndrome experienced by some AIDS patients.”

http://atlantadailyworld.com/2014/06/05/marijuana-can-treat-autoimmune-diseases-scientific-study-states/