The role of fatty acid hydrolase gene variants in inflammatory bowel disease.

“Recent studies suggest a role for the endocannabinoid system, including fatty acid amide hydrolase (FAAH), in intestinal inflammation.

AIM:

To analyse FAAH expression and the FAAH 385 C/A (p.Pro129Thr; rs324420) single nucleotide polymorphism (SNP) in-patients with Crohn’s disease (CD) and ulcerative colitis (UC).

CONCLUSION:

The FAAH p.Pro129Thr polymorphism may modulate the CD phenotype.”

http://www.ncbi.nlm.nih.gov/pubmed/19053981

Role of cannabinoid receptors and RAGE in inflammatory bowel disease.

“The endocannabinoid system is involved in many inflammatory diseases, such as Crohn’s disease (CD) and ulcerative colitis (UC). The distribution and expression of cannabinoid receptors 1 (CNR1) and 2 (CNR2) in combination with inflammatory cytokines and RAGE (receptor of advanced glycation end products), which is also overactive in these diseases, in dependency of the extent of inflammation and alteration of the colon barrier is still unclear and needs to be elucidated…

 

CONCLUSION:

We showed that cannabinoid receptors are expressed differentially in inflammatory bowel disease and that the expression seems to be influenced by the underlying disease and by localized inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/21472688

The pathophysiologic rationale for biological therapies in inflammatory bowel disease.

“Inflammatory bowel disease is driven by an excessive immune response in the gut wall. This review summarises important new developments in understanding this immune response and the downstream mechanisms of intestinal injury, alongside their potential role in opening up new avenues of treatment…

Understanding the immunology of inflammatory bowel disease continues to underpin the vast majority of new therapies and identifies new targets.

Novel approaches, such as exploiting the antiinflammatory role of cannabinoid receptors, may also prove productive in the future.”

http://www.ncbi.nlm.nih.gov/pubmed/15930983

Cannabinoids for gastrointestinal diseases: potential therapeutic applications.

“Delta(9)-Tetrahydrocannabinol (the active ingredient of marijuana), as well as endogenous and synthetic cannabinoids, exert many biological functions by activating two types of cannabinoid receptors, CB(1) and CB(2) receptors. CB(1) receptors have been detected on enteric nerves, and pharmacological effects of their activation include gastroprotection, reduction of gastric and intestinal motility and reduction of intestinal secretion.

 The digestive tract also contains endogenous cannabinoids (i.e., the endocannabinoids anandamide and 2-aracidonylglycerol) and mechanisms for endocannabinoid inactivation (i.e., endocannabinoids uptake and enzymatic degradation). Cannabinoid receptors, endocannabinoids and the proteins involved in endocannabinoids inactivation are collectively referred as the ‘endogenous cannabinoid system’.

 A pharmacological modulation of the endogenous cannabinoid system could provide new therapeutics for the treatment of a number of gastrointestinal diseases, including nausea and vomiting, gastric ulcers, irritable bowel syndrome, Crohn’s disease, secretory diarrhoea, paralytic ileus and gastroesophageal reflux disease. Some cannabinoids are already in use clinically, for example, nabilone and delta(9)-tetrahydrocannabinol are used as antiemetics.”

http://www.ncbi.nlm.nih.gov/pubmed/12517253

Endocannabinoids and the gastrointestinal tract.

“In the past centuries, different preparations of marijuana have been used for the treatment of gastrointestinal (GI) disorders, such as GI pain, gastroenteritis and diarrhea.

 Delta9-tetrahydrocannabinol (THC; the active component of marijuana), as well as endogenous and synthetic cannabinoids, exert their biological functions on the gastrointestinal tract by activating two types of cannabinoid receptors, cannabinoid type 1 receptor (CB1 receptor) and cannabinoid type 2 receptor (CB2 receptor). While CB1 receptors are located in the enteric nervous system and in sensory terminals of vagal and spinal neurons and regulate neurotransmitter release, CB2 receptors are mostly distributed in the immune system, with a role presently still difficult to establish.

Under pathophysiological conditions, the endocannabinoid system conveys protection to the GI tract, eg from inflammation and abnormally high gastric and enteric secretion.

 For such protective activities, the endocannabinoid system may represent a new promising therapeutic target against different GI disorders, including frankly inflammatory bowel diseases (eg, Crohn’s disease), functional bowel diseases (eg, irritable bowel syndrome), and secretion- and motility-related disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/16751708

The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract.

“Numerous investigations have recently demonstrated the important roles of the endocannabinoid system in the gastrointestinal (GI) tract under physiological and pathophysiological conditions.

 In the GI tract, cannabinoid type 1 (CB1) receptors are present in neurons of the enteric nervous system and in sensory terminals of vagal and spinal neurons, while cannabinoid type 2 receptors are located in immune cells. Activation of CB1 receptors was shown to modulate several functions in the GI tract, including gastric secretion, gastric emptying and intestinal motility.

Under pathophysiological conditions induced experimentally in rodents, the endocannabinoid system conveys protection to the GI tract (e.g. from inflammation and abnormally high gastric and enteric secretions).

Such protective activities are largely in agreement with anecdotal reports from folk medicine on the use of Cannabis sativa extracts by subjects suffering from various GI disorders.

 Thus, the endocannabinoid system may serve as a potentially promising therapeutic target against different GI disorders, including frankly inflammatory bowel diseases (e.g. Crohn’s disease), functional bowel diseases (e.g. irritable bowel syndrome) and secretion- and motility-related disorders.

As stimulation of this modulatory system by CB1 receptor agonists can lead to unwanted psychotropic side effects, an alternative and promising avenue for therapeutic applications resides in the treatment with CB1 receptor agonists that are unable to cross the blood-brain barrier, or with compounds that inhibit the degradation of endogenous ligands (endocannabinoids) of CB1 receptors, hence prolonging the activity of the endocannabinoid system.”

http://www.ncbi.nlm.nih.gov/pubmed/16133420

[Marihuana and cannabinoids as medicaments].

“Biological activity of cannabinoids is caused by binding to two cannabinoid receptors CB1 and CB2. Psychoactive is not only tetrahydrocannabinol (THC) but also: cannabidiol, cannabigerol or cannabichromen. Formerly, the usefulness of hemp was assessed in the relation to temporary appeasement of the symptoms of some ailments as nausea or vomiting.

 Present discoveries indicates that cannabis-based drugs has shown ability to alleviate of autoimmunological disorders such as: Multiple sclerosis (MS), Rheumatoid arthritis (RA) or inflammatory bowel disease. Another studies indicates that cannabinoids play role in treatment of neurological disorders like Alzheimer disease or Amyotrophic lateral sclerosis (ALS) or even can reduce spreading of tumor cells.

 Cannabinoids stand out high safety profile considering acute toxicity, it is low possibility of deadly overdosing and side-effects are comprise in range of tolerated side-effects of other medications.

In some countries marinol and nabilone are used as anti vomiting and nausea drug. First cannabis-based drug containg naturally occurring cannabinoids is Sativex. Sativex is delivered in an mucosal spray for patients suffering from spasticity in MS, pain relevant with cancer and neuropathic pain of various origin. Despite the relatively low acute toxicity of cannabinoids they should be avoid in patients with psychotic disorders, pregnant or breastfeeding woman. Cannabinoids prolong a time of reaction and decrease power of concentration that’s why driving any vehicles is forbidden.

 Cannabis side-effects varies and depend from several factors like administrated dose, rout of administration and present state of mind. After sudden break from long-lasting use, withdrawal symptoms can appear, although they entirely disappear after a week or two.”

http://www.ncbi.nlm.nih.gov/pubmed/23421098

Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease.

“Inflammatory bowel disease (IBD) is an incurable disease which affects millions of people in industrialised countries. Anecdotal and scientific evidence suggest that Cannabis use may have a positive impact in IBD patients.

 Here, we investigated the effect of cannabigerol (CBG), a non-psychotropic Cannabis-derived cannabinoid, in a murine model of colitis…

  In conclusion, CBG attenuated murine colitis, reduced nitric oxide production in macrophages (effect being modulated by the CB(2) receptor) and reduced ROS formation in intestinal epithelial cells.

CBG could be considered for clinical experimentation in IBD patients.”

http://www.ncbi.nlm.nih.gov/pubmed/23415610

Latest advances in cannabinoid receptor agonists.

“Since the discovery of cannabinoid receptors and their endogenous ligands in early 1990s, the endocannabinoid system has been shown to play a vital role in several pathophysiological processes. It has been targeted for the treatment of several diseases including neurodegenerative diseases (Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and MS), cancer, obesity, inflammatory bowel disease, neuropathic and inflammatory pain. The last decade has witnessed remarkable advances in the development of cannabinergic ligands displaying high selectivity and potency towards two subtypes of cannabinoid receptors, namely CB1 and CB2.”

 “…we highlight the latest advances made in the development of cannabinoid agonists and summarize recently disclosed, novel chemical scaffolds as CB-selective agonists…”

 

“CONCLUSIONS:

Our analysis reveals prolific patenting activity mainly in the CB2 selective agonist area. Limiting the BBB penetrability, thereby, leading to peripherally restricted CB1/CB2 agonists and enhancing CB2-selectivity emerge as likely prerequisites for avoidance of adverse central CB1 mediated side effects.”

http://www.ncbi.nlm.nih.gov/pubmed/19939187

From cannabis to the endocannabinoid system: refocussing attention on potential clinical benefits.

Image result for West Indian Med J

“Cannabis sativa is one of the oldest herbal remedies known to man. Over the past four thousand years, it has been used for the treatment of numerous diseases but due to its psychoactive properties, its current medicinal usage is highly restricted. In this review, we seek to highlight advances made over the last forty years in the understanding of the mechanisms responsible for the effects of cannabis on the human body and how these can potentially be utilized in clinical practice. During this time, the primary active ingredients in cannabis have been isolated, specific cannabinoid receptors have been discovered and at least five endogenous cannabinoid neurotransmitters (endocannabinoids) have been identified. Together, these form the framework of a complex endocannabinoid signalling system that has widespread distribution in the body and plays a role in regulating numerous physiological processes within the body. Cannabinoid ligands are therefore thought to display considerable therapeutic potential and the drive to develop compounds that can be targeted to specific neuronal systems at low enough doses so as to eliminate cognitive side effects remains the ‘holy grail’ of endocannabinoid research.”

http://www.ncbi.nlm.nih.gov/pubmed/23155985