“Cannabinoids modulate intestinal permeability through CB1.
The endocannabinoid-like compounds oleoylethanolamine (OEA) and palmitoylethanolamine (PEA) play an important role in digestive regulation, and we hypothesized they would also modulate intestinal permeability.
OEA and PEA have endogenous roles and potential therapeutic applications in conditions of intestinal hyperpermeability and inflammation.”
“In ancient medicine, extracts of the marijuana plant Cannabis sativa were used against diseases of the gastrointestinal (GI) tract.
Today, our knowledge of the ingredients of the Cannabis plant has remarkably advanced enabling us to use a variety of herbal and synthetic cannabinoid (CB) compounds to study the endocannabinoid system (ECS), a physiologic entity that controls tissue homeostasis with the help of endogenously produced CBs and their receptors.
After many anecdotal reports suggested beneficial effects of Cannabis in GI disorders, it was not surprising to discover that the GI tract accommodates and expresses all the components of the ECS.
Cannabinoid receptors and their endogenous ligands, the endocannabinoids, participate in the regulation of GI motility, secretion, and the maintenance of the epithelial barrier integrity.
In addition, other receptors, such as the transient receptor potential cation channel subfamily V member 1 (TRPV1), the peroxisome proliferator-activated receptor alpha (PPARα) and the G-protein coupled receptor 55 (GPR55), are important participants in the actions of CBs in the gut and critically determine the course of bowel inflammation and colon cancer.
The following review summarizes important and recent findings on the role of CB receptors and their ligands in the GI tract with emphasis on GI disorders, such as irritable bowel syndrome, inflammatory bowel disease, and colon cancer.”
“Cannabis has been used to treat gastrointestinal (GI) conditions that range from enteric infections and inflammatory conditions to disorders of motility, emesis and abdominal pain. The mechanistic basis of these treatments emerged after the discovery of Delta(9)-tetrahydrocannabinol as the major constituent of Cannabis. Further progress was made when the receptors for Delta(9)-tetrahydrocannabinol were identified as part of an endocannabinoid system, that consists of specific cannabinoid receptors, endogenous ligands and their biosynthetic and degradative enzymes. Anatomical, physiological and pharmacological studies have shown that the endocannabinoid system is widely distributed throughout the gut, with regional variation and organ-specific actions. It is involved in the regulation of food intake, nausea and emesis, gastric secretion and gastroprotection, GI motility, ion transport, visceral sensation, intestinal inflammation and cell proliferation in the gut. Cellular targets have been defined that include the enteric nervous system, epithelial and immune cells. Molecular targets of the endocannabinoid system include, in addition to the cannabinoid receptors, transient receptor potential vanilloid 1 receptors, peroxisome proliferator-activated receptor alpha receptors and the orphan G-protein coupled receptors, GPR55 and GPR119. Pharmacological agents that act on these targets have been shown in preclinical models to have therapeutic potential. Here, we discuss cannabinoid receptors and their localization in the gut, the proteins involved in endocannabinoid synthesis and degradation and the presence of endocannabinoids in the gut in health and disease. We focus on the pharmacological actions of cannabinoids in relation to GI disorders, highlighting recent data on genetic mutations in the endocannabinoid system in GI disease.”
“The endocannabinoid system mainly consists of endogenously produced cannabinoids (endocannabinoids) and two G protein-coupled receptors (GPCRs), cannabinoid receptors 1 and 2 (CB1 and CB2). This system also includes enzymes responsible for the synthesis and degradation of endocannabinoids and molecules required for the uptake and transport of endocannabinoids. In addition, endocannabinoid-related lipid mediators and other putative endocannabinoid receptors, such as transient receptor potential channels and other GPCRs have been identified. Accumulating evidence indicates that the endocannabinoid system is a key modulator of gastrointestinal physiology, influencing satiety, emesis, immune function, mucosal integrity, motility, secretion, and visceral sensation. In light of therapeutic benefits of herbal and synthetic cannabinoids, the vast potential of the endocannabinoid system for the treatment of gastrointestinal diseases has been demonstrated. This review focuses on the role of the endocannabinoid system in gut homeostasis and in the pathogenesis of intestinal disorders associated with intestinal motility, inflammation and cancer. Finally, links between gut microorganisms and the endocannabinoid system are briefly discussed.”
“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.
“Cannabis has been used medicinally for centuries to treat a variety of disorders, including those associated with the gastrointestinal tract.
The discovery of our bodies’ own “cannabis-like molecules” and associated receptors and metabolic machinery – collectively called the endocannabinoid system – enabled investigations into the physiological relevance for the system, and provided the field with evidence of a critical function for this endogenous signaling pathway in health and disease.
Recent investigations yield insight into a significant participation for the endocannabinoid system in the normal physiology of gastrointestinal function, and its possible dysfunction in gastrointestinal pathology. Many gaps, however, remain in our understanding of the precise neural and molecular mechanisms across tissue departments that are under the regulatory control of the endocannabinoid system.
This review highlights research that reveals an important – and at times surprising – role for the endocannabinoid system in the control of a variety of gastrointestinal functions, including motility, gut-brain mediated fat intake and hunger signaling, inflammation and gut permeability, and dynamic interactions with gut microbiota.”
“Inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn’s disease affects over a million people in the United States, with an estimated indirect cost from work loss of $3.6 billion annually. Many of these individuals suffer from pain, diarrhea and poor ability to digest their food, and in up to half of those with IBD, the disease is so severe that it ultimately requires surgery to remove the affected bowel segment.
Historically, marijuana has been used to treat diarrhea and has been advocated for the treatment of a variety of other gastrointestinal problems, including Crohn’s disease.
More recent pharmacological studies have clearly established that cannabinoids inhibit gastrointestinal motility and secretion by acting on CB1 receptors located on the terminals of both intrinsic and extrinsic submucosal neurons.
When administered to mice with chemically induced enteritis, cannabinoids also reduce inflammation and fluid accumulation in the gut.
Cannabinoids inhibit motility and secretion in the intestine.
They are now assigned the additional task of curbing excessive inflammation, suggesting that drugs targeting the endogenous cannabinoid system could be exploited for inflammatory bowel disease.
These findings may offer a new therapeutic approach to IBD.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2516444/
“Cannabis sativa has long been known for its psychotropic effect. Only recently with the discovery of the cannabinoid receptors, their endogenous legends and the enzymes responsible for their synthesis and degradation, the role of this ‘endocannabinoid system’ in different pathophysiologic processes is beginning to be delineated.
There is evidence that CB1 receptor stimulation with synthetic cannabinoids or Cannabis sativa extracts rich in Δ9-tetrahydrocannabinol inhibit gastric acid secretion in humans and experimental animals.
This is specially seen when gastric acid secretion is stimulated by pentagastrin, carbachol or 2-deoxy-d-glucose.
Cannabis and/or cannabinoids protect the gastric mucosa against noxious challenge with non-steroidal anti-inflammatory drugs, ethanol as well as against stress-induced mucosal damage.
Cannabis/cannabinoids might protect the gastric mucosa by virtue of its antisecretory, antioxidant, anti-inflammatory, and vasodilator properties.”
“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
“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.”