Category Archives: Gastrointestinal Disorders

Cannabinoid Receptors in Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance.

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“Cannabinoid receptors are fundamentally involved in all aspects of intestinal physiology, such as motility, secretion, and epithelial barrier function. They are part of a broader entity, the so-called endocannabinoid system which also includes their endocannabinoid ligands and the ligands’ synthesizing/degrading enzymes.

The system has a strong impact on the pathophysiology of the gastrointestinal tract and is believed to maintain homeostasis in the gut by controlling hypercontractility and by promoting regeneration after injury.

For instance, genetic knockout of cannabinoid receptor 1 leads to inflammation and cancer of the intestines. Derivatives of Δ9-tetrahydrocannabinol, such as nabilone and dronabinol, activate cannabinoid receptors and have been introduced into the clinic to treat chemotherapy-induced emesis and loss of appetite; however, they may cause many psychotropic side effects.

New drugs that interfere with endocannabinoid degradation to raise endocannabinoid levels circumvent this obstacle and could be used in the future to treat emesis, intestinal inflammation, and functional disorders associated with visceral hyperalgesia.”

https://www.ncbi.nlm.nih.gov/pubmed/28161834

The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease

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“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.

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.”

https://www.ncbi.nlm.nih.gov/pubmed/27561826

Role of cannabis in digestive disorders.

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“Cannabis sativa, a subspecies of the Cannabis plant, contains aromatic hydrocarbon compounds called cannabinoids.

Tetrahydrocannabinol is the most abundant cannabinoid and is the main psychotropic constituent.

Cannabinoids activate two types of G-protein-coupled cannabinoid receptors: cannabinoid type 1 receptor and cannabinoid type 2 receptor.

There has been ongoing interest and development in research to explore the therapeutic potential of cannabis. Tetrahydrocannabinol exerts biological functions on the gastrointestinal (GI) tract.

Cannabis has been used for the treatment of GI disorders such as abdominal pain and diarrhea.

The endocannabinoid system (i.e. endogenous circulating cannabinoids) performs protective activities in the GI tract and presents a promising therapeutic target against various GI conditions such as inflammatory bowel disease (especially Crohn’s disease), irritable bowel syndrome, and secretion and motility-related disorders.

The present review sheds light on the role of cannabis in the gut, liver, and pancreas and also on other GI symptoms, such as nausea and vomiting, cannabinoid hyperemesis syndrome, anorexia, weight loss, and chronic abdominal pain.

Although the current literature supports the use of marijuana for the treatment of digestive disorders, the clinical efficacy of cannabis and its constituents for various GI disorders remains unclear.”

https://www.ncbi.nlm.nih.gov/pubmed/27792038

Central Aspects of Nausea and Vomiting in GI Disorders.

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“Nausea and vomiting result from continuous interactions among gastrointestinal, central nervous system, and autonomic nervous system. Despite being closely associated, central pathways of nausea and vomiting appear to be at least partly different and nausea is no longer considered only a penultimate step of vomiting. Although our understanding of central pathways of nausea has improved over the last one decade, it is still very basic.

Afferent pathways from gastrointestinal tract via vagus, vestibular system, and chemoreceptor trigger zone project to nucleus tractus solitarius which, in turn, relays the signal to central pattern generator initiating multiple downstream pathways. This central nausea pathway appears to be under constant modulation by autonomic nervous system and cerebral cortex.

There is also some evidence that central pathway of chronic nausea is different from that of acute nausea and closely resembles that of neuropathic pain. This improved understanding has modified the way we can approach the treatment of acute and chronic nausea.

While conventional therapies such as antiemetics (antiserotoninergic, antihistaminic, antidopaminergic) and prokinetics are commonly used to manage acute nausea, they are not as effective in improving chronic nausea.

Recently, neuromodulators such as tricyclic antidepressants, gabapentin, olanzapine, benzodiazepines, and cannabinoids have been shown to have antinausea effect.

There is a need to study the utility of these drugs in managing chronic functional nausea. Improving our understanding of central and peripheral circuitry of nausea will allow us to better utilize the currently available drugs and develop new therapeutic options.”

https://www.ncbi.nlm.nih.gov/pubmed/27734216

Cannabinoids and GI Disorders: Endogenous and Exogenous.

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“Despite the political and social controversy affiliated with it, the medical community must come to the realization that cannabinoids exist as a ubiquitous signaling system in many organ systems. Our understanding of cannabinoids and how they relate not only to homeostasis but also in disease states must be furthered through research, both clinically and in the laboratory. The identification of the cannabinoid receptors in the early 1990s have provided us with the perfect target of translational research. Already, much has been done with cannabinoids and the nervous system. Here, we explore the implications it has for the gastrointestinal tract. Most therapeutics currently on the market presently target only one aspect of the cannabinoid system. Our main purpose here is to highlight areas of research and potential avenues of discovery that the cannabinoid system has yet to reveal.”

https://www.ncbi.nlm.nih.gov/pubmed/27699625

May cannabinoids prevent the development of chemotherapy-induced diarrhea and intestinal mucositis? Experimental study in the rat.

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“The antineoplastic drug 5-fluoruracil (5-FU) is a pirimidine analog, which frequently induces potentially fatal diarrhea and mucositis.

Cannabinoids reduce gastrointestinal motility and secretion and might prevent 5-FU-induced gut adverse effects.

Here, we asked whether cannabinoids may prevent diarrhea and mucositis induced by 5-FU in the rat.

CONCLUSIONS AND INFERENCES:

5-FU-induced diarrhea, but not mucositis, was partly prevented by WIN at a low dose.

Cannabinoids might be useful to prevent chemotherapy-induced diarrhea.”

https://www.ncbi.nlm.nih.gov/pubmed/27686064

Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability in vitro via TRPV1 and PPARα.

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“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.”

http://www.ncbi.nlm.nih.gov/pubmed/27623929

The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease.

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“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.

PURPOSE:

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.”

http://www.ncbi.nlm.nih.gov/pubmed/27561826

Cannabinoids and the gut: new developments and emerging concepts.

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“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.”

https://www.ncbi.nlm.nih.gov/pubmed/20117132/

Endocannabinoids in the gut.

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“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.”

http://www.ncbi.nlm.nih.gov/pubmed/27538961