Category Archives: Gastrointestinal Disorders

Cannabidiol and Other Non-Psychoactive Cannabinoids for Prevention and Treatment of Gastrointestinal Disorders: Useful Nutraceuticals?

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ijms-logo“Cannabis sativa is an aromatic annual flowering plant with several botanical varieties, used for different purposes, like the production of fibers, the production of oil from the seeds, and especially for recreational or medical purposes.

Phytocannabinoids (terpenophenolic compounds derived from the plant), include the well-known psychoactive cannabinoid Δ9-tetrahydrocannabinol, and many non-psychoactive cannabinoids, like cannabidiol.

The endocannabinoid system (ECS) comprises of endocannabinoid ligands, enzymes for synthesis and degradation of such ligands, and receptors. This system is widely distributed in the gastrointestinal tract, where phytocannabinoids exert potent effects, particularly under pathological (i.e., inflammatory) conditions.

Herein, we will first look at the hemp plant as a possible source of new functional food ingredients and nutraceuticals that might be eventually useful to treat or even prevent gastrointestinal conditions.

Subsequently, we will briefly describe the ECS and the general pharmacology of phytocannabinoids. Finally, we will revise the available data showing that non-psychoactive phytocannabinoids, particularly cannabidiol, may be useful to treat different disorders and diseases of the gastrointestinal tract.

With the increasing interest in the development of functional foods for a healthy life, the non-psychoactive phytocannabinoids are hoped to find a place as nutraceuticals and food ingredients also for a healthy gastrointestinal tract function.”

https://www.ncbi.nlm.nih.gov/pubmed/32357565

https://www.mdpi.com/1422-0067/21/9/3067

Marijuana, Ondansetron, and Promethazine Are Perceived as Most Effective Treatments for Gastrointestinal Nausea.

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 SpringerLink“Many anti-nausea treatments are available for chronic gastrointestinal syndromes, but data on efficacy and comparative effectiveness are sparse.

AIMS:

To conduct a sectional survey study of patients with chronic nausea to assess comparative effectiveness of commonly used anti-nausea treatments.

RESULTS:

One hundred and fifty-three patients completed the survey. The mean efficacy score of all anti-nausea treatments evaluated was 1.73. After adjustment, three treatments had scores statically higher than the mean, including marijuana (2.75, p < 0.0001), ondansetron (2.64, p < 0.0001), and promethazine (2.46, p < 0.0001). Several treatments, including many neuromodulators, complementary and alternative treatments, erythromycin, and diphenhydramine had scores statistically below average. Patients with more severe nausea responded better to marijuana (p = 0.036) and diphenhydramine (p < 0.001) and less so to metoclopramide (p = 0.020). There was otherwise no significant differential response by age, gender, nausea localization, underlying gastrointestinal cause of nausea, and GCSI.

CONCLUSIONS:

When treating nausea in patients with chronic gastrointestinal syndromes, clinicians may consider trying higher performing treatments first, and forgoing lower performing treatments. Further prospective research is needed, particularly with respect to highly effective treatments.”

https://www.ncbi.nlm.nih.gov/pubmed/32185665

https://link.springer.com/article/10.1007%2Fs10620-020-06195-5

Cannabinoids Improve Gastrointestinal Symptoms in a Parenteral Nutrition-Dependent Patient With Chronic Intestinal Pseudo-Obstruction.

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Journal of Parenteral and Enteral Nutrition“Chronic intestinal pseudo-obstruction (CIPO) is a rare and challenging cause of pediatric intestinal failure, requiring long-term parenteral nutrition in most cases. Despite optimal management, some patients experience chronic abdominal pain and recurrent obstructive episodes with a major impact on their quality of life.

Cannabinoids have been successfully used in some conditions. However, their use in CIPO has never been reported in the literature.

We report a case of successful use of medicinal cannabinoids in a patient with CIPO, resulting in a significant reduction of abdominal pain, vomiting, and subocclusive episodes and increased appetite and weight, without major adverse events.

Although further observations are required to consolidate these findings, this case may be helpful for other patients suffering from the same condition.”

https://www.ncbi.nlm.nih.gov/pubmed/32181915

https://onlinelibrary.wiley.com/doi/abs/10.1002/jpen.1821

Localization of cannabinoid and cannabinoid related receptors in the cat gastrointestinal tract.

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Image result for Histochem Cell Biol journal “A growing body of literature indicates that activation of cannabinoid receptors may exert beneficial effects on gastrointestinal inflammation and visceral hypersensitivity.

The present study aimed to immunohistochemically investigate the distribution of the canonical cannabinoid receptors CB1 (CB1R) and CB2 (CB2R) and the putative cannabinoid receptors G protein-coupled receptor 55 (GPR55), nuclear peroxisome proliferator-activated receptor alpha (PPARα), transient receptor potential ankyrin 1 (TRPA1), and serotonin receptor 5-HT1a 5-HT1aR) in tissue samples of the gastrointestinal tract of the cat.

CB1R-immunoreactivity (CB1R-IR) was observed in gastric epithelial cells, intestinal enteroendocrine cells (EECs) and goblet cells, lamina propria mast cells (MCs), and enteric neurons. CB2R-IR was expressed by EECs, enterocytes, and macrophages. GPR55-IR was expressed by EECs, macrophages, immunocytes, and MP neurons. PPARα-IR was expressed by immunocytes, smooth muscle cells, and enteroglial cells. TRPA1-IR was expressed by enteric neurons and intestinal goblet cells. 5-HT1a receptor-IR was expressed by gastrointestinal epithelial cells and gastric smooth muscle cells.

Cannabinoid receptors showed a wide distribution in the feline gastrointestinal tract layers. Although not yet confirmed/supported by functional evidences, the present research might represent an anatomical substrate potentially useful to support, in feline species, the therapeutic use of cannabinoids during gastrointestinal inflammatory diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/32095931

Impact of Cannabinoids on Symptoms of Refractory Gastroparesis: A Single-center Experience.

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“Cannabinoids are increasingly used for medicinal purposes, including neuropathy.

Gastroparesis is a neuromuscular disorder and neuropathy plays a large role in its pathogenesis. It is thus reasonable that cannabinoids can serve a beneficial role in the management of gastroparesis.

Our study evaluates the effect of cannabinoids on gastroparesis symptoms.

A significant improvement in the GCSI total symptom composite score was seen with either cannabinoid treatment (mean score difference of 12.8, 95% confidence interval 10.4-15.2; p-value < 0. 001). Patients prescribed marijuana experienced a statistically significant improvement in every GCSI symptom subgroup. Significant improvement in abdominal pain score was also seen with either cannabinoid treatment (mean score difference of 1.6; p-value <0.001).

Conclusions: Cannabinoids dramatically improve the symptoms of gastroparesis. Furthermore, an improvement in abdominal pain with cannabinoids represents a breakthrough for gastroparesis-associated abdominal pain treatment, for which there are currently no validated therapies.”

https://www.ncbi.nlm.nih.gov/pubmed/31993268

“In conclusion, cannabinoids dramatically improve refractory gastroparesis symptoms, including abdominal pain. Marijuana may be superior to dronabinol in improving these symptoms, though both cannabinoids seem to be promising as novel therapeutic options in gastroparesis.”

https://www.cureus.com/articles/25832-impact-of-cannabinoids-on-symptoms-of-refractory-gastroparesis-a-single-center-experience

Endocannabinoid system in irritable bowel syndrome and cannabis as a therapy.

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Complementary Therapies in Medicine“Irritable bowel syndrome (IBS) global burden is underestimated despite its high prevalence. It’s a gastrointestinal disease having obscure pathophysiology with multiple therapies yet unsatisfactory remedies.

The Endocannabinoid system (ECS) of our body plays a key role in maintaining normal physiology of the gastrointestinal tract as well as involves abnormalities including functional diseases like IBS. This review highlights the importance of the Endocannabinoid system, its connections with the normal gastrointestinal functions and abnormalities like IBS.

It also discusses the role of cannabis as medical therapy in IBS patients.

A literature search for articles related to endocannabinoids in IBS and medical cannabis in PubMed and Google Scholar was conducted. The studies highlighted the significant participation of ECS in IBS. However, the breach in obtaining the promising therapeutic model for IBS needed further investigation in ECS and uncover other treatments for IBS.

This review summarizes ECS, highlights the relationship of ECS with IBS and explores cannabis as a potential therapy to treat IBS.”

https://www.ncbi.nlm.nih.gov/pubmed/31987224

https://www.sciencedirect.com/science/article/pii/S0965229919310179?via%3Dihub

Gastrointestinal Adverse Events of Cannabinoid 1 Receptor Inverse Agonists suggest their Potential Use in Irritable Bowel Syndrome with Constipation: A Systematic Review and Meta-Analysis.

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 Image result for J Gastrointestin Liver Dis“Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal (GI) disorders characterized by pain and impaired bowel movements. Currently available drugs show limited efficacy.

Cannabinoid 1 receptor (CB1) inverse agonists (CB1-RAN) cause diarrhea and may be candidates for the treatment of constipation-predominant IBS (IBS-C). We evaluated the effects of CB1-RAN in clinical trials for their potential use in IBS-C.

METHODS:

Database search identified all clinical trials published up to May 2018 that reported rimonabant and taranabant treatment for at least one month and detailed the GI adverse events (AEs). Categorical outcomes (subgroups of AEs) were analyzed using the odds ratio (OR).

RESULTS:

Eighteen trials met the inclusion criteria. Rimonabant 20 mg produced significantly more overall AEs (OR=1.35, CI: 1.19-1.52, p<0.0001), psychiatric events (OR=1.79, CI: 1.46-2.21, p<0.001) and GI AEs (OR=2.05, CI: 1.65-2.55, p<0.001) compared to placebo. Taranabant at doses ranging from 0.5 to 8 mg produced significantly more overall AEs (OR=1.36, CI: 1.13-1.64, p<0.002), psychiatric AEs (1.82, CI: 1.54-2.16, p<0.001) and GI AEs (OR=1.75, CI: 1.29-2.37, p<0.001) compared to placebo.

CONCLUSIONS:

The approach to target CB1 in the gut for the treatment of IBS-C or chronic constipation seems a promising therapeutic option. Prospective clinical trials on the possible targeting of CB1 and the endocannabinoid system are warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/31826058

https://www.jgld.ro/jgld/index.php/jgld/article/view/265

Cannabinoids and the Microbiota-Gut-Brain-Axis: Emerging Effects of Cannabidiol and Potential Applications to Alcohol Use Disorders.

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Alcoholism: Clinical and Experimental Research banner“The endocannabinoid system (ECS) has emerged in recent years as a potential treatment target for alcohol use disorders (AUD).

In particular, the non-psychoactive cannabinoid cannabidiol (CBD) has shown preclinical promise in ameliorating numerous clinical symptoms of AUD.

There are several proposed mechanism(s) through which cannabinoids (and CBD in particular) may confer beneficial effects in the context of AUD. First, CBD may directly impact specific brain mechanisms underlying AUD to influence alcohol consumption and the clinical features of AUD. Second, CBD may influence AUD symptoms through its actions across the digestive, immune, and central nervous systems, collectively known as the microbiota-gut-brain-axis (MGBA).

Notably, emerging work suggests that alcohol and cannabinoids exert opposing effects on the MGBA.

Alcohol is linked to immune dysfunction (e.g., chronic systemic inflammation in the brain and periphery) as well as disturbances in gut microbial species (microbiota) and increased intestinal permeability. These MGBA disruptions have been associated with AUD symptoms such as craving and impaired cognitive control.

Conversely, existing preclinical data suggest that cannabinoids may confer beneficial effects on the gastrointestinal and immune system, such as reducing intestinal permeability, regulating gut bacteria and reducing inflammation. Thus, cannabinoids may exert AUD harm-reduction effects, at least in part, through their beneficial actions across the MGBA.

This review will provide a brief introduction to the ECS and the MGBA, discuss the effects of cannabinoids (particularly CBD) and alcohol in the brain, gut, and immune system (i.e., across the MGBA), and put forth a theoretical framework to inform future research questions.”

https://www.ncbi.nlm.nih.gov/pubmed/31803950

https://onlinelibrary.wiley.com/doi/abs/10.1111/acer.14256

Cannabinoids: A Guide for Use in the World of Gastrointestinal Disease.

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Image result for ovid journal“Cannabinoids have been known as the primary component of cannabis for decades, but the characterization of the endocannabinoid system (ECS) in the 1990s opened the doors for cannabis’ use in modern medicine.

The 2 main receptors of this system, cannabinoid receptors 1 and 2, are found on cells of various tissues, with significant expression in the gastrointestinal (GI) tract. The characterization of the ECS also heralded the understanding of endocannabinoids, naturally occurring compounds synthesized in the human body.

Although research on the effects of both endogenous and exogenous cannabinoids has been slow due to the complicated legal history of cannabis, discoveries of cannabinoids‘ treatment potential have been found in various fields of medicine, including the GI world.

Medical cannabis has since been offered as a treatment for a myriad of conditions and malignancies, including cancer, human immunodeficiency virus/acquired immunodeficiency syndrome, multiple sclerosis, chronic pain, nausea, posttraumatic stress disorder, amyotrophic lateral sclerosis, cachexia, glaucoma, and epilepsy.

This article hopes to create an overview of current research on cannabinoids and the ECS, detail the potential advantages and pitfalls of their use in GI diseases, and explore possible future developments in this field.”

https://www.ncbi.nlm.nih.gov/pubmed/31789770

https://insights.ovid.com/crossref?an=00004836-900000000-97668

Marijuana Use in Patients with Symptoms of Gastroparesis: Prevalence, Patient Characteristics, and Perceived Benefit.

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“Marijuana may be used by some patients with gastroparesis (Gp) for its potential antiemetic, orexigenic, and pain-relieving effects.

The aim of this study was to describe the use of marijuana by patients for symptoms of Gp, assessing prevalence of use, patient characteristics, and patients’ perceived benefit on their symptoms of Gp.

RESULTS:

Fifty-nine of 506 (11.7%) patients with symptoms of Gp reported current marijuana use, being similar among patients with delayed and normal gastric emptying and similar in idiopathic and diabetic patients. Patients using marijuana were younger, more often current tobacco smokers, less likely to be a college graduate, married or have income > $50,000. Patients using marijuana had higher nausea/vomiting subscore (2.7 vs 2.1; p = 0.002), higher upper abdominal pain subscore (3.5 vs 2.9; p = 0.003), more likely to be using promethazine (37 vs 25%; p = 0.05) and dronabinol (17 vs 3%; p < 0.0001). Of patients using marijuana, 51% had been using it for more than 2 years, 47% were using this once or more per day, and 81% of marijuana users rated their benefit from marijuana as better or much better.

CONCLUSIONS:

A subset of patients (12%) with symptoms of Gp use marijuana. Patients with severe nausea and abdominal pain were more likely to use marijuana and perceive it to be beneficial for their symptoms.”

https://www.ncbi.nlm.nih.gov/pubmed/31758430

https://link.springer.com/article/10.1007%2Fs10620-019-05963-2

“Marijuana, Ondansetron, and Promethazine Are Perceived as Most Effective Treatments for Gastrointestinal Nausea”

https://pubmed.ncbi.nlm.nih.gov/32185665/