Cannabinoid-induced relief of hypermotility in a rat model of the irritable bowel syndrome.

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“Cannabinoid-2 receptor agonists may be useful in treating intestinal motility disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31094052

https://onlinelibrary.wiley.com/doi/abs/10.1111/nmo.13613

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Cannabis Oil Use by Adolescents and Young Adults With Inflammatory Bowel Disease.

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“The aim of the study was to describe use of oral or sublingual cannabis oil (CO) by adolescent and young adult patients with inflammatory bowel disease (IBD).

METHODS:

A descriptive study of IBD patients 13 to 23 years of age seen between January 2015 through December 2017 at Children’s Hospital Colorado. Information obtained included chart abstraction, electronic and interview self-report, and serum cannabinoid levels. We compared CO users and cannabis non-users for clinical characteristics and perceptions of risk. Users of CO provided information on routes, patterns, motivations, and perceived benefits and problems with use.

RESULTS:

The 15 users and 67 non-users were similar for clinical characteristics and pain and appetite scores. 9 of 15 (60%) CO users had used in the past 30 days, an average of 22 ± 9 times; and 4 used daily. A variety of strengths and CBD:THC ratios were reported. Most common perceived effect of use was on sleep quality, nausea, and increase in appetite. Of the 15 users, 6 used only CO and no additional forms of cannabis. Of these 6 CO only users, 5 reported a medical reason for use, most commonly to relieve pain.

CONCLUSIONS:

Adolescent and young adults with IBD used oral CO and many used other cannabis products as well. Users perceived some medical benefit. Care teams should strive for open communication about use until further information on safety and efficacy becomes available.”

https://www.ncbi.nlm.nih.gov/pubmed/30801394

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Palmitoylethanolamide and Cannabidiol Prevent Inflammation-induced Hyperpermeability of the Human Gut In Vitro and In Vivo—A Randomized, Placebo-controlled, Double-blind Controlled Trial

Inflammatory Bowel Diseases

“We aimed to examine, for the first time, the effect of cannabidiol (CBD) and palmitoylethanolamide (PEA) on the permeability of the human gastrointestinal tract in vitro, ex vivo, and in vivo.

Results
In vitro, PEA, and CBD decreased the inflammation-induced flux of dextrans (P< 0.0001), sensitive to PPARα and CB1 antagonism, respectively. Both PEA and CBD were prevented by PKA, MEK/ERK, and adenylyl cyclase inhibition (P < 0.001). In human mucosa, inflammation decreased claudin-5 mRNA, which was prevented by CBD (P < 0.05). Palmitoylethanolamide and cannabidiol prevented an inflammation-induced fall in TRPV1 and increase in PPARα transcription (P< 0.0001). In vivo, aspirin caused an increase in the absorption of lactulose and mannitol, which were reduced by PEA or CBD (P < 0.001).

Conclusion

Cannabidiol and palmitoylethanolamide reduce permeability in the human colon. These findings have implications in disorders associated with increased gut permeability, such as inflammatory bowel disease.”

https://academic.oup.com/ibdjournal/advance-article-abstract/doi/10.1093/ibd/izz017/5341970?redirectedFrom=fulltext

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Activation of cannabinoid 2 receptor relieves colonic hypermotility in a rat model of irritable bowel syndrome.

Neurogastroenterology &amp; Motility banner

“Irritable bowel syndrome (IBS) is a common disease with intestinal dysmotility, whose mechanism remains elusive.

The endocannabinoid system is emerging as an important modulator of gastrointestinal (GI) motility in multiple diseases, but its involvement in IBS is unknown.

We aimed to determine whether cannabinoid 2 (CB2) receptor modulates intestinal motility associated with stress-induced IBS.

CONCLUSION:

CB2 receptor may exert an important inhibitory effect in stress-induced colonic hypermotility by modulating NO synthesis through p38 mitogen-activated protein kinase signaling. AM1241 could be used as a potential drug to treat disorders with colonic hypermotility.”

https://www.ncbi.nlm.nih.gov/pubmed/30793435

https://onlinelibrary.wiley.com/doi/abs/10.1111/nmo.13555

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Cannabis and Turmeric as Complementary Treatments for IBD and Other Digestive Diseases.

 “Complementary therapies for inflammatory bowel disease (IBD) have earned growing interest from patients and investigators alike, with a dynamic landscape of research in this area. In this article, we review results of the most recent studies evaluating the role of cannabis and turmeric for the treatment of IBD and other intestinal illnesses.

RECENT FINDINGS:

Cannabinoids are well-established modulators of gut motility and visceral pain and have demonstrated anti-inflammatory properties. Clinical trials suggest that there may be a therapeutic role for cannabinoid therapy in the treatment of IBD, irritable bowel syndrome (IBS), nausea and vomiting, and GI motility disorders. Recent reports of serious adverse effects from synthetic cannabinoids highlight the need for additional investigation of cannabinoids to establish their efficacy and safety. Turmeric trials have demonstrated some promise as adjuvant treatment for IBD, though not in other GI disease processes. Evidence suggests that the use of cannabis and turmeric is potentially beneficial in IBD and IBS; however, neither has been compared to standard therapy in IBD, and thus should not be recommended as alternative treatment for IBD. For cannabis in particular, additional investigation regarding appropriate dosing and timing, given known adverse effects of its chronic use, and careful monitoring of potential bleeding complications with synthetic cannabinoids are imperative.”

https://www.ncbi.nlm.nih.gov/pubmed/30635796

https://link.springer.com/article/10.1007%2Fs11894-019-0670-0

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The novel peripherally active cannabinoid type 1 and serotonin type 3 receptor agonist AM9405 inhibits gastrointestinal motility and reduces abdominal pain in mouse models mimicking irritable bowel syndrome.

European Journal of Pharmacology

“The endocannabinoid system (ECS) plays a crucial role in numerous physiological processes in the central and peripheral nervous systems. In the gastrointestinal (GI) tract, selective cannabinoid (CB) receptor agonists exert potent inhibitory actions on motility and pain signalling. In the present study, we used mouse models of diarrhea, hypermotility, and abdominal pain to examine whether a novel synthetic CB1 receptor agonist AM9405 [(2-(2,6-dihydroxy-4-(2-methyloctan-2-yl)phenyl)-1,3-dimethyl-1H-benzo[d]imidazol-3-ium bromide); also known as GAT379] exhibits effects of potential therapeutic relevance. AM9405 significantly slowed mouse intestinal motility in physiological conditions. Moreover, AM9405 reversed hypermotility and reduced pain in mouse models mimicking symptoms of functional GI disorders, such as stress-induced diarrhoea and writhing test. Interestingly, some of the effects of AM9405 were blocked by a 5-HT3 antagonist suggesting interaction with 5-HT3 receptors. In our study we show that combining CB1 agonism with 5-HT3 agonism may alter physiological functions and experimental pathophysiologies in a manner that make such compounds promising drugs for the future treatment of functional GI disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/30121173

https://www.sciencedirect.com/science/article/pii/S0014299918304734?via%3Dihub

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Cannabinoid pharmacology and therapy in gut disorders.

Biochemical Pharmacology

“Cannabis sp and their products (marijuana, hashish…), in addition to their recreational, industrial and other uses, have a long history for their use as a remedy for symptoms related with gastrointestinal diseases.

After many reports suggesting these beneficial effects, it was not surprising to discover that the gastrointestinal tract expresses endogenous cannabinoids, their receptors, and enzymes for their synthesis and degradation, comprising the so-called endocannabinoid system.

This system participates in the control of tissue homeostasis and important intestinal functions like motor and sensory activity, nausea, emesis, the maintenance of the epithelial barrier integrity, and the correct cellular microenvironment. Thus, different cannabinoid-related pharmacological agents may be useful to treat the main digestive pathologies.

To name a few examples, in irritable bowel syndrome they may normalize dysmotility and reduce pain, in inflammatory bowel disease they may decrease inflammation, and in colorectal cancer, apart from alleviating some symptoms, they may play a role in the regulation of the cell niche.

This review summarizes the main recent findings on the role of cannabinoid receptors, their synthetic or natural ligands and their metabolizing enzymes in normal gastrointestinal function and in disorders including irritable bowel syndrome, inflammatory bowel disease, colon cancer and gastrointestinal chemotherapy-induced adverse effects (nausea/vomiting, constipation, diarrhea).”

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Endocannabinoid-related compounds in gastrointestinal diseases.

Journal of Cellular and Molecular Medicine

“The endocannabinoid system (ECS) is an endogenous signalling pathway involved in the control of several gastrointestinal (GI) functions at both peripheral and central levels. In recent years, it has become apparent that the ECS is pivotal in the regulation of GI motility, secretion and sensitivity, but endocannabinoids (ECs) are also involved in the regulation of intestinal inflammation and mucosal barrier permeability, suggesting their role in the pathophysiology of both functional and organic GI disorders. Genetic studies in patients with irritable bowel syndrome (IBS) or inflammatory bowel disease have indeed shown significant associations with polymorphisms or mutation in genes encoding for cannabinoid receptor or enzyme responsible for their catabolism, respectively. Furthermore, ongoing clinical trials are testing EC agonists/antagonists in the achievement of symptomatic relief from a number of GI symptoms. Despite this evidence, there is a lack of supportive RCTs and relevant data in human beings, and hence, the possible therapeutic application of these compounds is raising ethical, political and economic concerns. More recently, the identification of several EC-like compounds able to modulate ECS function without the typical central side effects of cannabino-mimetics has paved the way for emerging peripherally acting drugs. This review summarizes the possible mechanisms linking the ECS to GI disorders and describes the most recent advances in the manipulation of the ECS in the treatment of GI diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/28990365

http://onlinelibrary.wiley.com/doi/10.1111/jcmm.13359/abstract

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Medicinal Uses of Marijuana and Cannabinoids

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“In the past two decades, there has been increasing interest in the therapeutic potential of cannabis and single cannabinoids, mainly cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). THC and cannabis products rich in THC exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). Since 1975, 140 controlled clinical trials using different cannabinoids or whole-plant preparations for the treatment of a large number of disorders and symptoms have been conducted. Results have led to the approval of cannabis-based medicines [dronabinol, nabilone, and the cannabis extract nabiximols (Sativex®, THC:CBD = 1:1)] as well as cannabis flowers in several countries. Controlled clinical studies provide substantial evidence for the use of cannabinoid receptor agonists in cancer chemotherapy induced nausea and vomiting, appetite loss and cachexia in cancer and HIV patients, neuropathic and chronic pain, and in spasticity in multiple sclerosis. In addition, there is also some evidence suggesting a therapeutic potential of cannabis-based medicines in other indications including Tourette syndrome, spinal cord injury, Crohn’s disease, irritable bowel syndrome, and glaucoma. In several other indications, small uncontrolled and single-case studies reporting beneficial effects are available, for example in posttraumatic stress disorder, attention deficit hyperactivity disorder, and migraine. The most common side effects of THC and cannabis-based medicines rich in THC are sedation and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting. In recent years there is an increasing interest in the medical use of CBD, which exerts no intoxicating side effects and is usually well-tolerated. Preliminary data suggest promising effects in the treatment of anxiety disorders, schizophrenia, dystonia, and some forms of epilepsy. This review gives an overview on clinical studies which have been published over the past 40 years.”

http://www.tandfonline.com/doi/abs/10.1080/07352689.2016.1265360?needAccess=true&journalCode=bpts20

“Review Identifies 140 Controlled Clinical Trials Related to Cannabis”  http://blog.norml.org/2017/06/04/review-identifies-140-controlled-clinical-trials-related-to-cannabis/

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Cannabinoids for treating inflammatory bowel diseases: where are we and where do we go?

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“Fifty years after the discovery of Δ9-tetrahydrocannabinol (THC) as the psychoactive component of Cannabis, we are assessing the possibility of translating this herb into clinical treatment of inflammatory bowel diseases (IBDs).

Here, a discussion on the problems associated with a potential treatment is given.

From first surveys and small clinical studies in patients with IBD we have learned that Cannabis is frequently used to alleviate diarrhea, abdominal pain, and loss of appetite.

Single ingredients from Cannabis, such as THC and cannabidiol, commonly described as cannabinoids, are responsible for these effects. Synthetic cannabinoid receptor agonists are also termed cannabinoids, some of which, like dronabinol and nabilone, are already available with a narcotic prescription.

Recent data on the effects of Cannabis/cannabinoids in experimental models of IBD and in clinical trials with IBD patients have been reviewed using a PubMed database search. A short background on the endocannabinoid system is also provided.

Expert commentary: Cannabinoids could be helpful for certain symptoms of IBD, but there is still a lack of clinical studies to prove efficacy, tolerability and safety of cannabinoid-based medication for IBD patients, leaving medical professionals without evidence and guidelines.”

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