Category Archives: Inflammatory Bowel Disease

The Modulatory Effects and Therapeutic Potential of Cannabidiol in the Gut

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“Cannabidiol (CBD) is a major non-psychotropic phytocannabinoid that exists in the Cannabis sativa plant.

CBD has been found to act on various receptors, including both cannabinoid and non-cannabinoid receptors. In addition, CBD has antioxidant effects that are independent of receptors. CBD has demonstrated modulatory effects at different organ systems, such as the central nervous system, immune system, and the gastrointestinal system. Due to its broad effects within the body and its safety profile, CBD has become a topic of therapeutic interest.

This literature review summarizes previous research findings with regard to the effect of CBD on the gastrointestinal (GI) system, including its effects at the molecular, cellular, organ, and whole-body levels. Both pre-clinical animal studies and human clinical trials are reviewed.

The results of the studies included in this literature review suggest that CBD has significant impact on intestinal permeability, the microbiome, immune cells and cytokines. As a result, CBD has been shown to have therapeutic potential for GI disorders such as inflammatory bowel disease (IBD).

Furthermore, through interactions with the gut, CBD may also be helpful in the treatment of disorders outside the GI system, such as non-alcoholic liver disease, postmenopausal disorders, epilepsy, and multiple sclerosis. In the future, more mechanistic studies are warranted to elucidate the detailed mechanisms of action of CBD in the gut. In addition, more well-designed clinical trials are needed to explore the full therapeutic potential of CBD on and through the gut.”

https://pubmed.ncbi.nlm.nih.gov/39404382/

“CBD has exhibited modulatory effects on both the intestinal barrier permeability and the gut microbiome. In addition, CBD has displayed therapeutic potential for the treatment of GI disorders such as IBD. Furthermore, CBD may produce therapeutic effects on diseases outside the GI system by regulating gut–liver, gut–bone, and gut–brain axes.”

https://www.mdpi.com/2073-4409/13/19/1618

Meta-analysis of the Therapeutic Impact of Cannabinoids in Inflammatory Bowel Disease

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“Background: With the increasing legalization of medical and recreational cannabis, patients and providers have growing interest in the role of cannabinoids in treating inflammatory bowel disease. Prior meta-analysis has shown inconclusive evidence for efficacy of cannabinoids. We sought to produce an up-to-date meta-analysis that pools new data to evaluate the therapeutic effects of cannabinoids in both Crohn’s disease (CD) and ulcerative colitis (UC).

Methods: PubMed, Embase, CENTRAL and CINAHL were queried for randomized-controlled trials evaluating the impact cannabinoids in CD or UC. Random effects modeling was used to compute pooled estimates of risk difference. Heterogeneity was assessed using I2.

Results: Eight studies, including 4 studies of CD, 3 studies of UC, and 1 study of both diseases met inclusion criteria. Among 5 studies of CD, a statistically significant decrease in clinical disease activity following intervention was observed (risk ratios [RR], -0.91; 95% CI, CI:1.54 to CI:0.28, I2 = 71.9%). Clinical disease activity in UC was not significantly lower in the pooled analysis (RR, -2.13; 95% CI, -4.80 to 0.55; I2 = 90.3%). Improvement in quality of life (QoL) was observed in both CD and UC combined (RR, 1.79; 95% CI, 0.92-0.2.66; I2 = 82.8%), as well as individually. No differences were observed in the analysis on endoscopic disease activity and inflammatory markers.

Conclusions: This meta-analysis of clinical trials suggests that cannabinoids are associated with improved quality of life in both CD and UC, as well as improved disease activity but not inflammation.”

https://pubmed.ncbi.nlm.nih.gov/39197096/

https://academic.oup.com/ibdjournal/advance-article-abstract/doi/10.1093/ibd/izae158/7743320?redirectedFrom=fulltext&login=false

Cannabinoids for Inflammatory Bowel Disease: A Scoping Review

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“Purpose: Inflammatory bowel disease (IBD) has two main variants, ulcerative colitis (UC) and Crohn’s disease (CD), which are characterized by a cycle of remission and relapse. The aim of this scoping review is to understand the landscape of unprescribed and prescribed cannabis use among patients with IBD and investigate objective clinical benefits. 

Methodology: A literature search was performed across Medline, Embase via Ovid, Scopus, and Cochrane Library databases. We included 40 studies (14 abstracts/letters, 7 randomized controlled trials [RCTs], 6 cohort studies [2 case-matched], 10 cross-sectional surveys, and 3 meta-analyses) in the review. 

Results: Between 11% and 17.6% of surveyed patients used cannabis for symptom control with a lifetime prevalence of 39.8-78.2%. Patients reported reduced abdominal pain, emotional distress, stool frequency, and anorexia. There was a higher rate of depression, tobacco, and alcohol use among patients with IBD who used cannabis. Individual studies showed patients who were prescribed cannabis were more likely to have had surgery for IBD (14.5% vs. 4.7%, p = 0.0008), require future abdominal surgery (odds ratio = 5.03), report a lower quality of life (p = 0.0001), currently be on corticosteroids (18.1% vs. 10.4%, p = 0.04) and opioids (27.7% vs. 6.4%, p = 0.0001). RCTs of cannabinoids reported mild reductions in disease activity and variable endoscopic inflammation improvement. 

Conclusions: Patients who use cannabis for IBD are a cohort with refractory disease and lower quality of life who report improvements in symptom management. However, the ability to reduce underlying disease activity appears very modest. Further trials using refined cannabinoid formulations may define a use in IBD.”

https://pubmed.ncbi.nlm.nih.gov/39029906/

https://www.liebertpub.com/doi/10.1089/can.2024.0061

High cannabigerol hemp extract moderates colitis and modulates the microbiome in an inflammatory bowel disease model

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“Cannabis sativa L. has a long history of medicinal use, particularly for gastrointestinal diseases. Patients with inflammatory bowel disease (IBD) report using cannabis to manage their symptoms, despite little data to support the use of cannabis or cannabis products to treat the disease.

In this study, we utilize the well-described dextran sodium sulfate (DSS) model of colitis in mice to assess the impact of commercially available, non-euphorigenic, high cannabigerol (CBG) hemp extract (20 mg/mL cannabigerol, 20.7 mg/mL cannabidiol, 1 mg/mL cannabichromene) on IBD activity and the colonic microbiome. Mice were given 2% DSS in drinking water for 5 days, followed by 2 days of regular drinking water. Over the 7 days, mice were dosed daily with either high CBG hemp extract or matched vehicle control.

Daily treatment with high CBG hemp extract dramatically reduces the severity of disease at the histological and organismal levels as measured by decreased disease activity index, increased colon length, and decreases in percent colon tissue damage. 16S rRNA gene sequencing of the fecal microbiota reveals high CBG hemp extract treatment results in alterations in the microbiota, that may be beneficial for colitis. Finally, using metabolomic analysis of fecal pellets, we find that mice treated with high CBG hemp extract have a normalization of several metabolic pathways, including those involved in inflammation.

Taken together these data suggest that high CBG hemp extracts may offer a novel treatment option for patients. 

Significance Statement Using the DSS model of colitis, we show that treatment with high CBG hemp extract reduces the severity of symptoms associated with colitis. Additionally, we show that treatment modulates both the fecal microbiota and metabolome with potential functional significance.”

https://pubmed.ncbi.nlm.nih.gov/39009468/

https://jpet.aspetjournals.org/content/early/2024/07/15/jpet.124.002204

Effects of Cannabinoids on Intestinal Motility, Barrier Permeability, and Therapeutic Potential in Gastrointestinal Diseases

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“Cannabinoids and their receptors play a significant role in the regulation of gastrointestinal (GIT) peristalsis and intestinal barrier permeability. This review critically evaluates current knowledge about the mechanisms of action and biological effects of endocannabinoids and phytocannabinoids on GIT functions and the potential therapeutic applications of these compounds.

The results of ex vivo and in vivo preclinical data indicate that cannabinoids can both inhibit and stimulate gut peristalsis, depending on various factors. Endocannabinoids affect peristalsis in a cannabinoid (CB) receptor-specific manner; however, there is also an important interaction between them and the transient receptor potential cation channel subfamily V member 1 (TRPV1) system.

Phytocannabinoids such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) impact gut motility mainly through the CB1 receptor. They were also found to improve intestinal barrier integrity, mainly through CB1 receptor stimulation but also via protein kinase A (PKA), mitogen-associated protein kinase (MAPK), and adenylyl cyclase signaling pathways, as well as by influencing the expression of tight junction (TJ) proteins.

The anti-inflammatory effects of cannabinoids in GIT disorders are postulated to occur by the lowering of inflammatory factors such as myeloperoxidase (MPO) activity and regulation of cytokine levels. In conclusion, there is a prospect of utilizing cannabinoids as components of therapy for GIT disorders.”

https://pubmed.ncbi.nlm.nih.gov/38928387/

“In summary, our narrative review highlights the complex interaction between cannabinoids and gastrointestinal physiology, shedding light on their potential therapeutic applications in the treatment of GIT diseases.

The findings highlight the diverse effects of cannabinoids on motility, intestinal permeability, and inflammation, which are mediated by interactions with endocannabinoids and cannabinoid receptors. It is noteworthy that cannabinoids such as THC and CBD exhibit receptor-specific effects on GIT motility via CB1 receptors, causing inhibition of muscle contractility, which may suggest targets for therapeutic interventions. Moreover, the involvement of CB1 and CB2 receptors in regulating intestinal permeability underscores the complexity of mechanisms mediated by cannabinoids in gastrointestinal health.

In addition, cannabinoids show promise as anti-inflammatory agents, offering potential benefits in the treatment of Crohn’s disease, ulcerative colitis, and IBD. Moreover, their role in modulating intestinal motility and relieving pain implicates cannabinoids as potential agents for improving quality of life in gastrointestinal disorders, especially chronic such as IBS. The results of clinical trials and data on the adverse effects of phytocannabinoids indicate that further research is needed to elucidate the exact mechanisms and optimize therapeutic strategies to realize the full potential of cannabinoids in clinical practice.”

https://www.mdpi.com/1422-0067/25/12/6682

Cannabidiol-Loaded Solid Lipid Nanoparticles Ameliorate the Inhibition of Proinflammatory Cytokines and Free Radicals in an In Vitro Inflammation-Induced Cell Model

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“Cannabidiol (CBD) is a non-psychoactive compound derived from Cannabis sativa. It has demonstrated promising effects in combating inflammation and holds potential as a treatment for the progression of chronic inflammation. However, the clinical application of CBD is limited due to its poor solubility and bioavailability.

This study introduces an effective method for preparing CBD-loaded solid lipid nanoparticles (CBD-SLNs) using a combination of low-energy hot homogenization and ultrasonication. We enhanced this process by employing statistical optimization with response surface methodology (RSM). The optimized CBD-SLN formulation utilizes glyceryl monostearate as the primary lipid component of the nanocarrier. The CBD-SLN formulation is screened as a potential tool for managing chronic inflammation. Stable, uniformly dispersed spherical nanoparticles with a size of 123 nm, a surface charge of -32.1 mV, an encapsulation efficiency of 95.16%, and a drug loading of 2.36% were obtained.

The CBD-SLNs exhibited sustained release properties, ensuring prolonged and controlled CBD delivery, which could potentially amplify its therapeutic effects. Additionally, we observed that CBD-SLNs significantly reduced both reactive oxygen and nitrogen species and proinflammatory cytokines in chondrocyte and macrophage cell lines, with these inhibitory effects being more pronounced than those of free CBD.

In conclusion, CBD-SLNs demonstrated superiority over free CBD, highlighting its potential as an effective delivery system for CBD.”

https://pubmed.ncbi.nlm.nih.gov/38731964/

https://www.mdpi.com/1422-0067/25/9/4744

[Phytotherapeutic recommendations in medical guidelines for the treatment of gastroenterological diseases – a systematic review]

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“Phytotherapeutics are gaining influence in the treatment of gastroenterological diseases. Their popularity and growing evidence of efficacy contribute to their integration into medical guidelines. A systematic screening identified recommended phytotherapeutic approaches. Based on current scientific data, some recommendations for the use of phytotherapeutic agents are given. For irritable bowel syndrome the use of peppermint oil is “strongly recommended”, especially for pain and flatulence. Other phytotherapeutics such as STW-5, Tibetan Padma Lax or warm caraway oil pads have proven effective in alleviating symptoms. It is “recommended” to integrate them into the treatment concept. For chronic constipation, 30g of fiber per day is recommended. Best data exists for plantago psyllium with moderate evidence and chicory inulin. In case of ulcerative colitis, plantago psyllium as well as the combination of myrrh, chamomile flower extract, and coffee charcoal can be used as a complementary treatment in maintaining remission. There is also an “open recommendation” for curcumin for both, remission induction and maintenance. Some phytotherapeutic treatments (e.g., Artemisia absintium, Boswellia serata) show evidence of effectiveness for the treatment of Crohn’s disease, but data are not yet sufficient for recommendations. Cannabis-based medicines can be considered for abdominal pain and clinically relevant appetite loss if standard therapy is ineffective or contraindicated, but they should not be used for acute inflammation in active Crohn’s disease. Further recommendations for other gastroenterological diseases are discussed. The safety and tolerability of the phytotherapeutics were rated as predominantly “very good” to “acceptable”. Some clear recommendations for the use of phytotherapeutics to treat gastroenterological diseases show their great potential. Due to their wide range of effects, phytotherapeutics can be used very well as a complement to conventional medicines in case of complex regulatory disorders. However, further methodologically well-conducted impact studies would be helpful in order to be able to make further recommendations.”

https://pubmed.ncbi.nlm.nih.gov/38604221/

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-2279-5045


Multi-targeting inulin-based nanoparticles with cannabidiol for effective prevention of ulcerative colitis

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“The pathogenesis of ulcerative colitis (UC) is closely related to severe inflammation, damaged colonic mucosal barrier, increased oxidative stress and intestinal ecological imbalance. However, due to the nonspecific distribution and poor bioavailability of drugs, UC treatment is still a serious challenge. Here, a mitochondria/colon dual targeted nanoparticles based on redox response was developed to effectively alleviate UC.

Cannabidiol nanoparticles (CBD NPs) with a particle size of 143.2 ± 3.11 nm were prepared by self-assembly using polymers (TPP-IN-LA) obtained by modifying inulin with (5-carboxypentyl) triphenyl phosphonium bromide (TPP) and α-lipoic acid (α-LA). Excitingly, the constructed CBD NPs showed excellent mitochondrial targeting, with a Pearson correlation coefficient of 0.76 at 12 h.

The results of animal imaging in vivo showed that CBD NPs could be effectively accumulated in colon tissue. Not only that, CBD showed significant glutathione stimulated release in the presence of 10 mM glutathione at pH 7.4.

The results of in vivo animal experiments showed that CBD NPs significantly ameliorated DSS-induced colonic inflammation by modulating the TLR4-NF-κB signaling pathway. Moreover, CBD NPs significantly improved the histological damage of colon in UC mice, increased the expression level of tight junction protein ZO-1, and effectively restored the intestinal mucosal barrier function and intestinal mucosal permeability.

More importantly, CBD NPs significantly improved the species composition, abundance and amount of short chain fatty acids of intestinal flora in UC mice, thus effectively maintaining the balance of intestinal flora. The dual-targeted and glutathione-responsive nanoparticles prepared in this study provide a promising idea for achieving targeted delivery of CBD for effective treatment of UC.”

https://pubmed.ncbi.nlm.nih.gov/38318477/

https://linkinghub.elsevier.com/retrieve/pii/S2590006424000243

Medical Cannabis Increases Appetite but Not Body Weight in Patients with Inflammatory Bowel Diseases

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“We aimed to elucidate the effect of Medical Cannabis (MC) on appetite and nutritional status among patients with inflammatory bowel disease (IBD). A case series of patients with IBD were initiating treatment with MC for disease-related symptoms, at the IBD clinic of a tertiary referral medical center. Patients’ demographics, anthropometrics, medical history and treatment and MC use were systematically recorded. An appetite and food frequency questionnaire (SNAQ and FFQ) were filled before, and at 3 and 6 months of treatment. Patients with IBD initiating MC were enrolled (n = 149, age 39.0 ± 14.1 years, 42.3% female), and 33.6% (n = 50) were treated for improvement of nutritional status. A modest increase in appetite after 3 months was detected among all patients enrolled (Pv = 0.08), but there were no significant differences in energy or macronutrient intake, and in patients’ body mass index (BMI). A significant appetite improvement after 3 months was detected among 34.0% (n = 17) of patients, but this was not associated with increased caloric intake or BMI at 3 or 6 months. Among patients without increased appetite after 3 months of MC therapy, BMI decreased at 6 months (24.1 ± 3.7 vs. 23.4 ± 3.6, Pv = 0.010). MC may be a potential strategy to improve appetite among some patients with IBD, but not caloric intake or BMI.”

https://pubmed.ncbi.nlm.nih.gov/38201908/

“MC may be a potential strategy to increase appetite among some patients with IBD, which may prevent further weight loss, but is not associated with a significant increase in caloric intake or in BMI.”

https://www.mdpi.com/2072-6643/16/1/78

Dietary Cannabidiol Activates PKA/AMPK Signaling and Attenuates Chronic Inflammation and Leaky Gut in DSS-Induced Colitis Mice

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“Scope: Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gut, accompanied by impaired epithelial integrity, increased macrophage infiltration, and enhanced colon cancer risk.

Methods and results: Cannabidiol (CBD), a phytocannabinoid isolated from cannabis plants, is supplemented into mice diet, and its beneficial effects against dextran sulfate sodium (DSS)-induced experimental colitis is evaluated. Eight-week-old mice were fed a standard diet supplemented with or without CBD (200 mg kg-1 ) for 5 weeks. In the 4th week of dietary treatment, mice were subjected to 2.5% DSS induction for 7 days, followed by 7 days of recovery, to induce colitis. CBD supplementation reduced body weight loss, gross bleeding, fecal consistency, and disease activity index. In addition, CBD supplementation protected the colonic structure, promoted tissue recovery, and ameliorated macrophage infiltration in the colonic tissue, which was associated with the activation of cyclic AMP-protein kinase A, extracellular signal-regulated kinase ½, and AMP-activated protein kinase signaling pathways. CBD supplementation also suppressed NLRP3 inflammasome activation and related pro-inflammatory marker secretion. Consistently, CBD feeding reduced tight junction protein claudin2 and myosin light chain kinase in DSS-treated mice.

Conclusion: Dietary CBD protects against inflammation and colitis symptoms induced by DSS, providing an alternative approach to IBD management.”

https://pubmed.ncbi.nlm.nih.gov/38175840/

https://onlinelibrary.wiley.com/doi/10.1002/mnfr.202300446