Category Archives: Inflammatory Bowel Disease

Efficacy of Exogenous Cannabinoids in Pre-Clinical Models of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

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“Background: Exogenous cannabinoids are considered promising therapeutic candidates for inflammatory bowel disease (IBD). However, robust pre-clinical evidence supporting its efficacy remains limited. This systematic review and meta-analysis aimed to evaluate the therapeutic effects of exogenous cannabinoids in animal models of IBD.

Methods: Controlled experimental studies involving animal models of IBD that evaluated the effects of exogenous cannabinoids compared to untreated models were included. Four databases (PubMed, Embase, Web of Science, and the Cochrane Library) were searched up to August 26, 2025. Two independent reviewers conducted study selection, data extraction, and the risk-of-bias assessment. The risk-of-bias assessment was performed using the Systematic Review Center for Laboratory Animal Experimentation tool. Meta-analyses were performed using standardized mean differences (SMDs) and random-effects models. The study was registered in INPLASY (INPLASY202540009).

Results: Twenty-seven pre-clinical studies involving 408 animals were included. Compared with controls, exogenous cannabinoids significantly reduced disease activity index (SMD = -3.43; 95% confidence interval [CI]: -4.98 to -1.89; I2 = 83%) and histopathological score (SMD = -4.46; 95% CI: -6.37 to -2.54; I2 = 84%). It also decreased levels of myeloperoxidase (MPO), TNF-α, IL-6, and IL-1β. However, substantial heterogeneity was noted across several outcomes.

Interpretation: Exogenous cannabinoids show beneficial effects in pre-clinical IBD models, likely through anti-inflammatory, antioxidant, and barrier-enhancing mechanisms. These findings provide a supportive foundation for future translational research. Nevertheless, the overall certainty of the evidence is limited by unclear randomization, lack of blinding, high heterogeneity, and small sample sizes. Although some clinical trials have already begun exploring its therapeutic potential, further rigorous and standardized animal studies are needed to clarify mechanisms, optimize dosing, and reinforce the translational pathway.”

https://pubmed.ncbi.nlm.nih.gov/41804536

The dual roles of natural cannabidiol in combating oxidative stress and inflammation: A potential intestinal guardian

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“Cannabidiol (CBD), a non-psychoactive and non-addictive phytocannabinoid derived from Cannabis sativa L., has attracted increasing attention for its therapeutic potential in intestinal diseases.

Accumulating evidence indicates that CBD exerts prominent antioxidant and anti-inflammatory effects within the gastrointestinal tract. Oxidative stress and redox imbalance are key drivers of epithelial barrier dysfunction, chronic inflammation, and disease progression in disorders such as inflammatory bowel disease (IBD) and colorectal cancer (CRC).

This review focuses on the redox-related mechanisms underlying CBD’s intestinal protective actions, highlighting its ability to regulate reactive oxygen species (ROS) production, activate the Nrf2-Keap1 antioxidant pathway, and modulate redox-sensitive inflammatory signaling, including NF-κB and the NLRP3 inflammasome.

In parallel, CBD engages the endocannabinoid system (ECS) and related receptors to preserve epithelial barrier integrity, regulate gut microbiota composition, and modulate intestinal oxidative stress and inflammation. We further discuss emerging evidence linking CBD’s regulation in the gut to systemic effects along the gut-organ axis, including the gut-brain and gut-liver axes.

Overall, this review synthesizes current evidence on how CBD integrates redox modulation, inflammation control, and intestinal barrier protection, providing a mechanistic framework for its potential application in intestinal disease and health.”

https://pubmed.ncbi.nlm.nih.gov/41713221

“CBD, as a non-psychoactive phyto-CB, has demonstrated substantial therapeutic potential for gastrointestinal health. By modulating the ECS, CBD enhances intestinal barrier integrity, regulates GM composition, and mitigates oxidative stress and inflammation. These effects contribute to its promising role in treating oxidative stress-related gastrointestinal conditions and maintaining intestinal homeostasis.”

https://www.sciencedirect.com/science/article/pii/S2213231726000492?via%3Dihub

Altered endocannabinoid system gene expression in inflammatory bowel disease mucosa: New perspectives in inflammatory bowel disease management

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“Background: Inflammatory bowel disease (IBD) is a broad classification including various chronic inflammatory gastrointestinal conditions that comprises two main disorders: Crohn’s disease (CD) and ulcerative colitis (UC). The key components of the endocannabinoid system (ECS) are highly expressed within the gastrointestinal tract, playing a crucial role in maintaining homeostasis and providing protection against intestinal inflammation.

Aim: To investigate possible impairment of the genes belonging to ECS by analyzing their expression levels in IBD patients and controls.

Methods: The paired biopsies of endoscopically inflamed (IM) and noninflamed (NIM) colonic mucosa from 30 IBD-diagnosed patients (17 UC and 13 CD), and the colonic mucosa from 17 non-IBD controls, were collected and analyzed. The messenger RNA expression level of cannabinoid receptor (CNR) 1, CNR 2, diacylglycerol lipase alpha, diacylglycerol lipase beta, fatty acid amide hydrolase (FAAH), G protein-coupled receptor (GPR) 18, GPR55, monoglyceride lipase, peroxisome proliferator-activated receptor gamma (PPARG), and transient receptor potential cation channel, subfamily V, member 1 (TRPV1) was determined by quantitative polymerase chain reaction.

Results: Six out of the 10 investigated genes were found to be dysregulated in at least one comparison. Specifically, in IBD patients, FAAH, PPARG, and TRPV1 were significantly downregulated in IM compared to NIM (FAAH, P = 0.012; PPARG, P = 0.001; TRPV1, P = 0.032) and in IM compared to controls (FAAH, P < 0.001; PPARG, P < 0.001; TRPV1, P = 0.002). An opposite trend was reported for CNR2 and GPR55, which showed an upregulation in IM compared to NIM (CNR2, P = 0.005; GPR55, P = 0.001).

Conclusion: We found a significant impairment of the ECS in IBD patients. Further analyses on larger cohorts are needed for a better understanding of the potential of cannabinoids in managing IBD.”

https://pubmed.ncbi.nlm.nih.gov/41700170

“The role of ECS in gastrointestinal physiology and the exact involvement of this system in IBD are still under investigation. Given this, our preliminary findings of the impairment of analyzed ECS genes in the IBD mucosa may serve as a basis for more in-depth research in larger cohorts to better understand the potential of cannabinoids in the management of IBD. After the introduction of artificial intelligence in the multi-omics drug delivery pipeline, future therapeutic targets should emerge, allowing for an even more personalized approach to IBD patients.”

https://www.wjgnet.com/1948-5190/full/v18/i2/113576.htm?appgw_azwaf_jsc=pjmb6U0PmJ8Jhw6KK0wkG7dIIANmqb_h-_TRqMyZe5S0n2nN12xjj6IEXzXltFiMGkrPy5gdVTqeL9FpqEwxg2IRdQtlxGphrdrCTC-8UB5iTS-53eOUekwL8V6ddoD3rUPUEsVlA14gjfLy8jmezIuYPV2vjfZ-Qoy-hEGym4pY7k9iS4yH7a1n8E6oEldBMV5stbazp3UctrqNhXMRb1bGo8NvE8b14zuvRdlvOI8MhNFNMTV-JysZCgnImMJg1XC1kSYNzlziNr4LuxGaowrDxyFS9KaRq_rQ_cNEf6ip8MXlhXSmgIWPhdPyy1s0xQclW9zOboCaV9pRBR83KQ

Hemp seed mitigates colonic inflammation through macrophage polarization and microbiota-barrier axis restoration

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“Hemp seed, historically considered a byproduct of the hemp fiber industry, has gained increasing attention for its nutritional and functional properties. Recent advances in hemp seed research have elucidated its benefits for gut health; however, its impact on colitis remains unclear.

In this study, we demonstrate that hemp seed consumption reduced colonic inflammation and mitigated tissue injury in an experimental colitis mouse model.

Notably, hemp seed reduced macrophage infiltration and promoted a phenotypic shift from pro-inflammatory M1 to anti-inflammatory M2 macrophages. It also enhanced intestinal barrier function by restoring goblet cells, upregulating tight junction proteins, and reducing systemic lipopolysaccharide translocation. Furthermore, hemp seed optimized gut microbiota composition by enriching beneficial taxa, particularly Bifidobacterium, while suppressing colitis-associated genera.

Collectively, these findings indicate that hemp seed, as a whole-food dietary approach, confers protection against colitis by modulating immune responses, preserving barrier integrity, and reshaping gut microbiome.

These results underscore the potential of hemp seed as a sustainable nutritional strategy for promoting gut health.”

https://pubmed.ncbi.nlm.nih.gov/41328036

“The present study demonstrates that dietary hemp seed reduced colonic inflammation and alleviated tissue injury in the DSS-induced colitis mouse model.”

“Collectively, our study provides insights into the role of hemp seed in gut health and reinforces its potential as a promising and sustainable dietary intervention for IBD management.”

https://pubs.rsc.org/en/content/articlelanding/2026/fo/d5fo04119h

Combination of CBD with minor cannabinoid CBDV suppresses CXCR4 via CB2 receptor and alleviates colitis in mice

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“Cannabis extracts, particularly those rich in cannabinoids like cannabidiol (CBD), have shown potential anti-inflammatory properties and are being examined in managing conditions involving inflammation.

One proposed mechanism is their modulation of chemokine expression and function in immune cells. C-X-C chemokine receptor type 4 (CXCR4) plays a pivotal role in immune cell trafficking and is implicated in the pathogenesis of inflammatory bowel disease (IBD).

Given emerging evidence that cannabinoids can influence chemokine signaling, we explored whether they could downregulate CXCR4 in immune cells.

In this study, we show that the combination of CBD and cannabidivarin (CBDV) at a 20:1 ratio significantly reduces CXCR4 expression in MOLT-4 cells, murine splenocytes and human peripheral blood mononuclear cells. This reduction in CXCR4 expression correlated with impaired chemotactic responses and suppressed actin polymerization, effects that were abrogated by CB2 receptor inhibition. In vivo, the CBD:CBDV combination ameliorated disease severity in a murine model of DSS-induced colitis, improving disease activity index, colon length, and histological outcomes. These therapeutic benefits were absent in CB2 knockout mice, confirming CB2 dependence.

Our findings support a CB2-mediated mechanism by which the CBD:CBDV combination downregulates CXCR4, providing a mechanistic basis for the entourage effect and highlighting the significance of CBDV as a modulator of the CBD effect.

Overall, this study implicates cannabinoid combinations as a promising therapeutic strategy for treating IBD.”

https://pubmed.ncbi.nlm.nih.gov/41237459

Isoorientin Modulates Gut Microbes and Their Metabolites to Alleviate Caco-2 Cell Monolayer Inflammation by Reducing Intestinal Permeability via P-Gp/eCBs

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“Introduction: Isoorientin (ISO) is a naturally occurring flavonoid that studies have shown to have strong experimental antioxidant, anti-inflammatory, anti-diabetic and anti-obesity properties. It has been shown that ISO alleviates Dextran sodium sulfate (DSS) induced colitis in mice by modulating gut microbes and their metabolites. The aim of this study was to modulate gut microbes and their metabolism by ISO to investigate its anti-inflammatory effects and its specific molecular mechanisms in a lipopolysaccharide (LPS)-induced monolayer inflammation model in Caco-2 cells.

Methods: Feces from ISO-treated DSS colitis mice were collected and gut flora culture supernatants were prepared. Detection of the effect of intestinal flora supernatants on the monolayer barrier of Caco-2 cells by inoculation of Caco-2 cells into the Transwell transmembrane culture system to simulate the intestinal mucosal barrier.

Results: The results revealed that ISO-conditioned intestinal flora supernatant significantly increased TEER values, decreased intestinal epithelial FITC-dextran flux permeability, and restored LPS-induced occludin, ZO-1 protein expression in Caco-2 cells. Meanwhile, intestinal flora supernatant significantly ameliorated the LPS-induced inflammatory response. In addition, ISO further enhanced its protective effect on intestinal permeability by regulating the expression of P-glycoprotein (P-gp) and endogenous cannabinoid system (eCB)-related proteins, which may attenuate the inflammatory response by activating the P-gp/eCB signaling pathway.

Conclusion: The present study offers fresh perspectives into the application of ISO-conditioned intestinal flora supernatant as a potential anti-inflammatory agent and intestinal barrier protector in vitro. The unique regulation of the P-gp/eCBs pathway by ISO-conditioned intestinal flora supernatant was the novel mechanistic insights provided in this study.”

https://pubmed.ncbi.nlm.nih.gov/41126978/

“Overall, these findings could be instrumental in formulating treatment approaches involving ISO for managing inflammation-associated conditions in patients with IBD.”

https://www.dovepress.com/isoorientin-modulates-gut-microbes-and-their-metabolites-to-alleviate–peer-reviewed-fulltext-article-JIR

“Isoorientin is a flavonoid found in cannabis and hemp plants.”

  • “Hemp seed: Isoorientin has been detected in the seeds of Cannabis sativa (hemp) and shown to possess bioactivity, including neuroprotective effects.
  • Cannabis plant: The overall flavonoid content, including isoorientin, can vary depending on environmental factors like growing conditions.”

Efficacy of non-psychotropic Cannabis sativa L. standardized extracts in a model of intestinal inflammation

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“Background: The use of Cannabis sativa L. (Cannabis) was reported by observational studies on inflammatory bowel diseases (IBD) patients. However, this indication is poorly supported by clinical trials. Several pre-clinical studies demonstrated the anti-inflammatory activity of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and cannabidiol (CBD) at intestinal level. On the contrary, minor cannabinoids, such as cannabigerol (CBG), were less investigated. Moreover, several authors suggested that complex Cannabis extracts might display a higher efficacy in respect to pure cannabinoids against inflammatory disorders.

Methods: This study was aimed at investigating the role of Cannabis extracts, standardized in CBD and CBG content, in a model of in vitro-induced intestinal inflammation using CaCo-2 cells. Inflammatory mediators at transcriptional (PCR arrays) and protein level (ELISA assays) were investigated and correlated with enterocyte layer permeability. The two evaluated extracts, A and B, come from the mix of the same Cannabis varieties (Cannabis sativa L. Chemotype III and Chemotype IV), and are standardized in CBD and CBG at the same level, by changing the polarity of the primary extraction solvents.

Results: Pro-inflammatory cytokines involved in IBD, such as IL-1β and IFN-γ, induced the expression and the release of chemokines for lymphocytes (CXCL-9, CXCL-10, CCL20) in CaCo-2, while Cannabis extracts (100 µg/mL) or individual compounds (8 µM) showed inhibitory activity. After simulated digestion, extract A abrogated the release of CCL-20, while extract B abrogated the release of CXCL-9 and CXCL-10. The inhibition of CXCL-9 was demonstrated at transcriptional level also. The inhibitory activity paralleled with the content of CBD or CBG, acting at least in part through NF-κB impairment (-42% and – 66%, respectively). However, Cannabis extracts showed greater effect in the CaCo-2-THP-1 co-culture inflammation model compared to individual cannabinoids, thus partially recovering the epithelial barrier measured by transepithelial electrical resistance (TEER), and zonula occludens (ZO-1) expression.

Conclusions: Data collected within this study showed the importance of standardization and extraction method reproducibility through manufacturing and process control, besides demanding future investigations focusing on the effect of Cannabis extracts against intestinal inflammation, which show in this context effects higher than individual cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/41053843/

“At the best of our knowledge, this is one of the few works in which the biological properties of standardized Cannabis extracts were compared with their major cannabinoids. More generally, the role of CBG in intestinal inflammation is matter of interest for its non-psychotropics nature, but it was investigated by few articles before. However, our data suggest that the use of Cannabis extracts against intestinal inflammation might be preferred in respect to single cannabinoids. Nevertheless, specific studies should be conducted with the aim to translate the evidence to in vivo models.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00335-2

Orally Administered CBD/CBG Hemp Extract Reduces Severity of Ulcerative Colitis and Pain in a Murine Model

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“Background: Ulcerative colitis (UC) is an autoimmune disorder characterized by inflammation of the mucosa that gives rise to a disrupted epithelial morphology. Persistent or recurrent inflammation and the debilitating nature of the associated symptoms make treatment of UC challenging. Cannabinoids derived from Cannabis sativa L. have been used for treatment of gastrointestinal disorders due to the wide-ranging therapeutic benefits of these compounds. 

Methods: We evaluated a commercial hemp extract, high in cannabigerol (CBG) and cannabidiol (CBD), as a novel treatment for UC symptoms using the dextran sodium sulfate (DSS) model in mice. Hemp extract was administered via two different routes of administration, intraperitoneal (i.p) and oral (p.o). 

Results: Specifically, we observed that cannabinoid treatment reduced damage to the colonic epithelium. We also observed that CBG/CBD rich hemp extracts help reduce pain-related responses in these animals. 

Conclusions: Together, the data suggest that cannabinoid administration has the potential to be an effective alternate therapeutic option for UC management.”

https://pubmed.ncbi.nlm.nih.gov/40943856/

“Our current findings suggest that minor cannabinoids, particularly CBD and CBG, may prove to be useful, novel therapies for treating IBD. These findings are important because patients already report using cannabis and cannabinoid-based products for managing their symptoms, despite little clinical data to support the use of high-THC products for treating IBD.

In conclusion, our data suggest that HE enriched for CBD and CBG may offer therapeutic potential as a treatment for IBD patients.”

https://www.mdpi.com/2077-0383/14/17/6095

Cannabidiol Enhances the Therapeutic Efficacy of Olsalazine and Cyclosporine in a Murine Model of Colitis

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“Current therapies for inflammatory bowel disease (IBD), such as olsalazine and cyclosporine, often exhibit limited long-term efficacy and are associated with adverse effects. Cannabidiol (CBD), a non-psychoactive phytocannabinoid, shows promise for its anti-inflammatory properties, though its effectiveness as a monotherapy remains inconclusive.

This study investigates the therapeutic potential of combining low-dose CBD (10 mg/kg) with olsalazine (50 mg/kg) or cyclosporine (2.5, 5 mg/kg) in dextran sulphate sodium (DSS)-induced acute and chronic colitis models in mice.

Disease severity was assessed via disease activity index (DAI), colon morphology, cytokine and chemokine expression, myeloperoxidase (MPO) activity, systemic inflammatory markers, and glucagon-like peptide-1 (GLP-1) regulation. Safety evaluations included haematology and plasma biochemistry. DSS-treated mice showed elevated DAI scores, colon shortening, heightened inflammation, and organ enlargement. Combination therapies significantly ameliorated colitis, reducing DAI, MPO activity, and inflammatory cytokines, while restoring colon length and GLP-1 levels-without inducing liver or kidney toxicity.

These findings demonstrate that combining a low dose of CBD with standard IBD drugs enhances therapeutic efficacy while minimizing side effects, supporting its integration into future combination strategies for more effective and safer IBD management.”

https://pubmed.ncbi.nlm.nih.gov/40869234/

“Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has emerged as a promising therapeutic candidate for the treatment of inflammatory conditions, including IBD. CBD’s anti-inflammatory, antioxidant, and immunomodulatory effects are mediated through multiple pathways, including the modulation of cytokine production, inhibition of oxidative stress, and interaction with the endocannabinoidome (eCBome).”

“Collectively, our data provide a strong preclinical rationale for leveraging low-dose CBD to enhance the efficacy of existing IBD therapies. The reproducible synergistic effects observed in acute and chronic colitis models—spanning clinical, morphological, molecular, metabolic, and safety domains—underscore CBD’s potential as a safer adjunct agent. CBD co-therapy with CSA or olsalazine offers a multifaceted approach to IBD treatment—achieving superior disease suppression, preserving intestinal and systemic homeostasis, and maintaining an acceptable safety profile. This strategy holds promise for improving patient outcomes while potentially reducing the doses and side effects of conventional IBD drugs. Clinical trials will be essential to confirm safety and efficacy in human IBD patients.”

https://www.mdpi.com/1422-0067/26/16/7913

Inflammatory bowel disease patients believe cannabis and cannabidiol oil relieve symptoms

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“Background: Patients with Inflammatory bowel disease (IBD) often seek alternative therapies for symptom management. This study investigates the perceptions, consumption patterns, and reported outcomes of cannabis and cannabidiol (CBD) oil use among IBD patients and controls.

Methods: A 37-question survey was administered to 139 participants (IBD patients, n = 93; control/non-IBD participants, n = 33) to assess usage frequency and beliefs regarding cannabis and CBD oil as treatment for IBD. The survey also evaluated the impact of these substances on IBD symptoms, quality of life, and opioid use.

Results: Cannabis consumption was higher in IBD patients (57, 53.8%) than controls (15, 45.5%) with both groups strongly supporting medical cannabis use (IBD; 92, 86.8% vs. controls; 29, 84.9%). Most IBD patients believed cannabis (67, 63.2%), CBD oil (60, 56.6%), corticosteroids (77, 73.3%), and biologics/immunosuppressants (85, 81.0%) had a somewhat-extremely beneficial effect in relieving IBD symptoms. Over 50% of IBD cannabis users reported relief from abdominal pain, other pain, stress, anxiety, depression, and nausea/vomiting, with Crohn’s disease patients experiencing significantly more relief than ulcerative colitis patients for certain symptoms (p < 0.05). Notably, 19.4% of IBD patients reported decreased opioid use, and 14.5% reported induced remission with cannabis or CBD oil.

Conclusions: Consumption of cannabis and CBD oil was perceived as beneficial for relieving IBD, with many reporting significant symptom relief from using these substances. The strong support of cannabis and CBD oil as medical treatments and therapeutic effects highlights the potential for cannabis and CBD oil as treatments in IBD.”

https://pubmed.ncbi.nlm.nih.gov/40687272/

“Recent preclinical studies have suggested that cannabinoids, including CBD and THC, may reduce gastrointestinal inflammation and modulate intestinal motility. The presence of cannabinoid receptors in the gut, along with the anti-inflammatory effects of some cannabinoids, has led researchers to explore the potential for therapeutic applications of cannabis in the treatment of IBD.”

“Animal studies of the chemistry and physiology of cannabinoids have shown potential anti-inflammatory, antidiarrheal, and nociceptive-limiting effects, paralleling the growing interest in cannabis as a treatment option for IBD.

Human studies have also indicated that there may be a benefit in controlling IBD symptoms and improving quality of life. Additionally, anecdotal reports and observational studies have highlighted potential benefits in reducing disease activity and managing symptoms like abdominal pain, cramping, joint pain, and diarrhea.”

https://www.academia.edu/2994-435X/2/2/10.20935/AcadMed7773