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

“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

Peptide profiling and antioxidant characterization of the simulated gastrointestinal digest of hemp seed proteins

“Hemp seeds have a long history as a foodstuff and are traditionally associated with longevity in China.

In this study, the simulated digestion of hemp seed protein (HSP) was investigated to evaluate its health benefits.

After digestion, a higher degree of hydrolysis, elevated DPPH and ABTS radical-scavenging activities, and enhanced FRAP reducing power were observed, reflecting the digestibility and antioxidant potential of HSP. Moreover, the HSP digest improved HepG2 cell viability under H2O2-induced oxidative stress.

Peptidomic analysis identified 1101 peptides (75 % < 1 kDa), among which 89 were predicted to be bioactive. From these, 27 water-soluble, non-toxic peptides were further examined. Molecular docking showed that most peptides had stronger binding affinities to ABTS, DPPH, and Keap1 than glutathione.

A 100-ns molecular dynamics simulation further confirmed the antioxidant potential of the peptides, highlighting HSP digest as a promising source of antioxidant peptides with direct radical-scavenging activity and potential Nrf2-pathway activation.”

https://pubmed.ncbi.nlm.nih.gov/41075652

“This study demonstrated that simulated gastrointestinal digestion of HSP yields a peptide-rich hydrolysate with potent antioxidant effects. The HSP digest showed significantly improved free-radical scavenging capacity and protection against oxidative stress in cells.”

https://www.sciencedirect.com/science/article/abs/pii/S030881462503910X?via%3Dihub

The effect of medical cannabis on gastrointestinal symptoms in fibromyalgia and disorders of gut-brain interaction: a patient‑centred real‑world observational study

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“Objectives: Fibromyalgia (FM) is frequently associated with gastrointestinal (GI) disorders such as disorders of gut-brain interaction (DGBIs). Current treatments for FM offer limited relief, leading to the exploration of alternative therapies such as medical cannabis. This study evaluates in the impact of Bedrocan® medical cannabis in FM patients and GI symptoms over six months.

Methods: Sixty FM patients were enrolled, receiving a Bedrocan® cannabis treatment for 6 months. A standardised questionnaire evaluating upper and lower GI symptoms and the Revised Fibromyalgia Impact Questionnaire (FIQR) evaluating FM severity were administered at enrolment and 3 and 6-month follow-up evaluations. DGBIs, in particular, irritable bowel syndrome (IBS), and functional dyspepsia (FD) were diagnosed according to Rome IV criteria.

Results: Forty-six/60 (76.6%) FM patients fulfilled the diagnostic criteria for at least one DGBI; 10/60 (16.7%) FM patients fulfilled the diagnostic criteria for IBS, 17/60 (28.3%) for FD, and 19/60 (31.7%) for both IBS/FD. The FIQR severity score log-transformed significantly decreased during the months-by-month comparison period (repeated-measures ANOVA, p<0.001). Among GI symptoms, the log-transformed intensity-frequency score of epigastric pain, epigastric burning, abdominal pain, abdominal distension, and bloating significantly decreased during the month-by-month comparison period (repeated-measures ANOVA, p<0.01).

Conclusions: This study supports Bedrocan® medical cannabis as an alternative treatment for FM with a potential effect on FD and IBS symptoms. Despite positive outcomes, the study acknowledges limitations, such as the small sample size and absence of a control group. Further research is required to confirm the efficacy of medical cannabis in FM patients, particularly regarding its effects on GI symptoms.”

https://pubmed.ncbi.nlm.nih.gov/40556630/

https://www.clinexprheumatol.org/abstract.asp?a=22389

Targeting Gastrointestinal Cancers with Cannabidiol: Mechanisms, Challenges, and Therapeutic Implications

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“Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, has gained significant attention for its potential therapeutic effects across various types of cancer.

This manuscript presents a systematic review of the current evidence on the application of CBD in gastrointestinal (GI) malignancies, with a focus on gastric and colorectal cancers.

The review aims to explore CBD’s mechanisms of action, including its effects on apoptosis, cell cycle regulation, angiogenesis, inflammation, and its potential to enhance the efficacy of conventional therapies. Furthermore, it examines the challenges involved in translating preclinical findings into clinical settings, such as issues related to bioavailability and regulatory hurdles.

The review also addresses future directions for the use of CBD in combination therapies and its potential to overcome resistance mechanisms in GI cancers. By analyzing the molecular pathways modulated by CBD, this manuscript seeks to offer a comprehensive understanding of its therapeutic potential, contributing to the future of GI cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/40461928/

https://link.springer.com/article/10.1007/s12032-025-02790-6

Complex forming properties of cannabinoid acids in a green solvent and bioassays focused on gastric disease caused by Helicobacter pylori infection

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“The main objective of the present study was to determine the protolytic and coordination properties of two bioactive cannabinoid acids (cannabidiolic acid and cannabigerolic acid) in ethyl alcohol-water mixture (50/50, v/v).

The complexation properties of these acids with copper(II) and zinc(II) ions were determined by potentiometric and ESI-MS methods. UV-Vis absorption spectra for the copper(II) systems confirmed the speciation models with one type of complex indicating coordination with completely deprotonated dinegative ligand molecule. The occurrence of precipitation at lower pH values limited the ability to determine complexes under these conditions.

The research also aimed to identify potential biological and medicinal applications of cannabinoid acids and their complexes with zinc(II). The ability of these compounds to influence the growth of human Hs68 skin fibroblasts and AGS gastric adenocarcinoma cells was investigated. Furthermore, these structures were tested against Helicobacter pylori strains, one of the factors promoting gastric cancer development.

At concentrations that were not-toxic to healthy cells (after dilution of the solutions, the composition of the ethanol/water mixture was approximately 1/99, v/v), the ligands exhibited bacterial inhibitory activity and cytotoxic properties against AGS cancer cells. Zinc(II) complexes, on the other hand, being biologically safe for all cells, had strong antibacterial properties, both inhibitory and bactericidal.”

https://pubmed.ncbi.nlm.nih.gov/40436988/

“Naturally occurring compounds known as plant cannabinoids or phytocannabinoids, responsible for the physiological effects of cannabis, have been used medicinally for thousands of years.”

https://www.nature.com/articles/s41598-025-03442-5

Targeting the Gut-Brain Axis with Plant-Derived Essential Oils: Phytocannabinoids and Beyond

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“Background: The gut-brain axis (GBA) is a complex bidirectional communication system that links the gastrointestinal tract and the central nervous system. Essential oils (EOs) have emerged as promising natural compounds capable of modulating this axis. 

Methods: A comprehensive analysis of the recent literature was conducted, focusing on studies investigating the effects of EOs on the GBA.

Particular attention was given to the endocannabinoid system, the role of cannabis-derived EOs, and other plant-based EOs with potential neuroprotective and gut microbiota-modulating effects. 

Results: Among the EOs analyzed, cannabis essential oil (CEO) gained attention for its interaction with cannabinoid receptors (CBR1 and CBR2), modulating gut motility, immune responses, and neurotransmission. While acute administration of the CEO reduces inflammation and gut permeability, chronic use has been associated with alterations in gut microbiota composition, potentially impairing cognitive function. Other EOs, such as those from rosemary, lavender, eucalyptus, and oregano, demonstrated effects on neurotransmitter modulation, gut microbiota balance, and neuroinflammation, supporting their potential therapeutic applications in GBA-related disorders. 

Conclusions: EOs demonstrate promising potential in modulating the GBA through mechanisms including neurotransmitter regulation, gut microbiota modulation, and anti-inflammatory activity. At the same time, phytocannabinoids offer therapeutic value; their long-term use warrants caution due to potential impacts on microbiota. Future research should aim to identify EO-based interventions that can synergistically restore GBA homeostasis and mitigate neurodegenerative and gastrointestinal disorders.”

https://pubmed.ncbi.nlm.nih.gov/40362887/

https://www.mdpi.com/2072-6643/17/9/1578

The Endocannabinoid System: Implications in Gastrointestinal Physiology and Pathology

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“The endocannabinoid system (ECS), composed of receptors, endocannabinoids, and enzymes that regulate biosynthesis and degradation, plays a fundamental role in the physiology and pathology of the gastrointestinal tract, particularly in the small and large intestine and liver.

Specifically, cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 (CB2R), located principally in the nervous system and immune cells, orchestrate processes such as intestinal motility, intestinal and hepatic inflammation, and energy metabolism, respectively.

The main endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), influence appetite, body weight regulation, and inflammatory states and thus have implications in obesity, non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS).

Recent studies have highlighted the therapeutic potential of targeting the ECS to modulate gastrointestinal and metabolic diseases. In particular, peripheral CB1R antagonists and CB2R agonists have shown efficacy in treating intestinal inflammation, reducing hepatic steatosis, and controlling IBS symptoms. Moreover, the ECS is emerging as a potential target for the treatment of colorectal cancer, acting on cell proliferation and apoptosis.

This review highlights the opportunity to exploit the endocannabinoid system in the search for innovative therapeutic strategies, emphasizing the importance of a targeted approach to optimize treatment efficacy and minimize side effects.”

https://pubmed.ncbi.nlm.nih.gov/39941074/

“In conclusion, these findings suggest that the ECS offers a versatile approach for modulating gastrointestinal physiological aspects and treating conditions such as obesity and its complications, IBS, and CRC. Future research should refine ECS-targeted therapies to maximize their efficacy and minimize adverse effects, unlocking new opportunities for innovative treatments of disordered metabolism, inflammation, and cancer.

Clinical studies show that medical cannabis could be a valuable adjunct to cancer and treatments for inflammation, providing symptom relief and improving patients’ overall quality of life. However, further research is needed to refine treatment protocols and explore their full therapeutic potential.”

https://www.mdpi.com/1422-0067/26/3/1306

Medicinal Cannabis and the Intestinal Microbiome

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“Historically, the multiple uses of cannabis as a medicine, food, and for recreational purposes as a psychoactive drug span several centuries.

The various components of the plant (i.e., seeds, roots, leaves and flowers) have been utilized to alleviate symptoms of inflammation and pain (e.g., osteoarthritis, rheumatoid arthritis), mood disorders such as anxiety, and intestinal problems such as nausea, vomiting, abdominal pain and diarrhea.

It has been established that the intestinal microbiota progresses neurological, endocrine, and immunological network effects through the gut-microbiota-brain axis, serving as a bilateral communication pathway between the central and enteric nervous systems.

An expanding body of clinical evidence emphasizes that the endocannabinoid system has a fundamental connection in regulating immune responses. This is exemplified by its pivotal role in intestinal metabolic and immunity equilibrium and intestinal barrier integrity.

This neuromodulator system responds to internal and external environmental signals while also serving as a homeostatic effector system, participating in a reciprocal association with the intestinal microbiota.

We advance an exogenous cannabinoid-intestinal microbiota-endocannabinoid system axis potentiated by the intestinal microbiome and medicinal cannabinoids supporting the mechanism of action of the endocannabinoid system. An integrative medicine model of patient care is advanced that may provide patients with beneficial health outcomes when prescribed medicinal cannabis.”

https://pubmed.ncbi.nlm.nih.gov/39770543/

“Furthermore, other modes of delivery of medicinal cannabis, such as oro-buccal, sublingual and inhaled/smoked alternatives, provide cannabinoids that have rapid access to the systemic circulation, bypassing the intestinal tract.”

https://www.mdpi.com/1424-8247/17/12/1702

Hemp Extract (Extractum Cannabis) in the Treatment of Gastrointestinal Distress and Dyspepsia: Historical Insights from Barcelona, Spain

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“This study explores the trajectory of interest in and use of Extractum Cannabis (hemp extract, i.e., extract of Cannabis sativa L.) for the symptomatic treatment of minor gastrointestinal distress and dyspepsia in nineteenth- and early twentieth-century Barcelona (Catalonia, Spain) prior to 1939, through a review of primary sources.

The objective of this paper is to present a historical pharmaceutical and applied review of the medical use of the hemp genus (Cannabis L.) prior to its prohibition, thereby contributing to its recognition as a medicinal product.

The information provided demonstrates evidence of the medicinal use of cannabis within the historical context studied. The interactions between this legacy medical use and the contemporary body of pharmacological and toxicological knowledge (on hemp, its constituents, and the endocannabinoid system in gastrointestinal and stomach disorders) are discussed, providing new possible clinical perspectives.

Within its limitations-including the scope, limited accessibility to, and varying quality of archives-this research contributes to a more granular understanding of the historical embeddedness of psychoactive hemp medicines in northeastern Spain, suggesting that medical and pharmaceutical traditions could play a role in informing contemporary approaches to “medical marijuana”.”

https://pubmed.ncbi.nlm.nih.gov/39770428/

https://www.mdpi.com/1424-8247/17/12/1585

Relief in Gastrointestinal Symptoms with Medical Marijuana Over 1 Year

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“Introduction: Subjective improvement in gastrointestinal (GI) symptoms was assessed among patients using medical marijuana (MMJ).

Methods: Participants completed surveys at 0 days, 30 days, 6 months, and 12 months with questions about the severity of their GI symptoms on a scale from 1 (mild) to 3 (severe).

Results: In each survey, participants reported a significant decrease in GI symptom severity when using MMJ versus when not using MMJ (p < 0.05). The most common self-reported side effects from using MMJ were increased appetite (12-21.4%), fatigue (6-16.7%), anxiety (4-11.9%), cough (4-11.9%), headache (6-7.9%), and dry mouth (4-7.1%).

Conclusion: In patients with chronic GI symptoms, MMJ may provide persistent symptom severity improvement. Limited product availability and mild to moderate side effects are factors to consider before trialing MMJ.”

https://pubmed.ncbi.nlm.nih.gov/39015606/

“Overall, this study suggests there may be a role for MMJ to treat GI symptoms.”

https://karger.com/mca/article/7/1/80/907598/Relief-in-Gastrointestinal-Symptoms-with-Medical