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Research: Cannabis as a Treatment for Digestive Diseases

Liquid Life Research: Cannabis and Digestive Diseases

Introductions and image by @SuperFunker.

1) Borrelli et al (2013) expanded the understanding of the phytocannabinoids found in Cannabis by assessing the effect of CBG (cannabigerol) - not CBD (cannabidiol) - on inflammatory bowel disease. A nominal dose of 1 mg/kg was an effective preventive treatment and 5 mg/kg proved to have a curative effect. The most potent curative dose was 30 mg/kg which reduced inflammation, corrected intestinal permeability, counteracted oxidative stress and protected gut flora.

Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease.

Abstract
Inflammatory bowel disease (IBD) is an incurable disease which affects millions of people in industrialised countries. Anecdotal and scientific evidence suggest that Cannabis use may have a positive impact in IBD patients. Here, we investigated the effect of cannabigerol (CBG), a nonpsychotropic Cannabis-derived cannabinoid, in a murine model of colitis. Colitis was induced in mice by intracolonic administration of dinitrobenzene sulphonic acid (DNBS). Inflammation was assessed by evaluating inflammatory markers/parameters (colon weight/colon length ratio and myeloperoxidase activity), by histological analysis and immunohistochemistry; interleukin-1β, interleukin-10 and interferon-γ levels by ELISA, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) by western blot and RT-PCR; CuZn-superoxide dismutase (SOD) activity by a colorimetric assay. Murine macrophages and intestinal epithelial cells were used to evaluate the effect of CBG on nitric oxide production and oxidative stress, respectively. CBG reduced colon weight/colon length ratio, myeloperoxidase activity, and iNOS expression, increased SOD activity and normalized interleukin-1β, interleukin-10 and interferon-γ changes associated to DNBS administration. In macrophages, CBG reduced nitric oxide production and iNOS protein (but not mRNA) expression. Rimonabant (a CB1 receptor antagonist) did not change the effect of CBG on nitric oxide production, while SR144528 (a CB2 receptor antagonist) further increased the inhibitory effect of CBG on nitric oxide production. In conclusion, CBG attenuated murine colitis, reduced nitric oxide production in macrophages (effect being modulated by the CB2 receptor) and reduced ROS formation in intestinal epithelial cells. CBG could be considered for clinical experimentation in IBD patients.

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2) Lin et al (2018) explored the use of a variety of complementary and alternative medicines among patients with inflammatory bowel disease. Up to 60% of those who suffer from inflammatory bowel disease add alternative medicines to prescribed treatment, because:

  • They feel that herbal remedies are less toxic.
  • Conventional therapy does not work.
  • Pharmaceuticals may be plagued by side-effects.
  • And they seek more control over the disease so as to improve the quality of their life.

Cannabis as an alternative therapy may:

  • Attenuate colitis.
  • Reduce inflammation.
  • Relieve pain.
  • Mitigate nausea.
  • And control diarrhea. 

The Use of Complementary and Alternative Medicine in Patients With Inflammatory Bowel Disease.

Abstract
Complementary and alternative medicine (CAM) includes products or medical practices that encompass herbal and dietary supplements, probiotics, traditional Chinese medicines, and a variety of mind-body techniques. The use of CAM in patients with inflammatory bowel disease (IBD) is increasing as patients seek ways beyond conventional therapy to treat their chronic illnesses. The literature behind CAM therapies and their application, efficacy, and safety is limited when compared to studies of conventional, allopathic therapies. Thus, gastroenterologists are often ill equipped to engage with their patients in informed and meaningful discussions about the role of CAM in IBD. The aims of this article are to provide a comprehensive summary and discussion of various CAM modalities and to appraise the evidence for their use.

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3) Naftali (2019) offered the following editorial review in the Israel Medical Association Journal. Naftali highlights that Cannabis users who suffer from inflammatory bowel disease regard Cannabis as “very helpful” in relieving abdominal pain, nausea and diarrhea. Those who use Cannabis and suffer from ulcerative colitis, demonstrated a lower prevalence of colectomies, lessened bowel obstructions and shorter hospital stays. Although Cannabis appears to exhibit a therapeutic benefit, the dynamic phytochemical profile, various modes of consumption and differing dosages have not yet been fully rationalized.

Cannabis for Inflammatory Bowel Disease: Should We Follow the Wisdom of the Crowd?

Abstract
Inflammatory bowel diseases (IBD) are chronic debilitating diseases affecting the gastrointestinal tract. Crohn’s disease may affect any part of the gastrointestinal tract, and the inflammation may penetrate through the bowel wall into the abdominal cavity. Ulcerative colitis, however, will solely affect the large intestine and inflammation is limited to the superficial epithelial layer of the bowel wall. Despite the progress made in the treatment of IBD in the last decades, response to treatment is still limited to only 40 to 60%of patients, with 30% requiring surgery. Consequently, many patients turn to alternative medicine, including medical cannabis.

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4) Zhang et al (2019) obtained human gastric cancer SGC-7901 cells to test the anti-cancer function of CBD. The results demonstrated that CBD effectively inhibited colony formation, induced cell cycle arrest and caused death of the cancer cells. Specifically:

  • "Protein expression levels of CDK2 and cyclin E in the SGC-7901 cells decreased after CBD treatment, which in turn reduced the formation of CDK2/cyclin E complexes, ultimately arresting SGC-7901 cells at the G0–G1 phase."
  • "After treatment with CBD, ATM protein expression levels increased, and the ATM protein was activated in SGC-7901 cells. Meanwhile, CBD increased the expression of p21 and downregulated the expression of p53 in SGC-7901 cells, which in turn led to cell cycle arrest at the G0–G1 phase."
  • "Considering that the mitochondria-mediated caspase-dependent pathway is a major apoptotic pathway, we then examined the levels of anti- and pro-apoptotic Bcl-2 family proteins in the mitochondria-dependent apoptotic pathway. We found that CBD upregulated Bax and downregulated Bcl-2 in CBD-treated SGC-7901 cells, leading to a decrease in the ratio of Bcl-2/Bax."
  • "CBD significantly decreased the mitochondrial transmembrane potential, released mitochondrial cytochrome C into the cytoplasm, and activated Apaf-1 and caspase-9 and -3, which ultimately resulted in SGC-7901 cell apoptosis."
  • "These results indicated that CDB-induced cell cycle arrest and cell apoptosis of SGC-7901 cells were associated with the increasing intracellular ROS levels."

In conclusion, Zhang maintains that his results support the development of a CBD protocol to directly treat gastric cancer.

Cannabidiol Induces Cell Cycle Arrest and Cell Apoptosis in Human Gastric Cancer SGC-7901 Cells.

Abstract
The main chemical component of cannabis, cannabidiol (CBD), has been shown to have antitumor properties. The present study examined the in vitro effects of CBD on human gastric cancer SGC-7901 cells. We found that CBD significantly inhibited the proliferation and colony formation of SGC-7901 cells. Further investigation showed that CBD significantly upregulated ataxia telangiectasia-mutated gene (ATM) and p53 protein expression and downregulated p21 protein expression in SGC-7901 cells, which subsequently inhibited the levels of CDK2 and cyclin E, thereby resulting in cell cycle arrest at the G0–G1 phase. In addition, CBD significantly increased Bax expression levels, decreased Bcl-2 expression levels and mitochondrial membrane potential, and then upregulated the levels of cleaved caspase-3 and cleaved caspase-9, thereby inducing apoptosis in SGC-7901 cells. Finally, we found that intracellular reactive oxygen species (ROS) increased after CBD treatment. These results indicated that CBD could induce G0–G1 phase cell cycle arrest and apoptosis by increasing ROS production, leading to the inhibition of SGC-7901 cell proliferation, thereby suggesting that CBD may have therapeutic effects on gastric cancer.

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