Is Cannabis of Potential Value as a Therapeutic for Inflammatory Bowel Disease?

Naftali, Timna

doi:10.1007/s10620-019-05763-8

Cited by 6 publications

(4 citation statements)

References 23 publications

(11 reference statements)

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“… 16 These results are consistent with decreased endocannabinoid levels being associated with increased colitis in humans, and relevant therapeutically in that endocannabinoids (and cannabis) are increasingly being explored for potential therapeutic activity against IBD. 16 , 17 , 65 …”

Section: Discussionmentioning

confidence: 99%

Diet high in linoleic acid dysregulates the intestinal endocannabinoid system and increases susceptibility to colitis in Mice

et al. 2023

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Inflammatory bowel disease (IBD) is a multifactorial disease with increasing incidence in the U.S. suggesting that environmental factors, including diet, are involved. It has been suggested that excessive consumption of linoleic acid (LA, C18:2 omega-6), which must be obtained from the diet, may promote the development of IBD in humans. To demonstrate a causal link between LA and IBD, we show that a high fat diet (HFD) based on soybean oil (SO), which is comprised of ~55% LA, increases susceptibility to colitis in several models, including IBD-susceptible IL10 knockout mice. This effect was not observed with low-LA HFDs derived from genetically modified soybean oil or olive oil. The conventional SO HFD causes classical IBD symptoms including immune dysfunction, increased intestinal epithelial barrier permeability, and disruption of the balance of isoforms from the IBD susceptibility gene Hepatocyte Nuclear Factor 4α (HNF4α). The SO HFD causes gut dysbiosis, including increased abundance of an endogenous adherent invasive Escherichia coli (AIEC), which can use LA as a carbon source. Metabolomic analysis shows that in the mouse gut, even in the absence of bacteria, the presence of soybean oil increases levels of LA, oxylipins and prostaglandins. Many compounds in the endocannabinoid system, which are protective against IBD, are decreased by SO both in vivo and in vitro . These results indicate that a high LA diet increases susceptibility to colitis via microbial and host-initiated pathways involving alterations in the balance of bioactive metabolites of omega-6 and omega-3 polyunsaturated fatty acids, as well as HNF4α isoforms.

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Section: Discussionmentioning

confidence: 99%

Diet high in linoleic acid dysregulates the intestinal endocannabinoid system and increases susceptibility to colitis in Mice

et al. 2023

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“…These results are consistent with decreased endocannabinoid levels being associated with increased colitis (Diab et al, 2019). Endocannabinoids (and cannabis) are increasingly being explored for potential therapeutic activity against IBD (Cani et al, 2016; Naftali, 2019).…”

Section: Discussionmentioning

confidence: 99%

Diet High in Soybean Oil Increases Susceptibility to Colitis in Mice

Deol

Reugger

Logan

et al. 2021

Preprint

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Soybean oil (SO), the most prevalent cooking oil in the United States, consists primarily of linoleic acid (LA, C18:2 omega-6), a polyunsaturated fatty acid positively linked to the development of ulcerative colitis (UC) in humans. Here, we show that dietary SO increases intestinal epithelial barrier permeability and susceptibility to colitis in mice. It also disrupts the balance of isoforms encoded by the UC susceptibility gene Hepatocyte Nuclear Factor 4α (HNF4α), which in turn impacts barrier function and IBD susceptibility. The SO diet causes gut dysbiosis, including an increased abundance of an adherent, invasive Escherichia coli (AIEC) which can use LA as a carbon source. Metabolomic analysis indicates that gut bacteria and the SO diet can alter levels of LA and its oxylipin and endocannabinoid metabolites in the gut. Our results suggest that an SO-enriched diet increases susceptibility to colitis due to effects on intestinal HNF4α, microbiota and LA metabolites.

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“…Based on our evaluation of the evidence, neither disease showed any improvement in response or remission. The use of marijuana as a drug to treat inflammatory bowel disease still requires much larger, well-designed drug trials [ 18 ]. In the current state, evidence-based medicine would recommend against its use as a treatment, given the lack of efficacy shown in these studies.…”

Section: Discussionmentioning

confidence: 99%

“…While marijuana may not be effective as a pharmacologic therapy for disease management, it may have a role as an adjunct to standard therapy [ 18 ]. Some studies have reported improvements in pain and overall improved disease outlook when patients took marijuana or its derivatives [ 6 , 7 , 12 ].…”

Section: Discussionmentioning

confidence: 99%

Evidence supporting the benefits of marijuana for Crohn’s disease and ulcerative colitis is extremely limited: a meta-analysis of the literatureEvidence supporting the benefits of marijuana for Crohn’s disease and ulcerative colitis is extremely limited: a meta-analysis of the literature

Desmarais

Smiddy

Reddy

et al. 2020

aog

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Background Medical marijuana is increasingly used to control inflammation and pain in inflammatory bowel disease (IBD). We performed a meta-analysis to investigate the effect of marijuana on the clinical response, induction of clinical remission, and maintenance of clinical remission compared to placebo/standard of care. Methods We performed a systematic search of PubMed, Embase, and Web of Science in June 2019, for cannabis/marijuana and IBD, Crohn’s disease or ulcerative colitis (UC). The statistical analysis was performed using Revman (version 5.3). GRADE methodology was used to assess the quality of the evidence. Results Of the 334 studies initially reviewed, 1 trial in UC and 2 trials in Crohn’s disease met eligibility. For UC, 29 patients were treated with marijuana and 31 with placebo/standard of care. There was no difference in failure to achieve clinical remission (relative risk [RR] 1.02, 95% confidence interval [CI] 0.76-1.37) or response (RR 0.99, 95%CI 0.65-1.21). Adverse events occurred in all patients receiving marijuana (RR 1.28, 95%CI 1.05-1.56). For Crohn’s disease, 21 patients were treated with marijuana and 19 with placebo/standard of care. There was no difference in failure to achieve clinical remission (RR 0.72, 95%CI 0.47-1.12) or failure to achieve clinical response (RR 0.15, 95%CI 0.02-1.05). Adverse events were not reported per patient. The quality of evidence was low to very low using GRADE methodology. Conclusions Data supporting the use of marijuana for the management of IBD are extremely limited. Further well-designed studies are needed before any positive conclusions regarding marijuana use can be drawn.

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Is Cannabis of Potential Value as a Therapeutic for Inflammatory Bowel Disease?

Cited by 6 publications

References 23 publications

Diet high in linoleic acid dysregulates the intestinal endocannabinoid system and increases susceptibility to colitis in Mice

Diet high in linoleic acid dysregulates the intestinal endocannabinoid system and increases susceptibility to colitis in Mice

Diet High in Soybean Oil Increases Susceptibility to Colitis in Mice

Evidence supporting the benefits of marijuana for Crohn’s disease and ulcerative colitis is extremely limited: a meta-analysis of the literatureEvidence supporting the benefits of marijuana for Crohn’s disease and ulcerative colitis is extremely limited: a meta-analysis of the literature

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