Pharmacogenetic Trial of a Cannabinoid Agonist Shows Reduced Fasting Colonic Motility in Patients With Nonconstipated Irritable Bowel Syndrome
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Background & aims Cannabinoid receptors are located on cholinergic neurons. Genetic variants that affect endocannabinoid metabolism are associated with colonic transit in patients with irritable bowel syndrome (IBS) with diarrhea. We compared the effects of dronabinol, a nonselective agonist of the cannabinoid receptor, with those of placebo on colonic motility and sensation in patients with IBS, and examined the effects of IBS subtype and specific genetic variants in cannabinoid mechanisms.Methods Seventy-five individuals with IBS (35 with IBS with constipation, 35 with IBS with diarrhea, and with 5 IBS alternating) were randomly assigned to groups that were given 1 dose of placebo or 2.5 mg or 5.0 mg dronabinol. We assessed left colonic compliance, motility index (MI), tone, and sensation during fasting and after a meal. We analyzed the single nucleotide polymorphisms CNR1 rs806378, fatty acid amide hydrolase (FAAH) rs324420, and MGLL rs4881.Results In all patients, dronabinol decreased fasting proximal left colonic MI compared with placebo (overall P = .05; for 5 mg dronabinol, P = .046), decreased fasting distal left colonic MI (overall P = .08; for 5 mg, P = .13), and increased colonic compliance (P = .058). The effects of dronabinol were greatest in patients with IBS with diarrhea or IBS alternating (proximal colonic MI, overall P = .022; compliance, overall P = .03). Dronabinol did not alter sensation or tone. CNR1 rs806378 (CC vs CT/TT) appeared to affect fasting proximal MI in all patients with IBS (P = .075). Dronabinol affected fasting distal MI in patients, regardless of FAAH rs324420 variant (CA/AA vs CC) (P = .046); the greatest effects were observed among IBS with constipation patients with the FAAH CC variant (P = .045). Dronabinol affected fasting proximal MI in patients with IBS with diarrhea or alternating with the variant FAAH CA/AA (P = .013).Conclusions In patients with IBS with diarrhea or alternating, dronabinol reduces fasting colonic motility; FAAH and CNR1 variants could influence the effects of this drug on colonic motility.
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Several recent studies have demonstrated bile acid malabsorption in a subset of patients with IBS.
“Several recent studies have demonstrated bile acid malabsorption in a subset of patients with IBS (1, 29, 93, 192).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [192]
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“CB, cannabinoid; DSE, depolarization-induced suppression of excitation; ENS, enteric nervous system; GI, gastrointestinal; IBS, irritable bowel syndrome”
ResultInfluentialCannabis and the Gastrointestinal Tract
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“Another study by Wong et al. (Wong et al., 2011) compared the effects of a single administration of placebo and dronabinol 2.5 or 5mg on colonic motility and sensation in 75 adult patients with IBS.”
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“In a 2011 clinical trial, dronabinol reduced fasting colonic motility in all IBS-D patients, particularly those carrying the CB1 receptor polymorphism rs806378 (Wong et al., 2011).”
BackgroundThe Endocannabinoid System: Implications in Gastrointestinal Physiology and Pathology
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“Reduced fasting colonic motility was shown in participants suffering from IBS-D and IBS-M after administration of dronabinol (Wong et al., 2011).”
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“Experimental studies demonstrated the presence of CBR in various sections of the gastrointestinal tract and a dysregulation of their expression has been reported in several gut pathologies, including diarrhoea [7], colon cancer [8], inflammatory and irritable bowel diseases [9,10].”
BackgroundNon-pharmaceutical treatments for irritable bowel syndrome
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“5 mg or 5 mg dronabinol and placebo Reduced colonic motility [135]”
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“Patients meeting the inclusion criteria had the following data col‐ lected through the survey:(1) gender; (2) age; (3) self‐identified ethnicity; (4) presence or absence of IBD; (5) medications;(6) num‐ ber of IBD‐related surgeries; (7)time since diagnosis; (8) SIBDQ (9) patterns of Cannabis use including duration, qu…”
Complementary and Alternative Medicine Therapies for Irritable Bowel Syndrome
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Cannabidiol and Intestinal Motility: a Systematic Review
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“…suffering neurological disorders, such as epilepsy [26]; (8) dealing better fear extinction [44–48]; (9) suffering irritable bowel syndrome [13,49,50]; (10) being obese (11) experiencing opioid-related effects in children [54–56]; (12) suffering myocardial infarction (13) feeling On the other…”
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- Authors
- Wong, B. S., Camilleri, M., Busciglio, I., Carlson, P., Szarka, L. A., Burton, D., & Zinsmeister, A. R.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Camilleri, Michael
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 141
- Issue
- 5
- Pages
- 1638-1647.e7
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC3202649
- OpenAlex
- W1987023043
- Cited by
- 100
- References
- 50
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 8 · 2022: 14 · 2021: 7 · 2020: 8 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 12 · 2015: 8 · 2014: 7 · 2013: 7 · 2012: 3
- FWCI
- 5.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Mayo Clinic
- Institute of Clinical and Translational Sciences
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK079866)
- National Center for Research Resources (UL1RR024150)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- irritable bowel syndrome, dronabinol, cannabinoid receptor agonists, colonic motility, colonic compliance, endocannabinoid system, irritable bowel syndrome with constipation, pharmacogenetics, single nucleotide polymorphisms
- MeSH terms
- Fatty Acid Amide Hydrolases, Adolescent, Adult, Aged, Amidohydrolases, Aryl Hydrocarbon Hydroxylases, Colon, Diarrhea, Double-Blind Method, Fasting, Female, Gastrointestinal Motility, Humans, Male, Middle Aged, Patient Compliance, Pharmacogenetics, Dronabinol, Comorbidity, Polymorphism, Single Nucleotide, Irritable Bowel Syndrome, Receptors, Cannabinoid, Young Adult, Cannabinoid Receptor Agonists, Cytochrome P-450 CYP2C9
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