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|Title||Pharmacogenetic Trial of a Cannabinoid Agonist Shows Reduced Fasting Colonic Motility in Patients with Non-Constipated Irritable Bowel Syndrome.|
|Author(s)||Wong BS, Camilleri M, Busciglio I, Carlson P, Szarka LA, Burton D, Zinsmeister AR.|
|Journal, Volume, Issue||Gastroenterology. 2011 Nov;141(5):1638-47.e1-7.|
|Major outcome(s)||Dronabinol reduces fasting motility of the colon in IBS patients with diarrhoea|
BACKGROUND: Cannabinoid receptors are located on cholinergic neurons. Genetic variants that affect endocannabinoid metabolism are associated with colonic transit in patients with irritable bowel syndrome with diarrhea (IBS-D). We compared the effects of dronabinol, a non-selective 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 [IBS-C], 35 with IBS-D, and with 5 IBS-alternating [IBS-A]) 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, the motility index (MI), tone, and sensation, during fasting and after a meal. We analyzed the single nucleotide polymorphisms CNR1 rs806378, FAAH rs324420, and MGLL rs11538700. 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-D or -A (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 FAAHrs324420 variant (CA/AA vs CC) (P=.046); the greatest effects were observed among IBS-C patients with the FAAH CC variant (P=.045). Dronabinol affected fasting proximal MI in patients with IBS-D or -A with the variant FAAH CA/AA (P=.013). CONCLUSION: In patients with IBS-D or -A, dronabinol reduces fasting colonic motility; FAAH and CNR1 variants could influence the effects of this drug on colonic motility.
|Participants||75 patients with irritable bowel syndrome|
|Type of publication||Medical journal|
|Address of author(s)||Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Rochester, Minnesota.|