Ayah Matar, MD, is a postdoctoral researcher at Mayo Clinic.

Ayah Matar, MD

Could a Smoking Cessation Drug Treat IBS Pain? New Data on Varenicline

 is widely considered to be one of the most challenging conditions to treat in gastroenterology, with chronic abdominal pain representing a particularly difficult therapeutic target. Existing options for centrally mediated visceral pain in IBS are limited, and the mechanisms driving pain sensitivity remain incompletely understood.

Early-phase data presented at Digestive Disease Week (DDW) 2026 in Chicago, IL, by Ayah Matar, MD, a postdoctoral researcher at Mayo Clinic, suggest varenicline, a nicotinic acetylcholine receptor partial agonist currently approved for smoking cessation, may offer a novel mechanism for addressing both pain and bowel symptoms in non-constipation IBS.

"Pain might be due to sensitivity at the nicotinic receptors," Matar told 

. "Since varenicline is a partial agonist at those receptors, we thought it might help with IBS — specifically the pain component."

The study was a prospective, open-label, 8-day trial of oral varenicline at doses approved for smoking cessation in eight patients with non-constipation IBS and chronic abdominal pain. Each participant served as their own control, given the wide variance in rectal sensation in IBS patients.

A 2-week run-in period preceded treatment, during which daily diary data were collected; eligibility to proceed required an average pain score of ≥ 3 over 7 consecutive days. At baseline and end of treatment, participants underwent barostat-based rectal compliance and sensory testing, and completed daily symptom diaries and the Hospital Anxiety and Depression questionnaire.

After 8 days of varenicline treatment, participants showed significant improvements across multiple symptom domains compared to baseline. Abdominal pain decreased on both the 100mm visual analog scale and the 0–4 Likert scale, and anxiety scores also improved, though depression scores did not change significantly. Bowel symptoms including bloating, urgency, stool frequency, and ease of passage all improved at the end of treatment.

Of note, varenicline did not alter rectal compliance, a finding Matar described as clinically meaningful rather than a limitation.

"The minimal effect on rectal compliance suggests a central afferent modulation effect," she said. "That is really interesting, and addresses an unmet need when it comes to pain and IBS."

Varenicline did significantly decrease rectal sensation at 24 mmHg distension for gas, but not at other sensory thresholds, further supporting a centrally mediated rather than peripherally mediated mechanism of action.

Matar said the rationale for investigating varenicline in IBS draws on prior evidence showing its efficacy for pain associated with opioid withdrawal, as well as preclinical data implicating nicotinic acetylcholine receptor signaling in visceral pain sensitivity. The current findings add a clinical signal to that mechanistic foundation, though the small sample size and open-label design require prospective confirmation.

She noted that next steps should include a placebo-controlled trial with a longer follow-up period to further characterize both efficacy and the safety profile beyond 8 days, a critical step before varenicline can be considered for broader clinical application in IBS.

Editor's note: Matar reports no relevant disclosures.

Matar A, Busciglio I, Linden DR, et al. Effect of Varenicline in Patients With Non-Constipation Irritable Bowel Syndrome and Pain. Presented at Digestive Disease Week (DDW) 2026; Chicago, IL; May 2–5, 2026.

Singh D, Saadabadi A. Varenicline. StatPearls. October 5, 2024. Accessed May 7, 2026. 

https://www.ncbi.nlm.nih.gov/books/NBK534846/

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Early data suggest varenicline may improve abdominal pain, bloating, and bowel symptoms in patients with IBS.

Varenicline Shows Early Promise for Pain, Bowel Symptoms in IBS, With Ayah Matar, MD

Rimegepant Linked to Increased Rectal Compliance, Reduced Rectal Sensation in IBS, With Ayah Matar, MD

New research on rimegepant for the treatment of 

 highlights reduced rectal sensation and increased rectal compliance in participants with non-constipation IBS and abdominal pain.

Ayah Matar, MD, a postdoctoral researcher at Mayo Clinic, presented the late-breaking abstract at the 

American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting

, evaluating the safety and efficacy of rimegepant by measuring abdominal pain, bowel movements, rectal compliance and sensation, and gastrointestinal/ colonic transit.

Calcitonin gene-related peptide (CGRP) is a neurotransmitter expressed by visceral afferents and digestive organs. Rimegepant, a CGRP receptor antagonist, is the 

 approved in the United States for the acute and preventive treatment of migraine. Preclinical studies have shown CGRP significantly reduces visceral hypersensitivity to colonic distension in rats.

In this randomized, double-blind, placebo-controlled study, investigators sought to assess whether rimegepant, at the same dosage used for migraine prevention, could alleviate IBS-related abdominal pain and bowel symptoms.

“There are multiple medication options [for IBS], but they have known side effects, and some of those medications can be only given to a specific population, such as women under 35,” said Matar in an interview with 

 “This leaves the remaining patients with unmet pharmacological needs and treatment.”

Participants received either a placebo (n = 12) or oral rimegepant 75 mg every other day (n = 12). Eligible participants had non-constipated IBS with abdominal pain meeting Rome III criteria. The study included a 2-week run-in, a 4-week treatment phase, and a 4-week post-treatment follow-up.

Abdominal pain and bowel movements were recorded in daily diaries throughout the study. Rectal compliance and sensory thresholds were assessed using a validated barostat method with stepwise distensions of 0–44 mmHg in 4 mmHg increments. During phasic rectal distensions at 12, 24, and 36 mmHg, investigators used a 100 mm visual analog scale to record sensations of gas, urgency, and pain.

According to data presented at ACG, no significant differences were observed between groups regarding abdominal pain or bowel movements at baseline or during treatment. Investigators saw an association between rimegepant treatment and reductions in sensations of gas, urgency, and pain during 24 mmHg rectal distensions (

 < .05), as well as gas and urgency sensations during 36 mmHg rectal distensions (

Compared with placebo, rimegepant was associated with modest differences in daily symptom scores and rectal compliance. Median change from baseline in abdominal pain was -22.6 (Interquartile Range [IQR], -30.3 to -8.1) with placebo and -12 (IQR, -16.9 to -6.4) with rimegepant (

For bowel movement frequency, investigators observed a median change of –0.2 (IQR, -0.8 to 0) with rimegepant (

 = .043) compared to -0.9 (IQR, -1 to -0.4) with placebo, indicating a statistically significant difference. No significant differences were observed for bowel movement consistency (

Investigators noted a statistically significant difference in rectal compliance between groups, with a median change of 2.1 (IQR, -1.3 to 7) for rimegepant (

 = .041) and -0.1 (IQR, -4.2 to 2.2) for placebo.

“When I say it reduced rectal compliance, I mean that patients had a stiffer rectum, yet we also saw a reduced sensation to pain. This tells us that rimegepant was acting on the visceral effects and not just reducing pain sensation because of a looser rectum,” said Matar. “It's not just about reducing the sensation of the rectum, it's also about increasing the threshold of pain, so there was a need for more pressure to get a response or pain in the participants who received rimegepant.”

Editor’s Note: Matar reports no relevant disclosures.

Matar, A, Halawi, H, Wang, I, et al. A Placebo-Controlled Trial of CGRP Antagonist Rimegepant on Visceral Sensation and Symptoms in Participants With Non-Constipated IBS Pain (Late-Breaking Abstract). Presented at the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting. Phoenix, Arizona. October 27-29, 2025.

. 2020;80(7):741-746. doi:https://doi.org/10.1007/s40265-020-01301-3

Late-breaking ACG 2025 data link rimegepant to increased rectal compliance and reduced rectal sensation in IBS without constipation.


Ayah Matar, MD

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