Anti-CGRP Drug Rimegepant Reduces Gut Pain Sensitivity in IBS Pilot Trial | Research

The takeaway

Rimegepant reduced rectal gas, urgency, and pain sensations during distension in IBS patients, supporting CGRP's role in visceral hypersensitivity despite not significantly reducing overall abdominal pain.

Gut sensitivity reduced
CGRP blockade significantly reduced gas, urgency, and pain sensations during rectal distension in IBS patients

What the researchers found

Rimegepant significantly reduced rectal gas, urgency, and pain sensations during 24/36 mmHg distension (all p<0.05) and decreased rectal compliance, despite not significantly reducing daily abdominal pain in 24 IBS patients.

Why it matters

IBS affects 10-15% of the global population with limited effective treatments. If CGRP blockade can reduce visceral hypersensitivity, it opens a new therapeutic approach.

How the study worked

Pilot RCT (NCT06221111), double-blind placebo-controlled, 24 adults with non-constipation IBS, rimegepant 75 mg every other day for 4 weeks, with barostat rectal distension and scintigraphy transit assessment.

What this study cannot tell us

Very small pilot (n=24). Primary endpoint not met. Every-other-day dosing may be suboptimal. Short 4-week treatment. Barostat endpoints are experimental.

How to read the evidence

Pilot RCT. Primary endpoint not met but significant mechanistic endpoints support further study. Very small sample limits conclusions.

When this study was published

Published in 2025, registered NCT06221111.

The bigger picture

CGRP's role extends beyond migraine to visceral pain. This pilot supports repurposing anti-CGRP drugs for the enormous IBS patient population.

Questions still open

Would daily rimegepant dosing produce better pain results?
Could anti-CGRP antibodies (longer-acting) be more effective for IBS?
Is there a subgroup of IBS patients with higher CGRP levels who would respond better?

Common questions

Could migraine drugs help with IBS?

This pilot study suggests yes — rimegepant (a CGRP blocker for migraines) reduced gut sensitivity in IBS patients. While it didn't eliminate daily pain, it reduced specific pain signals, supporting further research.

How does CGRP cause gut pain?

CGRP is a neuropeptide in the nerves lining the gut. In IBS, these nerves are hypersensitive. Blocking CGRP reduced the gut's overreaction to normal stretching and pressure.

Read the original research

A Pilot, Randomized, Placebo-Controlled Trial of Rimegepant on Visceral Sensation and Symptoms in Non-Constipation IBS Pain.

American journal of physiology. Gastrointestinal and liver physiology

View on PubMed ↗Publisher’s paper ↗

Citation

Halawi, Houssam; Matar, Ayah; Wang, Iris; Jencks, Kara J; Busciglio, Irene; Eckert, Deborah; Harmsen, William S; Camilleri, Michael. (2026). A Pilot, Randomized, Placebo-Controlled Trial of Rimegepant on Visceral Sensation and Symptoms in Non-Constipation IBS Pain.. American journal of physiology. Gastrointestinal and liver physiology. https://doi.org/10.1152/ajpgi.00394.2025