CB1 receptor blockers caused diarrhea so consistently they might actually treat constipation-dominant IBS | Research

The takeaway

A meta-analysis of 18 clinical trials found that CB1 receptor inverse agonists (rimonabant and taranabant) consistently caused gastrointestinal side effects, particularly diarrhea, suggesting they could be repurposed for constipation-predominant IBS.

People with IBS interested in cannabinoid-based treatments, and those interested in how the endocannabinoid system affects gut function.

CB1 blockers doubled GI adverse events vs placebo (OR 2.05), suggesting therapeutic potential for IBS-C

What the researchers found

Rimonabant 20mg produced significantly more GI adverse events than placebo (OR 2.05) and overall adverse events (OR 1.35). Taranabant showed similar patterns (GI AEs OR 1.75, overall OR 1.36). Both drugs also caused significantly more psychiatric adverse events.

Why it matters

IBS with constipation has limited treatment options. This creative approach of repurposing a known side effect (diarrhea from CB1 blockers) into a therapeutic benefit illustrates how understanding the endocannabinoid system's role in gut function could yield new treatments.

The numbers in context

18 trials analyzed. Rimonabant 20mg: GI AEs OR 2.05 (CI: 1.65-2.55, p<0.001), psychiatric AEs OR 1.79 (CI: 1.46-2.21). Taranabant 0.5-8mg: GI AEs OR 1.75 (CI: 1.29-2.37), psychiatric AEs OR 1.82 (CI: 1.54-2.16).

How the study worked

Systematic review and meta-analysis of 18 clinical trials published through May 2018 reporting at least one month of treatment with rimonabant or taranabant, analyzing gastrointestinal adverse events using odds ratios.

What this study cannot tell us

The trials analyzed were designed for obesity/metabolic conditions, not IBS. GI adverse events were secondary outcomes, not primary endpoints. Psychiatric side effects (which led to rimonabant's withdrawal) remain a barrier. No IBS-specific trials have been conducted.

How to read the evidence

Strong: meta-analysis of 18 clinical trials with consistent findings across two different drugs.

When this study was published

Published in 2019, analyzing trials through May 2018.

The bigger picture

Rimonabant was withdrawn from the market due to psychiatric side effects. However, peripherally-restricted CB1 antagonists that don't cross the blood-brain barrier could potentially deliver the gut effects without the psychiatric risks, opening a new avenue for IBS treatment.

Questions still open

Could peripherally-restricted CB1 antagonists provide GI benefits without psychiatric side effects? What would be the optimal dose for IBS-C specifically? Would these agents be effective for other forms of constipation beyond IBS?

Common questions

Could cannabinoid drugs help with IBS?

This meta-analysis suggests CB1 receptor blockers could help constipation-predominant IBS, based on their consistent diarrhea-causing effect. However, no IBS-specific trials have been conducted, and psychiatric side effects remain a concern.

Why were these drugs withdrawn if they could help IBS?

Rimonabant was withdrawn due to psychiatric side effects (anxiety, depression). Future research may focus on peripherally-restricted versions that act only in the gut without crossing into the brain.

Read the original research

Gastrointestinal Adverse Events of Cannabinoid 1 Receptor Inverse Agonists suggest their Potential Use in Irritable Bowel Syndrome with Constipation: A Systematic Review and Meta-Analysis.

Journal of gastrointestinal and liver diseases : JGLD, 28(4), 473-481

View on PubMed ↗Publisher’s paper ↗

Citation

Fabisiak, Adam; Włodarczyk, Marcin; Fabisiak, Natalia; Storr, Martin; Fichna, Jakub. (2019). Gastrointestinal Adverse Events of Cannabinoid 1 Receptor Inverse Agonists suggest their Potential Use in Irritable Bowel Syndrome with Constipation: A Systematic Review and Meta-Analysis.. Journal of gastrointestinal and liver diseases : JGLD, 28(4), 473-481. https://doi.org/10.15403/jgld-265