BackgroundOpioids inhibit motility and secretion of the gut and have been used for antidiarrheal treatment for centuries. However, the underlying mechanisms of opium tincture are not evident.AimTo investigate the effects of opium tincture on gastrointestinal motility, intestinal volumes, and water content of different gut segments assessed by magnetic resonance imaging (MRI).MethodsTwenty healthy volunteers were included in a randomized, placebo‐controlled, crossover study of 9 days of treatment with 30 drops of opium tincture per day. MRI was performed on day 1 (before treatment) and day 9 (during treatment). Measurements included assessments of gastric volume, gastric emptying, gastric motility, small bowel volume, small bowel water content, small bowel motility, colon volume, colon water content, and whole gut transit.Key ResultsOpium tincture delayed gastric emptying by a mean difference of 5.6 min [95% CI: 1.8–9.4], p = 0.004, and increased postprandial gastric meal volume (17–21%, p = 0.02). Small bowel endpoints did not change. Opium tincture delayed whole gut transit time (p = 0.027) and increased ascending colon volume by 59 mL [95% CI: 15–103], p = 0.004, and transverse colon volume by 48 mL [95% CI: 4–92], p = 0.027. T1‐relaxation time of the descending colon chyme was decreased during opium treatment, indicating dryer feces (difference: −173 ms [95% CI: −336 ‐11], p = 0.03).Conclusion and InferencesOpium tincture induced changes in the stomach and colon in healthy volunteers. An improved understanding of how opioids affect gut functions may lead to a better understanding and optimized management of diarrhea.